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Heartburn | Heartburn, also known as pyrosis, cardialgia or acid indigestion, is a burning sensation in the central chest or upper central abdomen. Heartburn is usually due to regurgitation of gastric acid (gastric reflux) into the esophagus. It is the major symptom of gastroesophageal reflux disease (GERD).Other common descriptors for heartburn (besides burning) are belching, nausea, squeezing, stabbing, or a sensation of pressure on the chest. The pain often rises in the chest (directly behind the breastbone) and may radiate to the neck, throat, or angle of the arm. Because the chest houses other important organs besides the esophagus (including the heart and lungs), not all symptoms related to heartburn are esophageal in nature.The cause will vary depending on ones family and medical history, genetics, if a person is pregnant or lactating, and age. As a result, the diagnosis will vary depending on the suspected organ and the inciting disease process. Work-up will vary depending on the clinical suspicion of the provider seeing the patient, but generally includes endoscopy and a trial of antacids to assess for relief.Treatment for heartburn may include medications and dietary changes. Medication include antacids. Dietary changes may require avoiding foods that are high in fats, spicy, high in artificial flavors, heavily reducing NSAID use, heavy alcohol consumption, and decreasing peppermint consumption. Lifestyle changes may help such as reducing weight.
Definition
The term indigestion includes heartburn along with a number of other symptoms. Indigestion is sometimes defined as a combination of epigastric pain and heartburn. Heartburn is commonly used interchangeably with gastroesophageal reflux disease (GERD) rather than just to describe a symptom of burning in ones chest.
Differential diagnosis
Heartburn-like symptoms and/or lower chest or upper abdomen may be indicative of much more sinister and/or deadly disease. Of greatest concern is to confuse heartburn (generally related to the esophagus) with a heart attack as these organs share a common nerve supply. Numerous abdominal and thoracic organs are present in that region of the body. Many different organ systems might explain the discomfort called heartburn.
Heart
The most common symptom for a heart attack is chest pain. However, as many as 30% of chest pain patients undergoing cardiac catheterization have findings that do not account for their chest discomfort. These are often defined as having "atypical chest pain" or chest pain of undetermined origin. Women experiencing heart attacks may also deny classic signs and symptoms and instead complain of GI symptoms. One article estimates that ischemic heart disease may appear to be GERD in 0.6% of people.
Esophagus
GERD (most common cause of heartburn) occurs when acid refluxes from the stomach and inflames the esophagus.
Esophageal spasms typically occur after eating or drinking and may be combined with difficulty swallowing.
Esophageal strictures
Esophageal cancers
Esophagitis
GERD
Eosinophilic esophagitis – a disease commonly associated with other atopic diseases such as asthma, food allergies, seasonal allergies, and atopic skin disease
Mallory-Weis tears – tears of the superficial mucosa of the esophagus that are subsequently exposed to gastric acid commonly due to vomiting and/or retching
Chemical esophagitis – related to the intake of caustic substances, excessive amounts of hot liquids, alcohol, or tobacco smoke
Infections may explain heartburn symptoms. These especially include CMV and certain fungal infections, most common in immunocompromised persons
Stomach
Peptic ulcer disease – can be secondary to H. Pylori infection or heavy NSAID use that weakens stomach mucosal layer. Pain often worsens with eating.
Stomach cancer
Intestines
Intestinal ulcers – generally secondary to other conditions such as H. Pylori infection or cancers of the GI tract. Pain often improves with eating.
Duodenitis – inflammation of the small intestine. May be the result of several conditions
Gallbladder
Gallstones
Pancreas
Pancreatitis – can be autoimmune, due to a gallstone obstructing the lumen, related to alcohol consumption.
Hematology
Pernicious anemia – can be autoimmune, due to atrophic gastritis.
Pregnancy
Heartburn is common during pregnancy having been reported in as high as 80% of pregnancies. It is most often due to GERD and results from relaxation of the lower esophageal sphincter (LES), changes in gastric motility, and/or increasing intra-abdominal pressure. The onset of symptoms can be during any trimester of pregnancy.
Hormonal – related to the increasing amounts of estrogen and progesterone and their effect on the LES
Mechanical – the enlarging uterus increasing intra-abdominal pressure, inducing reflux of gastric acid
Behavioral – as with other instances of heartburn, behavioral modifications can exacerbate or alleviate symptoms
Unknown origin
Functional heartburn is heartburn of unknown cause. It is commonly associated with psychiatric conditions like depression, anxiety, and panic attacks. It is also seen with other functional gastrointestinal disorders like irritable bowel syndrome and is the primary cause of lack of improvement post treatment with proton pump inhibitors (PPIs). Despite this, PPIs are still the primary treatment with response rates in about 50% of people. The diagnosis is one of elimination, based upon the Rome III criteria. It was found to be present in 22.3% of Canadians in one survey.
Diagnostic approach
Heartburn can be caused by several conditions and a preliminary diagnosis of GERD is based on additional signs and symptoms. The chest pain caused by GERD has a distinct burning sensation, occurs after eating or at night, and worsens when a person lies down or bends over. It also is common in pregnant women, and may be triggered by consuming food in large quantities, or specific foods containing certain spices, high fat content, or high acid content. In young persons (typically <40 years) who present with heartburn symptoms consistent with GERD (onset after eating, when laying down, when pregnant), a physician may begin a course of PPIs to assess clinical improvement before additional testing is undergone. Resolution or improvement of symptoms on this course may result in a diagnosis of GERD.Other tests or symptoms suggesting acid reflux is causing heartburn include:
Onset of symptoms after eating or drinking, at night, and/or with pregnancy, and improvement with PPIs
Endoscopy looking for erosive changes of the esophagus consistent with prolonged acid exposure (e.g. - Barretts esophagus)
Upper GI series looking for the presence of acid reflux
GI cocktail
Relief of symptoms 5 to 10 minutes after the administration of viscous lidocaine and an antacid increases the suspicion that the pain is esophageal in origin. This however does not rule out a potential cardiac cause as 10% of cases of discomfort due to cardiac causes are improved with antacids.
Biochemical
Esophageal pH monitoring: a probe can be placed via the nose into the esophagus to record the level of acidity in the lower esophagus. Because some degree of variation in acidity is normal, and small reflux events are relatively common, esophageal pH monitoring can be used to document reflux in real-time. Patients are able to record symptom onset to correlate lower esophageal pH with time of symptom onset.
Mechanical
Manometry: in this test, a pressure sensor (manometer) is passed via the mouth into the esophagus and measures the pressure of the LES directly.Endoscopy: the esophageal mucosa can be visualized directly by passing a thin, lighted tube with a tiny camera known as an endoscope attached through the mouth to examine the oesophagus and stomach. In this way, evidence of esophageal inflammation can be detected, and biopsies taken if necessary. Since an endoscopy allows a doctor to visually inspect the upper digestive tract the procedure may help identify any additional damage to the tract that may not have been detected otherwise.Biopsy: a small sample of tissue from the oesophagus is removed. It is then studied to check for inflammation, cancer, or other problems.
Treatment
Treatment plans are tailored to the specific diagnosis and etiology of the heartburn. Management of heartburn can be sorted into various categories.
Pharmacologic management
Antacids (i.e. calcium carbonate) are often taken to treat the immediate problem
H2 receptor antagonists or proton pump inhibitors are effective for the two most common causes of heartburn (e.g. gastritis and GERD)
Antibiotics are used if H. pylori is present.
Behavioral management
Taking medications 30–45 minutes before eating suppresses the stomachs acid generating response to food
Avoiding spicy foods, foods high in fats, peppermint, and chocolate
Avoiding reclining 2.5–3.5 hours after a meal to prevent the reflux of stomachs contents
Lifestyle modifications
Early studies show that diets that are high in fiber may show evidence in decreasing symptoms of dyspepsia.
Weight loss can decrease abdominal pressure that both delays gastric emptying and increases gastric acid reflux into the esophagus
Alternative and complementary therapies
Symptoms of heartburn may not always be the result of an organic cause. Patients may respond better to therapies targeting anxiety and symptoms of hyper-vigilance, through medications aimed towards a psychiatric etiology, osteopathic manipulation and acupuncture.
Psychotherapy may show a positive role in treatment of heartburn and the reduction of distress experienced during symptoms.
Acupuncture - in cases of functional heartburn (e.g. heartburn of unknown origin) acupuncture may be as effective if not more than PPIs alone.
Surgical management
In the case of GERD causing heartburn symptoms, surgery may be required if PPI is not effective. Surgery is not undergone if functional heartburn is the leading diagnosis.
Epidemiology
About 42% of the United States population has had heartburn at some point.
== References == |
Prepatellar bursitis | Prepatellar bursitis is an inflammation of the prepatellar bursa at the front of the knee. It is marked by swelling at the knee, which can be tender to the touch and which generally does not restrict the knees range of motion. It can be extremely painful and disabling as long as the underlying condition persists.
Prepatellar bursitis is most commonly caused by trauma to the knee, either by a single acute instance or by chronic trauma over time. As such, the condition commonly occurs among individuals whose professions require frequent kneeling.
A definitive diagnosis can usually be made once a clinical history and physical examination have been obtained, though determining whether or not the inflammation is septic is not as straightforward. Treatment depends on the severity of the symptoms, with mild cases possibly only requiring rest and localized icing. Options for presentations with severe sepsis include intravenous antibiotics, surgical irrigation of the bursa, and bursectomy.
Signs and symptoms
The primary symptom of prepatellar bursitis is swelling of the area around the kneecap. It generally does not produce a significant amount of pain unless pressure is applied directly. The area may be red (erythema), warm to the touch, or surrounded by cellulitis, particularly if infection is present, often accompanied by fever.: p. 608 Unlike arthritis, except in severe cases prepatellar bursitis generally does not affect the range of motion of the knee, though it may cause some discomfort in complete flexion of the joint.: p. 360 Flexion and extension of the knee may be accompanied by crepitus, the audible grating of bones, ligaments, or particles within the excess synovial fluid.: p. 20
Causes
In human anatomy, a bursa is a small pouch filled with synovial fluid. Its purpose is to reduce friction between adjacent structures. The prepatellar bursa is one of several bursae of the knee joint, and is located between the patella and the skin. Prepatellar bursitis is an inflammation of this bursa. Bursae are readily inflamed when irritated, as their walls are very thin.: p. 22 Along with the pes anserine bursa, the prepatellar bursa is one of the most common bursae to cause knee pain when inflamed.Prepatellar bursitis is caused by either a single instance of acute trauma to the knee, or repeated minor trauma to the knee. The trauma can cause extravasation of nearby fluids into the bursa, which stimulates an inflammatory response. This response occurs in two phases: The vascular phase, in which the blood flow to the surrounding area increases, and the cellular phase, in which leukocytes migrate from the blood to the affected area.: p. 22 Other possible causes include gout, sarcoidosis, CREST syndrome,: p. 359 diabetes mellitus, alcohol use disorder, uremia, and chronic obstructive pulmonary disease.: p. 22 Some cases are idiopathic, though these may be caused by trauma that the patient does not remember.: pp. 607–8 The prepatellar bursa and the olecranon bursa are the two bursae that are most likely to become infected, or septic. Septic bursitis typically occurs when the trauma to the knee causes an abrasion, though it is also possible for the infection to be caused by bacteria traveling through the blood from a pre-existing infection site. In approximately 80% of septic cases, the infection is caused by Staphylococcus aureus; other common infections are Streptococcus, Mycobacterium, and Brucella.: p. 359 It is highly unusual for septic bursitis to be caused by anaerobes, fungi, or Gram-negative bacteria.: p. 608 In very rare cases, the infection can be caused by tuberculosis.
Diagnosis
There are several types of inflammation that can cause knee pain, including sprains, bursitis, and injuries to the meniscus. A diagnosis of prepatellar bursitis can be made based on a physical examination and the presence of risk factors in the persons medical history; swelling and tenderness at the front of the knee, combined with a profession that requires frequent kneeling, suggest prepatellar bursitis. Swelling of multiple joints along with restricted range of motion may indicate arthritis instead.: p. 608 A physical examination and medical history are generally not enough to distinguish between infectious and non-infectious bursitis; aspiration of the bursal fluid is often required for this, along with a cell culture and Gram stain of the aspirated fluid.: p. 360 Septic prepatellar bursitis may be diagnosed if the fluid is found to have a neutrophil count above 1500 per microliter,: p. 608 a threshold significantly lower than that of septic arthritis (50,000 cells per microliter).: p. 360 A tuberculosis infection can be confirmed using a radiograph of the knee and urinalysis.
Prevention
It is possible to prevent the onset of prepatellar bursitis, or prevent the symptoms from worsening, by avoiding trauma to the knee or frequent kneeling.: p. 610 Protective knee pads can also help prevent prepatellar bursitis for those whose professions require frequent kneeling and for athletes who play contact sports, such as American football, basketball, and wrestling.
Treatment
Non-septic prepatellar bursitis can be treated with rest, the application of ice to the affected area, and anti-inflammatory drugs, particularly ibuprofen. Elevation of the affected leg during rest may also expedite the recovery process. Severe cases may require fine-needle aspiration of the bursa fluid, sometimes coupled with cortisone injections. However, some studies have shown that steroid injections may not be an effective treatment option. After the bursitis has been treated, rehabilitative exercise may help improve joint mechanics and reduce chronic pain.: p. 2320 Opinions vary as to which treatment options are most effective for septic prepatellar bursitis.: p. 360 McAfee and Smith recommend a course of oral antibiotics, usually oxacillin sodium or cephradine, and assert that surgery and drainage are unnecessary.: p. 609 Wilson-MacDonald argues that oral antibiotics are "inadequate", and recommends intravenous antibiotics for managing the infection. Some authors suggest surgical irrigation of the bursa by means of a subcutaneous tube.: p. 360 Others suggest that bursectomy may be necessary for intractable cases; the operation is an outpatient procedure that can be performed in less than half an hour.: p. 357
Epidemiology
The various nicknames associated with prepatellar bursitis arise from the fact that it commonly occurs among those individuals whose professions require frequent kneeling, such as carpenters, carpet layers, gardeners, housemaids, mechanics, miners, plumbers, and roofers.: p. 607 The exact incidence of the condition is not known; it is difficult to estimate because only severe septic cases require hospital admission, and mild non-septic cases generally go unreported.: p. 607 Prepatellar bursitis is more common among males than females. It affects all age groups, but is more likely to be septic when it occurs in children.
References
== External links == |
Pityriasis lichenoides | Pityriasis lichenoides is a form of pityriasis.
Types include:
Pityriasis lichenoides et varioliformis acuta
Pityriasis lichenoides chronica
References
External links
DermNet scaly/pityriasis-lichenoides |
Malocclusion | In orthodontics, a malocclusion is a misalignment or incorrect relation between the teeth of the upper and lower dental arches when they approach each other as the jaws close. The English-language term dates from 1864; Edward Angle (1855-1930), the "father of modern orthodontics", popularised it. The word "malocclusion" derives from occlusion, and refers to the manner in which opposing teeth meet (mal- + occlusion = "incorrect closure").
The malocclusion classification is based on the relationship of the mesiobuccal cusp of the maxillary first molar and the buccal groove of the mandibular first molar. If this molar relationship exists, then the teeth can align into normal occlusion. According to Angle, malocclusion is any deviation of the occlusion from the ideal.
However, assessment for malocclusion should also take into account aesthetics and the impact on functionality. If these aspects are acceptable to the patient despite meeting the formal definition of malocclusion, then treatment may not be necessary.
Causes
The aetiology of malocclusion is somewhat contentious, however, simply put it is multifactorial, with influences being both genetic and environmental. Malocclusion is already present in one of the Skhul and Qafzeh hominin fossils and other prehistoric human skulls. There are three generally accepted causative factors of malocclusion:
Skeletal factors – the size, shape and relative positions of the upper and lower jaws. Variations can be caused by environmental or behavioral factors such as muscles of mastication, nocturnal mouth breathing, and cleft lip and cleft palate.
Muscle factors – the form and function of the muscles that surround the teeth. This could be impacted by habits such as finger sucking, nail biting, pacifier and tongue thrusting
Dental factors – size of the teeth in relation to the jaw, early loss of teeth could result in spacing or mesial migration causing crowding, abnormal eruption path or timings, extra teeth (supernumeraries), or too few teeth (hypodontia)There is not one single cause of malocclusion, and when planning orthodontic treatment it is often helpful to consider the above factors and the impact they have played on malocclusion. These can also be influenced by oral habits and pressure resulting in malocclusion.
Behavioral and dental factors
In the active skeletal growth, mouthbreathing, finger sucking, thumb sucking, pacifier sucking, onychophagia (nail biting), dermatophagia, pen biting, pencil biting, abnormal posture, deglutition disorders and other habits greatly influence the development of the face and dental arches. Pacifier sucking habits are also correlated with otitis media. Dental caries, periapical inflammation and tooth loss in the deciduous teeth can alter the correct permanent teeth eruptions.
Primary vs. secondary dentition
Malocclusion can occur in primary and secondary dentition.
In primary dentition malocclusion is caused by:
Underdevelopment of the dentoalvelor tissue.
Over development of bones around the mouth.
Cleft lip and palate.
Overcrowding of teeth.
Abnormal development and growth of teeth.In secondary dentition malocclusion is caused by:
Periodontal disease.
Overeruption of teeth.
Premature and congenital loss of missing teeth.
Signs and symptoms
Malocclusion is a common finding, although it is not usually serious enough to require treatment. Those who have more severe malocclusions, which present as a part of craniofacial anomalies, may require orthodontic and sometimes surgical treatment (orthognathic surgery) to correct the problem.
The ultimate goal of orthodontic treatment is to achieve a stable, functional and aesthetic alignment of teeth which serves to better the patients dental and total health. The symptoms which arise as a result of malocclusion derive from a deficiency in one or more of these categories.The symptoms are as follows:
Tooth decay (caries): misaligned teeth will make it more difficult to maintain oral hygiene. Children with poor oral hygiene and diet will be at an increased risk.
Periodontal disease: irregular teeth would hinder the ability to clean teeth meaning poor plaque control. Additionally, if teeth are crowded, some may be more buccally or lingually placed, there will be reduced bone and periodontal support. Furthermore, in Class III malocclusions, mandibular anterior teeth are pushed labially which contributes to gingival recession and weakens periodontal support.
Trauma to anterior teeth: Those with an increased overjet are at an increased risk of trauma. A systematic review found that an overjet of greater than 3mm will double the risk of trauma.
Masticatory function: people with anterior open bites, large increased & reverse overjet and hypodontia will find it more difficult to chew food.
Speech impairment: a lisp is when the incisors cannot make contact, orthodontics can treat this. However, other forms of misaligned teeth will have little impact on speech and orthodontic treatment has little effect on fixing any problems.
Tooth impaction: these can cause resorption of adjacent teeth and other pathologies for example a dentigerous cyst formation.
Psychosocial wellbeing: malocclusions of teeth with perceived poor aesthetics can have a significant effect on self-esteem. This is subjective in nature and will vary widely, being subject cultural and racial influences.Malocclusions may be coupled with skeletal disharmony of the face, where the relations between the upper and lower jaws are not appropriate. Such skeletal disharmonies often distort sufferers face shape, severely affect aesthetics of the face, and may be coupled with mastication or speech problems. Most skeletal malocclusions can only be treated by orthognathic surgery.
Classification
Depending on the sagittal relations of teeth and jaws, malocclusions can be divided mainly into three types according to Angles classification system published 1899. However, there are also other conditions, e.g. crowding of teeth, not directly fitting into this classification.
Many authors have tried to modify or replace Angles classification. This has resulted in many subtypes and new systems (see section below: Review of Angles system of classes).
A deep bite (also known as a Type II Malocclusion) is a condition in which the upper teeth overlap the lower teeth, which can result in hard and soft tissue trauma, in addition to an effect on appearance. It has been found to occur in 15–20% of the US population.An open bite is a condition characterised by a complete lack of overlap and occlusion between the upper and lower incisors. In children, open bite can be caused by prolonged thumb sucking. Patients often present with impaired speech and mastication.
Overbites
This is a vertical measurement of the degree of overlap between the maxillary incisors and the mandibular incisors. There are three features that are analysed in the classification of an overbite:
Degree of overlap: edge to edge, reduced, average, increased
Complete or incomplete: whether there is contact between the lower teeth and the opposing teeth/tissue (hard palate or gingivae) or not.
Whether contact is traumatic or atraumaticAn average overbite is when the upper anterior teeth cover a third of the lower teeth. Covering less than this is described as ‘reduced’ and more than this is an ‘increased’ overbite. No overlap or contact is considered an ‘anterior open bite’.
Angles classification method
Edward Angle, who is considered the father of modern orthodontics, was the first to classify malocclusion. He based his classifications on the relative position of the maxillary first molar. According to Angle, the mesiobuccal cusp of the upper first molar should align with the buccal groove of the mandibular first molar. The teeth should all fit on a line of occlusion which, in the upper arch, is a smooth curve through the central fossae of the posterior teeth and cingulum of the canines and incisors, and in the lower arch, is a smooth curve through the buccal cusps of the posterior teeth and incisal edges of the anterior teeth. Any variations from this resulted in malocclusion types. It is also possible to have different classes of malocclusion on left and right sides.
Class I (Neutrocclusion): Here the molar relationship of the occlusion is normal but the incorrect line of occlusion or as described for the maxillary first molar, but the other teeth have problems like spacing, crowding, over or under eruption, etc.
Class II (Distocclusion (retrognathism, overjet, overbite)): In this situation, the mesiobuccal cusp of the upper first molar is not aligned with the mesiobuccal groove of the lower first molar. Instead it is anterior to it. Usually the mesiobuccal cusp rests in between the first mandibular molars and second premolars. There are two subtypes:
Class II Division 1: The molar relationships are like that of Class II and the anterior teeth are protruded.
Class II Division 2: The molar relationships are Class II but the central are retroclined and the lateral teeth are seen overlapping the centrals.
Class III: (Mesiocclusion (prognathism, anterior crossbite, negative overjet, underbite)) In this case the upper molars are placed not in the mesiobuccal groove but posteriorly to it. The mesiobuccal cusp of the maxillary first molar lies posteriorly to the mesiobuccal groove of the mandibular first molar. Usually seen as when the lower front teeth are more prominent than the upper front teeth. In this case the patient very often has a large mandible or a short maxillary bone.
Review of Angles system of classes and alternative systems
A major disadvantage of Angles system of classifying malocclusions is that it only considers two dimensions along a spatial axis in the sagittal plane in the terminal occlusion, but occlusion problems can be three-dimensional. It does not recognise deviations in other spatial axes, asymmetric deviations, functional faults and other therapy-related features.
Angles classification system also lacks a theoretical basis; it is purely descriptive. Its much-discussed weaknesses include that it only considers static occlusion, it does not account for the development and causes (aetiology) of occlusion problems, and it disregards the proportions (or relationships in general) of teeth and face. Thus, many attempts have been made to modify the Angle system or to replace it completely with a more efficient one, but Angles classification continues be popular mainly because of its simplicity and clarity.Well-known modifications to Angles classification date back to Martin Dewey (1915) and Benno Lischer (1912, 1933). Alternative systems have been suggested by, among others, Simon (1930, the first three-dimensional classification system), Jacob A. Salzmann (1950, with a classification system based on skeletal structures) and James L. Ackerman and William R. Proffit (1969).
Incisor classification
Besides the molar relationship, the British Standards Institute Classification also classifies malocclusion into incisor relationship and canine relationship.
Class I:
The lower incisor edges occlude with or lie immediately below the cingulum plateau of the upper central incisors
Class II:
The lower incisor edges lie posterior to the cingulum plateau of the upper incisors
Division 1 – the upper central incisors are proclined or of average inclination and there is an increase in overjet
Division 2 – The upper central incisors are retroclined. The overjet is usually minimal or may be increased.
Class III:
The lower incisor edges lie anterior to the cingulum plateau of the upper incisors. The overjet is reduced or reversed.
Canine relationship by Ricketts
Class I:
Mesial slope of upper canine coincides with distal slope of lower canine
Class II:
Mesial slope of upper canine is ahead of distal slope of lower canine
Class III:
Mesial slope of upper canine is behind to distal slope of lower canine
Crowding of teeth
Crowding is defined by the amount of space that would be required for the teeth to be in correct alignment. It is obtained in two ways. 1) by measuring the amount of space required and reducing this from calculating the space available via the width of the teeth. Or 2) by measuring the degree of overlap of the teeth.
The following criterion is used:0-4mm = Mild crowding
4-8mm = Moderate crowding
>8mm = Severe crowding
Causes
Genetic (inheritance) factors, extra teeth, lost teeth, impacted teeth, or abnormally shaped teeth have been cited as causes of crowding. Ill-fitting dental fillings, crowns, appliances, retainers, or braces as well as misalignment of jaw fractures after a severe injury are also known to cause crowding. Tumors of the mouth and jaw, thumb sucking, tongue thrusting, pacifier use beyond age three, and prolonged use of a bottle have also been identified.Lack of masticatory stress during development can cause tooth overcrowding. Children who chewed a hard resinous gum for two hours a day, showed increased facial growth. Experiments in animals have shown similar results. In an experiment on two groups of rock hyraxes fed hardened or softened versions of the same foods, the animals fed softer food had significantly narrower and shorter faces and thinner and shorter mandibles than animals fed hard food.A 2016 review found that breastfeeding lowers the incidence of malocclusions developing later on in developing infants.During the transition to agriculture, the shape of the human mandible went through a series of changes. The mandible underwent a complex shape changes not matched by the teeth, leading to incongruity between the dental and mandibular form. These changes in human skulls may have been "driven by the decreasing bite forces required to chew the processed foods eaten once humans switched to growing different types of cereals, milking and herding animals about 10,000 years ago."
Treatment
Orthodontic management of the condition includes dental braces, lingual braces, clear aligners or palatal expanders. Other treatments include the removal of one or more teeth and the repair of injured teeth. In some cases, surgery may be necessary.
Treatment
Malocclusion is often treated with orthodontics, such as tooth extraction, clear aligners, or dental braces, followed by growth modification in children or jaw surgery (orthognathic surgery) in adults. Surgical intervention is used only in rare occasions. This may include surgical reshaping to lengthen or shorten the jaw. Wires, plates, or screws may be used to secure the jaw bone, in a manner like the surgical stabilization of jaw fractures. Very few people have "perfect" alignment of their teeth with most problems being minor that do not require treatment.
Crowding
Crowding of the teeth is treated with orthodontics, often with tooth extraction, clear aligners, or dental braces, followed by growth modification in children or jaw surgery (orthognathic surgery) in adults. Surgery may be required on rare occasions. This may include surgical reshaping to lengthen or shorten the jaw (orthognathic surgery). Wires, plates, or screws may be used to secure the jaw bone, in a manner similar to the surgical stabilization of jaw fractures. Very few people have "perfect" alignment of their teeth. However, most problems are very minor and do not require treatment.
Class I
While treatment is not crucial in class I malocclusions, in severe cases of crowding can be an indication for intervention. Studies indicate that tooth extraction can have benefits to correcting malocclusion in individuals. Further research is needed as reoccurring crowding has been examined in other clinical trials.
Class II
A few treatment options for class II malocclusions include:
Functional appliance which maintains the mandible in a postured position to influence both the orofacial musculature and dentoalveolar development prior to fixed appliance therapy. This is ideally done through pubertal growth in pre-adolescent children and the fixed appliance during permanent dentition . Different types of removable appliances include Activator, Bionatar, Medium opening activator, Herbst, Frankel and twin block appliance with the twin block being the most widely used one.
Growth modification through headgear to redirect maxillary growth
Orthodontic camouflage so that jaw discrepancy no longer apparent
Orthognathic surgery – sagittal split osteotomy mandibular advancement carried out when growth is complete where skeletal discrepancy is severe in anterior-posterior relationship or in vertical direction. Fixed appliance is required before, during and after surgery.
Upper Removable Appliance – limited role in contemporary treatment of increased overjets. Mostly used for very mild Class II, overjet due to incisor proclination, favourable overbite.
Class II Division 1
Low- to moderate- quality evidence suggests that providing early orthodontic treatment for children with prominent upper front teeth (class II division 1) is more effective for reducing the incidence of incisal trauma than providing one course of orthodontic treatment in adolescence. There do not appear to be any other advantages of providing early treatment when compared to late treatment. Low-quality evidence suggests that, compared to no treatment, late treatment in adolescence with functional appliances is effective for reducing the prominence of upper front teeth.
Class II Division 2
Treatment can be undertaken using orthodontic treatments using dental braces. While treatment is carried out, there is no evidence from clinical trials to recommend or discourage any type of orthodontic treatment in children. A 2018 Cochrane systematic review anticipated that the evidence base supporting treatment approaches is not likely to improve occlusion due to the low prevalence of the condition and the ethical difficulties in recruiting people to participate in a randomized controlled trials for treating this condition.
Class III
The British Standard Institute (BSI) classify class III incisor relationship as the lower incisor edge lies anterior to the cingulum plateau of the upper incisors, with reduced or reversed over jet. The skeletal facial deformity is characterized by mandibular prognathism, maxillary retrognathism or a combination of the two. This effects 3-8% of UK population with a higher incidence seen in Asia.One of the main reasons for correcting Class III malocclusion is aesthetics and function. This can have a psychological impact on the person with malocclusion resulting in speech and mastication problems as well. In mild class III cases, the patient is quite accepting of the aesthetics and the situation is monitored to observe the progression of skeletal growth.Maxillary and mandibular skeletal changes during prepubertal, pubertal and post pubertal stages show that class III malocclusion is established before the prepubertal stage. One treatment option is the use of growth modification appliances such as the Chin Cap which has greatly improved the skeletal framework in the initial stages. However, majority of cases are shown to relapse into inherited class III malocclusion during the pubertal growth stage and when the appliance is removed after treatment.Another approach is to carry out orthognathic surgery, such as a bilateral sagittal split osteotomy (BSSO) which is indicated by horizontal mandibular excess. This involves surgically cutting through the mandible and moving the fragment forward or backwards for desired function and is supplemented with pre and post surgical orthodontics to ensure correct tooth relationship. Although the most common surgery of the mandible, it comes with several complications including: bleeding from inferior alveolar artery, unfavorable splits, condylar resorption, avascular necrosis and worsening of temporomandibular joint.Orthodontic camouflage can also be used in patients with mild skeletal discrepancies. This is a less invasive approach that uses orthodontic brackets to correct malocclusion and try to hide the skeletal discrepancy. Due to limitations of orthodontics, this option is more viable for patients who are not as concerned about the aesthetics of their facial appearance and are happy to address the malocclusion only, as well as avoiding the risks which come with orthognathic surgery.
Deep bite
The most common corrective treatments available are fixed or removal appliances (such as dental braces), which may or may not require surgical intervention. At this time there is no robust evidence that treatment will be successful.
Open bite
An open bite malocclusion is when the upper teeth dont overlap the lower teeth. When this malocclusion occurs at the front teeth it is known as anterior open bite. An open bite is difficult to treat due to multifactorial causes, with relapse being a major concern. This is particularly so for an anterior open bite. Therefore, it is important to carry out a thorough initial assessment in order to obtain a diagnosis to tailor a suitable treatment plan. It is important to take into consideration any habitual risk factors, as this is crucial for a successful outcome without relapse. Treatment approach includes behavior changes, appliances and surgery. Treatment for adults include a combination of extractions, fixed appliances, intermaxillary elastics and orthognathic surgery. For children, orthodontics is usually used to compensate for continued growth. With children with mixed dentition, the malocclusion may resolve on its own as the permanent teeth erupt. Furthermore, should the malocclusion be caused by childhood habits such as digit, thumb or pacifier sucking, it may result in resolution as the habit is stopped. Habit deterrent appliances may be used to help in breaking digit and thumb sucking habits. Other treatment options for patients who are still growing include functional appliances and headgear appliances.
Tooth size discrepancy
Identifying the presence of tooth size discrepancies between the maxillary and mandibular arches is an important component of correct orthodontic diagnosis and treatment planning.
To establish appropriate alignment and occlusion, the size of upper and lower front teeth, or upper and lower teeth in general, needs to be proportional. Inter-arch tooth size discrepancy (ITSD) is defined as a disproportion in the mesio-distal dimensions of teeth of opposing dental arches. The prevalence is clinically significant among orthodontic patients and has been reported to range from 17% to 30%.Identifying inter-arch tooth size discrepancy (ITSD) before treatment begins allows the practitioner to develop the treatment plan in a way that will take ITSD into account. ITSD corrective treatment may entail demanding reduction (interproximal wear), increase (crowns and resins), or elimination (extractions) of dental mass prior to treatment finalization.Several methods have been used to determine ITSD. Of these methods the one most commonly used is the Bolton analysis. Bolton developed a method to calculate the ratio between the mesiodistal width of maxillary and mandibular teeth and stated that a correct and harmonious occlusion is possible only with adequate proportionality of tooth sizes. Boltons formula concludes that if in the anterior portion the ratio is less than 77.2% the lower teeth are too narrow, the upper teeth are too wide or there is a combination of both. If the ratio is higher than 77.2% either the lower teeth are too wide, the upper teeth are too narrow or there is a combination of both.
Other conditions
Other kinds of malocclusions can be due to or horizontal, vertical, or transverse skeletal discrepancies, including skeletal asymmetries.
Increased vertical growth causes a long facial profile and commonly leads to an open bite malocclusion, while decreased vertical facial growth causes a short facial profile and is commonly associated with a deep bite malocclusion. However, there are many other more common causes for open bites (such as tongue thrusting and thumb sucking) and likewise for deep bites.The upper or lower jaw can be overgrown (macrognathia) or undergrown (micrognathia). It has been reported that patients with micrognathia are also affected by retrognathia (abnormal posterior positioning of the mandible or maxilla relative to the facial structure). These patients are majorly predisposed to a class II malocclusion. Mandibular macrognathia results in prognathism and predisposes patients to a class III malocclusion.Most malocclusion studies to date have focused on Class III malocclusions. Genetic studies for Class II and Class I malocclusion are more rare. An example of hereditary mandibular prognathism can be seen amongst the Hapsburg Royal family where one third of the affected individuals with severe class III malocclusion had one parent with a similar phenotype The frequent presentation of dental malocclusions in patients with craniofacial birth defects also supports a strong genetic aetiology. About 150 genes are associated with craniofacial conditions presenting with malocclusions. Micrognathia is a commonly recurring craniofacial birth defect appearing among multiple syndromes.
For patients with severe malocclusions, corrective jaw surgery or orthognathic surgery may be carried out as a part of overall treatment, which can be seen in about 5% of the general population.
See also
Crossbite
Elastics
Facemask (orthodontics)
Maximum intercuspation
Mouth breathing
Occlusion (dentistry)
References
Further reading
Peter S. Ungar, "The Trouble with Teeth: Our teeth are crowded, crooked and riddled with cavities. It hasnt always been this way", Scientific American, vol. 322, no. 4 (April 2020), pp. 44–49. "Our teeth [...] evolved over hundreds of millions of years to be incredibly strong and to align precisely for efficient chewing. [...] Our dental disorders largely stem from a shift in the oral environment caused by the introduction of softer, more sugary foods than the ones our ancestors typically ate."
== External links == |
Onychogryphosis | Onychogryphosis is a hypertrophy that may produce nails resembling claws or a rams horn.
Causes
Onychogryphosis may be caused by trauma or peripheral vascular disease, but most often secondary to self-neglect and failure to cut the nails for extended periods of time.: 783–4 This condition is most commonly seen in the elderly.
Diagnosis
Treatment
Some recommend avulsion of the nail plate with surgical destruction of the nail matrix with phenol or the carbon dioxide laser, if the blood supply is adequate.: 783–4 : 659
Epidemiology
Severe congenital onychogryphosis affecting all twenty nailbeds has been recorded in two families who exhibit the dominant allele for a certain gene. Congenital onychogryphosis of the fifth toe (the baby, little, pinky or small toe) is fairly common, but asymptomatic and seldom brought to the attention of medical professionals. Rather, it is brought to the attention of manicurists who routinely file the clawed toenail flat.
See also
List of cutaneous conditions
References
== External links == |
Laryngitis | Laryngitis is inflammation of the larynx (voice box). Symptoms often include a hoarse voice and may include fever, cough, pain in the front of the neck, and trouble swallowing. Typically, these last under two weeks.Laryngitis is categorised as acute if it lasts less than three weeks and chronic if symptoms last more than three weeks. Acute cases usually occur as part of a viral upper respiratory tract infection, other infections and trauma such as from coughing are other causes. Chronic cases may occur due to smoking, tuberculosis, allergies, acid reflux, rheumatoid arthritis, or sarcoidosis. The underlying mechanism involves irritation of the vocal cords.Concerning signs that may require further investigation include stridor, history of radiation therapy to the neck, trouble swallowing, duration of more than three weeks, and a history of smoking. If concerning signs are present the vocal cords should be examined via laryngoscopy. Other conditions that can produce similar symptoms include epiglottitis, croup, inhaling a foreign body, and laryngeal cancer.The acute form generally resolves without specific treatment. Resting the voice and sufficient fluids may help. Antibiotics generally do not appear to be useful in the acute form. The acute form is common while the chronic form is not. The chronic form occurs most often in middle age and is more common in men than women.
Signs and symptoms
The primary symptom of laryngitis is a hoarse voice.: 108 Because laryngitis can have various causes, other signs and symptoms may vary. They can include
Dry or sore throat
Coughing (both a causal factor and a symptom of laryngitis)
Frequent throat clearing
Increased saliva production
Dysphagia (difficulty swallowing)
Sensation of swelling in the area of the larynx (discomfort in the front of the neck)
Globus pharyngeus (feeling like there is a lump in the throat)
Cold or flu-like symptoms (which, like a cough, may also be a causal factor for laryngitis)
Swollen lymph nodes in the throat, chest, or face
Fever
General muscle pain (myalgia)
Shortness of breath, predominantly in children
Voice quality
Aside from a hoarse-sounding voice, changes to pitch and volume may occur with laryngitis. Speakers may experience a lower or higher pitch than normal, depending on whether their vocal folds are swollen or stiff. They may also have breathier voices, as more air flows through the space between the vocal folds (the glottis), quieter volume and a reduced range.
Causes
Laryngitis can be infectious as well as noninfectious in origin. The resulting inflammation of the vocal folds results in a distortion of the sound produced there. It normally develops in response to either an infection, trauma to the vocal folds, or allergies. Chronic laryngitis may also be caused by more severe problems, such as nerve damage, sores, polyps, or hard and thick lumps (nodules) on the vocal cords.[4]
Acute
Viral
Most acute cases of laryngitis are caused by viral infections, the most common of which tend to be rhinovirus, influenza virus, parainfluenza virus, adenovirus, coronavirus, and RSV. In patients who have a compromised immune system, other viruses such as herpes, HIV may also be potential causes.
Bacterial
This is another major cause of acute laryngitis, and may develop in conjunction with or due to a viral infection. Common bacterial strains are group A streptococcus, Streptococcus pneumoniae, C. diphtheriae, M. catarrhalis, Haemophilus influenzae, Bordetella pertussis, Bacillus anthracis, and M. tuberculosis. In developing countries, more unusual bacterial causes may occur, such as mycobacterial and syphilitic, though these may occur in developed nations as well.
Fungal
Laryngitis caused by fungal infection is common but not frequently diagnosed according to a review by BMJ and can account for up to 10% of acute laryngitis cases. Patients with both functioning and impaired immune systems can develop fungal laryngitis, which may develop as a result of recent antibiotic or inhaled corticosteroids use. Certain strains of fungi that may cause laryngitis include; Histoplasma, Blastomyces, Candida (especially in immunocompromised persons), and Cryptococcus and Coccidioides.
Trauma
Often due to excessive use of the vocal folds such as excessive yelling, screaming, or singing. Though this often results in damage to the outer layers of the vocal folds, the subsequent healing may lead to changes in the physiology of the folds. Another potential cause of inflammation may be overuse of the vocal cords.[5] [6] [7] [8] [9] Laryngeal trauma, including iatrogenic (caused by endotracheal intubation), can also result in inflammation of the vocal cords.
Chronic
Allergies
Findings are unclear as to whether asthma may cause symptoms commonly associated with laryngitis. Some researchers have posited that allergic causes of laryngitis are often misdiagnosed as being the result of acid reflux.
Reflux
One possible explanation of chronic laryngitis is that inflammation is caused by gastro-oesophageal reflux, which causes subsequent irritation of the vocal folds.
Autoimmune disorders
Approximately between 30 and 75% of persons with rheumatoid arthritis report symptoms of laryngitis.
Symptoms of laryngitis are present in only 0.5–5% of people that have sarcoidosis. According to a meta-analysis by Silva et al. (2007), this disease is often an uncommon cause of laryngeal symptoms and is frequently misdiagnosed as another voice disorder.
Diagnosis
Diagnosis of different forms of acute laryngitis
Laryngitis following trauma: This form of laryngitis is usually identified by obtaining a case history providing information on previous phono traumatic experiences, internal trauma caused by recent procedures as well as any previous neck injuries.
Acute viral laryngitis: This form of laryngitis is characterized by lower vocal pitch as well as hoarseness. The symptoms in this form of laryngitis are usually present for less than one week, however they can persist for 3–4 weeks. This form of laryngitis might also be accompanied by upper respiratory tract symptoms such as: sore throat, odynophagia, rhinorrhea, dyspnea, postnasal discharge, and congestion.
Fungal laryngitis: A biopsy and culture of abnormal lesion may help confirm fungal laryngitis.
Visual diagnosis
The larynx itself will often show erythema (reddening) and edema (swelling). This can be seen with laryngoscopy or stroboscopy (method depends on the type of laryngitis).: 108 Stroboscopy may be relatively normal or may reveal asymmetry, aperiodicity, and reduced mucosal wave patterns.Other features of the laryngeal tissues may include
Redness of the laryngeal tissues (acute)
Dilated blood vessels (acute)
Thick, yet dry laryngal tissue (chronic)
Stiff vocal folds
Sticky secretions between the vocal folds and nearby structures (the interarytenoid region)
Referral
Some signs and symptoms indicate the need for early referral. These include
Difficulty swallowing
Vocal stridor
Ear pain
Recent weight loss
History of smoking
Current or recent radiotherapy treatment (in the neck region)
Recent neck surgery or surgery involving endotracheal tubing
Person is a professional voice user (teacher, singer, actor, call center worker, and so on)
Differential diagnosis
Acute epiglottitis: This is more likely in those with stridor, drooling, and painful or trouble swallowing.
Spasmodic dysphonia
Reflux laryngitis
Chronic allergic laryngitis
Neoplasm
Croup: This presents with a barking cough, hoarseness of voice, and inspiratory stridor.
Treatment
Treatment is often supportive in nature, and depends on the severity and type of laryngitis (acute or chronic). General measures to relieve symptoms of laryngitis include behaviour modification, hydration and humidification.Vocal hygiene (care of the voice) is very important to relieve symptoms of laryngitis. Vocal hygiene involves measures such as: resting the voice, drinking sufficient water, reducing caffeine and alcohol intake, stopping smoking and limiting throat clearing.
Acute laryngitis
In general, acute laryngitis treatment involves vocal hygiene, painkillers (analgesics), humidification, and antibiotics.
Viral
The suggested treatment for viral laryngitis involves vocal rest, pain medication, and mucolytics for frequent coughing. Home remedies such as tea and honey may also be helpful. Antibiotics are not used for treatment of viral laryngitis.
Bacterial
Antibiotics may be prescribed for bacterial laryngitis, especially when symptoms of upper respiratory infection are present. However, the use of antibiotics is highly debated for acute laryngitis. This relates to issues of effectiveness, side effects, cost, and possibility of antibiotic resistance patterns. Overall, antibiotics do not appear to be very effective in the treatment of acute laryngitis.In severe cases of bacterial laryngitis, such as supraglottitis or epiglottitis, there is a higher risk of the airway becoming blocked. An urgent referral should be made to manage the airway. Treatment may involve humidification, corticosteroids, intravenous antibiotics, and nebulised adrenaline.
Fungal
Fungal laryngitis can be treated with oral antifungal tablets and antifungal solutions. These are typically used for up to three weeks and treatment may need to be repeated if the fungal infection returns.
Trauma
Laryngitis caused by excessive use or misuse of the voice can be managed though vocal hygiene measures.
Chronic laryngitis
Reflux
Laryngopharyngeal reflux treatment primarily involves behavioural management and medication. Behavioural management involves aspects such as
Wearing loose clothing
Eating smaller, more frequent meals
Avoiding certain foods (e.g. caffeine, alcohol, spicy foods)Anti-reflux medications may be prescribed for patients with signs of chronic laryngitis and hoarse voice. If anti-reflux treatment does not result in a decrease of symptoms, other possible causes should be examined. Over-the-counter medications for neutralizing acids (antacids) and acid suppressants (H-2 blockers) may be used. Antacids are often short-acting and may not be sufficient for treatment. Proton pump inhibitors are an effective type of medication. These should only be prescribed for a set period of time, after which the symptoms should be reviewed. Proton pump inhibitors do not work for everyone. A physical reflux barrier (e.g. Gaviscon Liquid) may be more appropriate for some. Antisecretory medications can have several side-effects.When appropriate, anti-reflux surgery may benefit some individuals.
Inflammatory
When treating allergic laryngitis, topical nasal steroids and immunotherapy have been found to be effective for allergic rhinitis. Antihistamines may also be helpful, but can create a dryness in the larynx. Inhaled steroids that are used for a long period can lead to problems with the larynx and voice.
Autoimmune
Mucous membrane pemphigoid may be managed with medication (cyclophosphamide and prednisolone).
Granulomatous
Sarcoidosis is typically treated with systemic corticosteroids. Less frequently used treatments include intralesional injections or laser resection.
Prognosis
Acute
Acute laryngitis may persist, but will typically resolve on its own within two weeks. Recovery is likely to be quick if the patient follows the treatment plan. In viral laryngitis, symptoms can persist for an extended period, even when upper respiratory tract inflammation has been resolved.
Chronic
Laryngitis that continues for more than three weeks is considered chronic. If laryngeal symptoms last for more than three weeks, a referral should be made for further examination, including direct laryngoscopy. The prognosis for chronic laryngitis varies depending on the cause of the laryngitis.
References
External links
Laryngitis at Curlie
Mayo Clinic |
Onychomatricoma | Onychomatricoma is a cutaneous condition characterized by a distinctive tumor of the nail matrix.This nail disease can mimic many nail problems and should be examined and biopsied by a dermatologist. In particular, a main concern is the malignant and destructive potential that may exist.
See also
Nail anatomy
List of cutaneous conditions
Nail disease
== References == |
Hemicrania continua | Hemicrania continua (HC) is a persistent unilateral headache that responds to indomethacin. It is usually unremitting, but rare cases of remission have been documented. Hemicrania continua is considered a primary headache disorder, meaning that it is not caused by another condition.
Symptoms
In hemicrania continua, basal pain is a dull aching pressure similar to that of TTHs that occurs nearly always on the same side of the head and face. Pain ranges from mild to severe and is characterized by fluctuations where it increases in intensity up to three to five times per 24-hour cycle. The range of duration of exacerbations has no boundaries and varies from a few seconds to up to two weeks. While attacks tend to be more frequent at night, no circadian periodicity such as in cluster headache can be observed.
The nature of pain changes during the exacerbation phase, becoming more piercing, throbbing, and intense, generally paired with other highly debilitating symptoms such as nausea, vomiting, dizziness, and sensitivity to light and sounds. During these exacerbation phases, hemicrania continua may mimic other primary and secondary headache disorders, with up to 70% of patients fulfilling the diagnostic criteria for migraine. Physical exertion,changes in sleep patterns, stress, or alcohol consumption can make the headache pain more severe in some patients.In addition to persistent daily headache of HC, which is usually mild to moderate (and frequently severe), HC can present other symptoms. These additional symptoms of HC can be divided into three main categories:
Autonomic symptoms:
conjunctival injection
tearing
rhinorrhea
nasal stuffiness
eyelid edema
forehead sweating
Stabbing headaches:
Short, "jabbing" headaches superimposed over the persistent daily headache.
Usually lasting less than one minute.
Migrainous features:
throbbing pain
nausea and/or vomiting
phonophobia
photophobia
Cause
The cause of hemicrania continua is unknown.
Diagnosis
The following diagnostic criteria are given for hemicrania continua:
Headache for more than 3 months fulfilling other 3 criteria:
All of the following characteristics:
Unilateral pain without side-shift
Daily and continuous, without pain-free periods
Moderate intensity, but with exacerbations of severe pain
At least one of the following autonomic features occurs during exacerbations and ipsilateral to the side of pain:
Conjunctival injection and/or lacrimation
Nasal congestion and/or rhinorrhea
Ptosis and/or miosis
Complete response to therapeutic doses of indomethacin, although cases of hemicrania continua that do not resolve with indomethacin treatment have been documented.A variant on hemicrania continua has also been described, in which the attacks may shift sides, although meeting the above criteria in all other respects.There is no definitive diagnostic test for hemicrania continua. Diagnostic tests such as imaging studies may be ordered to rule out other causes for the headache. When the symptoms of hemicrania continua are present, its considered "diagnostic" if they respond completely to indomethacin. The efficacy of indomethacin may not be long term for all patients, as can eventually become ineffective.
Differential diagnosis
The factor that allows hemicrania continua and its exacerbations to be differentiated from migraine and cluster headache is that hemicrania continua is characterized by complete response to therapeutic doses (25–300 mg) of indomethacin. The positive response to this drug is, in fact, a fundamental sine qua non criterion used in differential diagnosis. Triptans and other abortive medications do not affect hemicrania continua.
Classification
The International Headache Societys International Classification of Headache Disorders classifies hemicrania continua as a primary headache disorder.
Treatment
Hemicrania continua generally responds only to indomethacin 25–300 mg daily, which must be continued long term. Unfortunately, gastrointestinal side effects are a common problem with indomethacin, which may require additional acid-suppression therapy to control.In patients who are unable to tolerate indomethacin, the use of celecoxib 400–800 mg per day (Celebrex) and rofecoxib 50 mg per day (Vioxx - no longer available) have both been shown to be effective and are likely to be associated with fewer GI side effects. There have also been reports of two patients who were successfully managed with topiramate 100–200 mg per day (Topamax) although side effects with this treatment can also prove problematic.Greater occipital nerve (GON) block comprising 40 mg Depomedrone and 10 mls of 1% Lignocaine injected into the affected nerve is effective, up to a period of approximately three months. Changing the cocktail to include (for example) 10 mls of .5% Marcaine and changing to 2% Lignocaine, whilst in theory should increase the longevity, renders the injection completely ineffective. See 4.2 Posology and method of administration (flocculation).Occipital nerve stimulation may be highly effective when other treatments fail to relieve the intractable pain.
Epidemiology
Hemicrania was mentioned in 1881 in The Therapeutic Gazette Vol. 2, by G.S.Davis, and the incident has been cited in Kings American Dispensatory (1898 and later editions) in the description of the strong analgesic Jamaican Dogwood, a relatively low dose of which reportedly produced convulsions and prolonged respiratory depression over six hours in an elderly woman with this condition.In newer times, Hemicrania continua was described in 1981; at that time around 130 cases were described in the literature. However, rising awareness of the condition has led to increasingly frequent diagnosis in headache clinics, and it seems that it is not as rare as these figures would imply. The condition occurs more often in women than men and tends to present first in adulthood, although it has also been reported in children as young as 5 years old.
References
== External links == |
Lipodystrophy | Lipodystrophy syndromes are a group of genetic or acquired disorders in which the body is unable to produce and maintain healthy fat tissue. The medical condition is characterized by abnormal or degenerative conditions of the bodys adipose tissue. A more specific term, lipoatrophy ("lipo" is Greek for "fat", and "dystrophy" is Greek for "abnormal or degenerative condition"), is used when describing the loss of fat from one area (usually the face). This condition is also characterized by a lack of circulating leptin which may lead to osteosclerosis. The absence of fat tissue is associated with insulin resistance, hypertriglyceridemia, non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome.
Types
Lipodystrophy can be divided into the following types:: 495–7
Congenital lipodystrophy syndromes
Congenital generalized lipodystrophy (Berardinelli-Seip syndrome)
Familial partial lipodystrophy
Marfanoid–progeroid–lipodystrophy syndrome
Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome
Acquired lipodystrophy syndromes
Acquired partial lipodystrophy (Barraquer-Simons syndrome)
Acquired generalized lipodystrophy
Centrifugal abdominal lipodystrophy (Lipodystrophia centrifugalis abdominalis infantilis)
Lipoatrophia annularis (Ferreira-Marques lipoatrophia)
Localized lipodystrophy
HIV-associated lipodystrophy
Epidemiology
Congenital lipodystrophy (due to inherited genetic defect) is estimated to be extremely rare, possibly affecting only one per million persons. Acquired lipodystrophy is much more common, especially affecting persons with HIV infection.
Pathogenesis
Due to an insufficient capacity of subcutaneous adipose tissue to store fat, fat is deposited in non-adipose tissue (lipotoxicity), leading to insulin resistance. Patients display hypertriglyceridemia, severe fatty liver disease and little or no adipose tissue. Average patient lifespan is approximately 30 years before death, with liver failure being the usual cause of death. In contrast to the high levels seen in non-alcoholic fatty liver disease associated with obesity, leptin levels are very low in lipodystropy.
Insulin injections
A lipodystrophy can be a lump or small dent in the skin that forms when a person performs injections repeatedly in the same spot. These types of lipodystrophies are harmless and can be avoided by changing (rotating) the locations of injections. For those with diabetes, using purified insulins may also help.
One of the side-effects of lipodystrophy is the rejection of the injected medication, the slowing down of the absorption of the medication, or trauma that can cause bleeding that, in turn, will reject the medication. In any of these scenarios, the dosage of the medication, such as insulin for diabetics, becomes impossible to gauge correctly and the treatment of the disease for which the medication is administered is impaired, thereby allowing the medical condition to worsen.
In some cases, rotation of the injection sites may not be enough to prevent lipodystrophy.
Antiretroviral drugs
Lipodystrophy can be a possible side effect of antiretroviral drugs. Other lipodystrophies manifest as lipid redistribution, with excess, or lack of, fat in various regions of the body. These include, but are not limited to, having sunken cheeks and/or "humps" on the back or back of the neck (also referred to as buffalo hump) which also exhibits due to excess cortisol. Lipoatrophy is most commonly seen in patients treated with thymidine analogue nucleoside reverse transcriptase inhibitors like zidovudine (AZT) and stavudine (d4T).
Diagnosis
The diagnosis is a clinical diagnosis, established by an experienced endocrinologist. A genetic confirmation may be possible depending on the subtype. In up to ~40% of partial lipodystrophy patients, a causative gene has not been identified. Using a skinfold caliper to measure skinfold thickness in various parts of the body may or a total body composition scan using Dual-energy X-ray Absorptiometry may help identify the subtype. Dual-energy X-ray Absorptiometry may be useful by providing both regional %fat measurements, and direct visualization of fat distribution by means of a "fat shadow".
Treatment
Leptin replacement therapy with human recombinant leptin metreleptin has been shown to be an effective therapy to alleviate the metabolic complications associated with lipodystrophy, and has been approved by the FDA for the treatment of generalized lipodystrophy syndromes. In Europe based on EMA, metreleptin should be used in addition to diet to treat lipodystrophy, where patients have loss of fatty tissue under the skin and build-up of fat elsewhere in the body such as in the liver and muscles. The medicine is used in: adults and children above the age of two years with generalised lipodystrophy (Berardinelli-Seip syndrome and Lawrence syndrome) and in adults and children above the age of 12 years with partial lipodystrophy (including Barraquer-Simons syndrome), when standard treatments have failed.Volanesorsen is an Apo-CIII inhibitor that is currently being investigated as a potential therapeutic to reduce hypertriglycerides in Familial Partial Lipodystrophy patients in the BROADEN study.
Society and culture
Lipodystrophy United is an American organization founded and run by lipodystrophy patients to support each other and raise awareness about lipodystrophy syndromes.Lipodystrophy UK is a dedicated UK charity set up to support people affected by Lipodystrophy.March 31 is observed as the World Lipodystrophy Day.
See also
Keppen–Lubinsky syndrome
Lipoedema
References
== External links == |
Superficial vein thrombosis | Superficial vein thrombosis (SVT) is a blood clot formed in a superficial vein, a vein near the surface of the body. Usually there is thrombophlebitis, which is an inflammatory reaction around a thrombosed vein, presenting as a painful induration (thickening of the skin) with redness. SVT itself has limited significance (in terms of direct morbidity and mortality) when compared to a deep vein thrombosis (DVT), which occurs deeper in the body at the deep venous system level. However, SVT can lead to serious complications (as well as signal other serious problems, such as genetic mutations that increase ones risk for clotting), and is therefore no longer regarded as a benign condition. If the blood clot is too near the saphenofemoral junction there is a higher risk of pulmonary embolism, a potentially life-threatening complication.
SVT has risk factors similar to those for other thrombotic conditions and can arise from a variety of causes. Diagnosis is often based on symptoms. There are multiple possible treatments, with the goal of providing symptomatic relief and preventing complications.
Signs and symptoms
SVT is recognized by the presence of pain, warmth, redness, and tenderness over a superficial vein. The SVT may present as a "cord-like" structure upon palpation. The affected vein may be hard along its entire length. SVTs tend to involve the legs, though they can affect any superficial vein (e.g. those in the arms).
Complications
SVT in the lower extremities can lead to a dangerous complication in which the clot travels to the lungs, called pulmonary embolism (PE). This is because lower limb SVTs can migrate from superficial veins into deeper veins. In a French population, the percent of people with SVTs that also suffered from PEs was 4.7%. In the same population, deep vein thrombosis (DVT) was found in 24.6% of people with SVTs. However, because superficial veins lack muscular support, any clots that form are far less likely to be squeezed by muscle contraction, dislodged, and induce a PE.SVTs can recur after they resolve, which is termed "migratory thrombophlebitis." Migratory thrombophlebitis is a complication that may be due to more serious disorders, such as cancer and other hypercoagulable states.
Causes
SVTs of the legs are often due to varicose veins, though most people with varicose veins do not develop SVTs. SVTs of the arms are often due to the placement of intravenous catheters.Many of the risk factors that are associated with SVT are also associated with other thrombotic conditions (e.g. DVT). These risk factors include age, cancer, history of thromboembolism, pregnancy, use of oral contraceptive medications (containing estrogen), hormone replacement therapy, recent surgery, and certain autoimmune diseases (especially Behçets and Buergers diseases). Other risk factors include immobilization (stasis) and laparoscopy.Hypercoagulable states due to genetic conditions that increase the risk of clotting may contribute to the development of SVT, such as factor V Leiden, prothrombin 20210A mutation, and protein C, S, and antithrombin III and factor XII deficiency.
Mechanism
The mechanism for the development of an SVT depends upon the specific etiology of the SVT. For example, varicose veins and prolonged bed rest both may induce SVTs due to slowing the flow of blood through superficial veins.
Diagnosis
SVTs may be diagnosed based upon clinical criteria by a healthcare professional. A more specific evaluation can be made by ultrasound. An ultrasound can be useful in situations in which an SVT occurs above the knee and is not associated with a varicose vein, because ultrasounds can detect more serious clots like DVTs. The diagnostic utility of D-dimer testing in the setting of SVTs has yet to be fully established.
Classification
SVTs can be classified as either varicose vein (VV) or non-varicose (NV) associated. NV-SVTs are more likely to be associated with genetic procoagulable states compared to VV-SVTs. SVTs can also be classified by pathophysiology. That is, primary SVTs are characterized by inflammation that is localized to the veins. Secondary SVTs are characterized by systemic inflammatory processes.A subclass of SVTs are septic thrombophlebitis, which are SVTs that occur in the setting of an infection.
Treatment
The goal of treatment in SVT is to reduce local inflammation and prevent the SVT from extending from its point of origin. Treatment may entail the use of compression, physical activity, medications, or surgical interventions. The optimal treatment for many SVT sites (i.e. upper limbs, neck, abdominal and thoracic walls, and the penis) has not been determined.
Compression
Multiple compression bandages exist. Fixed compression bandages, adhesive short stretch bandages, and graduated elastic compression stockings have all be used in the treatment of SVTs. The benefit of compression stockings is unclear, though they are frequently used.
Physical activity
Inactivity is contraindicated in the aftermath of an SVT. Uninterrupted periods of sitting or standing may cause the SVT to elongate from its point of origin, increasing the risk for complications and clinical worsening.
Medications
Medications used for the treatment of SVT include anticoagulants, NSAIDs (except aspirin), antibiotics, and corticosteroids.
Anticoagulants
SVTs that occur within the great saphenous vein within 3 cm of the saphenofemoral junction are considered to be equivalent in risk to DVTs. These high risk SVTs are treated identically with therapeutic anticoagulation. Anticoagulation is also used for intermediate risk SVTs that are greater than 3 cm from the saphenofemoral junction or are greater than 4–5 cm in length.Anticoagulation for high risk SVTs includes the use of vitamin K antagonists or novel oral anticoagulants (NOACs) for 3 months. Anticoagulation for intermediate risk SVTs includes fondaparinux 2.5 mg daily for 45 days or the use of intermediate to therapeutic dose low molecular weight heparin for 4–6 weeks.
NSAIDs
NSAIDs (non-steroidal anti-inflammatory drugs) can be used in both oral or topical formulations for the relief of SVT symptoms. The British Committee for Standards in Haematology guidelines recommend the use of NSAIDs for low-risk SVTs (thrombus <4–5 cm in length, no additional risk factors for thromboembolic events). NSAIDs are used for treatment durations of 8–12 days.
Other
Antibiotics are used in the treatment of septic SVT. Corticosteroids are used for the treatment of SVTs in the setting of vasculitic and autoimmune syndromes.
Surgery
Surgical interventions are used for both symptomatic relief of the SVT as well as for preventing the development of more serious complications (e.g. pulmonary embolism). Surgical interventions include ligation of the saphenofemoral junction, ligation and stripping of the affected veins, and local thrombectomy. Because of the risk of symptomatic pulmonary embolism with surgery itself, surgical interventions are not recommended for the treatment of lower limb SVTs by the 2012 American College of Chest Physicians guidelines and the 2012 British Committee for Standards in Haematology guidelines. The use of surgery for the treatment of SVT is controversial.
Prognosis
SVT is often a mild, self-resolving medical condition. The inflammatory reaction may last up to 2–3 weeks, with possible recanalization of the thrombosed vein occurring in 6–8 weeks. The superficial vein may continue to be hyperpigmented for several months following the initial event.
Epidemiology
In a French population, SVT occurred in 0.64 per 1000 persons per year.
History
SVTs have been historically considered to be benign diseases, for which treatment was limited to conservative measures. However, an increased awareness of the potential risks of SVTs developing into more serious complications has prompted more research into the diagnosis, classification, and treatment of SVTs.
Research
A Cochrane review recommends that future research investigate the utility of oral, topical, and surgical treatments for preventing the progression of SVTs and the development of thromboembolic complications.
Footnotes
== References == |
Coalworkers pneumoconiosis | Coal workers pneumoconiosis (CWP), also known as black lung disease or black lung, is an occupational type of pneumoconiosis caused by long-term exposure to coal dust. It is common in coal miners and others who work with coal. It is similar to both silicosis from inhaling silica dust and asbestosis from inhaling asbestos dust. Inhaled coal dust progressively builds up in the lungs and leads to inflammation, fibrosis, and in worse cases, necrosis.
Coal workers pneumoconiosis, severe state, develops after the initial, milder form of the disease known as anthracosis (from the Greek άνθρακας, or anthracas —coal, carbon). This is often asymptomatic and is found to at least some extent in all urban dwellers due to air pollution. Prolonged exposure to large amounts of coal dust can result in more serious forms of the disease, simple coal workers pneumoconiosis and complicated coal workers pneumoconiosis (or progressive massive fibrosis, or PMF). More commonly, workers exposed to coal dust develop industrial bronchitis, clinically defined as chronic bronchitis (i.e. productive cough for 3 months per year for at least 2 years) associated with workplace dust exposure. The incidence of industrial bronchitis varies with age, job, exposure, and smoking. In nonsmokers (who are less prone to develop bronchitis than smokers), studies of coal miners have shown a 16% to 17% incidence of industrial bronchitis.
In 2013 CWP resulted in 25,000 deaths globally—down from 29,000 deaths in 1990. However, a later 2018 study by the National Institute of Occupational Safety and Health shows a resurgence, recording the highest rate of CWP in roughly two decades.
Pathogenesis
Coal dust is not as fibrogenic as silica dust. Coal dust that enters the lungs can neither be destroyed nor removed by the body. The particles are engulfed by resident alveolar or interstitial macrophages and remain in the lungs, residing in the connective tissue or pulmonary lymph nodes. Coal dust provides a sufficient stimulus for the macrophage to release various products, including enzymes, cytokines, oxygen radicals, and fibroblast growth factors, which are important in the inflammation and fibrosis of CWP. Aggregations of carbon-laden macrophages can be visualized under a microscope as granular, black areas. In serious cases, the lung may grossly appear black. These aggregations can cause inflammation and fibrosis, as well as the formation of nodular lesions within the lungs. The centers of dense lesions may become necrotic due to ischemia, leading to large cavities within the lung.
Appearance
Simple CWP is marked by the presence of 1–2 mm nodular aggregations of anthracotic macrophages, supported by a fine collagen network, within the lungs. Those 1–2 mm in diameter are known as coal macules, with larger aggregations known as coal nodules. These structures occur most frequently around the initial site of coal dust accumulation—the upper regions of the lungs around respiratory bronchioles. The coal macule is the basic pathological feature of CWP and has a surrounding area of enlargement of the airspace, known as focal emphysema. Focal emphysema extends into progressive centrilobular emphysema. Less commonly a variant of panacinar emphysema develops.Continued exposure to coal dust following the development of simple CWP may progress to complicated CWP with progressive massive fibrosis (PMF), wherein large masses of dense fibrosis develop, usually in the upper lung zones, measuring greater than 1 cm in diameter, with accompanying decreased lung function. These cases generally require a number of years to develop. Grossly, the lung itself appears blackened. Pathologically, these consist of fibrosis with haphazardly-arranged collagen and many pigment-laden macrophages and abundant free pigment. Radiographically, CWP can appear strikingly similar to silicosis. In simple CWP, small rounded nodules (see ILO Classification) predominate, tending to first appear in the upper lung zones. The nodules may coalesce and form large opacities (>1 cm), characterizing complicated CWP, or PMF.
Diagnosis
There are three basic criteria for the diagnosis of CWP:
Chest radiography consistent with CWP
An exposure history to coal dust (typically underground coal mining) of sufficient amount and latency
Exclusion of alternative diagnoses (mimics of CWP)Symptoms and pulmonary function testing relate to the degree of respiratory impairment but are not part of the diagnostic criteria. As noted above, the chest X-ray appearance for CWP can be virtually indistinguishable from silicosis. Chest CT, particularly high-resolution scanning (HRCT), are more sensitive than plain X-ray for detecting the small round opacities.
Treatment
There is no cure or discovered treatments for pneumoconiosis. Some patients are given oxygen to help with their breathing and are advised to stop smoking to prevent further decline in lung function. In the most extreme cases a lung transplant could be done to help prolong the patients life expectancy.
Prevention of pneumoconiosis
The main way to avoid contracting coal workers pneumoconiosis is to avoid the inhalation of coal dust. Some of the ways to prevent this disease include: not smoking, wearing ventilated masks when coming in contact with potentially dangerous airborne particles, regular pulmonary exams, and becoming educated about the risks of lung diseases in your work environment.
Epidemiology
In 2013 CWP resulted in 25,000 deaths down from 29,000 deaths in 1990. Between 1970 and 1974, prevalence of CWP among US coal miners who had worked over 25 years was 32%; the same group saw a prevalence of 9% in 2005–2006.
In Australia, CWP was considered to be eliminated in the 1970s due to strict hazard control measures. However, there has been a resurgence of CWP in Australia, with the first new cases being detected in May 2015. From 1999 to 2016, the average years of life lost due to CWP increased from 8.1 to 12.6 years, most likely due to the increased severity and progression of CWP.
History
Black lung is actually a set of conditions and until the 1950s its dangers were not well understood. The prevailing view was that silicosis was very serious but it was solely caused by silica and not coal dust. The miners union, the United Mine Workers of America, realized that rapid mechanization meant drills that produced much more dust, but under John L. Lewis they decided not to raise the black lung issue because it might impede the mechanization that was producing higher productivity and higher wages. Union priorities were to maintain the viability of the long-fought-for welfare and retirement fund, which would be sustained by higher outputs of coal. After the death of Lewis, the union dropped its opposition to calling black lung a disease and realized the financial advantages of a fund for its disabled members.
In the Federal Coal Mine Health and Safety Act of 1969, the US Congress set up standards to reduce dust and created the Black Lung Disability Trust. The mining companies agreed to a clause, by which a ten-year history of mine work, coupled with X-ray or autopsy evidence of severe lung damage, guaranteed compensation. Equally important was a "rate retention" clause that allowed workers with progressive lung disease to transfer to jobs with lower exposure without loss of pay, seniority, or benefits. Financed by a federal tax on coal, the Trust by 2009 had distributed over $44 billion in benefits to miners disabled by the disease and their widows. A miner who has spent 25 years in underground coal mines has a 5–10% risk of contracting the disease.
21st century
After the Federal Coal Mine Health and Safety Act of 1969 became law in the United States, the percentage of American miners with black lung disease decreased by about 90 percent. More recently, however, rates of the disease have been on the rise. The National Institute for Occupational Safety and Health (NIOSH) reported that close to 9 percent of miners with 25 years or more experience tested positive for black lung in 2005–2006, compared with 4 percent in the late 1990s.New findings have shown that CWP can be a risk for surface coal miners, who are 48% of the workforce. Data from the Coal Workers Health Surveillance Program of NIOSH, which examined chest X-rays from more than 2,000 miners in 16 US states from 2010 to 2011, showed that 2% of miners with greater than one year of surface mining experience developed CWP. 0.5% of these miners had PMF. Most of these workers had never worked in an underground mine prior to surface mining. A high proportion of the X-rays suggested that these miners had developed silicosis.
NIOSH, with support from the Mine Safety and Health Administration (MSHA), operates a Mobile Health Screening Program, which travels to mining regions around the United States. Miners who participate in the Program receive health evaluations once every five years, at no cost to themselves. Chest x-rays can detect the early signs of and changes in CWP, often before the miner is aware of any lung problems.A 2016-17 investigation by National Public Radio found that the National Institute for Occupational Safety and Health had under-reported cases of progressive massive fibrosis (a complication of black lung) by at least a factor of 20. NPR identified over 2,000 cases at certain clinics in Kentucky, Virginia, West Virginia, Pennsylvania, and Ohio, compared to 99 that NIOSH reported. NIOSH confirmed in 2018 the largest cluster of PMF ever scientifically documented, despite near-elimination of the disease in the 1990s. The causes of the spike are believed to include longer working shifts, mining of thinner coal seams (which causes mining machines to put more non-coal silica dust in the air), and retirements and layoffs that have prompted more former employees to visit health clinics.New U.S. Mine Safety and Health Administration rules took effect in August, 2016, that lowered maximum allowed dust concentrations for surface and underground mines, and exposure by miners who have been found to be developing pneumoconiosis.
Research
Work to investigate the relationship between respirable dust exposure and coal workers pneumoconiosis was carried out in Britain by the Institute of Occupational Medicine. This research was known as the Pneumoconiosis Field Research (PFR). The research underpinned the recommendations for more stringent airborne dust standards in British coalmines and the PFR was ultimately used as the basis for many national dust standards around the world.
See also
Black Lung Benefits Act of 1972
Caplan syndrome
References
External links
Faces of Black Lung - USDHHS on YouTube
NIOSH Mining Topic: Respiratory Diseases
NIOSH Coal Workers Health Surveillance Program
Mine Safety and Health Administration
42CFR27 Specifications of Medical Examinations of Underground Coal Miners
Institute of Occupational Medicines pneumoconiosis research |
Umbilical-urachal sinus | Umbilical-urachal sinus is a congenital disorder of the urinary bladder caused by failure of obliteration of proximal or distal part of the allantois, and the presentation of this anomaly is more common in children and rarer in adults.It is thought have been first described by Cabriolus in 1550.
Complications
Infection, with possible abscess formation.
Concurrent occurrence of a tumour.
See also
Urachus
== References == |
Variably protease-sensitive prionopathy | Variably protease-sensitive prionopathy (VPSPr) (formerly known as Protease Sensitive Prionopathy) is a sporadic prion protein disease first described in an abstract for a conference on prions in 2006, and this study was published in a 2008 report on 11 cases. The study was conducted by Gambetti P., Zou W.Q., and coworkers from the United States National Prion Disease Pathology Surveillance Center. It was first identified as a distinct disease in 2010 by Zou W.Q. and coworkers from the United States National Prion Disease Pathology Surveillance Center.VPSPr is very rare, occurring in just 2 or 3 out of every 100 million people. As of 2018, fourteen cases have been reported in the UK. It has similarities to Creutzfeldt–Jakob disease, but clinical manifestations differ somewhat, and the abnormal prion protein (PrP) is less resistant to digestion by proteases; some variants are more sensitive to proteases than others, hence the name: variably protease-sensitive.
Patients present with behavioral and psychiatric symptoms, speech deficits (aphasia and/or dysarthria) and progressive cognitive and motor decline (dementia, ataxia, parkinsonism, psychosis, aphasia and mood disorder). Average age at onset is 70 years, and duration of survival is 24 months. About 40% of patients have a family history of dementia. Like CJD, it can be mistaken for Alzheimers dementia.
Diagnosis is difficult, as pathognomonic signs on MRI such as cortical ribboning or hockey stick sign, periodic sharp wave complexes on EEG, and tests for 14-3-3 protein and tau protein are usually not helpful, and no mutations have been observed in the coding region of the PrP gene, unlike CJD and Variant CJD. The diagnosis can be made on pathological examination. There are unique microscopic and immunohistochemical features, and the prions cannot be digested using proteases. Because 8 out of 10 patients had a positive family history of dementia in the original study, a genetic cause was suspected.
Some have suggested the disease may be a sporadic form of Gerstmann–Sträussler–Scheinker syndrome (GSS).In 2013, Zou W.Q. and coworkers revealed that the peculiar protease-resistant PrP (PrPres) originally found in VPSPr is also detectable in the brain of patients with a genetic CJD linked to PrP Valine (V) to isoleucine (I) mutation at residue 180 (PrPV180I); moreover, they found that the pathological PrP from both VPSPr and gCJDPrPV180I shares a similar glycoform-selective prion formation mechanism.[8,9] Interestingly, the authors further demonstrated that the protease-resistant PrPres from both VPSPr and gCJDV180I lacks the PrP species glycosylated at the first N-linked glycosylation site at residue 181 and they proposed that the deficiency in PrP glycosylation may be involved in the pathogenesis of the two conditions. In 2014, Gambetti P., Zou W.Q., and coworkers found that approximately 54% of mice inoculated with VPSPr brain homogenates exhibited histopathologic lesions and 34% harbored abnormal PrP similar to that of VPSPr on the first passage but no prion disease was detected on the second passage,[10] suggesting that the infectivity of the pathological PrP from VPSPr is lower compared to that from the most common sporadic CJD.
See also
Creutzfeldt–Jakob disease
References
8. Xiao X, Yuan J, Haïk S, Cali I, Zhan YA, Moudjou M, Li B, Laplanche JL, Laude H, Langeveld J, Gambetti P, Kitamoto T, Kong Q, Brandel JP, Cobb BA, Petersen RB & Zou WQ. Glycoform-selective prion formation in sporadic and familial forms of prion disease. PLoS ONE, 2013; 8:e58786.
9. Zou, WQ, Gambetti P, Xiao X, Yuan J, Langeveld J & Pirisinu L. Prions in variably protease-sensitive prionopathy: An update. Pathogens 2013; 2(3): 457-471.
10. Notari S, Xiao X, Espinosa JC, Cohen Y, Qing L, Aguilar-Calvo P, Kofskey D, Cali I, Cracco L, Kong Q, Torres JM, Zou W & Gambetti P. Transmission characteristics of variably protease-sensitive prionopathy. Emerg Infect Dis 2014, 20:2006-14.
External links
Caroline Parkinson (13 August 2010). "Brain disease could affect more people, research finds". BBC News. |
Freeman–Sheldon syndrome | Freeman–Sheldon syndrome (FSS) is a very rare form of multiple congenital contracture (MCC) syndromes (arthrogryposes) and is the most severe form of distal arthrogryposis (DA). It was originally described by Ernest Arthur Freeman and Joseph Harold Sheldon in 1938.: 577 As of 2007, only about 100 cases had been reported in medical literature.
Signs and symptoms
The symptoms of Freeman–Sheldon syndrome include drooping of the upper eyelids, strabismus, low-set ears, a long philtrum, gradual hearing loss, scoliosis and walking difficulties. Gastroesophageal reflux has been noted during infancy, but usually improves with age. The tongue may be small, and the limited movement of the soft palate may cause nasal speech. Often there is an H- or Y-shaped dimpling of the skin over the chin.
Cause
FSS is caused by genetic changes. Krakowiak et al. (1998) mapped the distal arthrogryposis multiplex congenita (DA2B; MIM #601680) gene, a syndrome very similar in phenotypic expression to classic FSS, to 11p15.5-pter. Other mutations have been found as well. In FSS, inheritance may be either autosomal dominant, most often demonstrated. or autosomal recessive (MIM 277720). Alves and Azevedo (1977) note most reported cases of DA2A have been identified as new allelic variation. Toydemir et al. (2006) showed that mutations in embryonic myosin heavy chain 3 (MYH3; MIM *160270), at 17p-13.1-pter, caused classic FSS phenotype, in their screening of 28 (21 sporadic and 7 familial) probands with distal arthrogryposis type 2A. In 20 patients (12 and 8 probands, respectively), missense mutations (R672H; MIM *160270.0001 and R672C; MIM *160270.0002) caused substitution of arg672, an embryonic myosin residue retained post-embryonically. Of the remaining 6 patients in whom they found mutations, 3 had missense private de novo (E498G; MIM *160270.0006 and Y583S) or familial mutations (V825D; MIM *160270.0004); 3 other patients with sporadic expression had de novo mutations (T178I; MIM *160270.0003), which was also found in DA2B; 2 patients had no recognized mutations.
Diagnosis
Freeman–Sheldon syndrome is a type of distal arthrogryposis, related to distal arthrogryposis type 1 (DA1). In 1996, more strict criteria for the diagnosis of Freeman–Sheldon syndrome were drawn up, assigning Freeman–Sheldon syndrome as distal arthrogryposis type 2A (DA2A).On the whole, DA1 is the least severe; DA2B is more severe with additional features that respond less favourably to therapy. DA2A (Freeman–Sheldon syndrome) is the most severe of the three, with more abnormalities and greater resistance to therapy.Freeman–Sheldon syndrome has been described as a type of congenital myopathy.In March 2006, Stevenson et al. published strict diagnostic criteria for distal arthrogryposis type 2A (DA2A) or Freeman–Sheldon syndrome. These included two or more features of distal arthrogryposis: microstomia, whistling-face, nasolabial creases, and H-shaped chin dimple.
Management
Surgical and anesthetic considerations
Patients must have early consultation with craniofacial and orthopaedic surgeons, when craniofacial, clubfoot, or hand correction is indicated to improve function or aesthetics. Operative measures should be pursued cautiously, with avoidance of radical measures and careful consideration of the abnormal muscle physiology in Freeman–Sheldon syndrome. Unfortunately, many surgical procedures have suboptimal outcomes, secondary to the myopathy of the syndrome.When operative measures are to be undertaken, they should be planned for as early in life as is feasible, in consideration of the tendency for fragile health. Early interventions hold the possibility to minimise developmental delays and negate the necessity of relearning basic functions.Due to the abnormal muscle physiology in Freeman–Sheldon syndrome, therapeutic measures may have unfavourable outcomes. Difficult endotracheal intubations and vein access complicate operative decisions in many DA2A patients, and malignant hyperthermia (MH) may affect individuals with FSS, as well. Cruickshanks et al. (1999) reports uneventful use of non-MH-triggering agents. Reports have been published about spina bifida occulta in anaesthesia management and cervical kyphoscoliosis in intubations.
Medical emphasis
General health maintenance should be the therapeutic emphasis in Freeman–Sheldon syndrome. The focus is on limiting exposure to infectious diseases because the musculoskeletal abnormalities make recovery from routine infections much more difficult in FSS. Pneumonitis and bronchitis often follow seemingly mild upper respiratory tract infections. Though respiratory challenges and complications faced by a patient with FSS can be numerous, the syndromes primary involvement is limited to the musculoskeletal systems, and satisfactory quality and length of life can be expected with proper care.
Prognosis
There are little data on prognosis. Rarely, some patients have died in infancy from respiratory failure; otherwise, life expectancy is considered to be normal.
Epidemiology
By 1990, 65 patients had been reported in the literature, with no sex or ethnic preference notable. Some individuals present with minimal malformation; rarely patients have died during infancy as a result of severe central nervous system involvement or respiratory complications. Several syndromes are related to the Freeman–Sheldon syndrome spectrum, but more information is required before undertaking such nosological delineation.
Research directions
One research priority is to determine the role and nature of malignant hyperthermia in FSS. Such knowledge would benefit possible surgical candidates and the anaesthesiology and surgical teams who would care for them. MH may also be triggered by stress in patients with muscular dystrophies. Much more research is warranted to evaluate this apparent relationship of idiopathic hyperpyrexia, MH, and stress. Further research is wanted to determine epidemiology of psychopathology in FSS and refine therapy protocols.
Eponym
It is named for British orthopaedic surgeon Ernest Arthur Freeman (1900–1975) and British physician Joseph Harold Sheldon (1893–1972), who first described it in 1938.: 577
References
== External links == |
Emberger syndrome | The Emberger syndrome is a rare, autosomal dominant, genetic disorder caused by familial or sporadic inactivating mutations in one of the two parental GATA2 genes. The mutation results in a haploinsufficiency (i.e. reduction) in the levels of the genes product, the GATA2 transcription factor. This transcription factor is critical for the embryonic development, maintenance, and functionality of blood-forming, lympathic-forming, and other tissues. The syndrome includes as its primary symptoms: serious abnormalities of the blood such as the myelodysplastic syndrome and acute myeloid leukemia; lymphedema (i.e. fluid retention and tissue swelling caused by a compromised lymphatic system) of the lower limbs, and sensorineural hearing loss. However, the anomalies caused by GATA2 mutations are highly variable with some individuals showing little or no such symptoms even in old age while others exhibit non-malignant types of hematological anomalies; lymphedema in areas besides the lower limbs, little or no hearing loss; or anomalies in other tissues. The syndrome may present with relatively benign signs and/or symptoms and then progress rapidly or slowly (i.e. over years or decades) to the myelodysplastic syndrome and/or acute myeloid leukemia. Alternatively, it may present with one of the latter two life-threatening disorders.The Emberger syndrome is only one of the manifestations of inactivating GATA2 mutations. Other manifestations include: 1 Monocytopenia and Mycobacterium Avium Complex/Dendritic Cell, Monocyte, B and NK Lymphocyte deficiency (i.e. MonoMAC or MonoMAC/DCML); 2) familial myelodysplastic syndrome/acute myeloid leukemia (i.e. familial MDS/AML); 3) chronic myelomonocytic leukemia; 4) pediatric myelodysplastic syndrome; and 5) various other hematological abnormalities such as aplastic anemia, anemia, chronic neutropenia; and/or various immunological defects. Individuals with the Emberger syndrome may exhibit signs or symptoms that are more characteristic of the latter manifestations. Since most individuals with inactivating GATA2 mutations progress to a leukemic disorder, the Emberger syndrome is a Precancerous condition.The age of onset and types of symptoms that occur in individuals afflicted with the Emberger syndrome are highly variable even in family members presumed to have identical GATA2 gene mutations. This variability as well as the variability in the different manifestations of GATA2-inactivating mutations are not fully understood. They likely relate, at least in part, to: individual differences in the: 1) levels of the GATA2 transcription factor which are expressed; 2) genetic backgrounds; 3) occurrence of illnesses or other events that stress the bone marrow; and, possibly, 4) development of other "secondary" genetic abnormalities that often develop during the course of these disorders. Because of these many complexities, recent reports have grouped together all of the different manifestations of GATA2 inactivating mutations into a single pleotropic genetic disorder termed GATA2 deficiency, GATA2 haploinsufficiency, or the GATA2 deficiency syndrome. Even currently, however, the Emberger syndrome (e.g. its MIM entry is #614038) and MonoMac/DCML (e.g. its MIM entry is #614172) are often classified as distinct clinical disorders. The Emberger syndrome is here considered as a distinct disorder.
Signs and symptoms
The age of onset of the Emberger syndrome is variable with rare individuals showing first symptoms such as lymphedema occurring in early infancy while others are symptomless or develop first symptoms in their middle and latter years. This variability can occur between members of the same family who are documented to have the same GATA2 mutation. The syndromes most common times of onset are infancy and early childhood. The syndrome may present with unexplained lymphedema, hearing loss, and/or hematological defects like neutropenia, anemia, thrombocytopenia, and/or the circulation of abnormal blood cells. Other defects less commonly associated with and the syndrome include hypotelorism, epicanthic folds, hydrocele, webbed neck, and warts caused be human papillomavirus infection. In these case of relatively benign symptoms and signs, the syndrome commonly progresses rapidly or slowly to myelodysplastic syndrome followed by acute myeloid leukemia. Less commonly, Emberger syndrome presents with the myelodysplastic syndrome and/or acute myeloid leukemia.
Genetics
GATA2 gene
GATA2 is a member of the evolutionarily conserved GATA transcription factor family of genes:: all tested vertebrates express six GATA genes. The human GATA2 gene is located on the long arm (or "q" arm) of chromosome 3 at position 21.3 (i.e. located at 3q21.3). In humans, it is expressed in hematologic cells at the stem cell and later progenitor cell stages of their development. Increases and/or decreases in the genes expression regulate the progression of these immature cells toward their final forms as blood cells such as erythrocytess, certain types of lymphocytes, monocytes, and platelets) as well as certain types of tissue cells such as macrophages and mast cells. The GATA2 gene is also expressed in human endothelium, certain types of non-hematological stem cells, and, to lesser extents, prostate, endometrium, and some cancerous tissues.Monosomy of chromosome 7 (i.e. lose of one of the two chromosomes 7) or deletion of the "q" (i.e. short) in one of these two chromosomes often occurs in the various GATA2 deficiency manifestations including the Emberger syndrome. These genetic abnormalities are known causes of acute myeloid leukemia and, while not essential for, may contribute to the development of acute myeloid leukemia in the syndrome by, for example, lowering the age and/or increasing the chances of the disorder evolving into acute myeloid leukemia.
GATA2 transcription factor
The GATA2 transcription factor contains two zinc finger (i.e. ZnF) structural motifs. C-ZnF is located toward the proteins C-terminus and is responsible for binding to specific DNA sites. N-ZnF is located toward the proteins N-terminus and is responsible for interacting with various other nuclear proteins that regulate its activity. The transcription factor also contains two transactivation domains and one negative regulatory domain which interact with nuclear proteins to up-regulate and down-regulate, respectively, its activity.GATA2 binds to a specific nucleic acid sequence viz., (T/A(GATA)A/G) on the promoter and enhancer sites of its target genes and in doing so either stimulates or suppresses these genes expression. However, there are thousands of sites in human DNA with this nucleotide sequence but, for unknown reasons, GATA2 binds to <1% of these. Furthermore, all members of the GATA transcription factor family bind to this same nucleotide sequence and in doing so may interfere with GATA2 binding or even displace GATA2 already bound to these sites. For example, the displacement of GATA2 bond to this sequence by GATA1 appears important for the normal development of certain hematological stem cells. This phenomenon is termed the "GATA switch". Given these many variables, the GATA2 transcription factors actions in promoting or inhibiting its target genes is exceedingly complex and not completely understood.
Pathophysiology
The GATA2 transcription factor is critical for the emergence of hematologic stem cells from the hemogenic endothelium during embryogenesis. Deletion of both Gata2 genes in mice is lethal by about day 10 of embryogenesis due to collapse in the formation of mature blood cells. Inactivation of one mouse Gata2 gene is neither lethal nor associated with most of the signs of human GATA2 deficiency except that these animals have ~50% reduction in their hematologic stem cells. The latter findings as well as clinical studies in vitro experiments on human tissues support the notion that both parental GATA2 genes are needed to produce levels of the GATA2 transcription factor sufficient for developing and maintaining normal levels of hematological stem and progenitor cells in humans. The transcription factors role in performing this function involves complex and incompletely understood interactions with a network of hematopoietic transcription factors including RUNX1, TAL1, MYB, GFI1, FLI1, LYL1, and PU.1. It is not exactly clear how reduced levels of GATA2 cause any of Emberger syndromes hematological disorders.The role of GATA2 in promoting the normal development of the lymphatic stem cells may be responsible for the other two key features of the Emberger syndrome. That is, failure to develop competent valves and/or vessels in the lymphatic system, it is proposed, is responsible for the lymphedema of Emberger syndrome while failure to generate the perilymphatic space around the inner ears semicircular canals, it is proposed, is responsible for the syndromes sensorineural hearing loss.
Diagnosis
Examination of circulating blood cells, bone marrow cells, and the GATA2 nucleotide sequence of individuals with Emberger syndrome typically evidences abnormalities which are not distinctively different from those of individuals with other manifestations of GATA2 deficiency. The specific diagnosis of Emberger syndrome depends on detecting mutations of the GATA2 gene in a setting of clinical findings of hematological disorders, lymphedema, and neurosensory hearing loss. It may be especially difficult to diagnose the syndrome in the absence of at least one of the latter two clinical signs or in individuals who exhibit anomalies strongly associated with one of the other manifestations of GATA2 deficiency. DNA sequencing of the full GATA2 gene coding region including the intron4 enhancer by Sanger sequencing or high-throughput methods along with DNA copy number analysis should establish the presence of GATA2 gene mutations; comparison of detected gene mutations to the list of inactivating GATA2 gene mutations plus the clinical presentation and family history are essentials in making the diagnosis of the syndrome and its type of presentation.
Treatment
Standard measures are use for the treatment of lymphedema, sensorineural hearing loss, and the other non-malignant anomalies associated with the Emberger syndrome. However, treatment of the disorders myelodysplastic syndrome and acute myeloid leukemia differs somewhat from standard measures. Like other GATA2 insufficiencies, Emberger syndrome is associated with a deficiency of hematological stem and early progenitor cells that is often due to a hereditary loss of one GATA2 gene. Consequently, the use of radical myeloablative conditioning regimens to remove native bone marrow stem/progenitor cells in preparation for hematopoietic stem cell transplantation may entail excessive morbidity and mortality. While no controlled studies on the treatment of the hematological disorders of the syndrome have been reported, current recommendations by multiple authorities suggest the use of hematopoietic stem cell transplantation using non-myeloablative conditioning methods be used when indicated. The use of this procedure should be anticipatory and occur before the development of an excess of progenitor cells populate the bone marrow in cases of myelodyspasia as well as before the development of acute myeloid leukemia. Accordingly, individuals should be routinely monitored by bone marrow examinations and complete blood counts. Furthermore, the relatives of patients afflicted with the syndrome or any of other manifestations of GATA2 deficiency should be tested for GATA2 mutations. Individuals with such mutations are not candidates for donating their stem cells of Emberger syndrome patients. Reversion of the bone marrow to full immune restitution with improved expression of GATA2 can take up to several years after transplantation.
Prognosis
Prognosis of the Emberger syndrome depends heavily on the speed of its progression to bone marrow failure, myelodysplasia with excessive blast cells, or acute myeloid leukemia. Intervention with non-myeloablative hematopoietic stem cell transplantation before development of the latter two disorders is thought to improve survival indefinitely in most cases. While not yet tested, this transplantation intervention would seem to offer a similar benefit in cases of severe, potentially lethal bone marrow failure.
History
The Emberger syndrome was first described by J.M. Emberger in 1979 as an unusual and not previously described constellation of symptoms (sensorineural hearing loss, lower limb lymphedema, and hematological disorders) in 4 individuals from two generations of a single family. A subsequent study published in 2011 and conducted on three different families found that 8 members of these families with clinically diagnosed Emberger syndrome as well as six sporadic cases of individuals with this clinical diagnosis exhibited one of eight different mutations in one of their two parental GATA2 genes. Each mutation was predicted to reduce the levels of functional GATA2. Thus, reduced levels of functionally competent GATA2 transcription factor resulting from a mutation in one of its genes is responsible for the Emberger syndrome.
== References == |
Hibernoma | A hibernoma is a benign neoplasm of vestigial brown fat. The term was originally used by the French anatomist Louis Gery in 1914.
Signs and symptoms
Patients present with a slow-growing, painless, solitary mass, usually of the subcutaneous tissues. It is much less frequently noted in the intramuscular tissue. It is not uncommon for symptoms to be present for years.
Benign neoplasm with brown fat is noted.
Diagnosis
Imaging findings
In general, imaging studies show a well-defined, heterogeneous mass, usually showing a mass which is hypointense to subcutaneous fat on magnetic resonance T1-weight images. Serpentine, thin, low signal bands (septations or vessels) are often seen throughout the tumor.
Pathology findings
From a macroscopic perspective, there is a well-defined, encapsulated or circumscribed mass, showing a soft, yellow tan to deep brown mass. The size ranges from 1 to 27 cm, although the mean is about 10 cm.
The tumors histologically resemble brown fat. There are four histologic types recognized, but one is the most frequently seen (typical). There is a background of rich vascularity.
Lobular type: Variable degrees of differentiation of uniform, round to oval cells with granular eosinophilic cells with prominent borders, alternating with coarsely multivacuolated fat cells (pale cells). There are usually small centrally placed nuclei without pleomorphism. The cells have large cytoplasmic lipid droplets interspersed throughout.
Myxoid variant: Loose, basophilic matrix, with thick fibrous septa, and foamy histiocytes
Lipoma-like variant: Univacuolated lipocytes, with only isolated hibernoma cells
Spindle cell variant: Spindle cell lipoma combined with hibernoma
Histochemistry
Oil Red O-positive droplets of cytoplasmic lipid can be seen in most cases
Immunohistochemistry
The neoplastic cells are S100 protein positive (approximately 80%), and show membrane and vacuole CD31 immunoreactivity. Uncoupling protein 1 (UCP1), a unique brown fat mitochondrial protein, is also positive.
Cytogenetics
There are structural rearrangements of 11q13-21, which are considered most characteristic. This alteration can be detected by metaphase fluorescent in situ hybridization (FISH). MEN1 gene (11q13.1) is most frequently deleted, while GARP gene (11q13.5) may also be involved.
Cytology
The fine needle aspiration smears show small, round, brown fat-like cells, with uniform, small cytoplasmic vacuoles and regular, small, round nuclei. There is usually a rich vascular background of branching capillaries. It is not uncommon to also have mature fat cells.
Differential diagnoses
It is important to separate hiberoma from adult rhabdomyoma, a granular cell tumor and a true liposarcoma.
Classification
This lesion has been called a fetal lipoma, lipoma of embryonic fat or a lipoma of immature fat.
Management
Complete surgical excision is the treatment of choice, associated with an excellent long term clinical outcome.
Epidemiology
The tumor is rare, affecting adults in the 4th decade most commonly. Patients are usually younger than those who present with a lipoma. There is a slight male predominance. Hibernoma are most commonly identified in the subcutaneous and muscle tissue of the head and neck region (shoulders, neck, scapular), followed by thigh, back, chest, abdomen, and arms. In rare cases hibernoma may arise in bone tissue, however it is an incidental finding.
Additional images
See also
Lipoma
Skin lesion
List of cutaneous conditions
References
Further reading
Lester D. R. Thompson; Bruce M. Wenig (2011). Diagnostic Pathology: Head and Neck: Published by Amirsys. Hagerstown, MD: Lippincott Williams & Wilkins. pp. 8:42–43. ISBN 978-1-931884-61-7.
== External links == |
Piriformis syndrome | Piriformis syndrome is a condition which is believed to result from compression of the sciatic nerve by the piriformis muscle. Symptoms may include pain and numbness in the buttocks and down the leg. Often symptoms are worsened with sitting or running.Causes may include trauma to the gluteal muscle, spasms of the piriformis muscle, anatomical variation, or an overuse injury. Few cases in athletics, however, have been described. Diagnosis is difficult as there is no definitive test. A number of physical exam maneuvers can be supportive. Medical imaging is typically normal. Other conditions that may present similarly include a herniated disc.Treatment may include avoiding activities that cause symptoms, stretching, physiotherapy, and medication such as NSAIDs. Steroid or botulinum toxin injections may be used in those who do not improve. Surgery is not typically recommended. The frequency of the condition is unknown, with different groups arguing it is more or less common.
Signs and symptoms
The signs and symptoms include gluteal pain that may radiate down buttock and the leg, and that is made worse in some sitting positions.
Etiology
Causes of piriformis syndrome include the following
Anatomic anomalies, present since birth:Bipartite piriformis muscleSciatic nerve course/branching variations with respect to the piriformis muscle: In over 80% of the population, the sciatic nerve courses deep to and exits inferiorly to the piriformis muscle belly/tendon. Early (proximal) divisions of the sciatic nerve into its tibial and common peroneal components can predispose patients to piriformis syndrome, with these branches passing through and below the piriformis muscle or above and below the muscle.AcquiredSitting for prolonged periods (office workers, taxi drivers, bicycle riders)Overuse syndromes: Piriformis muscle hypertrophy (viz., in athletes)Trauma to the hip or buttock area
Pathophysiology
When the piriformis muscle shortens or spasms due to trauma or overuse, it can compress or strangle the sciatic nerve beneath the muscle. Generally, conditions of this type are referred to as nerve entrapment or as entrapment neuropathies; the particular condition known as piriformis syndrome refers to sciatica symptoms not originating from spinal roots and/or spinal disc compression, but involving the overlying piriformis muscle.In 17% of an assumed normal population the sciatic nerve passes through the piriformis muscle, rather than underneath it; however, in patients undergoing surgery for suspected piriformis syndrome such an anomaly was found only 16.2% of the time leading to doubt about the importance of the anomaly as a factor in piriformis syndrome. Some researchers discount the importance of this relationship in the etiology of the syndrome.MRI findings have shown that both hypertrophy (unusual largeness) and atrophy (unusual smallness) of the piriformis muscle correlate with the supposed condition.Piriformis syndrome may also be associated with direct trauma to the piriformis muscle, such as in a fall or from a knife wound.
Diagnosis
Piriformis syndrome occurs when the sciatic nerve is compressed or pinched by the piriformis muscle of the hip. It usually only affects one hip at a given time, though both hips may produce piriformis syndrome at some point in the patients lifetime, and having had it once greatly increases the chance that it will recur in one hip or the other at some future point unless action is taken to prevent it. Indications include sciatica (radiating pain in the buttock, posterior thigh, and lower leg) and the physical exam finding of tenderness in the area of the sciatic notch. If the piriformis muscle can be located beneath the other gluteal muscles, it will feel noticeably cord-like and will be painful to compress or massage. The pain is exacerbated with any activity that causes flexion of the hip including lifting, prolonged sitting, or walking.
The diagnosis is largely clinical and is one of exclusion. During a physical examination, attempts may be made to stretch the irritated piriformis and provoke sciatic nerve compression, such as the Freiberg test, the Pace test, the FABER test (flexion, abduction, external rotation), and the FAIR test (flexion, adduction, internal rotation). Sciatica secondary to conditions to be ruled out include herniated nucleus pulposus (HNP), facet arthropathy, spinal stenosis, and lumbar muscle strain. Pathology in the sacroiliac joint region, Sacroiliac joint dysfunction and Sacroiliitis are other conditions that present with pain in the low back and hip regions, which may radiate down along the back of the thigh, rarely going down below knee.
Wallet neuritis is an extra-spinal tunnel neuropathy of sciatic nerve, occurring mostly in men. Sitting down on a thick Wallet in the back pocket produces uneven pressure in the hip region that impinges on the Piriformis muscle and / or sciatic nerve. Wallet induced chronic sciatic nerve constriction produces gluteal and ipsilateral lower extremity pain, tingling, and burning sensation.Diagnostic modalities such as ultrasound Imaging, MRI, CT scan, and EMG are mostly useful in excluding other conditions. Increased thickness [iTh] and increased cross‐sectional area [iCSA] for piriformis muscle may be demonstrated on ultrasound imaging and MRI.Magnetic resonance neurography is a medical imaging technique that can show the presence of irritation of the sciatic nerve at the level of the sciatic notch where the nerve passes under the piriformis muscle. However, Magnetic resonance neurography is considered "investigational/not medically necessary" by some insurance companies. Neurography can determine whether or not a patient has a split sciatic nerve or a split piriformis muscle – this may be important in getting a good result from injections or surgery. Image guided injections carried out in an open MRI scanner, or other 3D image guidance can accurately relax the piriformis muscle to test the diagnosis. Other injection methods such as blind injection, fluoroscopic guided injection, ultrasound, or EMG guidance can work but are not as reliable and have other drawbacks.
Prevention
The most common etiology of piriformis syndrome is that resulting from a specific previous injury due to trauma. Large injuries include trauma to the buttocks while "micro traumas" result from small repeated bouts of stress on the piriformis muscle itself. To the extent that piriformis syndrome is the result of some type of trauma and not neuropathy, such secondary causes are considered preventable, especially those occurring in daily activities: according to this theory, periods of prolonged sitting, especially on hard surfaces, produce minor stress that can be relieved with bouts of standing. An individuals environment, including lifestyle factors and physical activity, determine susceptibility to trauma of any given type. Although empirical research findings on the subject have never been published, many believe that taking sensible precautions during high-impact sports and when working in physically demanding conditions may decrease the risk of experiencing piriformis syndrome, either by forestalling injury to the muscle itself or injury to the nerve root that causes it to spasm. In this vein, proper safety and padded equipment should be worn for protection during any type of regular, firm contact (i.e., American football, etc.). In the workplace, individuals are encouraged to make regular assessments of their surroundings and attempt to recognize those things in ones routine that might produce micro or macro traumas. No research has substantiated the effectiveness of any such routine, however, and participation in one may do nothing but heighten an individuals sense of worry over physical minutiae while have no effect in reducing the likeliness of experiencing or re-experiencing piriformis syndrome.Other suggestions from some researchers and physical therapists have included prevention strategies include warming up before physical activity, practicing correct exercise form, stretching, and doing strength training, though these are often suggested for helping treat or prevent any physical injury and are not piriformis-specific in their approach As with any type of exercise, it is thought that warmups will decrease the risk of injury during flexion or rotation of the hip. Stretching increases range of motion, while strengthening hip adductors and abductors theoretically allows the piriformis to tolerate trauma more readily.
Treatment
Immediate though temporary relief of piriformis syndrome can usually be brought about by injection of a local anaesthetic into the piriformis muscle. Symptomatic relief of muscle and nerve pain can also sometimes be obtained by nonsteroidal anti-inflammatory drugs and/or muscle relaxants, though the use of such medication or even more powerful prescription medication for relief of sciatica is often assessed by patients to be largely ineffective at relieving pain. Conservative treatment usually begins with stretching exercises, myofascial release, massage, and avoidance of contributory activities such as running, bicycling, rowing, heavy lifting, etc. Some clinicians recommend formal physical therapy, including soft tissue mobilization, hip joint mobilization, teaching stretching techniques, and strengthening of the gluteus maximus, gluteus medius, and biceps femoris to reduce strain on the piriformis. More advanced physical therapy treatment can include pelvic-trochanter isometric stretching, hip abductor, external rotator and extensor strengthening exercises, transcutaneous electrical nerve stimulation (TENS), and massage physiotherapy of the piriformis muscle region. One study of 14 people with what appeared to be piriformis syndrome indicated that rehabilitation programs that included physical therapy, low doses of muscle relaxants and pain relief medication were effective at alleviating most muscle and nerve pain caused by what the research subjects had been told was piriformis syndrome. However, as this study included very few individuals and did not have a control group not receiving treatment (both serious methodological flaws), it provides no insight as to whether the pain in the piriformis would have simply dissipated on its own without any treatment at all, and is therefore not only uninformative, it may actually be misleading. The injury is considered largely self-limiting and spontaneous recovery is usually on the order of a few days or a week to six weeks or longer if left untreated.
Stretching
Most practitioners agree that spasm, strain, or pain in any muscle can often be treated by regular stretching exercise of that muscle, no matter the cause of the pain. Stretching is recommended every two to three waking hours. Anterior and posterior movement of the hip joint capsule may help optimize the patients stretching capacity. The muscle can be manually stretched by applying pressure perpendicular to the long axis of the muscle and parallel to the surface of the buttocks until the muscle is relaxed. Another stretching exercise is to lie on the side opposite of the pain with the hip and knee of the upper leg flexed and adducted towards the ground while the torso is rotated so that the back of the upper shoulder touches the ground. Physical Therapists may suggest stretching exercises that will target the piriformis, but may also include the hamstrings and hip muscles in order to adequately reduce pain and increase range of motion. Patients with piriformis syndrome may also find relief from applications of ice which will help reduce inflammation and so may help limit pressure on the sciatic nerve. This treatment can be helpful when pain starts or immediately after an activity that is likely to cause pain. As the length of time progresses, heat may provide temporary relief from many types of muscle pain and will temporarily increase muscle flexibility.
Local injections
Failure of conservative treatments such as stretching and strengthening of the piriformis muscle or a high level of immediate pain intensity may bring into consideration various therapeutic injections such as local anesthetics (e.g., lidocaine), anti-inflammatory drugs and/or corticosteroids, botulinum toxin (BTX, Botox), or a combination of the three, all of which have a well-documented effectiveness at relieving muscle-related pain. Injection technique is a significant issue since the piriformis is a very deep-seated muscle. A radiologist may assist in this clinical setting by injecting a small dose of medication containing a paralysing agent such as botulinum toxin under high-frequency ultrasound or CT control. This inactivates the piriformis muscle for 3 to 6 months, without resulting in leg weakness or impaired activity. Though the piriformis muscle becomes inactivated, the surrounding muscles quickly take over its role without any noticeable change in strength or gait. Such treatments may be more or less curative (with no return to pain), or may have limited timespans of effectiveness.
Surgery
For rare cases with unrelenting chronic pain, surgery may be recommended. Surgical release of the piriformis muscle is often effective. Minimal access surgery using newly reported techniques has also proven successful in a large-scale formal outcome published in 2005. As with injections, the deactivated/ excised muscles role in leg movement is completely compensated for by surrounding hip muscles.
Failure of piriformis syndrome treatment may be secondary to an underlying internal obturator muscle injury.
Epidemiology
Piriformis syndrome (PS) data is often confused with other conditions due to differences in definitions, survey methods and whether or not occupational groups or general population are surveyed. This causes a lack of group harmony about the diagnosis and treatment of PS, affecting its epidemiology. In a study, 0.33% of 1293 patients with low back pain cited an incident for PS. A separate study showed 6% of 750 patients with the same incidence. About 6–8% of low back pain occurrences were attributed to PS, though other reports concluded about 5–36%. In a survey conducted on the general population, 12.2–27% included a lifetime occurrence of PS, while 2.2–19.5% showed an annual occurrence. However further studies show that the proportion of the sciatica, in terms of PS, is about 0.1% in orthopaedic practice. This is more common in women with a ratio of 3 to 1 and most likely due to the wider quadriceps femoris muscle angle in the os coxae. Between the years of 1991–1994, PS was found to be 75% prevalent in New York, Connecticut, New Jersey, Pennsylvania; 20% in other American urban centers; and 5% in North and South America, Europe, Asia, Africa and Australia. The common ages of occurrence happen between thirty and forty, and are scarcely found in patients younger than twenty; this has been known to affect all lifestyles.Piriformis syndrome is often left undiagnosed and mistaken with other pains due to similar symptoms with back pain, quadriceps pain, lower leg pain, and buttock pain. These symptoms include tenderness, tingling and numbness initiating in low back and buttock area and then radiating down to the thigh and to the leg.
A precise test for piriformis syndrome has not yet been developed and thus hard to diagnose this pain.
The pain is often initiated by sitting and walking for a longer period.
In 2012, 17.2% of low back pain patients developed piriformis syndrome.
Piriformis syndrome does not occur in children, and is mostly seen in women of age between thirty and forty. This is due to hormone changes throughout their life, especially during pregnancy, where muscles around the pelvis, including piriformis muscles, tense up to stabilize the area for birth.
In 2011, out of 263 patients between the ages of 45 to 84 treated for piriformis syndrome, 53.3% were female. Females are two times more likely to develop piriformis syndrome than males. Moreover, females had longer stay in hospital during 2011 due to high prevalence of the pain in females. The average cost of treatment was $29,070 for hospitalizing average 4 days.
References
Further reading
Jassal, Navdeep Singh (2017). "Piriformis Muscle Syndrome". In Pope, Jason E.; Deer, Timothy R (eds.). Treatment of Chronic Pain Conditions. pp. 269–71. doi:10.1007/978-1-4939-6976-0_78. ISBN 978-1-4939-6974-6.
== External links == |
Parkinsonism | Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. These are the four motor symptoms found in Parkinsons disease (PD), after which it is named, dementia with Lewy bodies (DLB), Parkinsons disease dementia (PDD), and many other conditions. This set of symptoms occurs in a wide range of conditions and may have many causes, including neurodegenerative conditions, drugs, toxins, metabolic diseases, and neurological conditions other than PD.
Signs and symptoms
Parkinsonism is a clinical syndrome characterized by the four motor symptoms found in Parkinsons disease: tremor, bradykinesia (slowed movements), rigidity, and postural instability.Parkinsonism gait problems can lead to falls and serious physical injuries. Other common symptoms include:
Tremors when resting (mostly in the hands)
Short, shuffling gait
Slow movements (bradykinesia)
Loss of sound perception leading to low, soft speech
Difficulty sleeping
Dry skin
Apathy
Lack of facial expressions
Balance problems
Frequent falls
Very small handwriting
Rigid, stiff muscles
Cogwheeling (jerky feeling in arm or leg)
Conditions
Parkinsonism occurs in many conditions.
Neurological
Neurodegenerative conditions and Parkinson plus syndrome that can cause parkinsonism include:
Corticobasal degeneration
Dementia with Lewy bodies
The relationship (if any) with essential tremor is not clear.
Frontotemporal dementia (Picks disease)
Gerstmann–Sträussler–Scheinker syndrome
Huntingtons disease
Lytico-bodig disease (ALS complex of Guam)
Multiple system atrophy (Shy–Drager syndrome)
Neuroacanthocytosis
Neuronal ceroid lipofuscinosis
Olivopontocerebellar atrophy
Pantothenate kinase-associated neurodegeneration, also known as neurodegeneration with brain iron accumulation
Parkin mutation (hereditary juvenile dystonia)
Parkinsons disease
Parkinsons disease dementia
Progressive supranuclear palsy
Wilsons disease
X-linked dystonia parkinsonism (Lubag syndrome)
Drug-induced ("pseudoparkinsonism")
About 7% of people with parkinsonism developed symptoms as a result of side effects of medications, mainly neuroleptic antipsychotics especially the phenothiazines (such as perphenazine and chlorpromazine), thioxanthenes (such as flupenthixol and zuclopenthixol) and butyrophenones (such as haloperidol), and rarely, antidepressants. Yet another drug that can induce parkinsonism is the antihistaminic medication cinnarizine, usually prescribed for motion sickness; this is because besides antagonizing histamine receptors this drug antagonizes the dopamine D2 receptors. The incidence of drug-induced parkinsonism increases with age. Drug-induced parkinsonism tends to remain at its presenting level and does not worsen like Parkinsons disease.Implicated medications include:
Antipsychotics
Lithium
Metoclopramide
MDMA addiction and frequent use
Tetrabenazine
Cinnarizine
Infectious
Creutzfeldt–Jakob disease
Encephalitis lethargica
HIV infection and AIDS
Toxins
Evidence exists of a link between exposure to pesticides and herbicides and PD; a two-fold increase in risk was seen with paraquat or maneb/mancozeb exposure.Chronic manganese (Mn) exposure has been shown to produce a parkinsonism-like illness characterized by movement abnormalities. This condition is not responsive to typical therapies used in the treatment of PD, suggesting an alternative pathway than the typical dopaminergic loss within the substantia nigra. Manganese may accumulate in the basal ganglia, leading to the abnormal movements. A mutation of the SLC30A10 gene, a manganese efflux transporter necessary for decreasing intracellular Mn, has been linked with the development of this parkinsonism-like disease. The Lewy bodies typical to PD are not seen in Mn-induced parkinsonism.Agent Orange may be a cause of parkinsonism, although evidence is inconclusive and further research is needed.Other toxins that have been associated with parkinsonism are:
Annonaceae
Carbon monoxide
Carbon disulfide
Cyanide
Ethanol
Hexane
Maneb/Mancozeb
Mercury
Methanol
MPTP
Paraquat
Rotenone
Toluene (inhalant abuse: "huffing")
Vascular
Binswangers disease (subcortical leukoencephalopathy)
Vascular dementia (multi-infarct)
Other
Chronic traumatic encephalopathy (boxers dementia or pugilistic encephalopathy)
Damage to the brain stem (especially dopaminergic nuclei of the substantia nigra),basal ganglia (especially globus pallidus) and the thalamus.
Hypothyroidism
Orthostatic tremor
Paraneoplastic syndrome: neurological symptoms caused by antibodies associated with cancers
Rapid onset dystonia parkinsonism
Autosomal recessive juvenile parkinsonism
Society and culture
In the United States, the 2021 National Defense Authorization Act (NDAA) added parkinsonism to the list of presumptive conditions associated with Agent Orange exposure, enabling affected service members to receive Veterans Affairs disability benefits.
References
External links
GeneReviews/NIH/NCBI/UW entry on Perry syndrome
GeneReviews/NCBI/NIH/UW entry on X-Linked Dystonia-Parkinsonism |
Heat edema | Heat edema is a cutaneous condition characterized by dependent edema from vasodilatory pooling.
Heat causes the blood vessels to expand (dilate), so body fluid moves into the hands or legs by gravity.
The balance of salt in the body is also a risk factor for heat edema. If salt loss is less than normal, the increased salt level draws fluid into the hands and legs.
Older adults have an increased risk of heat edema, especially if they have other medical conditions that affect their circulation.
People visiting hot climates from colder climates may also have an increased risk of heat edema.
See also
Heat illness
List of cutaneous conditions
== References == |
Permanent neonatal diabetes | Permanent neonatal diabetes mellitus (PNDM) is a newly identified and potentially treatable form of monogenic diabetes. This type of neonatal diabetes is caused by activating mutations of the KCNJ11 gene, which codes for the Kir6.2 subunit of the beta cell KATP channel. This disease is considered to be a type of maturity onset diabetes of the young (MODY).
Cause
It can be associated with GCK, KCNJ11, INS, and ABCC8.
Diagnosis
This results in congenital impairment of insulin release, although in the past, this was always being thought to be unusually early type 1 diabetes mellitus. The insulin deficiency results in intrauterine growth retardation with birth weight small for gestational age. The diabetes is usually diagnosed in the first 3 months of life due to continuing poor weight gain, polyuria, or diabetic ketoacidosis. Rare cases have been recognized as late as 6 months of age.
Treatment
Remarkably, this type of diabetes often responds well to sulfonylureas and insulin may not be necessary. More severe mutations in the KCNJ11 gene can cause early-onset diabetes which does not respond to the sulfonylurea drugs, as well as a syndrome of developmental delay and neurological features called the DEND syndrome. These forms of diabetes are very rare conditions, appearing in about 1/100,000 to 1/200,000 live births, and accounting for about 1/1000 of type 1 diabetes cases. Fewer than 5% of the cases assumed to exist have been diagnosed, and most diabetes clinics around the world are checking for KCNJ11 mutations in any persons who developed apparent insulin-dependent diabetes without the typical type 1 antibodies before 6 months of age. At least some of these people have been able to change from insulin to sulfonylurea pills after decades of injections.
See also
Transient neonatal diabetes mellitus
References
External links
GeneReviews/NCBI/NIH/UW entry on Permanent Neonatal Diabetes Mellitus
DiabetesGenes - Information about diagnosis, testing and treatment of neonatal diabetes |
Freys syndrome | Freys syndrome (also known as Baillargers syndrome, Dupuys syndrome, auriculotemporal syndrome, or Frey-Baillarger syndrome) is a rare neurological disorder resulting from damage to or near the parotid glands responsible for making saliva, and from damage to the auriculotemporal nerve often from surgery.The symptoms of Freys syndrome are redness and sweating on the cheek area adjacent to the ear (see focal hyperhidrosis). They can appear when the affected person eats, sees, dreams, thinks about or talks about certain kinds of food which produce strong salivation. Observing sweating in the region after eating a lemon wedge may be diagnostic.
Signs and symptoms
Signs and symptoms include erythema (redness or flushing) and sweating in the cutaneous distribution of the auriculotemporal nerve, usually in response to gustatory stimuli. There is sometimes pain in the same area, often burning in nature. Between attacks of pain there may be numbness or other altered sensations (anesthesia or paresthesia). This is sometimes termed "gustatory neuralgia".
Causes
Freys syndrome often results as a complication of surgeries of or near the parotid gland or due to injury to the auriculotemporal nerve, which passes through the parotid gland in the early part of its course. The auriculotemporal branch of the mandibular branch (V3) of the trigeminal nerve carries parasympathetic fibers to the parotid salivary gland and sympathetic fibers to the sweat glands of the scalp. As a result of severance and inappropriate regeneration, the parasympathetic nerve fibers may switch course to a sympathetic response, resulting in "gustatory sweating" or sweating in the anticipation of eating, instead of the normal salivary response.
It is often seen with patients who have undergone endoscopic thoracic sympathectomy, a surgical procedure wherein part of the sympathetic trunk is cut or clamped to treat sweating of the hands or blushing. The subsequent regeneration or nerve sprouting leads to abnormal sweating and salivation. It can also include discharge from the nose when smelling certain food.
Rarely, Freys syndrome can result from causes other than surgery, including accidental trauma, local infections, sympathetic dysfunction and pathologic lesions within the parotid gland.
An example of such rare trauma or localized infection can be seen in situations where a hair follicle has become ingrown, and is causing trauma or localized infection near or over one of the branches of the auriculotemporal nerve.
Diagnosis
Diagnosis is made based on clinical signs and symptoms and a starch-iodine test, also known as the Minor test. The affected area of the face is painted with iodine which is allowed to dry, then dry corn starch is applied to the face. The starch turns blue on exposure to iodine in the presence of sweat.
Treatments
Injection of botulinum toxin A
Surgical transection of the nerve fibers (a temporary treatment)
Application of an ointment containing an anticholinergic drug such as scopolamineCochrane reviews of interventions to either prevent or treat Freys syndrome have found little or no evidence to support their effectiveness or safety, and conclude that further clinical trials are needed.
Epidemiology
The condition is rare, although the exact incidence is unknown.The disorder most often occurs as a complication of the surgical removal of a parotid gland (parotidectomy). The percentage of individuals who develop Frey syndrome after a parotidectomy is controversial and reported estimates range from 30 to 50 percent. In follow-up examinations, approximately 15 percent of affected individuals rated their symptoms as severe. Frey syndrome affects males and females in equal numbers.
History
It is named after Łucja Frey-Gottesman. The disorder was first reported in medical literature by Baillarger in 1853. A neurologist from Poland, Dr. Lucja Frey, provided a detailed assessment of the disorder and coined the term "auriculotemporal syndrome" in 1923.
References
== External links == |
Koenens tumor | Koenens tumor (KT), also commonly termed periungual angiofibroma,: 668 is a subtype of the angiofibromas. Angiofibromas are benign papule, nodule, and/or tumor lesions that are separated into various subtypes based primarily on the characteristic locations of their lesions. KTs are angiofibromas that develop in and under the toenails and/or fingernails. KTs were once considered as the same as another subtype of the angiofibromas viz., acral angiofibromas. While the literature may still sometimes regard KTs as acral angiofibromas, acral angiofibromas are characteristically located in areas close to but not in the toenails and fingernails as well as in the soles of the feet and palms of the hands. KTs are here regarded as distinct from acral angiofibromas.
KTs most commonly develop in individuals who have the rare genetic disease, tuberous sclerosis (a heritable neurocutaneous disorder) and uncommonly in individuals that do not have this genetic disease. One individual with another rare genetic disease that has similarities to tuberous sclerosis, the Birt-Hogg-Dube syndrome, has also been reported to have typical KT findings.KTs are strictly benign (i.e. do not metastasize) but may be painful, disfiguring, and sometimes large and/or incapacitating lesions. They have often been treated by strictly local surgical resections. However, they do have a high rate of recurrence at the site of resection and therefore have been treated with various other non-invasive local measures in efforts to avoid recurrences; these other methods have also been preferred to treat numerous tumors in individuals, for cosmetic reasons, and/or to relieve tumor-induce incapacitations.
Presentation
In individuals with tuberous sclerosis, KTs commonly present with multiple firm red-colored to skin-colored nodules or tumors that emanate from the proximal nail fold or, less often, proximal skin beneath the nail. They often develop after puberty; increase in number over time; more frequently occur in the toenails than fingernails (the most common sites are on the big toe and thumb); are generally 5 to 10 mm in length but occasionally grow to far larger sizes; and may be or become disfiguring, painful, and/or incapacitating. Nearly 50% of post-puberty individuals with tuberous sclerosis have KTs. (Tuberous sclerosis is also associated with a second type of angiofibroma, adenoma sebaceum, also termed facial angiofibroma, in ~75% of cases.) Individuals presenting with KTs that do not have tuberous sclerosis commonly present with a single lesion in a nail bed. KT may also present as a recurrence of a lesion at the site where it was surgically removed. Rare cases of KTs have had a history of crushing trauma at the sites where the KTs later developed.
Pathology
Microscopic histopathological analyses of KTs commonly reveal a lesion with epidermal acanthosis (i.e. thickening of the skin), hyperkeratosis (i.e. thickening of the outermost layer of the epidermis), and skin features typical of angiofibroma viz., spindle-shaped or star-shaped fibroblasts and ectatic blood vessels in a dense collagen fiber connective tissue background.
Etiology
In cases associated with tuberous sclerosis, KTs appear to be a result of this diseases associated genetic abnormalies, i.e. loss-of-function mutations in one of the two normally paired TSC1 or one of the two normally paired TSC2 tumor suppressor genes. As a part of their functions, the TSC1 and TSC2 tumor suppressor genes act to suppress the abnormal growth of cells by contributing to the suppression of the mammalian target of rapamycin (i.e. mTOR) protein that promotes cell growth and proliferation. Inactivation of one of the TSC1 or TSC2 genes appears responsible for unleashing mTor and thereby promoting the growth of the many strictly benign lesions, including KTs, that develop in individuals with tuberous sclerosis. mTOR is inhibited by rapamycin, a drug which has been used as a topical application to successfully treat a few cases of Koenens tumors.A small number of cases in individuals including those that do not have tuberous sclerosis may develop KTs as reactions to local traumas.
Treatment
The treatment of KTs has varied depending on their size, numbers, locations, symptoms, damage to tissues, and disfiguring effects. Excision may be the treatment of choice for surgically accessible lesions. However, following surgical removal, KTs have a high rate of local recurrence, particularly in cases where the lesions are not completely removed. Other treatment methods, which may be used in combination with surgical removal and/or with each other include: carbon dioxide-based laser vaporization; electrocauterization; shave excision of the tumor with phenolization (i.e. excision of the tumor’s protruding portion followed by treatment of the proximal perionych [i.e., skin around a nail] with phenol to eradicate the root of the tumor); and in individuals with tuberous sclerosis, topical application of sirolimus, i.e. rapamycin, (1% solution). Some of the latter methods have been used in order to preserve the nail matrix and nailplate and may be ideal for younger patients with few tumors since they may leave a normal appearing nail.
See also
List of cutaneous conditions
Nail anatomy
== References == |
Pituitary stalk | The pituitary stalk (also known as the infundibular stalk, Fendersons funnel, or simply the infundibulum) is the connection between the hypothalamus and the posterior pituitary. The floor of the third ventricle is prolonged downward as a funnel-shaped recess—the infundibular recess—into the infundibulum, where the apex of the pituitary is attached.
It passes through the dura mater of the diaphragma sellae as it carries axons from the magnocellular neurosecretory cells of the hypothalamus down to the posterior pituitary where they release their neurohypophysial hormones, oxytocin and vasopressin, into the blood.
This connection is called the hypothalamo-hypophyseal tract or hypothalamo-neurohypophyseal tract.
Damage to the pituitary stalk blocks the release of antidiuretic hormone, resulting in polydipsia (excessive water intake) and polyuria (excessive urination).
The diameter of the pituitary stalk at the level of optic chiasm is 3.3 mm, and at the pituitary gland insertion site is measured at 1.9 mm.
See also
Pituitary stalk interruption syndrome
Additional images
== References == |
Erosive pustular dermatitis of the scalp | Erosive pustular dermatitis of the scalp presents with pustules, erosions, and crusts on the scalp of primarily older Caucasian females, and on biopsy, has a lymphoplasmacytic infiltrate with or without foreign body giant cells and pilosebaceous atrophy.: 650 : 761
See also
Skin lesion
Cicatricial alopecia
List of cutaneous conditions
== References == |
Occupational lung disease | Occupational lung diseases are work-related, lung conditions that have been caused or made worse by the materials a person is exposed to within the workplace. It includes a broad group of diseases, including occupational asthma, industrial bronchitis, chronic obstructive pulmonary disease (COPD), bronchiolitis obliterans, inhalation injury, interstitial lung diseases (such as pneumoconiosis, hypersensitivity pneumonitis, lung fibrosis), infections, lung cancer and mesothelioma. These diseases can be caused directly or due to immunological response to an exposure to a variety of dusts, chemicals, proteins or organisms.
Occupational cases of interstitial lung disease may be misdiagnosed as COPD, idiopathic pulmonary fibrosis, or a myriad of other diseases; leading to a delay in identification of the causative agent.
Types of occupational lung diseases
Asthma
Asthma is a respiratory disease that can begin or worsen due to exposure at work and is characterized by episodic narrowing of the respiratory tract. Occupational asthma has a variety of causes, including sensitization to a specific substance, causing an allergic response; or a reaction to an irritant that is inhaled in the workplace. Exposure to various substances can also worsen pre-existing asthma. People who work in isocyanate manufacturing, who use latex gloves, or who work in an indoor office environment are at higher risk for occupational asthma than the average US worker. Approximately 2 million people in the US have occupational asthma.
Bronchiolitis obliterans
Bronchiolitis obliterans, also known as constrictive bronchiolitis or obliterative bronchiolitis is a respiratory disease caused by injury to the smallest airways, called bronchioles. It has been reported to occur from exposure to inhaled toxins and gases including sulfur mustard gas, nitrogen oxides, diacetyl (used in many food and beverage flavorings), 2,3-pentanedione, fly ash and fiberglass.
COPD
Chronic obstructive pulmonary disease is a respiratory disease that can encompass chronic bronchitis and/or emphysema. 15% of the cases of COPD in the United States can be attributed to occupational exposure, including exposure to silica and coal dust. People who work in mining, construction, manufacturing (specifically textiles, rubber, plastic, and leather), building, and utilities are at higher risk for COPD than the average US worker.
Hypersensitivity pneumonitis
Hypersensitivity pneumonitis (HP; also called allergic alveolitis, bagpipe lung, or extrinsic allergic alveolitis, EAA) is an inflammation of the alveoli within the lung caused by hypersensitivity to inhaled organic dusts.
Lung cancer
Numerous categories of ionizing radiation, chemicals and mixtures, occupational exposures, metals, dust and fibers have been linked to occurrence of lung cancer.
Mesothelioma
Mesothelioma is a cancer of the mesothelium, part of which is the pleura, the lining of the lungs. Mesothelioma is caused by exposure to asbestos.
Pneumoconiosis
Pneumoconiosis are occupational lung diseases that are caused due to accumulation of dust in the lungs and bodys reaction to its presence. Most common pneumoconiosis are silicosis, coal workers’ pneumoconiosis (CWP), and asbestosis. Other examples include minerals (such kaolin, talc, mica), beryllium lung disease, hard metal disease and silicon carbide pneumoconiosis.
Smoke Inhalation
Inhaling smoke and other byproducts of combustion can cause pulmonary injury. A third of all burn victims admitted to a hospital are affected by pulmonary injury from inhaling smoke and fatality from inhalation injuries is higher than burn injuries - mortality exceeds 50% for burn victims with severe burn and inhalation injury. Tissue oxygenation is significantly affected and thermal injury to the upper airways, lower airways, and lung parenchyma occurs.
Poor tissue oxygenation is a life-threatening conditions and results from inhaling carbon monoxide, cyanide, a gas mixtures devoid of oxygen, or from an imbalance between alveolar ventilation and blood supply.
Carbon monoxide is a colorless and odorless gas, which can interfere with and impede respiration. Oxygens tendency to bind with hemoglobin is 250 times less than carbon monoxide, severely reducing the quantity of circulating oxygen and limiting tissue oxygenation in carbon monoxide poisoning. Exposure can be deliberate (suicidal) or accidental and can come from automobile exhaust pipes, inhaling smoke during a fire accident, and poorly vented gas heaters, generators, and other appliances.Cyanide is inhaled into the lungs in gaseous form – as hydrogen cyanide. Cyanide can also be diffused through the skin or ingested. Rapid infusion of high-dose cyanide cause cyanide poisoning. It is produced when nitroprusside is broken down into its constituents. It inhibits cells from properly utilizing oxygen by disrupting cytochrome oxidase, and can be more damaging to the brain and heart.Cyanide is a highly toxic chemical often used in industries and in laboratories. Finger nail glue remover products contain acetonitrile and its metabolic break down produces cyanide. In some plants such as in pits of apricots, cyanide can be found as glycosides can synthesize cyanide. Smoking cigarettes is a major avenue of exposure.
Pulmonary Aspiration Syndromes
Deglutition is the main cause for minute food and fluid to get aspirated into the lungs. Impaired consciousness and esophageal disorders can cause deglutition.
Acute Aspiration of Gastric Content (Mendelson Syndrome): pulmonary response to aspirated content depend on the quantity and constituent of aspirated gastric content. Chemical pneumonitis is severe if aspirated content is acidic and aspirated gastric acid – pH less than 2.5 – can inflame bronchial epithelium and cause bronchiolitis, hemorrhagen, and pulmonary edema.Chronic Aspiration of Gastric Contents: disorders of the larynx and the esophagus are major causes of chronic aspiration of gastric content – achalasia, esophageal stricture, systemic sclerosis (scleroderma), esophageal carcinoma, esophagitis, and gastro-esophageal reflux. Pulmonary aspiration can result when the lower intestinal sphincter relax and spill out gastric content into the esophagus.Smoking, consuming alcohol or caffeine, and the drug theophylline used in asthma patients are known to cause lower intestinal sphincter relaxation. Gastro-esophageal reflux and chronic aspiration are associated with few pulmonary disorders: asthma, chronic cough, bronchiectasis, and pulmonary fibrosis.Difficulty swallowing, ageing, dental problems impeding proper chewing, consuming alcohol, and taking sedatives cause café coronary, obstruction of the upper airways by food particles.Retaining an Aspirated Foreign Body: poor clearance of aspirated material out of the tracheobronchial tree can result in acute and chronic conditions including atelectasis, post obstructive hyperinflation, acute and recurrent pneumonia, bronchiectasis, and lung abscesses. Retained aspirated foreign body can sometimes get misdiagnosed as asthma, chronic obstructive pulmonary disease (COPD), or lung cancerAspirating an Inert Material: aspirating large inert material coupled with an impaired cough can cause asphyxiaHydrocarbon Pneumonitis: secondary aspiration following vomiting ingested petroleum products – gasoline, kerosene, furniture polish, and other petroleum products used around home environment – can injure lungs and result in hydrocarbon pneumonitisLipoid Pneumonia: is a chronic disorder common among older people who have difficulty swallowing, with aspiration of oily material - mineral oil, cod liver oil, and oily nose drops - as its mains cause
Occupational environmental exposure
Arsenic
Arsenic is classified as an IARC Group 1 carcinogen and is a cause of lung cancer. Workers can be exposed to arsenic through work with some pesticides or in copper smelting.
Asbestos
Asbestos is a mineral which was extensively used in the United States to fireproof buildings and textiles, among other items, in the 1950s-1980s. Workers are frequently exposed to asbestos during demolition and renovation work, which can cause asbestosis and/or mesothelioma. Asbestos exposure can also cause pleural effusion, diffuse pleural fibrosis, pleural plaques, and non-mesothelioma lung cancer. Smoking greatly increases the lung cancer risk of asbestos exposure.Residents and workers of asbestos mining centers such as the town of Asbest, Russia experience dangerous exposure to asbestos and asbestos dust.
BCME
BCME (Bis(chloromethyl) ether) is associated with small cell lung cancer in workers who have been exposed. Exposure can occur via direct manufacture of BCME or its presence as a byproduct.
Beryllium
Beryllium is classified as an IARC Group 1 carcinogen and can also cause interstitial lung disease. Manufacturing workers, dental technicians, machinists, jewelers, plumbers, electricians, precious metal reclamation workers, and welders are at risk for beryllium exposure.
Cadmium
Cadmium is classified as an IARC Group 1 carcinogen and it is a cause of several cancers, including lung cancer. Workers can be exposed to cadmium through welding, zinc smelting, copper smelting, lead smelting, electroplating, battery manufacture, plastics manufacture, and in alloying.
Chromium
Chromium is classified as an IARC Group 1 carcinogen and is linked to lung cancer. Workers can be exposed to chromium via welding, steel manufacturing, pigment/dye manufacturing, and electroplating.
Coal dust
Exposure to coal dust is the cause of coalworkers pneumoconiosis, also called "black lung disease", is an interstitial lung disease caused by long-term exposure (over 10 years) to coal dust. Symptoms include shortness of breath and lowered pulmonary function. It can be fatal when advanced. Between 1970 and 1974, prevalence of CWP among US coal miners who had worked over 25 years was 32%; the same group saw a prevalence of 9% in 2005–2006. It can also exacerbate or cause COPD.
Diesel exhaust
Diesel exhaust contains a variety of gaseous and particulate chemicals, including soot, polycyclic aromatic hydrocarbons, and other known carcinogens.
Flock
Flocking is the technique of adding small pieces of nylon or other material to a backing, usually a textile, to create a contrasting texture. Inhalation of flock can cause flock workers lung.
Indium lung
Indium lung is an interstitial lung disease caused by occupational exposure to indium tin oxide.
Nanoparticles
The high surface area to volume ratio of nanoparticles may make them an inhalation hazard for workers exposed to them. This is a topic of ongoing research as of 2015.
Nickel
Nickel is classified by the IARC as a Group 1 carcinogen; nickel compound exposure is associated with nasal cancer as well as lung cancer. Workers may be exposed to nickel in machining/grinding industry, nickel extraction/production, welding, and electroplating.
Polycyclic aromatic hydrocarbons
Polycyclic aromatic hydrocarbons (PAHs), fused-ring chemicals formed during the combustion of fossil fuels, are metabolized by the cytochrome P450 complex to highly reactive carbocations, which can mutate DNA and cause cancer. Workers may be exposed to PAHs while working in a foundry, in the roofing industry, or due to environmental tobacco smoke.
Silica
Exposure to silica can cause Silicosis, which is a fibrosing interstitial lung disease caused by inhaling fine particles of silica, most commonly in the form of quartz or cristobalite. Short-term exposures of large amounts of silica or long-term (10 years or more) exposure of lower levels of silica can cause silicosis. In 1968, more than 1060 US workers died of silicosis; this number fell to 170 by 2005.Besides causing silicosis, inhalation of silica can cause or exacerbate COPD. It can also impair lung function in general and cause cancer by oxidation damage. It is classified as a "known human carcinogen" (Group 1 carcinogen) by the IARC. Exposure is common for people working in tunneling, quarrying, construction, sandblasting, roadway repair, mining, and foundry work.
Silo-fillers disease
Silo-fillers disease (not to be confused with farmers lung associated with inhalation of biologic dusts) results from inhalation of nitrogen dioxide (NO2) gas from fresh silage. The presentation is variable depending on level of exposure. Often the gas penetrates throughout the lung and if severe can manifest as a form of acute respiratory distress syndrome, such as significant pulmonary edema, hyalinized alveolar membranes, congestion and other respiratory illnesses.
Tobacco smoke
Tobacco smoke is a known carcinogen. Workers in the hospitality industry may be exposed to tobacco smoke in the workplace, especially in environments like casinos and bars/restaurants.
Infectious exposure
Influenza
Health care professionals are at risk of occupational influenza exposure; during a pandemic influenza, anyone in a close environment is at risk, including those in an office environment.
Tuberculosis
Tuberculosis is a lung disease endemic in many parts of the world. Health care professionals and prison guards are at high risk for occupational exposure to tuberculosis, since they work with populations with high rates of the disease.
Others
World Trade Center lung
World Trade Center lung is a cluster of diseases caused by exposure to fallout at Ground Zero of the September 11 attacks in 2001. These diseases include asthma, asthmatic bronchitis, terminal airways disease, sarcoidosis, and acute eosinophilic pneumonia.
Examples
Pneumoconiosis
Asbestosis
Baritosis
Bauxite fibrosis
Berylliosis
Caplans syndrome
Chalicosis
Coalworkers pneumoconiosis (black lung)
Siderosis
Silicosis
Byssinosis
Hypersensitivity pneumonitis
Bagassosis
Bird fanciers lung
Farmers lung
== References == |
Gingival recession | Gingival recession, also known as receding gums, is the exposure in the roots of the teeth caused by a loss of gum tissue and/or retraction of the gingival margin from the crown of the teeth. Gum recession is a common problem in adults over the age of 40, but it may also occur starting in adolescence, or around the age of 10. It may exist with or without concomitant decrease in crown-to-root ratio (recession of alveolar bone).
Classification
Various classifications have been proposed to classify gingival recession, Miller’s classification system being the one that is most widely followed. Many cases which are encountered in daily clinical practice cannot be classified according to the criteria of the present classification systems. Kumar & Masamattis classification system gives a comprehensive depiction of recession defect that can be used to include cases that cannot be classified according to present classifications. A separate classification system for palatal recessions (PR) has been given. A new comprehensive classification system classifies recession on the basis of the position of interdental papilla and buccal/lingual/palatal recessions. Kumar & Masamattis classification system tries to overcome the limitations of Millers classification.
Causes
There are many possible causes for gingival recession:
By far the most common cause is gum disease (periodontal disease).
Overaggressive brushing also causes gum recession. One systemic review of the literature concluded that "The data to support or refute the association between tooth brushing and gingival recession are inconclusive," although aggressive or forceful brushing was not specifically addressed. A subsequent study found horizontal tooth brushing technique (versus Bass technique or circular methods), medium-hardness toothbrush use and brushing only once daily were associated with gingival recession.
Improper flossing (i.e., flossing too roughly or aggressively) which may cut into the gums.
Hereditary thin, fragile or insufficient gingival tissue predisposes to gingival recession.
Dipping tobacco, which affects the mucous membrane lining in the mouth and will cause receding gums over time
Self-inflicted trauma, such as habits like digging a fingernail or pencil into the gum. This type of recession more commonly associated with children and persons with psychiatric disorders.
Scurvy (lack of dietary vitamin C)
Acute necrotizing ulcerative gingivitis
Abnormal tooth position, such as tooth crowding, giving inadequate cover of one or more teeth by the jaw bone.
Piercings in the lip or tongue that wear away the gum by rubbing against it.
Intentional gingival retraction. For example, the adult tooth may not grow out of the gum, and to remedy this, a procedure called an exposure is done. It involves the gum tissue being cut open to allow the adult tooth to grow out. This is a less common cause of gum recession.
Symptoms
Gum recession is generally not an acute condition. In most cases, receding of gums is a progressive condition that occurs gradually over the years. This is one reason that it is common over the age of 40. Because the changes in the condition of the gums from one day to another are minimal, patients get used to the gums appearance and tend not to notice the recession visually. Receding gums may remain unnoticed until the condition starts to cause symptoms.
The following signs and symptoms may indicate gum recession:
Tooth mobility
Dentin hypersensitivity (over-sensitive teeth) - short, sharp pain is triggered by hot, cold, sweet, sour, or spicy food and drink. If the cementum covering the root is not protected anymore by the gums, it is easily abraded exposing the dentin tubules to external stimuli.
Teeth may also appear longer than normal (a larger part of the crown is visible if gums are receding)
The roots of the tooth are exposed and visible
The tooth feels notched at the gum line
Change in the tooth’s color (due to the color difference between enamel and cementum)
Spaces between teeth seem to grow (the space is the same, but it seems larger because the gums do not fill it any more)
Cavities below the gum lineIf the gum recession is caused by gingivitis, the following symptoms may also be present:
Puffy, red, or swollen (inflamed) gums
Gum bleeding while brushing or flossing
Bad breath (halitosis)In some cases, it is the treatment of gingivitis that reveals a gum recession problem, that was previously masked by the gums swelling.
Gingival grafting
Depending on the shape of the gum recession and the levels of bone around the teeth, areas of gum recession can be regenerated with new gum tissue using a variety of gum grafting "periodontal plastic surgery" procedures performed by a specialist in periodontics (a periodontist). These procedures are typically completed under local anesthesia with or without conscious sedation, as the patient prefers. This may involve repositioning of adjacent gum tissue to cover the recession (called a pedicle graft) or use of a free graft of gingival or connective tissue from the roof of the mouth (called a free gingival graft or a subepithelial connective tissue graft). Alternatively, a material called acellular dermal matrix (processed donated human skin allograft) may be used instead of tissue from the patients own palate.
Growth-factor techniques
Recent advances have seen the introduction of platelet-derived growth factor (PDGF) infused bone graft material. This material is usually combined with the cellular matrix to form a soft bone paste that is then covered by the allograft. The development of this type of bone and tissue cellular matrix (also known as ortho filler) results in greater osseointegration with the patients healthy bone and soft tissue.
Healing from such procedures requires 2–4 weeks. After a few months the results can be evaluated and in some cases the new tissue needs to be reshaped in a very minor procedure to get an optimal result. In cases where recession is not accompanied by periodontal bone loss, complete or near complete coverage of the recession area is achievable.
References
External links
An academic presentation on gingival recession
Highly informative overview article from the NYTimes. |
Chronic cerebrospinal venous insufficiency controversy | Chronic cerebrospinal venous insufficiency (CCSVI or CCVI) is a term invented by Italian researcher Paolo Zamboni in 2008 to describe compromised flow of blood in the veins draining the central nervous system. Zamboni hypothesized that it might play a role in the cause or development of multiple sclerosis (MS). Zamboni also devised a surgical procedure which the media nicknamed a liberation procedure or liberation therapy, involving venoplasty or stenting of certain veins. Zambonis ideas about CCSVI are very controversial, with significantly more detractors than supporters, and any treatments based on his ideas are considered experimental.There is no scientific evidence that CCSVI is related to MS, and there is no good evidence that the surgery helps MS patients. Zambonis first published research was neither blinded nor did it have a comparison group. Zamboni also did not disclose his financial ties to Esaote, the manufacturer of the ultrasound specifically used in CCSVI diagnosis. The "liberation procedure" has been criticized for possibly resulting in serious complications and deaths, while its purported benefits have not been proven. In 2012, the United States Food and Drug Administration states that it is not clear if CCSVI exists as a clinical entity and that these treatments may cause more harm. In 2017 they emphasized that this use of balloon angioplasty is not an approved use. In a 2017 study Zamboni et al. stated "Venous PTA cannot be recommended for patients with relapsing-remitting multiple sclerosis." In 2018 a study in Neurology concluded "Our data do not support the continued use of venoplasty of extracranial jugular and/or azygous venous narrowing to improve patient-reported outcomes, chronic MS symptoms, or the disease course of MS."Research on CCSVI was fast-tracked, but researchers have been unable to find a connection between CCSVI and MS. This has raised serious objections to the hypothesis of CCSVI originating multiple sclerosis. Additional research investigating the CCSVI hypothesis is underway. A 2013 study found that CCSVI is equally rare in people with and without MS, while narrowing of the cervical veins is equally common.
Hypothesis
Proposed consequences of CCSVI syndrome include intracranial hypoxia, delayed perfusion, reduced drainage of catabolites, increased transpulmonary pressure, and iron deposits around the cerebral veins. Multiple sclerosis has been proposed as a possible outcome of CCSVI.
Pathophysiology
Zamboni and colleagues claimed that in MS patients diagnosed with CCSVI, the azygos and IJV veins are stenotic (abnormally narrowed) in around 90% of cases. Zamboni theorized that malformed blood vessels cause increased deposition of iron in the brain, which in turn triggers autoimmunity and degeneration of the nerves myelin sheath. While the initial article on CCSVI claimed that abnormal venous function parameters were not seen in healthy people, others have noted that this is not the case. In the report by Zamboni none of the healthy participants met criteria for a diagnosis of CCSVI while all patients did. Such outstanding results have raised suspicions of a possible spectrum bias, which originates on a diagnostic test not being used under clinically significant conditions.Further studies of the relationship between CCSVI and MS have had variable results, with many failing to reproduce the association between MS and CCSVI. Moreover, the greatest predictor of positive results is researchers involvement in the administration of the "liberation procedure". This effect goes to the extent that, when only fully independent studies are considered, no association at all is found. The poor reproducibility across studies and diagnostic modalities has led some authors to conclude that CCVSI might be nothing more than a clinically irrelevant sonographic construct.Already by 2010, there were "a growing number of papers that raise serious questions about its (CCSVI) validity", although evidence had been "both for and against the controversial hypothesis". It was agreed that it was urgent to perform appropriate epidemiological studies to define the possible relationship between CCSVI and MS, although existing data did not support CCSVI as the cause of MS.
Venous malformations
Most of the venous problems in MS patients have been reported to be truncular venous malformations, including azygous stenosis, defective jugular valves and jugular vein aneurysms. Problems with the innominate vein and superior vena cava have also been reported to contribute to CCSVI. A vascular component in MS had been cited previously.Several characteristics of venous diseases make it difficult to include MS in this group. In its current form, CCSVI cannot explain some of the epidemiological findings in MS. These include risk factors such as Epstein-Barr infection, parental ancestry, date of birth and geographic location. MS is also more common in women, while venous diseases are more common in men. Venous pathology is commonly associated with hypertension, infarcts, edema and transient ischemia, and occurs more often with age, however these conditions are hardly ever seen in MS and the disease seldom appears after age 50. Finally, an organ-specific immune response is not seen in any other kind of venous disease.
Iron deposits
Iron deposition as a cause of MS received support when a relationship between venous pressure and iron depositions in MS patients was found in a neuroimaging study, and criticism as other researchers found normal ferritin levels in the cerebrospinal fluid of MS patients. Additionally iron deposition occurs in different neurological diseases such as Alzheimers disease or Parkinsons disease that are not associated with CCSVI. Evidence linking CCSVI and iron deposition is lacking, and dysregulation of iron metabolism in MS is more complex than simply iron accumulation in the brain tissue.
Genetics
A small genetic study looked at fifteen MS patients who also had CCSVI. It found 234 specific copy number variations in the human leukocyte antigen focus. Of these, GRB2, HSPA1L and HSPA1A were found to be specifically connected to both MS and angiogenesis, TAF11 was connected to both MS and artery passage, and HLA-DQA2 was suggestive of having an implication for angiogenesis as it interacts with CD4. A study in 268 MS patients and 155 controls reported more a frequency of CCSVI in the MS group that was more than twice as high as in the controls group and was also higher in the progressive MS group than in the non-progressive MS group. This study found no relationship between CCSVI and HLA DRB1*1501, a genetic variation that has been consistently linked to MS.
Diagnosis
CCSVI was first described using specialized extracranial and transcranial doppler sonography. Five ultrasound criteria of venous drainage have been proposed to be characteristic of the syndrome, although two are considered sufficient for diagnosis of CCSVI:
reflux in the internal jugular and vertebral veins,
reflux in the deep cerebral veins,
high-resolution B-mode ultrasound evidence of stenosis of the internal jugular vein,
absence of flow in the internal jugular or vertebral veins on Doppler ultrasound, and
reverted postural control of the main cerebral venous outflow pathways.It is still not clear whether magnetic resonance venography, venous angiography, or Doppler sonography should be considered the gold standard for the diagnosis of CCSVI. Use of magnetic resonance venography for the diagnosis of CCSVI in MS patients has been proposed by some to have limited value, and should be used only in combination with other techniques. Others have stated that magnetic resonance venography is a valid measure which has advantages over Doppler including the fact that results are more operator-independent.Diagnostic criteria have been criticized. Both the number of criteria and the need of being positive for two of them as enough for diagnosis are arbitrary ideas. Moreover, experienced groups in the use of ultrasound have not been able to show intracranial or extracranial reflux in MS patients or even healthy controls whereas the criterion of absence of flow and the criterion regarding stenosis are considered not valid since they are related to normal physiological processes and not pathology. These problems in the criteria have led some researchers to consider the criteria inadequate and more generally the concept of CCSVI flawed.
Treatment
All proposed treatments are experimental
Treatment based on the idea of CCSVI is considered experimental.
Further trials are required to determine if the benefits, if any, of the procedure outweigh its risks. Most experts, and medical and patients organizations, including the National Multiple Sclerosis Society of the USA or the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), recommend not using the proposed treatment outside clinical trials until its effectiveness is confirmed by controlled studies. Moreover, the CIRSE has stated that treatment research should begin by a small, placebo-controlled, prospective randomised trial which should be monitored by an independent organization. An exception has been the Society of Interventional Radiology in the US and Canada, which considered research on the effectiveness of CCSVI intervention to be inconclusive as of 2010. In March 2013 a press release indicated that the first prospective, placebo-controlled study of balloon angioplasty for MS had not shown any benefit of the therapy. The study, a phase II clinical trial designed to evaluate safety and efficacy of endovascular treatment, enrolled initially 10 patients that received the treatment and 20 more afterwards that were either allocated to receive angioplasty or a placebo intervention.Kuwait became the first country in the world where treatment of CCSVI, as of 2010, was explicitly allowed by the medical authorities and paid by the state health system. As of 2010, the procedure was performed privately in 40 countries, and, despite existing recommendations, as of 2013 it is believed that over 30,000 patients have undergone the procedure.
Procedures
Balloon angioplasty and stenting have been proposed as treatment options for CCSVI in MS. The proposed treatment has been termed "liberation therapy" though the name has been criticized for suggesting unrealistic results.Balloon angioplasty in a preliminary, uncontrolled, unblinded study by Zamboni improved symptoms in MS in a minority of treated people. Although the procedure pushes the vein open temporarily, the effect does not persist, supporters advise against using stents.Venous percutaneous transluminal angioplasty (PTA) has proven to be safe but due to its ineffectiveness is not recommended.
Adverse effects
While the procedure has been reported to be generally safe for MS patients, severe complications related to the angioplasty and stenting that have been reported include intracranial hemorrhage, stent migration into a renal vein, thrombosis and nerve compression syndrome of cranial nerves XI and XII. One death case appeared in the scientific literature, while 3 other deaths have been related to CCSVI treatment in the media. Some United States hospitals have banned the surgical procedure outside clinical trials due to safety concerns until more evidence to support its use is available.In May 2012 the U.S. Food and Drug Administration issued a safety communication on CCSVI, stating that MS patients undergoing angioplasty and/or stenting to treat CCSVI risk serious injuries or death. Furthermore, it also noted that the benefits of these experimental procedures have not been proven and that studies exploring a link between MS and CCSVI are inconclusive.
History
Venous pathology has been associated with MS for more than a century. Pathologist Georg Eduard Rindfleisch noted in 1863 that the inflammation-associated lesions were distributed around veins. Later, in 1935, Tracy Putnam was able to produce similar lesions in dogs blocking their veinsThe term "chronic cerebrospinal venous insufficiency" was coined in 2008 by Paolo Zamboni, who described it in patients with multiple sclerosis. According to Zamboni, CCSVI had a high sensitivity and specificity differentiating healthy individuals from those with multiple sclerosis. Zambonis results were criticized because his study was not blinded and his results needed to be verified by further studies. Zamboni had become interested in CCSVI in 1999 when his wife was diagnosed with MS.
Society and culture
Conflict of interest
Paolo Zamboni has patents related to the highly sensitive ultrasound diagnostic systems manufactured by Esaote which, he proposes, should be used to diagnose CCSVI. Moreover, Zambonis research center has also received support in the form of equipment and technical assistance from this manufacturer. These are potential conflicts of interest that he has never disclosed when publishing scientific articles, which would be against ethical practices of some countries such as the United States.
Media
CCSVI has received a great deal of attention in all media, the scientific literature and on the Internet. Moreover, the CCSVI case has been considered a good example of how new communication technologies and social media are modifying the traditional relationship between science, politics, medicine, and the general public. In this sense they have played a key role in effectively promoting the theory.Media coverage has been perceived by some as "hype", with exaggerated claims that have led to excessive expectations. This has been partially attributed to some of the investigators of the theory. Mainstream media initial approximations to Zambonis theory were enthusiastic and emphasized Zambonis effort to find a cure for his wife, along with the improvement of some patients after its alleged treatment. Initial difficulty reproducing results connecting MS and CCSVI, combined with reports of secondary effects of the surgical procedure, led to a more cautious discourse proposing that more investigation in the relationship between CCSVI and MS was needed. The first fatality related to CCSVI treatment was a pivotal development in this trend towards a less optimistic media view of the theory.The Internet has been extensively used by patient groups to obtain and disseminate information on CCSVI. People with MS often read extensively about the CCSVI theory and its development on Internet sites, and a search for "liberation procedure" in Google as of August 2010 yielded more than 2.5 million hits. The Internet has also been used to advertise places where stenting for CCSVI is performed, and to more generally disseminate all the information on CCSVI. Social media have served patient groups in their attempt to pressure official bodies to make decisions favoring funding of clinical trials, or the public coverage of stenting and venoplasty as treatments of MS. Likewise, social media have been accused of creating a division between CCSVI supporters and those who say it does not work. Indeed, they have been repeatedly used by advocates of the CCSVI theory to attack those who were more critical or cautious, most commonly with accusations of being tainted due to commercial relationships with pharmaceutical companies.Many patients who have had the surgical procedure report their improvements on social media websites such as structured patient databases and YouTube. Such stories are only anecdotal evidence of efficacy, and do not constitute a scientific proof of the efficacy of the treatment since, for example, those who have had a positive result are more prone to post their cases than those who had little or no improvement, and the reported improvements in patients condition can be attributed to the placebo effect. Patients reasons for not publishing negative results may include embarrassment about the money spent in the procedure without effect and the negative reaction they expect from other people with MS. Caution has been recommended regarding patients self-reports found on the web.Scientists and physicians transmitted their arguments regarding CCSVI inadequately, especially after the initial rising of the hypothesis. Their communication was characterized by an excessive hesitation and a lack of clear statements, as opposed to CCSVI proponents, who "won the communication battle, at least in the early rounds." A positive effect of the important media coverage may be that it forces the world of medical research to be self-critical and give appropriate responses to the questions that globalization of the theory raises, especially among people with MS.
Reception in Canada
While reasons are not completely clear, the CCSVI theory was received differently in Canada than other places. The public interest and number of media appearances were much greater than elsewhere, including Italy, and debate has been heated regarding funding. As an example, by the end of 2009, a public petition to the country health authorities in support of the "liberation treatment" had received over 17,000 signatures. The debate regarding funding in Canada has been considered to be specially informative as an example of extreme involvement of politics, due to public pressure, in decisions usually governed by scientific evidence.In 2009, the Multiple Sclerosis Society of Canada committed to funding research on the connection between CCSVI and MS, although later in 2010 it came under criticism for opposing clinical trials of CCSVI therapy. The MS Society of Canada in September 2010 reserved one million dollars toward CCSVI research "when a therapeutic trial is warranted and approved."At a political level there have been contradictory positions, with some provinces funding trials, others stating that since therapy is unproven they should wait, and others urging for a pan-Canadian trial. British Columbia, Alberta, and Newfoundland and Labrador funded observational studies in which patients who had already received the treatment were included. Over 2 million dollars were allocated to these studies. The province of Saskatchewan was more aggressive and provided 2.2 million dollars for some of its residents to be included in a clinical trial.The Canadian Institutes of Health Research (CIHR), the federal agency responsible for funding health research, recommended in 2010 against funding a pan-Canadian trial of liberation therapy because there was a lack of evidence on the safety or efficacy of the procedure. It suggested a scientific expert working group made up of the principal investigators for the seven MS Society-sponsored studies. The health minister accepted the CIHR recommendation and said that Canada was not going to fund clinical trials. The expert panel was created by the end of 2010 together between the CIHR and the MS Society of Canada. It has been proposed that the creation of this expert panel was partly directed to cope with the high levels of social pressure the CCSVI theory had raised and at the same time try to maintain a scientific perspective in the funding and investigation of CCSVI. The main task of the panel was to monitor the results of the ongoing studies in the relationship between CCSVI and MS and recommend the funding of a clinical trial in case that there was evidence of a true relationship between the two. In 2011, the Canadian federal government announced that they would fund clinical trials of the procedure to widen the veins since CIHR considered that evidence of venous abnormalities in MS was enough for small treatment trials. It has been proposed that the recommendation to fund phase I and II trials instead of a big study was a compromise between the high levels of social and political pressure and the low level of evidence on the theory.Two qualitative studies have investigated the motives and experiences of Canadian patients traveling abroad to get the "liberation procedure". One of the studies identified three factors contributing to patients going abroad seeking treatment: a loss of faith in the Canadian health system when it did not provide access to CCSVI treatment in Canada, hope in the new treatment as a solution for their worsening health, and trust in the MS community and the organizations, clinics and doctors facilitating or providing the desired operation. Conversely, the other study concluded that sense of community and cooperation (from family, MS groups and the general population) was a key motivating factor. Other motivating factors included media reports, perception of approval from their health providers, the apparent low risk of the operation, or accessibility of the hospital that offered the procedure directly or through a medical tourism company. On the other hand, hesitating factors included the cost and effort required for the operation, the mistrust of foreign health systems, the underlying rationale for the operation, or advice against the procedure from trusted health providers.In 2013, a case-control study found evidence against the involvement of chronic cerebrospinal venous abnormalities in MS. Later in 2013 a study found that vein narrowing appears to be present equally in those with and without MS on ultrasound and catheter venography. The results of the study were described as a "death knell" for Zambonis theory. Another study released by the University of British Columbia in 2017 was described as a "definitive debunking" of liberation therapy.
Organizations
Several national and international organizations have been created to further the research and dissemination of the CCSVI theory, such as the International Society for Neurovascular Disease and the National CCSVI Society of Canada. They are working together with already existing organizations like the International Union of Phlebology (Union internationale de phlébologie-UIP- in French, its original working language) of which Zamboni is a member. The UIP for example proposed that developmental abnormalities were the primary cause of CCSVI.
Research
There were further studies aimed at clarifying if there is a relationship between MS and CCSVI. In particular, the US and Canadian MS societies launched seven such studies. Recent reviewers have shown "no significant difference in prevalence of CCSVI in people with MS compared to people without MS". In 2014 imaging criteria for venous abnormalities were published to help with research on this topic.
See also
Chronic venous insufficiency
Pathophysiology of multiple sclerosis
Vascular myelopathy
References
Further reading
== External links == |
Adjustment disorder | Adjustment disorder is a maladaptive response to a psychosocial stressor. It is classified as a mental disorder. The maladaptive response usually involves otherwise normal emotional and behavioral reactions that manifest more intensely than usual (considering contextual and cultural factors), causing marked distress, preoccupation with the stressor and its consequences, and functional impairment.Diagnosis of adjustment disorder is common. Lifetime prevalence estimates for adults range from five percent to 21%. Adult women are diagnosed twice as often as men. Among children and adolescents, girls and boys are equally likely to be diagnosed with an Adjustment disorder.Adjustment disorder was introduced into the Diagnostic and Statistical Manual of Mental Disorders in 1980 (DSM-III).Other names for adjustment disorder are stress response syndrome (new name as of 2013) and situational depression since it is one of the most common symptoms.
Signs and symptoms
Some emotional signs of adjustment disorder are: sadness, hopelessness, lack of enjoyment, crying spells, nervousness, anxiety, desperation, feeling overwhelmed and thoughts of suicide, performing poorly in school/work etc.Common characteristics of Adjustment disorder include mild depressive symptoms, anxiety symptoms, and traumatic stress symptoms or a combination of the three. According to the DSM-5, there are six types of Adjustment disorder, which are characterized by the following predominant symptoms: depressed mood, anxiety, mixed depression and anxiety, disturbance of conduct, mixed disturbance of emotions and conduct, and unspecified. However, the criteria for these symptoms are not specified in greater detail. Adjustment disorder may be acute or chronic, depending on whether it lasts more or less than six months. According to the DSM-5, if the Adjustment disorder lasts less than six months, then it may be considered acute. If it lasts more than six months, it may be considered chronic. Moreover, the symptoms cannot last longer than six months after the stressor(s), or its consequences, have terminated.: 679 However, the stress-related disturbance does not only exist as an exacerbation of a pre-existing mental disorder.Unlike major depression, the disorder is caused by an outside stressor and generally resolves once the individual is able to adapt to the situation. The condition is different from anxiety disorder, which lacks the presence of a stressor, or post-traumatic stress disorder and acute stress disorder, which usually are associated with a more intense stressor.
Suicidal behavior is prominent among people with Adjustment disorder of all ages, and up to one-fifth of adolescent suicide victims may have an adjustment disorder. Bronish and Hecht (1989) found that 70% of a series of patients with Adjustment disorder attempted suicide immediately before their index admission and they remitted faster than a comparison group with major depression. Asnis et al. (1993) found that Adjustment disorder patients report persistent ideation or suicide attempts less frequently than those diagnosed with major depression. According to a study on 82 Adjustment disorder patients at a clinic, Bolu et al. (2012) found that 22 (26.8%) of these patients were admitted due to suicide attempt, consistent with previous findings. In addition, it was found that 15 of these 22 patients chose suicide methods that involved high chances of being saved. Henriksson et al. (2005) states statistically that the stressors are of one-half related to parental issues and one-third in peer issues.One hypothesis about Adjustment disorder is that it may represent a sub-threshold clinical syndrome.
Subtypes and Their Symptoms
Adjustment disorder has six different subtypes, and they are all based on what the main symptoms are.Those subtypes are as follows:
With depressed mood: depression, hopelessness, lack of interest or joy from previously enjoyed hobbies, tearfulness
With anxiety: anxiousness, being overwhelmed, trouble concentrating, worry, separation anxiety (common in children)
With anxiety and depressed mood: combination of symptoms from both subtypes above
With disturbance of conduct: acting destructive, reckless behavior, rebellious
With mixed disturbance of emotions and conduct: combination of symptoms from both subtypes above
Unspecified: symptoms that do not fall into above subtypes; often include physical symptoms and withdrawal from everyday activities
Risk factors
Those exposed to repeated trauma are at greater risk, even if that trauma is in the past. Age can be a factor due to young children having fewer coping resources and because they are less likely to realize the consequences of a potential stressor.A stressor is generally an event of a serious, unusual nature that an individual or group of individuals experience. Adjustment disorders can come from a wide range of stressors that can be traumatic or relatively minor, like the loss of a girlfriend/boyfriend, a poor report card, or moving to a new neighborhood. It is thought that the more often the stressor occurs, the more likely it is to produce Adjustment disorder. The objective nature of the stressor is of secondary importance. A stressor gains its pathogenic potential when the patient perceives it as stressful. The identification of a causal stressor is necessary if a diagnosis of adjustment disorder is to be made.There are certain stressors that are more common in different age groups:Adulthood:
Marital conflict
Financial conflict
Health issues with oneself, partner, or dependent children
Personal tragedy such as death or personal loss
Loss of job or unstable employment conditions e.g., corporate takeover or redundancyAdolescence and childhood:
Family conflict or parental separation
School problems or changing schools
Sexuality issues
Death, illness, or trauma in the familyIn a study conducted from 1990 to 1994 on 89 psychiatric outpatient adolescents, 25% had attempted suicide in which 37.5% had misused alcohol, 87.5% displayed aggressive behaviour, 12.5% had learning difficulties, and 87.5% had anxiety symptoms.
Diagnosis
DSM-5 classification
The basis of the diagnosis is the presence of a precipitating stressor and a clinical evaluation of the possibility of symptom resolution on removal of the stressor due to the limitations in the criteria for diagnosing Adjustment disorder. In addition, the diagnosis of Adjustment disorder is less clear when patients are exposed to stressors long-term, because this type of exposure is associated with Adjustment disorder and major depressive disorder (MDD) and generalized anxiety disorder (GAD).Some signs and criteria used to establish a diagnosis are important. First, the symptoms must clearly follow a stressor. The symptoms should be more severe than would be expected. There should not appear to be other underlying disorders. The symptoms that are present are not part of a normal grieving for the death of family member or other loved one.Adjustment disorders have the ability to be self-limiting. Within five years of when they are originally diagnosed, approximately 20–50% go on to be diagnosed with psychiatric disorders that are more serious.
ICD-11 classification
International Statistical Classification of Diseases and Related Health Problems (ICD), assigns codes to classify diseases, symptoms, complaints, social behaviors, injuries, and such medical-related findings.
ICD-11 classifies Adjustment disorder (6B43) under "Disorders specifically associated with stress".
Treatment
Individuals with an adjustment disorder and depressive or anxiety symptoms may benefit from treatments usually used for depressive or anxiety disorders. The use of different therapies can be beneficial for any age group. There is also a list of medications that can be used to help people with adjustment disorder whose symptoms are too severe for therapy alone. If a person is considering taking medication, they should talk to their doctor.
Specific treatment is based on factors of each individual separately. These factors include but are not limited to age, severity of symptoms, type of adjustment disorder, and personal preference.Different ways to help with the disorder include:
Individual Psychotherapy
Family Therapy
Peer Group Therapy
Medication (used only when the symptoms are severe or with a doctors approval)In addition to professional help, parents and caregivers can help their children with their difficulty adjusting by:
offering encouragement to talk about their emotions
offering support and understanding
reassuring the child that their reactions are normal
involving the childs teachers to check on their progress in school
letting the child make simple decisions at home, such as what to eat for dinner or what show to watch on TV
having the child engage in a hobby or activity they enjoy
Criticism
Like many of the items in the DSM, adjustment disorder receives criticism from a minority of the professional community as well as those in semi-related professions outside the healthcare field. First, there has been criticism of its classification. It has been criticized for its lack of specificity of symptoms, behavioral parameters, and close links with environmental factors. Relatively little research has been done on this condition.An editorial in the British Journal of Psychiatry described adjustment disorder as being so "vague and all-encompassing… as to be useless," but it has been retained in the DSM-5 because of the belief that it serves a useful clinical purpose for clinicians seeking a temporary, mild, non-stigmatizing label, particularly for patients who need a diagnosis for insurance coverage of therapy.In the US military there has been concern about its diagnosis in active duty military personnel.
Adjustment Disorder and the COVID-19 pandemic
A study was conducted in Poland, during the first phase of the pandemic. The study used self-report surveys to measure the prevalence and severity of symptoms of adjustment disorder compared to PTSD, depression, and anxiety. The data was collected in the first quarantine period between March 25 to April 27, 2020.Results from the study
The current COVID-19 pandemic was a highly stressful event for 75% of the participants and the most powerful predictor of adjustment disorder.
49% reported an increase in adjustment disorder symptoms, which were more common among females and those without a full-time job. 14% of the sample met the criteria for a diagnosis of adjustment disorder.
A significant proportion of the sample was also positive for generalized anxiety (44%) and depression (26%): the presumptive diagnosis rate of PTSD was 2.4%
References
Further reading
First, Michael B., ed. (2014). "Differential Diagnosis by the Trees". DSM-5 Handbook of Differential Diagnosis (1st ed.). Arlington, VA: American Psychiatric Publishing. doi:10.1176/appi.books.9781585629992.mf02. ISBN 978-1-58562-999-2. OCLC 864759427.
Casey, P. R., & Strain, J. J. (Eds.). (2015). Trauma-and Stressor-related Disorders: A Handbook for Clinicians. American Psychiatric Pub. ISBN 978-1585625055
== External links == |
Relapsing polychondritis | Relapsing polychondritis is a multi-systemic condition characterized by repeated episodes of inflammation and deterioration of cartilage. The often painful disease can cause joint deformity and be life-threatening if the respiratory tract, heart valves, or blood vessels are affected. The exact mechanism is poorly understood, but it is thought to be related to an immune-mediated attack on particular proteins that are abundant in cartilage.
The diagnosis is reached on the basis of the symptoms and supported by investigations such as blood tests and sometimes other investigations. Treatment may involve symptomatic treatment with painkillers or anti-inflammatory medications, and more severe cases may require suppression of the immune system.
Signs and symptoms
Though any cartilage in the body may be affected in persons with relapsing polychondritis, in many cases the disease affects several areas while sparing others. The disease may be variable in its signs and symptoms, resulting in a difficult diagnosis which may leads to delayed recognition for several months, years or decades.
Joint symptoms are often one of the first signs of the disease with cartilage inflammation initially absent in nearly half the cases.
Associated diseases
There are several other overlapping diseases associated with RP, that should also be taken into account. About one-third of people with RP might be associated with other autoimmune diseases, vasculitides and hematologic disorders. Systemic vasculitis is the most common association with RP, followed by rheumatoid arthritis and systemic lupus erythematosus.
The following table displays the main diseases in association with RP.
Cartilage inflammation
Cartilage inflammation (technically known as chondritis) that is relapsing is very characteristic of the disease and is required for the diagnosis of RP. These recurrent episodes of inflammation over the course of the disease may result in breakdown and loss of cartilage. The signs and symptoms of cartilage inflammation in various parts of the body will be described first.
Ear
Inflammation of the cartilage of the ear is a specific symptom of the disease and affects most people. It is present in about 20% of persons with RP at presentation and in 90% at some point. Both ears are often affected but the inflammation may alternate between either ear during a relapse. It is characteristic for the entire outer part of the ear except the earlobe to be swollen, red, or less often purplish, warm and painful to light touch.The inflammation of the ear usually lasts a few days or more, rarely a few weeks, and then resolves spontaneously and recurs at various intervals. Because of the loss of cartilage, after several flares cauliflower ear deformity may result. The outer part of the ear may be either floppy or hardened by calcifications of the scar tissue that replaces the cartilage. These cauliflower ear deformities occur in about 10% of persons with RP.
Nose
The inflammation of the cartilage of the nose involves the bridge of the nose and is often less marked than the ears. Statistics show that this clinical manifestation is present in 15% of persons with RP and occurs at some point in 65% of persons with RP.Nasal obstruction is not a common feature. Atrophy may eventually develop secondarily during the disease, this appears gradual and is not easily noticed. This can result in collapse of the nasal septum with saddle-nose deformity, which is painless but irreversible.
Respiratory tract
Inflammation occurs in the laryngeal, tracheal and bronchial cartilages. Both of these sites are involved in 10% of persons with RP at presentation and 50% over the course of this autoimmune disease, and is more common among females.
The involvement of the laryngotracheobronchial cartilages may be severe and life-threatening; it causes one-third of all deaths among persons with RP.
Laryngeal chondritis is manifested as pain above the thyroid gland and, more importantly, as dysphonia with a hoarse voice or transient aphonia. Because this disease is relapsing, recurrent laryngeal inflammation may result in laryngomalacia or permanent laryngeal stenosis with inspiratory dyspnea that may require emergency tracheotomy as a temporary or permanent measure.Tracheobronchial involvement may or may not be accompanied with laryngeal chondritis and is potentially the most severe manifestation of RP.The symptoms consist of dyspnea, wheezing, a nonproductive cough, and recurrent, sometimes severe, lower respiratory tract infections.
Obstructive respiratory failure may develop as the result of either permanent tracheal or bronchial narrowing or chondromalacia with expiratory collapse of the tracheobronchial tree. Endoscopy, intubation, or tracheotomy has been shown to hasten death.
Ribs
Involvement of the rib cartilages results in costochondritis. Symptoms include chest wall pain or, less often, swelling of the involved cartilage. The involvement of the ribs is seen in 35% of persons with RP but is rarely the first symptom.
Other manifestations
Relapsing polychondritis may affect many different organ systems of the body. At first, some people with the disease may have only nonspecific symptoms such as fever, weight loss, and malaise.
Joint
The second most common clinical finding of this disease is joint pain with or without arthritis, after chondritis.
All synovial joints may be affected.At presentation, around 33% of people have joint symptoms that involve Polyarthralgia and/or polyarthritis or oligoarthritis that affects various parts of the body and often appears to be episodic, asymmetric, migratory and non-deforming. The most common sites of involvement are the metacarpophalangeal joints, proximal interphalangeal joints and knees. After which is followed by the ankles, wrists, metatarsophalangeal joints and the elbows. Any involvement of the axial skeleton is considered to be very rare. Tests for rheumatoid factor are negative in affected persons with RP, unless there is a co-morbidity with RA.Less often it has been reported that persons may experience arthralgia, monoarthritis, or chronic polyarthritis that mimics rheumatoid arthritis, leading to a difficult diagnosis for this disease. The appearance of erosions and destruction, however, is exceedingly rare and this may point instead to rheumatoid arthritis as a cause.Diseases and inflammation of tendons have been reported in small numbers of people with RP. During the course of the disease, around 80% of people develop joint symptoms.
Eye
Involvement of the eye is rarely the initial symptom but develops in 60% of persons with RP. The most common forms of ocular involvement are usually mild and often consist of unilateral or bilateral episcleritis and/or scleritis, that is often anterior and could be lingering or relapsing. Scleritis that is necrotizing is found to be exceedingly rare. Less often, conjunctivitis occurs.
There are also other ocular manifestations that occur in persons with RP, these include keratoconjunctivitis sicca, peripheral keratitis (rarely with ulcerations), anterior uveitis, retinal vasculitis, proptosis, lid edema, keratoconus, retinopathy, iridocyclitis and ischemic optic neuritis that can lead to blindness.Cataract also is reported in relation to either the disease or to glucocorticoid exposure.
Neurological
The involvement of the peripheral or central nervous system is relatively rare and only occurs in 3% of persons affected with RP, and is sometimes seen in a relation with concomitant vasculitis.
The most common neurological manifestation are palsies of the cranial nerves V and VII. Also hemiplegia, ataxia, myelitis and polyneuropathy have been reported in scientific literature.
Very rare neurological manifestations include aseptic meningitis, meningoencephalitis, stroke, focal or generalized seizures and intracranial aneurysm.
Magnetic Resonance Imaging of the brain shows multifocal areas of enhancement consistent with cerebral vasculitis in some cases.
Kidney
The involvement of the kidney can be caused by primary renal parenchymal lesions, or an underlying vasculitis, or another associated autoimmune disease. Actual kidney involvement is quite rare, elevated creatinine levels are reported in approximately 10% of people with RP, and abnormalities in urinalysis in 26%. Involvement of the kidney often indicates a worse prognosis, with a 10-year survival rate of 30%.
The most common histopathologic finding is mild mesangial proliferation, that is followed by focal and segmental necrotizing glomerulonephritis with crescents. Other abnormalities that are found include glomerulosclerosis, IgA nephropathy and interstitial nephritis. Immunofluorescence studies most often reveal faint deposits of C3, IgG or IgM in the primarily mesangium.
Constitutional symptoms
These symptoms could consist of asthenia, fever, anorexia, and weight loss. They mostly occur during a severe disease flare.
Others
Skin and mucous membranes: 20 to 30% of people with relapsing polychondritis have skin involvement, including aphthous ulcers, genital ulcers, and a number of non-specific skin rashes including erythema nodosum, livedo reticularis, hives, and erythema multiforme.
Cardiovascular system: Relapsing polychrondritis may cause inflammation of the aorta. It can also cause leaky heart valves (aortic valve regurgitation in 4 to 10%, mitral valve regurgitation in 2%).
Causes
Relapsing polychondritis is an autoimmune disease in which the bodys immune system begins to attack and destroy the cartilage tissues in the body. It has been postulated that both cell-mediated immunity and humoral immunity are responsible.Reasons for disease onset are not known, but there is no evidence of a genetic predisposition to developing relapsing polychondritis. However, there are cases where multiple members of the same family have been diagnosed with this illness. Studies indicate that some genetic contribution to susceptibility is likely.
Diagnosis
There is no specific test for relapsing polychondritis. Some people may exhibit abnormal lab results while others may have completely normal labs even during active flares.
Diagnostic criteria
There are several clinical criteria used to diagnose this disease. McAdam et al. introduced the clinical criteria for RP in 1976. These clinical criteria have later been expanded by Damiani et al. in 1979 and finally Michet et al. modified them in 1986. See the following table for these diagnostic clinical criteria and the number of conditions required for an official diagnosis.
Laboratory findings
Patients presenting with acute episodes often have high levels of inflammatory markers such as erythrocyte sedimentation rate or C-reactive protein, ESR or CRP. Patients often have cartilage-specific antibodies present during acute relapsing polychondritis episodes. Antinuclear antibody reflexive panel, rheumatoid factor, and antiphospholipid antibodies are tests that may assist in the evaluation and diagnosis of autoimmune connective-tissue diseases.
Imaging studies
FDG positron emission tomography (PET) may be useful to detect the condition early. Other imaging studies including MRI, CT scans, and X-rays may reveal inflammation and/or damaged cartilage facilitating diagnosis.
Special tests
Biopsy
Biopsy of the cartilage tissue (for example, ear) may show tissue inflammation and destruction, and may help with the diagnosis. The Biopsy of cartilage in patients with relapsing polychondritis may demonstrate chondrolysis, chondritis, and perichondritis.
Pulmonary function tests
It is useful to do a full set of pulmonary function tests, including inspiratory and expiratory flow-volume loops. Patterns consistent with either extrathoracic or intrathoracic obstruction (or both) may occur in this disease. Pulmonary function tests (flow-volume loops) provide a useful noninvasive means of quantifying and following the degree of extrathoracic airway obstruction in relapsing polychondritis.
Differential diagnosis
A differential diagnosis should be taken into account with the following main RP manifestations.
Treatment
There are no prospective randomized controlled trials studying therapies for relapsing polychondritis. Evidence for efficacy of treatments is based on many case reports and series of small groups of patients. There are case reports that non-steroidal anti-inflammatories are effective for mild disease and that corticosteroids are effective for treatment of severe relapsing polychondritis. There are multiple case reports that dapsone is effective in doses from 25 mg/day to 200 mg/day. Corticosteroid-sparing medications such as azathioprine or methotrexate may be used to minimize steroid doses and limit the side effects of steroids. For severe disease cyclophosphamide is often given in addition to high dose intravenous steroids.
Prognosis
Many individuals have mild symptoms, which recur infrequently, while others may have persistent problems that become debilitating or life-threatening.
Epidemiology
Relapsing polychondritis occurs as often in men as in women. In a Mayo Clinic series, the annual incidence was about 3.5 cases per million. The highest incidence is between the ages of 40 and 50 years, but it may occur at any age.
History
In 1923, Rudolf Jaksch von Wartenhorst first discovered relapsing polychondritis while working in Prague and initially named it Polychondropathia.
His patient was a 32-year-old male brewer who presented with fever, asymmetric polyarthritis, and the ears and nose showed signs of swelling, deformity and were painful. Biopsy of nasal cartilage revealed loss of the cartilage matrix and a hyperplastic mucous
membrane. Jaksch von Wartenhorst considered this was an undescribed degenerative disorder of cartilage and named it Polychondropathia.
He even took his patients occupation into consideration, and related the cause to excessive alcohol intake.Since then, the disease has received many names. The following table shows the history of the nomenclature of relapsing polychondritis. The current name, Relapsing Polychondritis (RP), was introduced by Pearson and his colleagues in 1960 to emphasize the episodic course of the disease.
Research
There has been little research on neurological problems related to RP. If these cartilage structures get inflamed, they could press against nerves and cause a variety of problems that is seen in RP like peripheral neuropathy and many more.
References
Further reading
Sanders, Lisa (14 November 2021) [10 November 2021 (online)]. "A Doctor Asks Two Strange Questions That Reveal a Mysterious Disease". The New York Times Magazine. p. 22. Retrieved 10 November 2021.
Trentham DE, Le CH (July 1998). "Relapsing polychondritis". Ann. Intern. Med. 129 (2): 114–22. doi:10.7326/0003-4819-129-2-199807150-00011. PMID 9669970. S2CID 31763543. Archived from the original on 2014-11-08. Retrieved 2006-06-20. |
Woolly hair nevus | Woolly hair nevus (alternatively spelled "Wooly hair nevus") is a congenital condition in which hair in a circumscribed area of the scalp is kinked or woolly.
See also
Woolly hair
Naxos syndrome
Striate palmoplantar keratoderma, woolly hair, and left ventricular dilated cardiomyopathy
List of cutaneous conditions
References
== External links == |
Spinocerebellar ataxia type-13 | Spinocerebellar ataxia type 13 (SCA13) is a rare autosomal dominant disorder, which, like other types of SCA, is characterized by dysarthria, nystagmus, and ataxia of gait, stance and the limbs due to cerebellar dysfunction. Patients with SCA13 also tend to present with epilepsy, an inability to run, and increased reflexes. This cerebellar dysfunction is permanent and progressive. SCA13 is caused by mutations in KCNC3, a gene encoding a voltage-gated potassium channel KV3.3. There are two known mutations in this gene causative for SCA13. Unlike many other types of SCA, these are not polyglutamine expansions but, rather, point mutations resulting in channels with no current or altered kinetics.
Signs and symptoms
SCA13 is typified by early onset, mildly progressive cerebellar ataxia with accompanying dysarthria, mental retardation, and nystagmus. Symptoms and age of onset can vary slightly according to the causative mutation.
Pathophysiology
Mutations in KCNC3 are responsible for SCA13. This gene is expressed heavily in Purkinje cells, as is the case for some other SCA subtypes, where it is believed to play an important role in facilitating high-frequency action potential firing. There are two known mutations in this gene associated with SCA13. The first mutation, R420H, is located in the voltage-sensing S4 segment of the channel. As this mutation neutralizes a site important for voltage sensing, it is not surprising that it results in non-conducting channels. Neurons expressing such channels are unable to follow high-frequency input with adequate fidelity.The second SCA13 associated mutation, F448L, results in functional channels that have altered kinetics. The voltage for half activation of these channels (V½) is shifted 13mV hyperpolarized compared to wild-type. Deactivation of these channels is also slowed drastically compared to wild-type. This results in neurons with longer after-hyperpolarizations and thus, a decreased maximal firing rate.
Diagnosis
Treatment
Prognosis
There is no known prevention of spinocerebellar ataxia. Those who are believed to be at risk can have genetic sequencing of known SCA loci performed to confirm inheritance of the disorder.
Footnotes
External links
GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 13 |
Subcutaneous emphysema | Subcutaneous emphysema (SCE, SE) occurs when gas or air accumulates and seeps under the skin, where normally no gas should be present. Subcutaneous refers to the subcutaneous tissue, and emphysema refers to trapped air pockets resembling the pneumatosis seen in pulmonary emphysema. Since the air generally comes from the chest cavity, subcutaneous emphysema usually occurs around the upper torso, such as on the chest, neck, face, axillae and arms, where it is able to travel with little resistance along the loose connective tissue within the superficial fascia. Subcutaneous emphysema has a characteristic crackling-feel to the touch, a sensation that has been described as similar to touching warm Rice Krispies. This sensation of air under the skin is known as subcutaneous crepitation, a form of Crepitus.
Numerous etiologies of subcutaneous emphysema have been described. Pneumomediastinum was first recognized as a medical entity by Laennec, who reported it as a consequence of trauma in 1819. Later, in 1939, at The Johns Hopkins Hospital, Dr. Louis Hamman described it in postpartum woman; indeed, subcutaneous emphysema is sometimes known as Hammans syndrome. However, in some medical circles, it can instead be more commonly known as Macklins Syndrome after L. Macklin, in 1939, and M.T. and C.C. Macklin, in 1944, who cumulatively went on to describe the pathophysiology in more detail.Subcutaneous emphysema can result from puncture of parts of the respiratory or gastrointestinal systems. Particularly in the chest and neck, air may become trapped as a result of penetrating trauma (e.g., gunshot wounds or stab wounds) or blunt trauma. Infection (e.g., gas gangrene) can cause gas to be trapped in the subcutaneous tissues. Subcutaneous emphysema can be caused by medical procedures and medical conditions that cause the pressure in the alveoli of the lung to be higher than that in the tissues outside of them. Its most common causes are pneumothorax or a chest tube that has become occluded by a blood clot or fibrinous material. It can also occur spontaneously due to rupture of the alveoli, with dramatic presentation. When the condition is caused by surgery it is called surgical emphysema. The term spontaneous subcutaneous emphysema is used when the cause is not clear.
Subcutaneous emphysema is not typically dangerous in and of itself, however it can be a symptom of very dangerous underlying conditions, such as pneumothorax. Although the underlying conditions require treatment, subcutaneous emphysema usually does not; small amounts of air are reabsorbed by the body. However, subcutaneous emphysema can be uncomfortable and may interfere with breathing, and is often treated by removing air from the tissues, for example by using large bore needles, skin incisions or subcutaneous catheterization.
Symptoms and signs
Signs and symptoms of spontaneous subcutaneous emphysema vary based on the cause, but it is often associated with swelling of the neck and chest pain, and may also involve sore throat, neck pain, difficulty swallowing, wheezing and difficulty breathing. Chest X-rays may show air in the mediastinum, the middle of the chest cavity. A significant case of subcutaneous emphysema is easy to detect by touching the overlying skin; it feels like tissue paper or Rice Krispies. Touching the bubbles causes them to move and sometimes make a crackling noise. The air bubbles, which are painless and feel like small nodules to the touch, may burst when the skin above them is palpated. The tissues surrounding SCE are usually swollen. When large amounts of air leak into the tissues, the face can swell considerably. In cases of subcutaneous emphysema around the neck, there may be a feeling of fullness in the neck, and the sound of the voice may change. If SCE is particularly extreme around the neck and chest, the swelling can interfere with breathing. The air can travel to many parts of the body, including the abdomen and limbs, because there are no separations in the fatty tissue in the skin to prevent the air from moving.
Causes
Trauma
Conditions that cause subcutaneous emphysema may result from both blunt and penetrating trauma; SCE is often the result of a stabbing or gunshot wound.
Subcutaneous emphysema is often found in car accident victims because of the force of the crash.
Chest trauma, a major cause of subcutaneous emphysema, can cause air to enter the skin of the chest wall from the neck or lung. When the pleural membranes are punctured, as occurs in penetrating trauma of the chest, air may travel from the lung to the muscles and subcutaneous tissue of the chest wall. When the alveoli of the lung are ruptured, as occurs in pulmonary laceration, air may travel beneath the visceral pleura (the membrane lining the lung), to the hilum of the lung, up to the trachea, to the neck and then to the chest wall. The condition may also occur when a fractured rib punctures a lung; in fact, 27% of patients who have rib fractures also have subcutaneous emphysema. Rib fractures may tear the parietal pleura, the membrane lining the inside of chest wall, allowing air to escape into the subcutaneous tissues.Subcutaneous emphysema is frequently found in pneumothorax (air outside of the lung in the chest cavity) and may also result from air in the mediastinum, pneumopericardium (air in the pericardial cavity around the heart). A tension pneumothorax, in which air builds up in the pleural cavity and exerts pressure on the organs within the chest, makes it more likely that air will enter the subcutaneous tissues through pleura torn by a broken rib. When subcutaneous emphysema results from pneumothorax, air may enter tissues including those of the face, neck, chest, armpits, or abdomen.Pneumomediastinum can result from a number of events. For example, foreign body aspiration, in which someone inhales an object, can cause pneumomediastinum (and lead to subcutaneous emphysema) by puncturing the airways or by increasing the pressure in the affected lung(s) enough to cause them to burst.Subcutaneous emphysema of the chest wall is commonly among the first indications that barotrauma, damage caused by excessive pressure, has occurred; it suggests that the lung was subjected to significant barotrauma. Thus the phenomenon may occur in diving injuries.Trauma to parts of the respiratory system other than the lungs, such as rupture of a bronchial tube, may also cause subcutaneous emphysema. Air may travel upward to the neck from a pneumomediastinum that results from a bronchial rupture, or downward from a torn trachea or larynx into the soft tissues of the chest. It may also occur with fractures of the facial bones, neoplasms, during asthma attacks, when the Heimlich maneuver is used, and during childbirth.Injury with pneumatic tools, those that are driven by air, is also known to cause subcutaneous emphysema, even in extremities (the arms and legs). It can also occur as a result of rupture of the esophagus; when it does, it is usually as a late sign.
Medical treatment
Subcutaneous emphysema is a common result of certain types of surgery; for example it is not unusual in chest surgery. It may also occur from surgery around the esophagus, and is particularly likely in prolonged surgery. Other potential causes are positive pressure ventilation for any reason and by any technique, in which its occurrence is frequently unexpected. It may also occur as a result of oral surgery, laparoscopy, and cricothyrotomy. In a pneumonectomy, in which an entire lung is removed, the remaining bronchial stump may leak air, a rare but very serious condition that leads to progressive subcutaneous emphysema. Air can leak out of the pleural space through an incision made for a thoracotomy to cause subcutaneous emphysema. On infrequent occasions, the condition can result from dental surgery, usually due to use of high-speed tools that are air driven. These cases result in usually painless swelling of the face and neck, with an immediate onset, the crepitus (crunching sound) typical of subcutaneous emphysema, and often with subcutaneous air visible on X-ray.One of the main causes of subcutaneous emphysema, along with pneumothorax, is an improperly functioning chest tube. Thus subcutaneous emphysema is often a sign that something is wrong with a chest tube; it may be clogged, clamped, or out of place. The tube may need to be replaced, or, when large amounts of air are leaking, a new tube may be added.Since mechanical ventilation can worsen a pneumothorax, it can force air into the tissues; when subcutaneous emphysema occurs in a ventilated patient, it is an indication that the ventilation may have caused a pneumothorax. It is not unusual for subcutaneous emphysema to result from positive pressure ventilation. Another possible cause is a ruptured trachea. The trachea may be injured by tracheostomy or tracheal intubation; in cases of tracheal injury, large amounts of air can enter the subcutaneous space. An endotracheal tube can puncture the trachea or bronchi and cause subcutaneous emphysema.
Infection
Air can be trapped under the skin in necrotizing infections such as gangrene, occurring as a late sign in gas gangrene, of which it is the hallmark sign. Subcutaneous emphysema is also considered a hallmark of fournier gangrene. Symptoms of subcutaneous emphysema can result when infectious organisms produce gas by fermentation. When emphysema occurs due to infection, signs that the infection is systemic, i.e. that it has spread beyond the initial location, are also present.
Pathophysiology
Air is able to travel to the soft tissues of the neck from the mediastinum and the retroperitoneum (the space behind the abdominal cavity) because these areas are connected by fascial planes. From the punctured lungs or airways, the air travels up the perivascular sheaths and into the mediastinum, from which it can enter the subcutaneous tissues.Spontaneous subcutaneous emphysema is thought to result from increased pressures in the lung that cause alveoli to rupture. In spontaneous subcutaneous emphysema, air travels from the ruptured alveoli into the interstitium and along the blood vessels of the lung, into the mediastinum and from there into the tissues of the neck or head.
Diagnosis
Significant cases of subcutaneous emphysema are easy to diagnose because of the characteristic signs of the condition. In some cases, the signs are subtle, making diagnosis more difficult. Medical imaging is used to diagnose the condition or confirm a diagnosis made using clinical signs. On a chest radiograph, subcutaneous emphysema may be seen as radiolucent striations in the pattern expected from the pectoralis major muscle group. Air in the subcutaneous tissues may interfere with radiography of the chest, potentially obscuring serious conditions such as pneumothorax. It can also reduce the effectiveness of chest ultrasound. On the other hand, since subcutaneous emphysema may become apparent in chest X-rays before a pneumothorax does, its presence may be used to infer that of the latter injury. Subcutaneous emphysema can also be seen in CT scans, with the air pockets appearing as dark areas. CT scanning is so sensitive that it commonly makes it possible to find the exact spot from which air is entering the soft tissues. In 1994, M.T. Macklin and C.C. Macklin published further insights into the pathophysiology of spontaneous Macklins Syndrome occurring from a severe asthmatic attack.
The presence of subcutaneous emphysema in a person who appears quite ill and febrile after bout of vomiting followed by left chest pain is very suggestive of the diagnosis of Boerhaaves syndrome, which is a life-threatening emergency caused by rupture of the distal esophagus.
Subcutaneous emphysema can be a complication of CO2 insufflation with laparoscopic surgery. A sudden rise in end-tidal CO2 following the initial rise that occurs with insufflation (first 15-30 min) should raise suspicion of subcutaneous emphysema. Of note, there are no changes in the pulse oximetry or airway pressure in subcutaneous emphysema, unlike in endobronchial intubation, capnothorax, pneumothorax, or CO2 embolism.
Treatment
Subcutaneous emphysema is usually benign. Most of the time, SCE itself does not need treatment (though the conditions from which it results may); however, if the amount of air is large, it can interfere with breathing and be uncomfortable. It occasionally progresses to a state "Massive Subcutaneous Emphysema" which is quite uncomfortable and requires surgical drainage. When the amount of air pushed out of the airways or lung becomes massive, usually due to positive pressure ventilation, the eyelids swell so much that the patient cannot see. Also the pressure of the air may impede the blood flow to the areolae of the breast and skin of the scrotum or labia. This can lead to necrosis of the skin in these areas. The latter are urgent situations requiring rapid, adequate decompression. Severe cases can compress the trachea and do require treatment.In severe cases of subcutaneous emphysema, catheters can be placed in the subcutaneous tissue to release the air. Small cuts, or "blow holes", may be made in the skin to release the gas. When subcutaneous emphysema occurs due to pneumothorax, a chest tube is frequently used to control the latter; this eliminates the source of the air entering the subcutaneous space. If the volume of subcutaneous air is increasing, it may be that the chest tube is not removing air rapidly enough, so it may be replaced with a larger one. Suction may also be applied to the tube to remove air faster. The progression of the condition can be monitored by marking the boundaries with a special pencil for marking on skin.Since treatment usually involves dealing with the underlying condition, cases of spontaneous subcutaneous emphysema may require nothing more than bed rest, medication to control pain, and perhaps supplemental oxygen. Breathing oxygen may help the body to absorb the subcutaneous air more quickly.
Prognosis
Air in subcutaneous tissue does not usually pose a lethal threat; small amounts of air are reabsorbed by the body. Once the pneumothorax or pneumomediastinum that causes the subcutaneous emphysema is resolved, with or without medical intervention, the subcutaneous emphysema will usually clear. However, spontaneous subcutaneous emphysema can, in rare cases, progress to a life-threatening condition, and subcutaneous emphysema due to mechanical ventilation may induce ventilatory failure.
History
The first report of subcutaneous emphysema resulting from air in the mediastinum was made in 1850 in a patient who had been coughing violently. In 1900, the first recorded case of spontaneous subcutaneous emphysema was reported in a bugler for the Royal Marines who had had a tooth extracted: playing the instrument had forced air through the hole where the tooth had been and into the tissues of his face. Since then, another case of spontaneous subcutaneous emphysema was reported in a submariner for the US Navy who had had a root canal in the past; the increased pressure in the submarine forced air through it and into his face. In recent years a case was reported at the University Hospital of Wales of a young man who had been coughing violently causing a rupture in the esophagus resulting in SE. The cause of spontaneous subcutaneous emphysema was clarified between 1939 and 1944 by Macklin, contributing to the current understanding of the pathophysiology of the condition.
References
== External links == |
Lymphoid leukemia | Lymphoid leukemias are a group of leukemias affecting circulating lymphocytes, a type of white blood cell. The lymphocytic leukemias are closely related to lymphomas of the lymphocytes, to the point that some of them are unitary disease entities that can be called by either name (for example, adult T-cell leukemia/lymphoma). Such diseases are all lymphoproliferative disorders. Most lymphoid leukemias involve a particular subtype of lymphocytes, the B cells.
Classification
Historically, they have been most commonly divided by the stage of maturation at which the clonal (neoplastic) lymphoid population stopped maturing:
Acute lymphoblastic leukemia
Chronic lymphocytic leukemiaHowever, the influential WHO Classification (published in 2001) emphasized a greater emphasis on cell lineage. To this end, lymphoid leukemias can also be divided by the type of cells affected:
B-cell leukemia
T-cell leukemia
NK-cell leukemiaThe most common type of lymphoid leukemia is B-cell chronic lymphocytic leukemia.
B-cell leukemias
B-cell leukemia describes several different types of lymphoid leukemia which affect B cells.
Other types include (with ICD-O code):
9826/3 – Acute lymphoblastic leukemia, mature B-cell type
9833/3 – B-cell prolymphocytic leukemia
9940/3 – Hairy cell leukemia
T-cell leukemias
T-cell leukemia describes several different types of lymphoid leukemias which affect T cells.The most common T-cell leukemia is precursor T-cell lymphoblastic leukemia. It causes 15% of acute leukemias in childhood, and also 40% of lymphomas in childhood. It is most common in adolescent males. Its morphology is identical to that of precursor B-cell lymphoblastic leukemia. Cell markers include TdT, CD2, CD7. It often presents as a mediastinal mass because of involvement of the thymus. It is highly associated with NOTCH1 mutations.Other types include:
Large granular lymphocytic leukemia
Adult T-cell leukemia/lymphoma
T-cell prolymphocytic leukemiaIn practice, it can be hard to distinguish T-cell leukemia from T-cell lymphoma, and they are often grouped together.
NK cell leukemia
Aggressive NK-cell leukemia (ANKL) is a lymphoid leukemia that is a deficiency NK cells. Not very much is known about this disease due to its rarity, but it is highly aggressive. Most patients will die within 2 years.
Diagnosis
The requirements for diagnosing ANKL are as follows:
Immature-looking NK cells
Certain immunophenotypes
Germline configuration genes: TCR-β and IgH
Restricted cytotoxicityThe T-cell receptor (TCR) is an important factor when ANKL is being diagnosed along with T-cell leukemia. The TCR gene transcripts are normally positive for ANKL. Current Research is attempting to find the causation of ANKL. So far, the researchers have concluded that lineage of the T-cell receptor gene does not predict the behavior of the disease.
Treatment
ANKL is treated similarly to most B-cell lymphomas. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant. Most patients will die 2 years after diagnosis.
Diagnosis
Flow cytometry is a diagnostic tool in order to count/visualize the amount of lymphatic cells in the body. T cells, B cells and NK cells are nearly impossible to distinguish under a microscope, therefore one must use a flow cytometer to distinguish them.
Treatment
Targeted therapy
Several molecular tumor profiling protocols have been initiated in Europe (e.g., MOSCATO-01, iTHER, and ESMART) to identify actionable lesions for targeted treatment in specific subgroups of patients.
NK cell therapy
Natural killer (NK) cell therapy is used in pediatrics for children with relapsed lymphoid leukemia. These patients normally have a resistance to chemotherapy, therefore, in order to continue on, must receive some kind of therapy. In some cases, NK cell therapy is a choice.NK cells are known for their ability to eradicate tumor cells without any prior sensitization to them. One problem when using NK cells in order to fight off lymphoid leukemia is the fact that it is hard to amount enough of them to be effective. One can receive donations of NK cells from parents or relatives through bone marrow transplants. There are also the issues of cost, purity and safety. Unfortunately, there is always the possibility of Graft vs host disease while transplanting bone marrow.
NK cell therapy is a possible treatment for many different cancers such as Malignant glioma.
References
== External links == |
Lichen nitidus | Lichen nitidus is a chronic inflammatory disease of unknown cause characterized by 1–2 mm, discrete and uniform, shiny, flat-topped, pale flesh-colored or reddish-brown papules that may appear as hypopigmented against dark skin. Occasionally, minimal scaling is present or can be induced by rubbing the surface of the papules. The disease usually affects children and young adults and is painless and usually nonpruritic, although protracted itching may occur in some cases. It is sometimes referred to by dermatologists as "mini lichen planus".
Presentation
Linear arrangements of these papules is common (referred to as a Koebner phenomenon), especially on the forearms, but may occasionally be grouped, though not confluent, on flexural areas. Generally, the initial lesions are localized, and remain so, to the chest, abdomen, glans penis, and flexor aspects of the upper extremities; however, less commonly, the disease process can (1) be strictly isolated to the palms and soles, presenting with many hyperkeratotic, yellow papules that may coalesce into plaques that fissure or “...sometimes a non-specific keratoderma resembling chronic eczema,” or (2) become more widespread, with papules widely distributed on the body—the extensor surfaces of the elbows, wrists, and hands, folds of the neck, submammary region in females, groin, thighs, ankles, and feet—and fusing into erythematous, minimally scaled plaques, with redness that develops tints of violet, brown, and yellow.
Pathology
The histology of lichen nitidus is significant for a "...localized granulomatous lymphohistiocytic infiltrate in an expanded dermal papilla with thinning of overlying epidermis and downward extension of the rete ridges at the lateral margin of the infiltrate, producing a typical claw clutching a ball picture...."
Treatment
Generally, lichen nitidus is asymptomatic and self-limited; therefore, no treatment is required. However, if persistent pruritus is present, or the appearance “...interferes with daily activities or outlook...” topical glucocorticoids may be tried. If the disease process is symptomatic, generalized and extensive, oral glucocorticoids may be indicated. Other reported treatments include PUVA, UVA/UVB phototherapy, astemizole, acitretin, and etretinate.
When appears with sun/humidity; air conditioning (cool dry air) reduces swelling and discomfort.
History
Felix Pinkus first described the condition in 1907.
See also
Lichen planus
List of cutaneous conditions
References
External links
Lichen Nitidus at DermNet photo library |
Glycine encephalopathy | Glycine encephalopathy is a rare autosomal recessive disorder of glycine metabolism. After phenylketonuria, glycine encephalopathy is the second most common disorder of amino acid metabolism. The disease is caused by defects in the glycine cleavage system, an enzyme responsible for glycine catabolism. There are several forms of the disease, with varying severity of symptoms and time of onset. The symptoms are exclusively neurological in nature, and clinically this disorder is characterized by abnormally high levels of the amino acid glycine in bodily fluids and tissues, especially the cerebrospinal fluid.
Glycine encephalopathy is sometimes referred to as "nonketotic hyperglycinemia" (NKH), as a reference to the biochemical findings seen in patients with the disorder, and to distinguish it from the disorders that cause "ketotic hyperglycinemia" (seen in propionic acidemia and several other inherited metabolic disorders). To avoid confusion, the term "glycine encephalopathy" is often used, as this term more accurately describes the clinical symptoms of the disorder.
Signs and symptoms
It typically presents as a severe encephalopathy with myoclonic seizures, is rapidly progressive and eventually results in respiratory arrest. Standard evaluation for inborn errors of metabolism and other causes of this presentation does not reveal any abnormality (no acidosis, no hypoglycaemia, or hyperammonaemia and no other organ affected). Pronounced and sustained hiccups in an encephalopathic infant have been described as a typical observation in non-ketotic hyperglycinaemia.
Genetics
Glycine encephalopathy has an estimated incidence of 1 in 60,000, making it the second most common disorder of amino acid metabolism, after phenylketonuria. It is caused by a defect in the glycine cleavage system (GCS), which is made up of four protein subunits. Each of these four subunits is encoded by a separate gene. Defects in three of these four genes have been linked to glycine encephalopathy.: 790
There is a fourth unit in the complex, dihydrolipoamide dehydrogenase or GCSL. However, to date there have been no mutations in GCSL found to be associated with glycine encephalopathy.
A small percentage of affected individuals do not have detectable mutations in any of the three genes (listed above) that are typically associated with the disease. However, they still show defective glycine-cleavage enzymatic activity. It is thought that these patients may have mutations in the genes encoding one of the cofactors associated with the GCS complex.Defects in the GCS proteins can prevent the complex from functioning properly or can prevent the GCS complex from forming entirely. When the complex is unable to metabolize glycine properly, this causes excess glycine to build up to toxic levels in the bodys organs and tissues. Damage caused by elevated levels of glycine in the brain and cerebrospinal fluid is responsible for the characteristic seizures, breathing difficulties, movement disorders, and intellectual disability.This disorder is inherited in an autosomal recessive pattern. The term "autosomal" signifies that the gene associated with the disorder is located on an autosome. In an autosomal recessive inheritance pattern, two defective copies of the gene (one inherited from each parent) are required in order for a child to be born with the disorder. Therefore, each parent of an individual with an autosomal recessive disorder has at least one defective copy of the gene. With autosomal recessive disorders, individuals with only one copy of a defective gene (heterozygotes) are considered "carriers" for the disorder. Carriers usually do not show signs or symptoms of the disorder.
Pathophysiology
Glycine is the simplest amino acid, having no stereoisomers. It can act as a neurotransmitter in the brain, act as an inhibitor in the spinal cord and brain stem, while having excitatory effects in the cortex of the brain. Glycine is metabolized to final end products of ammonia and carbon dioxide through the glycine cleavage system (GCS), an enzyme complex made up of four protein subunits. Defects in these subunits can cause glycine encephalopathy, although some causes of the disease are still unknown. Normally, GCS shows its highest enzymatic activity in liver, brain and placental tissue. One of its main functions is to maintain normal glycine levels in the brain. Defects in GCS cause an increase of glycine concentration in blood plasma and cerebrospinal fluid. The exact pathophysiology of the disorder is not known, but it is considered likely that buildup of glycine in the brain is responsible for the symptoms.All forms of glycine encephalopathy show elevated levels of glycine in the plasma, as well as in cerebral spinal fluid (CSF).: 793 Glycine concentrations in the CSF of affected patients are typically more markedly elevated than in plasma, leading to a corresponding elevation in the ratio of glycine concentrations in the cerebral spinal fluid to that in the plasma. This ratio can also be slightly elevated in patients receiving valproic acid.: 811 Glycine encephalopathy (nonketotic hyperglycinemia, or NKH) should not be confused with other metabolic disorders that can produce elevated glycine levels. For example, certain inherited organic acidurias (aka organic acidemias) can produce elevated glycine in plasma and urine, although these disorders are not caused by defects in the glycine cleavage system, and they are not typically accompanied by corresponding elevations of glycine in cerebrospinal fluid (CSF). Glycine encephalopathy is unique in the fact that levels of glycine are disproportionately elevated in CSF (in addition to elevations in blood and urine), whereas CSF glycine levels are normal or near-normal in patients with inherited organic acidurias.
Glycine metabolism
Glycine is metabolized in the bodys cells to end products of carbon dioxide and ammonia. The glycine cleavage system, which is responsible for glycine metabolism in the mitochondria is made up of four protein subunits, the P-protein, H-protein, T-protein and L-protein.: 793
Diagnosis
Classification
There are several different forms of glycine encephalopathy, which can be distinguished by the age of onset, as well as the types and severity of symptoms. All forms of glycine encephalopathy present with only neurological symptoms, including intellectual disability (IQ scores below 20 are common), hypotonia, apneic seizures, and brain malformations.: 811 With the classical, or neonatal presentation of glycine encephalopathy, the infant is born after an unremarkable pregnancy, but presents with lethargy, hypotonia, apneic seizures and myoclonic jerks, which can progress to apnea requiring artificial ventilation, and often death. Apneic patients can regain spontaneous respiration in their second to third week of life. After recovery from the initial episode, patients have intractable seizures and profound intellectual disability, remaining developmentally delayed. Some mothers comment retrospectively that they noticed fetal rhythmic "hiccuping" episodes during pregnancy, most likely reflecting seizure episodes in utero. Patients with the infantile form of glycine encephalopathy do not show lethargy and coma in the neonatal period, but often have a history of hypotonia. They often have seizures, which can range in severity and responsiveness to treatment, and they are typically developmentally delayed. Glycine encephalopathy can also present as a milder form with episodic seizures, ataxia, movement disorders, and gaze palsy during febrile illness. These patients are also developmentally delayed, to varying degrees. In the later onset form, patients typically have normal intellectual function, but present with spastic diplegia and optic atrophy. The mild form of the disorder corresponds to greatly reduced but not fully absent GCS activity.Transient neonatal hyperglycinemia has been described in a very small number of cases. Initially, these patients present with the same symptoms and laboratory results that are seen in the classical presentation. However, levels of glycine in plasma and cerebrospinal fluid typically normalize within eight weeks, and in five of six cases there were no neurological issues detected at follow-up times up to thirteen years. A single patient was severely retarded at nine months. The suspected cause of transient neonatal hyperglicinemia is attributed to low activity of the glycine cleavage system in the immature brain and liver of the neonate.
Treatment
A treatment of sodium benzoate, which binds to glycine and forms hippurate, and dextromethorphan, which weakly inhibits the N-methyl-D-aspartate receptors that glycine acts on has been shown to improve outcomes in select cases where the disorder is present in attenuated form.
Prognosis
The prognosis is very poor. Two studies reported typical age of deaths in infancy or early childhood, with the first reporting a median age of death of 2.6 for boys and less than 1 month for girls.
Research
Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).
See also
List of amino acid metabolism disorders
inborn errors of metabolism
References
== External links == |
Prolonged labor | Prolonged labor is the inability of a woman to proceed with childbirth upon going into labor. Prolonged labor typically lasts over 20 hours for first time mothers, and over 14 hours for women that have already had children. Failure to progress can take place during two different phases; the latent phase and active phase of labor. The latent phase of labor can be emotionally tiring and cause fatigue, but it typically does not result in further problems. The active phase of labor, on the other hand, if prolonged, can result in long term complications.It is important that the vital signs of the woman and fetus are being monitored so preventive measures can be taken if prolonged labor begins. Women experiencing prolonged labor should be under supervision of a surgically equipped doctor. Prolonged labor is determined based on the information that is being collected regarding the strength and time between contractions. Medical teams track this data using intrauterine pressure catheter placement (IUPC) and continuous electronic fetal monitoring (EFM). IUPC is a straw that is inserted into the womb with a monitor that reads when contractions are coming and how strong they are. EFMs are used to track the fetal heart rate. If either devices indicate that vital signs are off and prolonged labor is beginning, it is important that the medical team begin discussing treatment and alternative options for delivery.
Prolonged labor can result from a variety of different issues, such as fetal malpresentation, issues with uterine contractions, cervical dystocia or stenosis, and cephalopelvic disproportion. Both fetal malpresentation and cervical dystocia may result in obstructed labor. The cause of prolonged labor will determine the medical intervention that needs to take place. Medical professionals can either engage in preventive measures or turn to surgical methods of removing the fetus. If not handled properly or immediately treated, both the woman and the fetus can suffer a variety of long term complications, the most serious of which is death. There is no "quick fix" to prolonged labor, but there are preventive measures that can be taken, such as oxytocin infusions. In order to properly and safely deliver the baby, doctors will often intervene in child birth and conduct assisted vaginal delivery through the use of forceps or a vacuum extractor, or perform a Caesarean section.
Signs and symptoms
Symptoms include:
Labor extends beyond 18 hours
Dehydration and exhaustion of the mother
Pain around the back, sides, and thighs of the mother as a result of extreme muscle pressure
Severe pain when labor begins
Increased heart rate of the mother
Swollen large intestine on either side of the uterus as a result of gas build up
Uterus sensitivity
Ketosis
Distress of the fetus
Uterine ruptures
Complications
Distress to the fetus as a result of decreasing oxygen levels
Internal bleeding of the fetuss head (intracranial hemorrhage)
Higher chance of operative delivery
Risks of long-term injuries to the infant such as hypoxic-ischemic encephalopathy (HIE) or cerebral palsy
Infection of the uterus
Damage to the birth canal
Postpartum infection
Postpartum hemorrhage
Prolonged latent labor
The term describes labor that occurs very slowly. This does not necessarily mean that the woman or fetuss health is being compromised, but it is painful and is an important indication for doctors to pay attention to warning signs of prolonged labor.
Prolonged active labor
The phase of labor that extends into multiple hours (at least 14). The cervix usually dilates to over 4 cm before active labor occurs. When it first begins, it is encouraged that women stand up, walk around, and eat or drink. If failure to progress extends beyond this point, preventive measures need to be taken.
Causes
Fetal malpresentations
Fetal malpresentations are irregular positions of the crown of the fetal head in relation to the mothers pelvis (the fetus is in an abnormal position). Some important ways to manage fetal malpresentation are making rapid evaluations of the condition of the women pertaining to vital signs as well as the heart rate of the fetus. If fetal heart rate is abnormal, and if membranes have ruptured and amniotic fluid is atypical, it is important for medical professionals to determine the presenting part of the fetus and the position of the fetal head. Possible delivery methods, if this is the case, are compound presentation, vaginal breech delivery, or caesarean section for breech presentation depending upon the severity of the malposition.
Uterine contractions
This refers to uterine conditions that result in the uterus not having enough coordination or strength to dilate the cervix and push the baby through the birth canal. Issues with uterine contractions are the main cause of prolonged labor during the latent phase. Contractions may not occur as of a result of uterine tumors. In addition, if the uterus is stretched, usually due to previous pregnancies or multiple gestation, contractions may be difficult. Irregular or weak contractions can be fixed through stimulation of the uterus or oxytocin infusions. Lack of contractions may be caused by an overwhelming amount of painkillers or anesthesia, by which the medications should be discontinued. In this case, it is appropriate for assisted vaginal delivery to be conducted.
Cervical stenosis
Cervical dystocia, or stenosis, occurs when the cervix fails to dilate after a practical amount of time during positive uterine pains. The main problems in cervical dystocia is the lack of uterine inertia and cervical abnormalities, which prevent the cervix from fully dilating. It is very typical of patients that have hypopituitarism. There are many preexisting complications that may result in stenosis. Common conditions that lead to stenosis are tumors, a full bladder, large size of the infant, multiple pregnancies, delay in rupture of membranes, or problems with the cervix. High stress may interfere with the progression of pregnancy in cases such as these, leading to prolonged labor.
Cephalopelvic disproportion
Cephalopelvic disproportion is the issue that arises when the fetus body or head is too large to pass through the woman’s pelvis. Common conditions that lead to CPD are diabetes, multiple pregnancies, small or abnormally shaped pelvis, atypical fetal positions, hereditary factors, and first time pregnancies. Medical professionals can usually estimate if fetal size is too large based on ultrasounds, but they are not always entirely accurate. Doctors typically determine CPD when labor begins and the use of oxytocin is not effective. The safest way for delivery to take place when CPD is a factor is through Caesarean sections.
Prevention
If the woman is being closely monitored and begins to show signs of prolonged labor, medical professionals can take preventive measures to better the chances of delivery within 24 hours. A precise initial diagnosis of prolonged labor based on signs and symptoms is extremely important in applying proper precautionary treatment. Oxytocin infusions upon an initial amniotomy is typically used to move normal labor back on track. The application of oxytocin is only effective if administered on the basis of fetal distress. This treatment method only pertains to specific states of the fetus. If the baby is experiencing malpresentation, for example, the only safe and reliable method to proceed with childbirth is medical interference.
Management
In terms of medical care, preventive treatment or assisted delivery are typically the first options doctors consider. There is usually no quick fix to prolonged labor, especially if preventive measures do not revert the mother back to normal labor. Often, medical professionals resort to intervention methods. If the state of the fetus and mother are not especially serious or threatening to their health, doctors will perform assisted vaginal deliveries.
Assisted vaginal delivery
There are two different methods of assisted vaginal delivery that medical professionals typically utilize to aid in delivery in order to avoid surgical methods of fetal extraction. These procedures are only applied if a vaginal delivery has proven to still be safe to the woman and the baby, based on their vital signs. Assisted vaginal delivery is usually only used in the latent phase. Delivery during the active phase is usually associated with more complications for the woman. One approach to assisted vaginal delivery is the use of forceps. The forceps doctors use resemble two large salad spoons and are inserted into the cervix, around the babys head and help to guide it out of the birth canal. The other option is the use of vacuum extraction. Vacuums used have a cup on the end and are inserted into the cervix. The cup attaches to the fetuss head by suction and aids in guiding delivery. The choice between forceps and vacuum extraction is usually made by the doctor based on preference. It is important that these methods are used properly, or else they can cause severe birth injuries to the baby that may be permanent.
Caesarean sections
Caesarean sections, also referred to as C-sections, are usually quick solutions to the issue of failure to progress. Often, C-sections are the best options to avoid harming the fetus or the woman, especially if labor proves to be life-threatening. One third of C-sections occur as a result of prolonged labor. C-sections are usually a necessary measure in prolonged labor to avoid serious birth complications. If the mother reaches the active phase of prolonged labor, a C-section is the safest solution. Caesarean sections need to be performed immediately if there are signs of fetal distress, uterine rupture, or cord prolapse. It is important that medical professionals are equipped and prepared in the case of an imperative C-section. There is a window of time by which Caesarean sections need to be executed if any warning signs present themselves. If there is a delay in the C-section, permanent damage can result to the baby, such as cerebral palsy or hypoxic-ischemic encephalopathy (HIE). Due to all the risk factors that are present in the event of prolonged labor, it is extremely important that medical teams are well-suited and prepared to conduct a C-section if needed.
References
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Basal-cell carcinoma | Basal-cell carcinoma (BCC), also known as basal-cell cancer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raised area with ulceration. Basal-cell cancer grows slowly and can damage the tissue around it, but it is unlikely to spread to distant areas or result in death.Risk factors include exposure to ultraviolet light, having lighter skin, radiation therapy, long-term exposure to arsenic and poor immune-system function. Exposure to UV light during childhood is particularly harmful. Tanning beds have become another common source of ultraviolet radiation. Diagnosis often depends on skin examination, confirmed by tissue biopsy.It remains unclear whether sunscreen affects the risk of basal-cell cancer. Treatment is typically by surgical removal. This can be by simple excision if the cancer is small; otherwise, Mohs surgery is generally recommended. Other options include electrodesiccation and curettage, cryosurgery, topical chemotherapy, photodynamic therapy, laser surgery or the use of imiquimod, a topical immune-activating medication. In the rare cases in which distant spread has occurred, chemotherapy or targeted therapy may be used.Basal-cell cancer accounts for at least 32% of all cancers globally. Of skin cancers other than melanoma, about 80% are basal-cell cancers. In the United States, about 35% of white males and 25% of white females are affected by BCC at some point in their lives.
Signs and symptoms
Individuals with a basal-cell carcinoma typically present with a shiny, pearly skin nodule. However, superficial basal-cell cancer can present as a red patch similar to eczema. Infiltrative or morpheaform basal-cell cancers can present as a skin thickening or scar tissue – making diagnosis difficult without using tactile sensation and a skin biopsy. It is often difficult to visually distinguish basal-cell cancer from acne scar, actinic elastosis, and recent cryodestruction inflammation.
Cause
The majority of basal-cell carcinomas occur on sun-exposed areas of the body.
Pathophysiology
Basal-cell carcinoma is named after the basal cells that populate the lowest layer of the epidermis due to the histological appearance of the cancer cells under the microscope. Nevertheless, not all basal-cell carcinomas actually originate within the basal layer. Basal-cell carcinomas are thought to develop from the folliculo–sebaceous–apocrine germinative cells known as trichoblasts. Trichoblastic carcinoma is a term used to describe a rare and potentially aggressive malignancy that is also thought to arise from trichoblasts and may resemble a benign trichoblastoma (differential diagnosis can be challenging). It has been suggested that lesions diagnosed as trichoblastic carcinoma may actually themselves be basal-cell carcinoma.Overexposure to sun leads to the formation of thymine dimers, a form of DNA damage. While DNA repair removes most UV-induced damage, not all crosslinks are excised. There is, therefore, cumulative DNA damage leading to mutations. Apart from the mutagenesis, overexposure to sunlight depresses the local immune system, possibly decreasing immune surveillance for new tumor cells.
Basal-cell carcinomas can often come in association with other lesions of the skin, such as actinic keratosis, seborrheic keratosis, squamous cell carcinoma. In a small proportion of cases, basal-cell carcinoma also develops as a result of basal-cell nevus syndrome, or Gorlin Syndrome, which is also characterized by keratocystic odontogenic tumors of the jaw, palmar or plantar (sole of the foot) pits, calcification of the falx cerebri (in the center line of the brain) and rib abnormalities. The cause of this syndrome is a mutation in the PTCH1 tumor suppressor gene located in chromosome 9q22.3, which inhibits the hedgehog signaling pathway. A mutation in the SMO gene, which is also on the hedgehog pathway, also causes basal-cell carcinoma.
Diagnosis
To diagnose basal-cell carcinomas, a skin biopsy is performed for histopathologic analyses. The most common method is a shave biopsy under local anesthesia. Most nodular basal-cell cancers can be diagnosed clinically; however, other variants can be very difficult to distinguish from benign lesions such as intradermal naevus, sebaceomas, fibrous papules, early acne scars, and hypertrophic scarring. Exfoliative cytology methods have high sensitivity and specificity for confirming the diagnosis of basal cell carcinoma when clinical suspicion is high but unclear usefulness otherwise.
Characteristics
Basal-cell carcinoma cells appear similar to epidermal basal cells, and are usually well differentiated.In uncertain cases, immunohistochemistry using BerEP4 can be used, having a high sensitivity and specificity in detecting only BCC cells.
Main classes
Basal-cell carcinoma can broadly be divided into three groups, based on the growth patterns.
Superficial basal-cell carcinoma, formerly referred to in-situ basal-cell carcinoma, is characterized by a superficial proliferation of neoplastic basal-cells. This tumor is generally responsive to topic chemotherapy, such as imiquimod, or fluorouracil, although surgical treatment is better able to ensure complete removal and confirm that there is not an underlying more aggressive subtype that was not sampled in the initial biopsy.
Infiltrative basal-cell carcinoma, which also encompasses morpheaform and micronodular basal-cell cancer, is more difficult to treat with conservative methods, given its tendency to penetrate into deeper layers of the skin.
Nodular basal-cell carcinoma includes most of the remaining categories of basal-cell cancer. It is not unusual to encounter heterogeneous morphologic features within the same tumor.
Nodular basal-cell carcinoma
Nodular basal-cell carcinoma (also known as "classic basal-cell carcinoma") accounts for 50% of all BCC. It most commonly occurs on the sun-exposed areas of the head and neck.: 748 : 646 Histopathology shows aggregates of basaloid cells with well-defined borders, showing a peripheral palisading of cells and one or more typical clefts. Such clefts are caused by shrinkage of mucin during tissue fixation and staining. Central necrosis with eosinophilic, granular features may be also present, as well as mucin. The heavy aggregates of mucin determine a cystic structure. Calcification may be also present, especially in long-standing lesions. Mitotic activity is usually not so evident, but a high mitotic rate may be present in more aggressive lesions. Adenoidal BCC can be classified as a variant of NBCC, characterized by basaloid cells with a reticulated configuration extending into the dermis.
Other subtypes
Other more specific subtypes of basal-cell carcinoma include:: 646–50
Aggressiveness patterns
There are mainly three patterns of aggressiveness, based mainly the cohesion of cancer cells:
Differential diagnoses
Radicality
In suspected but uncertain BCC cells close to the resection margins, immunohistochemistry with BerEp4 can highlight the BCC cells.
Prevention
Basal-cell carcinoma is a common skin cancer and occurs mainly in fair-skinned patients with a family history of this cancer. Sunlight is a factor in about two-thirds of these cancers; therefore, doctors recommend sunscreens with at least SPF 30. However, a Cochrane review examining the effect of solar protection (sunscreen only) in preventing the development of basal-cell carcinoma or cutaneous squamous cell carcinoma found that there was insufficient evidence to demonstrate whether sunscreen was effective for the prevention of either of these keratinocyte-derived cancers. The review did ultimately state that the certainty of these results was low, so future evidence could very well alter this conclusion. One-third occur in non-sun-exposed areas; thus, the pathogenesis is more complex than UV exposure as the cause.The use of a chemotherapeutic agent such as 5-Fluorouracil or imiquimod can prevent the development of skin cancer. It is usually recommended to individuals with extensive sun damage, history of multiple skin cancers, or rudimentary forms of cancer (i.e., solar keratosis). It is often repeated every 2 to 3 years to further decrease the risk of skin cancer.
Treatment
The following methods are employed in the treatment of basal-cell carcinoma (BCC):
Standard surgical excision
Surgery to remove the basal-cell carcinoma affected area and the surrounding skin is thought to be the most effective treatment. A disadvantage with standard surgical excision is a reported higher recurrence rate of basal-cell cancers of the face, especially around the eyelids, nose, and facial structures. There is no clear approach, nor a clear research comparing the effectiveness of Mohs micrographic surgery versus surgical excision for BCC of the eye.For basal cell carcinoma excisions on the lower lip the wound can be covered with a keystone flap. A keystone flap is achieved by creating a flap below the defect and pulling it superiorly to cover the wound. This can be performed if there is enough skin laxity to cover the defect and adequate blood supply to the flap.
Mohs surgery
For many new (primary) and all recurrent forms of basal cell carcinoma after previous surgery, especially on the head, neck, hands, feet, genitalia and anterior legs (shins), Mohs surgery should be considered.Mohs surgery (or Mohs micrographic surgery) is an outpatient procedure, developed by Frederic E. Mohs in the 1930s, in which the tumor is surgically excised and then immediately examined under a microscope. It is a form of pathology processing called CCPDMA, which means that the entire surgical margin (both edges and deep) is examined. During the surgery, after each removal of tissue and while the patient waits, the tissue is examined for cancer cells. That examination dictates the decision for additional tissue removal. Mohs surgery is also used for squamous-cell carcinoma, melanoma, atypical fibroxanthoma, dermatofibrosarcoma protuberans, Merkel cell carcinoma, microcystic adnexal carcinoma, and multiple other skin cancers; usually with cure rates higher than for other surgical and non-surgical treatments.An essential aspect of Mohs surgery is that the Mohs surgeon performs the surgery and personally reviews the Mohs pathology slides. Most standard excisions done in an office setting are sent to an outside laboratory for standard bread loafing method of processing. With this method, it is likely that less than 5% of the surgical margin is examined, as each slice of tissue is only 6 micrometres thick, about 3 to 4 serial slices are obtained per section, and only about 3 to 4 sections are obtained per specimen.
Cryosurgery
Cryosurgery is an old modality for the treatment of many skin cancers. When accurately utilized with a temperature probe and cryotherapy instruments, it can result in very good cure rate. Disadvantages include lack of margin control, tissue necrosis, over or under treatment of the tumor, and long recovery time. Overall, there are sufficient data to consider cryosurgery as a reasonable treatment for BCC. There are no good studies, however, comparing cryosurgery with other modalities, particularly with Mohs surgery, excision, or electrodesiccation and curettage so that no conclusion can be made whether cryosurgery is as efficacious as other methods. Also, there is no evidence on whether curetting the lesions before cryosurgery affects the efficacy of treatment. Several textbooks are published on the therapy, and a few physicians still apply the treatment to selected patients.
Electrodesiccation and curettage
Electrodesiccation and curettage (EDC, also known as curettage and cautery, simply curettage) is accomplished by using a round knife, or curette, to scrape away the soft cancer. The skin is then burned with an electric current. This further softens the skin, allowing for the knife to cut more deeply with the next layer of curettage. The cycle is repeated, with a safety margin of curettage of normal skin around the visible tumor. This cycle is repeated 3 to 5 times, and the free skin margin treated is usually 4 to 6 mm. Cure rate is very much user-dependent and depends also on the size and type of tumor. Infiltrative or morpheaform BCCs can be difficult to eradicate with EDC. Generally, this method is used on cosmetically unimportant areas like the trunk (torso). Some physicians believe that it is acceptable to utilize EDC on the face of elderly patients over the age of 70. However, with increasing life expectancy, such an objective criterion cannot be supported. The cure rate can vary, depending on the aggressiveness of the EDC and the free margin treated. Some advocate curettage alone without electrodesiccation, and with the same cure rate.
Chemotherapy
Some superficial cancers respond to local therapy with 5-fluorouracil, a chemotherapy agent. One can expect a great deal of inflammation with this treatment. Chemotherapy often follows Mohs surgery to eliminate the residual superficial basal-cell carcinoma after the invasive portion is removed. 5-fluorouracil has received FDA approval.
Removing the residual superficial tumor with surgery alone can result in large and difficult to repair surgical defects. One often waits a month or more after surgery before starting the inmunotherapy or chemotherapy to make sure the surgical wound has adequately healed. Some people advocate the use of curettage (see EDC below) first, followed by chemotherapy. These experimental procedures are not standard care.Vismodegib and sonidegib are drugs approved for specially treating BCC, but are expensive and cannot be used in pregnant women.
Itraconazole, traditionally an anti-fungal medication, has also garnered recent attention for its potential use in the treatment of BCC, especially those that cannot be removed surgically. Possessing anti-Hedgehog pathway activity, there is clinical evidence that itraconazole has some efficacy either alone or when combined with vismodegib/sonidegib for primary and recurrent BCC. There is one case report of efficacy in metastatic BCC.
Immunotherapy
This technique uses the bodys immune system to kill cancer cells. Improvement of the immune system works its way out up to the cancerous cells and treat the skin cancer.
Topical treatment with 5% Imiquimod cream (IMQ), with five applications per week for six weeks has a reported 70–90% success rate at reducing, even removing, the BCC [basal-cell carcinoma]. Imiquimod has received FDA approval, and topical IMQ is approved by the European Medicines Agency for treatment of small superficial basal-cell carcinoma. Off label use of imiquimod on invasive basal-cell carcinoma has been reported. Imiquimod may be used prior to surgery in order to reduce the size of the carcinoma.
Some advocate the use of imiquimod prior to Mohs surgery to remove the superficial component of the cancer.Research suggests that treatment using Euphorbia peplus, a common garden weed, may be effective. Australian biopharmaceutical company Peplin is developing this as topical treatment for BCC.
Radiation
Radiation therapy can be delivered either as external beam radiotherapy or as brachytherapy (mostly internal radiotherapy). Although radiotherapy is generally used in older patients who are not candidates for surgery, it is also used in cases where surgical excision will be disfiguring or difficult to reconstruct (especially on the tip of the nose, and the nostril rims). Radiation treatment with external radiation often takes as few as 5 visits to as many as 25 visits. Usually, the more visits scheduled for therapy, the less complication or damage is done to the normal tissue supporting the tumor. Radiotherapy can also be useful if surgical excision has been done incompletely or if the pathology report following surgery suggests a high risk of recurrence, for example if nerve involvement has been demonstrated. Cure rate can be as high as 95% for small tumor, or as low as 80% for large tumors. A variation of an external brachytherapy is the epidermal radioisotope therapy (e.g. with 188Re in form of the Rhenium-SCT). It is used in accordance to the general indications for brachytherapy and especially complex localisations or structures (e.g. earlobe) as well as the genitals.Usually, recurrent tumors after radiation are treated with surgery, and not with radiation. Further radiation treatment will further damage normal tissue, and the tumor might be resistant to further radiation. Radiation therapy may be contraindicated for treatment of nevoid basal-cell carcinoma syndrome. A 2008 study reported that radiation therapy is appropriate for primary BCCs and recurrent BCCs, but not for BCCs that have recurred following previous radiation treatment.
Photodynamic therapy
Photodynamic therapy (PDT) is a new modality for treatment of basal-cell carcinoma, which is administrated by application of photosensitizers to the target area. When these molecules are activated by light, they become toxic, therefore destroy the target cells. Methyl aminolevulinate is approved by EU as a photosensitizer since 2001. This therapy is also used in other skin cancer types. The 2008 study reported that PDT was a good treatment option for primary superficial BCCs and reasonable for primary low-risk nodular BCCs but a "relatively poor" option for high-risk lesions.
Prognosis
Prognosis is excellent if the appropriate method of treatment is used in early primary basal-cell cancers. Recurrent cancers are much harder to cure, with a higher recurrent rate with any methods of treatment. Although basal-cell carcinoma rarely metastasizes, it grows locally with invasion and destruction of local tissues. The cancer can impinge on vital structures like nerves and result in loss of sensation or loss of function or rarely death. The vast majority of cases can be successfully treated before serious complications occur. The recurrence rate for the above treatment options ranges from 50 percent to 1 percent or less.
Epidemiology
Basal-cell cancer is a very common skin cancer. It is much more common in fair-skinned individuals with a family history of basal-cell cancer and increases in incidence closer to the equator or at higher altitude. It is very common among elderly people over the age of 80. There are approximately 800,000 new cases yearly in the United States alone. Up to 30% of white people develop basal-cell carcinomas in their lifetime. In Canada, the most common skin cancer is basal-cell carcinoma (as much as one third of all cancer diagnoses), affecting 1 in 7 individuals over a lifetime.In the United States approximately 3 out of 10 White people develop a basal-cell carcinoma during their lifetime. This tumor accounts for approximately 70% of non-melanoma skin cancers. In 80 percent of all cases, basal-cell carcinoma affects the skin of head and neck. Furthermore, there appears to be an increase in the incidence of basal-cell cancer of the trunk in recent years.Most sporadic BCC arises in small numbers on sun-exposed skin of people over age 50, although younger people may also be affected. The development of multiple basal-cell cancer at an early age could be indicative of nevoid basal-cell carcinoma syndrome, also known as Gorlin Syndrome.
Notes
References
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Hypervolemia | Hypervolemia, also known as fluid overload, is the medical condition where there is too much fluid in the blood. The opposite condition is hypovolemia, which is too little fluid volume in the blood. Fluid volume excess in the intravascular compartment occurs due to an increase in total body sodium content and a consequent increase in extracellular body water. The mechanism usually stems from compromised regulatory mechanisms for sodium handling as seen in congestive heart failure (CHF), kidney failure, and liver failure. It may also be caused by excessive intake of sodium from foods, intravenous (IV) solutions and blood transfusions, medications, or diagnostic contrast dyes. Treatment typically includes administration of diuretics and limit the intake of water, fluids, sodium, and salt.
Signs and symptoms
The excess fluid, primarily salt and water, builds up in various locations in the body and leads to an increase in weight, swelling in the legs and arms (peripheral edema), and/or fluid in the abdomen (ascites). Eventually, the fluid enters the air spaces in the lungs (pulmonary edema) reduces the amount of oxygen that can enter the blood, leading to Anemia and causes shortness of breath (dyspnea) or enters pleural space by transudation (pleural effusion which also causes dyspnea), which is the best indicator of estimating central venous pressure is increased. It can also cause swelling of the face. Fluid can also collect in the lungs when lying down at night, possibly making nighttime breathing and sleeping difficult (paroxysmal nocturnal dyspnea).
Complications
Congestive heart failure is the most common result of fluid overload. Also, it may be associated with hyponatremia (hypervolemic hyponatremia).
Causes
Excessive sodium and/or fluid intake:
IV therapy containing sodium
As a transfusion reaction to a rapid blood transfusion.
High intake of sodiumSodium and water retention:
Heart failure
Liver cirrhosis
Nephrotic syndrome
Corticosteroid therapy
Hyperaldosteronism
Low protein intakeFluid shift into the intravascular space:
Fluid remobilization after burn treatment
Administration of hypertonic fluids, e.g. mannitol or hypertonic saline solution
Administration of plasma proteins, such as albumin
Treatment
Treatment includes diuretics, particularly loop diuretics.
See also
Volume status
Volume overload
Fluid balance
Edema
Anasarca (swelling of skin)
Pleural effusion (excess fluid in the pleural cavity)
Diuretics
Aquapheresis
Low pressure receptor zones
Apsia
References
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Chronic pain | Chronic pain is classified as pain that lasts longer than three to six months. In medicine, the distinction between acute and chronic pain is sometimes determined by the amount of time since onset. Two commonly used markers are pain that continues at three months and six months since onset, but some theorists and researchers have placed the transition from acute to chronic pain at twelve months. Others apply the term acute to pain that lasts less than 30 days, chronic to pain of more than six months duration, and subacute to pain that lasts from one to six months. A popular alternative definition of chronic pain, involving no fixed duration, is "pain that extends beyond the expected period of healing".Chronic pain may originate in the body, or in the brain or spinal cord. It is often difficult to treat. Epidemiological studies have found that 8–11.2% of people in various countries have chronic widespread pain. Various non-opioid medicines are initially recommended to treat chronic pain, depending on whether the pain is due to tissue damage or is neuropathic. Psychological treatments including cognitive behavioral therapy and acceptance and commitment therapy may be effective for improving quality of life in those with chronic pain. Some people with chronic pain may benefit from opioid treatment while others can be harmed by it. People with non-cancer pain who have not been helped by non-opioid medicines might be recommended to try opioids if there is no history of substance use disorder and no current mental illness.People with chronic pain tend to have higher rates of depression and although the exact connection between the comorbidities is unclear, a 2017 study on neuroplasticity found that "injury sensory pathways of body pains have been shown to share the same brain regions involved in mood management." Chronic pain can contribute to decreased physical activity due to fear of making the pain worse. Pain intensity, pain control, and resilience to pain can be influenced by different levels and types of social support that a person with chronic pain receives, and are also influenced by the persons socioeconomic status.
One approach to predicting a persons experience of chronic pain is the biopsychosocial model, according to which an individuals experience of chronic pain may be affected by a complex mixture of their biology, psychology, and their social environment.
Classification
The International Association for the Study of Pain defines chronic pain as pain with no biological value, that persists past normal tissue healing. The DSM-5 recognizes one chronic pain disorder, somatic symptom disorders. The criteria include pain lasting longer than six months.The International Classification of Disease, Eleventh Revision (ICD-11) suggests seven categories for chronic pain.
Chronic primary pain: defined by 3 months of persistent pain in one or more regions of the body that is unexplainable by another pain condition.
Chronic cancer pain: defined as cancer or treatment related visceral (within the internal organs), musculoskeletal, or bony pain.
Chronic post-traumatic pain: pain lasting 3 months after an injury or surgery, excluding infectious or pre-existing conditions.
Chronic neuropathic pain: pain caused by damage to the somatosensory nervous system.
Chronic headache and orofacial pain: pain that originates in the head or face, and occurs for 50% or more days over a 3 months period.
Chronic visceral pain: pain originating in an internal organ.
Chronic musculoskeletal pain: pain originating in the bones, muscles, joints or connective tissue.Chronic pain may be divided into "nociceptive" (caused by inflamed or damaged tissue activating specialized pain sensors called nociceptors), and "neuropathic" (caused by damage to or malfunction of the nervous system).Nociceptive pain can be divided into "superficial" and "deep", and deep pain into "deep somatic" and "visceral". Superficial pain is initiated by activation of nociceptors in the skin or superficial tissues. Deep somatic pain is initiated by stimulation of nociceptors in ligaments, tendons, bones, blood vessels, fasciae and muscles, and is dull, aching, poorly-localized pain. Visceral pain originates in the viscera (organs). Visceral pain may be well-localized, but often it is extremely difficult to locate, and several visceral regions produce "referred" pain when damaged or inflamed, where the sensation is located in an area distant from the site of pathology or injury.Neuropathic pain is divided into "peripheral" (originating in the peripheral nervous system) and "central" (originating in the brain or spinal cord). Peripheral neuropathic pain is often described as "burning", "tingling", "electrical", "stabbing", or "pins and needles".
Causes
Pathophysiology
Under persistent activation, the transmission of pain signals to the dorsal horn may produce a pain wind-up phenomenon. This triggers changes that lower the threshold for pain signals to be transmitted. In addition, it may cause nonnociceptive nerve fibers to respond to, generate, and transmit pain signals. The type of nerve fibers that are believed to generate the pain signals are the C-fibers, since they have a slow conductivity and give rise to a painful sensation that persists over a long time. In chronic pain, this process is difficult to reverse or stop once established. In some cases, chronic pain can be caused by genetic factors which interfere with neuronal differentiation, leading to a permanently lowered threshold for pain.Chronic pain of different causes has been characterized as a disease that affects brain structure and function. MRI studies have shown abnormal anatomical and functional connectivity, even during rest involving areas related to the processing of pain. Also, persistent pain has been shown to cause grey matter loss, which is reversible once the pain has resolved.These structural changes can be explained by neuroplasticity. In the case of chronic pain, the somatotopic representation of the body is inappropriately reorganized following peripheral and central sensitization. This can cause allodynia or hyperalgesia. In individuals with chronic pain, EEGs showed altered brain activity, suggesting pain-induced neuroplastic changes. More specifically, the relative beta activity (compared to the rest of the brain) was increased, the relative alpha activity was decreased, and the theta activity was diminished.Dysfunctional dopamine management in the brain could potentially act as a shared mechanism between chronic pain, insomnia and major depressive disorder. Astrocytes, microglia, and satellite glial cells have also been found to be dysfunctional in chronic pain. Increased activity of microglia, alterations of microglial networks, and increased production of chemokines and cytokines by microglia might aggravate chronic pain. Astrocytes have been observed to lose their ability to regulate the excitability of neurons, increasing spontaneous neural activity in pain circuits.
Management
Pain management is a branch of medicine that uses an interdisciplinary approach. The combined knowledge of various medical professions and allied health professions is used to ease pain and improve the quality of life of those living with pain. The typical pain management team includes medical practitioners (particularly anesthesiologists), rehabilitation psychologists, physiotherapists, occupational therapists, physician assistants, and nurse practitioners. Acute pain usually resolves with the efforts of one practitioner; however, the management of chronic pain frequently requires the coordinated efforts of a treatment team. Complete, longterm remission of many types of chronic pain is rare.
Nonopioids
Initially recommended efforts are non opioid based therapies. Non-opioid treatment of chronic pain with pharmaceutical medicines might include acetaminophen (paracetamol) or NSAIDs.Various other nonopioid medicines can be used, depending on whether the pain is a result of tissue damage or is neuropathic (pain caused by a damaged or dysfunctional nervous system). There is limited evidence that cancer pain or chronic pain from tissue damage as a result of a conditions (e.g. rheumatoid arthritis) is best treated with opioids. For neuropathic pain other drugs may be more effective than opioids, such as tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and anticonvulsants. Some atypical antipsychotics, such as olanzapine, may also be effective, but the evidence to support this is in very early stages. In women with chronic pain, hormonal medications such as oral contraceptive pills ("the pill") might be helpful. When there is no evidence of a single best fit, doctors may need to look for a treatment that works for the individual person. It is difficult for doctors to predict who will use opioids just for pain management and who will go on to develop an addiction. It is also challenging for doctors to know which patients ask for opioids because they are living with an opioid addiction. Withholding, interrupting or withdrawing opioid treatment in people who benefit from it can cause harm.Interventional pain management may be appropriate, including techniques such as trigger point injections, neurolytic blocks, and radiotherapy. While there is no high quality evidence to support ultrasound, it has been found to have a small effect on improving function in non-specific chronic low back pain.Psychological treatments, including cognitive behavioral therapy and acceptance and commitment therapy can be helpful for improving quality of life and reducing pain interference. Brief mindfulness-based treatment approaches have been used, but they are not yet recommended as a first-line treatment. The effectiveness of mindfulness-based pain management (MBPM) has been supported by a range of studies.Among older adults psychological interventions can help reduce pain and improve self-efficacy for pain management. Psychological treatments have also been shown to be effective in children and teens with chronic headache or mixed chronic pain conditions.While exercise has been offered as a method to lessen chronic pain and there is some evidence of benefit, this evidence is tentative. For people living with chronic pain, exercise results in few side effects.
Opioids
In those who have not benefited from other measures and have no history of either mental illness or substance use disorder treatment with opioids may be tried. If significant benefit does not occur it is recommended that they be stopped. In those on opioids, stopping or decreasing their use may improve outcomes including pain.Some people with chronic pain benefit from opioid treatment and others do not; some are harmed by the treatment. Possible harms include reduced sex hormone production, hypogonadism, infertility, impaired immune system, falls and fractures in older adults, neonatal abstinence syndrome, heart problems, sleep-disordered breathing, opioid-induced hyperalgesia, physical dependence, addiction, abuse, and overdose.
Alternative medicine
Alternative medicine refers to health practices or products that are used to treat pain or illness that are not necessarily considered a part of conventional medicine. When dealing with chronic pain, these practices generally fall into the following four categories: biological, mind-body, manipulative body, and energy medicine.Implementing dietary changes, which is considered a biological-based alternative medicine practice, has been shown to help improve symptoms of chronic pain over time. Adding supplements to ones diet is a common dietary change when trying to relieve chronic pain, with some of the most studied supplements being: Acetyl-L-carnitine, alpha lipoic acid, and vitamin E. Vitamin E is perhaps the most studied out of the three, with strong evidence that it helps lower neurotoxicity in those with cancer, multiple sclerosis, and cardiovascular diseases.Hypnosis, including self-hypnosis, has tentative evidence. Hypnosis, specifically, can offer pain relief for most people and may be a safe alternative to pharmaceutical medication. Evidence does not support hypnosis for chronic pain due to a spinal cord injury.Preliminary studies have found medical marijuana to be beneficial in treating neuropathic pain, but not other kinds of long term pain. As of 2018, the evidence for its efficacy in treating neuropathic pain or pain associated with rheumatic diseases is not strong for any benefit and further research is needed. For chronic non-cancer pain, a recent study concluded that it is unlikely that cannabinoids are highly effective. However, more rigorous research into cannabis or cannabis-based medicines is needed.Tai chi has been shown to improve pain, stiffness, and quality of life in chronic conditions such as osteoarthritis, low back pain, and osteoporosis. Acupuncture has also been found to be an effective and safe treatment in reducing pain and improving quality of life in chronic pain including chronic pelvic pain syndrome.Transcranial magnetic stimulation for reduction of chronic pain is not supported by high quality evidence, and the demonstrated effects are small and short-term.Spa therapy could potentially improve pain in patients with chronic lower back pain, but more studies are needed to provide stronger evidence of this.While some studies have investigated the efficacy of St Johns Wort or nutmeg for treating neuropathic (nerve) pain, their findings have raised serious concerns about the accuracy of their results.Kinesio Tape has not been shown to be effective in managing chronic non-specific low-back pain.Myofascial release has been used in some cases of fibromyalgia, chronic low back pain, and tennis elbow but there is not enough evidence to support this as method of treatment.
Epidemiology
Chronic pain varies in different countries affecting anywhere from 8% to 55.2% of the population. It affects women at a higher rate than men, and chronic pain uses a large amount of healthcare resources around the globe.A large-scale telephone survey of 15 European countries and Israel found that 19% of respondents over 18 years of age had suffered pain for more than 6 months, including the last month, and more than twice in the last week, with pain intensity of 5 or more for the last episode, on a scale of 1 (no pain) to 10 (worst imaginable). 4839 of these respondents with chronic pain were interviewed in-depth. Sixty-six percent scored their pain intensity at moderate (5–7), and 34% at severe (8–10); 46% had constant pain, 56% intermittent; 49% had suffered pain for 2–15 years; and 21% had been diagnosed with depression due to the pain. Sixty-one percent were unable or less able to work outside the home, 19% had lost a job, and 13% had changed jobs due to their pain. Forty percent had inadequate pain management and less than 2% were seeing a pain management specialist.In the United States, chronic pain has been estimated to occur in approximately 35% of the population, with approximately 50 million Americans experiencing partial or total disability as a consequence. According to the Institute of Medicine, there are about 116 million Americans living with chronic pain, which suggests that approximately half of American adults have some chronic pain condition. The Mayday Fund estimate of 70 million Americans with chronic pain is slightly more conservative. In an internet study, the prevalence of chronic pain in the United States was calculated to be 30.7% of the population: 34.3% for women and 26.7% for men.In Canada it is estimated that approximately 1 in 5 Canadians live with chronic pain and half of those people have lived with chronic pain for 10 years or longer. Chronic pain in Canada also occurs more and is more severe in women and Canadas Indigenous communities.
Outcomes
Sleep disturbance, and insomnia due to medication and illness symptoms are often experienced by those with chronic pain. These conditions can be difficult to treat due to the high potential of medication interactions, especially when the conditions are treated by different doctors.Severe chronic pain is associated with increased risk of death over a ten-year period, particularly from heart disease and respiratory disease. Several mechanisms have been proposed for this increase, such as an abnormal stress response in the bodys endocrine system. Additionally, chronic stress seems to affect risks to heart and lung (cardiovascular) health by increasing how quickly plaque can build up on artery walls (arteriosclerosis). However, further research is needed to clarify the relationship between severe chronic pain, stress and cardiovascular health.
Psychology
Personality
Two of the most frequent personality profiles found in people with chronic pain by the Minnesota Multiphasic Personality Inventory (MMPI) are the conversion V and the neurotic triad. The conversion V personality expresses exaggerated concern over body feelings, develops bodily symptoms in response to stress, and often fails to recognize their own emotional state, including depression. The neurotic triad personality also expresses exaggerated concern over body feelings and develops bodily symptoms in response to stress, but is demanding and complaining.Some investigators have argued that it is this neuroticism that causes acute pain to turn chronic, but clinical evidence points the other way, to chronic pain causing neuroticism. When long term pain is relieved by therapeutic intervention, scores on the neurotic triad and anxiety fall, often to normal levels. Self-esteem, often low in people with chronic pain, also shows improvement once pain has resolved.It has been suggested that catastrophizing might play a role in the experience of pain. Pain catastrophizing is the tendency to describe a pain experience in more exaggerated terms than the average person, to think a great deal more about the pain when it occurs, or to feel more helpless about the experience. People who score highly on measures of catastrophization are likely to rate a pain experience as more intense than those who score low on such measures. It is often reasoned that the tendency to catastrophize causes the person to experience the pain as more intense. One suggestion is that catastrophizing influences pain perception through altering attention and anticipation, and heightening emotional responses to pain. However, at least some aspects of catastrophization may be the product of an intense pain experience, rather than its cause. That is, the more intense the pain feels to the person, the more likely they are to have thoughts about it that fit the definition of catastrophization.
Comorbidity with trauma
Individuals with posttraumatic stress disorder (PTSD) have a high comorbidity with chronic pain. Patients with both PTSD and chronic pain report higher severity of pain than those who do not have a PTSD comorbidity.
Effect on cognition
Chronic pains impact on cognition is an under-researched area, but several tentative conclusions have been published. Most people with chronic pain complain of cognitive impairment, such as forgetfulness, difficulty with attention, and difficulty completing tasks. Objective testing has found that people in chronic pain tend to experience impairment in attention, memory, mental flexibility, verbal ability, speed of response in a cognitive task, and speed in executing structured tasks. A review of studies in 2018 reports a relationship between people in chronic pain and abnormal results in test of memory, attention, and processing speed.
Social and personal impacts
Social support
Social support has important consequences for individuals with chronic pain. In particular, pain intensity, pain control, and resiliency to pain have been implicated as outcomes influenced by different levels and types of social support. Much of this research has focused on emotional, instrumental, tangible and informational social support. People with persistent pain conditions tend to rely on their social support as a coping mechanism and therefore have better outcomes when they are a part of larger more supportive social networks. Across a majority of studies investigated, there was a direct significant association between social activities or social support and pain. Higher levels of pain were associated with a decrease in social activities, lower levels of social support, and reduced social functioning.
Racial disparities
Evidence exists for unconscious biases and negative stereotyping against racial minorities requesting pain treatment, although clinical decision making was not affected, according to one 2017 review. Minorities may be denied diagnoses for pain and pain medications, and are more likely to go through substance abuse assessment, and are less likely to transfer for pain specialist referral. Preliminary research showed that health providers might have less empathy for black patients and underestimated their pain levels, resulting in treatment delays. Minorities may experience a language barrier, limiting the high level of engagement between the person with pain and health providers for treatment.
Perceptions of injustice
Similar to the damaging effects seen with catastrophizing, perceived injustice is thought to contribute to the severity and duration of chronic pain. Pain-related injustice perception has been conceptualized as a cognitive appraisal reflecting the severity and irreparability of pain- or injury-related loss (e.g., "I just want my life back"), and externalizing blame and unfairness ("I am suffering because of someone elses negligence."). It has been suggested that understanding problems with top down processing/cognitive appraisals can be used to better understand and treat this problem.
Chronic pain and COVID-19
COVID-19 has disrupted the lives of many, leading to major physical, psychological and socioeconomic impacts in the general population. Social distancing practices defining the response to the pandemic alter familiar patterns of social interaction, creating the conditions for what some psychologists are describing as a period of collective grief. Individuals with chronic pain tend to embody an ambiguous status, at times expressing that their type of suffering places them between and outside of conventional medicine. With a large proportion of the global population enduring prolonged periods of social isolation and distress, one study found that people with chronic pain from COVID-19 experienced more empathy towards their suffering during the pandemic.
Effect of chronic pain in the workplace
In the workplace, chronic pain conditions are a significant problem for both the person with the condition and the organization; a problem only expected to increase in many countries due to an aging workforce. In light of this, it may be helpful for organizations to consider the social environment of their workplace, and how it may be working to ease or worsen chronic pain issues for employees. As an example of how the social environment can affect chronic pain, some research has found that high levels of socially prescribed perfectionism (perfectionism induced by external pressure from others, such as a supervisor) can interact with the guilt felt by a person with chronic pain, thereby increasing job tension, and decreasing job satisfaction.
Mobility and road safety impacts
A 2022 systematic review found that chronic pain could increase crash risk among drivers. Chronic pain drivers report experiencing difficulties with safety maneuvers, such as shoulder checking for blind spots, merging with traffic, turning corners, and reversing the vehicle.
See also
Childhood chronic pain
Neuroinflammation
Neurodegeneration
Dopaminergic pathways
References
Further reading
External links
Chronic Pain Syndromes at Curlie
Media related to pain at Wikimedia Commons
International Association for the Study of Pain Archived 2021-05-01 at the Wayback Machine |
Pili annulati | Pili annulati (also known as "ringed hair") is a genetic trait in which the hair seems ‘banded‘ by alternating segments of light and dark color when seen in reflected light.: 767 : 640
See also
Pili pseudoannulati
List of cutaneous conditions
References
External links
Hair Transplant |
Craniofacial cleft | A facial cleft is an opening or gap in the face, or a malformation of a part of the face. Facial clefts is a collective term for all sorts of clefts. All structures like bone, soft tissue, skin etc. can be affected. Facial clefts are extremely rare congenital anomalies. There are many variations of a type of clefting and classifications are needed to describe and classify all types of clefting. Facial clefts hardly ever occur isolated; most of the time there is an overlap of adjacent facial clefts.
Classifications
There are different classifications about facial clefts. Two of the most used classifications are the Tessier classification and the Van der Meulen classification. Tessier is based on the anatomical position of the cleft and Van der Meulen classification is based on the embryogenesis.
Tessier classification
In 1976 Paul Tessier published a classification on facial clefts based on the anatomical position of the clefts. The different types of Tessier clefts are numbered 0 to 14. These 15 different types of clefts can be put into 4 groups, based on their position: midline clefts, paramedian clefts, orbital clefts and lateral clefts. The Tessier classification describes the clefts at soft tissue level as well as at bone level, because it appears that the soft tissue clefts can have a slightly different location on the face than the bony clefts.
Midline clefts
The midline clefts are Tessier number 0 ("median craniofacial dysplasia"), number 14 (frontonasal dysplasia), and number 30 ("lower midline facial cleft", also known as "median mandibular cleft"). These clefts bisect the face vertically through the midline. Tessier number 0 bisects the maxilla and the nose, Tessier number 14 comes between the nose and the frontal bone. The Tessier number 30 facial cleft is through the tongue, lower lip and mandible. The tongue may be absent, hypoplastic, bifid, or even duplicated. People with this condition may be tongue-tied.
Paramedian clefts
Tessier number 1, 2, 12 and 13 are the paramedian clefts. These clefts are quite similar to the midline clefts, but they are further away from the midline of the face. Tessier number 1 and 2 both come through the maxilla and the nose, in which Tessier number 2 is further from the midline (lateral) than number 1. Tessier number 12 is in extent of number 2, positioned between nose and frontal bone, while Tessier number 13 is in extent of number 1, also running between nose and forehead. Both 12 and 13 run between the midline and the orbit.
Orbital clefts
Tessier number 3, 4, 5, 9, 10 and 11 are orbital clefts. These clefts all have the involvement of the orbit. Tessier number 3, 4, and 5 are positioned through the maxilla and the orbital floor. Tessier number 9, 10 and 11 are positioned between the upper side of the orbit and the forehead or between the upper side of the orbit and the temple of the head.
Like the other clefts, Tessier number 11 is in extent to number 3, number 10 is in extent to number 4 and number 9 is in extent to number 5.
Lateral clefts
The lateral clefts are the clefts which are positioned horizontally on the face. These are Tessier number 6, 7 and 8. Tessier number 6 runs from the orbit to the cheek bone. Tessier number 7 is positioned on the line between the corner of the mouth and the ear. A possible lateral cleft comes from the corner of the mouth towards the ear, which gives the impression that the mouth is bigger. It’s also possible that the cleft begins at the ear and runs towards the mouth. Tessier number 8 runs from the outer corner of the eye towards the ear.
The combination of a Tessier number 6-7-8 is seen in the Treacher Collins syndrome. Tessier number 7 is more related to hemifacial microsomia and number 8 is more related to Goldenhar syndrome.
Van der Meulen classification
Van der Meulen classification divides different types of clefts based on where the development arrest occurs in the embryogenesis. A primary cleft can occur in an early stage of the development of the face (17 mm length of the embryo). The developments arrests can be divided in four different location groups: internasal, nasal, nasalmaxillar and maxillar. The maxillar location can be subdivided in median and lateral clefts.
Internasal dysplasia
Internasal dysplasia is caused by a development arrest before the union of the both nasal halves. These clefts are characterized by a median cleft lip, a median notch of the cupids bow or a duplication of the labial frenulum. Besides the median cleft lip, hypertelorism can be seen in these clefts. Also sometimes there can be an underdevelopment of the premaxilla.
Nasal dysplasia
Nasal dysplasia or nasoschisis is caused by a development arrest of the lateral side of the nose, resulting in a cleft in one of the nasal halves. The nasal septum and cavity can be involved, though this is rare. Nasoschisis is also characterized by hypertelorism.
Nasomaxillary dysplasia
Nasomaxillary dysplasia is caused by a development arrest at the junction of the lateral side of the nose and the maxilla, which results in a complete or non-complete cleft between the nose and the orbital floor (nasoocular cleft) or between the mouth, nose and the orbital floor (oronasal-ocular cleft). The development of the lip is normal.
Maxillary dysplasia
Maxillary dysplasia can manifest itself on two different locations in the maxilla: in the medial or the lateral part of the maxilla.
Median maxillary dysplasia is caused by a development failure of the medial part of the maxillary ossification centers. This results in secondary clefting of the lip, philtrum and palate. Clefting from the maxilla to the orbital floor has also been reported.
Lateral maxillary dysplasia is caused by a development failure of the lateral part of the maxillary ossification centers, which also results in secondary clefting of the lip and palate. Clefting of the lateral part of the lower eyelid is typical for lateral maxillary dysplasia.
Causes
It is possible that facial clefts are caused by a disorder in the migration of neural crest cells.Another theory is that facial clefts are caused by failure of the fusion process and failure of inwards growth of the mesoderm.
Other theories are that genetics play a part in the development of facial clefts or that they are caused by amniotic bands.
Genetics
Overview
Around one in 700 individuals are born with craniofacial clefts. There are multiple genetic and environmental factors which contribute to craniofacial development. Within craniofacial disorders and abnormalities, orofacial clefts, and specifically cleft lip (CL) and cleft palate (CP) are the most common in humans. Occurrences of CL/P are most often (around seventy percent of cases) isolated and nonsyndromic, meaning they are not associated with a syndrome or inherited genetic conditions. Around thirty percent occur with other structural variances, and over 500 syndromes have been identified in which clefting is a principal feature. Clefting can result from teratogens, an agent that disrupts embryo development such as, radiation, maternal infection, chemicals, or drugs. Chromosomal abnormalities or mutations at single gene loci have also contributed to clefting development. Genetic causes are linked with most craniofacial syndromes, and CL/P and other orofacial clefts are recognized as heterogeneous disorders, meaning there are multiple recognized causes. Orofacial clefts have great phenotypic diversity, and their associated genetic environments have called for vast research and investigation.
Environmental Interaction
Craniofacial disorders have high variance in phenotypic expression, and researchers have suggested this variance could be due to interactions between the mutated/deviated genes and other genes, along with interactions with environmental factors. Environmental causes have been found to contribute to craniofacial clefting, however, these are still influenced by and supported by genetic factors. Many studies, for example, have linked maternal smoking to increased CLP risk; however, the increased risk suggests that genes in metabolic pathways could still contribute to susceptibility or formation of CL/P.
Development and Inheritance
The craniofacial complex begins its progress in the fourth week of development, and results from neural crest cells migrating to form and fuse the facial primordia. Failures or deviations in this process result in craniofacial clefts, either CL or CP. The range of variation in phenotype aligns with ancestry. Studies have found increased amounts of clefting in the relatives of patients with clefts, suggesting genetic factors are the underlying cause for CL/P. Inheritance has a known and significant role in human craniofacial morphology. This is supported through cephalometric and anthropometric comparisons of family members including between triplets, twins, siblings, and parents and children.
Genetic Experimentation
Genetic factors of craniofacial clefting can be investigated and tracked through several methods including sequencing in humans, Genome-wide association studies (GWAs), fate mapping, expression analysis, and animal studies (knockout experiments or models with clefting from chemical mutagenesis). Twin studies and familial clustering have also revealed that facial structure and formation are genetically linked. Several genes have been associated with craniofacial disorders through experimentation, including sequencing Mendelian clefting syndromes. Over 25 loci have been identified as potential influencers of craniofacial clefts across populations.
Linked Genes
The transforming growth factor (TGF) family has provided multiple candidate genes linked with craniofacial development and malformation. TGF is involved in cell migration, differentiation, and proliferation, as well as regulating the extracellular matrix. Another gene that has been flagged as causal for craniofacial disorders, including CL/P, is interferon regulatory factor 6 or, IRF6. Mutations in IRF6 cause Van der Woude syndrome, the most common clefting syndrome. Ventral anterior homeobox 1, VAX1, and noggin, NOG, were identified with genome-wide significance for contributing to CL/P. Additionally, mutations in SPECC1L have recently been identified as influential to facial structure formation, and as causal for syndromic facial clefting. Nonsyndromic CL/P has been associated with the transcription factor forkhead box protein E1 (FOXE1), as mutations have resulted in cases of CL/P in mice. Other genes which have been found to interact with or contribute to craniofacial clefting include FGFRs, TWIST, MSXs, GREM1, TCOF1, PAXs, MAFB, ABCA4, and WNT allowing great cause for more research into the genetic basis for craniofacial disorders.
Prevention
Because the cause of facial clefts still is unclear, it is difficult to say what may prevent children being born with facial clefts. It seems that folic acid contributes to lowering the risk of a child being born with a facial cleft.
Treatment
There is no single strategy for treatment of facial clefts, because of the large amount of variation in these clefts. Which kind of surgery is used depends on the type of clefting and which structures are involved. There is much discussion about the timing of reconstruction of bone and soft tissue. The problem with early reconstruction is the recurrence of the deformity due to the intrinsic restricted growth. This requires additional operations at a later age to make sure all parts of the face are in proportion. A disadvantage of early bone reconstruction is the chance to damage the tooth germs, which are located in the maxilla, just under the orbit. The soft tissue reconstruction can be done at an early age, but only if the used skin flap can be used again during a second operation. The timing of the operation depends on the urgency of the underlying condition. If the operation is necessary to function properly, it should be done at early age. The best aesthetic result is achieved when the incisions are positioned in areas which attract the least attention (they cover up the scars). If, however, the function of a part of the face isn’t damaged, the operation depends on psychological factors and the facial area of reconstruction.
The treatment plan of a facial cleft is planned right after diagnosis. This plan includes every operation needed in the first 18 years of the patients life to reconstruct the face fully.
In this plan, a difference is made between problems that need to be solved to improve the health of the patient (coloboma) and problems that need to be solved for a better cosmetic result (hypertelorism).
The treatment of the facial clefts can be divided in different areas of the face: the cranial anomalies, the orbital and eye anomalies, the nose anomalies, the midface anomalies and the mouth anomalies.
Treatment of the cranial anomalies
The most common cranial anomaly seen in combination with facial clefts is encephalocele.
Encephalocele
The treatment of encephalocele is based on surgery to repair the bony gap and provide adequate protection of the underlying brain. The question remains if the external brain tissue should be put back into the skull or if it is possible to cut off that piece of brain tissue, because its claimed that the external piece of brain tissue often isn’t functional, with the exception of a basal encephalocele, in which the pituitary gland can be found in the mouth.
Treatment of orbital / eye anomalies
The most common orbital /eye anomalies seen in children with facial clefts are colobomas and vertical dystopia.
Coloboma
The coloboma which occurs often in facial clefts is a cleft in the lower or upper eyelid. This should be closed as soon as possible, to prevent drought of the eye and a consecutive loss of vision.
Vertical orbital dystopia
Vertical orbital dystopia can occur in facial clefts when the orbital floor and/or the maxilla is involved in the cleft. Vertical orbital dystopia means that the eyes do not lay on the same horizontal line in the face (one eye is positioned lower than the other). The treatment is based on the reconstruction of this orbital floor, by either closing the boney cleft or reconstructing the orbital floor using a bone graft.
Hypertelorism
There are many types of operations which can be performed to treat a hypertelorism. 2 options are: box osteotomy and facial bipartition (also referred to as a median fasciotomy).
The goal of the box osteotomy is to bring the orbits closer together by removing a part of the bone between the orbits, to detach both orbits from the surrounding bone structures and move both orbits more to the centre of the face.
The goal of the facial bipartition is not only to bring the orbits closer together, but also to create more space in the maxilla. This can be done by splitting the maxilla and the frontal bone, remove a triangular shaped piece of bone from the forehead and nasal bones and pulling the two pieces of forehead together. Not only will the hypertelorism be solved by pulling the frontal bone closer together, but because of this pulling, the space between the both parts of the maxilla will become wider.
Treatment of nose anomalies
The nose anomalies found in facial clefts vary. The main goal of the treatment is to reconstruct the nose to get a functional and esthetic acceptable result. A few possible treatment options are to reconstruct the nose with a forehead flap or reconstruct the nasal dorsum with a bone graft, for example a rib graft. The nasal reconstruction with a forehead flap is based on the repositioning of a skin flap from the forehead to the nose. A possible downside of this reconstruction is that once you performed it at a younger age, you can’t lengthen the flap at a later stage. A second operation is often needed if the operation is done on early age, because the nose has a restricted growth in the cleft area. Repair of the ala (wing of the nose) often requires the inset of cartilage graft, commonly taken from the ear.
Treatment of midface anomalies
The treatment of soft tissue parts of midface anomalies is often a reconstruction from a skin flap of the cheek. This skinflap can be used for other operations in the further, as it can be raised again and transposed again. In the treatment of midface anomalies there are generally more operations needed. Bone tissue reconstruction of the midface often occurs later than the soft tissue reconstruction. The most common method to reconstruct the midface is by using the fracture/ incision lines described by René Le Fort. When the cleft involves the maxilla, it is likely that the impaired growth will result in a smaller maxillary bone in all 3 dimensions (height, projection, width).
Treatment of mouth anomalies
There are several options for treatment of mouth anomalies like Tessier cleft number 2-3-7 . These clefts are also seen in various syndromes like Treacher Collins syndrome and hemifacial microsomia, which makes the treatment much more complicated. In this case, treatment of mouth anomalies is a part of the treatment of the syndrome.
See also
Related articles
Ectrodactyly–ectodermal dysplasia–cleft syndrome
Cleft hand
Cleft lip and palateSyndromes
Treacher Collins syndrome
Hemifacial microsomia
Goldenhar syndrome
== References == |
Pilon fracture | A pilon fracture, is a fracture of the distal part of the tibia, involving its articular surface at the ankle joint. Pilon fractures are caused by rotational or axial forces, mostly as a result of falls from a height or motor vehicle accidents. Pilon fractures are rare, comprising 3 to 10 percent of all fractures of the tibia and 1 percent of all lower extremity fractures, but they involve a large part of the weight-bearing surface of the tibia in the ankle joint. Because of this, they may be difficult to fixate and are historically associated with high rates of complications and poor outcome.Pilon is the French word for "pestle" and was introduced into orthopedic literature in 1911 by pioneer French radiologist Étienne Destot.
Classification
Pilon fractures are categorized by two main X-ray schemes, Ruedi-Allgower classification system. and Müller AO Classification of fractures.
Treatment
The treatment of pilon fractures depends on the extent of the injury. This includes the involvement of other bones such as the fibula and the talus, involvement of soft tissue, and the fracture pattern. Treatment strategies and fixation methods used include internal and external fixation, as well as staged approaches, with the aim of reducing the fracture, reconstructing the involved bones and restoration of articular surface congruence, with minimal insult to soft tissues. Appropriate wound management is important to reduce the high rate of infectious complications and secondary wound healing problems associated with open pilon fractures. Vacuum-assisted wound closure therapy and using a staged protocol (awaiting soft-tissue recovery before extensive reconstructive efforts) may play a positive role.
See also
Ankle fracture
References
== External links == |
Pustular bacterid | Pustular bacterid is a skin condition characterized by a symmetric, grouped, vesicular or pustular eruption on the palms and soles marked by exacerbations and remissions over long periods of time.: 205
See also
List of cutaneous conditions
References
== External links == |
Eosinophilic cellulitis | Eosinophilic cellulitis, also known as Wells syndrome (not to be confused with Weils disease), is a skin disease that presents with painful, red, raised, and warm patches of skin. The rash comes on suddenly, lasts for a few weeks, and often repeatedly comes back. Scar formation does not typically occur.Eosinophilic cellulitis is of unknown cause. It is suspected to be an autoimmune disorder. It may be triggered by bites from insects such as spiders, fleas, or ticks, or from medications or surgery. Diagnosis is made after other potential cases are ruled out. Skin biopsy of the affected areas may show an increased number of eosinophils. Other conditions that may appear similar include cellulitis, contact dermatitis, and severe allergic reactions such as anaphylaxis.Treatment is often with a corticosteroids. Steroids applied as a cream is generally recommended over the use of steroids by mouth. Antihistamines may be used to help with itchiness. Many times the condition goes away after a few weeks without treatment. The condition is uncommon. It affects both sexes with the same frequency. It was first described by George Crichton Wells in 1971.
Cause
Eosinophilic cellulitis is of unknown cause. It is suspected to be an autoimmune disorder. It may be triggered by bites from insects such as mosquitos, spiders, fleas, or ticks, or from medications or surgery.
Diagnosis
Diagnosis requires ruling out other potential causes. This includes ruling out vasculitis on skin biopsy.
Treatment
Treatment is often with a steroids. This can be either applied as a cream or taken by mouth. As the condition tends to get better on its own taking steroids by mouth should generally only be tried if the rash covers a large area and it does not get better with other measures.
References
External links
DermNet NZ Archived 2015-08-22 at the Wayback Machine entry |
Lenticonus | Lenticonus (/len·ti·co·nus/ (len″tĭ-ko´nus)) [lens + L. conus, cone] is a rare congenital anomaly of the eye characterized by a conical protrusion on the crystalline lens capsule and the underlying cortex. It can reach a diameter of 2 to 7 mm. The conus may occur anteriorly or posteriorly. If the bulging is spherical, instead of conical, the condition is referred to as lentiglobus. It produces a decrease in visual acuity and irregular refraction that cannot be corrected by either spectacle or contact lenses.Biomicroscopically lenticonus is characterized by a transparent, localized, sharply demarcated conical projection of the lens capsule and cortex, usually axial in localization. In an early stage, retro-illumination shows an oil dropletconfiguration. Using a narrow slit, the image of a conus is observed. In a more advanced stage associated subcapsular and cortical opacities appear. Retinoscopically the oil droplet produces a pathognomonic scissors movement of the light reflex. This phenomenon is due to the different refraction in the central and the peripheral area of the lens. Ultrasonography also can illustrate the existence of a lenticonus. A-scan ultrasonography may reveal an increased lens thickness and B- scanultrasonography may show herniated lenticular material, suggestive of a lenticonus. Amblyopia, cataract, strabismus and loss of central fixation may be observed in association with lenticonus posterior. Cataract, flecked retinopathy, posterior polymorphous dystrophy and corneal arcus juvenilis may be encountered in association with lenticonus anterior that occurs as a part of the Alport syndrome.There exist two distinct types of lenticonus based on the face of the lens affected.
Types
Lenticonus anterior; lenticonus anterior is part of the waardenburg syndrome
Lenticonus posterior; lenticonus posterior is more common than lenticonus anterior and is sometimes found in Lowe syndromeAlport syndrome mostly causes anterior lenticonus. It can rarely cause posterior lenticonus, but this is uncommon.
== References == |
Extensively drug-resistant tuberculosis | Extensively drug-resistant tuberculosis (XDR-TB) is a form of tuberculosis caused by bacteria that are resistant to some of the most effective anti-TB drugs. XDR-TB strains have arisen after the mismanagement of individuals with multidrug-resistant TB (MDR-TB).
Almost one in four people in the world is infected with TB bacteria. Only when the bacteria become active do people become ill with TB. Bacteria become active as a result of anything that can reduce the persons immunity, such as HIV, advancing age, or some medical conditions. TB can usually be treated with a course of four standard, or first-line, anti-TB drugs (i.e., isoniazid, rifampin and any fluoroquinolone). If these drugs are misused or mismanaged, multidrug-resistant TB (MDR-TB) can develop. MDR-TB takes longer to treat with second-line drugs (i.e., amikacin, kanamycin, or capreomycin), which are more expensive and have more side-effects. XDR-TB can develop when these second-line drugs are also misused or mismanaged and become ineffective. The World Health Organization (WHO) defines XDR-TB as MDR-TB that is resistant to at least one fluoroquinolone and a second-line injectable drug (amikacin, capreomycin, or kanamycin).XDR-TB raises concerns of a future TB epidemic with restricted treatment options, and jeopardizes the major gains made in TB control and progress on reducing TB deaths among people living with HIV/AIDS. It is therefore vital that TB control be managed properly and new tools developed to prevent, treat and diagnose the disease.
The true scale of XDR-TB is unknown as many countries lack the necessary equipment and capacity to accurately diagnose it. By June 2008, 49 countries had confirmed cases of XDR-TB. By the end of 2017, 127 WHO Member States reported a total of 10,800 cases of XDR-TB, and 8.5% of cases of MDR-TB in 2017 were estimated to have been XDR-TB.In August 2019, the Food and Drug Administration (FDA) approved the use of Pretomanid in combination with bedaquiline and linezolid for treating a limited and specific population of adult patients with extensively drug resistant, treatment-intolerant or nonresponsive multidrug resistant pulmonary TB.
Symptoms and signs
Symptoms of XDR-TB are no different from ordinary or drug-susceptible TB: a cough with thick, cloudy mucus (or sputum), sometimes with blood, for more than two weeks; fever, chills, and night sweats; fatigue and muscle weakness; weight loss; and in some cases shortness of breath and chest pain. A person with these symptoms does not necessarily have XDR-TB, but they should see a physician for diagnosis and a treatment plan. TB patients whose symptoms do not improve after a few weeks of treatment for TB and are taking treatment should inform their clinician or nurse.
Transmission
Like other forms of TB, XDR-TB is spread through the air. When a person with infectious TB coughs, sneezes, talks or spits, they propel TB germs, known as bacilli, into the air. XDR-TB cannot be spread by kissing, sharing food or drinks, or shaking someones hand. The bacterium has the ability to stay in the air for several hours. A person needs only to inhale a small number of these to be infected. People infected with TB bacilli will not necessarily become sick with the disease. The immune system "walls off" the TB bacilli which, protected by a thick waxy coat, can lie dormant for years.The spread of TB bacteria depends on factors such as the number and concentration of infectious people in any one place together with the presence of people with a higher risk of being infected (such as those with HIV/AIDS). The risk of becoming infected increases with the longer the time that a previously uninfected person spends in the same room as the infectious case. The risk of spread increases where there is a high concentration of TB bacteria, such as can occur in closed environments like overcrowded houses, hospitals or prisons. The risk will be further increased if ventilation is poor. The risk of spread will be reduced and eventually eliminated if infectious patients receive proper treatment.
Diagnosis
Successful diagnosis of XDR-TB depends on the patients access to quality health-care services. If TB bacteria are found in the sputum, the diagnosis of TB can be made in a day or two, but this finding will not be able to distinguish between drug-susceptible and drug-resistant TB. To evaluate drug susceptibility, the bacteria need to be cultivated and tested in a suitable laboratory. Final diagnosis in this way for TB, and especially for XDR-TB, may take from 6 to 16 weeks.The original method used to test for MDR-TB and XDR-TB was the Drug Susceptibility Testing (DST). DST is capable of determining how well four primary antitubercular drugs inhibit the growth of Mycobacterium Tuberculosis. The four primary antitubercular drugs are Isoniazid, Rifampin, Ethambutol and Pyrazinamide. Drug Susceptibility testing is done by making a Lowenstein-Jensen medium plate and spreading the bacteria on the plate. Disks containing one of the four primary drugs are added to the plate. After weeks of allowing the bacteria to grow the plate is checked for clear areas around the disk. If there is a clear area, the drug has killed the bacteria and most likely the bacteria are not resistant to that drug.As Mycobacterium tuberculosis evolved new strains of resistant bacteria were being found such as XDR-TB. The problem was that primary DST was not suitable for testing bacteria strains that were extensively drug resistant. This problem was starting to be fixed when drug susceptibility tests started including not just the four primary drugs, but secondary drugs. This secondary test is known as Bactec MGIT 960 System. Although Bactec MGIT 960 System was accurate it was still slow at determining the level of resistance.Diagnosis of MDR and XDR-TB in children is challenging. With an increasing number of cases being reported worldwide there is a great need for better diagnostic tools available for pediatric patients.In recent years drug resistant tuberculosis testing has shown a lot of progress. Some studies have found an in-house assay that could rapidly detect resistance to drugs involved in the definition of XDR-TB directly from smear-positive specimens. The assay is called Reverse Line Blot Hybridization Assay also known as RLBH. The study showed that the results of RLBH were as accurate as other drug susceptibility tests, but at the same time didn`t take weeks to get results. RLBH testing only took 3 days to determine how resistant the strain of bacteria was.The current research has shown progress in the testing of drug resistance. A recent study found that a research technique known as direct nitrate reductase assay (D-NRA) showed efficient accuracy for the rapid and simultaneous detection of resistance to isoniazid (INH), rifampicin (RIF), kanamycin (KAN) and ofloxacin (OFL). D-NRA results were obtained in 16.9 days, comparably less than other drug susceptibility testing. At the same time the study mentioned how D-NRA is a low-cost technology, easy to set up in clinical laboratories and suitable to be used for DST of M. tuberculosis in all smear-positive samples.
Prevention
Countries aim to prevent XDR-TB by ensuring that the work of their national TB control programmes, and of all practitioners working with people with TB, is carried out according to the International Standards for TB Care. These emphasize providing proper diagnosis and treatment to all TB patients, including those with drug-resistant TB; assuring regular, timely supplies of all anti-TB drugs; proper management of anti-TB drugs and providing support to patients to maximize adherence to prescribed regimens; caring for XDR-TB cases in a centre with proper ventilation, and minimizing contact with other patients, particularly those with HIV, especially in the early stages before treatment has had a chance to reduce the infectiousness. Also an effective disease control infrastructure is necessary for the prevention of XDR tuberculosis. Increased funding for research, and strengthened laboratory facilities are much required. Immediate detection through drug susceptibility testings are vital, when trying to stop the spread of XDR tuberculosis.
BCG vaccine
The BCG vaccine prevents severe forms of TB in children, such as TB meningitis. It would be expected that BCG would have the same effect in preventing severe forms of TB in children, even if they were exposed to XDR-TB. The vaccine has shown to be less effective at preventing the most common strains of TB and in blocking TB in adults. The effect of BCG against XDR-TB would therefore likely be very limited.
Treatment
The principles of treatment for MDR-TB and for XDR-TB are the same. Second-line drugs are more toxic than the standard anti-TB regimen and can cause a range of serious side-effects including hepatitis, depression, hallucinations, and deafness. Patients are often hospitalized for long periods, in isolation. In addition, second-line drugs are extremely expensive compared with the cost of drugs for standard TB treatment.
XDR-TB is associated with a much higher mortality rate than MDR-TB, because of a reduced number of effective treatment options. A 2008 study in the Tomsk oblast of Russia, reported that 14 out of 29 (48.3%) patients with XDR-TB successfully completed treatment. In 2018, the WHO reported that the treatment success rate for XDR-TB was 34% for the 2015 cohort, compared to 55% for MDR/RR-TB (2015 cohort), 77% for HIV-associated TB (2016 cohort), and 82% for TB (2016 cohort).A 2018 meta-analysis of 12,030 patients from 25 countries in 50 studies has demonstrated that treatment success increases and mortality decreases when treatment includes bedaquiline, later generation fluoroquinolones, and linezolid. One regimen for XDR-TB called Nix-TB, a combination pretomanid, bedaquiline, and linezolid, has shown promise in early clinical trials.Successful outcomes depend on a number of factors including the extent of the drug resistance, the severity of the disease and whether the patients immune system is compromised. It also depends on access to laboratories that can provide early and accurate diagnosis so that effective treatment is provided as soon as possible. Effective treatment requires that all six classes of second-line drugs be available to clinicians who have special expertise in treating such cases.
Enforced quarantine
Carriers who refuse to wear a mask in public have been indefinitely involuntarily committed to regular jails, and cut off from contacting the world. Some have run away from the USA, complaining of abuse.
Epidemiology
Studies have found that men have a higher risk of getting XDR-TB than women. One study showed that the male to female ratio was more than threefold, with statistical relevance (P<0.05) Studies done on the effect of age and XDR-TB have revealed that individuals who are 65 and up are less likely to get XDR-TB. A study in Japan found that XDR-TB patients are more likely to be younger.
XDR-TB and HIV/AIDS
TB is one of the most common infections in people living with HIV/AIDS. In places where XDR-TB is most common, people living with HIV are at greater risk of becoming infected with XDR-TB, compared with people without HIV, because of their weakened immunity. If there are a lot of HIV-infected people in these places, then there will be a strong link between XDR-TB and HIV. Fortunately, in most of the places with high rates of HIV, XDR-TB is not yet widespread. For this reason, the majority of people with HIV who develop TB will have drug-susceptible or ordinary TB, and can be treated with standard first-line anti-TB drugs. For those with HIV infection, treatment with antiretroviral drugs will likely reduce the risk of becoming infected with XDR-TB, just as it does with ordinary TB.
A research study titled "TB Prevalence Survey and Evaluation of Access to TB Care in HIV-Infected and Uninfected TB Patients in Asembo and Gem, Western Kenya", says that HIV/AIDS is fueling large increases in TB incidence in Africa, and a large proportion of cases are not diagnosed.
History
XDR-TB is defined as TB that has developed resistance to at least rifampicin and isoniazid (resistance to these first line anti-TB drugs defines Multi-drug-resistant tuberculosis, or MDR-TB), as well as to any member of the quinolone family and at least one of the following second-line anti-TB injectable drugs: kanamycin, capreomycin, or amikacin. This definition of XDR-TB was agreed by the World Health Organization (WHO) Global Task Force on XDR-TB in October 2006. The earlier definition of XDR-TB as MDR-TB that is also resistant to three or more of the six classes of second-line drugs, is no longer used, but may be referred to in older publications.
South African epidemic
XDR-TB was first widely publicised following the report of an outbreak in South Africa in 2006. 53 patients in a rural hospital in Tugela Ferry were found to have XDR-TB of whom 52 died. The median survival from sputum specimen collection to death was only 16 days and that the majority of patients had never previously received treatment for tuberculosis suggesting that they had been newly infected by XDR-TB strains, and that resistance did not develop during treatment. This was the first epidemic for which the acronym XDR-TB was used, and although TB strains that fulfill the current definition have been identified retrospectively, this was the largest group of linked cases ever found. Since the initial report in September 2006, cases have now been reported in most provinces in South Africa. As of 16 March 2007, there were 314 cases reported, with 215 deaths. It is clear that the spread of this strain of TB is closely associated with a high prevalence of HIV and poor infection control; in other countries where XDR-TB strains have arisen, drug resistance has arisen from mismanagement of cases or poor patient compliance with drug treatment instead of being transmitted from person to person. It is now clear that the problem has been around for much longer than health department officials have suggested, and is far more extensive.
See also
Multi-drug-resistant tuberculosis (MDR-TB)
Totally drug-resistant tuberculosis (TDR-TB)
Tuberculosis
Tuberculosis treatment
References
External links
World Health Organization Stop TB Department
Stop TB Partnership
The Global Plan to Stop TB
Advocacy to Control TB Internationally - ACTION
International Standards of TB Care
Video: Drug-Resistant TB in Russia July 24, 2007, Woodrow Wilson Center event featuring Salmaan Keshavjee and Murray Feshbach
XDRTB.org: Spread the Story. Stop the Disease. (photo documentary of XDR-TB by James Nachtwey)
TB Drug Resistance Mutation Database
British Red Cross helps combat TB
The Strange, Isolated Life of a Tuberculosis Patient in the 21st Century
Population Services International. |
Alkaptonuria | Alkaptonuria is a rare inherited genetic disease which is caused by a mutation in the HGD gene for the enzyme homogentisate 1,2-dioxygenase (EC 1.13.11.5); if a person inherits an abnormal copy from both parents (it is a recessive condition), the body accumulates an intermediate substance called homogentisic acid in the blood and tissues. Homogentisic acid and its oxidized form alkapton are excreted in the urine, giving it an unusually dark color. The accumulating homogentisic acid causes damage to cartilage (ochronosis, leading to osteoarthritis) and heart valves, as well as precipitating as kidney stones and stones in other organs. Symptoms usually develop in people over 30 years old, although the dark discoloration of the urine is present from birth.
Apart from treatment of the complications (such as pain relief and joint replacement for the cartilage damage), the drug nitisinone has been found to suppress homogentisic acid production, and research is ongoing as to whether it can improve symptoms. Alkaptonuria is a rare disease; it occurs in one in 250,000 people, but is more common in Slovakia and the Dominican Republic.
Signs and symptoms
Patients with alkaptonuria are asymptomatic as children or young adults, but their urine may turn brown or even inky black if collected and left exposed to open air. Pigmentation may be noted in the cartilage of the ear and other cartilage, and the sclera and corneal limbus of the eye.After the age of 30, people begin to develop pain in the weight-bearing joints of the spine, hips, and knees. The pain can be severe to the point that interferes with activities of daily living and may affect the ability to work. Joint-replacement surgery (hip and shoulder) is often necessary at a relatively young age. In the longer term, the involvement of the spinal joints leads to reduced movement of the rib cage and can affect breathing. Bone mineral density may be affected, increasing the risk of bone fractures, and rupture of tendons and muscles may occur.Valvular heart disease, mainly calcification and regurgitation of the aortic and mitral valves, may occur, and in severe and progressive cases, valve replacement may be necessary. Irregularities in the heart rhythm and heart failure affect a significant proportion of people with alkaptonuria (40% and 10%, respectively). Hearing loss affects 40% of people. Also, a propensity to developing kidney stones exists, and eventually also gallstones and stones in the prostate and salivary glands (sialolithiasis) can occur.
Pathophysiology
All people carry in their DNA two copies (one received from each parent) of the gene HGD, which contains the genetic information to produce the enzyme homogentisate 1,2-dioxygenase (HGD) which can normally be found in numerous tissues in the body (liver, kidney, small intestine, colon, and prostate). In people with alkaptonuria, both copies of the gene contain abnormalities that mean that the body cannot produce an adequately functioning enzyme. HGD mutations are generally found in certain parts (exons 6, 8, 10, and 13), but a total of over 100 abnormalities has been described throughout the gene. The normal HGD enzyme is a hexamer (it has six subunits) that are organized in two groups of three (two trimers) and contains an iron atom. Different mutations may affect the structure, function, or solubility of the enzyme. Very occasionally, the disease appears to be transmitted in an autosomal-dominant fashion, where a single abnormal copy of HGD from a single parent is associated with alkaptonuria; other mechanisms or defects in other genes possibly are responsible in those cases.
The HGD enzyme is involved in the metabolism (chemical processing) of the aromatic amino acids phenylalanine and tyrosine. Normally, these enter the bloodstream through protein-containing food and the natural turnover of protein in the body. Tyrosine is specifically required for a number of functions, such as hormones (e.g. thyroxine, the thyroid hormone), melanin (the dark pigment in the skin and hair), and certain proteins, but the vast majority (over 95%) is unused and is metabolized through a group of enzymes that eventually generate acetoacetate and malate. In alkaptonuria, the HGD enzyme cannot metabolize the homogentisic acid (generated from tyrosine) into 4-maleylacetoacetate, and homogentisic acid levels in the blood are 100-fold higher than would normally be expected, despite the fact that a substantial amount is eliminated into the urine by the kidneys.The homogentisic acid is converted to the related substance benzoquinone acetic acid which forms polymers that resemble the skin pigment melanin. These are deposited in the collagen, a connective tissue protein, of particular tissues such as cartilage. This process is called ochronosis (as the tissue looks ochre); ochronotic tissue is stiffened and unusually brittle, impairing its normal function and causing damage.
Diagnosis
If the diagnosis of alkaptonuria is suspected, it can be confirmed or excluded by collecting urine for 24 hours and determining the amount of homogentisic acid by means of chromatography. No assay of HGA in blood has been validated. The Genetic Testing Registry is used for maintaining information about the genetic test for alkaptonuria.The severity of the symptoms and response to treatment can be quantified through a validated questionnaire titled the AKU Severity Score Index. This assigns scores to the presence of particular symptoms and features, such as the presence of eye and skin pigmentation, joint pain, heart problems, and organ stones.
Treatment
No treatment modality has been unequivocally demonstrated to reduce the complications of alkaptonuria. Main treatment attempts have focused on preventing ochronosis through the reduction of accumulating homogentisic acid. Such commonly recommended treatments include large doses of ascorbic acid (vitamin C) or dietary restriction of amino acids phenylalanine and tyrosine. However, vitamin C treatment does not have definitively proven effectiveness and protein restriction (which can be difficult to adhere to) has not shown to be effective in clinical studies.Several studies have suggested that the herbicide nitisinone may be effective in the treatment of alkaptonuria. Nitisinone inhibits the enzyme 4-hydroxyphenylpyruvate dioxygenase, responsible for converting tyrosine to homogentisic acid, thereby blocking the production and accumulation of HGA. Nitisinone has been used for some time at much higher doses in the treatment of type I tyrosinemia. Nitisinone treatment has been shown to cause a larger than 95% reduction in plasma and urinary HGA. The main drawback is accumulation of tyrosine, the long-term risks of which are unknown; a particular concern exists about damage to the cornea of the eye. Long-term use requires frequent monitoring for complications.
Prognosis
Alkaptonuria does not appear to affect life expectancy, although the latest study on the topic is from 1985. The main impact is on quality of life; many people with alkaptonuria have disabling symptoms such as pain, poor sleep, and breathing symptoms. These generally start in the fourth decade. The typical age at requiring joint replacement surgery is 50–55 years.
Epidemiology
In most ethnic groups, the prevalence of alkaptonuria is between 1:100,000 and 1:250,000. In Slovakia and the Dominican Republic, the disease is much more common, with prevalence estimated at 1:19,000 people. As for Slovakia, this is not the result of a single mutation, but due to a group of 12 mutations in specific "hot spots" of the HGD gene. The Slovakian clustering probably arose in a small area in the northwest of the country and spread after the 1950s due to migration.
History
Alkaptonuria was one of the four diseases described by Archibald Edward Garrod, as being the result of the accumulation of intermediates due to metabolic deficiencies. He linked ochronosis with the accumulation of alkaptans in 1902, and his views on the subject, including its mode of heritance, were summarized in a 1908 Croonian Lecture at the Royal College of Physicians. The genetics of it was also studied by William Bateson in the 1902.The defect was narrowed down to homogentisic acid oxidase deficiency in a study published in 1958. The genetic basis was elucidated in 1996, when HGD mutations were demonstrated.A 1977 study showed that an ochronotic Egyptian mummy had probably suffered from alkaptonuria.
Research directions
Research collaborations by several national centres have been established to find a more definitive treatment for alkaptonuria. This has included studies on the use of nitisinone and investigations into antioxidants to inhibit ochronosis. The ideal treatment would replace HGD enzyme function without accumulating other substances.
See also
List of cutaneous conditions
List of radiographic findings associated with cutaneous conditions
References
== External links == |
Epispadias | An epispadias is a rare type of malformation in which the urethra ends, in males, in an opening on the upper aspect of the penis, and in females when the urethra develops too far anteriorly. It occurs in around 1 in 120,000 male and 1 in 500,000 female births.
Signs and symptoms
Most cases involve a small and bifid penis, which requires surgical closure soon after birth, often including a reconstruction of the urethra. Where it is part of a larger exstrophy, not only the urethra but also the bladder (bladder exstrophy) or the entire perineum (cloacal exstrophy) are open and exposed on birth, requiring closure. Many parts of this article are incorrect.
Relationship to other conditions
Despite the similarity of name, an epispadias is not a type of hypospadias, and involves a problem with a different set of embryologic processes.Women can also have this type of congenital malformation. Epispadias of the female may occur when the urethra develops too far anteriorly, exiting in the clitoris or even more forward. For females, this may not cause difficulty in urination but may cause problems with sexual satisfaction. Frequently, the clitoris is bifurcated at the site of urethral exit, and therefore clitoral sensation is less intense during sexual intercourse due to frequent stimulation during urination. However, with proper stimulation, using either manual or positional techniques, clitoral orgasm is definitely possible.
Causes
Epispadias is an uncommon and partial form of a spectrum of failures of abdominal and pelvic fusion in the first months of embryogenesis known as the exstrophy - epispadias complex. While epispadias is inherent in all cases of exstrophy it can also, much less frequently, appear in isolation as the least severe form of the complex spectrum. It occurs as a result of defective migration of the genital tubercle primordii to the cloacal membrane, and so malformation of the genital tubercle, at about the 5th week of gestation.
Treatment
The main treatment for isolated epispadias is a comprehensive surgical repair of the genito-urinary area usually during the first 7 years of life, including reconstruction of the urethra, closure of the penile shaft and mobilisation of the corpora. The most popular and successful technique is known as the modified Cantwell-Ransley approach. In recent decades however increasing success has been achieved with the complete penile disassembly technique despite its association with greater and more serious risk of damage.
Prognosis
Even with successful surgery, patients may have long-term problems with:
incontinence, where serious usually treated with some form of continent urinary diversion such as the Mitrofanoff
depression and psycho-social complications
sexual dysfunction
References
== External links == |
Immersion foot syndromes | Immersion foot syndromes are a class of foot injury caused by water absorption in the outer layer of skin. There are different subclass names for this condition based on the temperature of the water to which the foot is exposed. These include trench foot, tropical immersion foot, and warm water immersion foot.: 26–7 In one 3-day military study, it was found that submersion in water allowing for a higher skin temperature resulted in worse skin maceration and pain.
Causes
Trench foot
Trench foot is a medical condition caused by prolonged exposure of the feet to damp, unsanitary, and cold conditions. The use of the word trench in the name of this condition is a reference to trench warfare, mainly associated with World War I. Affected feet may become numb, affected by erythrosis (turning red) or cyanosis (turning blue) as a result of poor vascular supply, and feet may begin to have a decaying odour due to the possibility of the early stages of necrosis setting in. As the condition worsens, feet may also begin to swell. Advanced trench foot often involves blisters and open sores, which lead to fungal infections; this is sometimes called tropical ulcer (jungle rot).
If left untreated, trench foot usually results in gangrene, which can cause the need for amputation. If trench foot is treated properly, complete recovery is normal, though it is marked by severe short-term pain when feeling returns. As with other cold-related injuries, trench foot leaves those affected more susceptible to it in the future.
Tropical immersion foot
Tropical immersion foot (also known as "Paddy foot", and "Paddy-field foot") is a skin condition of the feet seen after continuous immersion of the feet in water or mud of temperature above 22 °C (72 °F) for two to ten days.: 27
Warm water immersion foot
Warm water immersion foot is a skin condition of the feet that results after exposure to warm, wet conditions for 48 hours or more and is characterized by maceration ("pruning"), blanching, and wrinkling of the soles, padding of toes (especially the big toe) and padding of the sides of the feet.
Foot maceration occur whenever exposed for prolonged periods to moist conditions. Large watery blisters appear which are painful when they open and begin to peel away from the foot itself. The heels, sides and bony prominences are left with large areas of extremely sensitive, red tissue, exposed and prone to infection. As the condition worsens, more blisters develop due to prolonged dampness which eventually covers the entire heel and/or other large, padded sections of the foot, especially the undersides as well as toes. Each layer in turn peels away resulting in deep, extremely tender, red ulcers.
Healing occurs only when the feet are cleansed, dried and exposed to air for weeks. Scarring is permanent with dry, thin skin that appears red for up to a year or more. The padding of the feet returns but healing can be painful as the nerves repair with characteristics of diabetic neuropathy. Antibiotics and/or antifungal are sometimes prescribed.
Foot immersion is a common problem with homeless individuals wearing one pair of socks and shoes for extensive periods of time, especially wet shoes and sneakers from rain and snow. The condition is exacerbated by excessive dampness of the feet for prolonged periods of time. Fungus and bacterial infections prosper in the warm, dark, wet conditions and are characterized by a sickly odor that is distinct to foot immersion.: 27
Prevention
In the British Army, policies were developed to help the soldiers keep their feet dry — the surest way of preventing the disease. Soldiers were told to dry their feet, and keep them dry by changing socks several times a day. After the first year of the First World War, British troops were instructed to keep at least three pairs of socks with them and to frequently change them. The use of whale oil was also successful in combating trench foot. A British battalion in front line positions could be expected to use ten gallons of whale oil every day.
References
== External links == |
Neonatal encephalopathy | Neonatal encephalopathy (NE), previously known as neonatal hypoxic-ischemic encephalopathy (neonatal HIE or NHIE), is defined as a encephalopathy syndrome with signs and symptoms of abnormal neurological function, in the first few days of life in an infant born after 35 weeks of gestation. In this condition there is difficulty initiating and maintaining respirations, a subnormal level of consciousness, and associated depression of tone, reflexes, and possibly seizures. Encephalopathy is a nonspecific response of the brain to injury which may occur via multiple methods, but is commonly caused by birth asphyxia, leading to cerebral hypoxia.
Signs and symptoms
In neonates born at or beyond 35 weeks, neonatal encephalopathy may present itself as the following symptoms:
Reduced level of consciousness
Seizures (which peak at 48 hours)
Difficulty initiating and maintaining respiration
Depression of tone and reflexes
Diagnosis
Cord blood gas analysis can be used to determine if there is perinatal hypoxia/asphyxia, which are potential causes of hypoxic-ischemic encephalopathy or cerebral palsy, and give insight into causes of intrapartum fetal distress. Cord blood gas analysis is indicated for high-risk pregnancies, in cases where C-sections occurred due to fetal compromise, if there were abnormal fetal heart rate patterns, Apgar scores of 3 or lower, intrapartum fever, or multifetal gestation.Evidence of brain injury related to the hypoxic-ischemic events that cause neonatal encephalopathy can be seen with brain MRIs, CTs, magnetic resonance spectroscopy imaging or ultrasounds. Neonatal encephalopathy may be assessed using Sarnat staging. Brain MRI is usually performed within eight days of life. Features that can be seen on MRI brain are: periventricular leukomalacia, basal ganglia and thalamus lesions, and multicystic encephalopathy. Besides that, diffusion MRI would show low apparent diffusion coefficient (ADC) values in the first seven days of life. This is followed by pseudonormalisation of ADC values (normalisation of ADC values despite having persistent underlying brain injuries) which can persists up to two weeks.
Treatment
In the past, treatment options were limited to supportive medical therapy. Currently, neonatal encephalopathy is treated using hypothermia therapy. This has been shown to reduce brain damage, reduce future disability, and improve survival. Hypothermia therapy is also sometimes termed hypothermic neural rescue therapy. Clinical trials are taking place to investigate the effectiveness of stem cell-based interventions, which are thought to have the potential to reduce mortality and improve the long-term development of newborn infants with neonatal encephalopathy.
Prognosis
HIE is a major predictor of neurodevelopmental disability in term infants. 25 percent have permanent neurological deficits.
Epidemiology
Overall, the relative incidence of neonatal encephalopathy is estimated to be between 2 and 9 per 1000 term births. 40% to 60% of affected infants die by 2 years old or have severe disabilities. In 2013 it was estimated to have resulted in 644,000 deaths down from 874,000 deaths in 1990.
References
== External links == |
Bladder outlet obstruction | Bladder outlet obstruction (or obstructive uropathy) occurs when urine is unable to flow from the kidneys through the ureters and out of the bladder through the urethra. Decreased flow of urine leads to swelling of the urinary tract, called hydronephrosis. This process of decreased flow of urine through the urinary tract can begin as early as during intrauterine life and it prevents normal development of fetal kidneys and fetal urine. Low levels of fetal urine leads to low amniotic fluid levels and incomplete lung maturation. Older children and adults can also experience bladder outlet obstruction; however, this process is usually reversible and isnt associated with as many poor outcomes as in infants with congenital bladder outlet obstruction.
Causes
Bladder outlet obstruction is classified based on where along the urinary tract the obstruction occurs, including upper urinary tract obstruction and lower urinary tract obstruction. Depending on the location of the obstruction, one or both sides of the urinary tract will be involved. In approximately 50% of cases of congenital hydronephrosis, there is no known cause. In many cases, obstruction along the urinary tract in utero leads to some form of CAKUT mentioned above.
Upper urinary tract obstruction
Upper urinary tract obstruction includes the renal pelvis and upper ureters.
Ureteropelvic junction obstruction
Ureteropelvic junction obstruction (UPJ obstruction) is an obstruction at the level of the ureter and renal pelvis. It is the most common cause of hydronephrosis detected in utero and is the most common anomaly detected on prenatal ultrasounds. It occurs in approximately 1 in every 1500 live births, is most commonly seen in males, involves the left ureter twice as often as the right ureter. UPJ obstruction is transient in most cases.
Lower urinary tract obstruction
Lower urinary tract obstruction involves the lower ureters, urinary bladder and the urethra.
Ureterovesicular junction obstruction
Ureterovesicular junction obstruction (UVJ obstruction) is an obstruction at the level of the ureter and bladder. It accounts for 20% of cases of hydronephrosis detected in utero. It is also most commonly seen in males and involved both sides of the urinary tract in approximately 25% of cases.
Posterior urethral valves
Posterior urethral valves (PUV) is an obstruction at the level of the urethra. It occurs in approximately 1 in every 5000 to 8000 live births and only occurs in males. Since PUV always affects both sides of the urinary tract, patients with posterior urethral valves are at the greatest risk for developing chronic kidney disease and end-stage renal disease due to obstructive uropathy.
Ureterocele
A ureterocele is a cystic dilation of the end of the ureter that can occur in the bladder and/or in the urethra. It occurs in approximately 1 in every 5000 live births, is most commonly seen in females and involves both ides of the urinary tract in approximately half of cases.
Urethral stenosis
Urethral stenosis is a narrowing of the urethra that prevents urine from exiting the bladder.
Diagnosis
Prenatal diagnosis
Bladder outlet obstruction can be identified during routine prenatal ultrasonography as dilation of the fetal urinary tract and decreased amniotic fluid levels. If dilation of the fetal urinary tract is suspected during pregnancy, an ultrasound of the infants kidneys and bladder should be obtained after birth.
Postnatal diagnosis
If patients aren’t diagnosed with dilation of their urinary tract via ultrasound in utero, they can present after birth with vague symptoms such as abdominal pain, blood in their urine or a urinary tract infection.
Associated syndromes
If patients have other congenital anomalies, their bladder outlet obstruction may be recognized during evaluation for their related syndromes. For example, VACTERL association is a constellation of congenital anomalies including vertebral, anal, cardiac, tracheoesophageal, renal and limb defects. Prune belly syndrome (or Eagle-Barrett syndrome) is another group of congenital disorders that involves the kidneys and includes absent abdominal wall musculature, severe urinary tract abnormalities and bilateral undescended testicles.
Dietl crisis
Patients with an undiagnosed ureteropelvic junction obstruction may experience abdominal or flank pain after increased fluid intake, when their bladder is full or when they exercise.
Terminology
Bladder neck obstruction is a condition where the bladder neck does not open enough during voiding.
Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
Bladder outlet obstruction is included in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). CAKUT is the most common cause of birth defects, occurring in 1 out of 1000 live births, and accounts for approximately half of all cases of chronic kidney disease and end-stage renal disease in children. CAKUT can be classified by the degree and type of malformation as follows:
Aplasia
Aplasia is a congenital absence of kidney tissue.
Simple hypoplasia
Kidneys that are small for age but still have normal renal architecture. This leads to a decrease in the number of nephrons, or functional units of the kidney.
Dysplasia
Malformation of kidney or bladder architecture. A dysplastic kidney is typically small for age and may contain cysts. A multicystic dysplastic kidney is an extreme example of renal dysplasia.
Isolated collecting duct dilation
Dilation of the renal pelvis, ureters, or both. Also called hydronephrosis.
Anomalies of position
Kidneys and ureters located in incorrect position, including horseshoe kidney and ectopic ureters.
See also
Overflow incontinence
References
== External links == |
Dicephalic parapagus twins | Dicephalic parapagus () is a rare form of partial twinning with two heads side by side on one torso. Infants conjoined this way are sometimes called "two-headed babies" in popular media. The condition is also called parapagus dicephalus.If carried to term, most dicephalic twins are stillborn, or die soon after birth. A small number are known to have survived to adulthood.The extent to which limbs and organs are duplicated varies from case to case. One head may be only partially developed (anencephalic), or both may be complete. In some cases, two complete hearts are present as well, which improves their chances of survival. The total number of arms may be two, three or four.Their prospects are best if no attempt is made to separate them, except in cases in which one twin is clearly dying.
Terminology
Dicephalus means two-headed. Parapagus means joined side by side.Dicephalic twins are called:
dibrachius if they have two arms altogether (one for each twin),
tribrachius, if they have three arms altogether,
tetrabrachius, if they have four arms altogether,
dipus, if they have two legs altogether (one for each twin).
Incidence
Conjoined twins appear in one in 50,000 to one in 100,000 births. Dicephalic twins represent about 11 percent of all conjoined twins.
Medical and social response
As late as the 1960s, some medical publications argued that newborn dicephalic twins should not be actively treated or resuscitated. An attempt at surgical separation was reported in a paper published in 1982, but did not result in long-term survival of either twin. In more recent cases in Turkey and Minnesota, doctors advised that separation surgery would not be appropriate.
Dicephalic twins who survived past infancy
Giacomo and Giovanni Battista Tocci (1877–1940), were Italian male dicephalus parapagus twins who survived to adulthood. Each had his own pair of arms. They had two legs all together, one of which was controlled by each twin. They were exhibited in freak shows as children and teenagers. The Toccis learned to speak several languages, but never learned to walk.Abby and Brittany Hensel, born in Minnesota in 1990, also are dicephalus parapagus twins. They were born with two functional arms, plus a vestigial third arm, which was surgically removed. Each twin has her own complete head, heart and spine, and controls one arm and one leg. They learned to walk around the same age as average children, went on to attend school, learn to drive, play sports, and completed courses at college.
Twin girls were born in Turkey in 2000. They were conjoined like the Tocci brothers, with four arms and two legs all together. As with the Toccis and the Hensels, it was found that each twin controlled one leg. Because of the size of their upper body, the Turkish twins needed a special program of exercises before they could learn to walk. After that, they learned to run and climb stairs without further specialist help, and at age 11 they were going to school with other children.
See also
Craniopagus parasiticus is another form of partial twinning which results in two heads kept alive by a single torso. In these cases a second, vestigial torso is present, and the heads are joined directly to one another.
Diprosopus is a condition in which there are duplicated facial features on one head.
Polycephaly is a general term about organisms with more than one head.
== References == |
Right bundle branch block | A right bundle branch block (RBBB) is a heart block in the right bundle branch of the electrical conduction system.During a right bundle branch block, the right ventricle is not directly activated by impulses travelling through the right bundle branch. The left ventricle, however, is still normally activated by the left bundle branch. These impulses are then able to travel through the myocardium of the left ventricle to the right ventricle and depolarize the right ventricle this way. As conduction through the myocardium is slower than conduction through the Bundle of His-Purkinje fibres, the QRS complex is seen to be widened. The QRS complex often shows an extra deflection that reflects the rapid depolarisation of the left ventricle followed by the slower depolarisation of the right ventricle.
Incomplete right bundle branch block
Incomplete right bundle branch block (IRBBB) is an conduction abnormality in the right bundle branch block. While a complete RBBB has a QRS duration of 120 ms or more, an incomplete block has a wave duration between 110 and 120 ms. It has a relatively high prevalence, a study conducted on young Swiss military conscripts with a mean age of 19 years found a prevalence of 13.5%. It affects patients of all ages, more commonly males and athletes, however is not always a benign finding. Therefore, if abnormalities are detected on the physical exam, further testing should be done to exclude heart disease.There is no consensus in the literature regarding criteria for diagnosis. However, according to the American Heart Association/American College of Cardiology Foundation/Heart Rhythm Foundation (AHA/ACCF/HRS) it is defined by the following finding in adults:
QRS wave duration between 110 and 120 ms.
rsr, rsR, or rSR in leads V1 or V2.
S wave of longer duration than R wave or greater than 40 ms in leads I and V6.
Normal R wave peak time in both V5 and V6, but greater than 50 ms in V1.The first three criteria are needed for diagnosis. The fourth is needed when a pure dominant R waver is present on V1.
Causes
Common causes include: normal variation, changes in bundle branch structure - such as mechanical stretching, chest trauma, right ventricular hypertrophy or strain, congenital heart disease such as atrial septal defect, and ischemic heart disease. In addition, a right bundle branch block may also result from Brugada syndrome, pulmonary embolism, rheumatic heart disease, myocarditis, cardiomyopathy, or hypertension.Causes for incomplete right bundle branch block are exercise-induced right ventricular remodeling, increased RV free wall thickness, especially in athletes due to prolonged endurance exercise.
Diagnosis
The criteria to diagnose a right bundle branch block on the electrocardiogram:
The heart rhythm must originate above the ventricles (i.e., sinoatrial node, atria or atrioventricular node) to activate the conduction system at the correct point.
The QRS duration must be more than 100 ms (incomplete block) or more than 120 ms (complete block).
There should be a terminal R wave in lead V1 (often called "R prime," and denoted by R, rR, rsR, rSR, or qR).
There must be a prolonged S wave in leads I and V6 (sometimes referred to as a "slurred" S wave).The T wave should be deflected opposite the terminal deflection of the QRS complex. This is known as appropriate T wave discordance with bundle branch block. A concordant T wave may suggest ischemia or myocardial infarction.
Treatment
The underlying condition may be treated by medications to control hypertension or diabetes, if they are the primary underlying cause. If coronary arteries are blocked, an invasive coronary angioplasty may relieve the impending RBBB.
Epidemiology
Prevalence of RBBB increases with age due to changes in the hearts conduction system. Its estimated up to 11.3% of the population by the age of 80 have RBBB.
Gallery
See also
Intraventricular block
Bundle branch block
Left bundle branch block
References
== External links == |
Alternating hemiplegia of childhood | Alternating hemiplegia of childhood is an ultra-rare neurological disorder named for the transient episodes, often referred to as "attacks", of hemiplegia (weakness or paralysis) from which those with the disorder suffer. It typically presents before the age of 18 months. These hemiplegic attacks can cause anything from mild weakness to complete paralysis on one or both sides of the body, and they can vary greatly in duration. Attacks may also alternate from one side of the body to the other, or alternate between affecting one or both sides during a single attack. Besides hemiplegia, symptoms of the disorder include an extremely broad range of neurological and developmental impairments which are not well understood. Normally, hemiplegia and other associated symptoms cease completely with sleep, but they may recur upon waking.Most frequently AHC is caused by a spontaneous mutation in the ATP1A3 gene. It is an extremely rare disorder – approximately 1 in 1,000,000 people have AHC. It was only recently discovered, having first been characterized in 1971.
Signs and symptoms
AHC patients exhibit a wide range of symptoms in addition to hemiplegic attacks. These can be further characterized as paroxysmal and non-paroxysmal symptoms. Paroxysmal symptoms are generally associated with hemiplegic attacks and may occur suddenly with hemiplegia or on their own. Paroxysmal symptoms may last for variable amounts of time. Non-paroxysmal symptoms tend to be side effects of AHC which are present at all times, not just during episodes or attacks. Epilepsy, which is also considered a paroxysmal symptom, plays an important role in the progression and diagnosis of AHC.
Hemiplegic attacks
Chronologically, hemiplegic attacks are not always the first symptom of AHC, but they are the most prominent symptom, as well as the symptom for which the disorder is named. Hemiplegic attacks may affect one or both sides of the body, and attacks which affect both sides of the body may be referred to as either bilateral or quadriplegic attacks. One of the unique characteristics of AHC is that hemiplegic attacks, as well as other symptoms which may co-occur with hemiplegia, cease immediately upon sleep. During strong attacks, the symptoms may reoccur upon waking. Hemiplegic attacks can occur suddenly or gradually, and the severity of an attack can vary over its duration. The attacks may alternate from one side of the body to another, though this is rare. The length of attacks may also vary from minutes to weeks, though length of attacks varies more greatly between people than between attacks for one person. Both bilateral and hemiplegic attacks are associated with pseudobulbar features such as dysphagia, dysarthria, and respiratory difficulty. Paralysis is also often accompanied by changes in skin color and temperature, sweating, restlessness, tremor, screaming, and the appearance of pain. Hemiplegic attacks happen irregularly and can occur with speech, eating, and swallowing impairment. Patients with AHC are frequently underweight due to these side effects. The average age of onset for hemiplegic episodes has been found to be 6–7 months of age. This early onset gives the name of this disorder the slightly misleading ending "of childhood". AHC is not exclusively limited to childhood – attacks in some cases become milder after the first ten years of life, but they never completely disappear.
Paroxysmal symptoms
AHC patients have exhibited various paroxysmal symptoms which manifest to different degrees in each person. Paroxysmal symptoms include tonic, tonic-clonic, or myoclonic limb movements, dystonic posturing, choreoathetosis, ocular nystagmus, and various other ocular motor abnormalities. Almost half of all people have dystonic symptoms prior to experiencing hemiplegia. These symptoms generally begin before 8 months of age. Ocular motor abnormalities occur early, and these are the most frequent early symptoms of AHC, particularly nystagmus. Almost 1/3 of people with this disorder had episodic ocular motor features within 1–2 days of birth. Many also experienced hemiplegia and dystonia before 3 months of age. A final symptom that may be considered paroxysmal is a temporary change in behavior - some patients will become unreasonable, demanding, and aggressive either before or after an attackNot all patients have all of these symptoms, and it is not known whether they are caused by AHC. Symptoms usually manifest in the first 3 months of the childs life, with an average onset of 2.5 months. Frequently, some of these symptoms will manifest in the neonatal period. These paroxysmal symptoms are often used to help diagnose AHC, since there is no simple test for it.In some cases, EEGs taken during these paroxysmal events were characterized by a generalized background slowing. Overall however, EEG during episodes and other investigative methods such as brain MRI, TACs, angiographic MRIs and CFS have normal results.
Non-paroxysmal symptoms
In the long term, many paroxysmal symptoms occur along with AHC, and while these symptoms vary in strength depending on the person, they are consistent features of AHC. It is thought that some of these symptoms are brought on or worsened by hemiplegic attacks, though it is not known for certain. Patients suffer persistent motor, movement (ataxia), and cognitive deficits. These deficits become more apparent over time and include developmental delays, social problems, and retardation. It is rare for someone with AHC not to have cognitive deficits, but a study in Japan did find two patients who met all of the diagnostic criteria for AHC but who were not mentally impaired. It is not known whether AHC is a progressive disease, but severe attacks are suspected to cause damage which result in permanent loss of function. 100% of children studied in the USA have had some form of mental impairment, which is usually described as mild to moderate, but varies greatly among individuals.
Epilepsy
At least 50% of AHC sufferers also suffer from epilepsy, and AHC is often misdiagnosed as epilepsy because of this. These epileptic events are distinguished from other episodes by an alteration of consciousness, as well as frequent tonic or tonic-clonic activity. Epileptic episodes are generally rare, though they do increase with age. Due to the rarity of epileptic episodes, there are few EEG confirmations of them.
Cause
Recent research suggests that AHC is caused by a de novo (spontaneous) genetic mutation in the ATP1A3 gene on chromosome 19 (locus 19q13.31) which encodes enzyme ATP1A3. A small number of cases seem to be caused by a mutation in the ATP1A2 gene. Where the mutation is inherited, it has the autosomal dominant pattern of inheritance.Previously AHC was thought to be a form of complicated migraine because of strong family histories of migraine reported in AHC cases. AHC has also been considered to be a movement disorder or a form of epilepsy. Suggested causes have included channelopathy, mitochondrial dysfunction, and cerebrovascular dysfunction. The disorder most closely related to AHC is familial hemiplegic migraine which is caused by a mutation in a gene for calcium channel receptors. It was thus thought that AHC may be caused by a similar channelopathy.
Diagnosis
As of 1993 only approximately 30 people with AHC had been described in scientific literature. Due to the rarity and complexity of AHC, it is not unusual for the initial diagnosis to be incorrect, or for diagnosis to be delayed for several months after the initial symptoms become apparent. The average age of diagnosis is just over 36 months. Diagnosis of AHC is not only difficult because of its rarity, but because there is no diagnostic test, making this a diagnosis of exclusion. There are several generally accepted criteria which define this disorder, however other conditions with a similar presentation, such as HSV encephalitis, must first be ruled out. Due to these diagnostic difficulties, it is possible that the commonness of the disease is underestimated.The following descriptions are commonly used in the diagnosis of AHC. The initial four criteria for classifying AHC were that it begins before 18 months of age, includes attacks of both hemiplegia on either side of the body, as well as other autonomic problems such as involuntary eye movement (episodic monocular nystagmus), improper eye alignment, choreoathetosis, and sustained muscle contractions (dystonia). Finally, patients suffer from intellectual disabilities, delayed development, and other neurological abnormalities. These diagnostic criteria were updated in 1993 to include the fact that all of these symptoms dissipate immediately upon sleeping. Diagnostic criteria were also expanded to include episodes of bilateral hemiplegia which shifted from one side of the body to the other.Recent criteria have been proposed for screening for AHC early, in order to improve the diagnostic timeline. These screening criteria include focal or unilateral paroxysmal dystonia in the first 6 months of life, as well as the possibility of flaccid hemiplegia either with or separate from these symptoms. Paroxysmal ocular movements should also be considered, and these should include both binocular and monocular symptoms which show in the first 3 months of life.
Treatments
Overall outcomes for AHC are generally poor, which is contributed to by AHCs various diagnostic and management challenges. In the long term, AHC is debilitating due to both the hemiplegic attacks and permanent damage associated with AHC. This damage can include cognitive impairment, behavioral and psychiatric disorders, and various motor impairments. There is, however, not yet any conclusive evidence that AHC is fatal or that it shortens life expectancy, but the relatively recent discovery of the disorder makes large data for this type of information unavailable. Treatment for AHC has not been extremely successful, and there is no cure. There are several drugs available for treatment, as well as management strategies for preventing and dealing with hemiplegic attacks.
Management strategies
Hemiplegic attacks can be brought on by particular triggers, and management of AHC often centers around avoiding common or known triggers. While triggers vary greatly from person to person, there are also some common ones which are prevalent in many patients. Common triggers include temperature changes, water exposure, bright lights, certain foods, emotional stress, and physical activity. While avoiding triggers may help, it cannot prevent all hemiplegic episodes because many occur without being triggered. Because attacks and other associated symptoms end with sleep, various sedatives can be used to help patients sleep.
Flunarizine
The most common drug used to treat AHC is flunarizine. Flunarizine functions by acting as a calcium channel blocker. Other drugs, in order of frequency of use are benzodiazepines, carbamazapine, barbiturates, and valproic acid. Flunarizine is prescribed for the purpose of reducing the severity of AHC attacks and the number of episodes, though it rarely stops attacks altogether. Minimizing the attacks may help reduce damage to the body from hemiplegic attacks and improve long-term outcomes as far as mental and physical disabilities are concerned.Experts differ in their confidence in flunarizines effectiveness. Some studies have found it to be very effective in reducing the duration, severity, and frequency of hemiplegic attacks. It is generally considered the best treatment available, but this drug is thought by some to be of little benefit to AHC patients. Many patients suffer adverse effects without seeing any improvement. Flunarizine also causes problems because it is difficult for patients to obtain, as it is not readily available in the United States.
Sodium oxybate
In 2009 through 2011 clinical research at the University of Utah investigated whether sodium oxybate, also known as Gamma-Hydroxybutyric acid is an effective treatment for AHC. Thus far, only a small number of patients have been sampled, and no conclusive results are yet available. While some success has been had thus far with the drug, AHC patients have been known to respond well initially to other drugs, but then the effectiveness will decline over time. Currently, sodium oxybate is used as a narcolepsy-cataplexy treatment, though in the past it has been used controversially in nutritional supplements. This drug was chosen to test because of a possible link between the causes of narcolepsy-cataplexy and AHC.
References
External links
Alternating Hemiplegia Information Page at NINDS
Homepage of the Alternating Hemiplegia of Childhood Foundation (AHCF). |
Aortic dissection | Aortic dissection (AD) occurs when an injury to the innermost layer of the aorta allows blood to flow between the layers of the aortic wall, forcing the layers apart. In most cases, this is associated with a sudden onset of severe chest or back pain, often described as "tearing" in character. Also, vomiting, sweating, and lightheadedness may occur. Other symptoms may result from decreased blood supply to other organs, such as stroke, lower extremity ischemia, or mesenteric ischemia. Aortic dissection can quickly lead to death from insufficient blood flow to the heart or complete rupture of the aorta.AD is more common in those with a history of high blood pressure; a number of connective tissue diseases that affect blood vessel wall strength including Marfan syndrome and Ehlers–Danlos syndrome; a bicuspid aortic valve; and previous heart surgery. Major trauma, smoking, cocaine use, pregnancy, a thoracic aortic aneurysm, inflammation of arteries, and abnormal lipid levels are also associated with an increased risk. The diagnosis is suspected based on symptoms with medical imaging, such as computed tomography, magnetic resonance imaging, or ultrasound used to confirm and further evaluate the dissection. The two main types are Stanford type A, which involves the first part of the aorta, and type B, which does not.Prevention is by blood pressure control and smoking cessation. Management of AD depends on the part of the aorta involved. Dissections that involve the first part of the aorta (adjacent to the heart) usually require surgery. Surgery may be done either by an opening in the chest or from inside the blood vessel. Dissections that involve the second part of the aorta can typically be treated with medications that lower blood pressure and heart rate, unless there are complications which then require surgical correction.AD is relatively rare, occurring at an estimated rate of three per 100,000 people per year. It is more common in men than women. The typical age at diagnosis is 63, with about 10% of cases occurring before the age of 40. Without treatment, about half of people with Stanford type A dissections die within three days and about 10% of people with Stanford type B dissections die within one month. The first case of AD was described in the examination of King George II of Great Britain following his death in 1760. Surgery for AD was introduced in the 1950s by Michael E. DeBakey.
Signs and symptoms
About 96% of individuals with AD present with severe pain that had a sudden onset. The pain may be described as a tearing, stabbing, or sharp sensation in the chest, back, or abdomen. About 17% of individuals feel the pain migrate as the dissection extends down the aorta. The location of pain is associated with the location of the dissection. Anterior chest pain is associated with dissections involving the ascending aorta, while interscapular back pain is associated with descending aortic dissections. If the pain is pleuritic in nature, it may suggest acute pericarditis caused by bleeding into the sac surrounding the heart. This is a particularly dangerous eventuality, suggesting that acute pericardial tamponade may be imminent. Pericardial tamponade is the most common cause of death from AD.While the pain may be confused with that of a heart attack, AD is usually not associated with the other suggestive signs, such as heart failure and ECG changes. Less common symptoms that may be seen in the setting of AD include congestive heart failure (7%), fainting (9%), stroke (6%), ischemic peripheral neuropathy, paraplegia, and cardiac arrest. If the individual fainted, about half the time it is due to bleeding into the pericardium, leading to pericardial tamponade. Neurological complications of aortic dissection, such as stroke and paralysis, are due to the involvement of one or more arteries supplying portions of the central nervous system.If the AD involves the abdominal aorta, compromise of one or both renal arteries occurs in 5–8% of cases, while ischemia of the intestines occurs about 3% of the time.
Blood pressure
People with AD often have a history of high blood pressure. The blood pressure is quite variable at presentation with acute AD. It tends to be higher in individuals with a distal dissection. In individuals with a proximal AD, 36% present with hypertension, while 25% present with hypotension. Proximal AD tends to be associated with weakening of the vascular wall due to cystic medial degeneration. In those who present with distal (Stanford type B) AD, 60–70% present with high blood pressure, while 2–3% present with low blood pressure.Severe hypotension at presentation is a grave prognostic indicator. It is usually associated with pericardial tamponade, severe aortic insufficiency, or rupture of the aorta. Accurate measurement of blood pressure is important. Pseudohypotension (falsely low blood-pressure measurement) may occur due to involvement of the brachiocephalic artery (supplying the right arm) or the left subclavian artery (supplying the left arm).
Aortic insufficiency
Aortic insufficiency (AI) occurs in half to two-thirds of ascending AD, and the diastolic heart murmur of aortic insufficiency is audible in about 32% of proximal dissections. The intensity (loudness) of the murmur depends on the blood pressure and may be inaudible in the event of low blood pressure.Multiple causes exist for AI in the setting of ascending AD. The dissection may dilate the annulus of the aortic valve, preventing the leaflets of the valve from coapting. The dissection may extend into the aortic root and detach the aortic valve leaflets. Alternatively, following an extensive intimal tear, the intimal flap may prolapse into the left ventricular outflow tract, causing intimal intussusception into the aortic valve, thereby preventing proper valve closure.
Myocardial infarction
Heart attack occurs in 1–2% of aortic dissections. Infarction is caused by the involvement of the coronary arteries, which supply the heart with oxygenated blood, in the dissection. The right coronary artery is involved more commonly than the left coronary artery. If the myocardial infarction is treated with thrombolytic therapy, the mortality increases to over 70%, mostly due to bleeding into the pericardial sac, causing cardiac tamponade.
Pleural effusion
A pleural effusion (fluid collection in the space between the lungs and the chest wall or diaphragm) can be due to either blood from a transient rupture of the aorta or fluid due to an inflammatory reaction around the aorta. If a pleural effusion were to develop due to AD, it is more common in the left hemithorax rather than the right hemithorax.
Causes
Aortic dissection is associated with hypertension (high blood pressure) and many connective tissue disorders. Vasculitis (inflammation of an artery) is rarely associated with aortic dissection. It can also be the result of chest trauma. About 72 to 80% of individuals who present with an aortic dissection have a previous history of hypertension. Illicit drug use with stimulants such as cocaine and methamphetamine is also a modifiable risk factor for AD. It can also be caused by smoking.
A bicuspid aortic valve (a type of congenital heart disease involving the aortic valve) is found in 7–14% of individuals who have an aortic dissection. These individuals are prone to dissection in the ascending aorta. The risk of dissection in individuals with bicuspid aortic valves is not associated with the degree of stenosis of the valve.Connective tissue disorders such as Marfan syndrome, Ehlers–Danlos syndrome, and Loeys–Dietz syndrome increase the risk of aortic dissection. Similarly, vasculitides such as Takayasus arteritis, giant cell arteritis, polyarteritis nodosa, and Behçets disease have been associated with a subsequent aortic dissection. Marfan Syndrome is found in 5–9% of individuals who had an aortic dissection. In this subset, the incidence in young individuals is increased. Individuals with Marfan syndrome tend to have aneurysms of the aorta and are more prone to proximal dissections of the aorta.Turner syndrome also increases the risk of aortic dissection, by aortic root dilatation.Chest trauma leading to aortic dissection can be divided into two groups based on cause: blunt chest trauma (commonly seen in car accidents) and iatrogenic. Iatrogenic causes include trauma during cardiac catheterization or due to an intra-aortic balloon pump.Aortic dissection may be a late sequela of heart surgery. About 18% of individuals who present with an acute aortic dissection have a history of open-heart surgery. Individuals who have undergone aortic valve replacement for aortic insufficiency are at particularly high risk because aortic regurgitation causes increased blood flow in the ascending aorta. This can cause dilatation and weakening of the walls of the ascending aorta.Syphilis only potentially causes aortic dissection in its tertiary stage.
Pathophysiology
As with all other arteries, the aorta is made up of three layers, the intima, the media, and the adventitia. The intima is in direct contact with the blood inside the vessel, and mainly consists of a layer of endothelial cells on a basement membrane; the media contains connective and muscle tissue, and the vessel is protected on the outside by the adventitia, comprising connective tissue.In an aortic dissection, blood penetrates the intima and enters the media layer. The high pressure rips the tissue of the media apart along the laminated plane splitting the inner two-thirds and the outer one-third of the media apart. This can propagate along the length of the aorta for a variable distance forward or backward. Dissections that propagate towards the iliac bifurcation (with the flow of blood) are called anterograde dissections and those that propagate towards the aortic root (opposite of the flow of blood) are called retrograde dissections. The initial tear is usually within 100 mm of the aortic valve, so a retrograde dissection can easily compromise the pericardium leading to a hemopericardium. Anterograde dissections may propagate all the way to the iliac bifurcation of the aorta, rupture the aortic wall, or recanalize into the intravascular lumen leading to a double-barrel aorta. The double-barrel aorta relieves the pressure of blood flow and reduces the risk of rupture. Rupture leads to hemorrhaging into a body cavity, and prognosis depends on the area of rupture. Retroperitoneal and pericardial ruptures are both possible.
The initiating event in aortic dissection is a tear in the intimal lining of the aorta. Due to the high pressures in the aorta, blood enters the media at the point of the tear. The force of the blood entering the media causes the tear to extend. It may extend proximally (closer to the heart) or distally (away from the heart) or both. The blood travels through the media, creating a false lumen (the true lumen is the normal conduit of blood in the aorta). Separating the false lumen from the true lumen is a layer of intimal tissue known as the intimal flap.The vast majority of aortic dissections originate with an intimal tear in either the ascending aorta (65%), the aortic arch (10%), or just distal to the ligamentum arteriosum in the descending thoracic aorta (20%).As blood flows down the false lumen, it may cause secondary tears in the intima. Through these secondary tears, the blood can re-enter the true lumen.While it is not always clear why an intimal tear may occur, quite often it involves degeneration of the collagen and elastin that make up the media. This is known as cystic medial necrosis and is most commonly associated with Marfan syndrome and is also associated with Ehlers-Danlos syndrome.In about 13% of aortic dissections, no evidence of an intimal tear is found. In these cases, the inciting event is thought to be an intramural hematoma (caused by bleeding within the media). Since no direct connection exists between the true lumen and the false lumen in these cases, diagnosing an aortic dissection by aortography is difficult if the cause is an intramural hematoma. An aortic dissection secondary to an intramural hematoma should be treated the same as one caused by an intimal tear.
Diagnosis
Because of the varying symptoms of aortic dissection, the diagnosis is sometimes difficult to make. Concern should be increased in those with low blood pressure, neurological problems, and an unequal pulses.While taking a good history from the individual may be strongly suggestive of an aortic dissection, the diagnosis cannot always be made by history and physical signs alone. Often, the diagnosis is made by visualization of the intimal flap on a diagnostic imaging test. Common tests used to diagnose an aortic dissection include a CT scan of the chest with iodinated contrast material and a transesophageal echocardiogram. The proximity of the aorta to the esophagus allows the use of higher-frequency ultrasound for better anatomical images. Other tests that may be used include an aortogram or magnetic resonance angiogram of the aorta. Each of these tests has pros and cons, and they do not have equal sensitivities and specificities in the diagnosis of aortic dissection.In general, the imaging technique chosen is based on the pretest likelihood of the diagnosis, availability of the testing modality, patient stability, and the sensitivity and specificity of the test.
D-dimer
A measurement of blood D-dimer level may be useful in diagnostic evaluation. A level less than 500 ng/ml may be considered evidence against a diagnosis of aortic dissection, although this guideline is only applicable in cases deemed "low risk" and within 24 hours of symptom onset. The American Heart Association does not advise using this test in making the diagnosis, as evidence is still tentative.
Chest X-ray
Chest radiography may although demonstrate a change in the morphology of the thoracic aorta which can be seen in aortic dissection. Classically, new widening of the mediastinum on radiograph is of moderate sensitivity for detecting an ascending aortic dissection; however, this finding is of low specificity, as many other conditions can cause apparent widening of the mediastinum.There are several other associated radiographic findings:
The "calcium sign" describes an apparent separation of the intimal calcification from the outer aortic margin by greater than 10 mm.
Pleural effusions, more commonly in descending aortic dissections, and typically left-sided.
Other: the obliteration of the aortic knob, depression of the left mainstem bronchus, loss of the paratracheal stripe, and tracheal deviation.Importantly, about 12 to 20% of aortic dissections are not detectable by chest radiograph; therefore, a "normal" chest radiograph does not rule out aortic dissection. If there is high clinical suspicion, a more sensitive imaging test (CT angiogram, MR angiography, or transesophageal echo) may be warranted.
Computed tomography
Computed tomography angiography is a fast, non-invasive test that gives an accurate three-dimensional view of the aorta. These images are produced by taking rapid, thin-cut slices of the chest and abdomen, and combining them in the computer to create cross-sectional slices. To delineate the aorta to the accuracy necessary to make the proper diagnosis, an iodinated contrast material is injected into a peripheral vein. Contrast is injected and the scan performed using a bolus tracking method. This type of scan is timed to injection to capture the contrast as it enters the aorta. The scan then follows the contrast as it flows through the vessel. It has a sensitivity of 96 to 100% and a specificity of 96 to 100%. Disadvantages include the need for iodinated contrast material and the inability to diagnose the site of the intimal tear.
MRI
Magnetic resonance imaging (MRI) is also used for the detection and assessment of aortic dissection, with a sensitivity of 98% and a specificity of 98%. An MRI examination of the aorta produces a three-dimensional reconstruction of the aorta, allowing the physician to determine the location of the intimal tear and the involvement of branch vessels, and to locate any secondary tears. It is a noninvasive test, does not require the use of iodinated contrast material, and can detect and quantitate the degree of aortic insufficiency.The disadvantage of the MRI scan in the face of aortic dissection is that it may be available only in larger hospitals, and the scan is relatively time-consuming, which could be dangerous in people who are already very unwell. Due to the high-intensity magnetic fields used during MRI, it cannot be used on individuals with metallic implants. In addition, some individuals experience claustrophobia while surrounded by the MRI magnet.
Ultrasound
The transesophageal echocardiogram (TEE) is a good test in the diagnosis of aortic dissection, with a sensitivity up to 98% and a specificity up to 97%. It has become the preferred imaging modality for suspected aortic dissection. It is a relatively noninvasive test, requiring the individual to swallow the echocardiography probe. It is especially good in the evaluation of AI in the setting of ascending aortic dissection and to determine whether the ostia (origins) of the coronary arteries are involved. While many institutions give sedation during transesophageal echocardiography for added patient comfort, it can be performed in cooperative individuals without the use of sedation. Disadvantages of TEE include the inability to visualize the distal ascending aorta (the beginning of the aortic arch), and the descending abdominal aorta that lies below the stomach. A TEE may be technically difficult to perform in individuals with esophageal strictures or varices.
Aortogram
An aortogram involves the placement of a catheter in the aorta and injection of contrast material while taking X-rays of the aorta. The procedure is known as aortography. Previously thought to be the diagnostic gold standard, it has been supplanted by other, less-invasive imaging modalities.
Classification
Several different classification systems have been used to describe aortic dissections. One such classification is based on chronicity and labels aortic dissections as hyperacute (<24 hours duration), acute (2–7 days), subacute (8–30 days), and chronic (>30 days). The systems commonly in use are based on either the anatomy of the dissection or the duration of onset of symptoms before the presentation. The Stanford system is used more commonly now, as it is more attuned to the management of the patient.
DeBakey
The DeBakey system, named after cardiothoracic surgeon Michael E. DeBakey, is an anatomical description of the aortic dissection. It categorizes the dissection based on where the original intimal tear is located and the extent of the dissection (localized to either the ascending aorta or descending aorta or involving both the ascending and descending aorta).
Type I – originates in ascending aorta, and propagates at least to the aortic arch and often beyond it distally. It is most often seen in patients less than 65 years of age and is the most lethal form of the disease.
Type II – originates in the ascending aorta and is confined to it.
Type III – originates in the descending aorta and rarely extends proximally, but will extend distally. It most often occurs in elderly patients with atherosclerosis and hypertension.
Stanford
The Stanford classification is divided into two groups, A and B, depending on whether the ascending aorta is involved.
A – involves the ascending aorta and/or aortic arch, and possibly the descending aorta. The tear can originate in the ascending aorta, the aortic arch, or more rarely, in the descending aorta. It includes DeBakey types I and II.
B – involves the descending aorta or the arch (distal to the left subclavian artery), without the involvement of the ascending aorta. It includes DeBakey type III.The Stanford classification is useful as it follows clinical practice, as type A ascending aortic dissections generally require primary surgical treatment, whereas type B dissections generally are treated medically as initial treatment with surgery reserved for any complications.The main indication for surgical repair of type A dissections is the prevention of acute hemorrhagic pericardial tamponade due to leakage of blood through the dissected layers of the intrapericardial proximal aorta. A secondary indication is acute aortic valve insufficiency (regurgitation): ascending aortic dissections often involve the aortic valve, which, having lost its suspensory support, telescopes down into the aortic root, resulting in aortic incompetence. The valve must be resuspended to be reseated, as well as to repair or prevent coronary artery injury. Also, the area of dissection is removed and replaced with a Dacron graft to prevent further dissection from occurring. However, type B dissections are not improved, from a mortality point of view, by the operation, unless leaking, rupture, or compromise to other organs, e.g. kidneys, occurs.
Prevention
Among the recognized risk factors for aortic dissection, hypertension, abnormally high levels of lipids (such as cholesterol) in the blood, and smoking tobacco are considered preventable risk factors.Repair of an enlargement of the ascending aorta from an aneurysm or previously unrecognized and untreated aortic dissections is recommended when greater than 5.5 cm (2.2 in) in size to decrease the risk of dissection. Repair may be recommended when greater than 4.5 cm (1.8 in) in size if the person has one of the several connective-tissue disorders or a family history of a ruptured aorta.
Management
In an acute dissection, treatment choice depends on its location. For Stanford type A (ascending aortic) dissection, surgical management is superior to medical management. For uncomplicated Stanford type B (distal aortic) dissections (including abdominal aortic dissections), medical management is preferred over surgery. Complicated Stanford type B aortic dissections require surgical intervention after initiation of medical therapy.The risk of death due to aortic dissection is highest in the first few hours after the dissection begins, and decreases afterward. Because of this, the therapeutic strategies differ for the treatment of an acute dissection compared to a chronic dissection. An acute dissection is one in which the individual presents within the first two weeks. If the individual has managed to survive this window period, their prognosis is improved. About 66% of all dissections present in the acute phase. Individuals who present two weeks after the onset of the dissection are said to have chronic aortic dissections. These individuals have been self-selected as survivors of the acute episode and can be treated with medical therapy as long as they are stable.
Medication
Aortic dissection generally presents as a hypertensive emergency, and the prime consideration of medical management is to decrease the shear stress in the aortic wall (dP/dt (force of ejection of blood from the left ventricle)) by decreasing blood pressure and the heart rate. The target blood pressure should be a mean arterial pressure (MAP) of 60 to 75 mmHg, or the lowest blood pressure tolerated. Initial decreases should be by about 20%. The target heart rate is less than 65 beats per minute. Long-term blood pressure control is required for every person who has experienced aortic dissection.Beta blockers are the first-line treatment for patients with acute and chronic aortic dissection. In acute dissection, fast-acting agents can be given intravenously and have doses that are easier to adjust (such as esmolol, propranolol, or labetalol) is preferred. Vasodilators such as sodium nitroprusside can be considered for people with ongoing high blood pressure, but they should never be used alone, as they often stimulate a reflexive increase in the heart rate.Calcium channel blockers can be used in the treatment of aortic dissection, particularly if a contraindication to the use of beta-blockers exists. The calcium channel blockers typically used are verapamil and diltiazem, because of their combined vasodilator and negative inotropic effects.If the individual has refractory hypertension (persistent hypertension on the maximum doses of three different classes of antihypertensive agents), involvement of the renal arteries in the aortic dissection plane should be considered.
Surgical
Indications for the surgical treatment of aortic dissection include an acute proximal aortic dissection and an acute distal aortic dissection with one or more complications. Complications include compromise of a vital organ, rupture or impending rupture of the aorta, retrograde dissection into the ascending aorta. These are more common with a history of Marfan syndrome or Ehlers-Danlos syndrome.The objective in the surgical management of aortic dissection is to resect (remove) the most severely damaged segments of the aorta and to obliterate the entry of blood into the false lumen (both at the initial intimal tear and any secondary tears along the vessel). While excision of the intimal tear may be performed, it does not significantly change mortality.The particular treatment used depends on the segment or segments of the aorta involved. Some treatments are:
Open aortic surgery with replacement of the damaged section of the aorta with a tube graft (often made of Dacron) when no damage to the aortic valve is seen
Bentall procedure – replacement of the damaged section of the aorta and replacement of the aortic valve
David procedure – replacement of the damaged section of the aorta and reimplantation of the aortic valve
Thoracic endovascular aortic repair, a minimally invasive surgical procedure usually combined with ongoing medical management
Replacement of the damaged section of the aorta with a sutureless vascular ring connector-reinforced Dacron graft: The vascular ring connector is a titanic ring used as a stent in the vascular graft to achieve a quick, blood-sealed, and sutureless anastomosis. Two furrows on the surface of the ring are for fixation of the vascular graft and the aorta. The tapes used to tie against the ring provide a larger contact surface area than the traditional stitches, thus it provides stronger anastomosis and better surgical results.A number of comorbid conditions increase the surgical risk of repair of an aortic dissection. These conditions include the following:
Prolonged preoperative evaluation (increased length of time prior to surgery)
Advanced age
Comorbid disease states (e.g.: coronary artery disease)
Aneurysm leakage
Cardiac tamponade
Shock - obstructive shock
Past history of myocardial infarction
History of kidney failure (either acute or chronic kidney failure)
Follow-up
The long-term follow-up in individuals who survive aortic dissection involves strict blood pressure control. The relative risk of late rupture of an aortic aneurysm is 10 times higher in individuals who have uncontrolled hypertension, compared to individuals with a systolic pressure below 130 mmHg.The risk of death is highest in the first two years after the acute event, and individuals should be followed closely during this time period. About 29% of late deaths following surgery are due to rupture of either a dissecting aneurysm or another aneurysm. In addition, a 17% to 25% incidence exists of new aneurysm formation, typically due to dilatation of the residual false lumen. These new aneurysms are more likely to rupture, due to their thinner walls.Serial imaging of the aorta is suggested, with MRI being the preferred imaging technique.
Prognosis
Of all people with aortic dissection, 40% die immediately and do not reach a |
Aortic dissection | hospital in time. Of the remainder, 1% die every hour, making prompt diagnosis and treatment a priority. Even after diagnosis, 5–20% die during surgery or in the immediate postoperative period. In ascending aortic dissection, if surgery is decided to be not appropriate, 75% die within 2 weeks. With aggressive treatment, 30-day survival for thoracic dissections may be as high as 90%.
Epidemiology
Establishing the incidence of aortic dissection has been difficult because many cases are only diagnosed after death (which may have been attributed to another cause), and is often initially misdiagnosed. Aortic dissection affects an estimated 2.0–3.5 people per every 100,000 every year. Studies from Sweden suggest that the incidence of aortic dissection may be rising. Men are more commonly affected than women: 65% of all people with aortic dissection are male. The mean age at diagnosis is 63 years. In females before the age of 40, half of all aortic dissections occur during pregnancy (typically in the third trimester or early postpartum period). Dissection occurs in about 0.6% of pregnancies.
History
The earliest fully documented case of aortic dissection is attributed to Frank Nicholls in his autopsy report of King George II of Great Britain, who had been found dead on 25 October 1760; the report describes a dissection of the aortic arch and into the pericardium. The term "aortic dissection" was introduced by the French physician J. P. Maunoir in 1802, and René Laennec labeled the condition "dissecting aneurysm". London cardiologist Thomas Bevill Peacock contributed to the understanding of the condition by publishing two series of the cases described in the literature so far: 19 cases in an 1843 review, and 80 in 1863. The characteristic symptom of tearing pain in the chest was recognized in 1855 when a case was diagnosed in life.Surgery for aortic dissection was first introduced and developed by Michael E. DeBakey, Denton Cooley, and Oscar Creech, cardiac surgeons associated with the Baylor College of Medicine, Houston, Texas, in 1954. DeBakey developed aortic dissection himself at age 97 in 2005, and underwent surgery in 2006. Endovascular treatment of aortic dissection was developed in the 1990s.
Society and culture
Ritter Rules are a compilation of reminders, symptoms, and risk factors designed to prevent the misdiagnosis of thoracic aortic dissection. The rules were named after Threes Company star John Ritter, who died from a thoracic aortic dissection in 2003 after he was misdiagnosed and accidentally treated for a heart attack by his two doctors. The rules were developed by Dianna Milewicz of the University of Texas Health Science Center at Houston seven years after Ritters premature death, and were jointly published by the non-profit organization in Ritters honor and the Thoracic Aortic Disease Coalition.Lucille Ball was diagnosed with dissecting aortic aneurysm and underwent surgery to repair her aorta and a successful seven-hour aortic valve replacement, but died days later. A greater incidence of aortic aneurysm is seen in cigarette smokers; Ball had been a heavy smoker most of her life.Playwright Jonathan Larson, best known for the musical Rent, died in 1996 of an aortic dissection believed to be due to undiagnosed Marfan Syndrome.
Days of Our Lives and Babylon 5 actor Richard Biggs died on May 22, 2004 at the age of 44 due to complications from aortic dissection.Lux Interior of The Cramps died at the Glendale Memorial Hospital on February 4, 2009, at the age of 62, following an aortic dissection which, contrary to initial reports about a pre-existing condition, was "sudden, shocking and unexpected".Alan Thicke died in 2016 of type-A aortic dissection at the Providence Saint Joseph Medical Center in Burbank, at the age of 69.Japanese actress Hiromi Tsuru died in her car from aortic dissection in 2017 at the age of 57.Taiwanese entertainer Alien Huang died in 2020 at the age of 36.Kentaro Miura, writer and artist of the manga Berserk, died from aortic dissection in 2021 at the age of 54.In August 2021, New Zealand cricketer Chris Cairns was put on full life support following an aortic dissection in his home in Canberra, Australia. He was transferred to Sydney, and became paralysed from the waist down due to sustaining a stroke during surgery.
41-year-old guitarist Richie Faulkner of the heavy metal band Judas Priest had an aortic aneurysm on September 27, 2021, in the middle of the final song of their 50-minute set at a music festival. He underwent 10+1⁄2 hours of open heart surgery to repair the aortic dissection.In May 2022, keyboardist Andy Fletcher, a founding member of the UK band Depeche Mode, died unexpectedly at home from an aortic dissection, at the age of 60.
See also
Carotid artery dissection
Vertebral artery dissection
References
== External links == |
Hypomagnesemia with secondary hypocalcemia | Hypomagnesemia with secondary hypocalcemia (HSH) is an autosomal recessive genetic disorder affecting intestinal magnesium absorption. Decreased intestinal magnesium reabsorption and the resulting decrease in serum magnesium levels is believed to cause lowered parathyroid hormone (PTH) output by the parathyroid gland. This results in decreased PTH and decreased serum calcium levels (hypocalcemia). This manifests in convulsions and spasms in early infancy which, if left untreated, can lead to mental retardation or death. HSH is caused by mutations in the TRPM6 gene.
Pathophysiology
HSH is caused by decreased intestinal magnesium reabsorption through TRPM6 channels. When expressed in cells, TRPM6 produces outwardly rectifying currents with the outward portion composed of Na+ ions and the inward portion of divalent cations (particularly magnesium and calcium). Inward flow of sodium ions is blocked by extracellular divalent cations. Increased intracellular magnesium concentrations also decrease current through TRPM6 channels. There are currently more than 30 known mutations in TRPM6 that are associated with HSH and these mutations are spreading throughout the gene (table 1). Of the eight HSH mutations that have been tested, none have shown to produce whole-cell current. The S141L mutation, one of the few missense mutations, has been of particular interest to researchers. They have found that it prevents coassembly with TRPM7 (and presumably other TRPM6 subunits) and lacks the ability to traffic to the membrane. Whether other mutants are able to traffic properly to the surface or coassemble has not yet been further studied.While the hypomagnesemia in patients with HSH is a direct result of TRPM6 mutations, hypocalcemia is an indirect, secondary result. Parathyroid gland secretion of PTH can be altered by changes in serum magnesium levels. The decreased serum magnesium levels seen in HSH result in decreased PTH secretion. PTH, in turn, controls the availability of serum calcium. Decreasing PTH levels cause a decrease in calcium availability in serum and, thus, the neurological symptoms of HSH.
Diagnosis
Diagnosis typically occurs during the first 6 months of life due to characteristic neurological symptoms. These symptoms include muscle spasms, tetany, and seizures. Laboratory testing indicates hypomagnesemia (decreased serum magnesium levels), hypocalcemia (decreased serum calcium levels), and little to no measurable parathyroid hormone levels. Diagnosis is confirmed with these symptoms and can be further solidified with genetic sequencing of the TRPM6 gene.
Treatment
Treatment of HSH involves administration of high doses of magnesium salts. These salts may be taken orally or otherwise (e.g. subcutaneously). This treatment works by increasing magnesium absorption through the non-TRPM6 mediated paracellular uptake pathways. This treatment must be continued throughout life.
History
HSH was originally believed to be an X-linked disorder due to the preponderance of affected males. With the finding that mutations in TRPM6 (on chromosome 9) are causative for the disorder this is no longer the case. Of recent interest, however, is the characterization of a patient with symptoms similar to HSH who has a translocation of the chromosomes 9 and X.
See also
Bartters syndrome
Gitelman syndrome
Hypomagnesemia
Hypocalcemia
References
Konrad M, Schlingmann K, Gudermann T (2004). "Insights into the molecular nature of magnesium homeostasis". Am J Physiol Renal Physiol. 286 (4): F599–605. doi:10.1152/ajprenal.00312.2003. PMID 15001450.
Footnotes
== External links == |
Neurosis | Neurosis is a class of functional mental disorders involving chronic distress, but neither delusions nor hallucinations. The term is no longer used by the professional psychiatric community in the United States, having been eliminated from the Diagnostic and Statistical Manual of Mental Disorders (DSM) in 1980 with the publication of DSM III. However, it is still used in the ICD-10 Chapter V F40–48.
Neurosis should not be mistaken for psychosis, which refers to a loss of touch with reality. Nor should it be mistaken for neuroticism, a fundamental personality trait proposed in the Big Five personality traits theory.
Etymology
The term is derived from the Greek word neuron (νεῦρον, nerve) and the suffix -osis (-ωσις, diseased or abnormal condition).
The term neurosis was coined by Scottish doctor William Cullen in 1769 to refer to "disorders of sense and motion" caused by a "general affection of the nervous system." Cullen used the term to describe various nervous disorders and symptoms that could not be explained physiologically. Physical features, however, were almost inevitably present, and physical diagnostic tests, such as exaggerated knee-jerks, loss of the gag reflex and dermatographia, were used into the 20th century. The meaning of the term was redefined by Carl Jung and Sigmund Freud over the early and middle 20th century, and has continued to be used in psychology and philosophy.The Diagnostic and Statistical Manual of Mental Disorders (DSM) eliminated the neurosis category in 1980, because of a decision by its editors to provide descriptions of behavior rather than descriptions of hidden psychological mechanisms. This change has been controversial. Likewise, according to the American Heritage Medical Dictionary, neurosis is "no longer used in psychiatric diagnosis."
Symptoms and causes
Neurosis may be defined simply as a "poor ability to adapt to ones environment, an inability to change ones life patterns, and the inability to develop a richer, more complex, more satisfying personality." There are many different neuroses, including:
obsessive–compulsive disorder
obsessive–compulsive personality disorder
impulse control disorder
anxiety disorder
histrionic personality disorder
dissociative disorder
a great variety of phobiasAccording to C. George Boeree, professor emeritus at Shippensburg University, the symptoms of neurosis may involve:
... anxiety, sadness or depression, anger, irritability, mental confusion, low sense of self-worth, etc., behavioral symptoms such as phobic avoidance, vigilance, impulsive and compulsive acts, lethargy, etc., cognitive problems such as unpleasant or disturbing thoughts, repetition of thoughts and obsession, habitual fantasizing, negativity and cynicism, etc. Interpersonally, neurosis involves dependency, aggressiveness, perfectionism, schizoid isolation, socio-culturally inappropriate behaviors, etc.
Jungian theory
Carl Jung found his approach particularly effective for patients who are well adjusted by social standards but are troubled by existential questions. Jung claims to have "frequently seen people become neurotic when they content themselves with inadequate or wrong answers to the questions of life".: 140 Accordingly, the majority of his patients "consisted not of believers but of those who had lost their faith".: 140 A contemporary person, according to Jung, …is blind to the fact that, with all his rationality and efficiency, he is possessed by powers that are beyond his control. His gods and demons have not disappeared at all; they have merely got new names. They keep him on the run with restlessness, vague apprehensions, psychological complications, an insatiable need for pills, alcohol, tobacco, food — and, above all, a large array of neuroses.: 82 Jung found that the unconscious finds expression primarily through an individuals inferior psychological function, whether it is thinking, feeling, sensation, or intuition. The characteristic effects of a neurosis on the dominant and inferior functions are discussed in his Psychological Types. Jung also found collective neuroses in politics: "Our world is, so to speak, dissociated like a neurotic.": 85
Psychoanalytic theory
According to psychoanalytic theory, neuroses may be rooted in ego defense mechanisms, though the two concepts are not synonymous. Defense mechanisms are a normal way of developing and maintaining a consistent sense of self (i.e., an ego). However, only those thoughts and behaviors that produce difficulties in ones life should be called neuroses.
A neurotic person experiences emotional distress and unconscious conflict, which are manifested in various physical or mental illnesses; the definitive symptom being anxiety. Neurotic tendencies are common and may manifest themselves as acute or chronic anxiety, depression, an obsessive–compulsive disorder, a phobia, or a personality disorder.
Horneys theory
In her final book, Neurosis and Human Growth, Karen Horney lays out a complete theory of the origin and dynamics of neurosis. In her theory, neurosis is a distorted way of looking at the world and at oneself, which is determined by compulsive needs rather than by a genuine interest in the world as it is. Horney proposes that neurosis is transmitted to a child from their early environment and that there are many ways in which this can occur:: 18
When summarized, they all boil down to the fact that the people in the environment are too wrapped up in their own neuroses to be able to love the child, or even to conceive of him as the particular individual he is; their attitudes toward him are determined by their own neurotic needs and responses.
The childs initial reality is then distorted by their parents needs and pretenses. Growing up with neurotic caretakers, the child quickly becomes insecure and develops basic anxiety. To deal with this anxiety, the childs imagination creates an idealized self-image:: 22
Each person builds up his personal idealized image from the materials of his own special experiences, his earlier fantasies, his particular needs, and also his given faculties. If it were not for the personal character of the image, he would not attain a feeling of identity and unity. He idealizes, to begin with, his particular "solution" of his basic conflict: compliance becomes goodness, love, saintliness; aggressiveness becomes strength, leadership, heroism, omnipotence; aloofness becomes wisdom, self-sufficiency, independence. What—according to his particular solution—appear as shortcomings or flaws are always dimmed out or retouched.
Once they identify themselves with their idealized image, a number of effects follow. They will make claims on others and on life based on the prestige they feel entitled to because of their idealized self-image. They will impose a rigorous set of standards upon themselves in order to try to measure up to that image. They will cultivate pride, and with that will come the vulnerabilities associated with pride that lacks any foundation. Finally, they will despise themselves for all their limitations. Vicious circles will operate to strengthen all of these effects.
Eventually, as they grow to adulthood, a particular "solution" to all the inner conflicts and vulnerabilities will solidify. They will be either
expansive, displaying symptoms of narcissism, perfectionism, or vindictiveness
self-effacing and compulsively compliant, displaying symptoms of neediness or codependence
resigned, displaying schizoid tendenciesIn Horneys view, mild anxiety disorders and full-blown personality disorders all fall under her basic scheme of neurosis as variations in the degree of severity and in the individual dynamics. The opposite of neurosis is a condition Horney calls self-realization, a state of being in which the person responds to the world with the full depth of their spontaneous feelings, rather than with anxiety-driven compulsion. Thus the person grows to actualize their inborn potentialities. Horney compares this process to an acorn that grows and becomes a tree: the acorn has had the potential for a tree inside it all along.
See also
Individuation
Neurotics Anonymous
Positive disintegration
References
Bibliography
Angyal, Andras. 1965. Neurosis and Treatment: A Holistic Theory, edited by E. Hanfmann and R. M. Jones.
Fenichel, Otto. 1945. The Psychoanalytic Theory of Neurosis. New York: Norton.
Freud, Sigmund. 1953–1974. The Standard Edition of the Complete Psychological Works of Sigmund Freud. (24 vols.), translated by J. Strachey. London: Hogarth.
Horney, Karen. 1937. The Collected Works. (2 vols.). Norton.
—— 1945. Our Inner Conflicts. Norton.
1950. Neurosis and Human Growth. Norton.
Horwitz, A. V. and J. C. Wakefield. 2007. The Loss of Sadness: How Psychiatry Transformed Normal Sorrow into Depressive Disorder. Oxford University Press. ISBN 978-0-19-531304-8.
Jung, Carl G. [1921] 1971. Psychological Types, (The Collected Works of C. G. Jung 6). Princeton University Press. ISBN 0-691-01813-8.
—— 1966. Two Essays on Analytical Psychology, (The Collected Works of C. G. Jung 7). Princeton University Press. ISBN 0-691-01782-4.
Jung, Carl G., and Aniela Jaffé. [1961] 1989. Memories, Dreams, Reflections. New York: Vantage Books. ISBN 0-679-72395-1
Jung, Carl G., et al. 1964. Man and His Symbols. New York: Anchor Books / Doubleday. ISBN 0-385-05221-9.
Ladell, R. M., and T. H. Hargreaves. 1947. "The Extent of Neurosis." British Medical Journal 2(4526):548–49. doi:10.1136/bmj.2.4526.548. PMC 2055884. PMID 20267012.
López-Piñero J.M. (1983) Historical Origins of the Concept of Neurosis (Translated by D. Berrios) Cambridge, Cambridge University Press
McWilliams, Nancy. 2011. Psychoanalytic Diagnosis: Understanding Personality Structure in the Clinical Process (2nd ed.). Guilford Press. ISBN 978-1-60918-494-0.
Russon, John. 2003. Human Experience: Philosophy, Neurosis, and the Elements of Everyday Life. Albany: State University of New York Press. ISBN 0-7914-5754-0
Winokur, Jon. 2005. Encyclopedia Neurotica. ISBN 0-312-32501-0.
External links
Janov, Arthur (1991). "Neurosis". Retrieved 2009-04-21. |
Brachioradial pruritus | Brachioradial pruritus (sometimes abbreviated BRP) is an intense itching sensation of the arm usually between the wrist and elbow of either or both arms.: 36 The itch can be so intense that affected individuals will scratch their own skin to a bleeding condition.
The condition is becoming increasingly common, presenting in patients who are usually fair skinned and middle aged and indulge in golf, tennis, outdoor table tennis, sailing, or other leisure outdoor activities in sunny climates.: 64 : 402 The cause is not known, although there are a few lines of thought on what causes it. No cure has been found, but depending on severity, good control with treatment can be achieved. For milder cases, the intense itch/scratch cycle can be broken by applying a topical skin coolant gel containing menthol, camphor, or other topical coolant to affected itchy areas, and then consistently applying 100+SPF sunscreen to affected skin of arms, shoulders, neck, etc., whenever they are expected to be exposed to the sun. A unique prescription topical combination of ketamine .5% and amitriptyline hydrochloride 1% has shown immediate and long term relief with no serious adverse events in at least one severe case.[1]
Many different medications and types of topical creams have been experimented with, but few seem to make any difference, except for the above. The application of ice packs to the affected area can also diminish the itch short-term.
Causes
Brachioradial pruritus (BRP) is a localized pruritus of the dorsolateral aspect of the arm. BRP is an enigmatic condition with a controversial cause; some authors consider BRP to be a photodermatosis, whereas other authors attribute BRP to compression of cervical nerve roots.
BRP may be attributed to a neuropathy, such as chronic cervical radiculopathy. The possibility of an underlying neuropathy should be considered in the evaluation and treatment of all patients with BRP.The main cause of BRP is not known, but there is evidence to suggest that BRP may arise in the nervous system. Cervical spine disease may also be an important contributing factor.
Patients with BRP may have underlying cervical spine pathology. Whether this association is causal or coincidental remains to be determined.
There is controversy regarding the cause of brachioradial pruritus: is it caused by a nerve compression in the cervical spine or is it caused by a prolonged exposure to sunlight?In many patients, itching of the arms or shoulders is seasonal. Some patients reported neck pain.BRP can be linked to the thyroid.
Diagnosis
Treatments
Symptom management may include the application of a unique prescription topical combination of ketamine .5% and amitriptyline hydrochloride 1%.[2]
Milder cases may use lidocaine or capsaicin, and/or cervical traction.
Treatment with lamotrigine has been reported. Treatment by acupuncture has been reported.Treatment with Gabapentin has been reported.
See also
List of cutaneous conditions
References
Further reading
Walcyk, Patricia J.; Elpern, D.J. (1986). "Brachioradial pruritus: a tropical dermopathy". British Journal of Dermatology. 115 (2): 177–80. doi:10.1111/j.1365-2133.1986.tb05714.x. PMID 3741783. S2CID 39609751.
Orton, D.I.; Wakelin, S.H.; George, S.A. (1996). "Brachioradial photopruritus - a rare chronic photodermatosis in Europe". British Journal of Dermatology. 135 (3): 486–7. doi:10.1046/j.1365-2133.1996.d01-1030.x. PMID 8949453. S2CID 41887835.
Dermatology 1977;195:414-5.
Brachioradial Pruritus at eMedicine
Veien, Niels K.; Hattel, Thais; Laurberg, Grete; Spaun, Eva (2001). "Brachioradial pruritus". Journal of the American Academy of Dermatology. 44 (4): 704–5. doi:10.1067/mjd.2001.112912. PMID 11260554.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackermans Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lippincott Williams & Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedons Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatricks Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weisss Soft Tissue Tumors. Fourth Edition. Mosby 2001. |
Intestinal pseudo-obstruction | Intestinal pseudo-obstruction (IPO) is a clinical syndrome caused by severe impairment in the ability of the intestines to push food through. It is characterized by the signs and symptoms of intestinal obstruction without any lesion in the intestinal lumen. Clinical features mimic those seen with mechanical intestinal obstructions and can include abdominal pain, nausea, abdominal distension, vomiting, dysphagia and constipation depending upon the part of the gastrointestinal tract involved.
It is a difficult condition to diagnose, requiring exclusion of any other mechanical cause of obstruction. Many patients are diagnosed late in the course of disease after additional symptoms are seen. Mortality is also difficult to accurately determine. One retrospective study estimated mortality to be between 10 and 25% for chronic intestinal pseudo-obstruction (CIPO) and to vary greatly depending on the etiology of the condition. When present for less than six months, it is diagnosed as acute IPO or Ogilvies Syndrome. Longer than this is considered chronic. Owing to the difficulty of diagnosis, few studies are available which have attempted to estimate its prevalence.The condition can begin at any age. Most studies describing CIPO are in pediatric populations. It can be a primary condition (idiopathic or inherited) or caused by another disease (secondary). It can be a result of myriad of etiologies including infectious, parasitic, autoimmune, genetic, congenital, neurologic, toxic, endocrinological, or anatomical pathology.
Treatment targets nutritional support, improving intestinal motility, and minimizing surgical intervention. Bacterial overgrowth of the small intestine can occur in chronic cases - presenting as malabsorption, diarrhea, and nutrient deficiencies - which may require the use of antibiotics.
Presentation
Clinical features of IPO can include abdominal pain, nausea, abdominal distension, vomiting, dysphagia, and constipation. Symptoms depend on the portion of the gastrointestinal tract involved and the duration of symptoms. Symptoms may occur intermittently and over a prolonged period of time. It is not unusual for patients to present several times owing to the nonspecific nature of the symptoms. Conditions and onset will vary if the disease is primary vs secondary and the underlying disease (if a secondary manifestation) and its management.
Symptoms indicative of advanced disease and possible intestinal failure include diarrhea, loss of appetite, sepsis, bloating, fatigue, signs of low volume status, and malabsorption including nutritional deficiencies and foul-smelling stools.
Causes
In primary CIPO (the majority of chronic cases) the condition results from disruption of the intestines ability to move food. These can be broadly classified as myopathic (affecting the smooth muscle), mesenchymopathic (affecting the interstitial cells of Cajal), or neuropathic (of the nervous system) of the gastrointestinal tract.In some cases there appears to be a genetic association. One form has been associated with DXYS154.Secondary chronic intestinal pseudo-obstruction can occur as a consequence of a number of other conditions including:
Hirschsprungs disease - the absence of colonic nerve cells
Chagas disease - a chronic parasitic infection of the colon leading to loss of nerve endings
Kawasaki disease - a rare presentation for this particular autoimmune disorder of the vasculature
Parkinsons disease - related to the neurodegeneration of gastrointestinal tract
Autoimmune conditions - conditions including systemic lupus erythematosus and scleroderma lead to collagen vascular deposition and gastrointestinal motility disruption
Mitochondrial disease - IPO is a known presentation for mitochondrial disease
Endocrine disorders
Certain medications.The term may be used synonymously with enteric neuropathy if a neurological cause is suspected.
Diagnosis
The symptoms of IPO are nonspecific. It is not unusual for patients to present repeatedly and to undergo numerous tests. Mechanical causes of intestinal obstruction must be excluded to reach a diagnosis of pseudo-obstruction. Attempts must also be made to determine whether the IPO is the result of a primary or secondary condition. A diagnostic work-up may include:
Gastric motility studies
Imaging studies:
X-rays - may show intestinal air fluid levels (seen with true mechanical intestinal obstruction)
CT scans
Barium enema
Blood tests
Upper and lower endoscopies
Manometry - used to measure pressure of esophagus and stomach
Treatment
Treatment for IPO (acute or chronic) is aimed at removing the disease process and/or managing the complications present. Focus is placed on management of pain, gastrointestinal symptoms, nutritional deficiencies, fluid status, infection control, and improving quality of life. When CIPO is secondary to another disease, treatment is addressed towards the underlying condition. Surgery is sometimes required in severe cases of CIPO.
Medical treatment
Prucalopride, pyridostigmine, metoclopramide, cisapride, erythromycin and octreotide are medications that aim to enhance intestinal motility.
Intestinal stasis, which may lead to bacterial overgrowth and subsequently, diarrhea or malabsorption, is treated with antibiotics.
Nutritional deficiencies are treated by encouraging patients to avoid foods that increase distention and are difficult to digest (e.g. those high in fat and fibre), consuming small frequent meals (5–6 per day), focusing on liquids and soft food. Reducing intake of poorly absorbed sugar alcohols may be of benefit. Referral to an accredited dietitian is recommended. If dietary changes are unsuccessful in meeting nutritional requirements and energy needs, enteral nutrition is used. Many patients eventually require parenteral nutrition.Total parenteral nutrition (TPN) is a form of long-term nutritional treatment reserved for patients that have severe pseudo-obstruction. TPN dependent patients require frequent checkups to monitor catheter function, check liver enzyme levels, and evaluate for signs of blood infections. TPN format is typically changed depending on loss/gain of weight and bloodwork results, and is specially formulated to meet each individual patients needs.
Procedures
Intestinal decompression by tube placement in a small stoma can also be used to reduce distension and pressure within the gut. The stoma may be a gastrostomy, jejunostomy, ileostomy or cecostomy. These may be used for feed (e.g. gastrostomy and jejunostomy) or to flush the intestines.
Colostomy or ileostomy can bypass affected parts if they are distal to (come after) the stoma. For instance, if only the colon is affected, an ileostomy may be helpful. Either of these ostomies are typically placed at or a few centimeters below the patients navel per doctor recommendation based on the affected area of the intestines as well as concerns for patient comfort and future physical growth for children.The total removal of the colon, called a colectomy or resection of affected parts of the colon may be needed if part of the gut dies (for instance toxic megacolon), or if there is a localized area of dysmotility.
Gastric and colonic pacemakers have been tried. These are strips placed along the colon or stomach which create an electric discharge intended to cause the muscle to contract in a controlled manner.
A potential solution, albeit radical, is intestinal transplantation. This is only appropriate in the case of intestinal failure. These procedures are most frequently described in pediatric cases of CIPO. One operation involving multi-organ transplant of the pancreas, stomach, duodenum, small intestine, and liver, and was performed by Doctor Kareem Abu-Elmagd on Gretchen Miller.
Potential Treatments
Further research is necessary into other treatments which may alleviate symptoms. These include stem-cell transplantation and fecal microbiota transplantation. Cannabis has not been studied with regards to CIPO. Any claims to its efficacy for use in CIPO are speculative.
Related disorders
Ogilvie syndrome: acute pseudoobstruction of the colon in severely ill debilitated patients.
Hirschsprungs disease: enlargement of the colon due to lack of development of autonomic ganglia.
Intestinal neuronal dysplasia: a disease of motor neurons leading to the bowels.
Bowel obstruction: mechanical or functional obstruction of the bowel, most commonly due to adhesions, hernias or neoplasms.
Enteric neuropathy: alternative name sometimes used for diagnosis in UK
References
External links
00530 at CHORUS |
Nevus spilus | Nevus spilus, also known as speckled lentiginous nevus, is a light brown or tan birth mark, speckled with small, dark spots or small bumps. If it occurs in a segmental pattern then it is sometimes referred to as a Zosteriform speckled lentiginous nevus.It may be associated with types of phakomatosis pigmentovascularis.Prevalence is between 0.2% and 2.8%.
See also
Phakomatosis pigmentokeratotica
Skin lesion
List of cutaneous conditions
References
== External links == |
Pemphigus erythematosus | Pemphigus erythematosus is simply a localized form of pemphigus foliaceus with features of lupus erythematosus.
See also
Pemphigus
List of cutaneous conditions
List of conditions caused by problems with junctional proteins
References
== External links == |
Dysfibrinogenemia | The dysfibrinogenemias consist of three types of fibrinogen disorders in which a critical blood clotting factor, fibrinogen, circulates at normal levels but is dysfunctional. Congenital dysfibrinogenemia is an inherited disorder in which one of the parental genes produces an abnormal fibrinogen. This fibrinogen interferes with normal blood clotting and/or lysis of blood clots. The condition therefore may cause pathological bleeding and/or thrombosis. Acquired dysfibrinogenemia is a non-hereditary disorder in which fibrinogen is dysfunctional due to the presence of liver disease, autoimmune disease, a plasma cell dyscrasias, or certain cancers. It is associated primarily with pathological bleeding. Hereditary fibrinogen Aα-Chain amyloidosis is a sub-category of congenital dysfibrinogenemia in which the dysfunctional fibrinogen does not cause bleeding or thrombosis but rather gradually accumulates in, and disrupts the function of, the kidney.Congenital dysfibrinogenemia is the commonest of these three disorders. Some 100 different genetic mutations occurring in more than 400 families have been found to cause it. All of these mutations as well as those causing hereditary fibrinogen Aα-Chain amyloidosis exhibit partial penetrance, i.e. only some family members with one of these mutant genes develop dysfibrinogenemia-related symptoms. While both of these congenital disorders as well as acquired dysfibrinogenemia are considered very rare, it is estimated that ~0.8% of individuals with venous thrombosis have either a congenital or acquired dysfibrinogenemia. Hence, the dysfibrinogenemia disorders may be highly under-diagnosed conditions due to isolated thrombotic events that are not appreciated as reflecting an underlying fibrinogen disorder.Congenital dysfibrinogenemia is distinguished from a similar inherited disorder, congenital hypodysfibrinogenemia. Both disorders involve the circulation of dysfunctional fibrinogen but in congenital hypodysfibrinogenemia plasma fibrinogen levels are low while in congenital dysfibrinogenemia they are normal. Furthermore, the two disorders involve different gene mutations and inheritance patterns as well as somewhat different symptoms.
Fibrinogen
Fibrinogen is a glycoprotein made and secreted into the blood primarily by liver hepatocyte cells. Endothelium cells also make what appears to be small amounts of fibrinogen but this fibrinogen has not been fully characterized; blood platelets and their precursors, bone marrow megakaryocytes, although once thought to make fibrinogen, are now known to take up and store but not make the glycoprotein. The final secreted, hepatocyte-derived glycoprotein is made of two trimers each of which is composed of three polypeptide chains, Aα (also termed α) encoded by the FGA gene, Bβ (also termed β) encoded by the FGB gene, and γ encoded by the FGG gene. All three genes are located on the long (i.e. "p") arm of human chromosome 4 (at positions 4q31.3, 4q31.3, and 4q32.1, respectively) and may contain mutations that are the cause of congenital dysfibrinogenemia. The heximer is assembled as a protein in the endoplasmic reticulum of hepatocytes and then transferred to the Golgi where Polysaccharides (i.e. complex sugars) and sialic acid are added by respective glycosylation and sialylation enzyme pathways thereby converting the heximer to a functional fibrinogen glycoprotein. The final circulating glycoprotein (notated as (AαBβγ)2, (αβγ)2, Aα2Bβ2γ2, or α2β2γ2) is arranged as a long flexible rod with nodules at both ends termed D domains and central nodule termed the E domain.The normal process of blood clot formation involves the coordinated operation of two separate pathways that feed into a final common pathway: 1) primary hemostasis, i.e. the adhesion, activation, and aggregation of circulating blood platelets at sites of vascular injury and 2) secondary hemostasis, i.e. cleavage of the Aα and Bβ chains of fibrinogen by thrombin to form individual fibrin strands plus the respective fibrinopeptides A and B formed from this cleavage. In the final common pathway fibrin is cross-linked by activated clotting factor XIII (termed factor XIIIa) to form mature gel-like fibrin clots. Subsequent fibrinolysis pathways act to limit clot formation and dissolve clots no longer needed. Fibrinogen and its Aα fibrin chain have several functions in this process:
Blood clotting: fibrinogen concentration is the rate-limiting factor in blood clot formation and along with blood platelets is critical to this formation (see Coagulation).
Platelet aggregation: fibrinogen promotes platelet aggregation by cross-linking platelet Glycoprotein IIb/IIIa receptors and thereby promotes blood clot formation through the primary hemostasis pathway.
Blood clot lysis: The Aα fibrin chain formed from fibrinogen binds tissue plasminogen activator, an agent that breaks down blood clots to participate thereby in promoting fibrinolysis.Based on these fibrinogen functions, a fibrinogen mutation may act either to inhibit or promote blood clot formation and/or lysis to thereby produce in individuals a diathesis to develop pathological bleeding, thrombosis, or both conditions.
Congenital dysfibrinogenemia
Presentation
Many cases of congenital dysfibrinogenemia are asymptomatic. Since manifestations of the disorder generally occur in early adulthood or middle-age, younger individuals with a gene mutation causing it may not have had time to develop symptoms while previously asymptomatic individuals of advanced age with such a mutation are unlikely to develop symptoms. Bleeding episodes in most cases of this disorder are mild and commonly involve easy bruising and menorrhagia. Less common manifestations of bleeding may be severe or even life-threatening; these include excessive bleeding after tooth extraction, surgery, vaginal birth, and miscarriage. Rarely, these individuals may suffer hemarthrosis or cerebral hemorrhage. In one study of 37 individuals >50 years old afflicted with this disorder, 19% had a history of thrombosis. Thrombotic complications occur in both arteries and veins and include transient ischemic attack, ischemic stroke, myocardial infarction, retinal artery thrombosis, peripheral artery thrombosis, and deep vein thrombosis. In one series of 33 individuals with a history of thrombosis due to congenital dysfibrinogenemia, five developed chronic pulmonary hypertension due to ongoing pulmonary embolism probably stemming form deep vein thrombosis. About 26% of individuals with the disorder suffer both bleeding and thrombosis complications.
Pathophysiology
Congenital dysfibrinogenemia is most often caused by a single autosomal dominant missense mutation in the Aα, Bβ, or γ gene; rarely, it is caused by a homozygous or compound heterozygous missense mutation, a deletion, frameshift mutation, insert mutation, or splice site mutation in one of these genes. The most frequent sites for these mutations code for the N-terminus of the Aα chain or the C-terminus of the γ chain that lead to defective assembly of fibrin in early clot formation and thereby a bleeding predisposition. Two particular missense mutations represent the majority (74% in one study of 101 individuals) of all mutations associated with dysfibrinogenemia and therefore represent prime sites to examine in the initial testing of individuals having a congenital dysfibrinogenmia bleeding disorder. These mutations alter the codon coded for the amino acid arginine at either the 35th position of FGA (termed Arg35; see fibrinogen Metz1 and fibrinogen Bicetre in the Table below) and or the 301st position of FGG (termed Arg301; see fibrinogen Baltimore IV in the Table below).The following Table lists examples of mutations causing congenital dysfibrinogenemias. It gives: a) the mutated proteins trivial name; b) the gene mutated (i.e. FGA, FGB, or FGG), its mutation site (i.e. numbered nucleotide in the cloned gene), and the names of the nucleotides (i.e. C, T, A, G) at these sites before>after the mutation; c) the altered fibrinogen peptide (Aα, Bβ, or λ) and the amino acids (using standard abbreviations) found in the normal-mutated circulating fibrinogen; d) the cause of the mutated fibrinogens misfunction(s); e) the clinical consequence(s) of the mutation; and f) comments. Unless noted as a deletion (del), frame shift (fs), or homozygous mutation, all mutations are heterozygous, missense mutations.
Diagnosis
The diagnosis of congenital dysfibrinogenmia is made by clinical laboratory studies that find normal levels of plasma fibrinogen but significant excess in the amount of immunologically detected compared to functionally detected (i.e. able to be clotted) fibrinogen. The ratio of functionally-detected to immunologically detected fibrinogen masses in these cases is <0.7. Partial thromboplastin time, activated partial thromboplastin time, thrombin time, and reptilase time tests are usually prolonged regardless of history of bleeding or thrombosis. Where available, laboratory analyses of the fibrinogen genes and peptide chains solidify the diagnosis. Initial examination of these genes or protein chains should search specifically for "hot spot" mutations, i.e. the most common mutations (see Pathophysiology section) that comprise the large bulk of mutations in the disorder. In cases of dysfibrinogenemia in which acquired disease is suspected, diagnosis requires a proper diagnosis of the presence of a causable disease.Congenital dysfibrinogenmia is initially distinguished form congenital hypodysfibrinogenemia by the finding of normal immunologically-detected levels of fibrinogen in congenital dysfibrinogenemia and sub-normal levels of immunologically-detected fibrinogen in congenital hypodysfibrinogenemia. Both disorders exhibit mass ratios of functionally-detected to immunologically-detected fibrinogen that are below <0.7. Genetic and protein analyses can definitively differentiate the two disorders.
Treatment
In a study of 189 individuals diagnosed with congenital dysfibrinogenemia, ~33% were asymptomatic, ~47% experienced episodic bleeding, and ~20% experienced episodic thromboses. Due to the rareness of this disorder, treatment of individuals with these presentations are based primarily on case reports, guidelines set by the United Kingdom, and expert opinions rather than controlled clinical studies.
Asymptomatic individuals
Treatment of asymptomatic congenital dysfibrinogenemia depends in part on the expectations of developing bleeding and/or thrombotic complications as estimated based on the history of family members with the disorder and, where available, determination of the exact mutation causing the disorder plus the propensity of the particular mutation type to develop these complications. In general, individuals with this disorder require regular follow-up and multidiscipline management prior to surgery, pregnancy, and giving childbirth. Women with the disorder appear to have an increased rate of miscarriages and all individuals with fibrinogen activity in clotting tests below 0.5 grams/liter are prone to bleeding and spontaneous abortions. Women with multiple miscarriages and individuals with excessively low fibrinogen activity levels should be considered for prophylaxis therapy with fibrinogen replacement during pregnancy, delivery, and/or surgery.
Symptomatic individuals
Individuals experiencing episodic bleeding as a result of congenital dysfibrinogenemia should be treated at a center specialized in treating hemophilia. They should avoid all medications that interfere with normal platelet function. During bleeding episodes, treatment with fibrinogen concentrates or in emergencies or when these concentrates are unavailable, infusions of fresh frozen plasma and/or cryoprecipitate (a fibrinogen-rich plasma fraction) to maintain fibrinogen activity levels >1 gram/liter. Tranexamic acid or fibrinogen concentrates are recommended for prophylactic treatment prior to minor surgery while fibrinogen concentrates are recommended prior to major surgery with fibrinogen concentrates usage seeking to maintain fibrinogen activity levels at >1 gram/liter. Women undergoing vaginal or Cesarean child birth should be treated at a hemophilia center with fibrinogen concentrates to maintain fibrinogen activity levels at 1.5 gram/liter. The latter individuals require careful observation for bleeding during their post-partum periods.Individuals experiencing episodic thrombosis as a result of congenital dysfibrinogenemia should also be treated at a center specialized in treating hemophilia using antithrombotic agents. They should be instructed on antithrombotic behavioral methods fur use in high risk situations such as long car rides and air flights. Venous thrombosis should be treated with low molecular weight heparin for a period that depends on personal and family history of thrombosis events. Prophylactic treatment prior to minor surgery should avoid fibrinogen supplementation and use prophylactic anticoagulation measures; prior to major surgery, fibrinogen supplementation should be used only if serious bleeding occurs; otherwise, prophylactic anticoagulation measures are recommended.
Hereditary fibrinogen Aα-Chain amyloidosis
Presentation
Individuals with hereditary fibrinogen Aα-chain amyloidosis present with evidence ranging from asymptomatic proteinuria to progressive renal impairment and end-stage kidney disease. They do not evidence pathological bleeding or thrombosis and their amyloidosis is non-systemic in that it is restricted to the kidney. In a report on 474 patients with renal amyloidosis, hereditary fibrinogen Aα chain disease represented only 1.3% of all cases whereas aberrant immunoglobulin-induced renal amyloidosis (e.g. AL amyloidosis) represented 86% of the cases). Hereditary fibrinogen Aα-Chain amyloidosis is, however, the most common form of familial renal amyloidosis.
Pathophysiology
Certain mutations in the fibrinogen Aα-chain gene cause a form of familial renal amyloidosis termed hereditary fibrinogen Aα-Chain amyloidosis. The disorder is due to autosomal dominant inheritance of Aα chain mutations the most common of which is hemoglobin Indianopolis, a heterzyogus missense (c.1718G>T: Arg554Leu) mutation. Other missense mutations causing this disorder are unnamed; they include 1634A>T: Glu526Val; c.1670C>A: Thr538lys; c.1676A.T:Glu540Val; and c1712C>A:Pro552His. A deletion mutation causing a frameshift viz., c.1622delT: Thr525Leu, is also a cause of the disorder. The fibrinogen bearing these mutant Aα-chains is secreted into the circulation and gradually accumulates in, and causes significant injury to, the kidney. The mutant fibrinogen does not appear to accumulate in, or injure, extra-renal tissues.
Diagnosis
The diagnosis of this disorder depends on demonstrating: 1) a dysfunctional plasma fibrinogen, i.e. significantly less functionally-detected compared to immunologically-detected fibrinogen; b) presence of signs and/or symptoms of kidney disease; and c) histological evidence of often massive obliteration of renal glomeruli by amyloid as detected by Congo red staining. There also should be no evidence for systemic amyloidosis. Specialized centers use immunological and genetic studies to define the nature of the renal amyloid deposits, the presence of FGA gene mutations, and the occurrence of these mutations in family members. The disorder exhibits a highly variable penetrance among family members. Hereditary fibrinogen Aα-Chain amyloidosis shows variable penetrance among family members, a distinctive histological appearance, proteinuria, progressive renal impairment, and markedly better survival rates than other forms of systemic renal amyloidosis.
Treatment
Treatment of hereditary fibrinogen Aα-Chain amyloidosis has relied on chronic maintenance hemodialysis and, where possible, kidney transplantation. While recurrence of amyloidosis in the transplanted kidney occurs and is to be expected, transplant survival rates for this form of amyloidosis are significantly better than those for transplants in other forms of systemic renal amyloidosis. Relatively healthy individuals with hereditary fibrinogen Aα-Chain-related renal amyloidosis may be considered for kidney and liver bi-transplantation with the expectation that survival of the transplanted kidney will be prolonged by replacing the fibrinogen Aα-Chain-producing liver with a non-diseased donor liver.
Acquired dysfibrinogenemia
Presentation
Acquired dysfibrinogenemia commonly present with signs, symptoms, and/or prior diagnoses of the underlying causative disease or drug intake in an individual with an otherwise unexplained bleeding tendency or episode. Bleeding appears to be more prominent in acquired compared to congenital dysfibrinogenemia; pathological thrombosis, while potentially occurring in these individuals as a complication of their underlying disease, is an uncommon feature of the acquired disorder.
Pathophysiology
Acquired dysfibrinogenemia occurs as a known or presumed consequence of an underlying disease which directly or indirectly interferes with the clotting function of fibrinogen. Individuals with acquired dysfibrinogenemias have a greater tendency for bleeding complications than those with congenital fibrinogenemia. The following Table gives some abnormalities, causes, and apparent pathophysiology along with some comments on examples of acquired dysfibrinogenemia.
Diagnosis
Diagnosis of acquired dysfibrinogenemia uses the same laboratory tests that are used for congenital dysfibrinogenemia plus evidence for an underlying causative disease.
Treatment
Treatment of acquired dysfibrinogenemia follows the guidelines recommended for congenital dysfibrinogenemia. In addition, treatment of any disease thought to be responsible for the dysfibrinogenemia might be useful. For example, therapeutic plasma exchange and chemotherapy to reduce monoclonal antibody levels has been used successfully to reverse otherwise uncontrollable bleeding in cases of multiple myeloma-associated dysfibrinogenemia.
References
== External links == |
Ureterocele | A ureterocele is a congenital abnormality found in the ureter. In this condition the distal ureter balloons at its opening into the bladder, forming a sac-like pouch. It is most often associated with a duplicated collection system, where two ureters drain their respective kidney instead of one. Simple ureterocele, where the condition involves only a single ureter, represents only twenty percent of cases.
Since the advent of the ultrasound, most ureteroceles are diagnosed prenatally. The pediatric and adult conditions are often found incidentally, i.e. through diagnostic imaging performed for unrelated reasons.
Classification
Intravesical
Confined within the bladder
Ectopic
Some part extends to the bladder neck or urethra
Stenotic
Intravesical ureterocele with a narrow opening
Sphincteric
Ectopic ureterocele with an orifice distal to the bladder neck
Sphincterostenotic
Orifice is both stenotic and distal to the bladder neck
Cecoureterocele
Ectopic ureterocele that extends into the urethra, but the orifice is in the bladder
Signs and symptoms
The signs and symptoms of ureterocele in the latter two forms can easily be confused with other medical conditions. Symptoms can include:
Frequent urinary tract infections
Pyelonephritis
Obstructive voiding symptoms
Urinary retention
Failure to thrive
Hematuria
Cyclic abdominal pain
Urolithiasis
Cobra head sign is seen in radiography
In females: salpingitis, hydrosalpinx with sepsis or torsion. T.O. mass.
Complications
Many other complications arise from ureteroceles. Redundant collection systems are usually smaller in diameter than single, and predispose the patient to impassable kidney stones. The effective "bladder within a bladder" compounds this problem by increasing the collision of uric acid particles, the process by which uric acid stones are formed. Ureterocele is also associated with poor kidney function. It can cause frequent blockage of the ureter leading to serious kidney damage. In other cases, a small, upper portion of the kidney is congenitally non-functional. Though often benign, this problem can necessitate the removal of non-functioning parts.
Causes
Definitive causes of ureterocele have not been found. While the abnormal growth occurs within the uterus, it has not been substantiated that genetics are to blame. Congenital abnormalities of the mesonephric duct in males can lead to the formation of a ureterocele, which often coincide with ipsilateral agenesis of the kidney (atrophic kidney) and seminal vesicle cysts, this is known as Zinner Syndrome.
Diagnosis
IVU-shows Adder head appearance or Cobra head appearance.
Cystoscopy-shows translucent cyst which is thin walled surrounding ureteric orifice
Treatment
Single-system ureterocele: initial management is usually endoscopic incision of the ureterocele, which can be followed by surgical ureteric re-implantation to preserve renal function and prevent reflux.
Duplex-system ureterocele: treatment options vary with the individual and include: endoscopic incision of the corresponding ureteric orifice in case of ureteric meatal stricture; upper pole nephrectomy for a poorly functioning unit with ureterectomy or, where there is useful renal function, ureteropyelostomy.
References
Further reading
== External links == |
Glutaric aciduria type 1 | Glutaric acidemia type 1 (GA1) is an inherited disorder in which the body is unable to completely break down the amino acids lysine, hydroxylysine and tryptophan. Excessive levels of their intermediate breakdown products (glutaric acid, glutaryl-CoA, 3-hydroxyglutaric acid, glutaconic acid) can accumulate and cause damage to the brain (and also other organs), but particularly the basal ganglia, which are regions that help regulate movement. GA1 causes secondary carnitine deficiency, as glutaric acid, like other organic acids, is detoxified by carnitine. Mental retardation may occur.
GA1 is an autosomal recessive disorder caused by deficiency of the enzyme glutaryl-CoA dehydrogenase (GCDH), encoded by the GCDH gene.
Signs and symptoms
The severity of glutaric acidemia type 1 varies widely; some individuals are only mildly affected, while others suffer severe problems. GA1 can be defined as two clinical entities: GA-1 diagnosed at birth or pre-birth and managed through dietary restrictions, and GA-1 diagnosed after an encephalopathic crisis. A crisis may occur under both headings, but the care of individuals diagnosed before a crisis can be managed to avoid most or all injury.
GA1 without encephalopathic crisis
Macrocephaly
Babies with glutaric acidemia type 1 often are born with unusually large heads (macrocephaly). Macrocephaly is amongst the earliest signs of GA1. It is thus important to investigate all cases of macrocephaly of unknown origins for GCDH deficiency, given the importance of the early diagnosis of GA1.
Macrocephaly is a pivotal clinical sign of many neurological diseases. Physicians and parents should be aware of the benefits of investigating for an underlying neurological disorder, particularly a neurometabolic one, in children with head circumferences in the highest percentiles.
GA1 after an encephalopathic crisis
Neuromotor aspects
Affected individuals may have difficulty moving and may experience spasms, jerking, rigidity or decreased muscle tone and muscle weakness (which may be the result of secondary carnitine deficiency). GA, in patients who have suffered a crisis, can be defined as a cerebral palsy of genetic origins.
Occupational therapy
A common way to manage striatal necrosis is to provide special seating. These special wheelchairs are designed to limit abnormal movements. However, spasticity can be worsened by constraint. Parents and caregivers can provide a more interactive occupational therapy by enabling the child to use his or her own excessive postural muscle tone to his or her own advantage (see picture; note the care with which minimal pressure is applied while ensuring safety).The excessive tone can also be managed with "jolly jumpers" and other aids to the upright stance that do not constrain the child but help him or her gradually tone down the rigidity.
Bleeding abnormalities
Some individuals with glutaric acidemia have developed bleeding in the brain or eyes that could be mistaken for the effects of child abuse.
Genetics
The condition is inherited in an autosomal recessive pattern: mutated copies of the gene GCDH must be provided by both parents to cause GA1. The GCDH gene encodes the enzyme glutaryl-CoA dehydrogenase. This enzyme is involved in degrading the amino acids lysine, hydroxylysine and tryptophan. Mutations in the GCDH gene prevent production of the enzyme or result in the production of a defective enzyme with very low residual activity, or an enzyme with relatively high residual activity but still phenotypic consequences. This enzyme deficiency allows glutaric acid, 3-hydroxyglutaric acid and to a lesser extent glutaconic acid to build up to abnormal levels, especially at times when the body is under stress. These intermediate breakdown products are particularly prone to affect the basal ganglia, causing many of the signs and symptoms of GA1.
GA1 occurs in approximately 1 of every 30,000 to 40,000 births. As a result of founder effect, it is much more common in the Amish community and in the Ojibway population of Canada, where up to 1 in 300 newborns may be affected.
Relatives of children with GA1 can have low GCDH activity: in an early study of GA1, GCDH activity was found to be 38%, 42%, and 42% in three of the four unaffected relatives tested, a pattern consistent with the 50% level that would be expected in heterozygous carriers. Those levels are close to those found in some heavily symptomatic GA1-affected children.
Diagnosis
Normally, magnetic resonance imaging shows the Sylvian fissure to be operculated, but in GA1-associated encephalopathy, operculation is absent. In many jurisdictions, GA1 is included in newborn screening panels. Elevated glutarylcarnitine can be detected by mass spectrometry in a dried blood spot collected shortly after birth. After a positive screening result, confirmatory testing is performed. This includes urine organic acid analysis, looking for glutaric acid and 3-hydroxyglutaric acid. Plasma and urine acylcarnitine analysis can also be informative. Molecular analysis, including gene sequencing and copy number analysis of GCDH, can be performed to confirm the diagnosis. Molecular testing can also provide information for family planning and prenatal testing, if desired.
Treatment
Correction of secondary carnitine depletion
Like many other organic acidemias, GA1 causes carnitine depletion. Whole-blood carnitine can be raised by oral supplementation. However, this does not significantly change blood concentrations of glutarylcarnitine or esterified carnitine, suggesting that oral supplementation is suboptimal in raising tissue levels of carnitine. Clinical nutrition researchers have likewise concluded that oral carnitine raises plasma levels but does not affect those in muscles, where most of it is stored and used.In contrast, regular intravenous infusions of carnitine cause distinct clinical improvements: "decreased frequency of decompensations, improved growth, improved muscle strength and decreased reliance on medical foods with liberalization of protein intake."Choline increases carnitine uptake and retention. Choline supplements are inexpensive, are safe (probably even in children requiring anticholinergics) and can increase exercise tolerance, truncal tone and general well-being, providing evidence of the suboptimal efficiency of carnitine supplementation alone.
Selective precursor restriction
Dietary control may help limit progression of the neurological damage.
Lysine
Lysine restriction, as well as carnitine supplementation, are considered the best predictors of a good prognosis for GA1. This excludes, however, patients who already suffered an encephalopathic crisis, for whom the prognosis is more related to the treatment of their acquired disorder (striatal necrosis, frontotemporal atrophy).
Protein restriction
Vegetarian diets and, for younger children, breastfeeding are common ways to limit protein intake without endangering tryptophan transport to the brain.
Tryptophan
Formulas such as XLys, XTrp Analog, XLys, XTrp Maxamaid, XLys, XTrp Maxamum or Glutarex 1 are designed to provide amino acids other than lysine and tryptophan, to help prevent protein malnutrition.
The entry of tryptophan into the brain is crucial in the proper synthesis of the neurotransmitter serotonin in the brain. One way to acutely cause depression, bulimia or anxiety in humans, in order to assess an individuals vulnerability to those disorders, is to supplement with a formula with all or most amino acids except tryptophan. Acute tryptophan depletion is a diagnostic procedure, not a treatment for GA1. The protein synthesis elicited by the amino acids leads circulating amino acids, including tryptophan, to be incorporated into proteins. Tryptophan is thus lowered in the brain as a result of the protein synthesis enhancement, causing circulating tryptophan to drop more than other amino acids. A relative excess of other large neutral amino acids may also compete with tryptophan for transport across the blood–brain barrier through the large neutral amino acid transporter 1. The consequence is acute tryptophan depletion in the brain and a consequent decrease in serotonin synthesis.
5-Hydroxytryptophan, a precursor of serotonin that is not metabolized to glutaryl-CoA, glutaric acid and secondary metabolites, could be used as an adjunct to selective tryptophan restriction, although it has risks. However, the evidence in favour of selective tryptophan restriction remains insufficient and the consensus is evolving towards the restriction of lysine only. In the Amish community, where GA1 is overrepresented, patients with GA1 typically do not receive tryptophan-free formulas, either as the sole source of amino acids or as a supplement to protein restriction.
Enhancement of precursor anabolic pathways
Lysine and hydroxylysine anabolic pathway enhancement
A possible way to prevent the build-up of metabolites is to limit lysine and hydroxylysine degradation, as lysine is one of the most abundant amino acids and tryptophan is one of the least abundant amino acids.
Interaction of GCDH deficiency with vitamin C levels
Humans lack the enzyme L-gulonolactone oxidase, which is necessary for the synthesis of ascorbic acid (vitamin C), leaving them dependent on dietary sources of this vitamin. Vitamin C is a necessary cofactor for the utilization of lysine in collagen synthesis. Collagen, the most abundant protein in the human body, requires great amounts of lysine, the most abundant amino acid in proteins. Ascorbic acid, the main hydroxyl radical quencher, works as the cofactor providing the hydroxyl radical required for collagen cross-linking; lysine thus becomes hydroxylysine.
GA1 worsens during stresses and catabolic episodes, such as fasts and infections. Endogenous catabolism of proteins could be an important route for glutaric acid production. It follows that collagen breakdown (and protein breakdown in general) should be prevented by all possible means.
Ascorbic acid is used to prevent multiple organ failure and to lessen mortality and morbidity in intensive care units. It thus appears reasonable to add sufficient doses of ascorbic acid to the treatment protocol during stresses and other challenges to growth in order to stimulate collagen synthesis and thus prevent lysine breakdown.
Tryptophan anabolic pathway enhancement
The conversion of tryptophan to serotonin and other metabolites depends on vitamin B6. If tryptophan catabolism has any impact on brain glutaric acid and other catabolite levels, vitamin B6 levels should be routinely assayed and normalized in the course of the treatment of GA1.
Management of intercurrent illnesses
Stress caused by infection, fever or other demands on the body may lead to worsening of the signs and symptoms, with only partial recovery.
Prognosis
A 2006 study of 279 patients found that of those with symptoms (185, 66%), 95% had suffered an encephalopathic crises, usually with following brain damage. Of the participants in the study, 49 children died and the median age of death was 6.6 years. A Kaplan–Meier analysis of the data estimated that about 50% of symptomatic people would die by the age of 25.
More recent studies provide an updated prognosis whereby individuals affected can, through proper dietary management and carnitine supplementation, manage the disease with a much improved prognosis. Newborn screening has allowed affected patients to avoid crises and live full lives without any injury to the brain. It is essential that patients with the disease be diagnosed at or before birth and that all variables be strictly managed in order to maintain quality of life. When suspected and in the absence of confirmed diagnosis (through genetic sequencing), it is critical that the individual maintain a diet restrictive of all proteins and that blood sugars be monitored rigorously. The WHO now considers this disease entirely manageable.
Epidemiology
GA1 can be described as a metabolic disorder, a neurometabolic disease, a cerebral palsy or a basal ganglia disorder (it may also be misdiagnosed as shaken baby syndrome).
Depending on the paradigm adopted, GA1 will mostly be managed with precursor restriction or with neurorehabilitation.
So-called "orphan diseases", such as GA1, can be adopted into wider groups of diseases (such as carnitine deficiency diseases, cerebral palsies of diverse origins, basal ganglia disorders, and others); Morton at al. (2003b) emphasize that acute striatal necrosis is a distinctive pathologic feature of at least 20 other disorders of very different etiologies, including, HIV encephalopathy–AIDS dementia complex, pneumococcal meningitis, hypoadrenal crisis, methylmalonic acidemia, propionic acidemia, middle cerebral artery occlusion, hypertensive vasculopathy, acute Mycoplasma pneumoniae infection, 3-nitropropionic acid intoxication, late-onset familial dystonia, cerebrovascular abrupt and severe neonatal asphyxia ("selective neuronal necrosis").
In a cohort of 279 patients who had been reported to have GA1, 185 were symptomatic (two-thirds); being symptomatic was seen as an indication of low treatment efficacy. Screening of those known to be at high risk, neonatal population screening and a diagnosis of macrocephaly are the ways to identify bearers of the GCDH mutation who are not frankly symptomatic. Macrocephaly remains the main sign of GA1 for those who have no relatives with GA1 and have not been included in a population screening program. GA1 is considered a treatable disease.
Two-thirds of the patients who have GA1 encephalopathy will receive little benefit from the treatment for GA1 but can benefit from treatments given to victims of middle cerebral artery occlusion, AIDS dementia and other basal ganglia disorders: brain implants, stem cell neurorestoration, growth factors, monoaminergic agents, and many other neurorehabilitation strategies.
References
Further reading
Mahfoud Hawilou, Antonieta; Domínguez Méndez, Carmen Luisa; Rizzo, Cristiano; Ribes Rubio, Antonia (2004). "Macrocefalia in utero como manifestación clínica de aciduria glutárica tipo I. Informe de una nueva mutación" [In utero macrocephaly as clinical manifestation of glutaric aciduria type I. Report of a novel mutation]. Revista de Neurología (in Spanish). 39 (10): 939–942. doi:10.33588/rn.3910.2004258. PMID 15573311.
Martínez Granero MA, Garcia Pérez A, Martínez-Pardo M, Parra E (2005). "[Macrocephaly the first manifestation of glutaric aciduria type I: the importance of early diagnosis.]". Neurologia (in Spanish). 20 (5): 255–60. PMID 15954035.
Strauss KA, Morton DH (2003). "Type I glutaric aciduria, part 2: a model of acute striatal necrosis" (PDF). Am J Med Genet C Semin Med Genet. 121C (1): 53–70. doi:10.1002/ajmg.c.20008. PMID 12888986. S2CID 22759360. Archived from the original (PDF) on January 30, 2005. see also Part 1 referenced above
External links
Glutaric aciduria type 1 at NLM Genetics Home Reference - Type 1 |
Marburg acute multiple sclerosis | Marburg acute multiple sclerosis, also known as Marburg multiple sclerosis or acute fulminant multiple sclerosis, is considered one of the multiple sclerosis borderline diseases, which is a collection of diseases classified by some as MS variants and by others as different diseases. Other diseases in this group are neuromyelitis optica (NMO), Balo concentric sclerosis, and Schilders disease. The graver course is one form of malignant multiple sclerosis, with patients reaching a significant level of disability in less than five years from their first symptoms, often in a matter of months.Sometimes Marburg MS is considered a synonym for tumefactive MS, but not for all authors.
Pathogenesis
Marburg MS has been reported to be closer to anti-MOG associated ADEM than to standard MS It has been reported to appear sometimes post-partum
MOG antibody‐associated demyelinating pseudotumor
Some anti-MOG cases satisfy the MS requirements (lesions disseminated in time and space) and are therefore traditionally considered MS cases. After the discovery of the anti-MOG disease this classification is into revision.
Diagnosis
It took its name from Otto Marburg. It can be diagnosed in vivo with an MRI scan.
If Marburg disease occurs in the form of a single large lesion, it can be radiologically indistinguishable from a brain tumor or abscess. It is usually lethal, but it has been found to be responsive to Mitoxantrone and Alemtuzumab, and it has also been responsive to autologous stem cell transplantation. Recent evidence shows that Marburgs presents a heterogeneous response to medication, as does standard MS.
Treatment
Historically, acute MS was a fatal disease, with death occurring within a year of onset, often secondary to extensive brain stem demyelination. Treatment recommendations, based on anecdotes, include plasma exchange in conjunction with high-dose glucocorticoids(e.g., 1 to 2 g/day of methylprednisolone for 10 days followed by a slow taper). For patients who survive the acute attack, follow-up treatments include immunosuppression (monthly mitoxantrone or cyclophosphamide) either alone or in combination with IFN beta or GA (glatiramer acetate).
Prognosis
Marburg variant of MS is an acute fulminant demyelinating process which in most cases progresses inexorably to death within 1–2 years. However, there are some reports of Marburg MS reaching stability by three years.
See also
Malignant multiple sclerosis
Tumefactive multiple sclerosis
References
== External links == |
Myopericytoma | Myopericytoma is a rare perivascular soft tissue tumour. It is usually benign and typically in the distal extremities.It is thought to overlap with myofibroma.
See also
Glomus tumour
References
== External links == |
Pinch mark | Pinch marks are a cutaneous condition, and when on the ears or in the genital region of male children may be suggestive of child abuse.
See also
Runners rump
List of cutaneous conditions
== References == |
Torus palatinus | A torus palatinus (pl. tori palatini), or palatal torus (pl. palatal tori), is a bony protrusion on the palate. Palatal tori are usually present on the midline of the hard palate. Most palatal tori are less than 2 cm in diameter, but their size can change throughout life.
Types
Sometimes, the tori are categorized by their appearance. Arising as a broad base and a smooth surface, flat tori are located on the midline of the palate and extend symmetrically to either side. Spindle tori have a ridge located at their midline. Nodular tori have multiple bony growths that each have their own base. Lobular tori have multiple bony growths with a common base.
Cause
Although some research suggest palatal tori to be an autosomal dominant trait, it is generally believed that palatal tori are caused by several factors. They are more common in early adult life and can increase in size. In some older people, the size of the tori may decrease due to bone resorption. It is believed that tori of the lower jaw are the result of local stresses and not due solely to genetic influences.
Treatment
Palatal tori are usually a clinical finding with no treatment necessary. It is possible for ulcers to form on the area of the tori due to repeated trauma. Also, the tori may complicate the fabrication of dentures. If removal of the tori is needed, surgery can be done to reduce the amount of bone present.
Surgical removal
A maxillary torus is only removed in instances where it is problematic. This includes cases where in an edentulous patient, it extends to the vibrating line, preventing a posterior seal of the denture and posterior seal at the fovea palatinae. Other indications for removal include frequent trauma to the torus, owing to its size or the thinness of the mucoperiosteum overlying it, disturbance of speech, and rapid growth in patients who are cancer-phobic.
Prevalence
Prevalence of palatal tori ranges from 9–60% and are more common than bony growths occurring on the mandible, known as torus mandibularis. Palatal tori are more common in Asian, Native American and Inuit populations, and are twice as common in females. In the United States, the prevalence is 20–35% of the population.
References
== External links == |
Gastrinoma | Gastrinomas are neuroendocrine tumors (NETs), usually located in the duodenum or pancreas, that secrete gastrin and cause a clinical syndrome known as Zollinger–Ellison syndrome (ZES). A large number of gastrinomas develop in the pancreas or duodenum, with near-equal frequency, and approximately 10% arise as primary neoplasms in lymph nodes of the pancreaticoduodenal region (gastrinoma triangle).Most gastrinomas are sporadic (75–80%), whereas approximately 20–25% are associated with multiple endocrine neoplasia type 1 (MEN-1). Over 50% of gastrinomas are malignant and can metastasize to regional lymph nodes and liver. One fourth of gastrinomas are related to multiple endocrine neoplasia type 1, Zollinger–Ellison syndrome, peptic ulcer disease.
Signs and symptoms
Gastrinoma in the early stages will have signs and symptoms of indigestion or similar to irritable bowel disease (IBD) such as:
Hypergastrinemia
Refractory or recurrent peptic ulcers involving duodenum
Chronic diarrhea
Generalized cancer symptoms
Abdominal pain
Gastrointestinal bleeding
Obstruction of intestine
Weight loss/poor appetite
Anemia (Due to vitamin B12 malabsorption, and bleeding)
Hematemesis
Gastroesophageal reflux disease
Esophageal complications (Barretts esophagus, esophagitis, stricture formation)
Vomiting
Steatorrhea
Pathophysiology
Gastrin is secreted by the G cells. G cells are primarily found in the pyloric antrum but can also be found in the duodenum and the pancreas. The primary function of gastrin is to induce the release of hydrochloric acid (HCl) from the parietal cells located in the fundus of the stomach. Parietal cells are responsible for hydrochloric (HCl) secretion along with intrinsic factor that binds to vitamin B12 and helps with its uptake in the terminal ileum. Other functions of gastrin include stimulating the growth of gastric mucosa and gastric motility and promoting gastric emptying. These mechanisms of the gastrointestinal tract (GIT) are up-regulated by the vagus nerve of the parasympathetic nervous system (PNS), which carries out the majority of its functions by the release of neurotransmitter Acetylcholine (Ach), and to a lesser extent gastrin releasing peptide (GRP) protein. On the contrary, the functions of GIT are down-regulated by the activation sympathetic nervous system (SNS), which carries out its functions mostly via neurotransmitter epinephrine.Meal consumption causes distention of the stomach, leading to stimulation of the parasympathetic vagus nerve in the gastric mucosa, which causes the release of GRP protein. In gastrinoma, GRP protein causes larger than normal amounts of gastrin secretion, which leads to hyperplasia of the parietal cells. Hyperplasia of parietal cells causes an abnormal release of HCl into the duodenum, which causes the ulcers of the duodenum. Excessive HCl production also causes hyperperistalsis, a condition marked by excessive rapidity of the passage of food through the stomach and intestine and inhibits the activity of lipase, causing severe fatty diarrhea known as steatorrhea. Evenly the long-standing hyper-secretion of gastrin stimulate proliferation of the enterochromaffin like cells (ECL). These cells are found along the side the gastric lumen of the digestive tract. They play a main role in regulation of gastric secretion and motility when stimulated by nervous system. These cells in return will undergo progressive dysplastic changes starting with hyperplasia to neoplasia throughout the gastrointestinal tract.
Diagnosis
In many cases, gastrinoma is diagnosed based on the patients history which is typically characterized by recurrent episodes of peptic ulcer disease or by severe reflux esophagitis and/or diarrhea or by acid-related symptoms which fail to respond to standard treatment regimens. To confirm the diagnosis of gastrinoma a series of blood tests must be made. One of those tests is the serum gastrin level, which is the most reliable test for patients with gastrinoma. The normal levels of gastrin are 150 pg/mL ( > 72.15 pmol/L); therefore elevated levels of > 1000 pg/mL (> 480 pmol/L) would establish the diagnosis of gastrinoma. Another test that can be conducted is the secretin stimulated test, which is useful in patients who have the sign and symptoms of gastrinoma but the gastrin levels are below < 1000 pg/mL. Usually, an Intravenous bolus consisting of secretin 2mcg/kg and is measured in 10 minute intervals up to 30 minutes total. Secretin, which is a hormone released from the duodenal S cells that induce the release of pancreatic bicarbonate (HCO3) that would neutralize the acidic environment due to high gastrin levels. Therefore, if the patients level of gastrin remains consistently high indicating gastrin release due to tumor such as gastrinoma.Other commonly used tests to further confirm the diagnosis are
CT scan of the abdominal area
Somatostatin receptor scintigraphy which is used to identify the location of the tumor
PET scan
Endoscopic ultrasound if there are no signs of tumor metastases.
Treatment
Surgery is first line treatment in gastrinomas; however it often fails to be curative.
Proton-pump inhibitors such as omeprazole. This group of medications suppress the acid secretion.
H2-receptor antagonist similarly decrease acid secretion.
Octreotide injections directly release somatostatin hormone that inhibits gastrin release.
Chemotherapy.
Prognosis
Patients with gastrinomas that are also known to be part of neuroendocrine neoplasms must have to deal with two factors related to this tumor. First, controlling the high amounts by using medications that inhibit gastrin levels. The second part is stabilizing the tumor progression. Gastrinomas have a rate of 60–90% that will become malignant. Patients who do not seek medical treatment such anti-ulcer medication have high rate of recurrence and death secondary to ulcer disease. The prognosis of gastrinoma depends on the level of metastases of the tumor. If patients present with hepatic metastases they might have remaining life span of one year with a five-year survival rate of 20–30%. In patients with localized tumor or localized lymph spread the survival rate of five years is 90%. Lastly, surgical resection of local tumor could lead to complete cure without recurrence in 20–25% of patients.
Epidemiology
Gastrinoma is the second most common functional pancreatic neuroendocrine tumor (pNET), with a yearly incidence of approximately 0.5 to 21.5 cases per a million of people worldwide. Gastrinomas are located predominantly in the duodenum (70%) and pancreas (25%). Pancreatic gastrinomas are larger than their duodenal counterparts, may occur in any portion of the pancreas, and comprise 25% of these tumors. Gastrinomas are also the most common functional and malignant pancreatic endocrine tumors. They are characterized by gastric hypersecretion that results in peptic ulcers and diarrhea; this condition is known as Zollinger–Ellison syndrome (ZES).
Research
Recently, research studies have been conducted to seek new medical advances in relation to gastrinoma and Zollinger–Ellison syndrome. The recent studies have shown improved understanding of pathogenesis of pancreatic neuroendocrine tumors, classifications of those tumors, new treatments/preventions to control the gastrin levels in the gastrointestinal tract, and the best and safest surgical approaches. The study concluded that the wide use of proton pump inhibitors itself might further induce hypergastrinemia (increased gastrin levels in circulatory system) by feedback inhibition. The body will try to induce further release when gastrin level is depleted. Some of the new treatments might include medication that is directed towards the liver such as embolization, chemoembolization, and radioembolization in addition to the currently offered treatments such as chemotherapy, somatostatin analogs. Other treatments that are still in phase three of clinical trials include liver transplantation and peptide-radioreceptor therapy.
See also
Pancreatic endocrine tumor
References
External links
Emedicine |
Centronuclear myopathy | Centronuclear myopathies (CNM) are a group of congenital myopathies where cell nuclei are abnormally located in the center of muscle cells instead of their normal location at the periphery.
Symptoms of CNM include severe hypotonia, hypoxia-requiring breathing assistance, and scaphocephaly. Among centronuclear myopathies, the X-linked myotubular myopathy form typically presents at birth, and is thus considered a congenital myopathy. However, some centronuclear myopathies may present later in life.
Presentation
As with other myopathies, the clinical manifestations of MTM/CNM are most notably muscle weakness and associated disabilities. Congenital forms often present with neonatal low muscle tone, severe weakness, delayed developmental milestones (particularly gross motor milestones such as head control, crawling, and walking) and pulmonary complications (presumably due to weakness of the muscles responsible for respiration). Involvement of the facial muscles may cause ophthalmoplegia or ptosis. A mutation in the RYR1 gene causing CNM may also cause susceptibility to malignant hyperthermia, a potentially life-threatening reaction to anesthesia. While some patients with centronuclear myopathies remain ambulatory throughout their adult life, others may never crawl or walk and may require wheelchair use for mobility. There is substantial variability in the degree of functional impairment among the various centronuclear myopathies. Although this condition only affects the voluntary muscles, several children have had cardiac arrest, possibly due to the additional stress placed on the heart.Other observed features have been high arched palate, long digits, bell shaped chest and long face. Myotubular myopathy only affects muscles and does not impact intelligence in any shape or form.X-linked myotubular myopathy was traditionally a fatal condition of infancy, with life expectancy of usually less than two years. There appears to be substantial variability in the clinical severity for different genetic abnormalities at that same MTM1 gene. Further, published cases show significant differences in clinical severity among relatives with the same genetic abnormality at the MTM1 gene. Most truncating mutations of MTM1 cause a severe and early lethal phenotype, while some missense mutations are associated with milder forms and prolonged survival (up to 54 years).Centronuclear myopathies typically have a milder presentation and a better prognosis. Autosomal dominant CNM tends to have a less severe phenotype than the autosomal recessive version. Recently, researchers discovered mutations at the gene dynamin 2 (DNM2 on chromosome 19, at site 19p13.2), responsible for the autosomal dominant form of centronuclear myopathy. This condition is now known as dynamin 2 centronuclear myopathy (abbreviated DNM2-CNM). Research has indicated that patients with DNM2-CNM have a slowly progressive muscular weakness usually beginning in adolescence or early adulthood, with an age range of 12 to 74 years.
Genetic
The genetic abnormality associated with the X-linked form of myotubular myopathy (XLMTM) was first localized in 1990 to the X chromosome at site Xq28. MTM1 codes for the myotubularin protein, a highly conserved lipid phosphatase involved in cellular transport, trafficking and signalling. Approximately 80% of males with myotubular myopathy diagnosed by muscle biopsy have mutations in MTM1, and about 7% of these mutations are genetic deletions.Centronuclear myopathies where the genetic abnormality is NOT sex-linked (e.g., not located on the X chromosome) are considered autosomal. Autosomal abnormalities can either be dominant or recessive, and are often referred to as AD for "autosomal dominant" or AR for "autosomal recessive").Many researchers use the term "myotubular myopathy" (MTM) only for cases when the genetic test has come back positive for abnormalities (genetic mutations) at the MTM1 gene on the X chromosome. Cases with a centronuclear (nucleus in the center) appearance on muscle biopsy but a normal genetic test for MTM1 would be referred to as centronuclear myopathy until such time as a specific genetic site is identified to give a more detailed sub-classification.The possible combinations of inheritance of myotubular myopathy are as follows:
Sporadic cases have also been reported where there is no previous family history (these cases are presumably due to a new mutation that was not present in either parent).
Pathology
On examination of muscle biopsy material, the nuclear material is located predominantly in the center of the muscle cells, and is described as having any "myotubular" or "centronuclear" appearance. In terms of describing the muscle biopsy itself, "myotubular" or "centronuclear" are almost synonymous, and both terms point to the similar cellular-appearance among MTM and CNM. Thus, pathologists and treating physicians use those terms almost interchangeably, although researchers and clinicians are increasingly distinguishing between those phrases.In general, a clinical myopathy and a muscle biopsy showing a centronuclear (nucleus in the center of the muscle cell) appearance would indicate a centronuclear myopathy (CNM). The most commonly diagnosed CNM is myotubular myopathy (MTM). However, muscle biopsy analysis alone cannot reliably distinguish myotubular myopathy from other forms of centronuclear myopathies, and thus genetic testing is required.Diagnostic workup is often coordinated by a treating neurologist. In the United States, care is often coordinated through clinics affiliated with the Muscular Dystrophy Association.
Diagnosis
Electrodiagnostic testing
Electrodiagnostic testing (also called electrophysiologic) includes nerve conduction studies which involves stimulating a peripheral motor or sensory nerve and recording the response, and needle electromyography, where a thin needle or pin-like electrode is inserted into the muscle tissue to look for abnormal electrical activity.
Electrodiagnostic testing can help distinguish myopathies from neuropathies, which can help determine the course of further work-up. Most of the electrodiagnostic abnormalities seen in myopathies are also seen in neuropathies (nerve disorders). Electrodiagnostic abnormalities common to myopathies and neuropathies include; abnormal spontaneous activity (e.g., fibrillations, positive sharp waves, etc.) on needle EMG and, small amplitudes of the motor responses compound muscle action potential, or CMAP during nerve conduction studies. Many neuropathies, however, cause abnormalities of sensory nerve studies, whereas myopathies involve only the muscle, with normal sensory nerves. The most important factor distinguishing a myopathy from a neuropathy on needle EMG is the careful analysis of the motor unit action potential (MUAP) size, shape, and recruitment pattern.
There is substantial overlap between the electrodiagnostic findings the various types of myopathy. Thus, electrodiagnostic testing can help distinguish neuropathy from myopathy, but is not effective at distinguishing which specific myopathy is present, here muscle biopsy and perhaps subsequent genetic testing are required.
Treatment
Currently there is no cure for myotubular or centronuclear myopathies. Treatment often focuses on trying to maximize functional abilities and minimize medical complications, and involvement by physicians specializing in Physical Medicine and Rehabilitation, and by physical therapists and occupational therapists.Medical management generally involves efforts to prevent pulmonary complications, since lung infections can be fatal in patients lacking the muscle strength necessary to clear secretions via coughing. Medical devices to assist with coughing help patients maintain clear airways, avoiding mucous plugs and avoiding the need for tracheostomy tubes.Monitoring for scoliosis is also important, since weakness of the trunk muscles can lead to deviations in spinal alignment, with resultant compromise of respiratory function. Many patients with congenital myopathies may eventually require surgical treatment of scoliosis.
Epidemiology
The overall incidence of myotubular myopathy is 1 in 50,000 male live births. The incidence of other centronuclear myopathies is extremely rare, with there only being nineteen families identified with CNM throughout the world. The symptoms currently range from the majority who only need to walk with aids, from a stick to a walking frame, to total dependence on physical mobility aids such as wheelchairs and stand aids, but this latter variety is so rare that only two cases are known to the CNM "community".
Approximately 80% of males with a diagnosis of myotubular myopathy by muscle biopsy will have a mutation in MTM1 identifiable by genetic sequence analysis.Many patients with myotubular myopathy die in infancy prior to receiving a formal diagnosis. When possible, muscle biopsy and genetic testing may still be helpful even after a neonatal death, since the diagnostic information can assist with family planning and genetic counseling as well as aiding in the accurate diagnosis of any relatives who might also have the same genetic abnormality.
History
In 1966, Dr. Spiro (a New York City neurologist) published a medical report of a boy with myopathy, which upon muscle biopsy, showed that the nuclei of the muscle cells were located in the center of the muscle cells, instead of their normal location of the periphery.
The nuclear appearance reminded him of the nucleus-in-the-center appearance during the "myotubular" stage of embryonic development. Thus, he coined the term "myotubular myopathy". Spiro speculated that the embryonic muscle development he had seen in the boy was due to growth arrest during the myotubular phase, causing the myopathy.More than three decades later, it is not fully understood whether this theory regarding halted (or delayed) embryonic muscle development is correct. Some research suggests that this theory may be acceptable for infant-onset myotubular myopathy (mutations at the MTM1 gene on the X chromosome) but may not be acceptable for the autosomal forms of centronuclear myopathy, while other research suggests that the growth arrest mechanism may be responsible for all forms of MTM and CNM.
Regardless of whether the myopathy is caused by arrest at the "myotubular" stage, for historical reasons the name myotubular myopathy persists and is widely accepted.As a reference to the term myotubular myopathy (MTM), when a genetic abnormality on the X chromosome was determined to be involved in a substantial percentage of individuals with the myotubular/centronuclear appearance on muscle biopsy, researchers named the gene segment MTM1. Similarly, the protein typically produced by that gene is called "myotubularin".
Advocacy
There are several global advocacy groups working closely to educate newly affected families on care guidelines. The Joshua Frase Foundation is a comprehensive resource for care guidelines for Centronuclear myopathies. In the United States, children with congenital myopathies often receive therapy services through Early Intervention Programs (EIP, providing services from birth to 3 years old) administered by the state of residence. After the child is 3 years old, Special Education services are provided under the federal Individuals with Disabilities Education Act (IDEA, with myopathies being eligible when classified under conditions causing muscular weakness). IDEA is meant to protect the rights of every disabled student to receive a free and appropriate public education (FAPE) in the least restrictive environment (ideally meaning integrated with non-disabled classmates).Centronuclear myopathies involve pathology at the skeletal muscles, generally without brain involvement or cognitive deficits. Even so, the motor deficits (weakness and associated impairments) may impede in individuals ability to access the educational curriculum (e.g., difficulties lifting or carrying books, difficulties grasping a writing instrument, endurance difficulties throughout the school day, etc.). Further, recurrent respiratory infections may result in missed school days.
Terminology
Although all forms of centronuclear myopathy are considered rare, the most commonly known form of CNM is Myotubular Myopathy (MTM). (The terms "centronuclear myopathy" and "myotubular myopathy" are sometimes equated.)Literally, a myopathy is a disease of the muscle tissue itself. Myo derives from the word muscle and pathos means disease. There are dozens of different myopathies, and myopathies are not the only conditions that can cause muscle weakness. Other diseases can cause weakness such as medical conditions affecting sites outside of the muscle itself, including problems in the brain (such as stroke, cerebral palsy, multiple sclerosis), or problems in the spinal cord and/or nerve (such as polio and spinal muscular atrophy).
References
External links
GeneReviews/NCBI/NIH/UW entry on X-Linked Myotubular Myopathy or Centronuclear Myopathy |
Granular corneal dystrophy | Granular corneal dystrophy is a slowly progressive corneal dystrophy that most often begins in early childhood.
Granular corneal dystrophy has two types:
Granular corneal dystrophy type I, also corneal dystrophy Groenouw type I, is a rare form of human corneal dystrophy. It was first described by German ophthalmologist Arthur Groenouw in 1890.
Granular corneal dystrophy type II, also called Avellino corneal dystrophy or combined granular-lattice corneal dystrophy is also a rare form of corneal dystrophy. The disorder was first described by Folberg et al. in 1988. The name Avellino corneal dystrophy comes from the first four patients in the original study each tracing their family origin to the Italian province of Avellino.
Presentation
Granular corneal dystrophy is diagnosed during an eye examination by an ophthalmologist or optometrist. The lesions consist of central, fine, whitish granular lesions in the cornea. Visual acuity is slightly reduced.
Genetics
Granular corneal dystrophy is caused by a mutation in the TGFBI gene, located on chromosome 5q31. The disorder is inherited in an autosomal dominant manner. This indicates that the defective gene responsible for the disorder is located on an autosome (chromosome 5 is an autosome), and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.
The gene TGFBI encodes the protein keratoepithelin.
Diagnosis
Treatment
Corneal transplant is not needed except in very severe and late cases.
Light sensitivity may be overcome by wearing tinted glasses.
See also
Corneal dystrophy
== References == |
Urachal fistula | A urachal fistula is a congenital disorder caused by the persistence of the allantois (later, urachus), the structure that connects an embryos bladder to the yolk sac. Normally, the urachus closes off to become the median umbilical ligament; however, if it remains open, urine can drain from the bladder to an opening by the umbilicus.This condition is a rare defect, mostly found in children, and is also known as an open or patent urachus.
== References == |
Primary familial brain calcification | Primary Indiana familial brain calcification (PFBC), also known as familial idiopathic basal ganglia calcification (FIBGC) and Fahrs disease, is a rare, genetically dominant, inherited neurological disorder characterized by abnormal deposits of calcium in areas of the brain that control movement. Through the use of CT scans, calcifications are seen primarily in the basal ganglia and in other areas such as the cerebral cortex.
Signs and symptoms
Symptoms of this disease include deterioration of motor functions and speech, seizures, and other involuntary movement. Other symptoms are headaches, dementia, and vision impairment.
Characteristics of Parkinsons Disease are also similar to PFBC.The disease usually manifests itself in the third to fifth decade of life but may appear in childhood or later in life. It usually presents with clumsiness, fatigability, unsteady gait, slow or slurred speech, difficulty swallowing, involuntary movements or muscle cramping. Seizures of various types are common. Neuropsychiatric symptoms, which may be the first or the most prominent manifestations, range from mild difficulty with concentration and memory to changes in personality and/or behavior, to psychosis and dementia.
Causes
This condition can be inherited in an autosomal dominant or recessive fashion. Several genes has been associated with this condition
Mutation
A locus at 14q has been suggested, but no gene has been identified. A second locus has been identified on chromosome 8 and a third has been reported on chromosome 2. This suggests there may be some genetic heterogeneity in this disease.A mutation in the gene encoding the type III sodium dependent phosphate transporter 2 (SLC20A2) located on chromosome 8 has been reported. Biochemical evidence suggests that phosphate transport may be involved in this disease.Two other genes have been associated with this condition: PDGFB on chromosome 22 and PDGFRB on chromosome 5. These genes are biochemically linked: PDGFRB encodes the platelet-derived growth factor receptor β and PDGFB encodes the ligand of PDGF-Rβ. These genes are active during angiogenesis to recruit pericytes which suggests that alterations in the blood brain barrier may be involved in the pathogenesis of this condition.A fourth gene associated with this condition is XPR1. This gene is the long arm of located on chromosome 1 (1q25.3).Another gene that has been associated with this condition is MYORG. This gene is located on the long arm of chromosome 9 (9p13.3). This gene is associated with an autosomal recessive inheritance pattern in this condition.Another gene junctional adhesion molecule 2 (JAM2) has been associated with an autosomal recessive form of this condition. Other genes that have been associated with this condition are Junctional adhesion molecule C (JAM3) and Occludin (OCLN).
Pathology
The most commonly affected region of the brain is the lenticular nucleus and in particular the internal globus pallidus. Calcifications in the caudate, dentate nuclei, putamen and thalami are also common. Occasionally calcifications begin or predominate in regions outside the basal ganglia.Calcification seems to be progressive, since calcifications are generally more extensive in older individuals and an increase in calcification can sometimes be documented on follow up of affected subjects.As well as the usual sites the cerebellar gyri, brain stem, centrum semiovale and subcortical white matter may also be affected. Diffuse atrophic changes with dilatation of the subarachnoid space and/or ventricular system may coexist with the calcifications. Histologically concentric calcium deposits within the walls of small and medium-sized arteries are present. Less frequently the veins may also be affected. Droplet calcifications can be observed along capillaries. These deposits may eventually lead to closure of the lumina of vessels.The pallidal deposits stain positively for iron. Diffuse gliosis may surround the large deposits but significant loss of nerve cells is rare. On electron microscopy the mineral deposits appear as amorphous or crystalline material surrounded by a basal membrane. Calcium granules are seen within the cytoplasm of neuronal and glial cells. The calcifications seen in this condition are indistinguishable from those secondary to hypoparathyroidism or other causes.
Diagnosis
In addition to the usual routine haematologic and biochemical investigations, the serum calcium, phosphorus, magnesium, alkaline phosphatase, calcitonin and parathyroid hormone should also be measured. The cerebrospinal fluid (CSF) should be examined to exclude bacteria, viruses and parasites. The Ellsworth Howard test (a 10-20 fold increase of urinary cyclic AMP excretion following stimulation with 200 micromoles of parathyroid hormone) may be worth doing also. Serology for toxoplasmosis is also indicated.
Brain CT scan is the preferred method of localizing and assessing the extent of cerebral calcifications.Elevated levels of copper, iron, magnesium and zinc but not calcium have been reported in the CSF but the significance of this finding — if any — is not known.The diagnosis requires the following criteria be met:
the presence of bilateral calcification of the basal ganglia
the presence of progressive neurologic dysfunction
the absence of an alternative metabolic, infectious, toxic or traumatic cause
a family history consistent with autosomal dominant inheritanceThe calcification is usually identified on CT scan but may be visible on plain films of the skull.
Differential diagnosis
Basal ganglia calcification may occur as a consequence of several other known genetic conditions and these have to be excluded before a diagnosis can be made.
Management
There is currently no cure for PFBC nor a standard course of treatment. The available treatment is directed symptomatic control. If parkinsonian features develop, there is generally poor response to levodopa therapy. Case reports have suggested that haloperidol or lithium carbonate may help with psychotic symptoms. One case report described an improvement with the use of a bisphosphonate.
Prognosis
The prognosis for any individual with PFBC is variable and hard to predict. There is no reliable correlation between age, extent of calcium deposits in the brain, and neurological deficit. Since the appearance of calcification is age-dependent, a CT scan could be negative in a gene carrier who is younger than the age of 55.Progressive neurological deterioration generally results in disability and death.
History
The disease was first noted by German pathologist Karl Theodor Fahr in 1930. A less common name for the condition is Chavany-Brunhes syndrome and Fritsches syndrome, the former named after Jacques Brunhes, Jean Alfred Émile Chavany, while the later named after R. Fritsche.Fewer than 20 families had been reported in the literature up to 1997.
In literature
Fahrs syndrome features in Norwegian Jo Nesbøs crime fiction novel "The Snowman" (the seventh novel in the Harry Hole detective series).
See also
Primrose syndrome
References
External links
Fahr Syndrome Images (MedPix)
National Organization for Rare Disorders (NORD)
National Institute on Aging (NIA)
National Institute of Mental Health (NIMH) |
Supernumerary kidney | A supernumerary kidney is an additional kidney to the number usually present in an organism. This often develops as the result of splitting of the nephrogenic blastema, or from separate metanephric blastemas into which partially or completely reduplicated ureteral stalks enter to form separate capsulated kidneys; in some cases the separation of the reduplicated organ is incomplete (fused supernumerary kidney).
Less than a hundred cases are known of one or two supernumerary kidneys.
See also
Supernumerary body part
References
Luciano A. Favorito; Ana Raquel M. Morais (May–June 2012). "Evaluation of supernumerary kidney with fusion using magnetic resonance image". IBJU. 38 (3): 428–429. doi:10.1590/s1677-55382012000300018. PMID 22765860. |
Polyonychia | Polyonychia also known as supernumerary nails is a condition in which two or more nails grow in the same finger or toe.
Signs and symptoms
The signs/symptoms of polyonychia are very easy to detect: two or more nails growing on the same finger or toe.
The nails can either be separate, small nails (micronychia) or one wide, almost complete nail, the digit affected could also be wider than normal
Causes
Polyonychia is generally caused by a congenital duplication of the distal phalange of the affected digit(s), this can be caused by congenital factors (sporadic without a genetic link) or by genetic factors (sporadic or familial with genetic link).
It can also be caused by polysyndactyly, which is characterized as one normal digit being connected/webbed (syndactyly) to an extra digit (polydactyly).
Polyonychia can also be acquired, such as after an accident that affected the nail bed causing it to split. This type of polyonychia is just referred to as "post-traumatic split nail" Polyonychias syndromic causes include:
Isolated congenital onychodysplasiaPolyonychias non-syndromic causes include:
Polyphalangism (more specifically of the distal phalange)
Polysyndactyly
See also
Polydactyly
Syndactyly
Polysyndactyly
== References == |
Hyperprolinemia | Hyperprolinemia is a condition which occurs when the amino acid proline is not broken down properly by the enzymes proline oxidase or pyrroline-5-carboxylate dehydrogenase, causing a buildup of proline in the body.
Genetics
Mutations in the ALDH4A1 and PRODH genes cause hyperprolinemia.Hyperprolinemia type I is caused by a mutation in the PRODH gene, which codes for the enzyme proline oxidase. This enzyme begins the process of degrading proline by starting the reaction that converts it to pyrroline-5-carboxylate.Hyperprolinemia type II is caused by a mutation in the ALDH4A1 gene, for the enzyme 1-pyrroline-5-carboxylate dehydrogenase. This enzyme helps to break down the pyrroline-5-carboxylate produced in the previous reaction, converting it to the amino acid glutamate. The conversion between proline and glutamine, and the reverse reaction controlled by different enzymes, are important factors required to maintain proper metabolism and protein production.
A deficiency of either proline oxidase or pyrroline-5-carboxylate dehydrogenase results in a buildup of proline in the body. A deficiency of the latter enzyme leads to higher levels of proline and a buildup of the intermediate breakdown product pyrroline-5-carboxylate, causing the signs and symptoms of hyperprolinemia type II.Hyperprolinemia is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are heterozygous carriers, having only one copy of the altered gene, without having signs and symptoms of the disorder.In about one-third of cases of hyperprolinemia, individuals carrying one copy of an altered PRODH gene have moderately elevated levels of proline in their blood, but these levels do not cause any health problems. Individuals with one altered ALDH4A1 gene have normal levels of proline in their blood.
Diagnosis
Types
Hyperprolinemia type I
It is difficult to determine the prevalence of hyperprolinemia type I, as many people with the condition are asymptomatic.
People with hyperprolinemia type I have proline levels in their blood between 3 and 10 times the normal level. Some individuals with type I exhibit seizures, intellectual disability, or other neurological problems.
Hyperprolinemia type II
Hyperprolinemia type II results in proline levels in the blood between 10 and 15 times higher than normal, and high levels of a related compound called pyrroline-5-carboxylate. This rare form of the disorder may appear benign at times, but often involves seizures, convulsions, and intellectual disability.Hyperprolinemia can also occur with other conditions, such as malnutrition or liver disease. In particular, individuals with conditions that cause elevated levels of lactic acid in the blood, such as lactic acidemia, are likely to have elevated proline levels, because lactic acid inhibits the breakdown of proline.
Treatment
Dietary restriction of protein intake.
Research
A 2005 study on rats suggested that hyperprolininemia causes cognitive dysfunction.
See also
List of amino acid metabolism disorders
Inborn error of metabolism
References
Further reading
Pyridoxal phosphate de-activation by pyrroline-5-carboxylic acid. Increased risk of vitamin B6 deficiency and seizures in hyperprolinemia type II
== External links == |
Koro | Koro may refer to:
Geography
Koro Island, a Fijian island
Koro Sea, in the Pacific Ocean
Koro, Ivory Coast
Koro, Mali
Koro, Wisconsin, United States, an unincorporated community
Languages
Koro language (India), an endangered language spoken in Arunachal Pradesh, India
Koro language (New Guinea)
Koro language (Vanuatu)
Koro, a variety of the Maninka language spoken in Ivory Coast
Polynesian culture
Oro, a god in Polynesian mythology
Koro (literally, "grandfather"), a term of respect in the Māori language for a male Kaumātua (tribal elder)
Other uses
Kōrō, a masculine Japanese given name
KORO, a Spanish-language television station in Corpus Christi, Texas, USA
Koro (incense burner), a Japanese incense burner
Koro (medicine), the syndrome in which someone believes their external genitals are retracting
Koro Wachi language, spoken in Nigeria
Musiliu Obanikoro, popularly known as Koro
Nkoroo language, Nigeria |
Ectopic pancreas | An ectopic pancreas is an anatomical abnormality in which pancreatic tissue has grown outside its normal location and without vascular or other anatomical connections to the pancreas. It is a congenital disease and is also known as heterotopic, accessory, or aberrant pancreas.
Signs and symptoms
Often, heterotopic pancreas is asymptomatic. When present, symptoms may include abdominal pain and distension. Often heterotopic pancreas is recognized as an incidental finding on imaging studies performed for an unrelated reason. Ectopic pancreatic tissue may occur anywhere in the abdominal cavity, though more than 90 percent are found in the stomach, duodenum or jejunum. Rarely, pancreatic heterotopic tissue may be found in the colon, spleen or liver.
Diagnosis
The diagnosis of ectopic pancreas can be challenging. Confirmation of the diagnosis requires tissue sampling, via biopsy or surgical resection.
Treatment
If no symptoms are present, then treatment is not necessary. When symptoms are present, treatment consists of surgical resection.
Epidemiology
The incidence of heterotopic pancreas is relatively low.
References
== External links == |
Posner–Schlossman syndrome | Posner–Schlossman syndrome (PSS) also known as glaucomatocyclitic crisis (GCC) is a rare acute ocular condition with unilateral attacks of mild granulomatous anterior uveitis and elevated intraocular pressure. It is sometimes considered as a secondary inflammatory glaucoma.
Signs and symptoms
Ocular hypertension (IOP 30 - 70 mmHg) with open angle of anterior chamber and unilateral mild granulomatous anterior uveitis are hallmark signs of Posner–Schlossman syndrome. On slit-lamp examination, conjunctival injections, epithelial corneal edema, small to medium-sized fine keratitic precipitates, aqueous cells and flare may also be noted. Blurring of vision, eye pain and discomfort are the main symptoms. Colored halos may occur due to elevated IOP. Symptoms last from several hours to weeks and may be recurrent. IOP and aqueous humor outflow return to normal in the remission periods.
Etiology
Exact etiology of PSS is unknown. Since it was first described, A number of noninfectious etiological theories have been proposed including autonomic dysregulation, allergy, variation of developmental glaucoma, autoimmune/HLA-Bw54 and abnormality of the ciliary vasculature. Initially, infectious etiologies were not considered because of the episodic nature of the acute attacks. Recently, infectious theories associated with organisms like H. pylori, Herpes simplex virus, Varicella zoster virus, Cytomegalovirus, B. burgdorferi etc. are also emerged in medical literature.
Treatment
Main aim of treatment is to reduce IOP and decrease inflammation.
Medical
Topical steroids, such as prednisolone acetate can be used to decrease the uveal inflammation. Topical or oral non-steroidal anti-inflammatory agents may be used to avoid steroid-induced complications like secondary glaucoma. Prostaglandin analogs such as latanoprost or bimatoprost, beta-blockers such as timolol, alpha-2 agonists such as brimonidine, muscarinic agents such as pilocarpine, hyperosmotic agents such as mannitol and carbonic anhydrase inhibitors such as acetazolamide, methazolamide or dorzolamide are the drugs used to decrease IOP.
Surgical
If the elevated IOP is not responsive to medical treatment, glaucoma surgeries may be considered to prevent visual field loss.
Epidemiology
It usually affects adults between the ages of twenty and fifty and is common in males than females. One study from Finland found that the incidence of disease is 0.4 and its prevalence is 1.9 out of 100,000.
History
Posner and Schlossman first identified and described the syndrome in 1948. They first reported a series of 9 cases and given the name glaucomatocyclitic crisis to describe this condition.
== References == |
Couvelaire uterus | Couvelaire uterus (also known as uteroplacental apoplexy) is a life-threatening condition in which loosening of the placenta (abruptio placentae) causes bleeding that penetrates into the uterine myometrium forcing its way into the peritoneal cavity. This condition makes the uterus very tense and rigid.
Symptoms and signs
Patients can have pain secondary to uterine contractions, uterine tetany or localized uterine tenderness. Signs can also be due to abruptio placentae including uterine hypertonus, fetal distress, fetal death, and rarely, hypovolemic shock (shock secondary to severe blood loss). The uterus may adopt a bluish/purplish, mottled appearance due to extravasation of blood into uterine muscle.
Pathophysiology
Couvelaire uterus is a phenomenon where the retroplacental blood may penetrate through the thickness of the wall of the uterus into the peritoneal cavity. This may occur after abruptio placentae. The hemorrhage that gets into the decidua basalis ultimately splits the decidua, and the haematoma may remain within the decidua or may extravasate into the myometrium (the muscular wall of the uterus). The myometrium becomes weakened and may rupture due to the increase in intrauterine pressure associated with uterine contractions. This may lead to a life-threatening obstetric emergency requiring urgent delivery of the fetus.
Prevention
The occurrence of Couvelaire uterus can be prevented by prevention of abruptio placentae. This includes proper management of hypertensive states of pregnancy; treatment of maternal diseases like diabetes mellitus, and other collagen disease complicating pregnancy; prevention of trauma during pregnancy; mothers should also avoid smoking or consumption of alcohol during pregnancy.
Treatment
The uterus should be evacuated and contractions should be stimulated using intravenous oxytocin; hysterectomy (the removal of the uterus) may be needed in some cases.
Prognosis
The foetus may be compromised if there is prolonged delivery because of the non-contractile uterus; severe bleeding may cause hypovolemic shock in the mother.
References
== External links == |
Valve stenosis | Valve stenosis may refer to:
Pulmonary valve stenosis
Aortic valve stenosis
Mitral valve stenosis |
Small-cell carcinoma | Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell carcinoma, small cell carcinoma has a shorter doubling time, higher growth fraction, and earlier development of metastases.
Extensive stage small cell lung cancer is classified as a rare disorder. Ten-year relative survival rate is 3.5%; however, women have a higher survival rate, 4.3%, and men lower, 2.8%. Survival can be higher or lower based on a combination of factors including stage, age, gender and race.
Types of SCLC
Small-cell lung carcinoma has long been divided into two clinicopathological stages, termed limited stage (LS) and extensive stage (ES). The stage is generally determined by the presence or absence of metastases, whether or not the tumor appears limited to the thorax, and whether or not the entire tumor burden within the chest can feasibly be encompassed within a single radiotherapy portal. In general, if the tumor is confined to one lung and the lymph nodes close to that lung, the cancer is said to be LS. If cancer has spread beyond that, it is said to be ES.
LS-SCLC
In cases of LS-SCLC, combination chemotherapy (usually cisplatin or carboplatin plus etoposide) is administered together with concurrent chest radiotherapy (RT).Chest RT has been shown to improve survival in LS-SCLC.Exceptionally high objective initial response rates (RR) of between 60% and 90% are seen in LS-SCLC using chemotherapy alone, with between 45% and 75% of individuals showing a "complete response" (CR), which is defined as the disappearance of all radiological and clinical signs of tumor. However, relapse rate remains high, and median survival is only 18 to 24 months.Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to chemotherapy and/or radiotherapy, there has been little role for surgery in this disease since the 1970s. However, recent work suggests that in cases of small, asymptomatic, node-negative SCLCs ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy ("adjuvant chemotherapy").
ES-SCLC
In ES-SCLC, platinum-based combination chemotherapy is the standard of care, with radiotherapy added only to palliate symptoms such as dyspnea, pain from liver or bone metastases, or for treatment of brain metastases, which, in small-cell lung carcinoma, typically have a rapid, if temporary, response to whole brain radiotherapy.Combination chemotherapy consists of a wide variety of agents, including cisplatin, cyclophosphamide, vincristine and carboplatin. Response rates are high even in extensive disease, with between 15% and 30% of subjects having a complete response to combination chemotherapy, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, and the evidence surrounding the risk of treatment compared to the potential benefit of chemotherapy for people who have extensive SCLC is not clear.If complete response to chemotherapy occurs in a subject with SCLC, then prophylactic cranial irradiation (PCI) is often used in an attempt to prevent the emergence of brain metastases. Although this treatment is often effective, it can cause hair loss and fatigue. Prospective randomized trials with almost two years of follow-up have not shown neurocognitive ill-effects. Meta-analyses of randomized trials confirm that PCI provides significant survival benefits.In August 2018, the FDA approved nivolumab to treat patients with metastatic small cell lung cancer (SCLC) who failed to respond to platinum-based chemotherapy and at least one other line of treatment. Nivolumab is approved in more than 60 countries. According to LUNGevity Foundation, “This approval marks a major milestone for the patients touched by this unrelenting disease and may motivate them to pursue further treatment where there previously were no other approved options.”In September 2018, the results from the global, randomized phase I/III IMpower 133 trial were announced at the World Congress on Lung Cancer in Toronto, ON. In this study, patients with ES-SCLC were treated with standard carboplatin plus etoposide and were randomized to receive atezolizumab or placebo. Atezolizumab was associated with a significant improvement in overall survival (HR for death = 0.70)
Signs and symptoms
Small-cell carcinoma of the lung usually presents in the central airways and infiltrates the submucosa leading to narrowing of bronchial airways. Common symptoms include cough, dyspnea, weight loss, and debility. Over 70% of patients with small-cell carcinoma present with metastatic disease; common sites include liver, adrenals, bone, and brain.Due to its high grade neuroendocrine nature, small-cell carcinomas can produce ectopic hormones, including adrenocorticotropic hormone (ACTH) and anti-diuretic hormone (ADH). Ectopic production of large amounts of ADH leads to syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).Lambert–Eaton myasthenic syndrome (LEMS) is a well-known paraneoplastic condition linked to small-cell carcinoma.
Small-cell lung cancer
When associated with the lung, it is sometimes called "oat cell carcinoma" due to the flat cell shape and scanty cytoplasm. Caution is required when diagnosing SCLC because small cell mesothelioma – an extremely rare subtype of lung cancer – can be mistaken for small cell lung cancer.It is thought to originate from neuroendocrine cells (APUD cells) in the bronchus called Feyrter cells (named for Friedrich Feyrter).
Hence, they express a variety of neuroendocrine markers, and may lead to ectopic production of hormones like ADH and ACTH that may result in paraneoplastic syndromes and Cushings syndrome. Approximately half of all individuals diagnosed with Lambert–Eaton myasthenic syndrome (LEMS) will eventually be found to have a small-cell carcinoma of the lung.Small-cell carcinoma is most often more rapidly and widely metastatic than non-small-cell lung carcinoma (and hence staged differently). There is usually early involvement of the hilar and mediastinal lymph nodes.
The mechanisms of its metastatic progression are not well-understood.
Combined small-cell lung carcinoma (c-SCLC)
Small-cell lung carcinoma can occur in combination with a wide variety of other histological variants of lung cancer, including extremely complex malignant tissue admixtures.
When it is found with one or more differentiated forms of lung cancer, such as squamous cell carcinoma or adenocarcinoma, the malignant tumor is then diagnosed and classified as a combined small cell lung carcinoma (c-SCLC). C-SCLC is the only currently recognized subtype of SCLC.Although combined small-cell lung carcinoma is currently staged and treated similarly to "pure" small-cell carcinoma of the lung, recent research suggests surgery might improve outcomes in very early stages of this tumor type.Smoking is a significant risk factor. Symptoms and signs are as for other lung cancers. In addition, because of their neuroendocrine cell origin, small-cell carcinomas will often secrete substances that result in paraneoplastic syndromes such as Lambert–Eaton myasthenic syndrome.
Extrapulmonary small-cell carcinoma
Very rarely, the primary site for small-cell carcinoma is outside of the lungs and pleural space; in these cases, it is referred to as extrapulmonary small-cell carcinoma (EPSCC). Outside of the respiratory tract, small-cell carcinoma can appear in the cervix, prostate, liver, pancreas, gastrointestinal tract, or bladder. It is estimated to account for 1,000 new cases a year in the U.S. Histologically similar to small-cell lung cancer, therapies for small-cell lung cancer are usually used to treat EPSCC. First-line treatment is usually with cisplatin and etoposide. In Japan, first-line treatment is shifting to irinotecan and cisplatin. When the primary site is in the skin, it is referred to as a Merkel-cell carcinoma.
Extrapulmonary small-cell carcinoma localized in the lymph nodes
This is an extremely rare type of small cell, and there has been little information in the scientific community. It appears to occur in only one or more lymph nodes, and nowhere else in the body. Treatment is similar to small cell lung cancer, but survival rates are much higher than other small-cell carcinomas.
Small-cell carcinoma of the prostate
Small-cell carcinoma of the prostate (SCCP) is a rare form of prostate cancer (approx. 1% of PC). Due to the fact that there is little variation in prostate specific antigen levels, SCCP is normally diagnosed at an advanced stage, after metastasis.
Symptomatic metastasis of SCCP to the brain is rare, and carries a poor prognosis.
Genetics
TP53 is mutated in 70 to 90% of SCLCs. RB1 and the retinoblastoma pathway are inactivated in most SCLCs. PTEN is mutated in 2 to 10%. MYC amplifications and amplification of MYC family members are found in 30% of SCLCs. Loss of heterozygocity on chromosome arm 3p is found in more than 80% of SCLCs, including the loss of FHIT. One hundred translocations have so far been reported in SCLCs (see the "Mitelman Database" and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,).
Diagnosis
When
Localized: the cancer is confined to the lung (aka: limited stage SCLC).
Regional: the cancer has spread to lymph nodes (or glands) within the chest (between limited and extensive stage SCLC). Lymph nodes act as a filtering system outside the lung, collecting cancer cells that are beginning to migrate out of the lung.
Distant: the cancer has spread (or metastasized) to other parts of the body (aka: extensive stage SCLC).At the time of diagnosis, 60–70% of people already have metastases.Small-cell carcinoma is an undifferentiated neoplasm composed of primitive-appearing cells. As the name implies, the cells in small-cell carcinomas are smaller than normal cells, and barely have room for any cytoplasm. Some researchers identify this as a failure in the mechanism that controls the size of the cells.
Treatment
Small-cell lung cancer is most commonly treated with a combination of two drugs, which is more effective than one drug alone.
Chemotherapy
Cisplatin and etoposide,
Carboplatin and etoposide.
Cisplatin-resistance
The drug paclitaxel may be useful in the treatment of cisplatin-resistant cancer. About 68.1% of cisplatin-resistant cells
appear to be sensitive to paclitaxel and 66.7% of paclitaxel-resistant cells to
cisplatin. The mechanism for this activity is unknown. Paclitaxel-based chemotherapy showed modest activity in SCLC patients refractory to both etoposide- and camptothecin-based chemotherapy. The newer agent lurbinectedin is active in relapsed SCLC and was approved for medical use in the United States in June 2020.
Immunotherapy
In 2018, the FDA approved two immunotherapies for small cell lung cancer:
1. Nivolumab (Opdivo), and
2. Atezolizumab (Tecentriq)
Funding controversy
Tecentriq treatment costs on average $13,200 per month, depending on the dosage schedule.
Despite updated data showing 30% more people with extensive stage small cell lung cancer are alive at 24 months compared to those who received chemotherapy alone, Canadian regulator had rejected to fund Tecentriq for extensive stage small-cell lung cancer "as too costly" followed by United Kingdom also citing "drug’s cost-effectiveness."
Radiation therapy
Chest radiation helps SCLC patients live longer by killing cancer cells and helping prevention of cancer recurrence. Another type of radiation, prophylactic cranial radiation, prevents central nervous system recurrence and can improve survival in patients with good performance status who have had a complete response or a very good partial response to chemoradiation in LD or chemotherapy in ED.
In case of relapse
If small cell lung cancer comes back after treatment, the following combination of drugs may be used as a salvage therapy:
Cyclophosphamide (Cytoxan, Procytox),
Doxorubicin (Adriamycin) and
Vincristine (Oncovin)
Paclitaxel (Taxol)
Irinotecan (Camptosar) Current guidelines recommend that patients who relapse > 6 months from initial therapy should be retreated with the original chemotherapy regimen. For patients who relapse in < 6 months, single-agent chemotherapy either topotecan second-line therapy, or paclitaxel can be used.
Novel agents
Several newer agents, including temozolomide and bendamustine, have activity in relapsed SCLC. Of note, temozolomide yielded a response rate of 38% for brain metastases due to SCLC.In a clinical trial of 50 patients, combination of olaparib and temozolomide in relapsed small-cell lung cancer yielded an overall response rate of 41.7%, median progression-free survival 4.2 months, and overall survival was 8.5 months.Lurbinectedin is the most promising new agent that substantially increased overall survival rate in relapsed small cell lung cancer among sensitive disease patients. As a single agent, lurbinectedin demonstrated following clinical results in refractory small cell lung cancer trial:
Overall survival rate of 15.2 months for sensitive disease (chemotherapy-free interval of ≥ 90 days) with a disease control rate of 79.3% and overall response rate of 46.6%, and
Overall survival rate of 5.1 months for resistant (chemotherapy-free interval of < 90 days) with a disease control rate of 46.8% and overall response rate 21.3%.Lurbinectedin is also being investigated in combination with doxorubicin as second-line therapy in a randomized phase 3 trial. While overall survival in this trial is not yet known, response rates at second line were
91.7% in sensitive disease with median progression-free survival of 5.8 months , and
33.3% in resistant disease with median progression-free of 3.5 months.Lurbinectedin is currently available in the U.S. under an expanded access program (EAP).Trilaciclib, a CKD4/6 inhibitor, reduces chemotheraphy-induced toxicity in patients being treated for small-cell lung cancer. Trilaciclib’s developer, G1 Therapeutics, makes the drug available in the U.S. under expanded access while the FDA considers its New Drug Application (NDA). An approval decision on the NDA is expected by February 15, 2021. On February 12, 2021, the FDA approved trilaciclib (brand name Cosela) as a treatment to reduce the frequency of chemotherapy-induced myelosuppression for patients receiving certain types of chemotherapy for extensive-stage small-cell lung cancer.
Prognosis
5-year survival rates for small cell lung cancer (extensive and limited) range between 3.6% and 32.2% for women, and between 2.2% and 24.5% for men. Relative 5-year survival rate for both sexes has increased from 3.6% in 1975 to 6.7% in 2014.Small-cell carcinoma is very responsive to chemotherapy and radiotherapy, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse and median survival remains low. The overall incidence and mortality rates of SCLC in the United States have decreased during the past few decades.
In limited-stage disease, relative 5-year survival rate (both sexes, all races, all ages) is 21.3%; however, women have higher 5-year survival rates, 26.9%, and men have lower survival rates, 21.3%.The prognosis is far grimmer in extensive-stage small-cell lung carcinoma where 5-year relative survival rate (both sexes, all races, all ages) is 2.8%; however, women have higher 5-year survival rates, 3.4%, and men have lower 5-year survival rates, 2.2%.Long-term survival of more than 5 years can be achieved with proper treatment. According to the 17th World Conference on Lung Cancer (WCLC), "patients who received chest radiation and prophylactic cranial irradiation along with a mean of five chemotherapy cycles could achieve a median survival of more than 5 years."In some cases, long-term survival of 10+ years is achieved with chemotherapy and radiation alone.
5-year survival rates
The SEER database tracks 5-year relative survival rates based on age, sex, and race and is considered the most accurate source of survival information. This database uses terms "Localized," "Regional," and "Distant" to describe various stages of small cell lung cancer.
5-year relative survival rate for "both sexes" and "all races" affected by
"Localized" small cell lung cancer is 28.5%;
"Regional" small cell lung cancer 14.9%; and for
"Distant" small cell lung cancer 2.9%.
Survival rates by sex
Women affected by small-cell lung cancer have higher 5-year survival rates than men.
Localized: Women – 32.2% | Men – 24.5%
Regional: Women – 17.0% | Men – 12.3%
Distant: Women – 3.6% | Men – 2.2%
Survival rates by race, sex, age
5-year relative survival statistics are more accurate and, in some cases, higher when specific race and age range are combined with sex and stage at diagnosis. For example,
Black / Female | Ages < 50 (at diagnosis) | Distant (ES SCLC) | = 7.0%.
White / Female | Ages < 50 (at diagnosis) | Distant (ES SCLC) | = 6.1%National Cancer Institutes SEER maintains publicly accessible database for specific survival rates.
Epidemiology
15% of lung cancers in the US are of this type. Small cell lung cancer occurs almost exclusively in smokers – most commonly in heavy smokers and rarely in non-smokers.
Recalcitrant Cancer Research Act
In 2013, the US Congress passed the Recalcitrant Cancer Research Act, which mandated increased attention to certain recalcitrant cancers, including small cell lung cancer. That led to the National Cancer Institute supporting small cell–specific research through a consortium.
As a result, new experimental drugs for small cell lung cancer are currently being tested, including Iadademstat (ORY-1001) and Keytruda (pembrolizumab).
Additional images
Notable cases
Dustin Diamond, perhaps best known as an actor on Saved by the Bell.
See also
Brown-Séquard syndrome
Cervical cancer
== References == |
Ant venom | Ant venom is any of, or a mixture of, irritants and toxins inflicted by ants. Most ants spray or inject a venom, the main constituent of which is formic acid only in the case of subfamily Formicinae.
Ant stings
Of all extant ant species, about 71% are considered to be stinging species, as some subfamilies have evolutionarily lost the ability to sting. Notable examples include a few species of medical importance, such as Solenopsis (fire ants), Pachycondyla, Myrmecia (bulldog ants), and Paraponera (bullet ants). In the case of fire ants, the venom consists mainly of alkaloid (>95%) and protein (<1%) components. Stinging ants cause a cutaneous condition that is different from that caused by biting venomous ants. Particularly painful are stings from fire ants, although the bullet ants sting is considered by some to be the most painful insect sting.: 450 First aid for fire ant bites includes external treatments and oral medicines.
External treatments: a topical steroid cream (hydrocortisone), or one containing Aloe vera
Oral medicines: antihistamines
Applying zinc oxide or calamine lotion .Severe allergic reactions can be caused by ant stings in particular and venomous stings in general, including severe chest pain, nausea, severe sweating, loss of breath, serious swelling, fever, dizziness, and slurred speech; they can be fatal if not treated.
See also
Acidopore
Poneratoxin, the neurotoxic component of bullet ant venom
Pulicosis (flea bites)
Skin lesion
Solenopsin, the primary toxin in fire ant venom
References
== External links == |
Bone cyst | A bone cyst or geode is a cyst that forms in bone.
Types include:
Unicameral bone cyst
Aneurysmal bone cyst
Traumatic bone cyst
Diagnosis
On CT scans, bone cysts that have a radiodensity of 20 Hounsfield units (HU) or less, and are osteolytic, tend to be aneurysmal bone cysts.In contrast, intraosseous lipomas have a lower radiodensity of -40 to -60 HU.
Treatment and Prevention
Simple (Unicameral) Bone Cyst
Some unicameral bone cysts may spontaneously resolve without medical intervention. Specific treatments are determined based on the size of the cyst, the strength of the bone, medical history, extent of the disease, activity level, symptoms an individual is experiencing, and tolerance for specific medications, procedures, or therapies. The types of methods used to treat this type of cyst are curettage and bone grafting, aspiration, steroid injections, and bone marrow injections. Watchful waiting and activity modifications are the most common nonsurgical treatments that will help resolve and help prevent unicameral bone cysts from occurring and reoccurring.
Aneurysmal Bone Cyst
Aneurysmal bone cysts can be treated with a variety of different methods. These methods include open curettage and bone grafting with or without adjuvant therapy, cryotherapy, sclerotherapy, ethibloc injections, radionuclide ablation, and selective arterial embolization. En-block resection and reconstruction with strut grafting are the most common treatments and procedures that prevent recurrences of this type of cyst.
Traumatic Bone Cyst
The traumatic bone cyst treatment consists of surgical exploration, curettage of the osseous socket and bony walls, subsequent filling with blood, and intralesional steroid injections. Young athletes can reduce their risk of traumatic bone cyst by wearing protective mouth wear or protective headgear.
History
Aneurysmal bone cysts are benign neoformations which can affect any bone. More than half occur in the metaphysis of long bones (especially femur and tibia) and between 12 and 30% in the spine. They were described in 1893 by Van Arsdale, who called these lesions "homerus ossifying haematoma". In 1940 Ewing used the term "aneurismal" to describe these lesions. Jaffé and Lichtenstein first coined the term "aneurismal cyst" in 1942 In 1950 they modified this term to "aneurismal bone cyst". They may be associated with bone tumors.
The simple bone cyst is a common, benign, fluid-containing lesion, most commonly found in the metaphysis of long bones, typically the proximal humerus or femur. Pathologic fractures are common, often with minor trauma. These cysts typically resolve after skeletal maturity and are not typically associated with bone tumors. The cause is unknown. These were first recognised as a distinct entity in 1910. Jaffe and Lichtenstein provided a detailed discussion of simple bone cysts in 1942.The traumatic bone cyst, also referred to as a simple bone cyst or hemorrhagic cyst, is a pseudocyst that most commonly affects the mandible of young individuals. It is a benign empty or fluid-containing cavity within the mandible body that does not have evidence of a true epithelial lining. This type of bone cyst is a condition found in the long bones and jaws. There is no definitive cause, though it relates to trauma in the oral region. The likelihood of males being affected by this condition is frequently greater than in females. It appears on radiographs as a unilocular radiolucent area with an irregular but well-defined outline. This term was first described by Lucas in 1929.
References
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Ectopic kidney | Ectopic kidney describes a kidney that is not located in its usual position. It results from the kidney failing to ascend from its origin in the true pelvis or from a superiorly ascended kidney located in the thorax.It has an incidence of approximately 1/900.
See also
Crossed dystopia
References
== External links == |
Acral persistent papular mucinosis | Acral persistent papular mucinosis is a skin condition caused by fibroblasts producing abnormally large amounts of mucopolysaccharides, characterized by bilaterally symmetrical, flesh-colored papules localized to the hands and wrists.: 185
See also
Papular mucinosis
List of cutaneous conditions
References
== External links == |
Zieves syndrome | Zieves syndrome is an acute metabolic condition that can occur during withdrawal from prolonged heavy alcohol use. It is defined by hemolytic anemia (with spur cells and acanthocytes), hyperlipoproteinaemia (excessive blood lipoprotein), jaundice (elevation of unconjugated bilirubin), and abdominal pain. The underlying cause is liver delipidization. This is distinct from alcoholic hepatitis which, however, may present simultaneously or develop later.Diagnosis of Zieves syndrome should be considered in patients with prolonged alcohol use (especially after an episode of binge drinking) with an elevation of unconjugated bilirubin and without obvious signs of gastrointestinal bleeding.
Pathogenesis
The proposed mechanism of the characteristic haemolytic anaemia in Zieves syndrome is due to alteration of the red cell metabolism, namely pyruvate kinase instability leaving them susceptible to circulating hemolysin such as lysolecithin. Changes in membrane lipid compositions such as increased cholesterol and polyunsaturated fatty acid (PUFA) have been reported during the hemolytic phase.
Diagnosis
The diagnosis is demonstrated by the triad of alcoholic hepatitis or cirrhosis, hemolytic anemia, and hyperlipidemia.
Treatment
Definitive treatment for Zieves syndrome is alcohol cessation. Individuals with markedly elevated triglycerides, particularly with a history of pancreatitis or intracerebral hemorrhage, may require plasmapharesis to avoid complications associated with hypertriglyceridemia.
History
Zieves syndrome was initially described in 1958. Dr. Leslie Zieve described patients with a combination of alcoholic liver disease, hemolytic anemia and hypertriglyceridemia.
References
== External links == |
Thyrotoxic periodic paralysis | Thyrotoxic periodic paralysis (TPP) is a condition featuring attacks of muscle weakness in the presence of hyperthyroidism (overactivity of the thyroid gland). Hypokalemia (a decreased potassium level in the blood) is usually present during attacks. The condition may be life-threatening if weakness of the breathing muscles leads to respiratory failure, or if the low potassium levels lead to cardiac arrhythmias (irregularities in the heart rate). If untreated, it is typically recurrent in nature.The condition has been linked with genetic mutations in genes that code for certain ion channels that transport electrolytes (sodium and potassium) across cell membranes. The main ones are the L-type calcium channel α1-subunit and potassium inward rectifier 2.6; it is therefore classified as a channelopathy. The abnormality in the channel is thought to lead to shifts of potassium into cells, under conditions of high thyroxine (thyroid hormone) levels, usually with an additional precipitant.
Treatment of the hypokalemia, followed by correction of the hyperthyroidism, leads to complete resolution of the attacks. It occurs predominantly in males of Chinese, Japanese, Vietnamese, Filipino, and Korean descent. TPP is one of several conditions that can cause periodic paralysis.
Signs and symptoms
An attack often begins with muscle pain, cramping, and stiffness. This is followed by weakness or paralysis that tends to develop rapidly, usually in late evening or the early hours of the morning. The weakness is usually symmetrical; the limb muscles closer to the trunk (proximal) are predominantly affected, and weakness tends to start in the legs and spread to the arms. Muscles of the mouth and throat, eyes, and breathing are usually not affected, but occasionally weakness of the respiratory muscles can cause life-threatening respiratory failure. Attacks typically resolve within several hours to several days, even in the absence of treatment. On neurological examination during an attack, flaccid weakness of the limbs is noted; reflexes are usually diminished, but the sensory system is unaffected. Mental status is not affected.Attacks may be brought on by physical exertion, drinking alcohol, or eating food high in carbohydrates or salt. This may explain why attacks are more common in summer when more people drink sugary drinks and engage in exercise. Exercise-related attacks tend to occur during a period of rest immediately after exercise; exercise may, therefore, be recommended to abort an attack.There may be symptoms of thyroid overactivity, such as weight loss, a fast heart rate, tremor, and perspiration; but such symptoms occur in only half of all cases. The most common type of hyperthyroidism, Graves disease, may additionally cause eye problems (Graves ophthalmopathy) and skin changes of the legs (pretibial myxedema). Thyroid disease may also cause muscle weakness in the form of thyrotoxic myopathy, but this is constant rather than episodic.
Causes
Genetics
Genetic mutations in the L-type calcium channel α1-subunit (Cav1.1) have been described in Southern Chinese with TPP. The mutations are located in a different part of the gene from those described in the related condition familial periodic paralysis. In TPP, the mutations described are single-nucleotide polymorphisms located in the hormone response element responsive to thyroid hormone, implying that transcription of the gene and production of ion channels may be altered by increased thyroid hormone levels. Furthermore, mutations have been reported in the genes coding for potassium voltage-gated channel, Shaw-related subfamily, member 4 (Kv3.4) and sodium channel protein type 4 subunit alpha (Na41.4).Of people with TPP, 33% from various populations were demonstrated to have mutations in KCNJ18, the gene coding for Kir2.6, an inward-rectifier potassium ion channel. This gene, too, harbors a thyroid response element.Certain forms of human leukocyte antigen (HLA)—especially B46, DR9, DQB1*0303, A2, Bw22, AW19, B17, and DRW8—are more common in TPP. Linkage to particular forms of HLA, which plays a central role in the immune response, might imply an immune system cause, but it is uncertain whether this directly causes TPP or whether it increases the susceptibility to Graves disease, a known autoimmune disease.
Thyroid disease
The most common underlying form of thyroid disease associated with TPP is Graves disease, a syndrome due to an autoimmune reaction that leads to overproduction of thyroid hormone. TPP has also been described in people with other thyroid problems such as thyroiditis, toxic nodular goiter, toxic adenoma, TSH-producing pituitary adenoma, excessive ingestion of thyroxine or iodine, and amiodarone-induced hyperthyroidism.
Mechanism
The muscle weakness and increased risk of irregular heart beat in TPP result from markedly reduced levels of potassium in the bloodstream. Potassium is not in fact lost from the body, but increased Na+/K+-ATPase activity (the enzyme that moves potassium into cells and keeps sodium in the blood) leads to shift of potassium into tissues, and depletes the circulation. In other types of potassium derangement, the acid-base balance is usually disturbed, with metabolic alkalosis and metabolic acidosis often being present. In TPP, these disturbances are generally absent. Hypokalemia leads to hyperpolarization of muscle cells, making the neuromuscular junction less responsive to normal nerve impulses and leading to decreased contractility of the muscles.It is not clear how the described genetic defects increase the Na+/K+-ATPase activity, but it is suspected that the enzyme becomes more active due to increased thyroid hormone levels. Hyperthyroidism increases the levels of catecholamines (such as adrenaline) in the blood, increasing Na+/K+-ATPase activity. The enzyme activity is then increased further by the precipitating causes. For instance, increased carbohydrate intake leads to increased insulin levels; this is known to activate Na+/K+-ATPase. Once the precipitant is removed, the enzyme activity returns to normal levels. It has been postulated that male hormones increase Na+/K+-ATPase activity, and that this explains why males are at a higher risk of TPP despite thyroid disease being more common in females.TPP is regarded as a model for related conditions, known as "channelopathies", which have been linked with mutations in ion channels; the majority of these conditions occurs episodically.
Diagnosis
Hypokalemia (low blood potassium levels) commonly occurs during attacks; levels below 3.0 mmol/L are typically encountered. Magnesium and phosphate levels are often found to be decreased. Creatine kinase levels are elevated in two thirds of cases, usually due to a degree of muscle injury; severe elevations suggestive of rhabdomyolysis (muscle tissue destruction) are rare. Electrocardiography (ECG/EKG) may show tachycardia (a fast heart rate) due to the thyroid disease, abnormalities due to cardiac arrhythmia (atrial fibrillation, ventricular tachycardia), and conduction changes associated with hypokalemia (U waves, QRS widening, QT prolongation, and T wave flattening). Electromyography shows changes similar to those encountered in myopathies (muscle diseases), with a reduced amplitude of the compound muscle action potentials (CMAPs); they resolve when treatment has commenced.TPP is distinguished from other forms of periodic paralysis (especially hypokalemic periodic paralysis) with thyroid function tests on the blood. These are normal in the other forms, and in thyrotoxicosis the levels of thyroxine and triiodothyronine are elevated, with resultant suppression of TSH production by the pituitary gland. Various other investigations are usually performed to separate the different causes of hyperthyroidism.
Treatment
In the acute phase of an attack, administration of potassium will quickly restore muscle strength and prevent complications. However, caution is advised as the total amount of potassium in the body is not decreased, and it is possible for potassium levels to overshoot ("rebound hyperkalemia"); slow infusions of potassium chloride are therefore recommended while other treatment is commenced.The effects of excess thyroid hormone typically respond to the administration of a non-selective beta blocker, such as propranolol (as most of the symptoms are driven by increased levels of adrenaline and its effect on the β-adrenergic receptors). Subsequent attacks may be prevented by avoiding known precipitants, such as high salt or carbohydrate intake, until the thyroid disease has been adequately treated.Treatment of the thyroid disease usually leads to resolution of the paralytic attacks. Depending on the nature of the disease, the treatment may consist of thyrostatics (drugs that reduce production of thyroid hormone), radioiodine, or occasionally thyroid surgery.
Epidemiology
TPP occurs predominantly in males of Chinese, Japanese, Vietnamese, Filipino, and Korean descent, as well as Thais, with much lower rates in people of other ethnicities. In Chinese and Japanese people with hyperthyroidism, 1.8–1.9% experience TPP. This is in contrast to North America, where studies report a rate of 0.1–0.2%. Native Americans, who share a genetic background with East Asians, are at an increased risk.The typical age of onset is 20–40. It is unknown why males are predominantly affected, with rates in males being 17- to 70-fold those in females, despite thyroid overactivity being much more common in women.
History
After several case reports in the 18th and 19th centuries, periodic paralysis was first described in full by the German neurologist Carl Friedrich Otto Westphal (1833–1890) in 1885. In 1926 the Japanese physician Tetsushiro Shinosaki, from Fukuoka, observed the high rate of thyroid disease in Japanese people with periodic paralysis. The first English-language report, in 1931, originated from Dunlap and Kepler, physicians at the Mayo Clinic; they described the condition in a patient with features of Graves disease. In 1937 periodic paralysis was linked with hypokalemia, as well as precipitation of attacks with glucose and insulin. This phenomenon has been used as a diagnostic test.In 1974 it was discovered that propranolol could prevent attacks. The concept of channelopathies and the link with specific ion channel mutations emerged at the end of the 20th century.
References
== External links == |
Herpes simplex | Herpes simplex is a viral infection caused by the herpes simplex virus. Infections are categorized based on the part of the body infected. Oral herpes involves the face or mouth. It may result in small blisters in groups often called cold sores or fever blisters or may just cause a sore throat. Genital herpes, often simply known as herpes, may have minimal symptoms or form blisters that break open and result in small ulcers. These typically heal over two to four weeks. Tingling or shooting pains may occur before the blisters appear. Herpes cycles between periods of active disease followed by periods without symptoms. The first episode is often more severe and may be associated with fever, muscle pains, swollen lymph nodes and headaches. Over time, episodes of active disease decrease in frequency and severity. Other disorders caused by herpes simplex include: herpetic whitlow when it involves the fingers, herpes of the eye, herpes infection of the brain, and neonatal herpes when it affects a newborn, among others.There are two types of herpes simplex virus, type 1 (HSV-1) and type 2 (HSV-2). HSV-1 more commonly causes infections around the mouth while HSV-2 more commonly causes genital infections. They are transmitted by direct contact with body fluids or lesions of an infected individual. Transmission may still occur when symptoms are not present. Genital herpes is classified as a sexually transmitted infection. It may be spread to an infant during childbirth. After infection, the viruses are transported along sensory nerves to the nerve cell bodies, where they reside lifelong. Causes of recurrence may include: decreased immune function, stress, and sunlight exposure. Oral and genital herpes is usually diagnosed based on the presenting symptoms. The diagnosis may be confirmed by viral culture or detecting herpes DNA in fluid from blisters. Testing the blood for antibodies against the virus can confirm a previous infection but will be negative in new infections.The most effective method of avoiding genital infections is by avoiding vaginal, oral, and anal sex. Condom use decreases the risk. Daily antiviral medication taken by someone who has the infection can also reduce spread. There is no available vaccine and once infected, there is no cure. Paracetamol (acetaminophen) and topical lidocaine may be used to help with the symptoms. Treatments with antiviral medication such as aciclovir or valaciclovir can lessen the severity of symptomatic episodes.Worldwide rates of either HSV-1 or HSV-2 are between 60% and 95% in adults. HSV-1 is usually acquired during childhood. Since there is no cure for either HSV-1 or HSV-2, rates of both inherently increase as people age. Rates of HSV-1 are between 70% and 80% in populations of low socioeconomic status and 40% to 60% in populations of improved socioeconomic status. An estimated 536 million people worldwide (16% of the population) were infected with HSV-2 as of 2003 with greater rates among women and those in the developing world. Most people with HSV-2 do not realize that they are infected.
Etymology
The name is from Greek: ἕρπης herpēs, which is related to the meaning "to creep", referring to spreading blisters. The name does not refer to latency.
Signs and symptoms
HSV infection causes several distinct medical disorders. Common infection of the skin or mucosa may affect the face and mouth (orofacial herpes), genitalia (genital herpes), or hands (herpetic whitlow). More serious disorders occur when the virus infects and damages the eye (herpes keratitis), or invades the central nervous system, damaging the brain (herpes encephalitis). People with immature or suppressed immune systems, such as newborns, transplant recipients, or people with AIDS, are prone to severe complications from HSV infections. HSV infection has also been associated with cognitive deficits of bipolar disorder, and Alzheimers disease, although this is often dependent on the genetics of the infected person.
In all cases, HSV is never removed from the body by the immune system. Following a primary infection, the virus enters the nerves at the site of primary infection, migrates to the cell body of the neuron, and becomes latent in the ganglion. As a result of primary infection, the body produces antibodies to the particular type of HSV involved, which can help reduce the odds of a subsequent infection of that type at a different site. In HSV-1-infected individuals, seroconversion after an oral infection helps prevent additional HSV-1 infections such as whitlow, genital herpes, and herpes of the eye. Prior HSV-1 seroconversion seems to reduce the symptoms of a later HSV-2 infection, although HSV-2 can still be contracted.
Many people infected with HSV-2 display no physical symptoms—individuals with no symptoms are described as asymptomatic or as having subclinical herpes. However, infection with herpes can be fatal.
Other
Neonatal herpes simplex is a HSV infection in an infant. It is a rare but serious condition, usually caused by vertical transmission of HSV-1 or -2 from mother to newborn. During immunodeficiency, herpes simplex can cause unusual lesions in the skin. One of the most striking is the appearance of clean linear erosions in skin creases, with the appearance of a knife cut. Herpetic sycosis is a recurrent or initial herpes simplex infection affecting primarily the hair follicles.: 369 Eczema herpeticum is an infection with herpesvirus in patients with chronic atopic dermatitis may result in spread of herpes simplex throughout the eczematous areas.: 373 Herpetic keratoconjunctivitis, a primary infection, typically presents as swelling of the conjunctiva and eyelids (blepharoconjunctivitis), accompanied by small white itchy lesions on the surface of the cornea.
Herpetic sycosis is a recurrent or initial herpes simplex infection affecting primarily the hair follicle.: 369
Bells palsy
Although the exact cause of Bells palsy—a type of facial paralysis—is unknown, it may be related to reactivation of HSV-1. This theory has been contested, however, since HSV is detected in large numbers of individuals having never experienced facial paralysis, and higher levels of antibodies for HSV are not found in HSV-infected individuals with Bells palsy compared to those without. Antivirals may improve the condition slightly when used together with corticosteroids in those with severe disease.
Alzheimers disease
HSV-1 has been proposed as a possible cause of Alzheimers disease. In the presence of a certain gene variation (APOE-epsilon4 allele carriers), HSV-1 appears to be particularly damaging to the nervous system and increases ones risk of developing Alzheimers disease. The virus interacts with the components and receptors of lipoproteins, which may lead to its development.
Pathophysiology
Herpes is contracted through direct contact with an active lesion or body fluid of an infected person. Herpes transmission occurs between discordant partners; a person with a history of infection (HSV seropositive) can pass the virus to an HSV seronegative person. Herpes simplex virus 2 is typically contracted through direct skin-to-skin contact with an infected individual, but can also be contracted by exposure to infected saliva, semen, vaginal fluid, or the fluid from herpetic blisters. To infect a new individual, HSV travels through tiny breaks in the skin or mucous membranes in the mouth or genital areas. Even microscopic abrasions on mucous membranes are sufficient to allow viral entry.
HSV asymptomatic shedding occurs at some time in most individuals infected with herpes. It can occur more than a week before or after a symptomatic recurrence in 50% of cases. Virus enters into susceptible cells by entry receptors
such as nectin-1, HVEM and 3-O sulfated heparan sulfate. Infected people who show no visible symptoms may still shed and transmit viruses through their skin; asymptomatic shedding may represent the most common form of HSV-2 transmission. Asymptomatic shedding is more frequent within the first 12 months of acquiring HSV. Concurrent infection with HIV increases the frequency and duration of asymptomatic shedding. Some individuals may have much lower patterns of shedding, but evidence supporting this is not fully verified; no significant differences are seen in the frequency of asymptomatic shedding when comparing persons with one to 12 annual recurrences to those with no recurrences.Antibodies that develop following an initial infection with a type of HSV can reduce the odds of reinfection with the same virus type. In a monogamous couple, a seronegative female runs a greater than 30% per year risk of contracting an HSV infection from a seropositive male partner. If an oral HSV-1 infection is contracted first, seroconversion will have occurred after 6 weeks to provide protective antibodies against a future genital HSV-1 infection. Herpes simplex is a double-stranded DNA virus.
Diagnosis
Classification
Herpes simplex virus is divided into two types. However, each may cause infections in all areas.
HSV-1 causes primarily mouth, throat, face, eye, and central nervous system infections.
HSV-2 causes primarily anogenital infections.
Examination
Primary orofacial herpes is readily identified by examination of persons with no previous history of lesions and contact with an individual with known HSV infection. The appearance and distribution of sores is typically presents as multiple, round, superficial oral ulcers, accompanied by acute gingivitis. Adults with atypical presentation are more difficult to diagnose. Prodromal symptoms that occur before the appearance of herpetic lesions help differentiate HSV symptoms from the similar symptoms of other disorders, such as allergic stomatitis. When lesions do not appear inside the mouth, primary orofacial herpes is sometimes mistaken for impetigo, a bacterial infection. Common mouth ulcers (aphthous ulcer) also resemble intraoral herpes, but do not present a vesicular stage.Genital herpes can be more difficult to diagnose than oral herpes, since most people have none of the classical symptoms. Further confusing diagnosis, several other conditions resemble genital herpes, including fungal infection, lichen planus, atopic dermatitis, and urethritis.
Laboratory testing
Laboratory testing is often used to confirm a diagnosis of genital herpes. Laboratory tests include culture of the virus, direct fluorescent antibody (DFA) studies to detect virus, skin biopsy, and polymerase chain reaction to test for presence of viral DNA. Although these procedures produce highly sensitive and specific diagnoses, their high costs and time constraints discourage their regular use in clinical practice.Until the 1980s serological tests for antibodies to HSV were rarely useful to diagnosis and not routinely used in clinical practice. The older IgM serologic assay could not differentiate between antibodies generated in response to HSV-1 or HSV-2 infection. However, a glycoprotein G-specific (IgG) HSV test introduced in the 1980s is more than 98% specific at discriminating HSV-1 from HSV-2.
Differential diagnosis
It should not be confused with conditions caused by other viruses in the herpesviridae family such as herpes zoster, which is caused by varicella zoster virus. The differential diagnosis includes hand, foot and mouth disease due to similar lesions on the skin. Lymphangioma circumscriptum and dermatitis herpetiformis may also have a similar appearance.
Prevention
As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than men. On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from infected male to female is about 8–11%.
This is believed to be due to the increased exposure of mucosal tissue to potential infection sites. Transmission risk from infected female to male is around 4–5% annually. Suppressive antiviral therapy reduces these risks by 50%. Antivirals also help prevent the development of symptomatic HSV in infection scenarios, meaning the infected partner will be seropositive but symptom-free by about 50%. Condom use also reduces the transmission risk significantly. Condom use is much more effective at preventing male-to-female transmission than vice versa. Previous HSV-1 infection may reduce the risk for acquisition of HSV-2 infection among women by a factor of three, although the one study that states this has a small sample size of 14 transmissions out of 214 couples.However, asymptomatic carriers of the HSV-2 virus are still contagious. In many infections, the first symptom people will have of their own infections is the horizontal transmission to a sexual partner or the vertical transmission of neonatal herpes to a newborn at term. Since most asymptomatic individuals are unaware of their infection, they are considered at high risk for spreading HSV.In October 2011, the anti-HIV drug tenofovir, when used topically in a microbicidal vaginal gel, was reported to reduce herpes virus sexual transmission by 51%.
Barrier methods
Condoms offer moderate protection against HSV-2 in both men and women, with consistent condom users having a 30%-lower risk of HSV-2 acquisition compared with those who never use condoms. A female condom can provide greater protection than the male condom, as it covers the labia. The virus cannot pass through a synthetic condom, but a male condoms effectiveness is limited because herpes ulcers may appear on areas not covered by it. Neither type of condom prevents contact with the scrotum, anus, buttocks, or upper thighs, areas that may come in contact with ulcers or genital secretions during sexual activity. Protection against herpes simplex depends on the site of the ulcer; therefore, if ulcers appear on areas not covered by condoms, abstaining from sexual activity until the ulcers are fully healed is one way to limit risk of transmission. The risk is not eliminated, however, as viral shedding capable of transmitting infection may still occur while the infected partner is asymptomatic. The use of condoms or dental dams also limits the transmission of herpes from the genitals of one partner to the mouth of the other (or vice versa) during oral sex. When one partner has a herpes simplex infection and the other does not, the use of antiviral medication, such as valaciclovir, in conjunction with a condom, further decreases the chances of transmission to the uninfected partner. Topical microbicides that contain chemicals that directly inactivate the virus and block viral entry are being investigated.
Antivirals
Antivirals may reduce asymptomatic shedding; asymptomatic genital HSV-2 viral shedding is believed to occur on 20% of days per year in patients not undergoing antiviral treatment, versus 10% of days while on antiviral therapy.
Pregnancy
The risk of transmission from mother to baby is highest if the mother becomes infected around the time of delivery (30% to 60%), since insufficient time will have occurred for the generation and transfer of protective maternal antibodies before the birth of the child. In contrast, the risk falls to 3% if the infection is recurrent, and is 1–3% if the woman is seropositive for both HSV-1 and HSV-2, and is less than 1% if no lesions are visible. Women seropositive for only one type of HSV are only half as likely to transmit HSV as infected seronegative mothers. To prevent neonatal infections, seronegative women are recommended to avoid unprotected oral-genital contact with an HSV-1-seropositive partner and conventional sex with a partner having a genital infection during the last trimester of pregnancy. Mothers infected with HSV are advised to avoid procedures that would cause trauma to the infant during birth (e.g. fetal scalp electrodes, forceps, and vacuum extractors) and, should lesions be present, to elect caesarean section to reduce exposure of the child to infected secretions in the birth canal. The use of antiviral treatments, such as aciclovir, given from the 36th week of pregnancy, limits HSV recurrence and shedding during childbirth, thereby reducing the need for caesarean section.Aciclovir is the recommended antiviral for herpes suppressive therapy during the last months of pregnancy. The use of valaciclovir and famciclovir, while potentially improving compliance, have less-well-determined safety in pregnancy.
Management
No method eradicates herpes virus from the body, but antiviral medications can reduce the frequency, duration, and severity of outbreaks. Analgesics such as ibuprofen and paracetamol (acetaminophen) can reduce pain and fever. Topical anesthetic treatments such as prilocaine, lidocaine, benzocaine, or tetracaine can also relieve itching and pain.
Antiviral
Several antiviral drugs are effective for treating herpes, including aciclovir (acyclovir), valaciclovir, famciclovir, and penciclovir. Aciclovir was the first discovered and is now available in generic. Valaciclovir is also available as a generic and is slightly more effective than aciclovir for reducing lesion healing time.Evidence supports the use of aciclovir and valaciclovir in the treatment of herpes labialis as well as herpes infections in people with cancer. The evidence to support the use of aciclovir in primary herpetic gingivostomatitis is weaker.
Topical
A number of topical antivirals are effective for herpes labialis, including aciclovir, penciclovir, and docosanol.
Alternative medicine
Evidence is insufficient to support use of many of these compounds, including echinacea, eleuthero, L-lysine, zinc, monolaurin bee products, and aloe vera. While a number of small studies show possible benefit from monolaurin, L-lysine, aspirin, lemon balm, topical zinc, or licorice root cream in treatment, these preliminary studies have not been confirmed by higher-quality randomized controlled studies.
Prognosis
Following active infection, herpes viruses establish a latent infection in sensory and autonomic ganglia of the nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of the nucleus of a nerves cell body. HSV latency is static; no virus is produced; and is controlled by a number of viral genes, including latency-associated transcript.Many HSV-infected people experience recurrence within the first year of infection. Prodrome precedes development of lesions. Prodromal symptoms include tingling (paresthesia), itching, and pain where lumbosacral nerves innervate the skin. Prodrome may occur as long as several days or as short as a few hours before lesions develop. Beginning antiviral treatment when prodrome is experienced can reduce the appearance and duration of lesions in some individuals. During recurrence, fewer lesions are likely to develop and are less painful and heal faster (within 5–10 days without antiviral treatment) than those occurring during the primary infection. Subsequent outbreaks tend to be periodic or episodic, occurring on average four or five times a year when not using antiviral therapy.
The causes of reactivation are uncertain, but several potential triggers have been documented. A 2009 study showed the protein VP16 plays a key role in reactivation of the dormant virus. Changes in the immune system during menstruation may play a role in HSV-1 reactivation. Concurrent infections, such as viral upper respiratory tract infection or other febrile diseases, can cause outbreaks. Reactivation due to other infections is the likely source of the historic terms cold sore and fever blister.
Other identified triggers include local injury to the face, lips, eyes, or mouth; trauma; surgery; radiotherapy; and exposure to wind, ultraviolet light, or sunlight.The frequency and severity of recurrent outbreaks vary greatly between people. Some individuals outbreaks can be quite debilitating, with large, painful lesions persisting for several weeks, while others experience only minor itching or burning for a few days. Some evidence indicates genetics play a role in the frequency of cold sore outbreaks. An area of human chromosome 21 that includes six genes has been linked to frequent oral herpes outbreaks. An immunity to the virus is built over time. Most infected individuals experience fewer outbreaks and outbreak symptoms often become less severe. After several years, some people become perpetually asymptomatic and no longer experience outbreaks, though they may still be contagious to others. Immunocompromised individuals may experience longer, more frequent, and more severe episodes. Antiviral medication has been proven to shorten the frequency and duration of outbreaks. Outbreaks may occur at the original site of the infection or in proximity to nerve endings that reach out from the infected ganglia. In the case of a genital infection, sores can appear at the original site of infection or near the base of the spine, the buttocks, or the back of the thighs.
HSV-2-infected individuals are at higher risk for acquiring HIV when practicing unprotected sex with HIV-positive persons, in particular during an outbreak with active lesions.
Epidemiology
Worldwide rates of either HSV-1 and/or HSV-2 are between 60 and 95% in adults. HSV-1 is more common than HSV-2, with rates of both increasing as people age. HSV-1 rates are between 70% and 80% in populations of low socioeconomic status and 40% to 60% in populations of improved socioeconomic status. An estimated 536 million people or 16% of the population worldwide were infected with HSV-2 as of 2003 with greater rates among women and in those in the developing world. Rates of infection are determined by the presence of antibodies against either viral species.In the US, 58% of the population is infected with HSV-1 and 16% are infected with HSV-2. Among those HSV-2-seropositive, only 19% were aware they were infected. During 2005–2008, the prevalence of HSV-2 was 39% in blacks and 21% in women.The annual incidence in Canada of genital herpes due to HSV-1 and HSV-2 infection is not known (for a review of HSV-1/HSV-2 prevalence and incidence studies worldwide, see Smith and Robinson 2002). As many as one in seven Canadians aged 14 to 59 may be infected with herpes simplex type 2 virus and more than 90 per cent of them may be unaware of their status, a new study suggests. In the United States, it is estimated that about 1,640,000 HSV-2 seroconversions occur yearly (730,000 men and 910,000 women, or 8.4 per 1,000 persons).In British Columbia in 1999, the seroprevalence of HSV-2 antibody in leftover serum submitted for antenatal testing revealed a prevalence of 17%, ranging from 7% in women 15–19 years old to 28% in those 40–44 years.In Norway, a study published in 2000 found that up to 70–90% of genital initial infections were due to HSV-1.In Nova Scotia, 58% of 1,790 HSV isolates from genital lesion cultures in women were HSV-1; in men, 37% of 468 isolates were HSV-1.
History
Herpes has been known for at least 2,000 years. Emperor Tiberius is said to have banned kissing in Rome for a time due to so many people having cold sores. In the 16th-century Romeo and Juliet, blisters "oer ladies lips" are mentioned. In the 18th century, it was so common among prostitutes that it was called "a vocational disease of women". The term herpes simplex appeared in Richard Boultons A System of Rational and Practical Chirurgery in 1713, where the terms herpes miliaris and herpes exedens also appeared. Herpes was not found to be a virus until the 1940s.Herpes antiviral therapy began in the early 1960s with the experimental use of medications that interfered with viral replication called deoxyribonucleic acid (DNA) inhibitors. The original use was against normally fatal or debilitating illnesses such as adult encephalitis, keratitis, in immunocompromised (transplant) patients, or disseminated herpes zoster. The original compounds used were 5-iodo-2-deoxyuridine, AKA idoxuridine, IUdR, or(IDU) and 1-β-D-arabinofuranosylcytosine or ara-C, later marketed under the name cytosar or cytarabine. The usage expanded to include topical treatment of herpes simplex, zoster, and varicella. Some trials combined different antivirals with differing results. The introduction of 9-β-D-arabinofuranosyladenine, (ara-A or vidarabine), considerably less toxic than ara-C, in the mid-1970s, heralded the way for the beginning of regular neonatal antiviral treatment. Vidarabine was the first systemically administered antiviral medication with activity against HSV for which therapeutic efficacy outweighed toxicity for the management of life-threatening HSV disease. Intravenous vidarabine was licensed for use by the U.S. Food and Drug Administration in 1977. Other experimental antivirals of that period included: heparin, trifluorothymidine (TFT), Ribivarin, interferon, Virazole, and 5-methoxymethyl-2-deoxyuridine (MMUdR). The introduction of 9-(2-hydroxyethoxymethyl)guanine, AKA aciclovir, in the late 1970s raised antiviral treatment another notch and led to vidarabine vs. aciclovir trials in the late 1980s. The lower toxicity and ease of administration over vidarabine has led to aciclovir becoming the drug of choice for herpes treatment after it was licensed by the FDA in 1998. Another advantage in the treatment of neonatal herpes included greater reductions in mortality and morbidity with increased dosages, which did not occur when compared with increased dosages of vidarabine. However, aciclovir seems to inhibit antibody response, and newborns on aciclovir antiviral treatment experienced a slower rise in antibody titer than those on vidarabine.
Society and culture
Some people experience negative feelings related to the condition following diagnosis, in particular if they have acquired the genital form of the disease. Feelings can include depression, fear of rejection, feelings of isolation, fear of being found out, and self-destructive feelings. Herpes support groups have been formed in the United States and the UK, providing information about herpes and running message forums and dating websites for affected people. People with the herpes virus are often hesitant to divulge to other people, including friends and family, that they are infected. This is especially true of new or potential sexual partners whom they consider casual.In a 2007 study, 1,900 people (25% of which had herpes) ranked genital herpes second for social stigma, out of all sexually transmitted diseases (HIV took the top spot for STD stigma).
Support groups
United States
An important source of support is the National Herpes Resource Center which arose from the work of the American Sexual Health Association (ASHA). The ASHA was created in 1914 in response to the increase in sexually transmitted diseases that had spread during World War I. During the 1970s, there was an increase in sexually transmitted diseases. One of the diseases that increased dramatically was genital herpes. In response, ASHA created the National Herpes Resource Center in 1979. The Herpes Resource Center (HRC) was designed to meet the growing need for education and awareness about the virus. One of the projects of the HRC was to create a network of local support (HELP) groups. The goal of these HELP groups was to provide a safe, confidential environment where participants can get accurate information and share experiences, fears, and feelings with others who are concerned about herpes.
UK
In the UK, the Herpes Association (now the Herpes Viruses Association) was started in 1982, becoming a registered charity with a Dept of Health grant in 1985. The charity started as a string of local group meetings before acquiring an office and a national spread.
Research
Research has gone into vaccines for both prevention and treatment of herpes infections. Unsuccessful clinical trials have been conducted for some glycoprotein subunit vaccines. As of 2017 |
Herpes simplex | , the future pipeline includes several promising replication-incompetent vaccine proposals while two replication-competent (live-attenuated) HSV vaccine are undergoing human testing.A genomic study of the herpes simplex type 1 virus confirmed the human migration pattern theory known as the out-of-Africa hypothesis.
References
External links
Herpes simplex at Curlie |
Paroxysmal extreme pain disorder | Paroxysmal extreme pain disorder originally named familial rectal pain syndrome, is a rare disorder whose most notable features are pain in the mandibular, ocular and rectal areas as well as flushing. PEPD often first manifests at the beginning of life, perhaps even in utero, with symptoms persisting throughout life. PEPD symptoms are reminiscent of primary erythromelalgia, as both result in flushing and episodic pain, though pain is typically present in the extremities for primary erythromelalgia. Both of these disorders have recently been shown to be allelic, both caused by mutations in the voltage-gated sodium channel NaV1.7 encoded by the gene SCN9A. A different mutation in "SCN9A" causes congenital insensitivity to pain.
Symptoms and signs
The most distinctive feature of PEPD is episodic burning pain of the rectum, ocular, and mandibular regions. It should be stressed that while pain often originates or is centered in these areas it can also spread or be diffuse in nature. Pain experienced by patients with this disorder should not be underestimated as women with the disorder who have also given birth describe PEPD pain as worse than labor pain. Concomitant with this pain is typically flushing, often in an area associated with the pain.During attacks in infants, the child often looks startled or terrified and can scream inconsolably. These attacks can be precipitated by injections, defecation, wiping of the perineum, eating, or the consumption of oral medication. When attacks occur due to such precipitation, pain and flushing are often present in the area of attack precipitation, though symptoms may also be diffuse in nature.Other symptoms may include hypersalivation when attacks are localized in the mandibular region, or leg weakness after foot trauma. A prominent non-physical symptom are tonic non-epileptic seizures. Such seizures are more common in infancy and childhood than during adulthood. In older children, inconsolable screaming usually precedes such attack, followed by apnea, paleness, and stiffness. Such stiffness can last from seconds to a few minutes.Attack precipitants are usually physical in nature, such as defecation, eating, or taking medicine. Some less common precipitants are micturition, coitus, and painful stimuli. There are also non-physical precipitants, such as the thought or sight of food. In general attacks tend to occur in the precipitated area, though this is not always the case. While some individuals have described a build-up to attacks, in general they tend to be abrupt. The duration of these attacks can be from a few seconds to two hours.Patients are largely normal between attacks. The only notable interictal problem is constipation, likely due to apprehension of precipitating an attack. This symptom often decreases with age, likely due to coping mechanisms such as the use of stool softeners.
Cause
The voltage-gated sodium channel NaV1.7 is expressed in nociceptive and sympathetic neurons, where it aids in action potential creation and regulation. The mutations in this gene that have received study all alter the channels ability to inactivate. Sodium channel inactivation is vital for the proper cessation of action potentials. The decreased inactivation caused by these mutations, then, is expected to cause prolonged action potentials and repetitive firing. Such altered firing will cause increased pain sensation and increased sympathetic nervous system activity, producing the phenotype observed in patients with PEPD.
Pathophysiology
There are a total of 8 mutations that account for the disorder in 8 of 14 studied families. These mutations are clustered in four regions throughout the channel: the linker between domains 2 and 3 (D2-3), the intracellular segment linking segments 4 and 5 in domain 3 (D3S4-5), the linker between domains 3 and 4 (D3-4) and the intracellular segment linking segments 4 and 5 in domain 4 (D4S4-5). The mutations in the D3S4-5 region (I1461T, F1462V and T1461I) are located in or next to an IFM motif that is conserved across all voltage-gated sodium channels. Mutagenesis studies of this region have shown that it acts as part of the inactivation gate, pivoting to block the central pore. Not surprisingly then, the two of these mutations that have received further study show incomplete inactivation. When the IFM motif pivots to block the central pore it interacts with residues in the D3S4-5 region. There are three mutations in this region (V1298F, F1298D and V1299F) that are believed to alter the interaction with the inactivation gate. While this region has been studied by mutagenesis these specific mutations have not all received attention, though they are expected to produce changes similar to the aforementioned IFM region mutations. The M1627K mutation in the D4S4-5 region may also affect a residue involved in interacting with the IFM inactivation motif. This would explain the observed alteration of inactivation and the broadening of a window current. One of the affected families with the R996C mutation, pedigree 12, has a single individual who also has the V1298D mutation. The individual in this family with the compound mutation is the most severely affected, suggesting that the R996C mutation may cause a less severe phenotype. The less severe phenotype of the pedigree 4 family is in concordance with this theory. It is unclear how the R996C mutation affects channel function.
Diagnosis
Hematological, biochemical and metabolic investigations on blood and urine between attacks are normal, as are karyotyping and EKG recordings. EKG recordings during attacks show sinus tachycardia. CT, MRI, EMG and nerve conduction studies produce normal results. EEG recordings are normal between attacks but show early-onset tachycardia during attacks. On the Neuropathic Pain Questionnaire patients indicated that pain during attacks is extremely unpleasant and typically felt deep, though also superficial on occasion. Aside from presentation of typical symptoms (see Signs and symptoms above) mutation of the gene SCN9A aids in appropriate diagnosis as this gene is mutated in 8 of 14 studied families.
Treatment
Carbamazepine is at least partly effective at reducing the number or severity of attacks in the majority of PEPD patients. High doses of this drug may be required, perhaps explaining the lack of effect in some individuals. While other anti-epileptic drugs, gabapentin and topiramate, have limited effect in some patients, they have not been shown to be generally effective. Opiate derived analgesics are also largely ineffective, with only sporadic cases of beneficial effect.
Epidemiology
PEPD is an extremely rare disorder with only 15 known affected families. There are some cases, however, of individuals originally diagnosed with epilepsy who are later determined to have PEPD. This suggests that rates of PEPD may be higher than currently believed.
History
PEPD was originally described by Hayden and Grossman in 1959. At that time it was not given a specific name. A later report, by Dugan in 1972, labeled this disorder as familial rectal pain syndrome. This name was used for 33 years, until a consortium of patients and clinicians was formed in the hopes of discovering the genetic cause of PEPD. During this process a number of patients expressed dissatisfaction with the name and after considerable discussion between patients and clinicians the name paroxysmal extreme pain disorder was agreed upon in 2005.
References
== External links == |
Dissociated vertical deviation | Dissociated vertical deviation (DVD) is an eye condition which occurs in association with a squint, typically infantile esotropia. The exact cause is unknown, although it is logical to assume it is from faulty innervation of eye muscles.
Presentation
The eye drifts upward spontaneously or after being covered. The condition usually affects both eyes, but can occur unilaterally or asymmetrically. It is often associated with latent or manifest-latent nystagmus and, as well as occurring with infantile esotropia, can also be found associated with exotropias and vertical deviations.
DVDs are usually controlled from occurring with both eyes open, but may become manifest with inattention. Usually some level of dissociative occlusion is required - to trigger the brain to suppress vision in that eye and then not control a DVD from occurring. The level of dissociative occlusion required may involve using a red filter, a darker filter or complete occlusion (e.g. with a hand).
Onset
DVD typically becomes apparent between 18 months and three years of age, however, the difficulties of achieving the prolonged occlusion required for accurate detection in the very young make it possible that onset is generally earlier than these figures suggest.
Mechanism
Dissociation refers to the situation where the innervation of one eye causes it to move involuntarily and independently of the other eye. Usually both eyes work together as described by Herings and Sherringtons laws of innervation. A DVD is a slow upward and sometimes temporal movement of one eye, with cortical suppression of the vision in that eye while it is deviated. On returning downward and possibly inward to take up fixation, the DVD slow movement will be reversed.
The dissociative movement seen objectively should not be confused with the dissociation that occurs subjectively - as when the brain begins to not visualise both images simultaneously (by ignoring or suppressing vision in that eye).
Diagnosis
A test called the Bielschowsky Darkening Wedge Test can be used to reveal and diagnose the presence of dissociated vertical deviation, although any (or no) amount of dissociative occlusion may also prompt it to occur.
The patient is asked to look at a light. One eye is covered and a filter is placed in front of the other eye. The density or opacity of this filter is gradually increased, and the behaviour of the eye under the cover (not of the eye beneath the filter) is observed. Initially, if DVD is present, the covered eye will have elevated, but as the filter opacity is increased the eye under the cover will gradually move downwards. This Bielschowsky phenomenon is present in over 50% of persons with prominent DVD, all the more if the DVD is asymmetric and amblyopia is present as well.The Bielschowsky phenomenon is also present in the horizontal plane in patients with prominent DHD (dissociated horizontal deviation).
Differential diagnosis
DVD is often mistaken for over-action of the inferior oblique extra-ocular muscles. DVD can be revealed on ocular movement testing when one eye is occluded by the nose on lateral gaze. This eye will then elevate, simulating an inferior oblique over action. However, in a unilateral case, overaction of the superior rectus muscle in the unaffected dominant eye, can also be a causing factor as well as causing a V pattern exophoria.
Treatment
Management of this condition is surgical and typically involves reducing the strength of the superior rectus muscle or anterior transposition of the inferior oblique muscle of the affected eyes.Several different surgical procedures exist for the correction of DVD including: inferior oblique anteriorization, inferior oblique anteriorization plus resection, superior rectus recession, superior rectus recession plus posterior fixation suture, and inferior oblique myectomy, though there is insufficient evidence to determine which procedure results in the best outcomes for patients.
See also
Strabismus
Strabismus surgery
Pediatric ophthalmology
Infantile esotropia
== References == |
Recurrent painful ophthalmoplegic neuropathy | Recurrent painful ophthalmoplegic neuropathy (RPON), previously known as ophthalmoplegic migraine (OM), is a rare neurological disorder that is characterized by repeated headache attacks and reversible ipsilateral paresis of one or more ocular cranial nerves (CN). Oculomotor nerve (CNIII) is by far the most common cranial nerve involves in RPON, while abducens nerve (CNVI) and trochlear nerve (CNIV) involvements are also reported. Globally, RPON was estimated to have an annual incidence rate of 0.7 per million as of 1990, no further epidemiological studies have been conducted. It occurs more often in children and females.Although the etiology of RPON is unknown owing to the rarity of this disease, various potential theories including migrainous and neuropathic mechanisms have been developed. Diagnosis is based on physical examination, magnetic resonance imaging (MRI), and ruling out other possible causes. Despite the fact that there are currently no evidence-based treatment guidelines for RPON, the most commonly used medications are corticosteroids that have been proven effective in alleviating the symptoms. As for people who are unresponsive to steroids, other treatments, such as anti-migraine drugs, botulinum toxin injection and strabismus surgery, may be utilized. For prevention, several medications including calcium channel blockers may be used. However, none have been proved consistently effective. RPON has a good overall prognosis as a result of the self-limiting nature of the condition, but permanent neurological damage may accumulate over repeated episodes.
Signs and symptoms
The typical symptoms of RPON are recurrent headaches and ipsilateral paralysis of the extraocular muscles (ophthalmoplegia) that are responsible for controlling eye movements. People with RPON experience different severity of pain, duration of symptoms, and frequency of attacks, which are also dependent on the treatment they received. The attacks of RPON usually occur on the same side of the head in subsequent episodes.
Headache
The most common type of headache is migraine-like, usually accompanied by symptoms such as nausea, vomiting, photophobia, or phonophobia. Less commonly, RPON can occur without migrainous headache nor accompanied by the classical migrainous symptoms. The frequency of headaches can range from several times per month to once in several years, while the duration varies from several days to a week, which lasts longer than that of a typical migraine.
Ophthalmoplegia
Ophthalmoplegia usually occurs either concurrently or within 1 week after the onset of headache, and less commonly up to 2 weeks. The ocular manifestation of RPON depend on which ocular cranial nerve is being affected. CNIII is involved in the vast majority of cases, but the involvement of CNVI and CNIV is also reported in studies. Typical ocular signs involving CNIII include outwards and downwards drifting of eyes (strabismus), difficulty in controlling inward and upward eye movements, drooping of eyelid (ptosis) and double vision. Pupil dilation (mydriasis) and reduction in pupillary light reflexes can also be observed as pupillomotor fibers are also affected by CNIII paralysis. Rare cases involve abducens nerve paralysis affects lateral eye movement while trochlear nerve paralysis affects vertical eye movement. Similar to headache, ophthalmoplegia usually resolve gradually and completely over time, but recovery may be incomplete after several episodes.
Pathophysiology
The etiology of RPON is still unknown and remains controversial - some scientists believe that RPON is a subtype of migraine, while others believe that it is a neuropathic disorder. As such, different potential etiologic mechanisms have been proposed based on case reports, including migrainous and neuropathic mechanisms. Yet, the renaming of RPON from OM indicates that the neuropathic cause may play a more important role than the migrainous cause in the pathophysiology of RPON.
Migrainous mechanism
RPON was previously thought to be having a migrainous origin since it shares some common characteristics with migraine, and their only differences are the intensity and duration of headaches. Therefore, it was postulated that migraine caused ophthalmoplegia in RPON. However, the major argument against a migrainous origin is the long latency period between the onset of headache and ophthalmoplegia (up to 14 days), which is not consistent with a typical migraine. Nevertheless, several migrainous mechanisms have been proposed.
Nerve compression
Compression mechanism is the first theory postulated regarding the pathophysiology of RPON. It is proposed that headache is caused by direct pressure on CNIII (compression neuropathy) within the cavernous sinus due to edema of the walls of the internal carotid artery (ICA) or posterior cerebral artery (PCA) during migraine episodes.
Ischemia
Cavernous section of the ICA and a perforating vessel from the proximal PCA are responsible for supplying CNIII, CNIV, and CNVI. During migraine attacks, vasoconstriction of the ICA and PCA may lead to a reversible and ischemic breakdown of the blood-brain barrier. The blood-brain barrier breakdown results in vasogenic edema, which promotes the development of RPON.
Neuropeptides-induced
Alternatively, it is proposed that migraine-related release of neuropeptides from trigeminal nerve fibers terminating on the circle of Willis might be the cause. Some of the neuropeptides released are potentially toxic, and may induce blood-brain barrier breakdown that accounts for ophthalmoplegia.
Neuropathic mechanism
Additional models have been proposed to explain the cause of RPON. The thickened and enhanced symptomatic nerve, as shown in recent MRI findings, might be indicative of the existence of structural nerve damage in RPON. Therefore, neuropathy is suggested as the primary cause of RPON, either induced by recurrent viral infections or immune-mediated inflammation. However, cerebrospinal fluid (CSF) analyses are normal in the vast majority of RPON cases, which is inconsistent with the findings of autoimmune or inflammatory-mediated pathomechanism. Nevertheless, several neuropathic mechanisms have been proposed.
Benign viral infection
The enhancement and thickening of the oculomotor nerve can occur in a variety of infectious inflammatory conditions. However, spontaneous resolution is unlikely to occur in viral infection, except for benign viral infection that usually causes mild or no symptoms in humans. Therefore, benign viral infection could be an explanation for the development of RPON.
Immune-mediated inflammation
Recent MRI findings have led to the current understanding of RPON as an inflammation-induced neuropathy. Recurrent demyelinating neuropathy is proposed as a pathophysiological pathway because similar MRI findings have been observed in both RPON and chronic inflammatory demyelinating neuropathy. Inflammatory demyelination of the ocular cranial nerves would likely lead to the release of neuropeptides, such as calcitonin gene-related peptide, to the trigeminovascular system. This would irritate the trigeminal sensory fibers, and consequently, a headache as manifested in RPON is triggered.
Diagnosis
Diagnostic criteria
To be diagnosed with RPON, a person must have a minimum of 2 unilateral headache attacks with ipsilateral ocular cranial nerve paralysis that cannot be explained by other causes of headache in ICHD-3 after investigation.
Diagnostic tests
RPON is a diagnosis of exclusion, meaning that other conditions with similar clinical presentation, such as vascular, inflammatory, neoplastic, and infectious causes, must be ruled out before the confirmation of RPON diagnosis. Physical examination, neuroimaging, and laboratory tests are routinely conducted in clinical practice to evaluate this disease.
Physical examination
After obtaining the medical history of people with suspected RPON, thorough eye examination and neurological examination are usually performed to assess the extent of neurological impairment, localize the brain regions being affected, and rule out other possible causes for the symptoms. These involve the assessments of visual acuity, eye movements and alignment, pupillary responses, and mental status.
Neuroimaging
Contrast-enhanced magnetic resonance imaging (MRI) is a diagnostic tool that can facilitate the differentiation of RPON from other diseases. The transient, reversible enhancement or thickening of the ocular motor nerve(s), which can be observed in the MRI scans of a small proportion of affected individuals during acute attacks, is a distinguishing feature of RPON. Cranial nerve enhancement resulted from RPON would gradually disappear as the symptoms subside after an episode, but spontaneous resolution of nerve enhancement is very unlikely to be seen in neoplastic (e.g. schwannoma), inflammatory and infectious diseases. Contrast-enhanced MRI results can also reveal the location of nerve inflammation for disease diagnosis. Although Tolosa–Hunt syndrome (THS) and RPON share many clinical features, THS can be identified by the presence of granulomatous inflammation in the cavernous sinus, superior orbital fissure, or orbit in MRI scans.Magnetic resonance angiography (MRA) or CT angiography (CTA) can be used to examine cerebral blood vessels and to rule out vascular abnormalities, such as an aneurysm. In cases where intracranial vascular lesions, for example, subarachnoid hemorrhage cannot be completely ruled out after performing MRA or CTA, physicians may consider using traditional digital subtraction angiography (DSA) for more detailed investigation.
Laboratory tests
Lumbar punctures and blood tests might be performed on those with RPON to identify other possible causes of cranial neuropathy, including diabetes, inflammatory diseases, infections, tumors, and other systemic diseases that involve either the central nervous system or the peripheral nervous system. The detection of abnormalities in these tests suggests that RPON is highly unlikely to be the culprit in cranial neuropathy, and more diagnostic tests should be done to find out the underlying condition.
Treatment
To date, no clinical trials or treatment guidelines for RPON have been published. Since the evaluation of effective treatments is entirely based on evidence from a limited number of case reports, there is some uncertainty surrounding the proposed efficacy of the drugs for treating RPON.
Potential treatments for RPON can be divided into three main categories: preventative therapy, symptomatic treatment, and management of residual symptoms.
Preventative therapy
Migraine preventive medications, including beta-blockers (e.g. propranolol), calcium channel blockers (e.g. flunarizine), anticonvulsants (e.g. valproate), and antidepressants (e.g. amitriptyline), may be given to those with RPON with the intent of preventing RPON recurrence. Although the efficacy of these preventives has been proposed in various published case studies, there is a lack of compelling evidence suggesting that these anti-migraine drugs have long-term prophylactic effect on future RPON attacks. The initiation of migraine preventive therapy in RPON is only recommended for people who have typical migraine with frequent attacks as a concurrent condition.
Symptomatic treatment
Corticosteroids are the most frequently reported drugs for treating acute symptoms of RPON. The rationale behind their use in RPON treatment is to reduce ocular cranial nerve inflammation, which is indicated by the presence of nerve enhancement and is also theorized to be a pathophysiological mechanism of RPON, in affected individuals. Early implementation of corticosteroid therapy is considered beneficial to the majority (96.2%) of people with RPON because it can shorten their recovery time and reduce the severity of existing symptoms. Even though various studies have documented the success of using this medication to induce symptomatic relief in affected individuals, the improvement is not as rapid and significant as observed in other inflammatory diseases, such as THS and temporal arteristis. In addition, some steroid non-responders may have worsened RPON symptoms after taking these drugs, suggesting that corticosteroids are not suitable for treating every patient with the condition.Other drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), ergotamine, triptan and acetaminophen, have been investigated for the acute treatment of RPON. However, their efficacy is currently unknown.
Management of residual symptoms
Depending on the severity of symptoms, various treatment options are available to people with persistent ophthalmoplegia. For mild conditions, prism glasses can be prescribed to correct specific types of double vision. In more extreme cases, additional intervention such as botulinum toxin injection and strabismus surgery, might be required to rebalance the actions of the extraocular muscles. This would improve the alignment of the eyes when they are in primary position. Similarly, surgical correction can be performed on individuals with severe ptosis.
Prognosis
The prognosis of RPON is generally considered favorable, with most affected individuals having spontaneous symptom resolution after an attack. However, the accumulated nerve damage from repeated RPON attacks might increase the severity and persistence of ophthalmoplegia. Among people with recurrent episodes of RPON, about 30-54% develop permanent neurological sequelae, such as persistent mydriasis, ptosis, strabismus and double vision.
== References == |
Malum perforans | Malum perforans is a long-lasting, usually painless ulcer that penetrates deep into or through the skin, usually on the sole of the foot (in which case it may be called malum perforans pedis). It is often a complication in diabetes mellitus and other conditions affecting the nerves.
Presentation
These ulcers have punched-out edge and slough in floor, resembling gummatous ulcer. Surrounding area might have loss of sensation.
Cause
This condition results from denervation of areas exposed to day-to-day friction of bony prominences. The denervation may be result of any of the following diseases:
Spinal injuries
Leprosy
Peripheral nerve injury
Diabetic neuropathy
Tabes dorsalis
Transverse myelitis
Meningomyelocele
Syringomyelia
Pathophysiology
Normal pressure and pain sensations are essential for protecting the foot from excessive and prolonged pressures over bony prominences. In insensitive foot, such as in diabetic neuropathy, soft tissues are exposed to excessive pressures without knowledge of the individual. In other words, by nerve damage in the feet, the patients get no feedback on the impact of the feet when walking. These ulcers start with callosity under which suppuration takes place. The pus comes out and a hole forms under which the lesion grows deeper. This leads to punched-out, painless ulcers usually under metatarsal heads, tip of toe, or proximal interphalangeal joint of a hammertoe or on the heel. In non-ambulatory patients, these ulcers are found on buttocks and back of the heel.
Diagnosis
Diagnosis is clinical. Sensation is tested using graded monofilament.
Treatment
The underlying cause of the neuropathy is first treated. Necrotic portions of the wound are removed and the wound is kept moist at all occasions. Infected ulcers are administered antibiotics.
Skin grafting is one option. It has been shown that ultrasound may increase the acceptance of a graft at trophic ulcer sites.
See also
List of cutaneous conditions
References
== External links == |
Brittle asthma | Brittle asthma is a type of asthma distinguishable from other forms by recurrent, severe attacks. There are two subtypes divided by symptoms: Type 1 and Type 2, depending on the stability of the patients maximum speed of expiration, or peak expiratory flow rate (PEFR). Type 1 is characterized by a maintained wide PEF variability despite considerable medical therapy including a dose of inhaled steroids, and Type 2 is characterized by sudden acute attacks occurring in less than three hours without an obvious trigger on a background of well controlled asthma.Brittle asthma is one of the "unstable" subtypes of "difficult asthma", a term used to characterize the less than 5% of asthma cases that do not respond to maximal inhaled treatment, including high doses of corticosteroids combined with additional therapies such as long-acting beta-2 agonists.
Diagnosis
Types
The 2005 Oxford Textbook of Medicine distinguishes type 1 brittle asthma by "persistent daily chaotic variability in peak flow (usually greater than 40 per cent diurnal variation in PEFR more than 50 per cent of the time)", while type 2 is identified by "sporadic sudden falls in PEFR against a background of usually well-controlled asthma with normal or near normal lung function". In both types, patients are subject to recurrent, severe attacks. The cardinal symptoms of an asthma attack are shortness of breath (dyspnea), wheezing, and chest tightness. Individuals with type 1 suffer chronic attacks in spite of ongoing medical therapy, while those with type 2 experience sudden, acute and even potentially life-threatening attacks even though otherwise their asthma seems well managed.When first defined by Margaret Turner-Warwick in 1977, the term brittle asthma was used specifically to describe type 1, but as studies into the phenotype were conducted the second type was also distinguished.
Treatment
In addition to any issues of treatment compliance, and maximised corticosteroids (inhaled or oral) and beta agonist, brittle asthma treatment also involves for type 1 additional subcutaneous injections of beta2 agonist and inhalation of long acting beta-adrenoceptor agonist, whilst type 2 needs allergen avoidance and self-management approaches. Since catastrophic attacks are unpredictable in type 2, patients may display identification of the issue, such as a MedicAlert bracelet, and carry an epinephrine autoinjector.
Epidemiology
The condition is rare. 1999s Difficult Asthma estimates a prevalence of approximately 0.05% brittle asthma sufferers among the asthmatic population. Though found in all ages, it is most commonly found in individuals between the ages of 18 and 55; it is present in both sexes, though type 1 has been diagnosed in three times as many women as men. Hospitalization is more frequent for type 1 than type 2.
== References == |
Cannabis (drug) | Cannabis, also known as marijuana among other names, is a psychoactive drug from the Cannabis plant. Native to Central and South Asia, the cannabis plant has been used as a drug for both recreational and entheogenic purposes and in various traditional medicines for centuries. Tetrahydrocannabinol (THC) is the main psychoactive component of cannabis, which is one of the 483 known compounds in the plant, including at least 65 other cannabinoids, including cannabidiol (CBD). Cannabis can be used by smoking, vaporizing, within food, or as an extract.Cannabis has various mental and physical effects, which include euphoria, altered states of mind and sense of time, difficulty concentrating, impaired short-term memory, impaired body movement (balance and fine psychomotor control),: p7 relaxation, and an increase in appetite. Onset of effects is felt within minutes when smoked, but may take up to 90 minutes when eaten. The effects last for two to six hours, depending on the amount used. At high doses, mental effects can include anxiety, delusions (including ideas of reference), hallucinations, panic, paranoia, and psychosis. There is a strong relation between cannabis use and the risk of psychosis, though the direction of causality is debated. Physical effects include increased heart rate, difficulty breathing, nausea, and behavioral problems in children whose mothers used cannabis during pregnancy; short-term side effects may also include dry mouth and red eyes. Long-term adverse effects may include addiction, decreased mental ability in those who started regular use as adolescents, chronic coughing, susceptibility to respiratory infections, and cannabinoid hyperemesis syndrome.
Cannabis is mostly used recreationally or as a medicinal drug, although it may also be used for spiritual purposes. In 2013, between 128 and 232 million people used cannabis (2.7% to 4.9% of the global population between the ages of 15 and 65). It is the most commonly used illegal drug in the world, though it is legal in some jurisdictions, with the highest use among adults (as of 2018) in Zambia, the United States, Canada, and Nigeria.While cannabis plants have been grown since at least the 3rd millennium BCE, evidence suggests that it was being smoked for psychoactive effects at least 2,500 years ago in the Pamir Mountains, Asia. Since the early 20th century, cannabis has been subject to legal restrictions. The possession, use, and cultivation of cannabis is illegal in most countries. In 2013, Uruguay became the first country to legalize recreational use of cannabis. Other countries to do so are Canada, Georgia, Malta, Mexico, and South Africa. In the United States, the recreational use of cannabis is legal in 19 states, two territories, and the District of Columbia, though the drug remains federally illegal.
Uses
Medical
Medical cannabis, or medical marijuana, refers to the use of cannabis to treat disease or improve symptoms; however, there is no single agreed-upon definition (e.g., cannabinoids derived from cannabis and synthetic cannabinoids are also used). The rigorous scientific study of cannabis as a medicine has been hampered by production restrictions and by the fact that it is classified as an illegal drug by many governments. There is limited evidence suggesting cannabis can be used to reduce nausea and vomiting during chemotherapy, to improve appetite in people with HIV/AIDS, or to treat chronic pain and muscle spasms. Its use for other medical applications is insufficient for drawing conclusions about safety or efficacy. There is evidence supporting the use of cannabis or its derivatives in the treatment of chemotherapy-induced nausea and vomiting, neuropathic pain, and multiple sclerosis. Lower levels of evidence support its use for AIDS wasting syndrome, epilepsy, rheumatoid arthritis, and glaucoma.So far, the medical use of cannabis is legal only in a limited number of territories, including Canada, Belgium, Australia, the Netherlands, New Zealand, Spain, and many U.S. states. This usage generally requires a prescription, and distribution is usually done within a framework defined by local laws.
Recreational
According to DEA Chief Administrative Law Judge, Francis Young, "cannabis is one of the safest therapeutically active substances known to man." Being under the effects of cannabis is usually referred to as being "high" or "stoned." Cannabis consumption has both psychoactive and physiological effects. The "stoned" experience can vary widely, based (among other things) on the users prior experience with cannabis, and the type of cannabis consumed.: p647 When smoking cannabis, a euphoriant effect can occur within minutes of smoking.: p104 Aside from a subjective change in perception and mood, the most common short-term physical and neurological effects include increased heart rate, increased appetite, impairment of short-term and working memory, and psychomotor coordination.Additional desired effects from consuming cannabis include relaxation, a general alteration of conscious perception, increased awareness of sensation, increased libido and distortions in the perception of time and space. At higher doses, effects can include altered body image, auditory and/or visual illusions, pseudohallucinations and ataxia from selective impairment of polysynaptic reflexes. In some cases, cannabis can lead to dissociative states such as depersonalization and derealization.
Spiritual
Cannabis has held sacred status in several religions and has served as an entheogen – a chemical substance used in religious, shamanic, or spiritual contexts – in the Indian subcontinent since the Vedic period. The earliest known reports regarding the sacred status of cannabis in the Indian subcontinent come from the Atharva Veda, estimated to have been composed sometime around 1400 BCE.
The Hindu god Shiva is described as a cannabis user, known as the "Lord of bhang.: p19 In modern culture, the spiritual use of cannabis has been spread by the disciples of the Rastafari movement who use cannabis as a sacrament and as an aid to meditation.
Modes of cannabis consumption
Cannabis is consumed in many different ways, all of which involve heating to decarboxylate THCA in the plant into THC. Common available forms are:
Smoking, which typically involves burning and inhaling vaporized cannabinoids ("smoke") from small pipes, bongs (portable versions of hookahs with a water chamber), paper-wrapped joints or tobacco-leaf-wrapped blunts, and other items.
Vaporizer, which heats any form of cannabis to 165–190 °C (329–374 °F), causing the active ingredients to evaporate into vapor without burning the plant material (the boiling point of THC is 157 °C (315 °F) at atmospheric pressure).
Cannabis tea, which contains relatively small concentrations of THC because THC is an oil (lipophilic) and is only slightly water-soluble (with a solubility of 2.8 mg per liter). Cannabis tea is made by first adding a saturated fat to hot water (e.g. cream or any milk except skim) with a small amount of cannabis.
Edibles, where cannabis is added as an ingredient to one of a variety of foods, including butter and baked goods. In India it is commonly made into a beverage, bhang.
Tincture of cannabis, sometimes known as green dragon, is an alcoholic cannabis concentrate.
Capsules, typically containing cannabis oil, and other dietary supplement products, for which some 220 were approved in Canada in 2018.
Adverse effects
Short-term
Acute negative effects may include anxiety and panic, impaired attention and memory, an increased risk of psychotic symptoms, the inability to think clearly, and an increased risk of accidents. Cannabis impairs a persons driving ability, and THC was the illicit drug most frequently found in the blood of drivers who have been involved in vehicle crashes. Those with THC in their system are from three to seven times more likely to be the cause of the accident than those who had not used either cannabis or alcohol, although its role is not necessarily causal because THC stays in the bloodstream for days to weeks after intoxication.Some immediate undesired side effects include a decrease in short-term memory, dry mouth, impaired motor skills, reddening of the eyes, dizziness, feeling tired and vomiting. Some users may experience an episode of acute psychosis, which usually abates after six hours, but in rare instances, heavy users may find the symptoms continuing for many days.Legalization has increased the rates at which children are exposed to cannabis, particularly from edibles. While the toxicity and lethality of THC in children is not known, they are at risk for encephalopathy, hypotension, respiratory depression severe enough to require ventilation, somnolence and coma.
Fatality
Cannabis is suspected of being a potential, and under-reported, contributory factor or direct cause in cases of sudden death, due to the strain it can place on the cardiovascular system. Multiple deaths have been attributed to cannabinoid hyperemesis syndrome.A 16-month survey of Oregon and Alaska emergency departments found a report of the death of an adult who had been admitted for acute cannabis toxicity.
Long-term
Psychological effects
A 2015 meta-analysis found that, although a longer period of abstinence was associated with smaller magnitudes of impairment, both retrospective and prospective memory were impaired in cannabis users. The authors concluded that some, but not all, of the deficits associated with cannabis use were reversible. A 2012 meta-analysis found that deficits in most domains of cognition persisted beyond the acute period of intoxication, but was not evident in studies where subjects were abstinent for more than 25 days. Few high quality studies have been performed on the long-term effects of cannabis on cognition, and the results were generally inconsistent. Furthermore, effect sizes of significant findings were generally small. One review concluded that, although most cognitive faculties were unimpaired by cannabis use, residual deficits occurred in executive functions. Impairments in executive functioning are most consistently found in older populations, which may reflect heavier cannabis exposure, or developmental effects associated with adolescent cannabis use. One review found three prospective cohort studies that examined the relationship between self reported cannabis use and intelligence quotient (IQ). The study following the largest number of heavy cannabis users reported that IQ declined between ages 7–13 and age 38. Poorer school performance and increased incidence of leaving school early were both associated with cannabis use, although a causal relationship was not established. Cannabis users demonstrated increased activity in task-related brain regions, consistent with reduced processing efficiency.A reduced quality of life is associated with heavy cannabis use, although the relationship is inconsistent and weaker than for tobacco and other substances. The direction of cause and effect, however, is unclear.The long-term effects of cannabis are not clear. There are concerns surrounding memory and cognition problems, risk of addiction, and the risk of schizophrenia in young people.
Neuroimaging
Although global abnormalities in white matter and grey matter are not consistently associated with heavy cannabis use, reduced hippocampal volume is consistently found. Amygdala abnormalities are sometimes reported, although findings are inconsistent.Cannabis use is associated with increased recruitment of task-related areas, such as the dorsolateral prefrontal cortex, which is thought to reflect compensatory activity due to reduced processing efficiency. Cannabis use is also associated with downregulation of CB1 receptors. The magnitude of down regulation is associated with cumulative cannabis exposure, and is reversed after one month of abstinence. There is limited evidence that chronic cannabis use can reduce levels of glutamate metabolites in the human brain.
Cannabis dependence
About 9% of those who experiment with marijuana eventually become dependent according to DSM-IV (1994) criteria. A 2013 review estimates daily use is associated with a 10–20% rate of dependence. The highest risk of cannabis dependence is found in those with a history of poor academic achievement, deviant behavior in childhood and adolescence, rebelliousness, poor parental relationships, or a parental history of drug and alcohol problems. Of daily users, about 50% experience withdrawal upon cessation of use (i.e. are dependent), characterized by sleep problems, irritability, dysphoria, and craving. Cannabis withdrawal is less severe than withdrawal from alcohol.According to DSM-V criteria, 9% of those who are exposed to cannabis develop cannabis use disorder, compared to 20% for cocaine, 23% for alcohol and 68% for nicotine. Cannabis use disorder in the DSM-V involves a combination of DSM-IV criteria for cannabis abuse and dependence, plus the addition of craving, without the criterion related to legal troubles.
Psychiatric
At an epidemiological level, a dose–response relationship exists between cannabis use and increased risk of psychosis and earlier onset of psychosis. Although the epidemiological association is robust, evidence to prove a causal relationship is lacking. But a biological causal pathway is plausible, especially if there is a genetic predisposition to mental illness, in which case cannabis may be a trigger.Cannabis may also increase the risk of depression, but insufficient research has been performed to draw a conclusion. Cannabis use is associated with increased risk of anxiety disorders, although causality has not been established.A review in 2019 found that research was insufficient to determine the safety and efficacy of using cannabis to treat schizophrenia, psychosis, or other mental disorders. Another found that cannabis during adolescence was associated with an increased risk of developing depression and suicidal behavior later in life, while finding no effect on anxiety.
Physical
Heavy, long-term exposure to marijuana may have physical, mental, behavioral and social health consequences. It may be "associated with diseases of the liver (particularly with co-existing hepatitis C), lungs, heart, and vasculature". A 2014 review found that while cannabis use may be less harmful than alcohol use, the recommendation to substitute it for problematic drinking was premature without further study. Various surveys conducted between 2015 and 2019 found that many users of cannabis substitute it for prescription drugs (including opioids), alcohol, and tobacco; most of those who used it in place of alcohol or tobacco either reduced or stopped their intake of the latter substances.Cannabinoid hyperemesis syndrome (CHS) is a severe condition seen in some chronic cannabis users where they have repeated bouts of uncontrollable vomiting for 24–48 hours.
Four cases of death have been reported as a result of CHS.A limited number of studies have examined the effects of cannabis smoking on the respiratory system. Chronic heavy marijuana smoking is associated with coughing, production of sputum, wheezing, and other symptoms of chronic bronchitis. The available evidence does not support a causal relationship between cannabis use and chronic obstructive pulmonary disease. Short-term use of cannabis is associated with bronchodilation. Other side effects of cannabis use include cannabinoid hyperemesis syndrome (CHS), a condition which involves recurrent nausea, cramping abdominal pain, and vomiting.Cannabis smoke contains thousands of organic and inorganic chemical compounds. This tar is chemically similar to that found in tobacco smoke, and over fifty known carcinogens have been identified in cannabis smoke, including; nitrosamines, reactive aldehydes, and polycylic hydrocarbons, including benz[a]pyrene. Cannabis smoke is also inhaled more deeply than tobacco smoke. As of 2015, there is no consensus regarding whether cannabis smoking is associated with an increased risk of cancer. Light and moderate use of cannabis is not believed to increase risk of lung or upper airway cancer. Evidence for causing these cancers is mixed concerning heavy, long-term use. In general there are far lower risks of pulmonary complications for regular cannabis smokers when compared with those of tobacco. A 2015 review found an association between cannabis use and the development of testicular germ cell tumors (TGCTs), particularly non-seminoma TGCTs. Another 2015 meta-analysis found no association between lifetime cannabis use and risk of head or neck cancer. Combustion products are not present when using a vaporizer, consuming THC in pill form, or consuming cannabis foods.There is concern that cannabis may contribute to cardiovascular disease, but as of 2018, evidence of this relationship was unclear. Research in these events is complicated because cannabis is often used in conjunction with tobacco, and drugs such as alcohol and cocaine that are known to have cardiovascular risk factors. Smoking cannabis has also been shown to increase the risk of myocardial infarction by 4.8 times for the 60 minutes after consumption.There is preliminary evidence that cannabis interferes with the anticoagulant properties of prescription drugs used for treating blood clots. As of 2019, the mechanisms for the anti-inflammatory and possible pain relieving effects of cannabis were not defined, and there were no governmental regulatory approvals or clinical practices for use of cannabis as a drug.
Emergency Department Visits
Emergency room (ER) admissions associated with cannabis use rose significantly from 2012 to 2016; adolescents from age 12-17 had the highest risk.
At one Colorado medical center following legalization, approximately two percent of ER admissions were classified as cannabis users. The symptoms of one quarter of these users were partially attributed to cannabis (a total of 2567 out of 449,031 patients); other drugs were sometimes involved. Of these cannabis admissions, one quarter were for acute psychiatric effects, primarily suicidal ideation, depression, and anxiety. An additional third of the cases were for gastrointestinal issues including Cannabinoid hyperemesis syndrome.According to the United States Department of Health and Human Services, there were 455,000 emergency room visits associated with cannabis use in 2011. These statistics include visits in which the patient was treated for a condition induced by or related to recent cannabis use. The drug use must be "implicated" in the emergency department visit, but does not need to be the direct cause of the visit. Most of the illicit drug emergency room visits involved multiple drugs. In 129,000 cases, cannabis was the only implicated drug.
Reproductive health
There is sufficient evidence of reproductive health harms from cannabis that its use when trying to conceive, during pregnancy, and while breastfeeding, is not advisable.It has been recommended that cannabis use be stopped before and during pregnancy as it can result in negative outcomes for both the mother and baby. However, maternal use of marijuana during pregnancy does not appear to be associated with low birth weight or early delivery after controlling for tobacco use and other confounding factors.
Pharmacology
Mechanism of action
The high lipid-solubility of cannabinoids results in their persisting in the body for long periods of time. Even after a single administration of THC, detectable levels of THC can be found in the body for weeks or longer (depending on the amount administered and the sensitivity of the assessment method). Investigators have suggested that this is an important factor in marijuanas effects, perhaps because cannabinoids may accumulate in the body, particularly in the lipid membranes of neurons.Researchers confirmed that THC exerts its most prominent effects via its actions on two types of cannabinoid receptors, the CB1 receptor and the CB2 receptor, both of which are G protein-coupled receptors. The CB1 receptor is found primarily in the brain as well as in some peripheral tissues, and the CB2 receptor is found primarily in peripheral tissues, but is also expressed in neuroglial cells. THC appears to alter mood and cognition through its agonist actions on the CB1 receptors, which inhibit a secondary messenger system (adenylate cyclase) in a dose-dependent manner.
Via CB1 receptor activation, THC indirectly increases dopamine release and produces psychotropic effects. CBD also acts as an allosteric modulator of the μ- and δ-opioid receptors. THC also potentiates the effects of the glycine receptors. It is unknown if or how these actions contribute to the effects of cannabis.
Chemistry
Chemical composition
The main psychoactive component of cannabis is THC, which is formed via decarboxylation of THCA from the application of heat. Raw leaf is not psychoactive because the cannabinoids are in the form of carboxylic acids.
Cannabinoids
Detection in body fluids
THC and its major (inactive) metabolite, THC-COOH, can be measured in blood, urine, hair, oral fluid or sweat using chromatographic techniques as part of a drug use testing program or a forensic investigation of a traffic or other criminal offense. The concentrations obtained from such analyses can often be helpful in distinguishing active use from passive exposure, elapsed time since use, and extent or duration of use. These tests cannot, however, distinguish authorized cannabis smoking for medical purposes from unauthorized recreational smoking. Commercial cannabinoid immunoassays, often employed as the initial screening method when testing physiological specimens for marijuana presence, have different degrees of cross-reactivity with THC and its metabolites. Urine contains predominantly THC-COOH, while hair, oral fluid and sweat contain primarily THC. Blood may contain both substances, with the relative amounts dependent on the recency and extent of usage.The Duquenois–Levine test is commonly used as a screening test in the field, but it cannot definitively confirm the presence of cannabis, as a large range of substances have been shown to give false positives. Researchers at John Jay College of Criminal Justice reported that dietary zinc supplements can mask the presence of THC and other drugs in urine. However, a 2013 study conducted by researchers at the University of Utah School of Medicine refute the possibility of self-administered zinc producing false-negative urine drug tests.
Varieties and strains
CBD is a 5-HT1A receptor agonist, which is under laboratory research to determine if it has an anxiolytic effect. It is often claimed that sativa strains provide a more stimulating psychoactive high while indica strains are more sedating with a body high. However, this is disputed by researchers.A 2015 review found that the use of high CBD-to-THC strains of cannabis showed significantly fewer positive symptoms, such as delusions and hallucinations, better cognitive function and both lower risk for developing psychosis, as well as a later age of onset of the illness, compared to cannabis with low CBD-to-THC ratios.
Psychoactive ingredients
According to the United Nations Office on Drugs and Crime (UNODC), "the amount of THC present in a cannabis sample is generally used as a measure of cannabis potency." The three main forms of cannabis products are the flower/fruit, resin (hashish), and oil (hash oil). The UNODC states that cannabis often contains 5% THC content, resin "can contain up to 20% THC content", and that "Cannabis oil may contain more than 60% THC content."A 2012 review found that the THC content in marijuana had increased worldwide from 1970 to 2009. It is unclear, however, whether the increase in THC content has caused people to consume more THC or if users adjust based on the potency of the cannabis. It is likely that the higher THC content allows people to ingest less tar. At the same time, CBD levels in seized samples have lowered, in part because of the desire to produce higher THC levels and because more illegal growers cultivate indoors using artificial lights. This helps avoid detection but reduces the CBD production of the plant.Australias National Cannabis Prevention and Information Centre (NCPIC) states that the buds (infructescences) of the female cannabis plant contain the highest concentration of THC, followed by the leaves. The stalks and seeds have "much lower THC levels". The UN states that the leaves can contain ten times less THC than the buds, and the stalks one hundred times less THC.After revisions to cannabis scheduling in the UK, the government moved cannabis back from a class C to a class B drug. A purported reason was the appearance of high potency cannabis. They believe skunk accounts for between 70 and 80% of samples seized by police (despite the fact that skunk can sometimes be incorrectly mistaken for all types of herbal cannabis). Extracts such as hashish and hash oil typically contain more THC than high potency cannabis infructescences.
Laced cannabis and synthetic cannabinoids
Hemp buds (or low-potency cannabis buds) laced with synthetic cannabinoids started to be sold as cannabis street drug in 2020.The short term effects of cannabis can be altered if it has been laced with opioid drugs such as heroin or fentanyl. The added drugs are meant to enhance the psychoactive properties, add to its weight, and increase profitability, despite the increased danger of overdose.
Preparations
Marijuana
Marijuana or marihuana (herbal cannabis) consists of the dried flowers and fruits and subtending leaves and stems of the female Cannabis plant. This is the most widely consumed form, containing 3% to 20% THC, with reports of up to 33% THC. This is the stock material from which all other preparations are derived. Although herbal cannabis and industrial hemp derive from the same species and contain the psychoactive component (THC), they are distinct strains with unique biochemical compositions and uses. Hemp has lower concentrations of THC and higher concentrations of CBD, which gives lesser psychoactive effects.
Kief
Kief is a powder, rich in trichomes, which can be sifted from the leaves, flowers and fruits of cannabis plants and either consumed in powder form or compressed to produce cakes of hashish. The word "kif" derives from colloquial Arabic كيف kēf/kīf, meaning pleasure.
Hashish
Hashish (also spelled hasheesh, hashisha, or simply hash) is a concentrated resin cake or ball produced from pressed kief, the detached trichomes and fine material that falls off cannabis fruits, flowers and leaves. or from scraping the resin from the surface of the plants and rolling it into balls. It varies in color from black to golden brown depending upon purity and variety of cultivar it was obtained from. It can be consumed orally or smoked, and is also vaporized, or vaped. The term "rosin hash" refers to a high quality solventless product obtained through heat and pressure.
Tincture
Cannabinoids can be extracted from cannabis plant matter using high-proof spirits (often grain alcohol) to create a tincture, often referred to as "green dragon".: p17 Nabiximols is a branded product name from a tincture manufacturing pharmaceutical company.
Hash oil
Hash oil is a resinous matrix of cannabinoids obtained from the Cannabis plant by solvent extraction, formed into a hardened or viscous mass. Hash oil can be the most potent of the main cannabis products because of its high level of psychoactive compound per its volume, which can vary depending on the plants mix of essential oils and psychoactive compounds. Butane and supercritical carbon dioxide hash oil have become popular in recent years.
Infusions
There are many varieties of cannabis infusions owing to the variety of non-volatile solvents used. The plant material is mixed with the solvent and then pressed and filtered to express the oils of the plant into the solvent. Examples of solvents used in this process are cocoa butter, dairy butter, cooking oil, glycerine, and skin moisturizers. Depending on the solvent, these may be used in cannabis foods or applied topically.
Marihuana prensada
Marihuana prensada (pressed marijuana) is a cannabis-derived product widespread among the lower classes of South America, especially from the 90s. Locally it is known as "paraguayo" or "paragua", since its main producer is Paraguay. Marijuana is dried and mixed with binding agents that make it toxic and highly harmful to health. It is cut into the shape of bricks (ladrillos) and sold for a low price in Argentina, Brazil, Chile, Peru, Venezuela, and even the United States.
History
Ancient history
Cannabis is indigenous to Central Asia and the Indian subcontinent, and its uses for fabric and rope dates back to the Neolithic age in China and Japan. It is unclear when cannabis first became known for its psychoactive properties. The oldest archeological evidence for the burning of cannabis was found in Romanian kurgans dated 3,500 BC, and scholars suggest that the drug was first used in ritual ceremonies by Proto-Indo-European tribes living in the Pontic-Caspian steppe during the Chalcolithic period, a custom they eventually spread throughout western Eurasia during the Indo-European migrations. Some research suggests that the ancient Indo-Iranian drug soma, mentioned in the Vedas, sometimes contained cannabis. This is based on the discovery of a basin containing cannabis in a shrine of the second millennium BC in Turkmenistan.Cannabis was known to the ancient Assyrians, who discovered its psychoactive properties through the Iranians. Using it in some religious ceremonies, they called it qunubu (meaning "way to produce smoke"), a probable origin of the modern word "cannabis". The Iranians also introduced cannabis to the Scythians, Thracians and Dacians, whose shamans (the kapnobatai – "those who walk on smoke/clouds") burned cannabis infructescences to induce trance. The plant was used in China before 2800 BC, and found therapeutic use in |
Cannabis (drug) | India by 1000 BC, where it was used in food and drink, including bhang.
Cannabis has an ancient history of ritual use and has been used by religions around the world. The earliest evidence of cannabis smoking has been found in the 2,500-year-old tombs of Jirzankal Cemetery in the Pamir Mountains in Western China, where cannabis residue were found in burners with charred pebbles possibly used during funeral rituals. Hemp seeds discovered by archaeologists at Pazyryk suggest early ceremonial practices like eating by the Scythians occurred during the 5th to 2nd century BC, confirming previous historical reports by Herodotus. It was used by Muslims in various Sufi orders as early as the Mamluk period, for example by the Qalandars. Smoking pipes uncovered in Ethiopia and carbon-dated to around c. AD 1320 were found to have traces of cannabis.
Modern history
Cannabis was introduced to the New World by the Spaniards in 1530–45. Following an 1836–1840 travel in North Africa and the Middle East, French physician Jacques-Joseph Moreau wrote on the psychological effects of cannabis use; he was a member of Paris Club des Hashischins. In 1842, Irish physician William Brooke OShaughnessy, who had studied the drug while working as a medical officer in Bengal with the East India Company, brought a quantity of cannabis with him on his return to Britain, provoking renewed interest in the West. Examples of classic literature of the period featuring cannabis include Les paradis artificiels (1860) by Charles Baudelaire and The Hasheesh Eater (1857) by Fitz Hugh Ludlow.
Cannabis was criminalized in various countries beginning in the 19th century. The colonial government of Mauritius banned cannabis in 1840 over concerns on its effect on Indian indentured workers; the same occurred in Singapore in 1870. In the United States, the first restrictions on sale of cannabis came in 1906 (in the District of Columbia). Canada criminalized cannabis in The Opium and Narcotic Drug Act, 1923, before any reports of the use of the drug in Canada, but eventually legalized its consumption for recreational and medicinal purposes in 2018.In 1925, a compromise was made at an international conference in The Hague about the International Opium Convention that banned exportation of "Indian hemp" to countries that had prohibited its use, and requiring importing countries to issue certificates approving the importation and stating that the shipment was required "exclusively for medical or scientific purposes". It also required parties to "exercise an effective control of such a nature as to prevent the illicit international traffic in Indian hemp and especially in the resin". In the United States in 1937, the Marihuana Tax Act was passed, and prohibited the production of hemp in addition to cannabis.
In 1972, the Dutch government divided drugs into more- and less-dangerous categories, with cannabis being in the lesser category. Accordingly, possession of 30 grams (1.1 oz) or less was made a misdemeanor. Cannabis has been available for recreational use in coffee shops since 1976. Cannabis products are only sold openly in certain local "coffeeshops" and possession of up to 5 grams (0.18 oz) for personal use is decriminalized, however: the police may still confiscate it, which often happens in car checks near the border. Other types of sales and transportation are not permitted, although the general approach toward cannabis was lenient even before official decriminalization.In Uruguay, President Jose Mujica signed legislation to legalize recreational cannabis in December 2013, making Uruguay the first country in the modern era to legalize cannabis. In August 2014, Uruguay legalized growing up to six plants at home, as well as the formation of growing clubs (Cannabis social club), and a state-controlled marijuana dispensary regime.
As of 17 October 2018 when recreational use of cannabis was legalized in Canada, dietary supplements for human use and veterinary health products containing not more than 10 parts per million of THC extract were approved for marketing; Nabiximols (as Sativex) is used as a prescription drug in Canada.The United Nations World Drug Report stated that cannabis "was the worlds most widely produced, trafficked, and consumed drug in the world in 2010", and estimated between 128 million and 238 million users globally in 2015.
Society, culture, legal status, and economics
Society and culture
Cannabis has been one of the most used psychoactive drugs in the world since the late 20th century, following only tobacco and alcohol in popularity. According to Vera Rubin, the use of cannabis has been encompassed by two major cultural complexes over time: a continuous, traditional folk stream, and a more circumscribed, contemporary configuration. The former involves both sacred and secular use, and is usually based on small-scale cultivation: the use of the plant for cordage, clothing, medicine, food, and a "general use as an euphoriant and symbol of fellowship." The second stream of expansion of cannabis use encompasses "the use of hemp for commercial manufacturers utilizing large-scale cultivation primarily as a fiber for mercantile purposes"; but it is also linked to the search for psychedelic experiences (which can be traced back to the formation of the Parisian Club des Hashischins).
Legal status
Since the beginning of the 20th century, most countries have enacted laws against the cultivation, possession or transfer of cannabis. These laws have had an adverse effect on cannabis cultivation for non-recreational purposes, but there are many regions where handling of cannabis is legal or licensed. Many jurisdictions have lessened the penalties for possession of small quantities of cannabis so that it is punished by confiscation and sometimes a fine, rather than imprisonment, focusing more on those who traffic the drug on the black market.
In some areas where cannabis use had been historically tolerated, new restrictions were instituted, such as the closing of cannabis coffee shops near the borders of the Netherlands, and closing of coffee shops near secondary schools in the Netherlands. In Copenhagen, Denmark in 2014, mayor Frank Jensen discussed possibilities for the city to legalize cannabis production and commerce.Some jurisdictions use free voluntary treatment programs and/or mandatory treatment programs for frequent known users. Simple possession can carry long prison terms in some countries, particularly in East Asia, where the sale of cannabis may lead to a sentence of life in prison or even execution. Political parties, non-profit organizations, and causes based on the legalization of medical cannabis and/or legalizing the plant entirely (with some restrictions) have emerged in such countries as China and Thailand.In December 2012, the U.S. state of Washington became the first state to officially legalize cannabis in a state law (Washington Initiative 502) (but still illegal by federal law), with the state of Colorado following close behind (Colorado Amendment 64). On 1 January 2013, the first marijuana "club" for private marijuana smoking (no buying or selling, however) was allowed for the first time in Colorado. The California Supreme Court decided in May 2013 that local governments can ban medical marijuana dispensaries despite a state law in California that permits the use of cannabis for medical purposes. At least 180 cities across California have enacted bans in recent years.In December 2013, Uruguay became the first country to legalize growing, sale and use of cannabis. After a long delay in implementing the retail component of the law, in 2017 sixteen pharmacies were authorized to sell cannabis commercially. On 19 June 2018, the Canadian Senate passed a bill and the Prime Minister announced the effective legalization date as 17 October 2018. Canada is the second country to legalize the drug.In November 2015, Uttarakhand became the first state of India to legalize the cultivation of hemp for industrial purposes. Usage within the Hindu and Buddhist cultures of the Indian subcontinent is common, with many street vendors in India openly selling products infused with cannabis, and traditional medical practitioners in Sri Lanka selling products infused with cannabis for recreational purposes and well as for religious celebrations. Indian laws criminalizing cannabis date back to the colonial period. India and Sri Lanka have allowed cannabis to be taken in the context of traditional culture for recreational/celebratory purposes and also for medicinal purposes.On 17 October 2015, Australian health minister Sussan Ley presented a new law that will allow the cultivation of cannabis for scientific research and medical trials on patients.On 17 October 2018, Canada legalized cannabis for recreational adult use making it the second country in the world to do so after Uruguay and the first G7 nation. The Canadian Licensed Producer system aims to become the Gold Standard in the world for safe and secure cannabis production, including provisions for a robust craft cannabis industry where many expect opportunities for experimenting with different strains. Laws around use vary from province to province including age limits, retail structure, and growing at home.As the drug has increasingly been seen as a health issue instead of criminal behavior, marijuana has also been legalized or decriminalized in: Czech Republic, Colombia, Ecuador, Portugal, South Africa and Canada. Medical marijuana was legalized in Mexico in mid-2017; legislators plan to legalize its recreational use by late 2019.On 28 June 2021, Clarence Thomas, one of the U.S. Supreme Courts most conservative justices, possibly opened the door to federal legalization of cannabis in the United States when he wrote "A prohibition on interstate use or cultivation of marijuana may no longer be necessary or proper to support the federal governments piecemeal approach."
Legality by country
Currently, Uruguay and Canada are the only countries that have fully legalized the cultivation, consumption and bartering of recreational cannabis nationwide. In the United States, 19 states, 2 territories, and the District of Columbia have legalized the recreational use of cannabis – though the drug remains illegal at the federal level. Laws vary from state to state when it comes to the commercial sale. Court rulings in Georgia and South Africa have led to the legalization of cannabis consumption, but not legal sales. A policy of limited enforcement has also been adopted in many countries, in particular Spain and the Netherlands where the sale of cannabis is tolerated at licensed establishments. Contrary to popular belief, cannabis is not legal in the Netherlands but it has been decriminalized since the 1970s. In 2021, Malta was the first European Union member to legalize the use of cannabis for recreational purposes. In Estonia, it is only legal to sell cannabis products with a THC content of less than 0.2%, although products may contain more cannabidiol. Lebanon has recently become the first Arab country to legalize the plantation of cannabis for medical use.Penalties for illegal recreational use ranges from confiscation or small fines to jail time and even death. In some countries citizens can be punished if they have used the drug in another country, including Singapore and South Korea.
Usage
In 2013, between 128 and 232 million people used cannabis (2.7% to 4.9% of the global population between the ages of 15 and 65). Cannabis is by far the most widely used illicit substance.
United States
Between 1973 and 1978, eleven states decriminalized marijuana. In 2001, Nevada reduced marijuana possession to a misdemeanor and since 2012, several other states have decriminalized and even legalized marijuana.In 2018, almost half of the people in the United States had tried marijuana, 16% had used it in the past year, and 11% had used it in the past month. In 2014, daily marijuana use amongst US college students had reached its highest level since records began in 1980, rising from 3.5% in 2007 to 5.9% in 2014 and had surpassed daily cigarette use.In the US, men are over twice as likely to use marijuana as women, and 18–29-year-olds are six times more likely to use as over-65-year-olds. In 2015, a record 44% of the US population has tried marijuana in their lifetime, an increase from 38% in 2013 and 33% in 1985.Marijuana use in the United States is three times above the global average, but in line with other Western democracies. Forty-four percent of American 12th graders have tried the drug at least once, and the typical age of first-use is 16, similar to the typical age of first-use for alcohol but lower than the first-use age for other illicit drugs.
Economics
Production
Sinsemilla (Spanish for "without seed") is the dried, seedless (i.e. parthenocarpic) infructescences of female cannabis plants. Because THC production drops off once pollination occurs, the male plants (which produce little THC themselves) are eliminated before they shed pollen to prevent pollination, thus inducing the development of parthenocarpic fruits gathered in dense infructescences. Advanced cultivation techniques such as hydroponics, cloning, high-intensity artificial lighting, and the sea of green method are frequently employed as a response (in part) to prohibition enforcement efforts that make outdoor cultivation more risky.
"Skunk" refers to several named strains of potent cannabis, grown through selective breeding and sometimes hydroponics. It is a cross-breed of Cannabis sativa and C. indica (although other strains of this mix exist in abundance). Skunk cannabis potency ranges usually from 6% to 15% and rarely as high as 20%. The average THC level in coffee shops in the Netherlands is about 18–19%.The average levels of THC in cannabis sold in the United States rose dramatically between the 1970s and 2000. This is disputed for various reasons, and there is little consensus as to whether this is a fact or an artifact of poor testing methodologies. According to Daniel Forbes writing for slate.com, the relative strength of modern strains are likely skewed because undue weight is given to much more expensive and potent, but less prevalent, samples. Some suggest that results are skewed by older testing methods that included low-THC-content plant material such as leaves in the samples, which are excluded in contemporary tests. Others believe that modern strains actually are significantly more potent than older ones.
Price
The price or street value of cannabis varies widely depending on geographic area and potency. Prices and overall markets have also varied considerably over time.
In 1997, cannabis was estimated to be overall the number four value crop in the US, and number one or two in many states, including California, New York, and Florida. This estimate is based on a value to growers of ~60% of retail value, or $3,000 per pound ($6,600/kg).
In 2006, cannabis was estimated to have been a $36 billion market. This estimate has been challenged as exaggerated. The UN World Drug Report (2008) estimated that 2006 street prices in the US and Canada ranged from about US$8.8 to $25 per gram (approximately $250 to $700 per ounce), depending on quality. Typical U.S. retail prices were $10–15 per gram (approximately $280–420 per ounce).
In 2017, the U.S. was estimated to constitute 90% of the worldwide $9.5 billion legal trade in cannabis.After some U.S. states legalized cannabis, street prices began to drop. In Colorado, the price of smokable buds (infructescences) dropped 40 percent between 2014 and 2019, from $200 per ounce to $120 per ounce ($7 per gram to $4.19 per gram).The European Monitoring Centre for Drugs and Drug Addiction reports that typical retail prices in Europe for cannabis varied from €2 to €20 per gram in 2008, with a majority of European countries reporting prices in the range €4–10.
Cannabis as a gateway drug
The gateway hypothesis states that cannabis use increases the probability of trying "harder" drugs. The hypothesis has been hotly debated as it is regarded by some as the primary rationale for the United States prohibition on cannabis use. A Pew Research Center poll found that political opposition to marijuana use was significantly associated with concerns about the health effects and whether legalization would increase weed use by children.Some studies state that while there is no proof for the gateway hypothesis, young cannabis users should still be considered as a risk group for intervention programs. Other findings indicate that hard drug users are likely to be poly-drug users, and that interventions must address the use of multiple drugs instead of a single hard drug. Almost two-thirds of the poly drug users in the 2009–2010 Scottish Crime and Justice Survey used cannabis.The gateway effect may appear due to social factors involved in using any illegal drug. Because of the illegal status of cannabis, its consumers are likely to find themselves in situations allowing them to acquaint with individuals using or selling other illegal drugs. Studies have shown that alcohol and tobacco may additionally be regarded as gateway drugs; however, a more parsimonious explanation could be that cannabis is simply more readily available (and at an earlier age) than illegal hard drugs. In turn, alcohol and tobacco are typically easier to obtain at an earlier age than is cannabis (though the reverse may be true in some areas), thus leading to the "gateway sequence" in those individuals, since they are most likely to experiment with any drug offered.A related alternative to the gateway hypothesis is the common liability to addiction (CLA) theory. It states that some individuals are, for various reasons, willing to try multiple recreational substances. The "gateway" drugs are merely those that are (usually) available at an earlier age than the harder drugs. Researchers have noted in an extensive review that it is dangerous to present the sequence of events described in gateway "theory" in causative terms as this hinders both research and intervention.In 2020, the National Institute on Drug Abuse released a study backing allegations that marijuana is a gateway to harder drugs, though not for the majority of marijuana users. The National Institute on Drug Abuse determined that marijuana use is "likely to precede use of other licit and illicit substances" and that "adults who reported marijuana use during the first wave of the survey were more likely than adults who did not use marijuana to develop an alcohol use disorder within 3 years; people who used marijuana and already had an alcohol use disorder at the outset were at greater risk of their alcohol use disorder worsening. Marijuana use is also linked to other substance use disorders including nicotine addiction." It also reported that "These findings are consistent with the idea of marijuana as a "gateway drug." However, the majority of people who use marijuana do not go on to use other, "harder" substances. Also, cross-sensitization is not unique to marijuana. Alcohol and nicotine also prime the brain for a heightened response to other drugs and are, like marijuana, also typically used before a person progresses to other, more harmful substances."
Research issues
Cannabis research is challenging since the plant is illegal in most countries. Research-grade samples of the drug are difficult to obtain for research purposes, unless granted under authority of national regulatory agencies, such as the US Food and Drug Administration.There are also other difficulties in researching the effects of cannabis. Many people who smoke cannabis also smoke tobacco. This causes confounding factors, where questions arise as to whether the tobacco, the cannabis, or both that have caused a cancer. Another difficulty researchers have is in recruiting people who smoke cannabis into studies. Because cannabis is an illegal drug in many countries, people may be reluctant to take part in research, and if they do agree to take part, they may not say how much cannabis they actually smoke.
See also
Cannabis rights
Glossary of cannabis terms
References
Footnotes
Citations
External links
Media related to Cannabis at Wikimedia Commons
Wiktionary Appendix of Cannabis slang |
Fetal trimethadione syndrome | Fetal trimethadione syndrome (also known as paramethadione syndrome, German syndrome, tridione syndrome, among others) is a set of birth defects caused by the administration of the anticonvulsants trimethadione (also known as Tridione) or paramethadione to epileptic mothers during pregnancy.Fetal trimethadione syndrome is classified as a rare disease by the National Institute of Healths Office of Rare Diseases, meaning it affects less than 200,000 individuals in the United States.The fetal loss rate while using trimethadione has been reported to be as high as 87%.
Presentation
Fetal trimethadione syndrome is characterized by the following major symptoms as a result of the teratogenic characteristics of trimethadione.
Cranial and facial abnormalities which include; microcephaly, midfacial flattening, V-shaped eyebrows and a short nose
Cardiovascular abnormalities
Absent kidney and ureter
Meningocele, a birth defect of the spine
Omphalocele, a birth defect where portions of the abdominal contents project into the umbilical cord
A delay in mental and physical development
Diagnosis
Treatment
Surgery may help alleviate the effects of some physical defects, but prognosis is poor, especially for those with severe cardiovascular and cognitive problems. Speech and physical therapy, as well as special education is required for surviving children.
References
== External links == |
Complement receptor | A complement receptor is a membrane-bound receptor belonging to the complement system, which is part of the innate immune system. Complement receptors bind effector protein fragments that are produced in response to antigen-antibody complexes or damage-associated molecules. Complement receptor activation contributes to the regulation of inflammation, leukocyte extravasation, and phagocytosis; it also contributes to the adaptive immune response. Different complement receptors can participate in either the classical complement pathway, the alternative complement pathway, or both.
Expression and function
White blood cells, particularly monocytes and macrophages, express complement receptors on their surface. All four complement receptors can bind to fragments of complement component 3 or complement component 4 coated on pathogen surface, but the receptors trigger different downstream activities. Complement receptor (CR) 1, 3, and 4 function as opsonins which stimulate phagocytosis, whereas CR2 is expressed only on B cells as a co-receptor.
Red blood cells (RBCs) also express CR1, which enables RBCs to carry complement-bound antigen-antibody complexes to the liver and spleen for degradation.
a.^ B: B cell. E: erythrocyte. Endo: endothelial cell. D: dendritic cell. FDC: follicular dendritic cell. Mac: macrophage. MC: mast cell. M0: monocyte. Pha: phagocyte. PMN: polymorphonuclear leukocyte.
Clinical significance
Deficits in complement receptor expression can cause disease. Mutations in complement receptors which alter receptor function can also increase risk of certain diseases.
See also
Complement system
Humoral immunity
Immune system
References
External links
Complement+receptors at the US National Library of Medicine Medical Subject Headings (MeSH) |
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