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Brachydactyly type D | Brachydactyly type D, also known as short thumb or stub thumb and inaccurately referred to as clubbed thumb, is a condition clinically recognised by a thumb being relatively short and round with an accompanying wider nail bed. The distal phalanx of affected thumbs is approximately two-thirds the length of full-length thumbs. It is the most common type of brachydactyly, or shortness of digits, affecting approximately 2–3% of the population, and is associated with the HOXD13 gene, located on chromosome 2q31.1
Physiology
Brachydactyly type D is a skeletal condition which exhibits a partial fusion or premature closing of the epiphysis with the distal phalanx of the thumb, according to Goodman et alia (1965). J.K. Breithenbecher (1923) found that distal phalanges of stub thumbs were one-half the length of full-length thumbs, while R.M. Stecher (1957) claimed that it is approximately two-thirds. The condition may either be unilateral (affecting one thumb) or bilateral (affecting both).
Genetics
A genetic trait, brachydactyly type D exhibits autosomal dominance and is commonly developed or inherited independently of other hereditary traits. The condition is associated with the HOXD13 gene, which is central in digital formation and growth.Various other studies supported an autosomal dominant pattern with reduced penetrance.
Hereditary trait
A 1965 scientific study in Israel found that 3.05% of Palestinians in Israel had one or two stub thumbs, compared with 1.57% among Ashkenazi as well as non-Ashkenazi Jews. However, as the surveys Arab test persons were mainly recruited from a handful of large and closely related clans living in a particular village, said percentage should be considered with some reservation, according to Goodman et alia (1965).
Cases of stub thumbs have also been found in Eastern Nepal for Jirel ethnic individuals from their participation in various epidemiologic studies. Some studies included taking radiographs of hands and wrists to examine their skeletal structure. Of the studied sample (which included 2,130 participants; 969 male and 1,161 female), 3.55% were found to have brachydactyly type D.
Terminology
The condition is known under numerous names. The most commonly used name is clubbed thumb, or club thumb. American researcher R.A. Hefner used the terms "short thumb" and "brachymegalodactylism" in 1924, and "short thumb" has continued to be used in a few other studies since then, including the study that defined Rubinstein–Taybi syndrome in 1963. "Stub thumb" is the common term preferred by the online database Online Mendelian Inheritance in Man and was first used in a 1965 study. Stub thumbs have also been called murderers thumb (allegedly among fortune tellers), bohemian thumb, toe thumb, and potters thumb.The term "clubbed thumb" should not be confused with nail clubbing, which is a clinical sign associated with a number of diseases.
== References == |
Ganglioneuroblastoma | Ganglioneuroblastoma is a variant of neuroblastoma that is surrounded by ganglion cells.
It can be difficult to diagnose.Nodular ganglioneuroblastoma can be divided by prognosis.
Neuroblastic tumors
It is contained within the neuroblastic tumors group, which includes:
Ganglioneuroma (benign)
Ganglioneuroblastoma (intermediate).
Neuroblastoma (aggressive)
See also
Neuroblastoma
References
== External links == |
Dacryoadenitis | Dacryoadenitis is inflammation of the lacrimal glands.
Symptoms
Swelling of the outer portion of the upper lid, with possible redness and tenderness
Pain in the area of swelling
Excess tearing or discharge
Swelling of lymph nodes in front of the ear
Complications
Swelling may be severe enough to put pressure on the eye and distort vision. Some patients first thought to have dacryoadenitis may turn out to have a malignancy of the lacrimal gland.
Causes
Acute dacryoadenitis is most commonly due to viral or bacterial infection. Common causes include mumps, Epstein-Barr virus, staphylococcus, and gonococcus.
Chronic dacryoadenitis is usually due to noninfectious inflammatory disorders. Examples include sarcoidosis, thyroid eye disease, and orbital pseudotumor.
Diagnosis
Dacryoadenitis can be diagnosed by examination of the eyes and lids. Special tests such as a CT scan may be required to search for the cause. Sometimes biopsy will be needed to be sure that a tumor of the lacrimal gland is not present.
Prevention
Mumps can be prevented by immunization. Gonococcus, bacteria can be avoided by the use of condoms. Most other causes cannot be prevented.
Treatment
If the cause of dacryoadenitis is a viral condition such as mumps, simple rest and warm compresses may be all that is needed. For other causes, the treatment is specific to the causative disease.
Prognosis
Most patients will fully recover from dacryoadenitis. For conditions with more serious causes, such as sarcoidosis, the prognosis is that of the underlying condition.
References
External links
Source (NIH/Medline)
eMedicine
Diseases Database (DDB): 3430 |
Hereditary progressive mucinous histiocytosis | Hereditary progressive mucinous histiocytosis is a very rare, benign, non-Langerhans cell histiocytosis. An autosomal dominant or X-linked hereditary disease described on the skin, it has been found almost exclusively in women. One case of the disease in a male patient has been reported.
See also
Non-X histiocytosis
References
== External links == |
Fechtner syndrome | Fechtner syndrome is a variant of Alport syndrome characterized by leukocyte inclusions, macrothrombocytopenia, thrombocytopenia, nephritis, and sensorineural hearing loss. Some patients may also develop cataracts.
References
== External links == |
Breast hematoma | Breast hematoma is a collection of blood within the breast. It arises from internal bleeding (hemorrhage) and may arise due to trauma (breast injury or surgery) or due to a non-traumatic cause.
Symptoms
Symptoms may include visible discoloring (ecchymosis), breast pain, and swelling.
The symptoms may be similar to those of fibrocystic breast changes.
Causes
A breast hematoma may appear due to direct trauma to the breast, for example from a sports injury or a road accident, for example a vehicle collision in which a seat belt injury occurs.
Hematoma can also be a consequence of breast surgery, usually due to post-operative bleeding. Bleeding may occur shortly after the intervention or a number of days later and can occur for cosmetic surgery (for example breast reduction or breast enhancement) and for non-cosmetic surgery (for example lymph node removal, lumpectomy, or mastectomy). More rarely, hematoma can result from breast biopsy.
Rarely, a breast hematoma can also occur spontaneously due to a rupture of blood vessels in the breast, especially in persons with coagulopathy or after long-term use of blood-thinning drugs such as aspirin or ibuprofen.
Pathophysiology
Small breast hematomas often resolve on their own within several days or weeks by means of reabsorption of the blood. Larger hematomas are more likely to lead to inflammation or fibrosis.
Breast hematomas can sometimes lead to skin discoloration, inflammation, or fever. When a hematoma resolves, it may become fibrotic, leaving behind scar tissue. A resolving hematoma may liquify to form a seroma.
Post-surgical breast hematomas can also impede wound healing and therefore impact the cosmetic outcome. Hematomas are furthermore one of the risk factors for breast surgical site infections. There is preliminary evidence that, after breast implant surgery, the presence of hematoma increases the risk of developing capsular contracture.In mammography screening, scar tissue resulting from a breast hematoma can easily be confused with tumor tissue, especially in the first years following surgery. Ultimately, fat necrosis may occur in the concerned region of the breast.
Diagnosis
When there is post-operative swelling after breast surgery or core needle biopsy, a breast ultrasound examination may be indicated in order to differentiate between a hematoma and other possible post-surgical complications such as abscess or seroma, A recent hematoma is usually visible in a mammogram. and it also shows typical signal intensities on MR imaging. If a differentiation from breast cancer is necessary, a hematoma biopsy may be indicated.
A careful consideration of the case history is important for the diagnosis of a breast hematoma.
Treatment
Small breast hematomas that cause no discomfort often require merely clinical observation, with ultrasound being used to monitor the resolution of the hematoma.
Large breast hematomas, or those that are not becoming smaller or that are causing discomfort, usually require drainage. Also hematomas that occur after surgery for excision of a malignant tumor are drained, because a hematoma to which irradiation is applied is unlikely to ever resolve. A recent hematoma can be drained by means of needle aspiration or (rarely) open surgical drainage.
References
== External links == |
Hereditary elliptocytosis | Hereditary elliptocytosis, also known as ovalocytosis, is an inherited blood disorder in which an abnormally large number of the persons red blood cells are elliptical rather than the typical biconcave disc shape. Such morphologically distinctive erythrocytes are sometimes referred to as elliptocytes or ovalocytes. It is one of many red-cell membrane defects. In its severe forms, this disorder predisposes to haemolytic anaemia. Although pathological in humans, elliptocytosis is normal in camelids.
Presentation
Pathophysiology
Common hereditary elliptocytosis
A number of genes have been linked to common hereditary elliptocytosis (many involve the same gene as forms of Hereditary spherocytosis, or HS):
These mutations have a common end result; they destabilise the cytoskeletal scaffold of cells. This stability is especially important in erythrocytes as they are constantly under the influence of deforming shear forces. As disc-shaped erythrocytes pass through capillaries, which can be 2-3 micrometres wide, they are forced to assume an elliptical shape in order to fit through. Normally, this deformation lasts only as long as a cell is present in a capillary, but in hereditary elliptocytosis the instability of the cytoskeleton means that erythrocytes deformed by passing through a capillary are forever rendered elliptical. These elliptical cells are taken up by the spleen and removed from circulation when they are younger than they would normally be, meaning that the erythrocytes of people with hereditary elliptocytosis have a shorter than average life-span (a normal persons erythrocytes average 120 days or more).
EL2 and EL3: The most common genetic defects (present in two-thirds of all cases of hereditary elliptocytosis) are in genes for the polypeptides α-spectrin or β-spectrin. These two polypeptides combine with one another in vivo to form an αβ heterodimer. These αβ heterodimers then combine to form spectrin tetramers. These spectrin tetramers are among the basic structural subunits of the cytoskeleton of all cells in the body. Although there is much interindividual variability, it is generally true that α-spectrin mutations result in an inability of α-spectrin to interact properly with β-spectrin to form a heterodimer. In contrast, it is generally true that β-spectrin mutations lead to αβ heterodimers being incapable of combining to form spectrin tetramers. In both cases the end result is a weakness in the cytoskeleton of the cell. Individuals with a single mutation in one of the spectrin genes are usually asymptomatic, but those who are homozygotes or are compound heterozygotes (i.e. they are heterozygous for two different elliptocytosis-causing mutations) have sufficient cell membrane instability to have a clinically significant haemolytic anaemia.
EL1: Less common than spectrin mutations are band 4.1 mutations. Spectrin tetramers must bind to actin in order to create a proper cytoskeleton scaffold, and band 4.1 is an important protein involved in the stabilisation of the link between spectrin and actin. Similarly to the spectrin mutations, band 4.1 mutations cause a mild haemolytic anaemia in the heterozygous state, and a severe haemolytic disease in the homozygous state.
EL4: Southeast Asian ovalocytosis is associated with the Band 3 protein.
Another group of mutations that lead to elliptocytosis are those that cause glycophorin C deficiencies. There are three phenotypes caused by abnormal glycophorin C, these are named Gerbich, Yus and Leach (see glycophorin C for more information). Only the rarest of the three, the Leach phenotype, causes elliptocytosis. Glycophorin C has the function of holding band 4.1 to the cell membrane. It is thought that elliptocytosis in glycophorin C deficiency is actually the consequence of a band 4.1 deficit, as glycophorin C deficient individuals also have reduced intracellular band 4.1 (probably due to the reduced number of binding sites for band 4.1 in the absence of glycoprotein C).Inheritance of multiple mutations tends to infer more serious disease. For instance, the most common genotype responsible for HPP occurs when the affected individual inherits an α-spectrin mutation from one parent (i.e. one parent has hereditary elliptocytosis) and the other parent passes on an as-yet-undefined defect that causes the affected individuals cells to preferentially produce the defective α-spectrin rather than normal α-spectrin.
Diagnosis
The diagnosis of hereditary elliptocytosis is usually made by coupling a family history of the condition with an appropriate clinical presentation and confirmation on a blood smear. In general it requires that at least 25% of erythrocytes in the specimen are abnormally elliptical in shape, though the observed percentage of elliptocytes can be 100%. This is in contrast to the rest of the population, in which it is common for up to 15% of erythrocytes to be elliptical.If some doubt remains regarding the diagnosis, definitive diagnosis can involve osmotic fragility testing, an autohaemolysis test, and direct protein assaying by gel electrophoresis.
Treatment
The vast majority of those with hereditary elliptocytosis require no treatment whatsoever. They have a mildly increased risk of developing gallstones, which is treated surgically with a cholecystectomy if pain becomes problematic. This risk is relative to the severity of the disease.Folate helps to reduce the extent of haemolysis in those with significant haemolysis due to hereditary elliptocytosis.Because the spleen breaks down old and worn-out blood cells, those individuals with more severe forms of hereditary elliptocytosis can have splenomegaly. Symptoms of splenomegaly can include:
Vague, poorly localised abdominal pain
Fatigue and dyspnoea
Growth failure
Leg ulcers
Gallstones.Removal of the spleen (splenectomy) is effective in reducing the severity of these complications, but is associated with an increased risk of overwhelming bacterial septicaemia, and is only performed on those with significant complications. Because many neonates with severe elliptocytosis progress to have only a mild disease, and because this age group is particularly susceptible to pneumococcal infections, a splenectomy is only performed on those under 5 years old when it is absolutely necessary.
Prognosis
Those with hereditary elliptocytosis have a good prognosis, only those with very severe disease have a shortened life expectancy.
Epidemiology
The incidence of hereditary elliptocytosis is hard to determine, as many sufferers of the milder forms of the disorder are asymptomatic and their condition never comes to medical attention. Around 90% of those with this disorder are thought to fall into the asymptomatic population. It is estimated that its incidence is between 3 and 5 per 10,000 in the United States, and that those of African and Mediterranean descent are of higher risk. Because it can confer resistance to malaria, some subtypes of hereditary elliptocytosis are significantly more prevalent in regions where malaria is endemic. For example, in equatorial Africa its incidence is estimated at 60-160 per 10,000, and in Malayan natives its incidence is 1500-2000 per 10,000. Almost all forms of hereditary elliptocytosis are autosomal dominant, and both sexes are therefore at equal risk of having the condition. The most important exception to this rule of autosomal dominance is for a subtype of hereditary elliptocytosis called hereditary pyropoikilocytosis (HPP), which is autosomal recessive.There are three major forms of hereditary elliptocytosis: common hereditary elliptocytosis, spherocytic elliptocytosis and southeast Asian ovalocytosis.
Common hereditary elliptocytosis is the most common form of elliptocytosis, and the form most extensively researched. Even when looking only at this form of elliptocytosis, there is a high degree of variability in the clinical severity of its subtypes. A clinically significant haemolytic anaemia occurs only in 5-10% of sufferers, with a strong bias towards those with more severe subtypes of the disorder.Southeast Asian ovalocytosis and spherocytic elliptocytosis are less common subtypes predominantly affecting those of south-east Asian and European ethnic groups, respectively.
The following categorisation of the disorder demonstrates its heterogeneity:
Common hereditary elliptocytosis (in approximate order from least severe to most severe)
With asymptomatic carrier status - individuals have no symptoms of disease and diagnosis is only able to be made on blood film
With mild disease - individuals have no symptoms, with a mild and compensated haemolytic anaemia
With sporadic haemolysis - individuals are at risk of haemolysis in the presence of particular comorbidities, including infections, and vitamin B12 deficiency
With neonatal poikilocytosis - individuals have a symptomatic haemolytic anaemia with poikilocytosis that resolves in the first year of life
With chronic haemolysis - individual has a moderate to severe symptomatic haemolytic anaemia (this subtype has variable penetrance in some pedigrees)
With homozygosity or compound heterozygosity - depending on the exact mutations involved, individuals may lie anywhere in the spectrum between having a mild haemolytic anaemia and having a life-threatening haemolytic anaemia with symptoms mimicking those of HPP (see below)
With pyropoikilocytosis (HPP) - individuals are typically of African descent and have a life-threateningly severe haemolytic anaemia with micropoikilocytosis (small and misshapen erythrocytes) that is compounded by a marked instability of erythrocytes in even mildly elevated temperatures (pyropoikilocytosis is often found in burns victims and is the term is commonly used in reference to such people)
South-east Asian ovalocytosis (SAO) (also called stomatocytic elliptocytosis) - individuals are of South-East Asian descent (typically Malaysian, Indonesian, Melanesian, New Guinean or Filipino, have a mild haemolytic anaemia, and has increased resistance to malaria
Spherocytic elliptocytosis (also called hereditary haemolytic ovalocytosis) - individuals are of European descent and elliptocytes and spherocytes are simultaneously present in their blood
History
Elliptocytosis was first described in 1904, and was first recognised as a hereditary condition in 1932. More recently it has become clear that the severity of the condition is highly variable, and there is much genetic variability amongst those affected.
See also
AMMECR1
List of hematologic conditions
References
External links
Hereditary Elliptocytosis Image of hereditary elliptocytosis
MedlinePlus Entry |
Sneddons syndrome | Sneddons syndrome is a form of arteriopathy characterized by several symptoms, including:
Severe, transient neurological symptoms or stroke
Livedo reticularis, or livedo racemosa
Signs and symptoms
Sneddons syndrome generally manifests with stroke or severe, transient neurological symptoms, and a skin rash (livedo reticularis). Livedo reticularis appears as a bluish-purple, netlike mottling of the skin. Sneddons syndrome may instead present with livedo racemosa, which involves larger, less organized patches of bluish-purple mottling of the skin. Both are generally found first in the extremities, both worsen in cold and either may occur without Sneddons Syndrome or any other systemic disease.Sneddons Syndrome can be characterized by: transient amnesia, transient aphasia, palsy, headaches, hypertension, transient ischemic attacks (TIA), stroke, coronary disease and dementia. The skin manifestations may precede the neurologic symptoms by years.
Pathogenesis
Sneddons syndrome is a progressive, noninflammatory arteriopathy leading to the characteristic skin condition and to cerebrovascular problems, including stroke, transient ischemic attack (TIA), severe but transient neurological symptoms thought to be caused by cerebral vasospasm, coronary disease and early-onset dementia. Progressive compromise of arterial linings in Sneddons produces clotting, for which high-dose warfarin is most commonly prescribed, and can also cause the development of systemic arterial plaque when cholesterol levels are normal.
Diagnosis
There are no diagnostic tests on which all Sneddons patients will have abnormal results, although brain MRI and skin biopsy are often abnormal. The diagnosis is based on a detailed history and physical examination. About 40-60% of patients with the syndrome test positive for antiphospholipid antibodies.
Treatment
Sneddons patients are generally treated with warfarin, maintaining a high INR of 3–4. Because most will experience significant relief of symptoms after several months of consistent INR in this range, treatment with warfarin is often used as a diagnostic tool.
Epidemiology
Sneddons syndrome is a rare condition that is usually misdiagnosed. It occurs in families and may be inherited in an autosomal dominant fashion. Sneddons Syndrome most often becomes apparent in women in their thirties, though cases do occur in men and in children. Generally, Livedo precedes cerebrovascular involvement by roughly ten years, and many years of cerebrovascular involvement precede the development of dementia, when it occurs.
History
It is named for Ian Bruce Sneddon. In 1965, Dr. Sneddon first reported 6 patients with a distinct skin rash and cerebrovascular accidents (strokes).Sneddons Syndrome was formerly understood to be a type of autoimmune disease called antiphospholipid syndrome, although it has been reclassified as a noninflammatory cerebrovascular disease. It should be considered in patients diagnosed with vasculitis when standard treatments fail.
See also
Livedoid vasculopathy
List of cutaneous conditions
References
Further reading
Schellong S, Weissenborn K, Niedermeyer J, Wollenhaupt J, Sosada M, Ehrenheim C, Lubach D (1997). "Classification of Sneddons syndrome". Vasa. 26 (3): 215–21. PMID 9286155.
== External links == |
Cerebellopontine angle syndrome | The cerebellopontine angle syndrome is a distinct neurological syndrome of deficits that can arise due to the closeness of the cerebellopontine angle to specific cranial nerves. Indications include unilateral hearing loss (85%), speech impediments, disequilibrium, tremors or other loss of motor control. The cerebellopontine angle cistern is a subarachnoid cistern formed by the cerebellopontine angle that lies between the cerebellum and the pons. It is filled with cerebrospinal fluid and is a common site for the growth of acoustic neuromas or schwannomas.
Signs and Symptoms
Tumors within the nerve canaliculi initially present with unilateral sensorineural hearing loss, unilateral tinnitus, or disequilibrium (vertigo is rare, on account of the slow growth of neuromas). Speech discrimination out of proportion to hearing loss, difficulty talking on the telephone are frequent accompaniments. Tumors extending into the CPA will likely present with disequilibrium or ataxia depending on the amount of extension on the brainstem. With brainstem extension, midfacial and corneal hypesthesia, hydrocephalus, and other cranial neuropathies become more prevalent.
For example, involvement of CN V from a cerebellopontine mass lesion often results in loss of the ipsilateral (same side of the body) corneal reflex (involuntary blink).
Patients with larger tumours can develop Bruns nystagmus (dancing eyes) due to compression of the flocculi.
Causes
In most cases, the cause of acoustic neuromas is unknown. The only statistically significant risk factor for developing an acoustic neuroma is having a rare genetic condition called neurofibromatosis type 2 (NF2). There are no confirmed environmental risk factors for acoustic neuroma. There are conflicting studies on the association between acoustic neuromas and cellular phone use and repeated exposure to loud noise. In 2011, an arm of the World Health Organization released a statement listing cell phone use as a low grade cancer risk. The Acoustic Neuroma Association recommends that cell phone users use a hands-free device.
Meningiomas are significantly more common in women than in men; they are most common in middle-aged women. Two predisposing factors associated with meningiomas for which at least some evidence exists are exposure to ionizing radiation (cancer treatment of brain tumors) and hormone replacement therapy.
Pathophysiology
Various kinds of tumors, usually primary and benign, are represented in the pathology. Lesions in the area of cerebellopontine angle cause signs and symptoms secondary to compression of nearby cranial nerves, including cranial nerve V (trigeminal), cranial nerve VII (facial), and cranial nerve VIII (vestibulocochlear). The most common cerebellopontine angle (CPA) tumor is a vestibular schwannoma affecting cranial nerve VIII (80%), followed by meningioma (10%). The cranial nerves affected are (from most common to least common) : VIII (cochlear component), VIII (vestibular component), V
Acoustic neuroma/vestibular schwannoma
Meningioma, a tumor of the meninges or membranes that surround the nerves passing through the CPA
Cerebellar astrocytoma, a malignant tumor of star-shaped glial cells called astrocytes in the cerebellum
Intracranial epidermoid cyst
Lipoma
Glomus jugulare associated with the glossopharyngeal nerve
Idiopathic hypertrophic pachymeningitis
IgG4-related hypertrophic pachymeningitis
CPA Metastases in cancer patients with inner ear symptoms (rare)
Diagnosis
Radiography
Subsequent to diagnosis of sensorineural hearing loss, and differential diagnosis of retrocochlear or neural etiologies,
radiological assessment of the CPA is performed to assess the presence of anatomical retrocochlear lesions.
Traditional protocols
Before the advent of MRI, electronystagmography and Computed Tomography were employed for diagnosis of acoustic neuroma.
Auditory brainstem response audiometry and adjunct tests
The auditory brainstem response (ABR) test gives information about the inner ear (cochlea) and nerve pathways for hearing via ongoing electrical activity in the brain measured by electrodes placed on the scalp. Five different waves (I to V) are measured for each ear. Each waveform represents specific anatomical points along the auditory neural pathway. Delays of one side relative to the other suggest a lesion in cranial nerve VIII between the ear and brainstem or in the brainstem itself. The most reliable indicator for acoustic neuromas from the ABR is the interaural latency differences in wave V: the latency in the impaired ear is prolonged. Different studies have indicated the sensitivity of ABR for detection of acoustic neuromas 1cm or larger to be between 90 and 95%. Sensitivity for neuromas smaller than 1cm are 63-77%. A newer technology, stacked ABR, may have sensitivity as high as 95% with specificity 88% for smaller tumors. ABR is considerably more cost effective, but MRI provides more information.
Stapedius reflex (SR) and caloric vestibular response (CVR) are non-invasive otologic tests for auditory neural function. These are not primary diagnostics for CPA neuromas, and are usually used in conjunction
with ABR.
Magnetic resonance imaging
Several different types of magnetic resonance imaging (MRI) may be employed in diagnosis: MRI without contrast, Gd contrast enhanced T1-weighted MRI (GdT1W) or T2-weighted enhanced MRI (T2W or T2*W). Non-contrast enhanced MRI is considerably less expensive than any of the contrast enhanced MRI scans. The gold standard in diagnosis is GdT1W MRI.
The reliability of non-contrast enhanced MRI is highly dependent on the sequence of scans, and the experience of the operator.
Management
Acoustic neuromas are managed by either surgery, radiation therapy, or observation with regular MRI scanning. With treatment, the likelihood of hearing preservation varies inversely with the size of the tumor; for large tumors, preservation of hearing is rare. Because acoustic neuromas, meningiomas and most other CPA tumors are benign, slow growing or non-growing, and non-invasive, observation is a viable management option.
Stereotactic radiosurgery
The objective of irradiation is to halt the growth of the acoustic neuroma tumour, it does not excise it from the body, as the term radiosurgery or gammaknife implies. Radiosurgery is only suitable for small to medium size tumors.
Surgical
There are three modalities of surgical treatment (excision) depending on where the anatomical location of the incision to access the tumor is made: retrosigmoid (a variant of what was formerly called suboccipital), translabyrinthine, and middle fossa.
The goals of surgery are to control the tumor, and preserve hearing as well as facial nerves. Especially in the case of larger tumors, there may be a tradeoff between tumor removal and preservation of nerve functionality.
There are different defined degrees of surgical excision, termed subtotal resection, radical subtotal resection, near-total resection, and total resection in order or increasing proportion of tumor removed. Lesser amount of tumor removal may increase likelihood of preservation of nerve function (hence better post-operative hearing), but also likelihood of tumor regrowth, necessitating additional treatment.
Outcome and complications
The overall complication rate following surgery is around 20%; cerebrospinal fluid leak is the most common.
See also
Cerebellum
Pons
References
== External links == |
Protruding ear | Prominent ear, otapostasis or bat ear is an abnormally protruding human ear. It may be unilateral or bilateral. The concha is large with poorly developed antihelix and scapha. It is the result of malformation of cartilage during primitive ear development in intrauterine life. The deformity can be corrected anytime after six years of age. The surgery is preferably done at the earliest possible age in order to avoid psychological distress. Correction by otoplasty involves changing the shape of the ear cartilage so that the ear is brought closer to the side of the head. The skin is not removed, but the shape of the cartilage is altered. The surgery does not affect hearing. It is done for cosmetic purposes only. The complications of the surgery, though rare, are keloid formation, hematoma formation, infection and asymmetry between the ears.
See also
Cauliflower ear
Incisionless Fritsch otoplasty
== References == |
Palisaded encapsulated neuroma | Palisaded encapsulated neuroma (PEN) is a rare, benign cutaneous condition characterized by small, firm, non-pigmented nodules or papules. They typically occur as a solitary (single) lesion near the mucocutaneous junction of the skin of the face, although they can occur elsewhere on the body.
Symptoms
PEN tumours are always painless, solid masses felt on the skin that, due to their slow-growing nature, typically take many years to grow to a size where they are noticeable. There are never any symptoms associated with systemic disease.
Diagnosis
As mentioned previously, PEN is a benign, firm, flesh-coloured lesion that typically occurs in dermis of the skin of the face. The lesions are typically between 2–6mm and are slow-growing.On the face, the lesions can be found on the eyelid, nose and in the oral mucosa, however, the lesions can also occur on the shoulder, arm, hand, foot and the glans of the penis.PEN is diagnosed by clinical recognition of the lesion and on subsequent histologic examination. Typically, the lesions are suspected to be schwannomas or neurofibromas clinically with PEN being an incidental finding on histology.PEN is typically diagnosed in patients between the ages of 40 and 60 years and occurs more frequently in females than males. The diagnosis of PEN may be difficult, even with confirmatory histology, due to its histological similarities with schwannomas and neurofibromas. It is imperative that the correct diagnosis is made the misdiagnosis of a neurofibroma may lead to unnecessary further investigation into associated systemic syndromes such as neurofibromatosis type 1 or multiple endocrine neoplasia syndrome.The differential diagnosis for PEN includes a neurofibroma, basal cell carcinoma, melanocytic nevus, epidermoid cyst and a skin appendage.
Treatment
The only definitive treatment of PEN is surgical excision. Excision is curative and rarely recur.
Gallery
See also
List of cutaneous conditions
References
== External links == |
Esthiomene | Esthiomene is a medical term referring to elephantiasis of the female genitals. In the past the term has also referred to elephantiasis of the male genitalia.Esthiomene is generally the visible result of lymphogranuloma venereum, lymphatic infection by Chlamydia trachomatis. This sexually transmitted infection produces inflammation of the lymphatic channels in the female genitalia, followed by abscesses, fistulae, ulcerations, and fibrosis of the tissues. The tissues swell, sometimes severely, and the genitalia may grow to a massive size. Esthiomene can also be the result of tuberculosis when the infection takes hold in the genitalia, or of cancer or filariasis, infection with parasitic roundworms.The condition is painful and sometimes disabling. People with the condition can experience mental distress from the pain and physical deformation of their genitalia. Masses can become so large they make walking difficult.Treatment of the condition includes treatment of bacterial chlamydial infections with antibiotics such as doxycycline, or treatment of other infections present. Remaining tissue deformity can be treated with surgery such as labiaplasty to reduce the size of hypertrophied labia minora. Goals of surgery include pain relief, restoration of sexual function, and cosmetic improvement.
== References == |
March fracture | March fracture, is the fracture of the distal third of one of the metatarsals occurring because of recurrent stress. It is more common in soldiers, but also occurs in hikers, organists, and people whose duties entail much standing (such as hospital doctors). March fractures most commonly occur in the second and third metatarsal bones of the foot. It is a common cause of foot pain, especially when people suddenly increase their activities.
Signs and symptoms
The onset is not dramatic. When the boot or shoes are taken off, there is a cramp-like pain in the affected forefoot, and moderate local edema appears on the dorsal aspect. On moving each toe in turn, that of the involved metatarsal causes pain, and when the bone is palpated from the dorsal surface, a point of tenderness is found directly over the lesion. Radiography at this stage is negative, but the condition is diagnosed correctly by military surgeons without the aid of x-rays. In civil life, it is seldom diagnosed correctly for a week or two, when, because of lack of immobilization, there is an excessive deposit of callus (which may be palpable) around the fracture.
Diagnosis
X-ray is seldom helpful, but a CT scan and an MRI study may help in diagnosis.
Bone scans are positive early on. Dual energy X-ray absorptiometry is also helpful to rule out comorbid osteoporosis.
Differential diagnosis
Acute metatarsal fracture
Hallux rigidus
Jones fracture
Sesamoid stress fracture
Acute sesamoid fracture
Proximal fifth metatarsal avulsion fracture
Treatment
The first line treatment should be reduction of movements for 6 to 12 weeks. Wooden-soled shoes or a cast should be given for this purpose. In rare cases in which stress fracture occurs with a cavus foot, plantar fascia release may be appropriate.
Occurrence
Stress fractures can occur at many sites in the body; "march fracture" simply refers to a stress fracture specifically of the metatarsals, so named because the injury is sometimes sustained by soldiers during sustained periods of marching. Although march fractures can occur to the 5th metatarsal, fractures of this bone are more likely to be trauma-related fractures to the diaphysis, termed Jones fractures. In runners, march fracture occurs most often in the metatarsal neck, while in dancers it occurs in the proximal shaft. In ballet dancers, fracture mostly occurs at the base of the second metatarsal and at Lisfranc joints. This fracture always occurs following a prolonged stress or weight bearing, and the history of direct trauma is very rare. Consideration should always be given to osteoporosis and osteomalacia. Cavus feet are a risk factor for march fracture.
References
== External links == |
Koilonychia | Koilonychia, also known as spoon nails,: 782 is a nail disease that can be a sign of hypochromic anemia, especially iron-deficiency anemia.: 656 It refers to abnormally thin nails (usually of the hand) which have lost their convexity, becoming flat or even concave in shape. In a sense, koilonychia is the opposite of nail clubbing. In early stages nails may be brittle and chip or break
easily.
Koilonychia is associated with Plummer–Vinson syndrome and iron deficiency anemia. It has also been associated with lichen planus, syphilis, and rheumatic fever. The term is from the Greek: κοῖλος, koilos, "hollow", ὄνυξ, onyx, "nail".
Even though Koilonychia has been associated with iron deficiency in case reports, it is more likely seen as an occupational change in nails and may be idiopathic; ruling out iron deficiency anemia in these patients is the only work-up necessary in this condition.
See also
Kyrle disease
List of cutaneous conditions
References
External links
DermAtlas 1726262099 |
Lobomycosis | Lobomycosis is a fungal infection of the skin. It usually presents with bumps in the skin, firm swellings, deep skin lesions, or malignant tumors.It is caused by Lacazia loboi (formerly named Loboa loboi). Transmission is generally by direct contact with contaminated water, soil, vegetation, or by direct contact with an infected dolphin.Diagnosis is by identifying Lacazia laboi in a lesion.This disease is usually found in humans and bottlenose dolphins, with the possible risk of transmission from one species to the other.It was discovered by Brazilian dermatologist Jorge Lobo. Other names which were given to the disease are: keloidal blastomycosis, Amazonian blastomycosis, blastomycoid granuloma, miraip and piraip. These last two names were given by natives of the Amazon and mean that which burns.
Signs and symptoms
The disease is endemic in rural regions in South America and Central America.Infection most commonly develops after minor scratches or insect bites, but many patients cannot recall any skin trauma. Human-to-human transmission does not occur, and the disease is only acquired from the environment. The disease manifests as chronic keloidal nodular lesions on the ears, legs, or arms.
Diagnosis of Lobos disease is made by taking a sample of the infected skin (a skin biopsy) and examining it under the microscope. Lacazia loboi is characterized by long chains of spherical cells interconnected by tubules. The cells appear to be yeast-like with a diameter of 5 to 12 μm. Attempts to culture L. loboi have so far been unsuccessful.
Diagnosis
Differential diagnosis
The disease is often misdiagnosed as Blastomyces dermatitidis or Paracoccidiodes brasiliensis due to its similar morphology.
Treatment
Surgical excision or cryosurgery is the treatment of choice. Treatment with antifungals has been considered ineffective, but the use of clofazimine and dapsone in patients with leprosy and lobomycosis has been found to improve the latter. This treatment regimen, with concomitant itraconazole, has been used to prevent recurrence after surgery.
Other animals
Lesions in dolphins occur on the dorsal fin, head, flukes, and peduncle. In January 2006, a potential epidemic of lobomycosis was reported in dolphins of the Indian River Lagoon in Florida.
See also
List of cutaneous conditions
References
Further reading
Bermudez, L., M.F. van Bressem, O. Reyes-Jaimes, A.J. Sayegh & A.E. Paniz Mondolfi (2009) Lobomycosis in man and lobomycosis-like disease in bottlenose dolphin, Venezuela. Emerg. Infect. Dis., 15: 1301–1303.
Carvalho, K. A. D., Floriano, M. C., Enokihara, M. M. S., & Mascarenhas, M. R. M. (2015). Jorge Lobo’s disease. Anais brasileiros de dermatologia, 90(4), 586–588.
Esperon, F., D. Garcia-Parraga, E.N. Belliere & J.M. Sanchez-Vizcaino (2012) Molecular diagnosis of lobomycosis-like disease in a bottlenose dolphin in captivity. Med. Mycol., 50: 106–109.
Francesconi, V. A., Klein, A. P., Santos, A. P. B. G., Ramasawmy, R., & Francesconi, F (2014) Lobomycosis: epidemiology, clinical presentation, and management options. Therapeutics and Clinical Risk Management, 10, 851.
Rodríguez-Toro G (May 1993). "Lobomycosis". Int. J. Dermatol. (Review). 32 (5): 324–32. doi:10.1111/j.1365-4362.1993.tb01466.x. PMID 8505156. S2CID 221814305.
Paniz-Mondolfi, A., C. Talhari, L.S. Hoffmann, D.L. Connor and S. Talhari & al. (2012) Lobomycosis: An emerging disease in humans and delphinidae. Mycoses, 55: 298-309 | résumé.
Reif, J.S., A.M. Schaefer & G.D. Bossart (2013) Lobomycosis: Risk of zoonotic transmission from dolphins to humans. Vector Borne Zoonotic Dis., 13: 689–693.
Schaefer, A. M., Reif, J. S., Guzmán, E. A., Bossart, G. D., Ottuso, P., Snyder, J., ... & McCarthy, P. J. (2016). Toward the identification, characterization and experimental culture of Lacazia loboi from Atlantic bottlenose dolphin (Tursiops truncatus). Sabouraudia, 54(6), 659–665.
== External links == |
Proliferating angioendotheliomatosis | Proliferating Angioendotheliomatosis has historically been divided into two groups, (1) a reactive, involuting type and (2) a malignant, rapidly fatal type.: 598 The reactive involuting type, reactive Angioendotheliomatosis is an rare cutaneous condition characterized histologically by a dense proliferation of small capillaries, and occurs in people with various diseases including subacute bacterial endocarditis and end-stage atherosclerotic disease. These people present with various skin lesions and rashes - most commonly on the thighs. Treatment aimed at the underlying condition hastens the resolution of the lesions.
The malignant type is an intravascular lymphoma, usually of the diffuse B-cell type, known as intravascular large B-cell lymphoma. It progresses rapidly through involvement of multiple body systems and mortality occurs in less than a year from the initial diagnosis. The average age of diagnosis being 55 years. The causative mechanism is unknown. In a few cases treatment with palliative chemotherapy has been effective.: 598
Classification of Proliferating Angioendotheliomatosis
Proliferating angioendotheliomatosis may be divided into two types:
a reactive type – Reactive angioendotheliomatosis
a malignant type – Intravascular large B-cell lymphoma
Treatment
In few cases palliative chemotherapy is effective.
A 30-year-old woman was diagnosed with cutaneous proliferating angioendotheliomatosis. She was treated with a local excision and radiotherapy.
See also
List of cutaneous conditions
References
External links
== External links == |
Plateau iris | Plateau iris is a less common medical condition of the eye resulting from anterior displacement of the peripheral iris by the ciliary body causing angle closure glaucoma. First line treatment for all causes of narrow angle glaucoma is laser iridotomy. If narrow angle glaucoma persists after iridotomy then it is called plateau iris syndrome and subsequently managed either medically (miotics) or surgically (laser peripheral iridoplasty). Plateau iris is a less common form of narrow angle glaucoma and is sometimes discovered after an iridotomy causes a rapid increase in eye pressure. Since this condition is not common, most ophthalmologists are unfamiliar with, and have little experience with, the anatomy of and treatments for this condition.
References
Further reading
Wand, M; Grant, WM; Simmons, RJ; Hutchinson, BT (January 1977). "Plateau iris syndrome". Transactions. Section on Ophthalmology. American Academy of Ophthalmology and Otolaryngology. 83 (1): 122–130. PMID 898466. NAID 10029605696.
Pavlin, Charles J.; Ritch, Robert; Foster, F. Stuart (April 1992). "Ultrasound Biomicroscopy in Plateau Iris Syndrome". American Journal of Ophthalmology. 113 (4): 390–395. doi:10.1016/s0002-9394(14)76160-4. PMID 1558112.
Ritch, Robert (April 1992). "Plateau Iris Is Caused by Abnormally Positioned Ciliary Processes". Journal of Glaucoma. 1 (1): 23–26. doi:10.1097/00061198-199204000-00006. S2CID 72047734.
Diniz Filho, Alberto; Cronemberger, Sebastião; Mérula, Rafael Vidal; Calixto, Nassim (October 2008). "Plateau iris". Arquivos Brasileiros de Oftalmologia. 71 (5): 752–758. doi:10.1590/S0004-27492008000500029. PMID 19039479.
Ritch, Robert; Tham, Clement C.Y; Lam, Dennis S.C (January 2004). "Long-term success of argon laser peripheral iridoplasty in the management of plateau iris syndrome". Ophthalmology. 111 (1): 104–108. doi:10.1016/j.ophtha.2003.05.001. PMID 14711720.
Kumar, Rajesh S.; Baskaran, Mani; Chew, Paul T.K.; Friedman, David S.; Handa, Swati; Lavanya, Raghavan; Sakata, Lisandro M.; Wong, Hon-Tym; Aung, Tin (March 2008). "Prevalence of Plateau Iris in Primary Angle Closure Suspects". Ophthalmology. 115 (3): 430–434. doi:10.1016/j.ophtha.2007.07.026. PMID 17900691.
Kumar, Rajesh S.; Tantisevi, Visanee; Wong, Melissa H.; Laohapojanart, Kobkuea; Chansanti, Orathai; Quek, Desmond T.; Koh, Victor T.; MohanRam, Lakshmana S.; Lee, Kelvin Y.; Rojanapongpun, Prin; Aung, Tin (12 October 2009). "Plateau Iris in Asian Subjects With Primary Angle Closure Glaucoma". Archives of Ophthalmology. 127 (10): 1269–1272. doi:10.1001/archophthalmol.2009.241. PMID 19822841.
Viet Tran, H; Liebmann, Jeffrey M; Ritch, Robert (January 2003). "Iridociliary apposition in plateau iris syndrome persists after cataract extraction". American Journal of Ophthalmology. 135 (1): 40–43. doi:10.1016/S0002-9394(02)01842-1. PMID 12504695.
Pavlin, Charles J; Foster, F.Stuart (September 1999). "Plateau iris syndrome: changes in angle opening associated with dark, light, and pilocarpine administration". American Journal of Ophthalmology. 128 (3): 288–291. doi:10.1016/s0002-9394(99)00149-x. PMID 10511021. |
Proctocolitis | Proctocolitis is a general term for inflammation of the rectum and colon.
Signs and symptoms
Cause
Proctocolitis has many possible causes. Common infectious causes of proctocolitis include Chlamydia trachomatis, LGV (Lymphogranuloma venereum), Neisseria gonorrhoeae, HSV, and Helicobacter species. It can also be idiopathic (see colitis), vascular (as in ischemic colitis), or autoimmune (as in inflammatory bowel disease).
Diagnosis
Anoscopy can be used to diagnose the majority of cases of proctocolitis.
Treatment
Antibiotics, such as ceftriaxone and doxycycline, if there is infection
See also
Colitis
Proctitis
References
== External links == |
Cheyletiella | Cheyletiella is a genus of mites that live on the skin surface of dogs, cats, and rabbits.The adult mites are about 0.385 millimeters long, have eight legs with combs instead of claws, and have palpi that end in prominent hooks. They do not burrow into the skin, but live in the keratin level. Their entire 21-day life cycle is on one host. They cannot survive off the host for more than 10 days.
Cheyletiellosis
Cheyletiellosis (also known as Cheyletiella dermatitis)," is a mild dermatitis caused by mites of the genus Cheyletiella. It is also known as walking dandruff due to skin scales being carried by the mites.
Cheyletiellosis is seen more commonly in areas where fleas are less prevalent, because of the decreased use of flea products that are also efficacious for the treatment of this mite.Cheyletiellosis is highly contagious. Transmission is by direct contact with an affected animal.
Presentation
Symptoms in animals vary from no signs to intense itching, scales on the skin, and hair loss. The lesions are usually on the back of the animal. Symptoms in humans include multiple red, itchy bumps on the arms, trunk, and buttocks. Because humans are not a host for the mite, the symptoms usually go away in about three weeks. Though the medical community does not consider a human mite infestation a legitimate diagnosis, it will treat the symptoms if necessary.
Diagnosis
Diagnosis is by finding the mites or eggs microscopically in a skin scraping, combing, or on acetate tape applied to the skin.
Treatment
The most common treatment in animals is weekly use of some form of topical pesticide appropriate for the affected animal, often an antiflea product. Fipronil works well, especially in cats. Cats can also be treated with a lime sulfur insecticide dip or a shampoo with non-pyrethrin insecticide for two weeks beyond the conclusion of symptoms.In unresponsive cases, ivermectin is used. Selamectin is also recommended for treatment. None of these products are approved for treatment of cheyletiellosis. Other pets in the same household should also be treated, and the house or kennel must be treated with an environmental flea spray.
Species
Cheyletiella blakei Smiley, 1970 — infests cats (Felis catus), USA (Washington DC)
Cheyletiella parasitivorax — infests rabbits (Oryctolagus cuniculus), France
Cheyletiella romerolagi (Fain, 1972) — infests Romerolagus diazi, USA (New York)
Cheyletiella strandtmanni Smiley, 1970 — infests hares (Lepus spp.), Taiwan
Cheyletiella yasguri Smiley, 1965 — infests dogsC. yasguri and C. blakei can transiently affect humans.
See also
List of mites associated with cutaneous reactions
Mange
== References == |
Reinkes edema | Reinkes edema is the swelling of the vocal cords due to fluid (edema) collected within the Reinkes space. First identified by the German anatomist Friedrich B. Reinke in 1895, the Reinkes space is a gelatinous layer of the vocal cord located underneath the outer cells of the vocal cord. When a person speaks, the Reinkes space vibrates to allow for sound to be produced (phonation). The Reinkes space is sometimes referred to as the superficial lamina propria.Reinkes edema is characterized by the "sac-like" appearance of the fluid-filled vocal cords. The swelling of the vocal folds causes the voice to become deep and hoarse. Therefore, the major symptom of Reinkes edema is a hoarseness similar to laryngitis. The major cause associated with Reinkes edema is smoking. In fact, 97% of patients diagnosed with Reinkes edema are habitual smokers. Other identified risk factors include overuse of the vocal cords, gastroesophageal reflux, and hypothyroidism. The disease is more often cited in women than in men, because lower voice changes are more noticeable in women.The first cases of Reinkes edema were recorded in 1891 by M. Hajek, followed by F. Reinke in 1895. In his investigations, Reinke injected a stained glue into the superficial lamina propria (Reinkes space) to mimic edema. Reinkes edema is considered to be a benign (non-cancercous) polyp (protrusion) that represents 10% of all benign laryngeal pathologies. Treatment of Reinkes edema starts with the elimination of associated risk factors, such as smoking, gastric reflux, and hypothyroidism. Advanced cases may undergo phonosurgery to remove the fluid from the vocal cords.
Signs and symptoms
List of common symptoms:
"sac-like" appearance of the vocal folds
Hoarseness and deepening of the voice
Trouble speaking (Dysphonia)
Reduced vocal range with diminished upper limits
Stretching of the mucosa (Distension)
Shortness of breath (Dyspnoea)Reinkes edema is characterized by a "sac-like" appearance of the vocal folds. The edema is a white translucent fluid that causes a bulging (distension) of the vocal cord. The most common clinical symptom associated with Reinkes edema is an abnormally low pitched voice with hoarseness. The low pitch voice is a direct result of increased fluid in the Reinkes space, which vibrates at a lower frequency than normal (females <130 Hz; males <110 Hz). Hoarseness is a common problem of many laryngeal diseases, such as laryngitis. It is described as a harsh and breathy tone of voice. Hoarseness is often seen alongside dysphonia, a condition in which the individual has difficulty speaking.The swelling of the vocal cords and the lowering of the voice are warning signs that an individual has Reinkes edema. At the microscopic level, an examination of the vocal cords in patients with Reinkes edema will show lowered levels of collagen, elastin, and extracellular matrix proteins. These characteristics can be used to diagnose Reinkes edema. Reinkes edema is considered a benign polyp that may become precancerous if smoking is involved. An indicator of cancer is the development of leukoplakia, which manifests as white patches on the vocal folds.Smoking, gastric reflux, and hypothyroidism are all risk factors for Reinkes edema. The symptoms of Reinkes edema are considered to be chronic symptoms because they develop gradually over time and depend on how long the individual is exposed to the risk factor. In the case of smoking, as long as the individual continues the habit of smoking, the Reinkes edema will continue to progress. This is true for other risk factors as well, such as untreated gastric reflux and overuse of the voice, which is common to professions such as singers and radio announcers.
Causes
Smoking is the number one cause of Reinkes edema. Other factors include gastroesophageal reflux, hypothyroidism and chronic overuse of the voice. Smoking and reflux are the only risk factors that may lead to cancer. Additionally, the combination of several risk factors increase the likelihood of an individual developing Reinkes edema. For example, an individual who smokes and also has gastric reflux would have an increased susceptibility for developing Reinkes edema over time.Reinkes edema is commonly diagnosed in middle-aged females with a history of smoking (aged 50 years or older). Because males have lower pitched voices than females, males are less likely to observe a significant changes in the voice, and are therefore less likely to seek treatment. Females also report more physical discomfort due to Reinkes edema. The risk of Reinkes edema increases with age and also with prolonged exposure to smoking. Additionally, individuals in professions that require constant use of the voice, such as singers, teachers, and radio hosts, may be at an increased risk for developing the disease.Because the disease is heavily linked to smoking, there is no established way to screen for Reinkes edema. Similarly, the only way to prevent Reinkes edema is to avoid smoking. By adopting a non-smoking lifestyle after being diagnosed with Reinkes edema, it is possible to stop the diseases progression, although it is not possible to reverse it. Therefore, it is critical to maintain a non-smoking lifestyle even after surgery, because the fluid can re-emerge. In fact, in many cases surgeons will not perform surgery without the guarantee that the individual will stop smoking.
Mechanism
The vocal cords consist of five layers of cells:
Squamous epithelium
Superficial lamina propria (Reinkes space)
Intermediate lamina propria
Deep lamina propria
Vocalis muscleIn order for humans to produce sound for speech, the vocal folds must readily vibrate. The two layers of the vocal cords that vibrate are the Reinkes space and the overlying epithelium. In fact, these layers move freely over the more rigid intermediate and deep lamina proprias. Accumulation of fluid within the Reinkes space alters the elasticity of the vocal cord, making it less stiff and more gelatinous. This slows the vocal cord vibration, which results in a deepened and hoarse voice. Because men normally have a lower voice than women, the change is more noticeable in women.Edema usually occurs on both vocal cords. This is known as bilateral Reinkes edema. The pathophysiology or mechanism of Reinkes edema is not well known, however, chemicals contained within cigarette smoke are associated with an increased vascular permeability of blood vessels, which results in fluid leaking into the Reinkes space. Normally, the vocal cords are surrounded by neatly aligned blood vessels, however, these blood vessels can become disarranged and fragile in Reinkes edema. In addition, cigarette smoke can create reactive oxygen species that alter the environment of the vocal cords. Tissue analysis of Reinkes edema shows decreased amounts of the proteins fibronectin, elastin, collagens I and III, and extracellular matrix proteins. This leads to an overall decreased stiffness of the tissue layer, which vibrates more slowly and produces a deeper sounding voice.The progression of Reinkes edema is gradual and is directly related to the duration of exposure to risk factors, such as smoking and gastric reflux. Disease progression is divided into two types: "pale" and "livid". The “pale” type of Reinkes edema is defined by a glazed appearance of the vocal cords with a clear (colorless) fluid underneath. This represents the early stage of the disease. The advanced “livid” type of Reinkes edema is identified by an increased amount of fluid, accompanied by a color change from colorless to yellow-grey. The swelling of the vocal folds cause ballooned-like appearance, known as a polyp. The polyps of Reinkes edema are usually benign, however, there may be a risk of cancer if the patient is a smoker. Additionally, if the edema becomes too severe, patients may experience difficulty breathing due to blockage of the airway.
Diagnosis
Reinkes edema is often diagnosed by an Ear, Nose & Throat (ENT) specialist or an Otolaryngologist by examination of the vocal cords. First, the doctor will review the patients medical history and symptoms, such as hoarseness, dysphonia, and reduced vocal range. There is no familial or hereditary link to Reinkes edema. Because Reinkes edema is linked heavily to smoking, the doctor will need to know if the patient is a habitual smoker. Once the patients history is reviewed, the vocal cords will be visualized using laryngoscopy, a technique in which a tube with a camera (endoscope) is passed through the nose and down the larynx. Laryngoscopes can be rigid or flexible. Flexible laryngoscopes, such as fiber laryngoscopes, allow the patient to produce sound as the tube is placed, and therefore allows the doctor to visualize movement of the vocal cord. The use of rigid laryngoscopes generally requires general anaesthesia due to the discomfort involved in distracting the soft tissues of the mouth and pharynx.
Based on the results of the laryngoscopy, Reinkes edema can be classified using a standardized system set in place by Yonekawa. This system characterizes the disease based disease severity.Yonekawa Classification:
Grade I – Lesions contact the anterior third of the vocal fold
Grade II – Lesions contact the anterior two-thirds of the vocal fold
Grade III – Lesions contact the entirety of the vocal foldIf further evaluation is needed, stroboscopy is used to examine mucosal waves of the vocal cords. Mucosal waves describe the waves produced by vibration of the vocal cords during speech. Stroboscopes produce flashes of light that are timed to the patients vocal frequency. Every time the light is flashed, it will create a still frame image of the vocal cords at that particular moment in time. These are combined to produce an image of the wave. In the case of Reinkes edema, structural changes to the vocal cords will result in abnormal wave patterns.
Treatment
The first step in treating Reinkes edema is to eliminate or control those risk factors that are causing the disease. This includes the cessation of smoking, the control of gastric reflux using antacids and/or Proton Pump Inhibitors (PPIs), and the discontinuation of activities that cause vocal distress. Those experiencing a hoarseness of the voice may choose to undergo voice therapy to improve the voices quality and range. Most cases of Reinkes edema are caused by the long term usage of cigarettes. In this case, it is important to make lifestyle changes to stop smoking. While this will not resolve or improve the edema, the cessation of smoking will halt the diseases progression.If the elimination of risk factors is not sufficient to improve the patients symptoms, surgery may be required. The most common type of surgery performed today for Reinkes edema is called surgical microlaryngoscopy. Most procedures follow the microflap technique set in place by Hirano. During surgery, an incision is made into the vocal cord using either microscissors or a CO2 laser. A flap of mucosa is lifted and the affected tissue is removed using suction or a microdebrider. The flap is then re-draped and trimmed to the appropriate size.Most cases of Reinkes Edema are bilateral - affecting both vocal cords - rather than unilateral. In the case of bilateral edema, the surgeon must choose whether to operate each side of the vocal cord in two separate surgeries or to operate both sides in a single surgery. The complication associated with removing tissue from both sides in a single surgery is that the raw, cut ends of the vocal cords may form an anterior glottis web, in which the two sides grow together in a continuous sheet. Other complications of surgery include tissue scarring due to damage to the vocal ligament during the incision and vocal cord stiffening due to over-suctioning of the superficial lamina propria (Reinkes space).While surgical microlaryngoscopy has its associated risks, if left untreated, Reinkes edema can lead to a variety of long-term complications. Besides dysphonia (impaired speech), the most serious of these complications is airway obstruction due to severe inflammation of the vocal cords. The risk of complications has decreased drastically with the creation of new tools, such as the CO2 laser for surgical microlaryngoscopy. Before the Hirano microflap method was developed in 1895, vocal stripping was the most common procedure used to correct Reinkes Edema. Vocal stripping was often performed without magnification and with a monocular laryngoscope, instead of a binocular scope. This led to major complications such as vocal ligament scarring.
Women are more likely than men to undergo surgery due to a greater change in vocal pitch and quality. Surgery is capable of restoring the voice, with the condition that smoking is not resumed after surgery. Post-operative voice therapy is also advised to restore the voices strength. Reinkes edema is not a fatal pathology unless the tissue becomes precancerous.
Research
Recent studies have examined the role of specific cell types in Reinkes edema, including the role of vocal cord fibroblasts. In normal tissue, these spindle-shaped CD34+ fibroblasts produce extracellular matrix proteins such as collagen and elastin. Recent findings have shown a morphological change in fibroblasts extracted from the tissue of Reinkes edema to a more dendritic-like shape with several protrusions. Large populations of these altered CD34+ fibroblasts have been found surrounding the areas of edema. They lack normal expression of several cluster of differentiation (CD) proteins and express additional proteins that are not expressed in normal vocal cord fibroblasts. Furthermore, cigarette smoke was discovered to increase COX-2 and PGE2 expression in fibroblasts, which could indicate the role of cigarette smoke in Reinkes edema.While smoking is a clear risk factor to Reinkes edema, other risk factors are being identified to explain Reinkes edema in nonsmokers. Research has suggested the role of bacterial colonies in non-neoplastic lesions such as Reinkes edema. Using pyrosequencing, strains of S. pseudopneumoniae were found as the dominant bacterial strain across most non-neoplastic lesions. Of all the sequences analyzed, streptococcus represented 72.9% of bacteria found within these lesions. While smoking, gastric reflux, and vocal abuse have been more widely agreed upon in literature as risk factors for Reinkes edema, the altered bacterial cultures could be developed as a diagnostic tool in the future.The majority of the research within the last ten years focuses on improving surgery for Reinkes edema. Due to the importance of the Reinkes space in speech, it is important that minimally invasive techniques be perfected that minimize the risk of complications. The CO2 laser has been successfully incorporated into the surgical technique, however, there are several other lasers being investigated for use in Reinkes edema. These include photoangiolytic lasers and potassium titanyl phosphate lasers.
See also
List of voice disorders
Histology of the Vocal Folds
References
Notes"Benign Vocal Lesions - Nodules, Polyps, Cysts". The Center for Voice at Northwestern University. Archived from the original on August 17, 2007. Retrieved July 24, 2007.
External links
"Illustration of Reinkes Edema". The Center for Voice at Northwestern University. Archived from the original on August 17, 2007. Retrieved July 24, 2007. |
Uremic pruritus | Uremic pruritus is caused by chronic kidney failure and is the most common internal systemic cause of itching.: 52–3 Nalfurafine, an orally-administered, centrally-acting κ-opioid receptor agonist, is approved to treat the condition in Japan.
See also
Pruritus
List of cutaneous conditions
References
== External links == |
Meigss syndrome | In medicine, Meigss syndrome, also Meigs syndrome or Demons–Meigs syndrome, is the triad of ascites, pleural effusion, and benign ovarian tumor (ovarian fibroma, fibrothecoma, Brenner tumour, and occasionally granulosa cell tumour). Meigs syndrome resolves after the resection of the tumor. Because the transdiaphragmatic lymphatic channels are larger in diameter on the right, the pleural effusion is classically on the right side. The causes of the ascites and pleural effusion are poorly understood. Atypical Meigs syndrome, characterized by a benign pelvic mass with right-sided pleural effusion but without ascites, can also occur. As in typical Meigs syndrome, pleural effusion resolves after removal of the pelvic mass.
Diagnosis
Differential diagnosis
Meigs syndrome may mimic other conditions, since it is tumor arising from ovaries, pathology of any organs present in the abdomen may show a similar set of symptoms. These include various gynecological disorders of the uterus such as endometrial tumor, sarcoma, leiomyoma (pseudo-Meigs syndrome); fallopian tube disorders such as hydrosalpinx, granulomatous salpingitis, fallopian tube malignancy; ovarian disorders such as serous, mucinous, endometrioid, or clear cell carcinoma, Brenner tumor, granulosa cell tumor, stromal tumor, dysgerminoma, fibroma, or metastatic tumor to the ovary.
Meigs syndrome is characterized by the presence of a benign solid ovarian tumor associated with ascites and right hydrothorax that disappear after tumor removal. Non-gynecological manifestations include:
ascites, portal vein obstruction, inferior vena cava obstruction, hypoproteinaemia, thoracic duct obstruction, tuberculosis, amyloidosis, pancreatitis, ovarian hyperstimulation, exudate pleural effusion, congestive heart failure, metastatic tumors to the peritoneal surfaces, collagen-vascular disease, and cirrhosis of the liver.
These entities must be clinically excluded.
Clinical condition characterized by ovarian mass, ascites, and right-sided pleural effusion. Ovarian malignancy and the other causes of pelvic mass, ascites, and pleural effusion to be considered, History of early satiety, weight loss with increased abdominal girth, bloating, intermittent abdominal pain, dyspnea, nonproductive cough may help in differentiating potential local factor causing such symptoms.
Treatment
Treatment of Meigs syndrome consists of thoracentesis and paracentesis to drain off the excess fluid (exudate), and unilateral salpingo-oophorectomy or wedge resection to correct the underlying cause.
Eponym
Meigs syndrome is named for Joe Vincent Meigs.
References
== External links == |
Urocanic aciduria | Urocanic aciduria is an autosomal recessive metabolic disorder caused by a deficiency of the enzyme urocanase. It is a secondary disorder of histidine metabolism.
Symptoms and signs
Urocanic aciduria is thought to be relatively benign. Although aggressive behavior and mental retardation have been reported with the disorder, no definitive neurometabolic connection has yet been established.
Genetics
Urocanic aciduria has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene – one copy inherited from each parent – are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but are usually not affected by the disorder.
Pathophysiology
The amino acid histidine, when catalyzed by the enzyme histidase, forms urocanic acid. Disruptions in this pathway, caused by a deficiency of histidase, is the underlying cause of histidinemia. This results in reduced levels of skin and serum urocanic acid, the primary indicator of insufficient histidase activity.In urocanic aciduria, increased urocanic acid in the urine indicates a deficiency of the enzyme urocanase.With normal to only slightly elevated levels of histidine present in the liver during urocanic aciduria, the only true metabolic indicator of the disorder can be found in the urine.
Diagnosis
Treatment
See also
Inborn errors of metabolism
Imidazole
Aromatic amino acids
Recessive disorders
References
== External links == |
Primary central nervous system lymphoma | Primary central nervous system lymphoma (PCNSL), also termed primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS), is a primary intracranial tumor appearing mostly in patients with severe immunodeficiency (typically patients with AIDS). It is a subtype and one of the most aggressive of the diffuse large B-cell lymphomas. PCNSLs represent around 20% of all cases of lymphomas in HIV infections. (Other types are Burkitts lymphomas and immunoblastic lymphomas). Primary CNS lymphoma is highly associated with Epstein-Barr virus (EBV) infection (> 90%) in immunodeficient patients (such as those with AIDS and those immunosuppressed), and does not have a predilection for any particular age group. Mean CD4+ count at time of diagnosis is ~50/uL. In immunocompromised patients, prognosis is usually poor. In immunocompetent patients (that is, patients who do not have AIDS or some other immunodeficiency), there is rarely an association with EBV infection or other DNA viruses. In the immunocompetent population, PCNSLs typically appear in older patients in their 50s and 60s. Importantly, the incidence of PCNSL in the immunocompetent population has been reported to have increased more than 10-fold from 2.5 cases to 30 cases per 10 million population. The cause for the increase in incidence of this disease in the immunocompetent population is unknown.
Signs and symptoms
A primary CNS lymphoma usually presents with seizure, headache, cranial nerve findings, altered mental status, or other focal neurological deficits typical of a mass effect. Systemic symptoms may include fever, night sweats, or weight loss. Other symptoms include
diplopia
dysphagia
vertigo
monocular vision loss
progressive dementia or stupor in patients with a nonfocal neurologic exam and minimal abnormalities on MRI (more common in AIDS patients)
facial hypoesthesia
Diagnosis
The current standard for diagnosis typically includes positive CSF cytology, vitreous biopsy, or brain/leptomeningeal biopsy. Histopathological confirmation is essential for definitive diagnosis.MRI or contrast enhanced CT classically shows multiple ring-enhancing lesions in the deep white matter. The major differential diagnosis (based on imaging) is cerebral toxoplasmosis, which is also prevalent in AIDS patients and also presents with a ring-enhanced lesion, although toxoplasmosis generally presents with more lesions and the contrast enhancement is typically more pronounced. Imaging techniques cannot distinguish the two conditions with certainty, and cannot exclude other diagnoses. Thus, patients undergo a brain biopsy or vitreous biopsy, if there is intraocular involvement.
Classification
Most PCNSLs are diffuse large B cell non-Hodgkin lymphomas.
Treatment
Surgical resection is usually ineffective because of the depth of the tumour. Treatment with irradiation and corticosteroids often only produces a partial response and tumour recurs in more than 90% of patients. Median survival is 10 to 18 months in immunocompetent patients, and less in those with AIDS. The addition of IV methotrexate and folinic acid (leucovorin) may extend survival to a median of 3.5 years. If radiation is added to methotrexate, median survival time may increase beyond 4 years. However, radiation is not recommended in conjunction with methotrexate because of an increased risk of leukoencephalopathy and dementia in patients older than 60. In AIDS patients, perhaps the most important factor with respect to treatment is the use of highly active anti-retroviral therapy (HAART), which affects the CD4+ lymphocyte population and the level of immunosuppression. The optimal treatment plan for patients with PCNSL has not been determined. Combination chemotherapy and radiotherapy at least doubles survival time, but causes dementia and leukoencephalopathy in at least 50% of patients who undergo it. The most studied chemotherapeutic agent in PCNSL is methotrexate (a folate analogue that interferes with DNA repair). Methotrexate therapy in patients with PCNSL typically requires hospitalization for close monitoring and intravenous fluids. Leucovorin is often given for the duration of the therapy. Standard chemotherapeutic regimens for lymphoma such as CHOP are ineffective in PCNSL, probably due to poor penetration of the agents through the blood brain barrier.Newer treatments, such as high dose chemotherapy combined with autologous stem cell transplant are proving to increase survival by years. New research to increase permeability of the blood brain barrier with NGR-hTNF followed by CHOP, produced responses in 75% cases. A phase 1 clinical trial of ibrutinib – an inhibitor of Brutons tyrosine kinase – in 13 patients reported responses in 10 (77%). Five of the responses were complete.
Prognosis
In immunocompetent patients
The initial response to radiotherapy is often excellent, and may result in a complete remission. However, the duration of response with radiotherapy alone remains short, with median survival after treatment with radiotherapy just 18 months. Methotrexate based chemotherapy markedly improves survival, with some studies showing median survival after methotrexate chemotherapy reaching 48 months.
In AIDS patients
Patients with AIDS and PCNSL have a median survival of only 4 months with radiotherapy alone. Untreated, median survival is only 2.5 months, sometimes due to concurrent opportunistic infections rather than the lymphoma itself. Extended survival has been seen, however, in a subgroup of AIDS patients with CD4 counts of more than 200 and no concurrent opportunistic infections, who can tolerate aggressive therapy consisting of either methotrexate monotherapy or vincristine, procarbazine, or whole brain radiotherapy. These patients have a median survival of 10–18 months. Of course, highly active antiretroviral therapy (HAART) is critical for prolonged survival in any AIDS patient, so compliance with HAART may play a role in survival in patients with concurrent AIDS and PCNSL.
References
External links
MedPix Teaching File MR Scans of Primary Brain Lymphoma |
Stomatitis nicotina | Stomatitis nicotina is a diffuse white patch on the hard palate, usually caused by tobacco smoking, usually pipe or cigar smoking. It is painless, and it is caused by a response of the palatal oral mucosa to chronic heat. A more pronounced appearance can occur with reverse smoking, sometimes distinguished from stomatitis nicotina by the term reverse smokers stomatitis. While stomatitis nicotina that is caused by heat is not a premalignant condition (i.e. it does not carry an increased risk of transformation to oral cancer), the condition that is caused by reverse smoking is premalignant.
Signs and symptoms
The palate may appear gray or white and contain many papules or nodules that are slightly elevated with red dots in their center. These red dots represent the ducts of minor salivary glands which have become inflamed by heat. The condition is painless. If a denture is normally worn while smoking, then the mucosa underneath the denture appears unaffected by the condition. In severe cases, the mucosa may show fissuring and develop a "dried lake bed" appearance. Other changes associated with tobacco use may be evident such as brown or black extrinsic staining of teeth from tar and other components of tobacco smoke.
Causes
The cause of nicotine stomatitis is thought to be chemical or thermally induced keratosis. The chemicals in tobacco may act as irritants in this condition. Chronic heat exposure is also responsible. Pipe smoking produces more heat on the palate than any other forms of smoking. Long-term drinking of very hot beverages can also cause a similar condition. The severity of the changes correlates with the frequency of the habit. The prevalence depends on a societys use of consuming hot beverages and of smoking in its various forms.
A similar, but more pronounced palatal keratosis occurs with reverse smoking. This is where the lit end of the cigar or cigarette is held in the mouth, another form of smoking associated with high levels of heat in the mouth. This form of the condition is sometimes termed "reverse smokers keratosis", and is a premalignant lesion. That is, the condition is associated with an increased risk of malignant transformation to oral squamous cell carcinoma (a type of oral cancer). Some sources do not distinguish between reverse smokers keratosis and smokers palate that is caused by heat. As such, these sources tend to state that stomatitis nicotina is a premalignant condition. Some reports show that there is an increased risk of tonsillar cancer, lung cancer and tumors of the posterior oral cavity in people who develop stomatitis nicotina.
Diagnosis
The diagnosis is normally made based upon the clinical appearance and history. Tissue biopsy is not usually indicated unless there are areas of ulceration or localized erythroplakia (red patches). The differential diagnosis is with other causes of white lesions (see leukoplakia for a more complete discussion). Specific conditions which can produce a similar appearance include Dariers disease, discoid lupus erythematosus, oral candidiasis, and oral lichen planus.If a biopsy is taken, the histopathologic appearance is one of hyperkeratosis and acanthosis. There may be squamous metaplasia of excretory ducts, which results in the visible papules if the ducts become hyperplastic. Neutrophils may fill some ducts. It is characterized as a "fissured" or "dried mud" appearance from excess keratin production by cells. Dysplasia is rarely seen.
Treatment
When the appearance is caused by heat, the lesion is usually completely reversible within a few weeks if the smoking habit is stopped. This is the case even if the condition has been present for decades. Without stopping smoking, spontaneous remission of the lesion is unlikely. If the lesion persists despite stopping smoking, this is usually then considered to be a true leukoplakia rather than a reactionary keratitis, and may trigger the decision to carry out a biopsy to confirm the diagnosis. Since this condition almost always develops in the setting of long term heavy smoking, it usually indicates the need for regular observation for cancers associated with smoking, e.g. lung cancer.
Epidemiology
The condition is uncommon. It occurs usually in elderly males who have a history of heavy pipe smoking, but it also can occur in cigar or cigarette smokers. The condition was once common, but has become more rare as habits such as pipe and cigar smoking have decreased in popularity.
See also
Smokers melanosis
Smokeless tobacco keratosis
References
Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001.
== External links == |
Steatopygia | Steatopygia is the state of having substantial levels of tissue on the buttocks and thighs. This build is not confined to the gluteal regions, but extends to the outside and front of the thighs, and tapers to the knee producing a curvilinear figure. The term is from the Greek stéar (στέαρ), meaning "tallow", and pugḗ (πυγή), meaning "rump".
Steatopygia, a genetic characteristic leading to increased accumulation of adipose tissue in the buttock region, is most notably (but not solely) found among the Khoisan of Southern Africa. It has also been observed among Pygmies of Central Africa and also the Andamanese people, such as the Onge tribe in the Andaman Islands. This genetic characteristic is prevalent among women but occurs to a lesser degree in men.Steatopygia would seem to have been a characteristic of a population which once extended from the Gulf of Aden to the Cape of Good Hope, from which peoples the Khoisan and Pygmies may be remnants. Among the Khoisan, it begins in infancy and is fully developed by the time of the first pregnancy.It has been suggested that this feature was once more widespread. Paleolithic Venus figurines, sometimes referred to as "Steatopygian Venus" figures, discovered from Europe to Asia presenting a remarkable development of the thighs, and even the prolongation of the labia minora, have been used to support this theory. Whether these were intended to be lifelike, exaggeratory, or idealistic is unclear. These figures, however, may not qualify as steatopygian, since they exhibit an angle of approximately 120 degrees between the back and the buttocks, while steatopygia is typically described with an angle of about 90 degrees only.In Victorian England, freak shows were known to have exploited a woman with steatopygia at least once. The most well-known example was a South African Khoikhoi woman named Saartjie Baartman, who is thought to have had lipedema.
See also
Female body shape
Feminine beauty ideal
References
== External links == |
Keratoderma blennorrhagicum | Keratoderma blennorrhagicum etymologically meaning keratinized (kerato-) skin (derma-) mucousy (blenno-) discharge (-rrhagia) (also called keratoderma blennorrhagica) are skin lesions commonly found on the palms and soles but which may spread to the scrotum, scalp and trunk. The lesions may resemble psoriasis.: 195 Keratoderma blennorrhagicum is commonly seen as an additional feature of reactive arthritis in almost 15% of male patients. The appearance is usually of a vesico-pustular waxy lesion with a yellow brown colour. These lesions may join to form larger crusty plaques with desquamating edges.
See also
Keratoderma
Keratosis
Blennorrhea
List of cutaneous conditions
References
== External links == |
Gerodermia osteodysplastica | Gerodermia osteodysplastica (GO) is a rare autosomal recessive connective tissue disorder included in the spectrum of cutis laxa syndromes.Usage of the name "Walt Disney dwarfism" is attributed to the first known case of the disorder, documented in a 1950 journal report, in which the authors described five affected members from a Swiss family as having the physical appearance of dwarves from a Walt Disney film.The terms "geroderma" or "gerodermia" can be used interchangeably with "osteodysplastica" or "osteodysplasticum", with the term "hereditaria" sometimes appearing at the end.
Presentation
Gerodermia osteodysplastica is characterized by symptoms and features which affect the connective tissues, skin and skeletal system.These are: wrinkly, loose skin over the face, abdomen, and extremities (hands, feet) on the dorsal sides usually worsened by chronic joint laxity and hyperextensibility; fragmented elastic fibers of the skin that are reduced in number, with disorientation of collagen fibers; osteopenia and osteoporosis, with associated fractures; malar hypoplasia (underdeveloped cheek bone), maxillary hypoplasia (underdeveloped upper jaw), mandibular prognathism (protrusion of the lower jaw and chin), bowed long bones, platyspondyly (flattened spine) related to vertebral collapse; kyphoscoliosis (scoliosis with kyphosis, or "hunch back"), metaphyseal peg (an unusual outgrowth of metaphyseal tissue which protrudes into the epiphyseal region of the bone, near the knee); and the overall physical effects and facial appearance of dwarfism with premature aging.Other features and findings include: intrauterine growth retardation, congenital hip dislocations, winged scapulae (shoulder blades), pes planus (fallen arches), pseudoepiphyses of the second metacarpals (upper bone of the fingers), hypotelorism (close-set eyes), malformed ears,developmental delay,failure to thrive and abnormal electroencephalograph (EEG) readings.Dental and orthodontal abnormalities in addition to maxillary hypoplasia and mandibular prognathism have also been observed in gerodermia osteodysplastica. Including malocclusion of the dental arches (the maxilla and mandible), radiological findings in some cases have indicated significant overgrowth of the mandibular premolar and molar roots;hypercementosis (overproduction of cementum) of the molars and maxillary incisors; enlarged, funnel-shaped mandibular lingula (spiny structures on the ramus of the mandible); and a radiolucent effect on portions of many teeth, increasing their transparency to x-rays.
Genetics
Originally believed to be inherited in an X-linked recessive fashion, gerodermia osteodysplastica is now known to display strictly autosomal recessive inheritance. This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.It has been associated with SCYL1BP1.
Diagnosis
Differential diagnosis
Many features of gerodermia osteodysplastica (GO) and another autosomal recessive form of cutis laxa, wrinkly skin syndrome (WSS, Online Mendelian Inheritance in Man (OMIM): 278250), are similar to such an extent that both disorders were believed to be variable phenotypes of a single disorder.Several delineating factors, however, suggest that gerodermia osteodysplastica and wrinkly skin syndrome are distinct entities, but share the same clinic spectrum.While the prevailing feature of wrinkly, loose skin is more localized with GO, it is usually systemic, yet eases in severity with age during the course of WSS. Also, as the fontanelles ("soft spots") are usually normal on the heads of infants with GO, they are often enlarged in WSS infants.While WSS is associated with mutations of genes on chromosomes 2, 5, 7, 11 and 14; GO has been linked to mutations in the protein GORAB. A serum sialotransferrin type 2 pattern, also observed with WSS, is not present in GO patients.But perhaps the most notable feature, differentiating GO from WSS and similar cutis laxa disorders, is the age-specific metaphyseal peg sometimes found in GO-affected long bone, near the knee. Not appearing until around age 4–5, then disappearing by physeal closure, this oddity of bone is thought to represent a specific genetic marker unique to GO and its effects on bone development.
Treatment
See also
Ehlers–Danlos syndromes
Progeria
Skeletal dysplasia
References
== External links == |
Unilateral nevoid telangiectasia | Unilateral nevoid telangiectasia presents with fine thread veins, typically over a segment of skin supplied by a particular nerve
on one side of the body. It most frequently involves the trigeminal and C3 and C4 or adjacent areas.The condition was named in 1970 by Victor Selmanowitz.
See also
Skin lesion
List of cutaneous conditions
References
== External links == |
Hypertensive urgency | A hypertensive urgency is a clinical situation in which blood pressure is very high (e.g., 220/125 mmHg) with minimal or no symptoms, and no signs or symptoms indicating acute organ damage. This contrasts with a hypertensive emergency where severe blood pressure is accompanied by evidence of progressive organ or system damage.
Definition
Hypertensive urgency is defined as severely high blood pressure with no evidence of end organ damage. The term "malignant hypertension" was also included under this category with grade III/IV hypertensive retinopathy. However, in 2018, European Society of Cardiology and the European Society of Hypertension issued a new guideline which put "malignant hypertension" under the category "hypertensive emergency", which emphasize on poor outcome if the condition is not treated urgently.
Treatment
In a hypertensive urgency blood pressure should be lowered carefully to ≤160/≤100 mmHg over a period of hours to days, this can often be done as an outpatient. There is limited evidence regarding the most appropriate rate of blood pressure reduction, although it is recommended that mean arterial pressure should be lowered by no more than 25 to 30 percent over the first few hours. Recommended medications for hypertensive urgencies include: captopril, labetalol, amlodipine, felodipine, isradipine, and prazosin. Sublingual nifedipine is not recommended in hypertensive urgencies. This is because nifedipine can cause rapid decrease of blood pressure which can precipitate cerebral or cardiac ischemic events. There is also lack of evidence on the benefits of nifedipine in controlling hypertension. Acute administration of drugs should be followed by several hours of observation to ensure that blood pressure does not fall too much. Aggressive dosing with intravenous drugs or oral agents which lowers blood pressure too rapidly carries risk; conversely there is no evidence that failure to rapidly lower blood pressure in a hypertensive urgency is associated with any increased short-term risk.
Epidemiology
Not much is known about the epidemiology of hypertensive urgencies. Retrospective analysis of data from 1,290,804 adults admitted to hospital emergency departments in United States from 2005 through 2007 found that severe hypertension with a systolic blood pressure ≥180 mmHg occurred in 13.8% of patients. Based on another study in a US public teaching hospital about 60% of hypertensive crises are due to hypertensive urgencies.Risk factors for severe hypertension include older age, female sex, obesity, coronary artery disease, somatoform disorder, being prescribed multiple antihypertensive medications, and non-adherence to medication.
== References == |
Lower motor neuron lesion | A lower motor neuron lesion is a lesion which affects nerve fibers traveling from the lower motor neuron(s) in the anterior horn/anterior grey column of the spinal cord, or in the motor nuclei of the cranial nerves, to the relevant muscle(s).One major characteristic used to identify a lower motor neuron lesion is flaccid paralysis – paralysis accompanied by loss of muscle tone. This is in contrast to an upper motor neuron lesion, which often presents with spastic paralysis – paralysis accompanied by severe hypertonia.
Signs and symptoms
Muscle paresis or paralysis
Fibrillations
Fasciculations – caused by increased receptor concentration on muscles to compensate for lack of innervation.
Hypotonia or atonia – Tone is not velocity dependent.
Hyporeflexia - Along with deep reflexes even cutaneous reflexes are also decreased or absent.
Strength – weakness is limited to segmental or focal pattern, Root innervated patternThe extensor plantar reflex is usually absent. Muscle paresis/paralysis, hypotonia/atonia, and hyporeflexia/areflexia are usually seen immediately following an insult. Muscle wasting, fasciculations and fibrillations are typically signs of end-stage muscle denervation and are seen over a longer time period. Another feature is the segmentation of symptoms – only muscles innervated by the damaged nerves will be symptomatic.
Causes
The most common causes of lower motor neuron injuries are trauma to peripheral nerves that serve the axons, and viruses that selectively attack ventral horn cells.
Disuse atrophy of the muscle occurs i.e., shrinkage of muscle fibre finally replaced by fibrous tissue (fibrous muscle)
Other causes include Guillain–Barré syndrome, West Nile fever, C. botulism, polio, and cauda equina syndrome; another common cause of lower motor neuron degeneration is amyotrophic lateral sclerosis.
Diagnosis
Differential diagnosis
Myasthenia gravis – synaptic transmission at motor end-plate is impaired
Amyotrophic lateral sclerosis – causes death of motor neurons, although exact cause is unknown it has been suggested that abnormal build-up of proteins proves toxic for the neurons.
See also
Lower motor neuron
Upper motor neuron
Upper motor neuron lesion
References
External links
http://library.med.utah.edu/neurologicexam/html/motor_anatomy.html#06 |
Hemoglobin C | Hemoglobin C (abbreviated as HbC) is an abnormal hemoglobin in which glutamic acid residue at the 6th position of the β-globin chain is replaced with a lysine residue due to a point mutation in the HBB gene. People with one copy of the gene for hemoglobin C do not experience symptoms, but can pass the abnormal gene on to their children. Those with two copies of the gene are said to have hemoglobin C disease and can experience mild anemia. It is possible for a person to have both the gene for hemoglobin S (the form associated with sickle cell anemia) and the gene for hemoglobin C; this state is called hemoglobin SC disease, and is generally more severe than hemoglobin C disease, but milder than sickle cell anemia.HbC was discovered by Harvey Itano and James V. Neel in 1950 in two African-American families. It has since been established that it is most common among people in West Africa. It confers survival benefits as individuals with HbC are naturally resistant to malaria caused by Plasmodium falciparum, albeit incompletely.
Symptoms and signs
People with one copy of the gene for hemoglobin C (termed heterozygous) do not experience significant symptoms, but can pass the abnormal gene onto their children; this condition is called hemoglobin C trait. When two hemoglobin C genes are present (termed homozygous), the individual is said to have hemoglobin C disease, and may develop mild anemia, as red blood cells containing hemoglobin C have a decreased lifespan. The anemia in hemoglobin C disease is classified as hemolytic, because it is caused by the destruction of red blood cells. An enlarged spleen, and sometimes jaundice, may also occur. Some persons with this disease may develop gallstones that require treatment. Continued hemolysis may produce pigmented gallstones, an unusual type of gallstone composed of the dark-colored contents of red blood cells.
Red blood cell abnormalities
The red blood cells of people with hemoglobin C disease are usually abnormally small (microcytic) with a high mean corpuscular hemoglobin concentration (MCHC). The high MCHC is caused by a decreased concentration of water inside the cells. Target cells, microspherocytes, and HbC crystals can be seen on microscopic examination of blood smears from homozygous patients.
Combinations with other conditions
HbC can combine with other abnormal hemoglobins and cause serious hemoglobinopathies. Individuals with sickle cell–hemoglobin C (HbSC), have inherited the gene for sickle cell disease (HbS) from one parent and the gene for hemoglobin C disease (HbC) from the other parent. Since HbC does not polymerize as readily as HbS, there is less sickling in most cases. There are fewer acute vaso-occlusive events and therefore in some cases fewer sickle cell crises. The peripheral smear demonstrates mostly target cells, occasional hemoglobin C crystals, and only a few sickle cells. However, persons with hemoglobin SC disease (HbSC) have more significant retinopathy, ischemic necrosis of bone, and priapism than those with pure SS disease.There are also a few cases of HbC in combination with HbO, HbD and beta thalassemia.
Genetics
Hemoglobin C is produced when a point mutation in the HBB gene causes amino acid substitution of glutamic acid to lysine at the 6th position of the β-globin chain of the hemoglobin. The mutation can be homozygous, occurring on both the chromosomes (alleles), or heterozygous, affecting only one allele. Under heterozygous condition, people are said to have hemoglobin C trait, or as hemoglobin C carriers, and they have one gene for HbC with either one HbA gene or HbS gene. Their red blood cells contain both hemoglobin C and either normal hemoglobin A or hemoglobin S. Hemoglobin C mutation is an autosomal recessive disorder that results from the biparental inheritance of the allele that encodes for hemoglobin C. If both parents are carriers of hemoglobin C, there is a chance of having a child with hemoglobin C disease. Assuming both parents are carriers, there is a 25% chance of having a child with hemoglobin C disease, a 50% chance of having a child who is a carrier of hemoglobin C, and a 25% chance of having a child who is neither a carrier nor affected by hemoglobin C disease.This mutated form reduces the normal plasticity of host erythrocytes causing a hemoglobinopathy. In those who are heterozygous for the mutation, about 28–44% of total hemoglobin (Hb) is HbC, and no anemia develops. In homozygotes, nearly all Hb is in the HbC form, resulting in mild hemolytic anemia, jaundice and enlargement of spleen.
Resistance to malaria
Individuals with HbC have reduced risk of P. falciparum malaria infection. HbC has been described as being more advantageous than HbS because, even in homozygous individuals, it is usually non-fatal. However, in contrast to HbS, it does not prevent malaria due to P. vivax, and is less effective in resistance to falciparum malaria in heterozygous conditions. Homozygous HbC is more resistant to heterozygous condition, or to thalassemias. But HbC mutation does not prevent the infection. P. falciparum do not survive in red blood cells with homozygous hemoglobins, but can survive in the presence of heterozygous hemoglobins. HbC reduced the binding force (cytoadherence) of P. falciparum by reducing the activity of PfEMP1. Evidences indicate that HbC reduced the level of PfEMP1, which is required for effective binding and invasion of RBC by the malarial parasite. It has been predicted that with the trend of HbC mutation and falciparum prevalence, HbC would replace HbS in central West Africa in the future.
Diagnosis
Physical examination may show an enlarged spleen. Tests that may be done include: complete blood count (CBC), hemoglobin electrophoresis, and peripheral blood smear.
Prevention
Genetic counseling may be appropriate for high-risk couples who wish to have a baby.
Treatment
Usually no treatment is needed. Folic acid supplementation may help produce normal red blood cells and improve the symptoms of anemia
Prognosis
Overall, hemoglobin C disease is one of the more benign hemoglobinopathies. Mild-to-moderate reduction in RBC lifespan may accompany from mild hemolytic anemia. Individuals with hemoglobin C disease have sporadic episodes of musculoskeletal (joint) pain. People with hemoglobin C disease can expect to lead a normal life.
Epidemiology
Hemoglobin C is found most abundantly in areas of West Africa, such as Nigeria, where Yorubas live. Hemoglobin C gene is found in 2-3% of African-Americans while 8% of African-Americans have hemoglobin S (Sickle) gene. Thus Hemoglobin SC disease is significantly more common than Hemoglobin CC disease. The trait also affects people whose ancestors came from Italy, Greece, Latin America, and the Caribbean region. However, it is possible for a person of any race or nationality to have hemoglobin C trait. In terms of geographic distribution, the hemoglobin C allele is found at the highest frequencies in West Africa, where it has been associated with protection against malaria. Hemoglobin C disease is present at birth, though some cases may not be diagnosed until adulthood. Both males and females are affected equally.
History
Studying the molecular basis of sickle cell disease, Linus Pauling and Harvey Itano at the California Institute of Technology discovered in 1949 that the disease was due to abnormal hemoglobin called HBS. In 1950, Itano and James V. Neel discovered from two African-American families a different blood condition very similar to sickle cell disease. Five of the ten individuals indicated sickled RBCs. But the condition was harmless as the individuals had no anaemia. Thus, it was not clear whether it was involved in sickle cell disease. Genetically, the abnormal hemoglobin was only in heterozygous condition. The next year, Neel and his colleagues established that the hemoglobin is associated with sickle cell disease.The hemoglobin was named hemoglobin III, but hemoglobin C was eventually used. By 1954, it was found that the mutant hemoglobin was highly prevalent in West Africa. In 1960, Vernon Ingram and J. A. Hunt at the University of Cambridge discovered that the mutation was a single amino acid replacement of glutamic acid with lysine.
References
External links
Hemoglobin+C at the US National Library of Medicine Medical Subject Headings (MeSH)
Hemoglobin+C+Disease at the US National Library of Medicine Medical Subject Headings (MeSH) |
Axis (anatomy) | In anatomy, the axis (from Latin axis, "axle") or epistropheus is the second cervical vertebra (C2) of the spine, immediately inferior to the atlas, upon which the head rests.
The axis defining feature is its strong odontoid process (bony protrusion) known as the dens, which rises dorsally from the rest of the bone.
Structure
The body is deeper in front or in the back and is prolonged downward anteriorly to overlap the upper and front part of the third vertebra.
It presents a median longitudinal ridge in front, separating two lateral depressions for the attachment of the longus colli muscles.
Dens
The dens, also called the odontoid process or the peg, is the most pronounced projecting feature of the axis. The dens exhibits a slight constriction where it joins the main body of the vertebra. The condition where the dens is separated from the body of the axis is called os odontoideum and may cause nerve and circulation compression syndrome. On its anterior surface is an oval or nearly circular facet for articulation with that on the anterior arch of the atlas. On the back of the neck, and frequently extending on to its lateral surfaces, is a shallow groove for the transverse atlantal ligament which retains the process in position. The apex is pointed and gives attachment to the apical odontoid ligament. Below the apex, the process is somewhat enlarged and presents on either side a rough impression for the attachment of the alar ligament; these ligaments connect the process to the occipital bone.
The internal structure of the odontoid process is more compact than that of the body. The odontoid peg is the ascension of the atlas fused to the ascension of the axis. The peg has an articular facet at its front and forms part of a joint with the anterior arch of the atlas. It is a non-weight bearing joint. The alar ligaments, together with the apical ligaments, are attached from the sloping upper edge of the odontoid peg to the margins of the foramen magnum. The inner ligaments limit rotation of the head and are very strong. The weak apical ligament lies in front of the upper longitudinal bone of the cruciform ligament and joins the apex of the deltoid peg to the anterior margin of the foramen magnum. It is the fibrous remnant of the notochord.
Other features
The pedicles are broad and strong, especially in the front, where they coalesce with the sides of the body and the root of the odontoid process. They are covered above by the superior articular surfaces.
The laminae are thick and strong. They play a large role in the stability of the cervical spine alongside the laminae of C7.The vertebral foramen is large, but smaller than the atlas.
The transverse processes are very small, and each ends in a single tubercle. Each process is perforated by the transverse foramen, which is directed obliquely upward and laterally.
The superior articular surfaces are round, slightly convex, directed upward and laterally, and are supported on the body, pedicles, and transverse processes.
The inferior articular surfaces have the same direction as those of the other cervical vertebrae.
The superior vertebral notches are very shallow, and lie behind the articular processes. The inferior vertebral notches lie in front of the articular processes, as in the other cervical vertebrae.
The spinous process is large, very strong, deeply channelled on its under surface, and presents a bifurcated extremity.
Variation
Contact sports are contraindicated for individuals with anomalous dens, as any violent impact may result in a catastrophic injury. This is because a malformed odontoid process may lead to instability between the atlas and axis (the C1 and C2 cervical vertebrae).
Development
The axis is ossified from five primary and two secondary centres.
The body and vertebral arch are ossified in the same manner as the corresponding parts in the other vertebrae, viz., one centre for the body, and two for the vertebral arch.
The centres for the arch appear about the seventh or eighth week of fetal life, while the centres for the body appear in about the fourth or fifth month.
The dens, or odontoid process, consist originally of a continuation upward of the cartilaginous mass, in which the lower part of the body is formed.
During about the sixth month of fetal life, two centres make their appearance in the base of this process: they are placed laterally, and join before birth to form a conical bilobed mass deeply cleft above; the interval between the sides of the cleft and the summit of the process is formed by a wedge-shaped piece of cartilage.
The base of the process is separated from the body by a cartilaginous disk, which gradually becomes ossified at its circumference, but remains cartilaginous in its center until advanced age.
In this cartilage, rudiments of the lower epiphyseal lamella of the atlas and the upper epiphyseal lamella of the axis may sometimes be found.
The apex of the odontoid process has a separate centre that appears in the second and joins about the twelfth year; this is the upper epiphyseal lamella of the atlas.
In addition to these, there is a secondary centre for a thin epiphyseal plate on the undersurface of the body of the bone.
Clinical significance
Fracture of dens
Fractures of the dens, not to be confused with Hangmans fractures, are classified into three categories according to the Anderson Alonso system:
Type I fracture - Extends through the tip of the dens. This type is usually stable.
Type II fracture - Extends through the base of the dens. It is the most commonly encountered fracture for this region of the axis. This type is unstable and has a high rate of non-union.
Type III fracture - Extends through the vertebral body of the axis. This type can be stable or unstable and may require surgery.[1]
Additional images
See also
References
This article incorporates text in the public domain from page 99 of the 20th edition of Grays Anatomy (1918)
External links
Netter, Frank. Atlas of Human Anatomy Archived 2017-11-20 at the Wayback Machine, "High Cervical Spine: C1-C2" |
Black heel and palm | Black heel and palm is a skin condition characterized by a sudden shower of minute, black, punctate macules occurring most often on the posterior edge of the plantar surface of one or both heels.: 43
See also
Skin lesion
List of cutaneous conditions
== References == |
Transplant glomerulopathy | Transplant glomerulopathy (TG) is a disease of the glomeruli in transplanted kidneys. It is a type of renal injury often associated with chronic antibody-mediated rejection. However, transplant glomerulopathy is not specific for chronic antibody-mediated rejection; it may be the result of a number of disease processes affecting the glomerular endothelium.
Pathology
It is characterized by glomerular basement membrane thickening (referred to as tram-tracking of the basement membrane), increased mesangial matrix and segmental and global glomerulosclerosis.The differential diagnosis of tram-tracking includes membranoproliferative glomerulonephritis (especially hepatitis C), and thrombotic microangiopathies.
See also
Kidney transplant
Chronic rejection
== References == |
Pseudobulbar palsy | Pseudobulbar palsy is a medical condition characterized by the inability to control facial movements (such as chewing and speaking) and caused by a variety of neurological disorders. Patients experience difficulty chewing and swallowing, have increased reflexes and spasticity in tongue and the bulbar region, and demonstrate slurred speech (which is often the initial presentation of the disorder), sometimes also demonstrating uncontrolled emotional outbursts.The condition is usually caused by the bilateral damage to corticobulbar pathways, which are upper motor neuron pathways that course from the cerebral cortex to nuclei of cranial nerves in the brain stem.
Signs and symptoms
Signs and symptoms of pseudobulbar palsy include:
Slow and indistinct speech
Dysphagia (difficulty in swallowing)
Small, stiff and spastic tongue
Brisk jaw jerk
Dysarthria
Labile affect
Gag reflex may be normal, exaggerated or absent
Examination may reveal upper motor neuron lesion of the limbs
Causes
Pseudobulbar palsy is the result of damage of motor fibers traveling from the cerebral cortex to the lower brain stem. This damage might arise in the course of a variety of neurological conditions that involve demyelination and bilateral corticobulbar lesions. Examples include:
Vascular causes: bilateral hemisphere infarction, CADASIL syndrome, artery of percheron infarct
Progressive supranuclear palsy
Amyotrophic lateral sclerosis
Parkinsons disease and related multiple system atrophy
Various motor neuron diseases, especially those involving demyelination
Multiple sclerosis and other inflammatory disorders
High brain stem tumors
Metabolic causes: osmotic demyelination syndrome
Neurological involvement in Behçets disease
Brain trauma
Pathophysiology
The proposed mechanism of pseudobulbar palsy points to the disinhibition of the motor neurons controlling laughter and crying, proposing that a reciprocal pathway exists between the cerebellum and the brain stem that adjusts laughter and crying responses, making them appropriate to context. The pseudobulbar crying could also be induced by stimulation in the region of the subthalamic nucleus of the brain.
Diagnosis
Diagnosis of pseudobulbar palsy is based on observation of the symptoms of the condition. Tests examining jaw jerk and gag reflex can also be performed. It has been suggested that the majority of patients with pathological laughter and crying have pseudobulbar palsy due to bilateral corticobulbar lesions and often a bipyramidal involvement of arms and legs. To further confirm the condition, MRI can be performed to define the areas of brain abnormality.
Treatment
Since pseudobulbar palsy is a syndrome associated with other diseases, treating the underlying disease may eventually reduce the symptoms of pseudobulbar palsy.Possible pharmacological interventions for pseudobulbar affect include the tricyclic antidepressants, serotonin reuptake inhibitors, and a novel approach utilizing dextromethorphan and quinidine sulfate. Nuedexta is an FDA approved medication for pseudobulbar affect. Dextromethorphan, an N-methyl-D-aspartate receptor antagonist, inhibits glutamatergic transmission in the regions of the brainstem and cerebellum, which are hypothesized to be involved in pseudobulbar symptoms, and acts as a sigma ligand, binding to the sigma-1 receptors that mediate the emotional motor expression.
See also
Corticobulbar tract
Bulbar palsy, a similar syndrome caused by the damage of lower motor neurons.
Motor neuron disease
References
== External links == |
Periorbital dermatitis | Periorbital dermatitis is a skin condition, a variant of perioral dermatitis, occurring on the lower eyelids and skin adjacent to the upper and lower eyelids.
See also
Granulomatous perioral dermatitis
Perioral dermatitis
== References == |
Langer–Giedion syndrome | Langer–Giedion syndrome (LGS) is a very uncommon autosomal dominant genetic disorder caused by a deletion of a small section of material on chromosome 8. It is named after the two doctors who undertook the main research into the condition in the 1960s. Diagnosis is usually made at birth or in early childhood.
Signs and symptoms
The features associated with this condition include: mild to moderate learning difficulties, short stature, unique facial features, small head and skeletal abnormalities including bony growths projecting from the surfaces of bones.
Craniofacial
Individuals with Langer–Giedion syndrome may display characteristic craniofacial abnormalities. These include a long prominent philtrum, a thin upper lip, wide spaced eyes, a bulbous nasal tip, a broad nasal bridge, wide nostrils, micrognathia, retrognathia, deep set eyes and large ears. The head itself is often unusually small in comparison to that of unaffected individuals of the same age and sex. Dental abnormalities, such as supernumerary central incisors and the absence of some teeth, may occur
Muscoskeletal
Langer–Giedion syndrome causes cone shaped epiphyses of the phalanges of the hands and short fingers and toes. The fifth fingers are sometimes bent. Skeletal abnormalities not affecting the hands and feet may also occur. These include winged scapula, thin ribs and scoliosis. In addition, individuals with Langer–Giedion syndrome may develop hip problems similar to those seen in Legg–Calvé–Perthes disease such as progressive degeneration of the head of the thigh bone.As affected individuals age they often develop benign boney growths called exostoses which project off the surfaces of the bones. Depending on the location of the exostoses they cause numerous complications such as compression of the spinal cord, asymmetric growth of the limbs and reduced mobility.Langer–Giedion syndrome initially causes joint hypermobility. This progresses to joint stiffness later in life when osteochondromas begin to develop, typically between infancy and mid-childhood, which decreases mobility. Hip dysplasia may be present, usually developing in early adulthood although it can occur in infancy or childhood.
Skin, hair, sweat glands and nails
Ectodermal dysplasia is a key feature of Langer–Giedion syndrome.The majority of individuals with Langer–Giedion syndrome have sparse scalp hair; this is particularly severe in males, who often experience alopecia shortly after puberty. Despite this the eyebrows may be unusually thick.
Cause
The syndrome occurs when a small piece of chromosome 8s long arm, which contains a number of genes, is missing. The loss of these genes is responsible for some of the overall characteristics of Langer–Giedion syndrome.The missing portion of the chromosome is 8q23.2–q24.1. This region includes the genes TRPS1 and EXT1.
Diagnosis
Diagnosis is based on clinical findings and can be confirmed by cytogenetic testing, when the deletion is in an average of 5 Mb (millions of base pairs). Nowadays, it is a common practice to run an aCGH (array chromosome hybridization genome) study on peripheral blood of the patient, in order to delineate the extent of the loss of the genomic area, and the deleted genes.
Treatment
While no genetic syndrome is capable of being cured, treatments are available for some symptoms. External fixators have been used for limbic and facial reconstructions.
See also
TRPS1
References
External links
Trichorhinophalangeal syndrome type 2 at NIHs Office of Rare Diseases |
Eruptive vellus hair cyst | Eruptive vellus hair cysts (or EVHC) are small lesions that occur most often in the chest wall, abdomen and extremities, often with a crusted surface.: 680 EVHC may occur randomly, or it can be inherited as an autosomal dominant trait. The condition affects males and females equally, and sporadic cases usually appear at 4–18 years of age. The cysts appear similar clinically to steatocystoma multiplex, as well as acneiform eruptions and milia. Therapeutic techniques that are safe and effective are rare, with incision and drainage being the primary form of treatment when sporadic regression does not occur. It was first described in 1977.
Signs/symptoms
Cause
Diagnosis
Histopathology is the basis of diagnosis. Stratified-squamous epithelium with a granular layer that surrounding a cystic space filled with laminated keratin and a variable number of vellus hair cysts is seen to be present. It can be difficult to distinguish from other skin conditions, including molluscum contagiosum and acne vulgaris but can be corroborated with histopathology.
Associations
It can be associated with Steatocystoma multiplex.
Treatment
The primary indication for treatment is cosmesis. Retinoids, surgery, and lasers are used as treatment modalities.
See also
Steatocystoma simplex
Milia
List of cutaneous conditions
References
Further reading
Torchia, Daniele; Vega, Janelle; Schachner, Lawrence A. (1 February 2012). "Eruptive Vellus Hair Cysts". American Journal of Clinical Dermatology. 13 (1): 19–28. doi:10.2165/11589050-000000000-00000. PMID 21958358. |
Obstructive shock | Obstructive shock is one of the four types of shock, caused by a physical obstruction in the flow of blood. Obstruction can occur at the level of the great vessels or the heart itself. Causes include pulmonary embolism, cardiac tamponade, and tension pneumothorax. These are all life-threatening. Symptoms may include shortness of breath, weakness, or altered mental status. Low blood pressure and tachycardia are often seen in shock. Other symptoms depend on the underlying cause.The physiology of obstructive shock is similar to cardiogenic shock. In both types, the hearts output of blood (cardiac output) is decreased. This causes a back-up of blood into the veins entering the right atrium. Jugular venous distension can be observed in the neck. This finding can be seen in obstructive and cardiogenic shock. With the decrease cardiac output, blood flow to vital tissues is decreased. Poor perfusion to organs leads to shock. Due to these similarities, some sources place obstructive shock under the category of cardiogenic shock.However, it is important to distinguish between the two types, because treatment is different. In cardiogenic shock, the problem is in the function of the heart itself. In obstructive shock, the underlying problem is not the pump. Rather, the input into the heart (venous return) is decreased or the pressure against which the heart is pumping (afterload) is higher than normal. Treating the underlying cause can reverse the shock. For example, tension pneumothorax needs rapid needle decompression. This decreases the pressure in the chest. Blood flow to and from the heart is restored, and shock resolves.
Signs and Symptoms
As in all types of shock, low blood pressure is a key finding in patients with obstructive shock. In response to low blood pressure, heart rate increases. Shortness of breath, tachypnea, and hypoxia may be present. Because of poor blood flow to the tissues, patients may have cold extremities. Less blood to the kidneys and brain can cause decreased urine output and altered mental status, respectively.Other signs may be seen depending on the underlying cause. For example, jugular venous distension is a significant finding in evaluating shock. This occurs in cardiogenic and obstructive shock. This is not observed in the other two types of shock, hypovolemic and distributive. Some particular clinical findings are described below.
A classic finding of cardiac tamponade is Becks triad. The triad includes hypotension, jugular vein distension, and muffled heart sounds. Kussmauls sign and pulsus paradoxus may also be seen. Low-voltage QRS complexes and electrical alternans are signs on EKG. However, EKG may not show these findings and most often shows tachycardia.Tension pneumothorax would have decreased breath sounds on the affected side. Tracheal deviation may also be present, shifted away from the affected side. Thus, a lung exam is important. Other findings may include decreased chest mobility and air underneath the skin (subcutaneous emphysema).Pulmonary embolism similarly presents with shortness of breath and hypoxia. Chest pain worse with inspiration is frequently seen. Chest pain can also be similar to a heart attack. This is due to the right ventricular stress and ischemia that can occur in PE. Other symptoms are syncope and hemoptysis. DVT is a common cause. Thus, symptoms including leg pain, redness, and swelling can be present. The likelihood of pulmonary embolism can be evaluated through various criteria. The Wells score is often calculated. It gives points based on these symptoms and patient risk factors.
Causes
Causes include any obstruction of blood flow to and from the heart. There are multiple, including pulmonary embolism, cardiac tamponade, and tension pneumothorax. Other causes include abdominal compartment syndrome, severe aortic valve stenosis, and disorders of the aorta. Constrictive pericarditis is a rare cause. Masses can grow to press on major blood vessels causing shock.
Tension pneumothorax
A pneumothorax occurs when air collects in the pleural space around the lungs. Normally, this space has negative pressure to allow the lung to fill. Pressure increases as more air enters this space. The lung collapses, impairing normal breathing. Surrounding structures may also shift. When severe enough to cause these shifts and hypotension, it is called a tension pneumothorax. This is life-threatening. The veins supplying the heart are compressed. Thus, venous return is decreased. With the heart unable to fill, cardiac output drops. Hypotension and shock ensue. If not rapidly treated, it can lead to cardiac arrest and death.
Pulmonary embolism
A pulmonary embolism (PE) is an obstruction of the pulmonary arteries. Deaths from PE have been estimated at ~100,000 per year in the United States. However, this may be higher in recent years. Most often, the obstruction is a blood clot that traveled from elsewhere in the body. Most commonly, this is from a deep vein thrombosis (DVT) in the legs or pelvis. Risk factors are conditions that increase the risk of clotting. This includes genetic (factor V Leiden) and acquired conditions (cancer). Trauma, surgery, and prolonged bed-rest are common risks. Covid-19 is a recent risk factor.This obstruction increases the pulmonary vascular resistance. If large enough, the clot increases the load on the right side of the heart. The right ventricle must work harder to pump blood to the lungs. With back-up of blood, the right ventricle can begin to dilate. Right heart failure can ensue, leading to shock and death.A PE is considered "massive" when it causes hypotension or shock. A submassive PE causes right heart dysfunction without hypotension.
Cardiac tamponade
A pericardial effusion is fluid in the pericardial sac. When large enough, the pressure compresses the heart. This causes shock by preventing the heart from filling with blood. This is called cardiac tamponade. The chambers of the heart can collapse from this pressure. The right heart has thinner walls and collapses more easily. With less venous return, cardiac output decreases. The lack of blood flow to vital organs can cause death.Various conditions can cause a pericardial effusion. Inflammation of the pericardium is called pericarditis. This is caused by infection, renal failure or autoimmune disease. Trauma can cause blood to fill the pericardium. Cancer can also cause effusions.
Whether an effusion causes tamponade depends on the amount of fluid and how long it took to accumulate. When fluid collects slowly, the pericardium can stretch. Thus, a chronic effusion can be as large as 1 liter. Acute effusions can cause tamponade when small because the tissue does not have time to stretch.
Diagnosis
Rapid evaluation of shock is essential given its life-threatening nature. Diagnosis requires a thorough history, physical exam, and additional tests. One must also consider the possibility of multiple types of shock being present. For example, a trauma patient may be hypovolemic from blood loss. This patient could also have tension pneumothorax due to trauma to the chest.Vital signs in obstructive shock may show hypotension, tachycardia, and/or hypoxia. A physical exam include be thorough, including jugular vein exam, cardiac and lung exams, and assessing skin tone and temperature. Response to fluids may aid in diagnosis. Labs including a metabolic panel can assess electrolytes and kidney and liver function. Lactic acid rises due to poor tissue perfusion. This may even be an initial sign of shock and rise before blood pressure decreases. Lactic acid should lower with appropriate treatment of shock. EKG should also be performed. Tachycardia is often present, but other specific findings may be present based on the underlying cause.At the bedside, point-of-care echocardiography should be used. This is non-invasive and can help diagnose the four types of shock. Echocardiography can look for ventricular dysfunction, effusions, or valve dysfunction. Measurement of the vena cava during the breathing cycle can help assess volume status. A point-of-care echocardiogram can also assess for causes of obstructive shock. The vena cava would be dilated due to the obstruction. In pulmonary embolism, the right ventricle will be dilated. Other findings include paradoxical septal motion or clots in the right heart or pulmonary artery. Echocardiography can assess for pericardial effusion. In tamponade, collapse of the right atrium and ventricle would be seen due to pressure in the pericardial sac.A chest X-ray can rapidly identify a pneumothorax, seen as absence of lung markings. Ultrasound can show the lack of lung sliding. However, imaging should not delay treatment. CT angiography is the standard of diagnosis of pulmonary embolism. Clots appear in the vasculature as filling defects.
Treatment
In any type of shock, rapid treatment is essential. Delays in therapy increase the risk of mortality. This is often done as diagnostic assessment is still occurring. Resuscitation addresses the ABCs - airway, breathing, and circulation. Supplemental oxygen is given, and intubation is performed if indicated. Intravenous fluids can increase blood pressure and maintain blood flow to organs.However, fluids should be given with caution. Too much fluid can cause overload and pulmonary edema. In some cases, fluids may be beneficial. Fluids can improve venous return. For example, tamponade prevents normal cardiac filling due to pressure compressing the heart. In this case, giving fluids can improve right heart filling. However, in other causes of obstructive shock, too much fluid can worsen cardiac output. Thus, fluid therapy should be monitored closely.After these stabilizing measures, further treatment depends on the cause. Treatment of the underlying condition can quickly resolve the shock. For tension pneumothorax, needle decompression should be done immediately. A chest tube is also inserted. Cardiac tamponade is treated through needle or surgical decompression. Needle pericardiocentesis can be done at the bedside. This is often the preferred therapy. A catheter may be placed for continued drainage. If these methods are not effective, surgery may be needed. Pericardial window is a surgery that is particularly in cases of cancer.Massive pulmonary embolism requires thrombolysis or embolectomy. Thrombolysis can be systemic via IV alteplase (tPA) or catheter-directed. tPA works to break up the clot. A major risk of tPA is bleeding. Thus, patients must be assessed for their risk of bleeding and contraindications. Catheter-directed therapy involves giving tPA locally in the pulmonary artery. It can also fragment and remove the clot itself (embolectomy). This local therapy has a lower risk of bleeding. Surgical embolectomy is a more invasive treatment, associated with 10-20% surgical mortality risk.
== References == |
Cleidocranial dysostosis | Cleidocranial dysostosis (CCD), also called cleidocranial dysplasia, is a birth defect that mostly affects the bones and teeth. The collarbones are typically either poorly developed or absent, which allows the shoulders to be brought close together. The front of the skull often does not close until later, and those affected are often shorter than average. Other symptoms may include a prominent forehead, wide set eyes, abnormal teeth, and a flat nose. Symptoms vary among people; however, intelligence is typically unaffected.The condition is either inherited from a persons parents or occurs as a new mutation. It is inherited in an autosomal dominant manner. It is due to a defect in the RUNX2 gene which is involved in bone formation. Diagnosis is suspected based on symptoms and X-rays with confirmation by genetic testing. Other conditions that can produce similar symptoms include mandibuloacral dysplasia, pyknodysostosis, osteogenesis imperfecta, and Hajdu-Cheney syndrome.Treatment includes supportive measures such as a device to protect the skull and dental care. Surgery may be performed to fix certain bone abnormalities. Life expectancy is generally normal.It affects about one per million people. Males and females are equally commonly affected. Modern descriptions of the condition date to at least 1896. The term is from cleido meaning collarbone, cranial from the Greek κρανιὀς meaning skull, and dysostosis meaning formation of abnormal bone.
Signs and symptoms
Cleidocranial dysostosis is a general skeletal condition so named from the collarbone (cleido-) and cranium deformities which people with it often have.
People with the condition usually present with a painless swelling in the area of the clavicles at 2–3 years of age. Common features are:
Clavicles (collarbones) can be partly missing leaving only the medial part of the bone. In 10% of cases, they are completely missing. If the collarbones are completely missing or reduced to small vestiges, this allows hypermobility of the shoulders including ability to touch the shoulders together in front of the chest. The defect is bilateral 80% of the time. Partial collarbones may cause nerve damage symptoms and therefore have to be removed by surgery.
The mandible is prognathic due to hypoplasia of maxilla (micrognathism) and other facial bones.
A soft spot or larger soft area in the top of the head where the fontanelle failed to close, or the fontanelle closes late.
Bones and joints are underdeveloped. People are shorter and their frames are smaller than their siblings who do not have the condition.
The permanent teeth include supernumerary teeth. Unless these supernumeraries are removed they will crowd the adult teeth in what already may be an underdeveloped jaw. If so, the supernumeraries will probably need to be removed to make space for the adult teeth. Up to 13 supernumerary teeth have been observed. Teeth may also be displaced. Cementum formation may be deficient.
Failure of eruption of permanent teeth.
Bossing (bulging) of the forehead.
Open skull sutures, large fontanelles.
Hypertelorism.
Delayed ossification of bones forming symphysis pubis, producing a widened symphysis.
Coxa vara can occur, limiting abduction and causing Trendelenburg gait.
Short middle fifth phalanges, sometimes causing short and wide fingers.
Vertebral abnormalities.
On rare occasions, brachial plexus irritation can occur.
Scoliosis, spina bifida and syringomyelia have also been described.Other features are: parietal bossing, basilar invagination (atlantoaxial impaction), persistent metopic suture, abnormal ear structures with hearing loss, supernumerary ribs, hemivertebrae with spondylosis, small and high scapulae, hypoplasia of illiac bones, absence of the pubic bone, short / absent fibular bones, short / absent radial bones, hypoplastic terminal phalanges.
Genetics
CCD is usually autosomal dominant, but in some cases its cause is not known. The main mechanism is thought to involve haploinsufficiency caused by mutations in CBFA1 (also known as Runx2), a gene located on the short arm of chromosome 6 (6p21), which encodes a transcription factor required for the differentiation of stem cells into osteoblasts. This results in delayed ossification of midline structures of the body and ensuing defects in membranous and endochondral bone formation.
Diagnosis
Different features of the dysostosis are significant. Radiological imaging helps confirm the diagnosis. During gestation (pregnancy), clavicular size can be calculated using available nomograms. Wormian bones can sometimes be observed in the skull.Diagnosis of CCD spectrum disorder is established in an individual with typical clinical and radiographic findings and/or by the identification of a heterozygous pathogenic variant in RUNX2 (CBFA1).
Treatment
Around 5 years of age, surgical correction may be necessary to prevent any worsening of the deformity. If the mother has dysplasia, caesarian delivery may be necessary. Craniofacial surgery may be necessary to correct skull defects. Coxa vara is treated by corrective femoral osteotomies. If there is brachial plexus irritation with pain and numbness, excision of the clavicular fragments can be performed to decompress it. In case of open fontanelle, appropriate headgear may be advised by the orthopedist for protection from injury.
Prognosis
Several studies have reported that life expectancy appears to be normal for people with CCD.
Epidemiology
Cleidocranial dysostosis affects about one per million people.
Notable cases
In 1987, a young girl named Jessica McClure fell down a narrow well pipe in her familys Texas property. Ron Short, a roofing contractor who was born without collarbones because of cleidocranial dysostosis and thus could collapse his shoulders to work in cramped corners, arrived at the site and offered to go down the shaft. The rescuers did not end up using him, though McClure was successfully recovered from the well.
Actor Gaten Matarazzo was born with cleidocranial dysplasia, which is incorporated into his character Dustin Hendersons storyline on Stranger Things.Sibling actress-singers Milly and Abby Shapiro were born with cleidocranial dysplasia, a trait they share with their mother.
References
External links
Cleidocranial dysostosis at Curlie |
Delayed pressure urticaria | Delayed pressure urticaria is known as one of the more painful subsets of physical urticaria due to formed hives being deep-seated and appearing after 4–6 hours.
Causes
Due to the delayed appearance of wheals, plausible causes are hard to establish; the natural course and/or clinical pattern is variable and inconclusive.
Treatment
It was noted that although antihistamines and anti-inflammatory drugs such as, colchicine, sulphasalazine, dapsone, and topical steroid are advocated for in the treatment of DPU, most if not all are unsatisfactory in relieving symptoms. Even a second generation antihistamine, ketotifen, was unable to efficiently and satisfactorily relieve symptoms of DPU
== References == |
Bruck syndrome | Bruck syndrome is characterized as the combination of arthrogryposis multiplex congenita and osteogenesis imperfecta. Both diseases are uncommon, but concurrence is extremely rare which makes Bruck syndrome very difficult to research. Bruck syndrome is thought to be an atypical variant of osteogenesis imperfecta most resembling type III, if not its own disease. Multiple gene mutations associated with osteogenesis imperfecta are not seen in Bruck syndrome. Many affected individuals are within the same family, and pedigree data supports that the disease is acquired through autosomal recessive inheritance. Bruck syndrome has features of congenital contractures, bone fragility, recurring bone fractures, flexion joint and limb deformities, pterygia, short body height, and progressive kyphoscoliosis. Individuals encounter restricted mobility and pulmonary function. A reduction in bone mineral content and larger hydroxyapatite crystals are also detectable Joint contractures are primarily bilateral and symmetrical, and most prone to ankles. Bruck syndrome has no effect on intelligence, vision, or hearing.
Genetics
The genetics of Bruck syndrome differs from osteogenesis imperfecta. Osteogenesis imperfecta involves autosomal dominant mutations to Col 1A2 or Col 1A2 which encode type 1 procollagen. Bruck syndrome is linked to mutations in two genes, and therefore is divided in two types. Bruck syndrome type 1 is caused by a homozygous mutation in the FKBP10 gene. Type 2 is caused by a homozygous mutation in the PLOD2 gene.
Mechanism
Type 1 encodes FKBP65, an endoplasmic reticulum associated peptidyl-prolyl cis/trans isomerase (PPIase) that functions as a chaperone in collagen biosynthesis. Osteoblasts deficient in FKBP65 have a buildup of procollagen aggregates in the endoplasmic reticulum which reduces their ability to form bone. Furthermore, Bruck syndrome type 1 patients have under-hydroxylated lysine residues in the collagen telopeptide and as a result show diminished hydroxylysylpyridinoline cross-links.Type 2 encodes the enzyme, lysyl hydroxylase 2, which catalyzes hydroxylation of lysine residues in collagen cross-links. PLOD2 is most expressed in active osteoblasts since collagen cross-linking is tissue-specific. Mutation in PLOD2 alters the structure of telopeptide lysyl hydroxylase and prevents fibril formation of collagen type 1. Bone analysis shows the lysine residues of telopeptides in collagen type 1 are under-hydroxylated.
Diagnosis
Diagnosis of Bruck syndrome must distinguish the association of contractures and skeletal fragility. Ultrasound is used for prenatal diagnosis. The diagnosis of a neonate bears resemblance to arthrogryposis multiplex congenital, and later in childhood to osteogenesis imperfecta.
Management
Until more molecular and clinical studies are performed there will be no way to prevent the disease. Treatments are directed towards alleviating the symptoms. To treat the disease it is crucial to diagnose it properly. Orthopedic therapy and fracture management are necessary to reduce the severity of symptoms. Bisphosphonate drugs are also an effective treatment.
History
The first case was in 1897 of a male who was described by Bruck as having bone fragility and bone contractures. Bruck was credited with the first description and the diseases eponym.
References
Further reading
Breslau-Siderius, E. J.; et al. (1998). "Brack syndrome: a rare combination of bone fragility and multiple congenital joint contractures". Journal of Pediatric Orthopaedics B. 7 (1): 35–38. doi:10.1097/01202412-199801000-00006.
== External links == |
Spindle cell rhabdomyosarcoma | Spindle cell rhabdomyosarcoma is a subtype of embryonal rhabdomyosarcoma first described by Cavazzana, Schmidt and Ninfo in 1992. This subtype has a more favorable clinical course and prognosis than usual embryonal rhabdomyosarcoma. Spindle cell rhabdomyosarcoma typically occurs in young males and most commonly occurs in paratesticular soft tissue, followed by the head and neck.
== References == |
Hereditary mucoepithelial dysplasia | Hereditary mucoepithelial dysplasia (HMD), or simply mucoepithelial dysplasia, is a rare autosomal dominant multiepithelial disorder causing systemic maldevelopment of the epithelia and mucous membranes that line the surface of tissues and structures throughout the body, particularly affecting systems affiliated with mucosa, which includes the respiratory, digestive, urinary, reproductive and immune systems. The disorder is attributed to improper formation of desmosomes and gap junctions, which prevents proper cornification of the epithelial layer of the skin.
Pathophysiology
Desmosomes are extracellular protein structures responsible for cellular adhesion, whereby cells of the same type are held closely together. Gap junctions are specialized channels located within the cell membrane of many animal cell types, which serve as gateways that connect the cytoplasmic interior of two adjacent cells, allowing the passage of small molecules such as ions, nucleotides, second messengers and others. The movement and exchange of small molecules between cells is an important part of intracellular communication processes like cell signaling.
Diagnosis
Treatment
References
== External links == |
Pancreas divisum | Pancreatic divisum is a congenital anomaly in the anatomy of the ducts of the pancreas in which a single pancreatic duct is not formed, but rather remains as two distinct dorsal and ventral ducts. Most individuals with pancreas divisum remain without symptoms or complications. A minority of people with pancreatic divisum may develop episodes of abdominal pain, nausea or vomiting due to acute or chronic pancreatitis. The presence of pancreas divisum is usually identified with cross sectional diagnostic imaging, such as MRI or computed tomography (CT) imaging. In some cases, endoscopic retrograde cholangiopancreatography (ERCP) is performed, revealing the diagnosis of pancreas divisum. If no symptoms or complications are present, then treatment is not necessary. However, if there is recurrent pancreatitis, then a sphincterotomy of the minor papilla may be indicated.
Causes
The human embryo begins life with two ducts in the pancreas, the ventral duct and the dorsal duct. Normally, the two ducts will fuse together to form one main pancreatic duct; this occurs in more than 90% of embryos. In approximately 10% of embryos the ventral and dorsal ducts fail to fuse together, resulting in pancreas divisum. In utero, the majority of the pancreas is drained by the dorsal duct which opens up into the minor duodenal papilla. The ventral duct drains the minority of the pancreas and opens into the major duodenal papilla. In adults however, this situation is reversed whereby 70% of the pancreas is drained by the ventral duct. Therefore in pancreas divisum, where fusion of the ducts does not occur, the major drainage of the pancreas is done by the dorsal duct which opens up into the minor papilla.
Diagnosis
The most common and accurate way of diagnosing an individual with this anomaly is by MRCP (Magnetic Resonance Cholangiopancreatography) or ERCP (Endoscopic Retrograde Cholangiopancreatography). This test can demonstrate the presence of two separately draining ducts within the pancreas. Other tests can assist doctors with diagnosis, such as a CT scan and an MRI.
Treatment
Pancreas divisum in individuals with no symptoms does not require treatment. For cases with mild and infrequent attacks, management may involve a low-fat diet, medications to reduce pain and gastrointestinal reactions, and pancreatic enzyme supplementation.A surgeon may attempt a sphincterotomy by cutting the minor papilla to enlarge the opening and allow pancreatic enzymes to flow normally. During surgery, a stent may be inserted into the duct to ensure that the duct will not close causing a blockage. This surgery can cause pancreatitis in patients, or in rare cases, kidney failure and death. Endoscopic approaches (ERCP) are sometimes used for symptomatic pancreas divisum, which offers the benefit of a less invasive approach compared with surgery. No large-scale clinical studies comparing surgical and endoscopic approaches are available.
Occurrence
Studies involving autopsy and imaging series indicate that between 6% and 10% of the population have pancreas divisum, but it is asymptomatic in the majority (>95%) of cases. In those who develop symptoms, the symptoms seen in pancreas divisum and pancreatitis with typical anatomy are the same: abdominal pain is common, typically of sudden onset and located in the left upper quadrant of the abdomen and often accompanied by nausea and vomiting. Pancreatic pain is characteristically described as a constant, severe, dull, epigastric pain that often radiates to the back and typically worsens after high-fat meals. However, many different pain patterns have been described, ranging from no pain to recurrent episodes of pain and pain free intervals, to constant pain with clusters of severe exacerbations.
References
External links
00303 at CHORUS |
Breastfeeding difficulties | Breastfeeding difficulties refers to problems that arise from breastfeeding, the feeding of an infant or young child with milk from a womans breasts. Although babies have a sucking reflex that enables them to suck and swallow milk, and human breast milk is usually the best source of nourishment for human infants, there are circumstances under which breastfeeding can be problematic, or even in rare instances, contraindicated.
Difficulties can arise both in connection with the act of breastfeeding and with the health of the nursing infant.
Breastfeeding problems
While breastfeeding difficulties are not uncommon, putting the baby to the breast as soon as possible after birth helps to avoid many problems. The policy of the American Academy of Pediatrics on breastfeeding instructs to, "delay weighing, measuring, bathing, needle-sticks, and eye prophylaxis until after the first feeding is completed." Many breastfeeding difficulties can be resolved with research based hospital procedures, properly trained nurses and hospital staff, speech pathologists and lactation consultants. Another source of information is the volunteer-based breastfeeding promotion organization, La Leche League.
A variety of factors and conditions can interfere with successful breastfeeding:
Ankyloglossia (tongue tie)
Formula feeding
Distractions or interruptions during feeds
Long separations from the mother
Tachypnea (rapid breathing) such as in transient tachypnea of the newborn, surfactant deficiency, respiratory distress syndrome or other infant medical conditions
Presence of an actual physical barrier between mother and infant
Swallowing difficulties such as with prematurity and coordination of sucking, swallowing and breathing, or gastro-intestinal tract abnormalities like tracheo-oesophageal fistula.
Pain resulting from surgical procedures like circumcision, blood tests, or vaccinations.
Latching onto the breast
Hypoplastic breasts/insufficient glandular tissue
Galactorrhea
Lactation failure
Polycystic ovarian syndrome
Diabetes
Maternal stress
Insufficient rest/support of the mother during the first 6 weeks post-partum
Early return to work due to lack of financial support/maternity leave of mother
Cleft palate
Thrush
Hypoglycemia or hyperglycemia
Hypotonia, or "low-tone" infant disorder
Hyperlactation syndrome
Overactive let-down
Premature babies can have difficulties coordinating their sucking reflex with breathing. They may need to be fed more frequently because their stomachs tend to be smaller, and they may get sleepier during feedings. Premature infants unable to take enough calories by mouth may need enteral or gavage feeding - inserting a feeding tube into the stomach to provide enough breast milk or a substitute. This is often done together with Kangaroo care (prolonged skin-to-skin contact with the mother) which makes later breastfeeding easier. For some suckling difficulties, such as may happen with cleft lip/palate, the baby can be fed with a Haberman Feeder.
Dysphoric milk ejection reflex (D-MER) is a newly recognized condition affecting lactating women that is characterized by an abrupt dysphoria, or negative emotions that occur just before milk release and continuing not more than a few minutes. Preliminary testing tells us that D-MER is treatable and preliminary research tells us that inappropriate dopamine activity at the time of the milk ejection reflex is the cause of D-MER.
Low milk supply
Primary lactation failure: occurs when the mother has a condition incompatible with full milk production, for example breast hypoplasia, breast reduction surgery, or bilateral mastectomy.
Secondary lactation failure: milk production that is low due to preventable factors, such as formula supplementation, poor milk transfer by the baby, or unrelieved breast engorgement.
Chronic low milk supply is estimated to be experienced by 10-15% of women.
Breast pain
Pain often interferes with successful breastfeeding. It is cited as the second most common cause for the abandonment of exclusive breastfeeding after perceived low milk supply.
Inverted nipples
Inverted or retracted nipples sometimes make attachment to the breast difficult. These mothers need additional support to feed their babies. Treatment is started after the birth of the baby. The nipple is manually stretched out several times a day. A pump or a plastic syringe is used to draw out the nipple and the baby is then put to the breast.
Engorgement
Breast engorgement is the sense of breast fullness experienced by most women within 36 hours of delivery. Normally, this is a painless sensation of "heaviness". Breastfeeding on demand is the primary way of preventing painful engorgement.
When the breast overfills with milk it becomes painful. Engorgement comes from not getting enough milk from the breast. It happens about 3 to 7 days after delivery and occurs more often in first time mothers. The increased blood supply, the accumulated milk and the swelling all contribute to the painful engorgement. Engorgement may affect the areola, the periphery of the breast or the entire breast, and may interfere with breastfeeding both from the pain and also from the distortion of the normal shape of the areola/nipple. This makes it harder for the baby to latch on properly for feeding. Latching may occur over only part of the areola. This can irritate the nipple more, and may lead to ineffective drainage of breast milk and more pain. Reverse pressure softening (RPS) is a technique that can soften the areola enabling deeper latching and more milk transfer; RPS involves gentle positive pressure in the direction of the chest wall from the fingertips around the areola. Engorgement may begin as a result of several factors such as nipple pain, improper feeding technique, infrequent feeding or infant-mother separation.
To prevent or treat engorgement, remove the milk from the breast, by breastfeeding, expressing or pumping. Gentle massage can help start the milk flow and so reduce the pressure. The reduced pressure softens the areola, perhaps even allowing the infant to feed. Warm water or warm compresses and expressing some milk before feeding can also help make breastfeeding more effective. Some researchers have suggested that after breastfeeding, mothers should pump and/or apply cold compresses to reduce swelling pain and vascularity even more. One published study suggested the use of "chilled cabbage leaves" applied to the breasts. Attempts to reproduce this technique met with mixed results. Nonsteroidal anti-inflammatory drugs or paracetamol (acetaminophen) may relieve the pain. A warm shower and using cold compresses to help ease the discomfort.
Nipple pain
Sore nipples (nipple pain, or thelalgia) are probably the most common complaint after the birth. They are generally reported by the second day after delivery but improve within 5 days. Pain beyond the first week, severe pain, cracking, fissures or localized swelling is not normal. The mother should see a doctor for further evaluation. Sore nipples, a common cause of pain, often come from the baby not latching on properly. Factors include too much pressure on the nipple when not enough of the areola is latched onto and an improper release of suction at the end of the feeding. Improper use of breast pumps or topical remedies can also contribute. Nipple pain can also be a sign of infection.
Candidiasis
Symptoms of candidiasis of the breast include pain, itching, burning and redness, or a shiny or white patchy appearance. The baby could have a white tongue that does not wipe clean. Candidiasis is common and may be associated with infant thrush.
Both mother and baby must be treated to get rid of this infection. First-line therapies include nystatin, ketaconazole or miconazole applied to the nipple and given by mouth to the baby. Strict cleaning of clothing and breast pumps is also required to eradicate the infection.Another non-prescription treatment of candidia is gentian violet. It usually works, and relief is rapid. It is messy, and will stain clothing. The babys lips will turn purple, but the purple will disappear after a few days.
Milk stasis
Milk stasis is when the milk ducts are blocked and cannot drain properly, usually due to swelling and insufficient breast emptying during the engorgement phase. This may affect only a part of the breast and is not associated with any infection. It can be treated by varying the babys feeding position and applying heat before feeding. If it happens more than once, further evaluation is needed. Milk stasis is an urgent matter for mothers who wish to breastfeed, as failure to remove milk from the breasts causes milk production to decrease and eventually stop.
Mastitis
Mastitis is an inflammation of the breast. It causes local pain (dolor), redness (rubor), swelling (tumor), and warmth (calor). Later stages of mastitis cause symptoms of systemic infection like fever and nausea. It mostly occurs 2–3 weeks after delivery but can happen at any time. Typically results from milk stasis with primary or secondary local, later systemic infection. Infectious organisms include Staphylococcus sp., Streptococcus sp. and E. coli. Continued breastfeeding, plenty of rest and adequate fluid supply is the best treatment for light cases.
Overactive let-down
Overactive let-down (OALD) is the forceful ejection of milk from the breast during breastfeeding. The forceful spray of milk can cause the baby to consume too much milk too quickly as well as to swallow air during the period of rapid swallowing following the let-down.
Raynauds of the nipple
Nipple pain can be caused by vasospasm of the nipple. In essence, blood does not flow properly to the nipple which causes the nipple to blanch. This can be caused by trauma to the nipple through early breastfeeding or candidal infection of the nipple. The pain is intense during the latch stage and in between breastfeeding sessions there is a throbbing pain when the nipple is blanched. The nipple can be massaged to help blood flow return to reduce pain, as well as avoiding cold. In some instances, heart medication, nifedipine, is used to help the blood flow return to the nipple.
Infant health problems
Infants with classic galactosemia cannot digest lactose and therefore cannot benefit from breast milk. Breastfeeding might harm the baby also if the mother has untreated pulmonary tuberculosis, is taking certain medications that suppress the immune system. has HIV, or uses potentially harmful substances such as cocaine, heroin, and amphetamines. Other than cases of acute poisoning, no environmental contaminant has been found to cause more harm to infants than lack of breastfeeding. Although heavy metals such as mercury are dispersed throughout the environment and are of concern to the nursing infant, the neurodevelopmental benefits of human milk tend to override the potential adverse effects of neurotoxicants.
Weak sucking reflex
Artificial teats (nipples) or dummies (pacifiers) can suppress the sucking reflex in infants. In addition, when a baby is put to the breast for shorter periods of time, milk production decreases. The time spent sucking by the infant on the pacifier or artificial teat reduces the time on the breast. The CDC also currently (2022) reports that early use of pacifiers can have a negative outcome on the success of breastfeeding and they suggest that it should be delayed until breastfeeding is firmly established.
Transmission of infection
Tuberculosis
It is not safe for mothers with active, untreated tuberculosis to breastfeed until they are no longer contagious. According to the American Academy of Pediatrics 2006 Redbook: Women with tuberculosis who have been treated appropriately for 2 or more weeks and who are not considered contagious may breastfeed. Women with tuberculosis disease suspected of being contagious should refrain from breastfeeding or any other close contact with the infant because of potential transmission through respiratory tract droplets (see Tuberculosis, p 678). Mycobacterium tuberculosis rarely causes mastitis or a breast abscess, but if a breast abscess caused by M. tuberculosis is present, breastfeeding should be discontinued until the mother no longer is contagious.
In areas where BCG vaccination is the standard of care, the WHO provides treatment recommendations and advises mothers to continue breastfeeding. TBC may be congenital, or perinatally acquired through airborne droplet spread.
HIV
Research published in the Lancet has highlighted a lower risk of HIV transmission with exclusive breastfeeding by HIV positive mothers (4% risk), compared to mixed feeding (10-40% risk). Research on the timing of HIV transmission in 2000 revealed that a "substantial transmission occurs early during breastfeeding," concluding that 75% of all breast milk transmission had occurred within the first 6 months during a randomized control trial in Kenya. This research is of particular importance in developing countries where infant formula is not widely available or safe to prepare. In fact, the World Health Organization recommended breastfeeding in 1987 and 1992 for seropositive and seronegative women in areas where malnutrition and infectious diseases are the major cause of infant mortality. In 1996 UNAIDS issued a recommendation that women in developing countries consider the risks and benefits of each feeding practice on an individual level; they recommended women make an informed choice about infant feeding. In the days before the AIDS epidemic was clearly understood, some researchers pointed to the need to increase breastfeeding rates and pointed to the risks of formula feeding, citing increased rates of marasmus and diarrhea. D Jelliffe and E Jelliffe also criticized the marketing of infant formulas by US companies to resource-poor countries, something they termed "comerciogenic malnutrition." A more recent article from 1992 describes how the health of an infant can be compromised by water, which in many resource-poor countries holds the risk of environmental pathogens that are not present in breastmilk.
Transmission of drugs and toxins
Medications
The vast majority of over the counter and prescription medicines are compatible with breastfeeding, but there are some that might be passed onto the child through the milk.
Tobacco smoke
If one does continue tobacco smoking after giving birth, however, it is still more beneficial to breastfeed than to completely avoid this practice altogether. There is evidence that breastfeeding offers protection against many infectious diseases, especially diarrhea. Even in babies exposed to the harmful effects of nicotine through breast milk, the likelihood of acute respiratory illness is significantly diminished when compared to infants whose mothers smoked but were formula fed. Regardless, the benefits of breastfeeding outweigh the risks of nicotine exposure.
The main concern about smoking and breastfeeding is that infants may have smoking-induced reductions to the milk iodine content. Smoking can adversely affect the lactation process by decreasing milk production and altering the milk composition. Smoking reduces daily milk output by roughly 250–300 mL. Not only will this be problematic on a daily basis for not producing enough milk, it will also cause the mother to wean her baby early. The altered milk composition also caused infants to exhibit daily behaviors such as colic and crying which can promote early weaning, again something that is not beneficial to the infant.Also, the nicotine obtained from smoking travels through a woman into her breast milk, thus giving nicotine to her child.Heavy use of cigarettes by the mother (more than 20 per day) has been shown to reduce the mothers milk supply and cause vomiting, diarrhoea, rapid heart rate, and restlessness in breastfed infants. Sudden Infant Death Syndrome (SIDS) is more common in babies exposed to a smoky environment. Breastfeeding mothers who smoke are counseled not to do so during or immediately before feeding their child, and are encouraged to seek advice to help them reduce their nicotine intake or quit.
Other substance abuse
With respect to alcohol, the American Academy of Pediatrics states that when breastfeeding, "moderation is definitely advised" and recommends waiting for 2 hours after drinking before nursing or pumping. A 2014 review found that "even in a theoretical case of binge drinking, the children would not be subjected to clinically relevant amounts of alcohol [through breastmilk]", and would have no adverse effects on children as long as drinking is "occasional".If the mother consumes too much caffeine, it can cause irritability, sleeplessness, nervousness and increased feeding in the breastfed infant. Moderate use (one to two cups per day of coffee, tea, or cola) usually produces no effect. Breastfeeding mothers are advised to restrict or avoid caffeine if her baby reacts negatively to it.
Cigarette smoking is thought to increase the effects of caffeine in the baby.
Cannabis
Cannabis is listed by the American Association of Pediatrics as a compound that transfers into human breast milk. Research demonstrated that certain compounds in marijuana have a very long half-life.
Diet
An exclusively breastfed baby depends on breast milk completely so it is important for the mother to maintain a healthy lifestyle, and especially a good diet. Consumption of 1500–1800 calories per day could coincide with a weight loss of 450 grams (one pound) per week. While mothers in famine conditions can produce milk with highly nutritional content, a malnourished mother may produce milk with decreased levels of several micronutrients such as iron, zinc, and vitamin B12. She may also have a lower supply than well-fed mothers.
There are no foods that are absolutely contraindicated during breastfeeding, but a baby may show sensitivity to particular foods that the mother eats.
Workplaces
Many mothers have to return to work soon after their babies have been born. If their employers and fellow employees do not support mothers in breastfeeding (for example, providing a private breastfeeding room containing a fridge where mothers can express and safely store breast milk), mothers might stop breastfeeding. This is not ideal for their infants. A Cochrane review assessed the effects of workplace interventions to support and promote breastfeeding among mothers returning to work after the birth of their babies. The review authors comprehensively searched in 2012 for studies addressing this question but found no eligible studies.
References
== External links == |
Hydrops fetalis | Hydrops foetalis or hydrops fetalis is a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments. By comparison, hydrops allantois or hydrops amnion is an accumulation of excessive fluid in the allantoic or amniotic space, respectively.
Signs and symptoms
Locations can include the subcutaneous tissue on the scalp, the pleura (pleural effusion), the pericardium (pericardial effusion) and the abdomen (ascites). Edema is usually seen in the fetal subcutaneous tissue, sometimes leading to spontaneous abortion. It is a prenatal form of heart failure, in which the heart is unable to satisfy demand (in most cases abnormally high) for blood flow.
Causes
Hydrops fetalis usually stems from fetal anemia, when the heart needs to pump a much greater volume of blood to deliver the same amount of oxygen. This anemia can have either an immune or non-immune cause. Non-immune hydrops can also be unrelated to anemia, for example if a fetal tumor or congenital cystic adenomatoid malformation increases the demand for blood flow. The increased demand for cardiac output leads to heart failure, and corresponding edema.
Immune pathophysiology
Erythroblastosis fetalis, also known as Rh disease, is the only immune cause of hydrops fetalis. Rh disease is a hemolytic disease of newborns. Pregnant mothers do not always have the same blood type as their child. During birth or throughout the pregnancy, the mother may be exposed to the infants blood. In the event of a pregnancy where the fetus has the Rh-D blood antigen and the mother does not, the mothers immune system will respond to the red blood cells as foreign and create antibodies against the Rh-D antigen on the fetal blood cells. Rh disease develops in the event of a second pregnancy where the mothers immune system launches an attack, via IgG, against the infants Rh-D positive blood cells. The immune response results in hemolysis of fetal red blood cells causing severe anemia.Hemolysis caused by the Rh incompatibility, causes extramedullary hematopoiesis in the fetal liver and bone marrow. The push to make more erythroblasts to help compensate with the hemolysis over works the liver causing hepatomegaly. The resulting liver dysfunction decreases albumin output which in turn decreases oncotic pressure. Consequentially, the decrease in pressure results in overall peripheral edema and ascites.Rh disease is currently an uncommon cause of immune-mediated hydrops fetalis. Due to preventative methods developed in the 1970s, the incidence of Rh disease has markedly declined. Rh disease can be prevented by administration of anti-D IgG (Rho(D) Immune Globulin) injections to RhD-negative mothers during pregnancy and/or within 72 hours of the delivery. However, a small percentage of pregnant mothers are still susceptible to Rh disease even after receiving anti-D IgG (Rho(D) Immune Globulin).
Non-immune pathophysiology
Severe anemia leads to hyperdynamic circulation, which means high-output cardiac failure causes the blood to circulate rapidly. The excessive pumping of blood causes the left side of the heart to fail leading to pulmonary edema. The build up of fluid in the lungs increases the pressure in the lungs leading to vasoconstriction. The coupled vasoconstriction and pulmonary hypertension causes the right side of the heart to fail which in turn, increases the venous hydrostatic pressure in the body. The summation of these effects ultimately leads to peripheral edema and ascites. All in all, the left side failure of the heart will lead to pulmonary edema whereas right side failure will lead to peripheral edema and ascites. The non-immune form of hydrops fetalis has many causes including:
Iron deficiency anemia
Paroxysmal supraventricular tachycardia resulting in heart failure
Deficiency of the enzyme beta-glucuronidase. This enzyme deficiency is the cause of the lysosomal storage disease called mucopolysaccharidosis type VII.
Congenital disorders of glycosylation
Parvovirus B19 (fifth disease) infection of the pregnant woman (most common cause)
Cytomegalovirus in mother
Congenital pulmonary airway malformation (formerly called congenital cystic adenomatoid malformation)
Maternal syphilis and maternal diabetes mellitus
Alpha-thalassemia can also cause hydrops fetalis when all four of the genetic loci for α globin are deleted or affected by mutation. This is termed Hb Barts (consists of y-4 tetramers).
Uncommonly, Niemann-Pick disease Type C (NPC) and Gaucher disease type 2 can present with hydrops fetalis.
Turner syndrome
Tumors, the most common type of fetal tumor being teratoma, particularly a sacrococcygeal teratoma.
Twin-twin transfusion syndrome (TTTS) in pregnancies in which twins share a single placenta (hydrops affects the recipient twin)
Twin anemia-polycythemia sequence (TAPS)
Twin reversed arterial perfusion sequence (TRAPS)
Maternal hyperthyroidism
Fetal cardiac defects and skeletal defects
Noonan syndrome
Mirror syndrome, in which fetal and placental hydrops develops in association with maternal preeclampsia, edema and hypertension
Down syndrome
Diagnosis
Hydrops fetalis can be diagnosed and monitored by ultrasound scans. An official diagnosis is made by identifying excess serous fluid in at least one space (ascites, pleural effusion, of pericardial effusion) accompanied by skin edema (greater than 5 mm thick). A diagnosis can also be made by identifying excess serous fluid in two potential spaces without accompanying edema. Prenatal ultrasound scanning enables early recognition of hydrops fetalis and has been enhanced with the introduction of MCA Doppler.
Treatment
The treatment depends on the cause and stage of the pregnancy.
Severely anemic fetuses, including those with Rh disease and alpha thalassemia major, can be treated with blood transfusions while still in the womb. This treatment increases the chance that the fetus will survive until birth.
Therapy for Cardiac tachyarrhythmia, supraventricular tachycardia, atrial flutter, or atrial fibrillation etiologies are maternal transplacental administration of antiarrhythmic medication(s). This type of treatment is recommended unless the fetus is close to term.
Therapy for Fetal anemia caused by a parvovirus infection or fetomaternal hemorrhage is fetal blood sampling followed by intrauterine transfusion. This treatment at an advanced gestational age poses risks and should not be performed if the risks associated with delivery are considered to be less than those associated with the procedure.
Fetal hydrothorax, chylothorax, or large pleural effusion associated with bronchopulmonary sequestration should be treated using a Fetal needle drainage of effusion or placement of thoracoamniotic shunt. This procedure can be performed prior to delivery if gestational age is advanced.
Hydrops Fetalis resulting from fetal CPAM can be treated using either a fetal needle drainage of effusion or placement of thoracoamniotic shunt or a maternal administration of corticosteroids, betamethasone 12.5 mg IM q24 h × 2 doses or dexamethasone 6.25 mg IM q12 h × 4 doses.
Therapy for hydrops fetalis derived from TTTS or TAPS requires laser ablation of placental anastomoses or selective termination.
Therapy for hydrops fetalis derived from TRAPS requires percutaneous radio frequency ablation.
See also
Mirror syndrome
== References == |
Trachonychia | Trachyonychia, is a condition characterized by rough accentuated linear ridges (longitudinal striations) on the nails of the fingers and toes. When the condition occurs on all the twenty nails of the fingers and toes, it is known as twenty-nail dystrophy, most evident in childhood, favoring males.Trachyonychia causes the nails to become opalescent, thin, dull, fragile, and finely longitudinally ridged, and, as a result, distally notched. It can be a manifestation of lichen planus, psoriasis, alopecia areata, immunoglobulin A deficiency, atopic dermatitis, and ichthyosis vulgaris."The longitudinal striations can occur as a normal part of the aging process", and not until the nails start to thin and get a sandpaper look is the condition called trachonychia. The nails are opalescent and frequently are brittle and split at the free margin. There has been evidence of the condition as a cutaneous manifestation of lichen planus. It has also been associated with other diseases such as eczema, psoriasis, alopecia areata, and atopic dermatitis. Trachonychia is often seen in vitiligo patients – suggesting that they are more susceptible to this condition.
References
== External links == |
Paraumbilical hernia | A paraumbilical (or umbilical) hernia is a hole in the connective tissue of the abdominal wall in the midline with close approximation to the umbilicus. If the hole is large enough there can be protrusion of the abdominal contents, including omental fat and/or bowel. These defects are usually congenital and are not noticed until they slowly enlarge over an individuals life time and abdominal contents herniate through the hole creating either pain or a visible lump on the abdominal wall. If abdominal contents get incarcerated (or stuck) in the hole this can cause pain. If the abdominal contents become strangulated by losing their blood supply from pinching or twisting those tissue will die. If it is omental fat this will cause pain and could potentially lead to an infection. If the strangulated contents are bowel then in addition to pain the individual will develop a bowel obstruction. And if the dead bowel is not surgically removed in an emergent fashion the condition could be fatal.
Treatment
There is no medical treatment to cure a hernia. It requires surgical intervention which involves closing the hole. If the hole is very small this can sometimes be accomplished by simply reapproximating the connective tissue. However for best long term success most hernias require a permanent barrier to cover the defect much like repairing a hole in a tire. This material is commonly referred to as mesh and can be made of different substances depending on the brand.
The operation is usually performed under a general anaesthetic.In most cases this is done as a day case without the need for an overnight stay.
References
== External links == |
Status marmoratus | Status marmoratus is a congenital condition due to maldevelopment of the corpus striatum associated with choreoathetosis, in which the striate nuclei have a marble-like appearance caused by altered myelination in the putamen, caudate, and thalamus (there are bilateral hyperdensities restricted to the thalamus). This results from acute total asphyxia in the basal nucleus of full-term infants. It is associated with athetoid cerebral palsy and spastic quadriplegia.
== References == |
Smouldering myeloma | Smouldering myeloma is a disease classified as intermediate in a spectrum of step-wise progressive diseases termed plasma cell dyscrasias. In this spectrum of diseases, a clone of plasma cells secreting monoclonal paraprotein (also termed myeloma protein or M protein) causes the relatively benign disease of monoclonal gammopathy of undetermined significance. This clone proliferates and may slowly evolve into more aggressive sub-clones that cause smouldering multiple myeloma. Further and more rapid evolution causes the overtly malignant stage of multiple myeloma and can subsequently lead to the extremely malignant stage of secondary plasma cell leukemia. Thus, some patients with smouldering myeloma progress to multiple myeloma and plasma cell leukemia. Smouldering myeloma, however, is not a malignant disease. It is characterised as a pre-malignant disease that lacks symptoms but is associated with bone marrow biopsy showing the presence of an abnormal number of clonal myeloma cells, blood and/or urine containing a myeloma protein, and a significant risk of developing into a malignant disease.
Diagnosis
Smouldering myeloma is characterised by:
Serum paraprotein >30 g/L or urinary monoclonal protein ≥500 mg per 24 h AND/OR
Clonal plasma cells >10% and <60% on bone marrow biopsy AND
No evidence of end organ damage that can be attributed to plasma cell disorder AND
No myeloma-defining event (>60% plasma cells in bone marrow OR Involved/Uninvolved light chain ratio>100)
Treatment
Treatment for multiple myeloma is focused on therapies that decrease the clonal plasma cell population and consequently decrease the signs and symptoms of disease. If the disease is completely asymptomatic (i.e. there is a paraprotein and an abnormal bone marrow population but no end-organ damage), as in smouldering myeloma, treatment is typically deferred, or restricted to clinical trials.They are generally responsive to IL-1β neutralisation.
Prognosis
Smouldering myeloma with an increasingly abnormal serum free light chain (FLC) ratio is associated with a higher risk for progression to active multiple myeloma.
References
== Further reading == |
Tricho–dento–osseous syndrome | Tricho–dento–osseous syndrome (TDO) is a rare, systemic, autosomal dominant genetic disorder that causes defects in hair, teeth, and bones respectively. This disease is present at birth. TDO has been shown to occur in areas of close geographic proximity and within families; most recent documented cases are in Virginia, Tennessee, and North Carolina. The cause of this disease is a mutation in the DLX3 (distal-less 3) gene, which controls hair follicle differentiation and induction of bone formation. All patients with TDO have two co-existing conditions called enamel hypoplasia and taurodontism in which the abnormal growth patterns of the teeth result in severe external and internal defects. The hair defects are characterized as being rough, course, with profuse shedding. Hair is curly and kinky at infancy but later straightens. Dental defects are characterized by dark-yellow/brownish colored teeth, thin and/or possibly pitted enamel, that is malformed. The teeth can also look normal in color, but also have a physical impression of extreme fragility and thinness in appearance. Additionally, severe underbites where the top and bottom teeth fail to correctly align may be present; it is common for the affected individual to have a larger, more pronounced lower jaw and longer bones. The physical deformities that TDO causes become more noticeable with age, and emotional support for the family as well as the affected individual is frequently recommended. Adequate treatment for TDO is a team based approach, mostly involving physical therapists, dentists, and oromaxillofacial surgeons. Genetic counseling is also recommended.
Signs and symptoms
Hair and bone abnormalities
Hair abnormalities are very prominent in majority of the cases of TDO. Kinky/curly hair that is unusually dry and easily sheds is present at birth. In 80% of cases, the hair has a more relaxed appearance by adolescence. The presence of this hair texture type is a defining characteristic between a diagnosis of TDO verses amelogenesis imperfecta with hypomaturation. Additionally, in TDO the nails are usually abnormally thin, brittle, and split frequently. Cranial deficiencies are marked by the presence of having a long skull relative to its width, or protrusive foreheads due to increased thickness of the cranial bones and premature closing of the associated sutures in the skull. The long bones in the body (arms, legs) are also abnormally long and tend to fracture very easily. Osteosclerosis, commonly seen in TDO cases is characterized by an increase in bone density, affecting the skull and the mastoid process located behind the jawbone on the skull, as well as a shortened ramus seen in people with TDO. There are no known pathological problems associated with hair and bone changes in people with this disease. Changes in the long bones tend to appear later in development, but changes in the teeth appear once the teeth being to form, called primary dentition. The hair and bone abnormalities are evaluated radiographically during initial diagnosis, and visually during the course of the disease. Radiographic exams may be repeated if there is suspect of fracture.
Oral abnormalities
In the oral cavity 100% of people diagnosed with TDO have taurodontism which is characterized by vertically enlarged pulp chambers at the expense of the roots of the teeth; the floor of the pulp chamber and furcation is moved apically down. This is due to the failure of the Hertwig epithelial root sheath which maps the shape of the forming tooth roots during active differentiation. Amelogenesis imperfecta, an abnormal formation of the enamel or external layer of the crown of the tooth, may also be present where the tooth enamel may be thin or absent. There are several clinical subsets of amelogenesis imperfecta, but common to TDO is the hypoplastic-hypomaturation subtype; the hypomaturation-hypoplastic is less common in individuals with TDO. The difference between the 2 dominant subtypes is the changes seen in the enamel matrix, and the phenotypic type that predominates. The hypoplastic-hypomaturation type of amelogenesis imperfecta with TDO occurs where the tooth enamel depicts a generalized pitted pattern, with open contacts between the teeth as well as an open bite. A smaller number of cases are of the hypomaturation-hypoplastic case type, in which the enamel structure is softer due to the under maturation of ameloblasts during development. Mandibular prognathism also called a severe underbite, is also a prominent feature in TDO. Prognathism defects are diagnosed based the level of severity that this condition interferes with being able to chew or speak properly.Due to improper tooth development, TDO patients have high rates of dental caries causing dental abscess. The under maturation of the enamel causes the tooth structure to be softer, and more susceptible to the effects of bruxism due to abnormalities in skeletal development. The oral abnormalities are evaluated by radiographs and visual examination. Oral radiographs are frequently repeated due to the high incidence of infection due to abnormal biting patterns seen in TDO cases.
Cause
TDO is caused by autosomal dominant mutations in the DLX gene family. Known mutations include a 4-basepair deletion in exon 3 of DLX3 on chromosome 17q21, causing a frameshift mutation.
Pathogenesis
DLX3 plays numerous significant roles during osseous, connective tissue, and dermal cell differentiation. It is expressed in the placenta and is important for embryonic development of hard bone tissue in the teeth, skull, and long bones such as in the arms and legs. During normal tooth development, DLX3 is predominantly expressed in the inner tooth enamel epithelium. In TDO cases, DLX3 is expressed in the outer enamel epithelium and leads to the abnormally thin enamel observed in the disease, which leads to tooth attrition and is most often the cause of dental abscess seen in TDO persons.
DLX3 in TDO is also responsible for upper cranial thickness, calvaria, osteosclerosis of the long bones, long narrow head (dolichocephaly), abnormally thin brittle nails, and premature closing of fibrous joints. Consequently, 95% of people with TDO that are 16 years old or younger show skeletal abnormalities before full maturation takes place.Lack of mastoid pneumatization by mastoid cells occurs in 82% of the cases and is rarely prevalent outside of TDO diagnosis. Mastoid pneumatization occurs at about 6 months of ages and acts to minimize pressure fluctuations in the Eustachian tubes of the ear. The mastoid lies posterior to the lower jawbone (mandible) and distal to the ear. The Eustachian tube connects the middle ear to the back of the nose, and acts to create a specific pressure in the ear canal that causes vibrations to the eardrum; if adequate pressure is not attained, muffled, dull hearing results. In addition to the mastoid pneumatization assisting the Eustachian tubes for normal hearing, lack of mastoid pneumatization causes inflammation of the ear, general irritation, and does not allow enough air in to assist with mucus flowing out. It is not completely understood why gene mutations occur, but it is known that genetic mutations that cause disease are acquired from either or both parents at fertilization.
Diagnosis
TDO is diagnosed by radiographic imaging, physical characteristics of the disease, and genetic testing. Radiographs such as cephalometric analysis or panoramic radiograph are used to detect skeletal abnormalities in TDO cases; these radiographs along with the phenotypic effects of the disease are often enough evidence for proper diagnosis. In TDO, radiologic imaging almost always shows evidence of hardening of bone tissue (sclerosis), lesions on the bone structures surrounding the teeth due to decay or trauma, or hard tissue mass. The radiographic testing is non-invasive, and involves the patient to be able to sit or stand in front of the radiographic device with their mouth closed and lips relaxed for approximately one minute. Oral abnormalities are diagnosed by a visual dental examination. A normal oral evaluation would show no signs of broken or fractured teeth, attrition of tooth enamel, no spacing between teeth, no soft tissue mass or sign of dental abscess, and a bite relationship where the mandibular (bottom) teeth interdigitate within a normal plane of 1-2mm behind and underneath the maxillary (top) teeth.
Overlapping diseases
It is phenotypically difficult to diagnose between TDO and Amelogenesis imperfecta of the hypomaturation-hypoplasia type with taurodontism (AIHHT) as they are very closely linked phenotypically during adulthood, and the only distinguishing characteristic is found during genetic analysis by Polymerase Chain Reaction (PCR) amplification. This type of test in diagnosis of TDO is only used during research or if there is a concern of genetic issue to a particular individual whose family member has been diagnosed with TDO.
Prevention
Preventive maintenance therapy for the oral effects of TDO involve frequent dental cleanings, professional application of desensitizing medication, diet counseling, and oral hygiene instructions in proper home care and maintenance; medicated dental rinses and toothpastes are also prescribed as people with TDO are more prone to oral hard tissue disease and early tooth loss. If restorative dentistry is performed without orthodontics to correct the protrusion of the lower jaw, a dental night guard worn at bedtimes on the upper or lower teeth to protect them from the effects of grinding may be recommended.In extreme cases, tooth loss is inevitable, and the patient will consult with a prosthodontist to determine tooth replacement options such as dental implants, or partial dentures. There is no cure for TDO, but managing its oral and systemic affects is key to having the most favorable outcome from the disease. As the person affected by TDO ages, increased bone fractures may occur. The person with TDO should watch for any pimple like masses on the gum tissue, pain or soreness in the teeth and gums, broken or chipped teeth, feeling of water in the ear or severe pain in the extremities which could indicate fracture.
Treatment
The hair, teeth, and skeletal side effects of TDO are lifelong, and treatment is used to manage those effects. A person with TDO has the same life expectancy as a person without TDO. There are no cures or medications used to treat systemic effects of TDO, but medications for the frequent ear and dental infections can be used to manage its symptoms. A team based approach between dental specialists, oral and maxillofacial surgeons, and physicians is necessary for treating the systemic effects and improves the prognosis. It is also recommended for affected individuals to seek counseling to be better able to cope with any psychosocial problems due to oral and facial abnormalities that occur with TDO.At home, a person with TDO may be instructed to use frequent deep conditioning treatments and low manipulation hair styling to control shedding and hair loss. Clinical treatment involves the use of radiology to determine the effects that TDO has had on the surrounding teeth and bone structures. A series of appointments with the healthcare team are usually necessary to correct TDO abnormalities with treatment duration lasting from several months to through full oral-facial maturation stages.Endodontic procedures are routinely recommended due to treatdental pulp exposure or periodontal abscess. Maxillofacial surgery may be required to establish a more appropriate mastication, skeletal, and esthetic relationship vertically between the teeth to improve functioning. Esthetic procedures such as dental crown (dentistry) or veneer (dentistry) are often performed to improve the physical look of the teeth and to strengthen the weak enamel caused by TDO.
Recent research
Amelogenesis imperfecta hypomaturation type with taurodontism are often confused. Amelogenesis imperfecta of the hypomaturation type with taurodontism (AIHHT) has no hair or bone changes which helps to differentiate between TDO cases and AIHHT. Polymerase chain reaction also known as PCR is used to amply pieces of DNA and observed for the 141 base pair allele as a result of a deletion of four nucleotides in exon 3 of the DLX-3 gene. Additionally, the current research shows that there is heavy reliance on the physical characteristics in the differentiation of TDO verses AIHHT and the severity and prevalence of their expression. For instance, taurodontism is severely expressed in TDO, but mildly expressed in AIHHT. Currently, researchers are trying to identify the reason for the alteration in the DLX-3 and DLX-7 genes that are responsible for AIHHT versus TDO.
See also
List of dental abnormalities associated with cutaneous conditions
Tricho–rhino–phalangeal syndrome
References
== External links == |
Embryonal rhabdomyosarcoma | Embryonal rhabdomyosarcoma (EMRS) is a rare histological form of cancer in the connective tissue wherein the mesenchymally-derived malignant cells resemble the primitive developing skeletal muscle of the embryo. It is the most common soft tissue sarcoma occurring in children. Embryonal rhabdomyosarcoma is also known as PAX-fusion negative or Fusion-Negative rhabdomyosarcoma, as tumors of this subtype are unified by their lack of a PAX3-FOXO1 fusion oncogene (or other PAX fusions seen in alveolar rhabdomyosarcoma). Fusion status refers to the presence or absence of a fusion gene, which is a gene formed from joining two different genes together through DNA rearrangements. These types of tumors are classified as embryonal rhabdomyosarcoma "because of their remarkable resemblance to developing embryonic and fetal skeletal muscle."
Classification
Embryonal rhabdomyosarcoma is the more common of the two major sub-types of rhabdomyosarcoma. ERMS accounts for 60% to 70% of rhabdomyosarcoma, the other being alveolar rhabdomyosarcoma (ARMS), also known as PAX-fusion positive or Fusion Positive rhabdomyosarcoma. Most often, ERMS is found in children during ages 0 to 5 years old, however ERMS can develop throughout any stage of life. Embryonal rhabdomyosarcoma can be further divided into three subcategories: the botryoid, spindle cell, and not-otherwise-specified (NOS). These two subtypes of rhabdomyosarcoma, ERMS and ARMS, also are caused by different genetic mutation pathways.The Horn-Enterline classification uses morphologic characteristics to divide rhabdomyosarcoma into the embryonal, alveolar, botryoid, and pleomorphic subtypes. However, due to recent advancements in molecular genetics, the genetic and epigenetic factors contributing to these morphological differences have been more closely examined. As a result, the World Health Organization currently takes into account both molecular genetics and morphology to classify rhabdomyosarcoma into the embryonal, alveolar, spindle cell/sclerosing, and pleomorphic subtypes.When examining Embroynal Rhabdomyosarcoma tumors vs. Alveolar Rhabdomyosarcoma tumors, a 2013 study had discovered that there were more rates of mutation in ERMS tumors. The study had use whole genome sequencing to sequence the DNA from 16 RMS tumors and found that RAS pathway mutations tend to be more associated with intermediate and high risk embryonal Rhabdomyosarcoma. Additionally, Embryonal Rhabdomyosarcoma tends to be more common in males versus females, with an occurrence of 1.4:1.
Histology
Embryonal rhabdomyosarcoma has been informally classified as a "small round blue cell tumor" because of the characteristic microscopic appearance of its cells after histological staining with hematoxylin and eosin. Histologically, embryonal rhabdomyosarcoma commonly presents as alternating loose and dense patches of cells, including round cell and spindle cell components. The heterogenous structure resembles striated muscle at various embryonal developmental stages.
Location
Embryonal rhabdomyosarcoma can develop in soft tissues throughout the body, however, it is commonly found in the "head and neck area or in the genital or urinary organs" The botryoid variant of ERMS occurs in mucosal-lined organs such as the common bile duct, bladder, and vagina. The etymology for this variant name comes from "grape clusters", referring to the gross appearance of grape-like masses.
Epidemiology of RMS
RMS has a higher incidence of affecting males compared to females. Embryonal rhabdomyosarcoma is the most common in young children but there has been report of a second age peak in adolescence years.
United States
As the most common form of soft tissue sarcoma, RMS affects around 4.5 people per million individuals under the age of 20 in the United States. From 1975 to 2005 in the United States, there is a lower incidence rate of rhabdomyosarcoma and better 5-year survival rates in Native Indian/Alaskan Native/Asian/Pacific Islander children compared to white or black children; however, Native Indian/Alaskan Native/Asian/Pacific Islander make up only 6.5% of the total population studied.
Global
The incidence of RMS in Europe is similar to that of the United States, while the incidence in some parts of Asia is half of the United States.
Etiology
Embryonal rhabdomyosarcoma results from copy number alterations as well as mutations in the RAS pathway. Genomic patterns associated with ERMS include the gains in chromosomes 8, 2, 11, 12, 13, and/or 20 and losses in chromosomes 10 and 15. Another common genomic alteration is loss of heterozygosity at chromosome 11p, the short arm of chromosome 11. It is believed that some of the identifying genetic mutations that can cause ERMS include p53 loss, RAS pathway activation, MYOD1 mutations. Patients in the fusion-negative group had different genetic mutation profiles than those in the fusion-positive group.Focusing on the fusion negative population, it was shown that the most fusion-negative tumors were caused by RAS isoform mutations. Approximately 50% of ERMS is associated with RAS mutations, with NRAS mutations more common in adolescent cases and HRAS and KRAS mutations occurring in 70% of infant cases. Embryonal rhabdomyosarcoma is commonly driven by a mutation in the RAS family of proto-oncogenes, creating a powerful signal which is now known to promote tumor growth by preventing muscle lineage progression by blocking expression of the transcription factor myogenin. Inhibition of this signaling pathway with a cancer medication, trametinib, has been recently shown to overcome this differentiation block and reduce tumor progression in animal models of embryonal rhabdomyosarcoma.Tumor suppressor gene mutations, such as TP53 mutations, were shown in about 13% in the mutations and MYOD1 mutations were seen in about 3% of the mutations. Tumor suppressors signal the cell to stop the cell cycle and start apoptosis, known as programmed cell death, when the cell senses damage or irregular cell cycle growth patterns. Approximately 10% of ERMS cases include a loss of function mutation at TP53, which results in anaplasia, poor cellular differentiation that can be identified through nuclei that are larger and darker-colored than normal. An international study of more than 600 people with RMS showed worst outcomes in cases with anaplasia, regardless of fusion-status.
Predisposing Conditions
Genetic conditions such as Gorlin syndrome, neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Li-Fraumeni syndrome, Noonan syndrome, Costello syndrome, and DICER1 syndrome have been shown to predispose individuals to embryonal rhabdomyosarcoma. Risk factors associated with embryonal rhabdomyosarcoma include cigarette smoking, older age of birth parent, x-ray exposure, and maternal drug use. Of note, the development of Noonan syndrome, Costello syndrome, and neurofibromatosis type 1 are RASopathies, associated with mutations in the RAS cell signaling pathway. ERMS caused by genetically inherited mutations is cannot be morphologically distinguished from spontaneously acquired ERMS.
Diagnosis
Rhabdomyosarcoma is diagnosed through the presence of embryonic myogenesis, or skeletal muscle formation, which can be identified through morphological examination as well as assays containing myogenic markers. Immunohistochemical assays use protein expression to determine the fusion status of the growth, differentiating fusion-negative rhabdomyosarcoma from fusion-positive rhabdomyosarcoma. In the recent years, there has been a shift to use molecular classification over histological classification as histology alone does not predict the fusion type of rhabdomyosarcoma. The performance of molecular genetic tests as well as matching the genotypic result to the clinical presentation are necessary to confirm the diagnosis of rhabdomyosarcoma as well as identify a subtype.
Immunochemistry
Fusion-status is determined through the expression of certain proteins that indicate muscle differentiation, or immunomarkers, although the specific assay panel used for diagnosis depends on the tumor morphology. These immunomarkers include desmin, muscle-specific actin, Myogenin, and MyoD1, the latter two being transcription factors that are involved in muscle differentiation. Embryonal rhabdomyosarcoma can be classified by its lack of PAX3–FOXO1 or PAX7–FOXO1 gene fusions, but approximately 20% of alveolar rhabdomyosarcomas are also determined to be fusion-negative. However, it is suggested that these "fusion-negative" ARMS may be a misclassification of embryonal rhabdomyosarcomas with predominantly dense morphology. The World Health Organization recommends considering "fusion-negative" ARMS as a "primitive form of ERMS". In either case, "fusion-negative" alveolar rhabdomyosarcoma have similar clinical presentation and outcome as embryonal rhabdomyosarcoma, thus risk stratification, prognosis, and treatment intensity of rhabdomyosarcoma are now determined by fusion-status instead of histological classification.
Imaging
After a physical exam, formal diagnosis of RMS in adult patients requires a computed tomography (CT) scan, which can assess the areas affected and to delineate the tumor. In children, physicians may opt for magnetic resonance imaging (MRI) to limit radiation exposure in younger populations. In the majority of individuals diagnosed with rhabdomyosarcoma, more than half are diagnosed before the age of 10.
Prognosis
The prognosis for rhabdomyosarcoma has improved greatly in recent decades, with over 70% of people surviving for five years after diagnosis. The combined use of radiotherapy and surgery has significantly reduced the mortality rates compared to patients who did not undergo any radiotherpay or chemotherapy treatments. Embryonal rhabdomyosarcoma is generally associated with better prognosis than alveolar rhabdomyosarcoma, with a 5-year survival prognosis of 82% and 53%, respectively. This may be due to the more aggressive and metastatic nature of ARMS that can be attributed to its PAX3–FOXO1 or PAX7–FOXO1 gene fusions. Nevertheless, some embryonal rhabdomyosarcoma patients with a rare Leu122Arg mutation in MYOD1 gene have a very poor outcome. In two different studies, none of the subjects with the MYOD1 mutation survived. Tumors due to this mutation commonly manifest in the head and neck area, causing the mutated protein to behave like an oncogene.There have not been many studies linking the genetic profile and clinical outcome of ERMS. However in "A Report From an International Consortium", the authors analyzed patient data from the Childrens Oncology Group (COG) and European paediatric Soft tissue sarcoma Study Group (EpSSG), hoping to identify and analyze any relationship between clinical outcomes and genetic mutations. The study comprised of 641 patients with sufficient data to analyze.Contrary to previous research, the findings of this study suggest that having RAS isoform mutations did not necessarily equate to a poor development of the disease. However, a pattern was found between the RAS isoform mutation seen and ones stage in life; HRAS isoform in infants, KRAS isoform in toddlers, and NRAS isoform in adolescence. This clinical study also found similar results as previous studies with the correlation of TP53 mutations and clinical outcome. TP53 mutations tended to result in a worsening development and clinical outcome of the disease. Although MYOD1 mutations make up a small percentage of ERMS, these mutations have been seen to have a negative prognosis and more studies should be conducted to understand how to treat the clinical condition of this specific mutation.
Tumor Location
Tumor location plays an important role as RMS located in the parameningeal area, retroperitonium, pelvic, vulva, uterus, vagina, or trunk area genereally have poor prognosis. The anatomical position of parameningeal RMS makes it difficult to completely resect the entire tumor via surgery and may lead to tumor recurrence. Additionally, imaging that shows a tumor greater than 5 cm, presence of metastases, or positive lymph node status can indicate poor prognosis. People that have more distant tumors — tumors that have spread to distant parts away from the primary site — have higher mortality rate when compared to people with only localized tumors.
Age of Diagnosis
In a 2020 case study of 464 adolescents aged 0–19 years diagnosed with rhabdomyosarcoma between 1988 to 2016, children who were diagnosed between ages 5–9 years had the most promising prognosis. In contrast, infants less than 1 years old had the worst outcome, which may be associated to the lower doses of chemotherapy and radiotherapy administered and naive immune system.
Treatment
Treatment for embryonal rhabdomyosarcoma involves the use of combination therapy consisting of chemotherapy, surgery, and/or radiation therapy. In order to create an optimal treatment plan for the individual, therapy is often based upon risk stratigication (low, intermediate, or high risk) based off of individuals disease stage, size of tumor, progression of disease, surgery resection, age at diagnosis, and site of tumor. In the US, a combination of Vincristine, Actinomycin D, and cyclophosphamide are often the chemotherapeutics used to treat rhabdomyosarcoma. In contrast, the regimen in Europe utilizes Vincristine, Actinomycin D, and ifosfamide. When the US and European regimen were studied side by side, the two regimens were comparable in terms of efficacy outcomes. Radiation therapy continues to be an integral component of rhabdomyosarcoma treatment, however, the long-term safety and treatment related complications remain a concern. Advancement in the use of radiation therapy includes using three-dimensional conformal radiation therapy (3D-CRT) to create a three-dimensional image of tumor so providers can determine the dose of radiation per patient while limiting radiation exposure to normal tissues. Techniques such as multi-field optimization (MFP) allows for more precise distribution of proton beams.
Treatment Plan
The first line of treatment for most people is surgery or resection of the tumor(s). The surgery involves removing the primary tumor and any tissue that may be infected with cancer cells. Resection of the tumor tends to be more favorable in cancers that have not yet metastisized. In the case that the tumor cannot be removed, the cancer can be treated with a combination of radiation and chemotherapy instead. In the majority of people, the surgery cannot remove all traces of the cancer and chemotherapy/radiation will be required as further treatment to eradicate any remaining cancer.
Chemotherapy is given in the US as a medication regimen abbreviated VAC, consisting of Vincristine, Actinomycin D, and Cyclophosphamide. The chemotherapy works to kill all the remaining cancer cells and to stop future growth of any possible cancerous cells. Safety concerns regarding the long term effects of chemotherapy remains a concern. Side effects of the VAC regimen include nausea, vomiting, liver damage, and immune system suppression. The length and dosing of the chemotherapy is oftentimes on a case by case basis based off the persons stage of cancer, site of tumor and age.
Radiation therapy utilizes high doses of radiation in order to kill the cancer cells. Most people are given external beam radiation therapy which is radiation given from a machine outside of the body. The number of radiation treatments are based off of the persons progression of disease. Side effects of radiation therapy include tiredness, skin irritation, and gastrointestinal issues.
Localized Rhabdomyosarcoma
In individuals with localized rhabdomyosarcoma, surgery and/or radiation therapy are primarily use to eliminate the tumor. Localized rhabdomyosarcoma can typically be treated successfully with the current standard of care and survival outcomes.
Metastatic Rhabdomyosarcoma
In individuals with metastatic rhabdomyosarcoma, combination therapy is not able to treat specific sites such as bone marrow or the lungs. Treatment for metastatic rhabdomyosarcoma has not changed over the last 3 decades and 5-year survival outcomes in those with high-risk rhabdomyosarcoma remain less than 40%. In terms of overall survival, metastatic rhabdomyosarcoma remains at 21% while recurrent rhadbomyosarcoma remains at 30%. In a European study on 174 adolescents with metastatic rhabdomyosarcoma, high dose chemotherapy compared to standard chemotherapy did not show a statistical difference in 5 year overall survival rates. In fact, those who received the high dose chemotherapy had experienced an increase in adverse events such as myelosuppression, peripheral neuropathy and later required a dose reduction. In individuals with more resistant rhabdomyosarcoma, more targeted therapies and immunotherapies in clinical trials have been of interest to gain better survival outcomes and reduce toxicities and treatment resistance.
References
== External links == |
Abfraction | Abfraction is a theoretical concept explaining a loss of tooth structure not caused by tooth decay (non-carious cervical lesions). It is suggested that these lesions are caused by forces placed on the teeth during biting, eating, chewing and grinding; the enamel, especially at the cementoenamel junction (CEJ), undergoes large amounts of stress, causing micro fractures and tooth tissue loss. Abfraction appears to be a modern condition, with examples of non-carious cervical lesions in the archaeological record typically caused by other factors.
Definition
Abfraction is a form of non-carious tooth tissue loss that occurs along the gingival margin. In other words, abfraction is a mechanical loss of tooth structure that is not caused by tooth decay, located along the gum line. There is theoretical evidence to support the concept of abfraction, but little experimental evidence exists.The term abfraction was first published in 1991 in a journal article dedicated to distinguishing the lesion. The article was titled "Abfractions: A New Classification of Hard Tissue Lesions of Teeth" by John O. Grippo. This article introduced the definition of abfraction as a "pathologic loss of hard tissue tooth substance caused by bio mechanical loading forces". This article was the first to establish abfraction as a new form of lesion, differing from abrasion, attrition, and erosion.Tooth tissue is gradually weakened causing tissue loss through fracture and chipping or successively worn away leaving a non-carious lesion on the tooth surface. These lesions occur in both the dentine and enamel of the tooth. These lesions generally occur around the cervical areas of the dentition.
Signs and symptoms
Abfraction lesions will generally occur in the region on the tooth where the greatest tensile stress is located. In statements such as these there is no comment on whether the lesions occur above or below the CEJ. One theory suggests that the abfraction lesions will only form above the CEJ. However, it is assumed that the abfraction lesions will occur anywhere in the cervical areas of affected teeth. It is important to note that studies supporting this configuration of abfraction lesions also state that when there is more than one abnormally large tensile stress on a tooth two or more abfraction lesions can result on the one surface.When looking at abfraction lesions there are generally three shapes in which they appear, appearing as either wedge, saucer or mixed patterns. Wedge and saucer shaped lesions are the most common, whereas mixed lesions are less frequently identified in the oral cavity. In reference to figure 1, wedge shaped lesions have the sharpest internal line angles and saucer/mixed shaped lesions are either smooth internally, or a variety.
Clinically, people with abfraction lesions can also present with tooth sensitivity in the associated areas. This occurs because as the abfraction lesions appear, dentine/cementum is exposed. The dentine and cementum are less dense than tooth enamel and therefore more susceptible to sensation from thermal/mechanical sources.
Causes
As abfraction is still a controversial theory there are various ideas on what causes the lesions. Because of this controversy the true causes of abfraction also remain disputable. Researchers have proposed that abfraction is caused by forces on the tooth from the teeth touching together, occlusal forces, when chewing and swallowing. These lead to a concentration of stress and flexion at the area where the enamel and cementum meet (CEJ). This theoretical stress concentration and flexion over time causes the bonds in the enamel of the tooth to break down and either fracture or be worn away from other stressors such as erosion or abrasion. The people who initially proposed the theory of abfraction believe the occlusal forces alone cause the lesions without requiring the added abrasive components such as toothbrush and paste or erosion.If teeth come together in a non-ideal bite the researchers state that this would create further stress in areas on the teeth. Teeth that come together too soon or come under more load than they are designed for could lead to abfraction lesions. The impacts of restorations on the chewing surfaces of the teeth being the incorrect height has also been raised as another factor adding to the stress at the CEJ.Further research has shown that the normal occlusal forces from chewing and swallowing are not sufficient to cause the stress and flexion required to cause abfraction lesions. However, these studies have shown that the forces are sufficient in a person who grinds their teeth (bruxism). Several studies have suggested that it is more common among those who grind their teeth, as the forces are greater and of longer duration. Yet further studies have shown that these lesions do not always appear in people with bruxism and others without bruxism have these lesions.There are other researchers who would state that occlusal forces have nothing to do with the lesions along the CEJ and that it is the result of abrasion from toothbrush with toothpaste that causes these lesions.Being theoretical in nature there is more than one idea on how abfraction presents clinically in the mouth. One theory of its clinical features suggests that the lesions only form above the cementoenamel junction (CEJ) (which is where the enamel and cementum meet on a tooth). If this is kept in mind, it serves as a platform for it to be distinguished from other non-carious lesions, such as tooth-brush abrasion.
Treatment
Treatment of abfraction lesions can be difficult due to the many possible causes. To provide the best treatment option the dental clinician must determine the level of activity and predict possible progression of the lesion. A No.12 scalpel is carefully used by the dental clinician to make a small indentation on the lesion, this is then closely monitored for changes. Loss of a scratch mark signifies that the lesion is active and progressing.
It is usually recommended when an abfraction lesion is less than 1 millimeter, monitoring at regular intervals is a sufficient treatment option. If there are concerns around aesthetics or clinical consequences such as dentinal hypersensitivity, a dental restoration (white filling) may be a suitable treatment option.
Aside from restoring the lesion, it is equally important to remove any other possible causative factors.
Adjustments to the biting surfaces of the teeth alter the way the upper and lower teeth come together, this may assist by redirecting the occlusal load. The aim of this is to redirect the force of the load to the long axis of the tooth, therefore removing the stress on the lesion. This can also be achieved by altering the tooth surfaces such as cuspal inclines, reducing heavy contacts and removing premature contacts. If bruxism is deemed a contributing factor an occlusal splint can be an effective treatment for eliminating the irregular forces placed on the tooth.
Controversy
Abfraction has been a controversial subject since its creation in 1991. This is due to the clinical presentation of the tooth loss, which often presents in a manner similar to that of abrasion or erosion. The major reasoning behind the controversy is the similarity of abfraction to other non carious lesions and the prevalence of multiple theories to potentially explain the lesion. One of the most prevalent theories is called "the theory of non-carious cervical lesions" which suggests that tooth flexion, occurring due to occlusion factors, impacts on the vulnerable area near the cementoenamel junction. This theory is not widely accepted among the professional community as it suggests that the only factor is occlusion. Many researchers argue that this is inaccurate as they contend that the abfraction lesion is a multifactorial (has many causative factors) lesion with other factors such as abrasion or erosion. This controversy around the causative factors, along with the recency of the lesion classification, are some of the reasons why many dental clinicians are looking at the lesion with some scepticism. More research is needed to fully clear up the controversy surrounding the abfraction lesion.
See also
Tooth wear
Abrasion
Attrition
Bruxism
Erosion
References
Summit, James B., J. William Robbins, and Richard S. Schwartz. Fundamentals of Operative Dentistry: A Contemporary Approach. 2nd edition. Carol Stream, Illinois, Quintessence Publishing Co, Inc, 2001. ISBN 0-86715-382-2.
Lee, WC.; Eakle, WS. (1984). "Possible role of tensile stress in the etiology of cervical erosive lesions of teeth". Journal of Prosthetic Dentistry. 52 (3): 374–380. doi:10.1016/0022-3913(84)90448-7. PMID 6592336. |
Porencephaly | Porencephaly is an extremely rare cephalic disorder involving encephalomalacia. It is a neurological disorder of the central nervous system characterized by cysts or cavities within the cerebral hemisphere. Porencephaly was termed by Heschl in 1859 to describe a cavity in the human brain. Derived from Greek roots, the word porencephaly means holes in the brain. The cysts and cavities (cystic brain lesions) are more likely to be the result of destructive (encephaloclastic) cause, but can also be from abnormal development (malformative), direct damage, inflammation, or hemorrhage. The cysts and cavities cause a wide range of physiological, physical, and neurological symptoms. Depending on the patient, this disorder may cause only minor neurological problems, without any disruption of intelligence, while others may be severely disabled or die before the second decade of their lives. However, this disorder is far more common within infants, and porencephaly can occur both before or after birth.
Signs and symptoms
Patients diagnosed with porencephaly display a variety of symptoms, from mild to severe effects on the patient. Patients with severe cases of porencephaly have epileptic seizures and developmental delays, whereas patients with a mild case of porencephaly display little to no seizures and typical neurodevelopment. Infants with extensive defects show symptoms of the disorder shortly after birth, and the diagnosis is usually made before the age of 1.The following text lists out common signs and symptoms of porencephaly in affected individuals along with a short description of certain terminologies.
Cause
Porencephaly is a rare disorder. The exact prevalence of porencephaly is not known; however, it has been reported that 6.8% of patients with cerebral palsy or 68% of patients with epilepsy and congenital vascular hemiparesis have porencephaly. Porencephaly has a number of different, often unknown, causes including absence of brain development and destruction of brain tissue. With limited research, the most commonly regarded cause of porencephaly is disturbances in blood circulation, ultimately leading to brain damage. However, a number of different and multiple factors such as abnormal brain development or damage to the brain tissue can also affect the development of porencephaly.The following text lists out potential risk factors of developing porencephaly and porencephalic cysts and cavities along with brief description of certain terminologies.
Cysts or cavities can occur anywhere within the brain and the locations of these cysts depend highly on the patient. Cysts can develop in the frontal lobe, parietal lobe, forebrain, hindbrain, temporal lobe, or virtually anywhere in the cerebral hemisphere.
Genetics
From recent studies, de novo and inherited mutations in the gene COL4A1, suggesting genetic predisposition within the family, that encodes type IV collagen α1 chain has shown to be associated with and present in patients with porencephaly. COL4A1 mutation causes a variety of phenotypes, including porencephaly, infantile hemiplegia, and cerebral small vessel diseases involving both stroke and infarction. Abnormal gene expression of COL4A1 can contribute to the development of porencephaly. COL4A1 gene expresses a type IV collagen (basement protein) that is present in all tissue and blood vessels and is extremely important for the structural stability of vascular basement membranes. The COL4A1 protein provides a strong layer around blood vessels. The mutation can weaken the blood vessels within the brain, elevating the probability of a hemorrhage, and eventually promoting internal bleeding then leading to porencephaly during neurodevelopment of infantile stage. Therefore, the formation of cavities can be a result of hemorrhages which promote cerebral degeneration. In a mouse model, mouse with COL4A1 mutations displayed cerebral hemorrhage, porencephaly, and abnormal development of vascular basement membranes, such as uneven edges, inconsistent shapes, and highly variable thickness. Purposely causing a mutation in the COL4A1 gene caused several mouse to develop cerebral hemorrhage and porencephaly-like diseases. Though, there is no direct correlation between mutations of the COL4A1 gene, it appears that it has an influential effect on the development of porencephaly.Another genetic mutation, factor V G1691A mutation, has been reported to show possible association to the development of porencephaly. A mutation in factor V G1691A increases the risk of thrombosis, blood clots, in neonates, infants, and children. Therefore, 76 porencephalic and 76 healthy infants were investigated for factor V G1691A mutation along with other different prothrombotic risk factors. The results indicated that there was higher prevalence of the factor V G1691A mutation in the porencephalic patient group. The prediction that childhood porencephaly is caused by hypercoagulable state, a condition where one has a higher chance of developing blood clots, was supported by the significance of the factor V G1691A mutation. Also, pregnant women in hypercoagulable state can cause the fetus to have the same risks, therefore possibly causing fetal loss, brain damage, lesions, and infections that lead to porencephaly. However, other different prothrombotic risk factors individually did not reach statistical significance to link it to the development of porencephaly, but a combination of multiple prothrombotic risk factors in the porencephaly group was significant. Overall, factor V G1691A mutation has been linked to the development of porencephaly. However, this one mutation is not the cause of porencephaly, and whether further prothrombiotic risk factors are associated with porencephaly still remains unknown.
Cocaine and other street drugs
In utero exposure to cocaine and other street drugs can lead to porencephaly.
Diagnostics
The presence of porencephalic cysts or cavities can be detected using trans-illumination of the skull of infant patients. Porencephaly is usually diagnosed clinically using the patients and families history, clinical observations, or based on the presence of certain characteristic neurological and physiological features of porencephaly. Advanced medical imaging with computed tomography (CT), magnetic resonance imaging (MRI), or with ultrasonography can be used as a method to exclude other possible neurological disorders. The diagnosis can be made antenatally with ultrasound. Other assessments include memory, speech, or intellect testing to help further determine the exact diagnose of the disorder.
Treatments
Currently, there is no cure for porencephaly because of the limited resources and knowledge about the neurological disorder. However, several treatment options are available. Treatment may include physical therapy, rehabilitation, medication for seizures or epilepsy, shunt (medical), or neurosurgery (removal of the cyst). According to the location, extent of the lesion, size of cavities, and severity of the disorder, combinations of treatment methods are imposed. In porencephaly patients, patients achieved good seizure control with appropriate drug therapy including valproate, carbamazepine, and clobazam. Also, anti-epileptic drugs served as another positive method of treatment.
Prognosis
The severity of the symptoms associated with porencephaly varies significantly across the population of those affected, depending on the location of the cyst and damage of the brain. For some patients with porencephaly, only minor neurological problems may develop, and those patients can live normal lives. Therefore, based on the level of severity, self-care is possible, but for the more serious cases lifelong care will be necessary. For those that have severe disability, early diagnosis, medication, participation in rehabilitation related to fine-motor control skills, and communication therapies can significantly improve the symptoms and ability of the patient with porencephaly to live a normal life. Infants with porencephaly that survive, with proper treatment, can display proper communication skills, movement, and live a normal life.
Research
Under the United States federal government, the National Institute of Neurological Disorders and Stroke and National Institute of Health are involved in conducting and supporting research related to normal and abnormal brain and nervous system development. Information gained from the research is used to develop understanding of the mechanism of porencephaly and used to offer new methods of treatment and prevention for developmental brain disorders such as porencephaly.
See also
Schizencephaly
References
External links
Porencephaly Information page, National Institute of Neurological Disorders and Stroke |
Corneal ulcers in animals | A corneal ulcer, or ulcerative keratitis, is an inflammatory condition of the cornea involving loss of its outer layer. It is very common in dogs and is sometimes seen in cats. In veterinary medicine, the term corneal ulcer is a generic name for any condition involving the loss of the outer layer of the cornea, and as such is used to describe conditions with both inflammatory and traumatic causes.
Corneal anatomy of the dog and cat
The cornea is a transparent structure that is part of the outer layer of the eye. It refracts light and protects the contents of the eye. The cornea is about one-half to one millimeter thick in the dog and cat. The trigeminal nerve supplies the cornea via the long ciliary nerves. There are pain receptors in the outer layers and pressure receptors deeper.
Transparency is achieved through a lack of blood vessels, pigmentation, and keratin, and through the organization of the collagen fibers. The collagen fibers cross the full diameter of the cornea in a strictly parallel fashion and allow 99 percent of the light to pass through without scattering.
There are four important layers in the dog and cat cornea. The outer layer is the epithelium, which is 25 to 40 micrometers and five to seven cell layers thick. The epithelium holds the tear film in place and also prevents water from invading the cornea and disrupting the collagen fibers. This prevents corneal edema, which gives it a cloudy appearance. It is also a barrier to infectious agents. The epithelium sticks to the basement membrane, which also separates the epithelium from the stroma. The corneal stroma comprises 90 percent of the thickness of the cornea. It contains the collagen fibers organized into lamellae. The lamellae are in sheets which separate easily. Posterior to the stroma is Descemets membrane, which is a basement membrane for the corneal endothelium. The endothelium is a single cell layer that separates the cornea from the aqueous humor.
Corneal healing
A healing of a corneal ulcer involves two processes: migration of surrounding epithelial cells followed by mitosis (dividing) of the cells, and introduction of blood vessels from the conjunctiva. Superficial small ulcers heal rapidly by the first process. However, larger or deeper ulcers often require the presence of blood vessels to supply inflammatory cells. White blood cells and fibroblasts produce granulation tissue and then scar tissue, effectively healing the cornea.
Superficial and deep corneal ulcers
Corneal ulcers are one of the most common eye diseases in dogs. They are caused by trauma, detergent burns, and infections. Other eye conditions can cause corneal ulcers, such as entropion, distichiae, corneal dystrophy, and keratoconjunctivitis sicca (dry eye). There have been at least two cases where corneal ulceration was caused by canine herpesvirus.Superficial ulcers involve a loss of part of the epithelium. Deep ulcers extend into or through the stroma and can result in severe scarring and corneal perforation. Descemetoceles occur when the ulcer extends through the stroma, exposing Descemets membrane. This type of ulcer is especially dangerous and can result in perforation.
The location of the ulcer depends somewhat on the cause. Central ulcers are typically caused by trauma, dry eye, or exposure from facial nerve paralysis or exophthalmos. Ulcers in the inferior nasal cornea may be caused by foreign material trapped under the third eyelid. Entropion or distichiae may cause ulceration of the peripheral cornea. Immune-mediated eye disease can cause ulcers at the border of the cornea and sclera.
Symptoms
Corneal ulcers are painful due to nerve exposure, and can cause tearing, squinting, and pawing at the eye. There may also be signs of anterior uveitis, such as miosis (small pupil), aqueous flare (protein in the aqueous humour), and redness of the eye. An axon reflex may be responsible for uveitis formation — stimulation of pain receptors in the cornea results in release inflammatory mediators such as prostaglandins, histamine, and acetylcholine.
Diagnosis
Diagnosis is through direct observation of the ulcer with the use of fluorescein stain, which is taken up by exposed corneal stroma and appears green (see photos above and below). With descemetoceles, Descemets membrane will bulge forward and after staining will appear as a dark circle with a green boundary, because it does not absorb the stain. Other tests that may be necessary include a Schirmers test for keratoconjunctivitis sicca and an analysis of facial nerve function for facial nerve paralysis.
Treatment
Treatment of corneal ulcers includes topical antibiotic therapy to prevent infection, and pain medications, including topical atropine to stop spasms of the ciliary muscle. Atropine may decrease tear production and interfere with corneal healing. Superficial ulcers usually heal in less than a week. Deep ulcers and descemetoceles may require corneal suturing, conjunctival grafts or conjunctival flaps, soft contact lenses, or corneal transplant. Topical corticosteroids and anesthetics should not be used on any type of corneal ulcer because they prevent healing and will often make them worse.
Bioscaffold
A new bioscaffold developed by TR BioSurgical is being evaluated for refractory corneal ulcers in dogs. The study is being conducted by board certified veterinary ophthalmologists and has shown promise in healing refractory ulcers that have failed conventional treatment .
Refractory corneal ulcers
Refractory corneal ulcers are superficial ulcers that heal poorly and tend to recur. They are also known as indolent ulcers or Boxer ulcers. They are believed to be caused by a defect in the basement membrane and a lack of hemidesmosomal attachments. They are recognized by undermined epithelium that surrounds the ulcer and easily peels back. Refractory corneal ulcers are most commonly seen in middle aged or older dogs and often occur in the other eye later. They are similar to Cogans cystic dystrophy in humans.
Commonly affected breeds
Alaskan Malamute
American Cocker Spaniel
Boston Terrier
Boxer
Brussels Griffon
Cairn Terrier
Chesapeake Bay Retriever
Chihuahua
Chinese Shar Pei
Dachshund
Bulldog
English Springer Spaniel
German Shepherd Dog
Golden Retriever
Irish Setter
Japanese Chin
Lhasa Apso
Maltese
Pekingese
Poodle
Pug
Rottweiler
Samoyed
Shih Tzu
Silky Terrier
Weimaraner
Welsh Corgi
Welsh Springer Spaniel
West Highland White Terrier
Wirehaired Fox Terrier
Treatment
Refractory corneal ulcers can take a long time to heal, sometimes months. Topical antibiotics are used continually to prevent infection. Pain medications are given as needed. Loose epithelium is removed with a dry cotton swab under topical anesthesia. This is in order to allow production of normal basement membrane and division of normal epithelium. Often further treatment is necessary, such as a keratotomy, which is superficial cutting or piercing of the cornea. There are two main types used in dogs: multiple punctate keratotomy (MPK) and grid keratotomy (GK). MPK involves making small superficial punctures into the cornea with a needle. GK is more commonly used and involves making parallel and perpendicular scratches in the corneal surface. Usually only topical anesthesia is necessary. By scoring the corneal surface, anchoring points are provided for attachment of new epithelium. Of course, these procedures should only be performed by a veterinarian, particularly one with some experience in this treatment. Complete healing takes about three to four weeks. Keratotomies may lead to corneal sequestration in cats. Other medications have been shown to be useful in topical treatment of refractory ulcers, including glycosaminoglycans such as sodium hyaluronate and chondroitin sulfate, aminocaproic acid, and acetylcysteine.
Melting ulcers
Melting ulcers are a type of corneal ulcer involving progressive loss of stroma in a dissolving fashion. This is most commonly seen in Pseudomonas infection, but it can be caused by other types of bacteria or fungi. These infectious agents produce proteases and collagenases which break down the corneal stroma. Complete loss of the stroma can occur within 24 hours. Treatment includes antibiotics and collagenase inhibitors such as acetylcysteine and homologous blood serum. Surgery may be necessary.
Corneal ulcers in cats
Corneal ulcers in cats can be caused by trauma, detergent burns, infections, and other eye diseases. One common cause not seen in dogs is infection with feline herpesvirus 1 (FHV-1). FHV-1 causes ulceration by direct infection of the epithelial cells. Lesions appear as round or dendritic (branching) ulcers. FHV-1 also suppresses healing of the cornea. Symptoms include conjunctivitis, squinting, eye discharge, and blood vessels on the cornea. It can cause severe scarring. Treatment is with topical antiviral drugs and antibiotics, and oral L-lysine, which competes with arginine and inhibits viral replication.
Corneal ulcers in horses
Corneal ulceration is a very common disease of the equine eye and can have sight-threatening consequences. Aggressive treatment is always indicated, as even apparently mild ulcers can progress quickly, causing serious complications.
Causes
A distinct cause for initial ulceration is not commonly found, although in many cases it can be assumed to be traumatic in origin. The horses eye is especially vulnerable to trauma due to its prominent position, compared with other species. Exposure keratitis (inflamed cornea) can occur in the horse, most commonly secondary to facial nerve paralysis. Hospitalised animals have been shown to have a decreased corneal reflex, and this corresponds to an increased incidence of ulcers in the hospitalised population. Foreign bodies embedded in the palpebral conjunctiva or the nictitating membrane can cause persistent irritation and ulceration. Often the shape and distribution of the lesion is suggestive of this aetiology, but even in the absence of a characteristic lesion their presence should be considered and sought out.
Bacterial and fungal infection occurs readily after the initial ulceration, as disruption of the corneal epithelium allows attachment and colonisation of the underlying tissues by normal corneal commensals. Commonly isolated bacteria include Staphylococcus, Streptococcus and Pseudomonas, and empirical anti-microbial therapy should be effective against these bacteria.
Symptoms
Ocular Pain
Blepharospasm
Increased lacrimation
Photophobia
Corneal Oedema (1⁰/2⁰)
Scleral injection
Conjunctivitis
Diagnosis
Differential diagnoses for the painful equine eye:
Ulceration
Uveitis
Blepharitis
Conjunctivitis
Glaucoma
DachrocystitisA full ocular exam should be performed for every case of eye pain. Fluoroscein staining is usually diagnostic for corneal ulcers, although staining with Rose Bengal is also recommended as it can pick up early viral/fungal lesions, which will appear as multifocal disturbances to the tear film.
Culture and sensitivity is recommended for rapidly progressive or deep corneal ulcers. Cotton swabbing is often inadequate, and corneal scraping, for example, with the blunt side of a scalpel blade is usually required. This can be greatly facilitated by the use of local nerve blocks and topical anaesthesia.
There is almost invariably a secondary uveitis present with corneal ulceration, and signs of this may also be seen: miosis, corneal oedema, aqueous flare, hypopyon, IOP changes.
Treatment
Medical therapy should be based upon the severity of disease initially, and then by the response to therapy. The aims of the initial therapy are:
Antibiosis
Analgesia
Anti-inflammatory
MydriaticThe initial choice of antibiotic depends upon personal choice, experience and availability, but could include chloramphenicol, chlortetracycline, bacitracin-neomycin-polymyxin (BNP), ciprofloxacin, ofloxacin and tobramycin. Topical gentamicin formulations are also available, but in the opinion of some, should be reserved for cases with stromal melting. Frequency of application can vary from q1h to q8h, depending on both the severity of the lesion, and the formulation used (ointment vs. drops).
Much of the pain associated with corneal ulceration is due to the secondary uveitis and miosis, and effective relief can often be gained with topical atropine(1%), leading to mydriasis. Dosing is generally q4h initially, and then as required to maintain dilation. Mydriasis is also important to avoid some of the complications associated with uveitis, such as synechiae formation and glaucoma. Pain is also associated with inflammatory response occurring in the adjacent sclera and conjunctiva, and systemic analgesia in the form of NSAIDs is usually indicated, for example, flunixin meglumin 1.1 mg/kg, BID. Topical NSAIDs are available (diclofenac, flurbiprofen) and effective, but have been shown to increase corneal healing time.
In horses that are difficult to treat, or in cases that require very frequent treatment, then placement of a sub-palpebral lavage system can be very useful. As an adjunct to therapy, physical protection of the eye may be required, in the form of a mask. Some horses will rub their eyes in response to pain, and this can cause further corneal damage. Box rest is also vital, as over-exertion has been linked to intra-ocular haemorrhage and increased severity of uveitis.
Success in your therapeutic regime can be judged by a reduction in pain, and a decrease in size of the ulcer. Healing generally occurs rapidly at first, followed by a slowing after 5–7 days. As a rough guide, a non-infected ulcer can be expected to heal at approximately 0.6mm/day.
Complications
In cases where the ulcer is not healing:
Is there a persistent source of irritation?
Foreign body
Self traumatisation
Iatrogenic.
Is it infected?
Review antibiotic therapy
C+S if not already performed.
Immunosuppression?
Cushings
Steroid therapy.
Compliance?
Is what youve prescribed getting onto the eye?
None of the above?
Abnormal epithelium may have formed, keratectomy may be appropriate.Melting ulcers reflect inappropriate collagenolysis of the corneal stroma, by matrix-metalloproteinases (MMPs). Bacterial pathogens (especially Pseudomonas and β-haemolytic Streptococcus) induce the corneal epithelial cells and resident leucocytes to upregulate pro-inflammatory, and MMP-activating cytokines (IL-1,-6 and -8). These bacteria can also produce their own proteinases. The combination of exogenous, and upregulated endogenous, proteinases leads to a rapid breakdown of collagen, with the characteristic melting appearance. Untreated this can lead to perforation within 12 hours (so act hard and fast!). There are several therapeutic options for inhibiting MMPs:
Autogenous serum – administer topically as often as possible. Keep refrigerated and change every 8 days.
EDTA - 0.05% q1h
Acetylcysteine – 5-10% q1h
Tetracyclines – Doxycycline especially has been shown to have anti-MMP effects
Tetanus antitoxin – can be delivered sub-conjunctivally. Contains macroglobulins with anti-collagenase effects.A combination of the above may be necessary early in the disease course. Effective antibiosis is also paramount, and gentamicin is a good empirical choice (although there are some reports of gentamicin-resistant Pseudomonas species). Obviously, treating an eye this frequently in practice will be difficult, so referral is probably the best option.
See also
Corneal abrasion
Keratitis
== References == |
Malignant multiple sclerosis | Malignant multiple sclerosis is used to describe MS patients who reach significant level of disability in a short period of time. Malignant MS cases are not common, less than 5% of patients with MS experience this type of progression.The National MS Society Advisory Committee on Clinical Trials of New Agents consensus defined it as: disease with a rapid progressive course, leading to significant disability in multiple neurologic systems or death in a relatively short time after disease onset. Reaching Expanded Disability Status Scale of 6.0 or higher, which is equivalent of needing unilateral support to ambulate (or worse) is generally considered this significant disability level.Patients with severe forms of more common relapsing remitting or progressive MS subtypes, as well as rare Marburg variant and Balo concentric sclerosis, could be considered to have malignant MS. Patients should be carefully worked up to rule out Neuromyelitis optica (Devics disease) due to the distinctive pathophysiology and management strategies of this disease.
Signs and symptoms
Some common physical symptoms may include: "weakness in extremities, difficulties with coordination and balance, spasticity, paresthesia, speech impediments, tremors, dizziness, hearing loss, vision impairments, bowel and bladder difficulties"
Diagnosis
Earlier signs include an increase in mobility over a short period of time. Malignant MS happens in patients that already have or have been diagnosed with MS. There is not a specific test to detect malignant MS; it is often confused with acute disseminated encephalomyelitis.
Malignant MS is diagnosed after clinical investigations. Doctors may access the symptoms and to rule out other disorders, a neurological exam is performed. Further diagnostics may include an analysis of the cerebrospinal fluid.Neurological testing may also be performed, such as "a magnetic resonance imaging (MRI), diffusion-tensor magnetic resonance imaging (DT-MRI), and computerized brain tomography are used to detect central nervous system lesions, myelin loss, white matter abnormalities, and other physical changes in the brain."
Treatment
Currently, there is no cure for malignant MS; however, "immunomodulatory therapy and other physical occupational therapies can help the management of symptoms and help them more easily perform everyday tasks such as handwriting, buttoning, and using eating utensils."Some mobility aids, such as canes, walkers, and wheelchairs may also be helpful as well for patients struggling with balance and walking.
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.
Autologous stem cell transplantation
Anecdotal evidence shows that autologous stem-cell transplantation, intensive immunosuppression combined with autologous stem cell therapy, may be an effective means for treating this life-threatening condition. The process of this therapy entails plasmapheresis or immunosuppression with mitoxantrone, cyclophosphamide, cladribine or bone marrow transplantation. In one study on a 17-year-old patient, researchers tried treating the patient with high-dose chemotherapy plus anti-thymocyte globulin followed by autologous stem cell transplantation. The findings of this study were positive. After being treated with a methylprednisolone (mPDN) i.v, the patient improved significantly. When the patient began to relapse/remit, they were treated again, resulting in improvement. After this, the patient remained stable for roughly 7 months before suffering their third relapse/remit.This therapy may be a therapy option for patients with malignant MS.
See also
Tumefactive multiple sclerosis
Marburg acute multiple sclerosis
Multiple sclerosis
Autologous stem cell transplantation
== References == |
Transient neonatal diabetes | Transient neonatal diabetes mellitus (TNDM) is a form of neonatal diabetes presenting at birth that is not permanent. This disease is considered to be a type of maturity onset diabetes of the young (MODY).
Types
Cause
This condition has to do with genetics and is often associated with having an added Chromosome 7 gene (mostly from the paternal side).The form on chromosome 6 can involve imprinting.
Diagnosis
Management
See also
Permanent neonatal diabetes mellitus
References
Further reading
GeneReview/NIH/UW entry on 6q24-Related Transient Neonatal Diabetes Mellitus
== External links == |
Dysglycemia | Dysglycemia is a general definition for any abnormalities in blood glucose levels. They include hyperglycemia, hypoglycemia, impaired glucose tolerance test, impaired fasting glucose, among others.
Hyperglycemia
If blood sugar levels remain too high the body suppresses appetite over the short term. Long-term hyperglycemia causes many health problems including heart disease, cancer, eye, kidney, and nerve damage.Blood sugar levels above 300 mg/dL can cause fatal reactions. Ketones will be very high (a magnitude higher than when eating a very low carbohydrate diet) initiating ketoacidosis. The Mayo Clinic recommends emergency room treatment above 300 mg/dL blood glucose.
The most common cause of hyperglycemia is diabetes. When diabetes is the cause, physicians typically recommend an anti-diabetic medication as treatment. From the perspective of the majority of patients, treatment with an old, well-understood diabetes drug such as metformin will be the safest, most effective, least expensive, most comfortable route to managing the condition. Diet changes and exercise implementation may also be part of a treatment plan for diabetes.
Hypoglycemia
Hypoglycemia is a fall in blood sugar to levels below normal. This may result in a variety of symptoms including clumsiness, trouble talking, confusion, loss of consciousness, seizures or death. A feeling of hunger, sweating, shakiness and weakness may also be present. Symptoms typically come on quickly.The most common cause of hypoglycemia is medications used to treat diabetes mellitus such as insulin and sulfonylureas. Risk is greater in diabetics who have eaten less than usual, exercised more than usual or have drunk alcohol. Other causes of hypoglycemia include kidney failure, certain tumors (such as insulinoma), liver disease, hypothyroidism, starvation, inborn error of metabolism, severe infections, reactive hypoglycemia and a number of drugs including alcohol. Low blood sugar may occur in otherwise healthy babies who have not eaten for a few hours.
== References == |
Genital trauma | Genital trauma is trauma to the genitalia.
History of studying genital trauma
Doctors and nurses have been conducting sexual assault examinations and have been collecting evidence for victims of assault for 20 years. But the amount of scientific data collected on genital injuries post-sexual assault are still minimal. Therefore, there is no available evidence to show specific patterns of injury resulting from sexual assault. The motivation for investigating and collecting data on genital injuries has primarily been within the context of the legal system, such as proving or disproving sexual assault, rather than for medical purposes. The studies that have been done in the past 25 years in relation to sexual assault cases in the judicial system has laid the groundwork for interpreting sexual assault injuries. It is important for there to research on genital injuries more broadly relating to sexual activity (and not just sexual assault) to improve medical knowledge on the subject. Methods of studying and documenting genital injury has greatly improved through the use of tissue staining dyes and colposcopy. The first studies that used newer methods were retrospective chart reviews done in a hospital by a doctor or nurse. These studies used several different methods to identify and document injuries, such as direct visualization, colposcopy, and/or tissue staining dyes. Earlier studies only used direct visualization for their data.
Vaginal trauma from consensual and non-consensual intercourse
Vaginal trauma is possible during and after consensual and non-consensual intercourse so it is difficult to determine the circumstances in which the trauma occurs only based on a physical examination. It can be difficult to differentiate between injuries from consensual sex and injuries from sexual assault in adolescents. Women are three times more likely to have vaginal injuries and intercourse-related injuries from a forced assault than from a consensual sexual experience. Vaginal lacerations that happen during consensual or non consensual intercourse might need surgery, but victims of a forced assault will need additional services such as police intervention and trauma counseling. There is little research on minor injuries in adult, pre-menopausal women, adolescent girls, and post-menopausal women that do not require surgery or treatment.
Why does vaginal trauma occur?
There are factors that can predispose women to vaginal injury during consensual sex. These things include: first sexual experience, pregnancy, vigorous penetration, vaginal atrophy and spasm, previous operation or radiation therapy, disproportionate genitalia, penile ornamentation, and congenital anomalies. During vaginal intercourse in the missionary position with legs tilted all the way back, the penis reaches its deepest penetration and the extreme rotation of the uterus leads to hyper distention of the vaginal wall, which in some cases can cause it to rupture. This position is the most likely position for vaginal laceration. The vaginal wall on the right side is the most commonly torn sight in this position. Vaginal lengthening and lubrication usually occurs naturally in a consensual sexual situation. Vaginal tearing can occur in rape victims because those two things will not occur. This is consistent with the fact that more injuries result from sexual assault than from consensual intercourse. An inability to produce adequate vaginal lubrication and dilatation is thought to be an underlying cause of severe tears in the upper area of the vagina.
Types of vaginal trauma
Intercourse-related lacerations can range from superficial tears to more severe lacerations, tears rarely extend into the rectal lumen and the peritoneal cavity. Recto-vaginal injuries are usually a result of assault with a foreign object, rape, or accidental gynecologic injury. Injuries of this severity that resulted from consensual sex are very rare. Posterior and right vaginal fornix lacerations have been known to occur during consensual vaginal intercourse. The location of these lacerations is usually based on a womans reproductive anatomy. It is common for women to have a uterus that lies slightly to the right, this exposes the right fornix and makes it easier for some type of tearing or trauma to occur. Lacerations to the posterior peri-cervical vagina tend to occur in the missionary position, hips and legs hyperflexed. Other positions can also expose the posterior vaginal wall that usually protected by the cervix, this allows for posterior fornix tears. Tears in the upper area of the vagina are more often reported in consensual intercourse than forced intercourse. Complications from severe vaginal lacerations, such as from an assault, can include hemoperitoneum, pneumoperitoneum, and retroperitoneal hematoma with or without vaginal perforation. Tears along the long axis of the vagina or the posterior fourchette lacerations are more likely to occur from rape. Lacerations or tears of the hymen are common but are not indicative of consensual or non-consensual intercourse.
Treatment of vaginal trauma
Diagnosing and treating vaginal trauma can often be difficult and delayed due to the sensitive and personal nature of these types of injuries; this also may be enhanced if the patient is young in age. The repair of most genital injuries require suture and the bleeding from the area is usually minimal. The bleeding that results from extreme vaginal tears can be copious, leading to hemorrhagic shock, and the patient may need a blood transfusion. Treatment of these lacerations could warrant surgical repair.
Vulvar trauma
Vulvar trauma is more common in prepubertal children due to small labial fat pads and more physical activity. Adults are more protected. Though some injuries are serious, most are accidental minor blunt traumas. The most common type of injury is a straddle injury, which can be incurred through normal activities like bicycle riding. Due to the vascularity of the vulva, it may form a large hematoma when injured. The vulva can also be injured through sexual assault. Vulvar trauma can occur concurrently with vaginal trauma, especially if a sharp object is involved.
Vaginal trauma
Vaginal trauma can occur when something is inserted into the vagina, for example, a sharp object, causing penetrating trauma. Vaginal trauma can occur as a result as an initial painful sexual experience or sexual abuse. Vaginal trauma can occur in children as a result of a straddle injury. Most of these, though distressing, are not serious injuries. In some instances a severe injury occurs and requires immediate medical attention especially if the bleeding wont stop. Vaginal trauma occurs during an episiotomy.
Penile trauma
Penile trauma can take several forms. Abrasions can be caused by a zipper injury, and fractures can be caused by sexual activity. One type of penile trauma is penile amputation. Penile amputation is a rare injury and is considered an emergency urological condition. Some of the reasons this may occur are self-mutilation with psychiatric disturbances, sexual need, accidents, iatrogenic injuries, or revenge and marriage breakdown. Since this is a rare injury there is no standardized method to treat this. Micro-surgical repair seems to be the most effective method to achieve a return of sensation and erectile function.
Testicular trauma
Testicular trauma is an injury to one or both testicles. Types of injuries include blunt, penetrating and degloving. The testes are located within the scrotum, which hangs outside of the body, and do not have the protection of muscles and bones. This makes it easier for the testes to be struck, hit, kicked or crushed, which occurs most often during contact sports. Testicles can be protected by wearing athletic cups during sports. Trauma to the testes can cause severe pain, bruising, swelling, and/or in severe cases even infertility. In most cases, the testes—which are made of a spongy material—can absorb some impact without serious damage.
See also
Groin attack
Penile fracture
Testicular rupture
Genital mutilation
== References == |
Generalized vaccinia | Generalized vaccinia is a cutaneous condition that occurs 6–9 days after vaccination, characterized by a generalized eruption of skin lesions, and caused by the vaccinia virus.: 391
See also
Vaccinia
Skin lesion
== References == |
Sitosterolemia | Sitosterolemia is a rare autosomal recessively inherited lipid metabolic disorder. It is characterized by hyperabsorption and decreased biliary excretion of dietary sterols (including the plant phytosterol beta-sitosterol). Healthy persons absorb only about 5% of dietary plant sterols, but sitosterolemia patients absorb 15% to 60% of ingested sitosterol without excreting much into the bile. The phytosterol campesterol is more readily absorbed than sitosterol.Sitosterolemia patients develop hypercholesterolemia, tendon and tuberous xanthomas, premature development of atherosclerosis, and abnormal hematologic and liver function test results.
Signs and symptoms
Sitosterolemia may share several clinical characteristics with the well-characterized familial hypercholesterolemia (FH), such as the development of tendon xanthomas in the first 10 years of life and the development of premature atherosclerosis. However, in contrast to FH patients, sitosterolemia patients usually have normal to moderately elevated total sterol levels and very high levels of plant sterols (sitosterol, campesterol, stigmasterol, avenosterol) and 5α-saturated stanols in their plasma. Plasma sitosterol levels in sitosterolemia patients are 10–25 times higher than in normal individuals (8–60 mg/dl). Not all patients with sitosterolemia have tendon xanthomas, thus absence of this should not be used to exclude this diagnosis.
Xanthomas may appear at any age, even in childhood. These may be present as subcutaneous xanthomas on the buttocks in children or in usual locations (e.g., Achilles tendon, extensor tendons of the hand) in children and adults. Xanthelasma and corneal arcus are less common. Decreased range of motion with possible redness, swelling, and warmth of joints due to arthritis may be present. In addition, sitosterolemia patients may develop hemolytic episodes and splenomegaly.
Untreated, the condition causes a significant increase in morbidity and mortality. Coronary heart disease and its inherent health consequences are the primary causes of illness and premature death in untreated patients.
Pathogenesis
Mammalian cells cannot use plant sterols. Normally, plant sterols are poorly absorbed from the gastrointestinal tract; fewer than 5% of plant sterols are absorbed compared to approximately 40% of cholesterol absorbed. The liver preferentially excretes plant sterols over cholesterol. Dietary sterols have recently been shown to passively enter intestinal cells, and subsequently the vast majority are pumped back into the gut lumen by ATP-binding cassette transporter (ABC transporter) proteins.
Sitosterolemia is inherited as a rare autosomal recessive condition. It has been shown to result from mutations in either of two adjacent and oppositely oriented genes (ABCG5 and ABCG8) located in chromosome 2 in band 2p21 and encode for ABC transporter proteins named sterolin-1 and sterolin-2, respectively. Thus, the active pumping back into the intestine of passively absorbed plant sterols is disrupted, and hepatic secretion of the resultant accumulation of these sterols is decreased.
The ability of the liver to preferentially excrete plant sterols into the bile is apparently impaired. While bile acid synthesis remains the same as in healthy people, the total excretion of sterols in the bile is reportedly less than 50% in subjects with sitosterolemia compared to control subjects. The mechanism for decreased hepatic secretion is unknown.
Patients have markedly reduced whole-body cholesterol biosynthesis associated with suppressed hepatic, ileal, and mononuclear leukocyte hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate-controlling enzyme in the cholesterol biosynthetic pathway. Whether or not the down-regulation is due to accumulated sitosterol is still debatable, but most recent data indicate that secondary effects of unknown regulators other than sitosterol can lead to reduced HMG-CoA reductase activity in the disease. This is coupled with significantly increased low-density lipoprotein (LDL) receptor expression.
Diagnosis
Diagnosis is made by measuring serum plant sterol concentrations.
Treatment
The disorder is treated by strictly reducing the intake of foods rich in plant sterols (e.g., vegetable oils, olives and avocados). However, dietary therapy is often never fully sufficient to control this disease since plant sterols are constituents of all plant-based foods. Statins have been used, and while these lower cholesterol levels and may ameliorate atherosclerotic disease, plant sterol levels are insufficiently lowered by their use alone.
If dietary treatment alone is insufficient, bile acid-binding resins (e.g., cholestyramine, colestipol) could be considered. In October 2002, a new cholesterol absorption inhibitor, ezetimibe, received US Food and Drug Administration (FDA) approval for use in sitosterolemia. This drug is now the standard of care, as it blocks sterol entry and can be used in combination with bile-acid resins.
Finally, ileal bypass has been performed in select cases to decrease the levels of plant sterols in the body, though this therapy was undertaken prior to the advent of ezetimibe.
Epidemiology
Around 80 cases have been reported in the literature worldwide, hence this condition appears to be relatively rare. More than likely, sitosterolemia is significantly underdiagnosed and many patients are probably misdiagnosed with hyperlipidemia.
See also
ABCG5 and ABCG8 Genes
Cerebrotendinous xanthomatosis
Notes
References
Lee M, Lu K, Patel SB (2001). "Genetic basis of sitosterolemia". Current Opinion in Lipidology. 12 (2): 141–149. doi:10.1097/00041433-200104000-00007. PMC 1350992. PMID 11264985.
Steiner R D. Sitosterolemia .[online] Available from : http://www.emedicine.com/ped/topic2110.htm [Accessed :12 July 2006]
Bazerbachi F.; et al. (2017). "Cryptogenic Cirrhosis and Sitosterolemia: A Treatable Disease If Identified but Fatal If Missed". Annals of Hepatology. 16 (6): 970–978. doi:10.5604/01.3001.0010.5290. PMID 29055934.
== External links == |
Interstitial keratitis | Interstitial keratitis (IK) is corneal scarring due to chronic inflammation of the corneal stroma. Interstitial means space between cells i.e. corneal stroma which lies between the epithelium and the endothelium. Keratitis means corneal inflammation.
Signs and symptoms
Acutely, early symptoms include a painful, photophobic, red watery eye. This is due to active corneal inflammation resulting in vascular invasion and stromal necrosis which can be diffuse or localized. This causes the pinkish discoloration of what was a clear transparent normal corneal tissue (called Salmon patch of Hutchinson).Such vascularization is likely to result in blurring of vision secondary to corneal stromal scarring, the presence of ghost vessels, and thinning of the cornea, especially if it involves the visual axis.
Cause
By far the most common cause of IK is syphilitic disease. However, there are two possible causes of the corneal inflammatory response: an infection and/or an immunological response, such as a hypersensitivity type reaction, or (rarely) Cogan syndrome. Infectious causes include syphilis (commonest), followed by other bacterial infections (TB, Leprosy and Lyme disease) and parasitic infections (Acanthamoeba, Onchocerciasis or river blindness, Leishmaniasis, Trypanosoma cruzi or Chagas disease, Trypanosoma brucei or African sleeping sickness and microsporidia)
Pathophysiology
The corneal scarring is the end result of the initial invasion of blood vessels into the corneal stroma as part of the inflammatory response. Since normal corneal tissue should be avascular (no blood vessel) and therefore clear to allow light to pass, the presence of blood vessel and the infiltration of cells as part of the inflammatory process results in scarring or hazing of the cornea.
Diagnosis
A positive VDRL of Treponema pallidum immobilization test confirms diagnosis of luetic(syphilitic) interstitial keratitis
Treatment
The underlying cause must be treated as soon as possible to stop the disease process. Corticosteroid drop can be used to minimize the scarring on the cornea along with antibiotic cover. However, residual scarring cannot be avoided which can result in long term visual impairment and corneal transplantation is not suitable due to high rejection rate from the corneal vascularization.
History
Previous long-standing eye infection which possibly during childhood time recalled as being treated with antibiotic and/or hospitalized over long period of time.
== References == |
Nonverbal learning disorder | Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by core deficits in visual-spatial processing in the presence of intact verbal ability. Additional diagnostic criteria include Average to Superior verbal intelligence and deficits in visuoconstruction abilities, fine-motor coordination, mathematical reasoning, visuospatial memory and social skills. In clinical settings, some diagnoses of attention deficit hyperactivity disorder would be more appropriately classified as NVLD.
Signs and symptoms
Considered to be neurologically based, nonverbal learning disorder is characterized by:
impairments in visuospatial processing
discrepancy between Average to Superior verbal abilities and impaired nonverbal abilities such as:
visuoconstruction
fine motor coordination
mathematical reasoning
visuospatial memory
socioemotional skillsPeople with NVLD may have trouble understanding charts, reading maps, assembling jigsaw puzzles, and using an analog clock to tell time. "Clumsiness" is not unusual in people with NVLD, especially children, and it may take a child with NVLD longer than usual to learn how to tie shoelaces or to ride a bicycle.At the beginning of their school careers, children with symptoms of NVLD struggle with tasks that require eye–hand coordination, such as coloring and using scissors, but often excel at memorizing verbal content, spelling, and reading once the shapes of the letters are learned. A child with NVLDs Average or Superior verbal skills can be misattributed to attention deficit hyperactivity disorder, defiant behavior, inattention, or lack of effort. Early researchers in the syndrome of NVLD Johnson and Myklebust characterize how the children appear in a classroom: "An example is the child who fails to learn the meaning of the actions of others....We categorize this child as having a deficiency in social perception, meaning that he has an inability which precludes acquiring the significance of basic nonverbal aspects of daily living, though his verbal level of intelligence falls within or above the average."In the adolescent years, when schoolwork becomes more abstract and the executive demands for time management, organization, and social interactions increase, students with NVLD begin to struggle. They focus on separate details and struggle to summarize information or to integrate ideas into a coherent whole, and they struggle to apply knowledge to other situations, to infer implicit information, to make predictions, and to organize information logically.As adults, tasks such as driving a car or navigating to an unfamiliar location may be difficult. Difficulty with keeping track of responsibilities or managing social interactions may affect job performance.People with NVLD may also fit the diagnostic criteria of dyscalculia, dysgraphia, or dyspraxia.
Cause
Research suggests that there is an association with an imbalance of neural activity in the right hemisphere of the brain connected to the white matter.
Diagnosis
Nonverbal learning disability (NVLD) is characterized by core deficits in visualspatial processing in the presence of intact verbal ability. Additional diagnostic criteria include Average to Superior verbal intelligence and deficits in visuoconstruction abilities, fine-motor coordination, mathematical reasoning, visuospatial memory and social skills."While NVLD is not classified into any distinct diagnosis in DSM-5 (American Psychiatric Association, 2013) or ICD-10 (World Health Organization, 1992), it does have a robust research base." "The majority of researchers and clinicians agree that the profile of NLD clearly exists...but they disagree on the need for a specific clinical category and on the criteria for its identification." (One researcher notes, "just because we cannot reasonably place such children into our present classification scheme does not mean they do not exist.")
Assorted diagnoses have been discussed as sharing symptoms with NVLD. In some cases, especially the form of autism previously called Asperger syndrome, the overlap can be so significant as to render NVLD a pointless duplication in the mind of its detractors, with the only difference being that NVLD criteria do not mention the presence or absence of either repetitive behaviors or narrow subject-matter interests. (These are not required for a diagnosis of autism.) These overlapping conditions include, among others:
attention deficit hyperactivity disorder (ADHD)
autism spectrum disorders, especially high-functioning autism
developmental coordination disorder
social communication disorder
right hemisphere brain damage and developmental right hemisphere syndrome
social-emotional processing disorder
Gerstmann syndromeThere is diagnostic overlap between nonverbal learning disorder and autism spectrum disorder, and some clinicians and researchers consider them to be the same condition. In clinical settings, some diagnoses of attention deficit hyperactivity disorder would be more appropriately classified as NVLD.
History
While various nonverbal learning difficulties were recognized since early studies in child neurology, there is ongoing debate as to whether/or the extent to which existing conceptions of NVLD provide a valid diagnostic framework.As presented in 1967, "nonverbal disabilities" (p. 44) or "disorders of nonverbal learning" was a category encompassing non-linguistic learning problems. "Nonverbal learning disabilities" were further discussed by Myklebust in 1975 as representing a subtype of learning "disability" with a range of presentations involving "mainly visual cognitive processing," social imperception, a gap between higher verbal ability and lower nonverbal processing, as well as difficulty with handwriting. Later neuropsychologist Byron Rourke sought to develop consistent criteria with a theory and model of brain functioning that would establish NVLD as a distinct syndrome (1989).Questions remain about how best to frame the perceptual, cognitive and motor issues associated with NVLD.
See also
Alexithymia – difficulty with understanding emotions
Childrens Nonverbal Learning Disabilities Scale
Deficits in attention, motor control and perception
References
Further reading
Books
Thompson, Sue (1997). The Source for Nonverbal Learning Disorders. East Moline, IL: LinguiSystems. ISBN 978-0760601631.
Palombo, Joseph (2006). Nonverbal Learning Disabilities: A Clinical Perspective. New York: W.W. Norton. ISBN 9780393704785.
Broitman, Jessica; Davis, John M. (2013). Treating NVLD in Children Professional Collaborations for Positive Outcomes. New York: Springer. ISBN 978-1461461791.
By Authors with NVLD
Murphy, Michael Brian (2016). NLD from the Inside Out: Talking to Parents, Teachers, and Teens about Growing Up with Nonverbal Learning Disabilities (Third ed.). Jessica Kingsley Publishers.
Fast, Yvona (2004). Employment for Individuals with Asperger Syndrome or Non-Verbal Learning Disability: Stories and Strategies. with other writers. London & Philadelphia: Jessica Kingsley Publishers. ISBN 9781846420153. OCLC 61493670.
Flom, Peter (2016). Screwed up Somehow but Not Stupid, Life with a Learning Disability. Peter Flom Consulting. ISBN 9780692611692.
External links
NVLD Project |
Hand-foot-genital syndrome | Hand-foot-genital syndrome (HFGS) is characterized by limb malformations and urogenital defects. Mild bilateral shortening of the thumbs and great toes, caused primarily by shortening of the distal phalanx and/or the first metacarpal or metatarsal, is the most common limb malformation and results in impaired dexterity or apposition of the thumbs. Urogenital abnormalities include abnormalities of the ureters and urethra and various degrees of incomplete Müllerian fusion in females and hypospadias of variable severity with or without chordee in males. Vesicoureteral reflux, recurrent urinary tract infections, and chronic pyelonephritis are common; fertility is normal.
Cause
Hand-foot-genital syndrome is inherited in an autosomal dominant manner. The proportion of cases caused by de novo mutations is unknown because of the small number of individuals described. If a parent of the proband is affected, the risk to the siblings is 50%. When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low. Each child of an individual with HFGS has a 50% chance of inheriting the mutation. Prenatal testing may be available through laboratories offering custom prenatal testing for families in which the disease-causing mutation has been identified in an affected family member.
Diagnosis
Diagnosis is based on physical examination including radiographs of the hands and feet and imaging studies of the kidneys, bladder, and female reproductive tract. HOXA13 is the only gene known to be associated with HFGS. Approximately 60% of mutations are polyalanine expansions. Molecular genetic testing is clinically available.
Additional findings
Additional findings that may be present in HFGS according to the latest research are:
Limited metacarpophalangeal flexion of the thumb or limited ability to oppose the thumb and fifth finger
Hypoplastic thenar eminences
Medial deviation of the great toe (hallux varus), a useful diagnostic sign when present
Small great toenail
Fifth-finger clinodactyly, secondary to a shortened middle phalanx
Short feet
Altered dermatoglyphics of the hands; when present, primarily involving distal placement of the axial triradius, lack of thenar or hypothenar patterning, low arches on the thumbs, thin ulnar loops (deficiency of radial loops and whorls), and a greatly reduced ridge count on the fingersRadiographic findings
Hypoplasia of the distal phalanx and first metacarpal of the thumbs and great toes
Pointed distal phalanges of the thumb
Lack of normal tufting of the distal phalanges of the great toes
Fusions of the cuneiform bones to other tarsal bones or trapezium-scaphoid fusion of the carpals
Short calcaneus
Occasional bony fusions of the middle and distal phalanges of the second, third, fourth, or fifth toes
Delayed carpal or tarsal maturation
Metacarpophalangeal profile reflecting shortening of the first metacarpal, the first and second phalanges, and the second phalanx of the second and fifth digitsUrogenital Defects
Females may have the following:
Vesicoureteral reflux secondary to ureteric incompetence
Ectopic ureteral orifices
Trigonal hypoplasia
Hypospadiac urethra
Subsymphyseal epispadias
Patulous urethra
Urinary incontinence (related to structural anomalies and weakness of the bladder sphincter muscle)
Small hymenal opening
Various degrees of incomplete Müllerian fusion with or without two cervices or a longitudinal vaginal septumMales may have the following:
Retrograde ejaculation (related to structural anomalies and weakness of the bladder sphincter muscle)
Treatment
References
== External links == |
Cerebral amyloid angiopathy | Cerebral amyloid angiopathy (CAA) is a form of angiopathy in which amyloid beta peptide deposits in the walls of small to medium blood vessels of the central nervous system and meninges. The term congophilic is sometimes used because the presence of the abnormal aggregations of amyloid can be demonstrated by microscopic examination of brain tissue after staining with Congo red. The amyloid material is only found in the brain and as such the disease is not related to other forms of amyloidosis.
Signs and symptoms
CAA is associated with brain hemorrhages, particularly microhemorrhages. Since CAA can be caused by the same amyloid protein that is associated with Alzheimers dementia, brain bleeds are more common in people who have a diagnosis of Alzheimers disease. However, they can also occur in those who have no history of dementia. The bleeding within the brain is usually confined to a particular lobe and this is slightly different compared to brain bleeds which occur as a consequence of high blood pressure (hypertension) – a more common cause of a hemorrhagic stroke (or bleeding in the brain).
Causes
CAA has been identified as occurring either sporadically (generally in elderly populations) or in familial forms such as Flemish, Iowa, and Dutch types. In all cases, it is defined by the deposition of amyloid beta (Aβ) in the leptomeningal and cerebral vessel walls. CAA occurring in the Flemish type has been observed to be linked to large dense-core plaques observed in this pedigree.The reason for increased deposition of Aβ in sporadic CAA is still unclear with both increased production of the peptide and abnormal clearance having been proposed as potential causes. Under normal physiology Aβ is cleared from the brain by four pathways: (1) endocytosis by astrocytes and microglial cells, (2) enzymatic degradation by neprilysin or insulysin (3) cleared by way of the blood brain barrier or (4) drained along periarterial spaces. Abnormalities in each of these identified clearance pathways have been linked to CAA.In familial forms of CAA, the cause of Aβ build up is likely due to increased production rather than poor clearance. Mutations in the amyloid precursor protein (APP), Presenilin (PS) 1 and PS2 genes can result in increased rates of cleavage of the APP into Aβ. An immune mechanism has also been proposed. apolipoprotein E (APOE) ε2 and ε4 are associated with increased risk of getting cerebral amyloid antipathy. The use of antiplatelet and anticoagulant therapy increases the risk of getting intracerebral haemorrhage in CAA.
Types
Several familial variants exist. The condition is usually associated with amyloid beta. However, there are types involving other amyloid peptides:
the "Icelandic type" is associated with Cystatin C amyloid (ACys).
the "British type" and "Danish type" are associated with British amyloid (ABri) and Danish amyloid (ADan) respectively. Both peptides are linked to mutations in ITM2B.
Familial amyloidosis-Finnish type is associated with gelsolin amyloid (AGel).
Pathophysiology
The vascular amyloid pathology characteristic of CAA can be classified as either Type 1 or Type 2, the latter type being the more common. Type 1 CAA pathology entails detectable amyloid deposits within cortical capillaries as well as within the leptomeningeal and cortical arteries and arterioles. In type 2 CAA pathology, amyloid deposits are present in leptomeningeal and cortical arteries and arterioles, but not in capillaries. Deposits in veins or venules are possible in either type but are far less prevalent.
Diagnosis
CAA can only be definitively diagnosed by a post-mortem autopsy. Biopsies can play a role in diagnosing probable cases. When no tissue is available for biopsy, the Boston Criteria are used to determine probable CAA cases from MRI or CT scan data. The Boston Criteria require evidence of multiple lobar or cortical hemorrhages to label a patient as probably having CAA. Susceptibility weighted imaging has been proposed as a tool for identifying CAA-related microhemorrhages.
Imaging
Cerebral amyloid angiopathy can be presented with lobar intracerebral hemorrhage or microbleeds in the brain. The bleeding usually occurs on the surfaces of the brain in contrast with intracranial haemorrhage due to high blood pressure which occurs in deep locations of the brain such as basal ganglia and pons. In lobar intracerebral bleed, computed tomography (CT) scan would show hyperdense haemorrhage area and hypodense odema around the haemorrhagic site.MRI sequence of gradient echo and susceptibility weighted imaging (SWI) are useful in detecting microbleeds and deposition of iron on the brain cortex (cortical superficial siderosis). Other MRI indicators of CAA include white matter hyperintensities and cortical thinning.
Management
The aim in cerebral amyloid angiopathy is to treat the symptoms, as there is no current cure. Physical, occupational and/or speech therapy may be helpful in the management of this condition.
History
Gustav Oppenheim was the first to report vascular amyloid β deposits on the vasculature of the central nervous system in 1909. The first paper focusing solely on what would come to be known as CAA was published in 1938 by WZ Scholz. In 1979, H. Okazaki published a paper implicating CAA in certain cases of lobar intracerebral hemorrhage. The Boston Criteria for CAA originated in a 1995 paper from Harvard Medical School.
References
Further reading
Chao, Christine P.; Kotsenas, Amy L.; Broderick, Daniel F. (September 1, 2006). "Cerebral Amyloid Angiopathy: CT and MR Imaging Findings". RadioGraphics. 26 (5): 1517–1531. doi:10.1148/rg.265055090. ISSN 0271-5333. PMID 16973779.
== External links == |
Hepatic encephalopathy | Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stages it can result in a coma.Hepatic encephalopathy can occur in those with acute or chronic liver disease. Episodes can be triggered by infections, GI bleeding, constipation, electrolyte problems, or certain medications. The underlying mechanism is believed to involve the buildup of ammonia in the blood, a substance that is normally removed by the liver. The diagnosis is typically based on symptoms after ruling out other potential causes. It may be supported by blood ammonia levels, an electroencephalogram, or a CT scan of the brain.Hepatic encephalopathy is possibly reversible with treatment. This typically involves supportive care and addressing the triggers of the event. Lactulose is frequently used to decrease ammonia levels. Certain antibiotics (such as rifaximin) and probiotics are other potential options. A liver transplant may improve outcomes in those with severe disease.More than 40% of people with cirrhosis develop hepatic encephalopathy. More than half of those with cirrhosis and significant HE live less than a year. In those who are able to get a liver transplant, the risk of death is less than 30% over the subsequent five years. The condition has been described since at least 1860.
Signs and symptoms
The mildest form of hepatic encephalopathy is difficult to detect clinically, but may be demonstrated on neuropsychological testing. It is experienced as forgetfulness, mild confusion, and irritability. The first stage of hepatic encephalopathy is characterised by an inverted sleep-wake pattern (sleeping by day, being awake at night). The second stage is marked by lethargy and personality changes. The third stage is marked by worsened confusion. The fourth stage is marked by a progression to coma.More severe forms of hepatic encephalopathy lead to a worsening level of consciousness, from lethargy to somnolence and eventually coma. In the intermediate stages, a characteristic jerking movement of the limbs is observed (asterixis, "liver flap" due to its flapping character); this disappears as the somnolence worsens. There is disorientation and amnesia, and uninhibited behaviour may occur. In the third stage, neurological examination may reveal clonus and positive Babinski sign. Coma and seizures represent the most advanced stage; cerebral edema (swelling of the brain tissue) leads to death.Encephalopathy often occurs together with other symptoms and signs of liver failure. These may include jaundice (yellow discolouration of the skin and the whites of the eyes), ascites (fluid accumulation in the abdominal cavity), and peripheral oedema (swelling of the legs due to fluid build-up in the skin). The tendon reflexes may be exaggerated, and the plantar reflex may be abnormal, namely extending rather than flexing (Babinskis sign) in severe encephalopathy. A particular smell on an affected persons breath (foetor hepaticus) may be detected.
Causes
In a small proportion of cases, the encephalopathy is caused directly by liver failure; this is more likely in acute liver failure. More commonly, especially in chronic liver disease, hepatic encephalopathy is triggered by an additional cause, and identifying these triggers can be important to treat the episode effectively.
Hepatic encephalopathy may also occur after the creation of a transjugular intrahepatic portosystemic shunt (TIPS). This is used in the treatment of refractory ascites, bleeding from oesophageal varices and hepatorenal syndrome. TIPS-related encephalopathy occurs in about 30% of cases, with the risk being higher in those with previous episodes of encephalopathy, higher age, female sex, and liver disease due to causes other than alcohol.
Pathogenesis
There are various explanations why liver dysfunction or portosystemic shunting might lead to encephalopathy. In healthy subjects, nitrogen-containing compounds from the intestine, generated by gut bacteria from food, are transported by the portal vein to the liver, where 80–90% are metabolised through the urea cycle and/or excreted immediately. This process is impaired in all subtypes of hepatic encephalopathy, either because the hepatocytes (liver cells) are incapable of metabolising the waste products or because portal venous blood bypasses the liver through collateral circulation or a medically constructed shunt. Nitrogenous waste products accumulate in the systemic circulation (hence the older term "portosystemic encephalopathy"). The most important waste product is ammonia (NH3). This small molecule crosses the blood–brain barrier and is absorbed and metabolised by the astrocytes, a population of cells in the brain that constitutes 30% of the cerebral cortex. Astrocytes use ammonia when synthesising glutamine from glutamate. The increased levels of glutamine lead to an increase in osmotic pressure in the astrocytes, which become swollen. There is increased activity of the inhibitory γ-aminobutyric acid (GABA) system and the energy supply to other brain cells is decreased. This can be thought of as an example of brain edema of the "cytotoxic" type.Despite numerous studies demonstrating the central role of ammonia, ammonia levels do not always correlate with the severity of the encephalopathy; it is suspected that this means that more ammonia has already been absorbed into the brain in those with severe symptoms whose serum levels are relatively low. Other waste products implicated in hepatic encephalopathy include mercaptans (substances containing a thiol group), short-chain fatty acids, and phenol.Numerous other abnormalities have been described in hepatic encephalopathy, although their relative contribution to the disease state is uncertain. Loss of glutamate transporter gene expression (especially EAAT 2) has been attributed to acute liver failure. Benzodiazepine-like compounds have been detected at increased levels as well as abnormalities in the GABA neurotransmission system. An imbalance between aromatic amino acids (phenylalanine, tryptophan and tyrosine) and branched-chain amino acids (leucine, isoleucine and valine) has been described; this would lead to the generation of false neurotransmitters (such octopamine and 2-hydroxyphenethylamine). Dysregulation of the serotonin system, too, has been reported. Depletion of zinc and accumulation of manganese may play a role. Inflammation elsewhere in the body may precipitate encephalopathy through the action of cytokines and bacterial lipopolysaccharide on astrocytes.
Diagnosis
Investigations
The diagnosis of hepatic encephalopathy can only be made in the presence of confirmed liver disease (types A and C) or a portosystemic shunt (type B), as its symptoms are similar to those encountered in other encephalopathies. To make the distinction, abnormal liver function tests and/or ultrasound suggesting liver disease are required, and ideally a liver biopsy. The symptoms of hepatic encephalopathy may also arise from other conditions, such as bleeding in the brain and seizures (both of which are more common in chronic liver disease). A CT scan of the brain may be required to exclude bleeding in the brain, and if seizure activity is suspected an electroencephalograph (EEG) study may be performed. Rarer mimics of encephalopathy are meningitis, encephalitis, Wernickes encephalopathy and Wilsons disease; these may be suspected on clinical grounds and confirmed with investigations.The diagnosis of hepatic encephalopathy is a clinical one, once other causes for confusion or coma have been excluded; no test fully diagnoses or excludes it. Serum ammonia levels are elevated in 90% of people, but not all hyperammonaemia (high ammonia levels in the blood) is associated with encephalopathy. A CT scan of the brain usually shows no abnormality except in stage IV encephalopathy, when brain swelling (cerebral oedema) may be visible. Other neuroimaging modalities, such as magnetic resonance imaging (MRI), are not currently regarded as useful, although they may show abnormalities. Electroencephalography shows no clear abnormalities in stage 0, even if minimal HE is present; in stages I, II and III there are triphasic waves over the frontal lobes that oscillate at 5 Hz, and in stage IV there is slow delta wave activity. However, the changes in EEG are not typical enough to be useful in distinguishing hepatic encephalopathy from other conditions.Once the diagnosis of encephalopathy has been made, efforts are made to exclude underlying causes (such as listed above in "causes"). This requires blood tests (urea and electrolytes, full blood count, liver function tests), usually a chest X-ray, and urinalysis. If there is ascites, a diagnostic paracentesis (removal of a fluid sample with a needle) may be required to identify spontaneous bacterial peritonitis (SBP).
Classification
West Haven criteria
The severity of hepatic encephalopathy is graded with the West Haven Criteria; this is based on the level of impairment of autonomy, changes in consciousness, intellectual function, behavior, and dependence on therapy.
Grade 0 - No obvious changes other than a potentially mild decrease in intellectual ability and coordination
Grade 1 - Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition or subtraction
Grade 2 - Lethargy or apathy; minimal disorientation for time or place; subtle personality change; inappropriate behaviour
Grade 3 - Somnolence to semistupor, but responsive to verbal stimuli; confusion; gross disorientation
Grade 4 - Coma
Types
A classification of hepatic encephalopathy was introduced at the World Congress of Gastroenterology 1998 in Vienna. According to this classification, hepatic encephalopathy is subdivided in type A, B and C depending on the underlying cause.
Type A (=acute) describes hepatic encephalopathy associated with acute liver failure, typically associated with cerebral oedema
Type B (=bypass) is caused by portal-systemic shunting without associated intrinsic liver disease
Type C (=cirrhosis) occurs in people with cirrhosis - this type is subdivided in episodic, persistent and minimal encephalopathyThe term minimal encephalopathy (MHE) is defined as encephalopathy that does not lead to clinically overt cognitive dysfunction, but can be demonstrated with neuropsychological studies. This is still an important finding, as minimal encephalopathy has been demonstrated to impair quality of life and increase the risk of involvement in road traffic accidents.
Minimal HE
The diagnosis of minimal hepatic encephalopathy requires neuropsychological testing by definition. Older tests include the "numbers connecting test" A and B (measuring the speed at which one could connect randomly dispersed numbers 1–20), the "block design test" and the "digit-symbol test". In 2009 an expert panel concluded that neuropsychological test batteries aimed at measuring multiple domains of cognitive function are generally more reliable than single tests, and tend to be more strongly correlated with functional status. Both the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and PSE-Syndrom-Test may be used for this purpose. The PSE-Syndrom-Test, developed in Germany and validated in several other European countries, incorporates older assessment tools such as the number connection test.
Treatment
Those with severe encephalopathy (stages 3 and 4) are at risk of obstructing their airway due to decreased protective reflexes such as the gag reflex. This can lead to respiratory arrest. Transferring the person to a higher level of nursing care, such as an intensive care unit, is required, and intubation of the airway is often necessary to prevent life-threatening complications (e.g., aspiration or respiratory failure). Placement of a nasogastric tube permits the safe administration of nutrients and medication.The treatment of hepatic encephalopathy depends on the suspected underlying cause (types A, B, or C) and the presence or absence of underlying causes. If encephalopathy develops in acute liver failure (type A), even in a mild form (grade 1–2), it indicates that a liver transplant may be required, and transfer to a specialist centre is advised. Hepatic encephalopathy type B may arise in those who have undergone a TIPS procedure; in most cases this resolves spontaneously or with the medical treatments discussed below, but in a small proportion of about 5%, occlusion of the shunt is required to address the symptoms.In hepatic encephalopathy type C, the identification and treatment of alternative or underlying causes is central to the initial management. Given the frequency of infection as the underlying cause, antibiotics are often administered empirically (without knowledge of the exact source and nature of the infection). Once an episode of encephalopathy has been effectively treated, a decision may need to be made on whether to prepare for a liver transplant.
Diet
In the past, it was thought that consumption of protein even at normal levels increased the risk of hepatic encephalopathy. This has been shown to be incorrect. Furthermore, many people with chronic liver disease are malnourished and require adequate protein to maintain a stable body weight. A diet with adequate protein and energy is therefore recommended.Dietary supplementation with branched-chain amino acids has shown improvement of encephalopathy and other complications of cirrhosis.Some studies have shown benefit of administration of probiotics ("healthy bacteria").
Lactulose/lactitol
Lactulose and lactitol are disaccharides that are not absorbed from the digestive tract. They are thought to decrease the generation of ammonia by bacteria, render the ammonia inabsorbable by converting it to ammonium (NH4+) ions, and increase transit of bowel content through the gut. Doses of 15-30 mL are typically administered three times a day; the result is aimed to be 3–5 soft stools a day, or (in some settings) a stool pH of <6.0. Lactulose may also be given by enema, especially if encephalopathy is severe. More commonly, phosphate enemas are used. This may relieve constipation, one of the causes of encephalopathy, and increase bowel transit.Lactulose and lactitol are beneficial for treating hepatic encephalopathy, and are the recommended first-line treatment. Lactulose does not appear to be more effective than lactitol for treating people with hepatic encephalopathy. Side effects of lactulose and lactitol include the possibility of diarrhea, abdominal bloating, gassiness, and nausea. In acute liver failure, it is unclear whether lactulose is beneficial. The possible side effect of bloating may interfere with a liver transplant procedure if required.
Antibiotics
The antibiotic rifaximin may be recommended in addition to lactulose for those with recurrent disease. It is a nonabsorbable antibiotic from the rifamycin class. This is thought to work in a similar way to other antibiotics but without the complications attached to neomycin or metronidazole. Due to the long history and lower cost of lactulose use, rifaximin is generally only used as a second-line treatment if lactulose is poorly tolerated or not effective. When rifaximin is added to lactulose, the combination of the two may be more effective than each component separately. Rifaximin is more expensive than lactulose, but the cost may be offset by fewer hospital admissions for encephalopathy.The antibiotics neomycin and metronidazole are other antibiotics used to treat hepatic encephalopathy. The rationale of their use was the fact that ammonia and other waste products are generated and converted by intestinal bacteria, and killing these bacteria would reduce the generation of these waste products. Neomycin was chosen because of its low intestinal absorption, as neomycin and similar aminoglycoside antibiotics may cause hearing loss and kidney failure if used by injection. Later studies showed that neomycin was indeed absorbed when taken by mouth, with resultant complications. Metronidazole, similarly, is less commonly used because prolonged use can cause nerve damage, in addition to gastrointestinal side effects.
L-ornithine and L-aspartate
The combination of L-ornithine and L-aspartate (LOLA) lowers the level of ammonia in a persons blood. Very weak evidence from clinical trials indicates that LOLA treatment may benefit people with hepatic encephalopathy. LOLA lowers ammonia levels by increasing the generation of urea through the urea cycle, a metabolic pathway that removes ammonia by turning it into the neutral substance urea. LOLA may be combined with lactulose and/or rifaximin if these alone are ineffective at controlling symptoms.
Epidemiology and prognosis
In those with cirrhosis, the risk of developing hepatic encephalopathy is 20% per year, and at any time about 30–45% of people with cirrhosis exhibit evidence of overt encephalopathy. The prevalence of minimal hepatic encephalopathy detectable on formal neuropsychological testing is 60–80%; this increases the likelihood of developing overt encephalopathy in the future. Once hepatic encephalopathy has developed, the prognosis is determined largely by other markers of liver failure, such as the levels of albumin (a protein produced by the liver), the prothrombin time (a test of coagulation, which relies on proteins produced in the liver), the presence of ascites and the level of bilirubin (a breakdown product of hemoglobin which is conjugated and excreted by the liver). Together with the severity of encephalopathy, these markers have been incorporated into the Child–Pugh score; this score determines the one- and two-year survival and may assist in a decision to offer liver transplantation.In acute liver failure, the development of severe encephalopathy strongly predicts short-term mortality and is almost as important as the nature of the underlying cause of the liver failure in determining the prognosis. Historically, widely used criteria for offering liver transplantation, such as Kings College Criteria, are of limited use and recent guidelines discourage excessive reliance on these criteria. The occurrence of hepatic encephalopathy in people with Wilsons disease (hereditary copper accumulation) and mushroom poisoning indicates an urgent need for a liver transplant.
History
The occurrence of disturbed behaviour in people with jaundice may have been described in antiquity by Hippocrates of Cos (c. 460–370 BCE). Celsus and Galen (first and third century respectively) both recognised the condition. Many modern descriptions of the link between liver disease and neuropsychiatric symptoms were made in the eighteenth and nineteenth century; for instance, Giovanni Battista Morgagni (1682–1771) reported in 1761 that it was a progressive condition.In the 1950s, several reports enumerated the numerous abnormalities reported previously, and confirmed the previously enunciated theory that metabolic impairment and portosystemic shunting are the underlying mechanisms behind hepatic encephalopathy, and that the nitrogen-rich compounds originate from the intestine. Professor Dame Sheila Sherlock (1918–2001) performed many of these studies at the Royal Postgraduate Medical School in London and subsequently at the Royal Free Hospital. The same group investigated protein restriction and neomycin.The West Haven classification was formulated by Professor Harold Conn (1925–2011) and colleagues at Yale University while investigating the therapeutic efficacy of lactulose.
References
== External links == |
Arcuate uterus | The arcuate uterus is a form of a uterine anomaly or variation where the uterine cavity displays a concave contour towards the fundus. Normally the uterine cavity is straight or convex towards the fundus on anterior-posterior imaging, but in the arcuate uterus the myometrium of the fundus dips into the cavity and may form a small septation. The distinction between an arcuate uterus and a septate uterus is not standardized.
Signs and symptoms
The condition may not be known to the affected individual and not result in any reproductive problems; thus normal pregnancies occur. Indeed, there is no consensus on the relationship of the arcuate uterus and recurrent pregnancy loss. Accordingly, the condition may be a variation or a pathology.One view maintains that the condition is associated with a higher risk for miscarriage, premature birth, and malpresentation. Thus a study that evaluated women with uterine bleeding by hysteroscopy found that 6.5% of subjects displayed the arcuate uterus and had evidence of reproductive impairments. A study based on hysterosalpingraphic detected arcuate lesions documented increased fetal loss and obstetrical complications as a risk for affected women. Woelfer found that the miscarriage risk is more pronounced in the second trimester. In contrast, a study utilizing 3-D ultrasonography to document the prevalence of the arcuate uterus in a gynecological population found no evidence of increased risk of reproductive loss; in this study 3.1% of women had an arcuate uterus making it the most common uterine anomaly; this prevalence was similar than in women undergoing sterilization and lower than in women with recurrent pregnancy loss.
Cause
The uterus is formed during embryogenesis by the fusion of the two Müllerian ducts. During this fusion a resorption process eliminates the partition between the two ducts to create a single cavity. This process begins caudally and advances cranially, thus an arcuate uterus represents an in the final stage incomplete absorption process.
Diagnosis
A transvaginal ultrasound can reveal the condition.
Helpful techniques to investigate the uterine structure are transvaginal ultrasonography and sonohysterography, hysterosalpingography, MRI, and hysteroscopy. More recently 3-D ultrasonography has been advocated as an excellent non-invasive method to delineate the condition.
Differential diagnosis
The major differential diagnosis is the uterine septum. The lack of agreement to separate these two entities makes it difficult to assess the results in the literature.
Management
Many patients with an arcuate uterus will not experience any reproductive problems and do not require any surgery. In patients with recurrent pregnancy loss thought to be caused by an arcuate uterus hysteroscopic resection can be performed.
Epidemiology
Most studies of uterine malformations are based on populations of women who have experienced a miscarriage and thus do not address the issue of the prevalence in the general population. A screening study by Woelfer et al. of women without a history of reproductive problems found that about 5% of women had an arcuate uterus when they defined an arcuate uterus any fundal protrusion into the cavity that had an apical angle of more than 90 degrees. Accordingly, it was the most common uterine anomaly, followed by septate uterus (3%) and bicornuate uterus (0.5%).
References
== External links == |
Feingold syndrome | Feingold syndrome (also called oculodigitoesophagoduodenal syndrome) is a rare autosomal dominant hereditary disorder. It is named after Murray Feingold, an American physician who first described the syndrome in 1975. Until 2003, at least 79 patients have been reported worldwide.
Presentation
Feingold syndrome is marked by various combinations of microcephaly, limb malformations, esophageal and duodenal atresias. Cognition is affected, and ranges from below-average IQ to mild intellectual disability.
Genetics
Feingold syndrome is caused by mutations in the neuroblastoma-derived V-myc avian myelocytomatosis viral-related oncogene (MYCN) which is located on the short arm of chromosome 2 (2p24.1). This syndrome has also been linked to microdeletions in the MIR17HG locus which encodes a micro RNA cluster known as miR-17/92.
Diagnosis
The diagnosis is based on the following clinical findings:
microcephaly
clinodactyly and shortness of index and little fingers
syndactyly of 2nd & 3rd and 4th & 5th toe
short palpebral fissures
esophageal and/or duodenal atresia
Treatment
There is no known treatment for the disorder, but surgery for malformations, special education, and treatment of hearing loss are important.
References
External links
GeneReview/NIH/UW entry on Feingold syndrome |
Aromatic L-amino acid decarboxylase deficiency | Aromatic L-amino acid decarboxylase deficiency is a rare genetic disorder caused by mutations in the DDC gene, which encodes an enzyme called aromatic L-amino acid decarboxylase.
Signs and symptoms
Babies with severe aromatic L-amino acid decarboxylase deficiency usually present during the first few months of life. Symptoms can include:
Hypotonia (floppiness)
Developmental delay
Oculogyric crises
Difficulty with initiating and controlling movements
Dystonia and dyskinesia
Gastointestinal dysmotility which can present at as vomiting, gastro-oesophageal reflux, diarrhoea and/or constipation
Autonomic symptoms including difficulties controlling temperature and blood sugar, excessive sweating and nasal congestionSome people may develop cerebral folate deficiency, because O-methylation of the excessive amounts of L-Dopa can deplete methyl donors such as S-adenosyl methionine and levomefolic acid. This deviation can be detected by measuring the levels of levomefolic acid in the cerebrospinal fluid, and can be corrected by folinic acid.
Genetics
Aromatic L-amino acid decarboxylase deficiency is an autosomal recessive condition, meaning an individual needs to have two faulty copies of the DDC gene in order to be affected. Usually, one copy is inherited from each parent.
Pathophysiology
The aromatic L-amino acid decarboxylase deficiency enzyme is involved in the synthesis of dopamine and serotonin, both of which are important neurotransmitters.
Diagnosis
Once there is a clinical suspicion of the diagnosis, neurotransmitters can be analysed in cerebrospinal fluid from a lumbar puncture. If these show the pattern of abnormalities typical for aromatic L-amino acid decarboxylase deficiency, the diagnosis can be confirmed by genetic testing and/or measurement of enzyme activity.
Treatment
There is no cure for aromatic L-amino acid decarboxylase deficiency, but medical and multidisciplinary treatment can relieve some of the symptoms. Individuals will require physiotherapy, occupational therapy, and speech and language therapy. Some will need enteral feeding (for example, a gastrostomy or jejunostomy) due to difficulties with chewing and swallowing.Various medications can help compensate for the missing neurotransmitters. Dopamine agonists such as rotigotine or pramipexole and monoamine oxidase inhibitors such as selegiline are commonly used. Individuals may also need to take a range of other medications to control dyskinesia, constipation and other symptoms.In July 2021, results of a small gene therapy phase I study reported observation of dopamine restoration on seven participants between 4 and 9 years old.As of May 2022, the gene therapy product eladocagene exuparvovec is recommended for approval by the European Commission.
References
== External links == |
Cardiospondylocarpofacial syndrome | Cardiospondylocarpofacial syndrome is a very rare genetic disorder which is characterized by cardiac, digital, osseous anomalies with facial dysmorphisms
Signs and symptoms
The following is a list of the symptoms most commonly exhibited:
Variable vertebral anomalies
Brachydactyly
Conductive hearing loss
High palate
Mitral regurgitation
Mitral valve prolapse
Short stature, nearing dwarfism
Short palms
Carpal bone synostosisLess common symptoms include:
Failure for permanent teeth to erupt
Teeth misalignment
Horseshoe kidney
Dentition anomalies
Ocular anomalies
Nostril anteversion
Epiphysis in the shape of a cone
Congenital hearing loss
Decresed testes size (males)
Skeletal maturation delay
Feeding difficulties
Freckles
Apple cheeks
Gastroesophageal reflux
Hypertelorism
Joint hypermobility
Long philtrum
Rotated ears
Pseudoepiphyses
High frequency of middle ear infections
Rib synostosis
Scoliosis
Small foot
Strabismus
Tarsal synostosis
Telecanthus
Upslanted parpebral fissures
Broad nasal bridge
Vesicoureteral reflux
Causes
It is caused by autosomal dominant mutations of the MAP3K7 gene in the long arm of chromosome 6.
Epidemiology
Only 12 cases worldwide have been described in medical literature.
== References == |
Tropical ataxic neuropathy | Tropical ataxic neuropathy (TAN, also known as Strachan-Scott Syndrome and prisoners of war neuropathy) is a disease or category of diseases that commonly causes disability and increases mortality. The causes of TAN are not understood; there is no generally accepted treatment, and the reported outcomes are inconsistent. The disease affects poor tropical populations; there are no good statistics on how many people are affected worldwide, but in some populations, more than a quarter of people are affected. Malnutrition may play a role.
Classification and signs and symptoms
TAN is one of many tropical myeloneuropathies. It was first described in Jamaica in 1897, by postmortems of 510 cases; in 1959, it was dubbed "tropical ataxic neuropathy". The diagnostic criteria were defined in 1968. TAN is defined by "bilateral optic atrophy, bilateral sensory neural deafness, predominant posterior column involvement, and pyramidal tract myelopathy, with ataxic polyneuropathy". The classification of TAN is still not settled, and researchers disagree about it.There are thought to be two neurological syndromes lumped together as TAN. One affects adolescents, appears with retrobulbar optic neuropathy and evidence of malnutrition, and improves with better nutrition. Half of these adolescents are seen to have spinal ataxia.The other affects middle-aged and elderly people. They suffer sensory polyneuropathy, including weakness and paresthesic sensations. Paresthesias include sensations of numbness, heat, cold, tightness, crawling motion, tingling, pins and needles, and a feeling of walking on cotton or pebbles. Weaknesses show as gait ataxia (lack of co-ordination). Affected people also suffer optic atrophy and sensory neural deafness, on both sides of the body. There is neurological damage to the pyramidal tract of the spinal cord. For these older patients, evidence of malnutrition is rarer, and improving nutrition does not improve symptoms.Most of those with the older-onset form have symptoms in their legs, but a third to a half also have arm symptoms. Symptoms tend to worsen during the rainy season (see monsoon, harmattan), and are often worse at night. Symptoms associated with the lower cranial nerve are rarer; most patients do not show them. These symptoms include dysarthria (difficulty articulating words), dysphagia (difficulty swallowing), shortness of breath, and dysphonia (difficulty speaking); dysphonia is more common in women, and shows as hypophonia (lack of co-ordination in the vocal cords) and an inability to shout.
Treatment
Nutritional improvements; supplying nutritional yeast, teaching improved cassava preparation, and ceasing cassava consumption.
Outlook
Unclear, with contradictory reports from different studies.
Research directions
A 2016 review listed twenty-one open research questions. The value of international co-operation on TAN research has also been highlighted.
Epidemiology
TAN has only been described as developing in Africa, South-east Asia, and the Caribbean (if Guiana be included). It does not seem to occur in temperate countries. People affected by TAN tend to be poor and live in rural areas. In some areas, more than a quarter of the population are affected. In India and Africa, more women are affected; in Africa, the elderly are most likely to suffer, and in India, people in their thirties. Historical data suggests that, in the 1960s, TAN in Africa was most common in people in their 30s and 40s.While the areas affected roughly correspond to the areas in which cassava is grown, some people in non-cassava-growing populations get TAN, and some cassava-growing populations do not get TAN. It is possible that there are several diseases being categorized as TAN.It has been estimated that 5% of surviving World War II prisoners of war held in the Far East acquired TAN; while they were held for 3.5 years or less, the TAN symptoms persisted chronically after they returned to temperate climates.
Other animals
The behaviour and neurology of malnourished and cassava-fed rats has been compared to that of humans with TAN.
See also
Konzo, a diet-based tropical neuropathy
Lathyrism, a diet-based neuropathy
Tropical spastic paraparesis, and infectious tropical myeloneuropathy
Neglected tropical diseases
Beri-beri
== References == |
Crouzonodermoskeletal syndrome | Crouzonodermoskeletal syndrome is a disorder characterized by the premature joining of certain bones of the skull (craniosynostosis) during development and a skin condition called acanthosis nigricans.Some of the signs and symptoms of Crouzonodermoskeletal syndrome are similar to those seen with Crouzon syndrome. They include prematurely fused skull bones, which affect the shape of the head and face; wide-set, bulging eyes due to shallow eye sockets; eyes that do not point in the same direction (strabismus); a small, beaked nose; and an underdeveloped upper jaw. People with these conditions are generally of normal intelligence.Several features distinguish Crouzonodermoskeletal syndrome from Crouzon syndrome. People with Crouzonodermoskeletal syndrome have acanthosis nigricans, a skin condition characterized by thick, dark, velvety skin in body folds and creases, including the neck and underarms. In addition, subtle changes may be seen in the bones of the spine (vertebrae). Noncancerous growths called cementomas may develop in the jaw during young adulthood.Crouzonodermoskeletal syndrome is rare; the condition is seen in about 1 per million people.
Genetics
Mutations in the FGFR3 gene cause Crouzonodermoskeletal syndrome. The protein made by the FGFR3 gene is a receptor that plays a role in the development and maintenance of bone and brain tissue. Researchers do not know how a mutation in FGFR3 leads to the characteristic features of this disorder, but changes in the receptor appear to disrupt the normal development of bones in the skull and affect skin pigmentation.This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.
Diagnosis
Treatment
References
Cohen MM Jr (1999). "Lets call it "Crouzonodermoskeletal syndrome" so we wont be prisoners of our own conventional terminology". Am J Med Genet. 84 (1): 74. doi:10.1002/(SICI)1096-8628(19990507)84:1<74::AID-AJMG14>3.0.CO;2-R. PMID 10213050.
External links
Online Mendelian Inheritance in Man (OMIM): 123500 |
Autosomal dominant hypophosphatemic rickets | Autosomal dominant hypophosphatemic rickets (ADHR) is a rare hereditary disease in which excessive loss of phosphate in the urine leads to poorly formed bones (rickets), bone pain, and tooth abscesses. ADHR is caused by a mutation in the fibroblast growth factor 23 (FGF23). ADHR affects men and women equally; symptoms may become apparent at any point from childhood through early adulthood. Blood tests reveal low levels of phosphate (hypophosphatemia) and inappropriately normal levels of vitamin D. Occasionally, hypophosphatemia may improve over time as urine losses of phosphate partially correct.ADHR may be lumped in with X-linked hypophosphatemia under general terms such as hypophosphatemic rickets. Hypophosphatemic rickets are associated with at least nine other genetic mutations. Clinical management of hypophosphatemic rickets may differ depending on the specific mutations associated with an individual case, but treatments are aimed at raising phosphate levels to promote normal bone formation.
References
Further reading
"Hereditary hypophosphatemic rickets". Genetics Home Reference. September 2010. Archived from the original on 17 September 2012. Retrieved 10 October 2012.
"Hypophosphatemic Rickets". The Merck Manual Home Health Handbook. Merck Sharp & Dohme Corp. December 2006. Archived from the original on 13 October 2012. Retrieved 10 October 2012.
== External links == |
Richters transformation | Richters syndrome (RS), also known as Richters transformation, is a transformation of B cell chronic lymphocytic leukemia (CLL) or hairy cell leukemia into a fast-growing diffuse large B cell lymphoma, a variety of non-Hodgkin lymphoma which is refractory to treatment and carries a bad prognosis. There is also a less common variant in which the CLL changes into a Hodgkins lymphoma. Rarely, transformations to a form of myeloid leukemia have been observed. These extraordinarily rare transformations carry a very poor prognosis.
Richters transformation affects about 5% of CLL patients at some point during their lives.
Signs and symptoms
Symptoms of Richter’s transformation in a CLL patient include fever (without infection), elevated serum levels of lactate dehydrogenase, and rapidly enlarging lymph nodes. While about 8% of all CLL patients will have elevated levels of serum lactate dehydrogenase (LDH), more than 50% of CLL patients with Richters transformation will have elevated LDH levels.Richters can appear suddenly, even in patients who were in remission.
Cause
A case of RS may have arisen by one of two different routes: a transformation of the CLL cells into lymphoma, or the appearance of an unrelated lymphoma.It is thought that genetic defects may introduce the additional abnormalities necessary to transform CLL cells into Richters syndrome cells.
Treatment
Treatment with conventional immunochemotherapy is usually indicated; in younger patients, allogeneic bone marrow transplantation may be curative.
Prognosis
The prognosis is generally poor. The RS score (Richter syndrome score), which is an estimate of the patients prognosis, is based on the patients performance status, LDH, platelet count, the size of the lymphoma tumors, and the number of prior therapies already received. Overall, the median survival is between five and eight months. Untreated, RS is invariably fatal.
The Hodgkins lymphoma variant of Richters carries a better prognosis than the predominant diffuse large B-cell lymphoma type, but a worse prognosis than a de novo case of Hodgkins.
Epidemiology
A SEER-based analysis estimated the risk of Richters transformation in Chronic Lymphocytic Leukemia (CLL) patients in the United States to be about 0.72%. The majority of transformations (85%) were Diffuse Large B-Cell Lymphoma (DLBCL), while transformation to Hodgkin occurred in 15% of cases. Most of those transformation events were nodal (74%). The most commonly involved extra-nodal sites were the GI tract (25%), skeletal system (19%), and the brain/CNS (12%). The median time from the diagnosis of CLL to the development of Richters transformation was about 4 years, with no significant difference in the time interval based on histology of the transformation event comparing DLBCL and Hodgkins. The median age at the time of Richters transformation was 66 years.
References
Further reading
Tsimberidou AM, OBrien S, Khouri I, Giles FJ, Kantarjian HM, Champlin R, Wen S, Do KA, Smith SC, Lerner S, Freireich EJ, Keating MJ (May 20, 2006). "Clinical Outcomes and Prognostic Factors in Patients With Richters Syndrome Treated With Chemotherapy or Chemoimmunotherapy With or Without Stem-Cell Transplantation". Journal of Clinical Oncology. 24 (15): 2343–2351. doi:10.1200/JCO.2005.05.0187. PMID 16710033. S2CID 25490586. |
Talon cusp | Talon cusp is a rare dental anomaly resulting in an extra cusp or cusp-like projection on an anterior tooth, located on the inside surface of the affected tooth. Sometimes it can also be found on the facial surface of the anterior tooth.The term talon cusp refers to the same condition as dens evaginatus; however, talon cusp is more specifically the manifestation of dens evaginatus on the anterior teeth. Talon cusp can be simply defined as hyperplasia of the cingulum of an anterior tooth.
Although talon cusp may not appear serious, and in some people may be completely benign, it can cause clinical, diagnostic and functional problems, and alters the appearance of a persons teeth. The condition was first described by W.H. Mitchell in 1982 and named by J. Kimball Mellor B.S., D.D.S. and Louis W. Ripa, D.D.S., M.S. due to its similar appearance to an eagles talon. Some sources define a talon cusp as an extra cusp which extends at least half the distance between the cementoenamel junction and the incisal edge of the tooth. Other sources classify all enlarged cingula as talon cusps, and classify them according to the degree of enlargement.The incidence of talon cusp has been found to range from 1% to 6% of the population. Talon cusp tends to occur on permanent teeth only, being very rare in deciduous teeth. In most cases, the involved teeth are the permanent maxillary lateral incisors (55%), followed by maxillary central incisors (33%), mandibular incisors (6%), and maxillary canines (4%).
Signs and symptoms
Talon cusp will show physical signs of the irregular dental formation of the teeth and cause other symptoms of the disease that could possibly lead to dental problems in the future, depending on severity of the deformity.
Most commonly, the extra cusp is located on the lingual surface, giving a three-pronged appearance. Rarely, however, the extra cusp may be situated on the facial surface, or there may be extra cusps on both lingual and facial surfaces. There may be a deep groove between the talon cusp and the rest of the tooth. The extra cusp typically contains pulp tissue. When viewing talon cusp from the occlusal, the projection will appear "x-shaped", as well as appears conical, and mimic the shape of an eagles talon.Symptoms of talon cusp include:
Interference with occlusion or bite
Irritation of soft tissues and tongue
Accidental cusp fracture
Susceptible to dental caries
Cause
The cause of talon cusp is unknown. The anomaly can occur due to genetic and environmental factors but the onset can be spontaneous. Prevention is difficult because the occurrence happens during the development of teeth.
Talon cusp affects men and women equally, however the majority of reported cases are of the male gender. Individuals of Asian, Arabic, Native American and Inuit descent are affected more commonly. Talon cusp is also highly observed in patients with orofacial digital II syndrome and Rubinstein Taybi syndrome. Other anomalies that occur with talon cusp can include peg laterals, supernumerary teeth, dens envaginatus, agenesis and impaction. A person belonging to one of these particular demographics or one who has any of these deformities or syndromes may have a higher risk of having a talon cusp.
Mechanism
The exact mechanism of the formation of dens evaginatus and talon cusp is unknown. It has been suggested that the anomaly is caused by an evagination. The formation of the "cusp" is due to excess layering of the internal enamel epithelium and dental papilla into the stellate reticulum. This occurs during the morphological differentiation stage of tooth development. During the developmental stages of tooth formation, certain dental follicle cells were differentiated incorrectly which formed the excess enamel and incorrect morphology of the affected tooth.
Talon cusp can progress into severe dental problems if the severity of the cusp affects the persons hygiene and oral functions.
Talon cusp may occur on its own or associated with other dental anomalies such as mesiodens, odontome, unerupted or impacted teeth, peg-shaped maxillary incisor, dens invaginatus, cleft lip, bilateral gemination, fusion, and supernumerary teeth.
Diagnosis
This anomaly is large enough to be seen with the naked eye. One can see the projection on the incisal edge of a tooth looking into the mouth of the affected person. The structure is described to be "Tshaped" or "X-shaped" however will differ depending on its shape, size, structure, location and site of origin. X-rays and radiographs can also show evidence of the abnormality. The digital images would show a tooth with talon cusp as if it were "double teeth".When looking at a radiograph some features to look for would be location, edge, shape and number. The location would be on an anterior tooth, the edge would be clear and well defined and can be seen even by the naked eye, and the shape would appear "talon-like" over the top portion or crown of the affected tooth. There could potentially be one, two or multiple protrusions depending on the type of cusp.
Talon cusp can fall under three categories: Type I, Type II and Type III. They are created based on the cusp formation shape and length of extension.
Type I - Talon: The additional cusp or talon projects from the palatal surface of a primary or permanent anterior (front) tooth that extends at least half of the distance from the cemento enamel junction to the incisal edge.
Type II - Semi Talon: The semi talon cusp measures about 1mm or more in length but extends less than half of the distance seen in Type I Talon.
Type III - Trace Talon: The projection originates from the cingulum (also known as the "cervical third") of the root and is enlarged or prominent in any form (conical, bifid or tubercle-like)Since many cases of Talon cusp go unreported, it is hard to draw linkage maps but it is safe to assume that dental formation is influenced by genetic factors. Talon cusp is also seen in association with conditions such as Rubinstein-Taybi syndrome, Mohr syndrome, Ellis–van Creveld syndrome, Incontinentia pigmenti achromians, Berardinelli-Seip syndrome, and Sturge–Weber syndrome.
Treatment
Treatment is only required if the occlusion or bite of the person is compromised and causing other dental problems. Multiple long-term clinical problems can arise such as occlusal interferences, aesthetic disturbances, loss of pulp vitality, irritation of tongue during mastication and speech, caries and displacement of the affected tooth. Most people with talon cusp will live their normal lives unless the case is severe and causes a cascade of other dental issues that lead to additional health problems. Generally talon cusps on lower teeth require no treatment, but talon cusps on upper teeth may interfere with the bite mechanics and may need to be removed or reduced.Small talon cusps that produce no symptoms or complication for a person can remain untreated. However large talon cusps should not.
Some common treatments include:
Fissure sealing
Composite resin restoration
Reduction of cusp
Pulpotomy
Root canal (endodontic treatment)
ExtractionThe condition is usually benign, but it can cause mild irritation to soft tissues around the teeth and the tongue, and if large enough, may pose an aesthetic problem. Talon cusps that are too large are filed down with a motorized file, and then endodontic therapy is administered.
In order to prevent any future dental complications, when talon cusp is present due to an early diagnosis it would be best to see a dentist regularly every six months for routine dental checkups, remain under observation, brush and floss properly and undergo regular topical applications of fluoride gel to prevent caries and to promote enamel strength.
Recent research
Future studies will look further into the relationship of talon cusp and Rubinstein-Taybi syndrome and other oral-facial-digital syndromes. A former study showed a direct correlation in which 45 affected patients with Rubinstein-Taybi syndrome, 92% of these patients had talon cusp. Other researchers are attempting to trace talon cusp to ancestors and comparing dentition to modern humans. Another study done in 2007 examined the dentition of 301 Native American Indian skeletons for the presence or absence of talon cusp. The results showed five skeletons (2 percent) in the population had the trait.In 2011, only 21 cases of talon cusp have been reported and are in literature. It appears that as of 2014 and 2015, additional research continues in hopes of finding the cause and mechanism of talon cusp. With the majority of cases of talon cusp being unreported, it remains difficult to conduct tests, come up with conclusions, conduct surgery and perform research with small numbers.
== References == |
Organic brain syndrome | Organic brain syndrome, also known as organic brain disease, organic brain disorder, organic mental syndrome, or organic mental disorder, refers to any syndrome or disorder of mental function whose cause is alleged to be known as organic (physiologic) rather than purely of the mind. These names are older and nearly obsolete general terms from psychiatry, referring to many physical disorders that cause impaired mental function. They are meant to exclude psychiatric disorders (mental disorders). Originally, the term was created to distinguish physical (termed "organic") causes of mental impairment from psychiatric (termed "functional") disorders, but during the era when this distinction was drawn, not enough was known about brain science (including neuroscience, cognitive science, neuropsychology, and mind-brain correlation) for this cause-based classification to be more than educated guesswork labeled with misplaced certainty, which is why it has been deemphasized in current medicine. While mental or behavioural abnormalities related to the dysfunction can be permanent, treating the disease early may prevent permanent damage in addition to fully restoring mental functions. An organic cause to brain dysfunction is suspected when there is no indication of a clearly defined psychiatric or "inorganic" cause, such as a mood disorder.
Types
Organic brain syndrome can be divided into 2 major subgroups: acute (delirium or acute confusional state) and chronic (dementia). A third entity, encephalopathy (amnestic), denotes a gray zone between delirium and dementia. The Diagnostic and Statistical Manual of Mental Disorders has broken up the diagnoses that once fell under the diagnostic category organic mental disorder into three categories: delirium, dementia, and amnestic.
Delirium
Delirium or Acute organic brain syndrome is a recently appearing state of mental impairment, as a result of intoxication, drug overdose, infection, pain, and many other physical problems affecting mental status. In medical contexts, "acute" means "of recent onset". As is the case with most acute disease problems, acute organic brain syndrome is often temporary, although this does not guarantee that it will not recur or progress to become chronic, that is, long-term. A more specific medical term for the acute subset of organic brain syndromes is delirium. Thinking, remembering, sleeping, and paying attention can become difficult during alcohol withdrawal, after surgery, or with dementia.
Dementia
Dementia or chronic organic brain syndrome is long-term. For example, some forms of chronic drug or alcohol dependence can cause organic brain syndrome due to their long-lasting or permanent toxic effects on brain function. Other common causes of chronic organic brain syndrome sometimes listed are the various types of dementia, which result from permanent brain damage due to strokes, Alzheimers disease, or other damaging causes which are irreversible. Amnestic pertains to amnesia and is the impairment in ability to learn or recall new information, or recall previously learned information. Although similar, it is not coupled with dementia or delirium.
Amnestic
Amnestic conditions denotes a gray zone between delirium and dementia; its early course may fluctuate, but it is often persistent and progressive. Damage to brain functioning could be due not only to organic (physical) injury (a severe blow to the head, stroke, chemical and toxic exposures, organic brain disease, substance use, etc.) and also to non-organic means such as severe deprivation, abuse, neglect, and severe psychological trauma.
Symptoms
Many of the symptoms of Organic Mental Disorder depend on the cause of the disorder, but are similar and include physical or behavioral elements. Dementia and delirium are the cause of the confusion, orientation, cognition or alertness impairment. Therefore, these symptoms require more attention because hallucinations, delusions, amnesia, and personality changes are the result. These effects of the dementia and delirium are not joined with the changes of sensory or perception abilities. Memory impairment, judgment, logical function and agitation are also some extremely common symptoms. The more common symptoms of OBS are confusion; impairment of memory, judgment, and intellectual function; and agitation. Often these symptoms are attributed to psychiatric illness, which causes a difficulty in diagnosis.
Associated conditions
Disorders that are related to injury or damage to the brain and contribute to OBS include, but are not limited to:
Alcoholism
Alzheimers disease
Attention deficit/hyperactivity disorder
Autism
Concussion
Encephalitis
Epilepsy
Fetal alcohol syndrome
Hypoxia
Parkinsons disease
Intoxication/overdose caused by substance use disorders including alcohol use disorder
Non-medical use of sedative hypnotics
Intracranial hemorrhage/trauma
Korsakoff syndrome
Mastocytosis
Meningitis
Psychoorganic syndrome
Stroke/transient ischemic attack (TIA)
Withdrawal from drugs, especially sedative hypnotics, e.g. alcohol or benzodiazepinesOther conditions that may be related to organic brain syndrome include: clinical depression, neuroses, and psychoses, which may occur simultaneously with the OBS.
Treatment
While the treatment depends on which particular disorder is involved in Organic Mental Disorder, a few that are possible. Treatments can include, but are not limited to, rehabilitation therapy such as physical or occupational, pharmacological modification of the neurotransmitter function, or medication. The affected parts of the brain can recover some function with the help of different types of therapy. Online therapy can be just as intense and helpful as rehabilitation therapy, in person, and can help those affected regain function in daily life.
Prognosis
Some disorders are short-term and treatable, and their prognosis is not as lengthy. Rest and medication are the most common courses of action for these treatable cases to help the patient return to proper health. Many of the cases are long-term, and there is not as much of a set and defined prognosis. The course of action can include extensive counseling and therapy. There are many reasons that the long-term cases are harder to treat and these include these cases normally get worse over time, and medication or therapy could not work. In this case, many of the prognosis tracks are to help the patient and their family become more comfortable and understand what will happen.
Associated conditions
Brain injury caused by trauma
Bleeding into the brain (intracerebral hemorrhage)
Bleeding into the space around the brain (subarachnoid hemorrhage)
Blood clot inside the skull causing pressure on brain (subdural hematoma)
Concussion
Breathing conditions
Low oxygen in the body (hypoxia)
High carbon dioxide levels in the body (hypercapnia)
Cardiovascular disorders
Abnormal heart rhythm (arrhythmias)
Brain injury due to high blood pressure (hypertensive brain injury)
Dementia due to many strokes (multi-infarct dementia)
Heart infections (endocarditis, myocarditis)
Stroke
Transient ischemic attack (TIA)
Degenerative disorders
Alzheimers disease (also called senile dementia, Alzheimers type)
Creutzfeldt–Jakob disease
Diffuse Lewy Body disease
Huntingtons disease
Multiple sclerosis
Normal pressure hydrocephalus
Parkinsons disease
Picks disease
Dementia due to metabolic causes
Drug and alcohol-related conditions
Alcohol withdrawal state
Intoxication from drug or alcohol use
Wernicke–Korsakoff syndrome (a long-term effect of excessive alcohol consumption or malnutrition)
Withdrawal from drugs (especially sedative-hypnotics and corticosteroids)
Infections
Any sudden onset (acute) or long-term (chronic) infection
Blood poisoning (sepsis)
Brain infection (encephalitis)
Meningitis (infection of the lining of the brain and spinal cord)
Prion infections such as mad cow disease
Late-stage syphilis (general paresis)
Other medical disorders
Cancer
Kidney disease
Liver disease
Thyroid disease (high or low)
Vitamin deficiency (B1, B12, or folate)
Lithium toxicity can cause permanent organic brain damage
Accumulation of metals in the brains
Aluminum
Mercury poisoning
References
External links
AllRefer Health.com. 13 December 2006. |
Progressive osseous heteroplasia | Progressive osseous heteroplasia is a cutaneous condition characterized by cutaneous or subcutaneous ossification.According to the Progressive Osseous Heteroplasia Association:
Progressive Osseous Heteroplasia (POH) is a rare genetic condition in which the body makes extra bone in locations where bone should not form. Extra bone develops inside skin, subcutaneous tissue (fat tissue beneath the skin), muscles, tendons, and ligaments. This ”out of place extra bone formation” is commonly referred to as heterotopic ossification. In people with POH, nodules and lace-like webs of extra bone extend from the skin into the subcutaneous fat and deep connective tissues, and may cross joints. Extra bone formation near the joints may lead to stiffness, locking, and permanent immobility.”
It is associated with GNAS.A telltale symptom of POH is osteoma cutis under the skin of a newborn. It was discovered in 1994 by physician Frederick Kaplan.
Diagnosis
Patients with POH have a distinctly different manifestation of symptoms than those with fibrodysplasia ossificans progressiva (FOP), though heterotopic ossification appears in both diseases. They lack the congenital abnormality of the big toe that is a diagnostic feature for FOP. People with POH also have ossification of the skin during infancy, which does not occur in FOP. Also, the pattern of ossification differs in POH, spreading in an intramembranous fashion rather than endochondral.
See also
Fibrodysplasia ossificans progressiva
Punctate porokeratosis
List of cutaneous conditions
Pseudopseudohypoparathyroidism
References
== External links == |
Cervical weakness | Cervical weakness, also called cervical incompetence or cervical insufficiency, is a medical condition of pregnancy in which the cervix begins to dilate (widen) and efface (thin) before the pregnancy has reached term. Definitions of cervical weakness vary, but one that is frequently used is the inability of the uterine cervix to retain a pregnancy in the absence of the signs and symptoms of clinical contractions, or labor, or both in the second trimester. Cervical weakness may cause miscarriage or preterm birth during the second and third trimesters. It has been estimated that cervical insufficiency complicates about 1% of pregnancies, and that it is a cause in about 8% of women with second trimester recurrent miscarriages.A sign of cervical weakness is funneling at the internal orifice of the uterus, which is a dilation of the cervical canal at this location.In cases of cervical weakness, dilation and effacement of the cervix may occur without pain or uterine contractions. In a normal pregnancy, dilation and effacement occurs in response to uterine contractions. Cervical weakness becomes a problem when the cervix is pushed to open by the growing pressure in the uterus as pregnancy progresses. If the responses are not halted, rupture of the membranes and birth of a premature baby can result.
The older terminology is perceived as blaming the woman for the miscarriage, as if she were an incompetent or insufficient person. Consequently, cervical weakness is the recommended term.
Risk factors
Risk factors for premature birth or stillbirth due to cervical weakness include:
diagnosis of cervical weakness in a previous pregnancy
previous preterm premature rupture of membranes
history of conization (cervical biopsy)
diethylstilbestrol exposure, which can cause anatomical defects, and
uterine anomaliesRepeated procedures (such as mechanical dilation, especially during late pregnancy) appear to create a risk. Additionally, any significant trauma to the cervix can weaken the tissues involved.
Diagnosis
Diagnosis of cervical weakness can be challenging and is based on a history of painless cervical dilation usually after the first trimester without contractions or labor and in the absence of other clear pathology. In addition to history, some providers use assessment of cervical length in second trimester to identify cervical shortening using ultrasound. However, short cervical length has actually been shown to be a marker of preterm birth rather than cervical weakness. Other diagnostic tests that have been suggested which have not been validated include hysterosalpingography and radiographic imaging of balloon traction on the cervix, assessment of the patulous cervix with Hegar or Pratt dilators, the use of a balloon elastance test, and use of graduated cervical dilators to calculate a cervical resistance index.Normally, the cervix should be at least 30 mm in length. Cervical weakness is variably defined. However, a common definition is a cervical length of less than 25 mm at or before 24 weeks of gestational age. The risk of preterm birth is inversely proportional to cervical length:
Less than 25 mm; 18% risk of preterm birth
Less than 20 mm; 25% risk of preterm birth
Less than 15 mm; 50% risk of preterm birth
Treatment
Cervical weakness is not generally treated except when it appears to threaten a pregnancy. Cervical weakness can be treated using cervical cerclage, a surgical technique that reinforces the cervical muscle by placing sutures above the opening of the cervix to narrow the cervical canal.Cerclage procedures usually entail closing the cervix through the vagina with the aid of a speculum. Another approach involves performing the cerclage through an abdominal incision. Transabdominal cerclage of the cervix makes it possible to place the stitch exactly at the level that is needed. It can be carried out when the cervix is very short, effaced or totally distorted. Cerclages are usually performed between weeks 12 to 14 of the pregnancy. The sutures are removed between weeks 36 and 38 to avoid problems during labor. The complications described in the literature have been rare: hemorrhage from damage to the veins at the time of the procedure; and fetal death due to uterine vessels occlusion.
No significant differences in pregnancy outcomes were found in a study evaluating pregnancy outcomes after cervical conization. This study suggests for women with cervical insufficiency due to prior cone biopsy, cerclage is not superior to no intervention. As cerclage can induce preterm contractions without preventing premature delivery, makes the recommendation that it be used sparingly in women with a history of conization.
A cervical pessary is being studied as an alternative to cervical cerclage since there are fewer potential complications. A silicone ring is placed at the opening to the cervix early in the pregnancy, and removed later in the pregnancy prior to the time of expected delivery. Further study is needed to determine whether a cervical pessary is equal or superiour to current management.
Notes
References
The first revision of this article was adapted from material from the public domain source "Summary Report: ICD-9-CM coordination and maintenance committee", published at https://web.archive.org/web/20051223102344/http://www.cms.hhs.gov/paymentsystems/icd9/icd111700.pdf.
== External links == |
Zoophilia | Zoophilia is a paraphilia involving a sexual fixation on non-human animals. Bestiality is cross-species sexual activity between humans and non-human animals. The terms are often used interchangeably, but some researchers make a distinction between the attraction (zoophilia) and the act (bestiality).In most countries, bestiality is illegal under animal abuse laws or laws dealing with sodomy or crimes against nature.
Terminology
General
Three key terms commonly used in regards to the subject—zoophilia, bestiality, and zoosexuality—are often used somewhat interchangeably. Some researchers distinguish between zoophilia (as a persistent sexual interest in animals) and bestiality (as sexual acts with animals), because bestiality is often not driven by a sexual preference for animals. Some studies have found a preference for animals is rare among people who engage in sexual contact with animals. Furthermore, some zoophiles report they have never had sexual contact with an animal. People with zoophilia are known as "zoophiles", though also sometimes as "zoosexuals", or even very simply "zoos". Zooerasty, sodomy, and zooerastia are other terms closely related to the subject but are less synonymous with the former terms, and are seldom used. "Bestiosexuality" was discussed briefly by Allen (1979), but never became widely established. Ernest Bornemann (1990, cited by Rosenbauer, 1997) coined the separate term zoosadism for those who derive pleasure – sexual or otherwise – from inflicting pain on animals. Zoosadism specifically is one member of the Macdonald triad of precursors to sociopathic behavior.
Zoophilia
The term zoophilia was introduced into the field of research on sexuality in Psychopathia Sexualis (1886) by Krafft-Ebing, who described a number of cases of "violation of animals (bestiality)", as well as "zoophilia erotica", which he defined as a sexual attraction to animal skin or fur. The term zoophilia derives from the combination of two nouns in Greek: ζῷον (zṓion, meaning "animal") and φιλία (philia, meaning "(fraternal) love"). In general contemporary usage, the term zoophilia may refer to sexual activity between human and non-human animals, the desire to engage in such, or to the specific paraphilia (i.e., the atypical arousal) which indicates a definite preference for animals over humans as sexual partners. Although Krafft-Ebing also coined the term zooerasty for the paraphilia of exclusive sexual attraction to animals, that term has fallen out of general use.
Zoosexuality
The term zoosexual was proposed by Hani Miletski in 2002 as a value-neutral term. Usage of zoosexual as a noun (in reference to a person) is synonymous with zoophile, while the adjectival form of the word – as, for instance, in the phrase "zoosexual act" – may indicate sexual activity between a human and an animal. The derivative noun "zoosexuality" is sometimes used by self-identified zoophiles in both support groups and on internet-based discussion forums to designate sexual orientation manifesting as sexual attraction to animals.
Bestiality
The legal term bestiality has three common pronunciations: [ˌbestʃiˈæləti] or [ˌbistʃiˈæləti] in the United States, and [ˌbestiˈæləti] in the United Kingdom. Some zoophiles and researchers draw a distinction between zoophilia and bestiality, using the former to describe the desire to form sexual relationships with animals, and the latter to describe the sex acts alone. Confusing the matter yet further, writing in 1962, Masters used the term bestialist specifically in his discussion of zoosadism.Stephanie LaFarge, an assistant professor of psychiatry at the New Jersey Medical School, and Director of Counseling at the ASPCA, writes that two groups can be distinguished: bestialists, who rape or abuse animals, and zoophiles, who form an emotional and sexual attachment to animals. Colin J. Williams and Martin Weinberg studied self-defined zoophiles via the internet and reported them as understanding the term zoophilia to involve concern for the animals welfare, pleasure, and consent, as distinct from the self-labelled zoophiles concept of "bestialists", whom the zoophiles in their study defined as focused on their own gratification. Williams and Weinberg also quoted a British newspaper saying that zoophilia is a term used by "apologists" for bestiality.
Extent of occurrence
The Kinsey reports rated the percentage of people in the general population who had at least one sexual interaction with animals as 8% for males and 5.1% for females (1.5% for pre-adolescents and 3.6% for post-adolescents females), and claimed it was 40–50% for the rural population and even higher among individuals with lower educational status, but some later writers dispute the figures, because the study lacked a random sample in that it included a disproportionate number of prisoners, causing sampling bias. Martin Duberman has written that it is difficult to get a random sample in sexual research, and that even when Paul Gebhard, Kinseys research successor, removed prison samples from the figures, he found the figures were not significantly changed.By 1974, the farm population in the USA had declined by 80 percent compared with 1940, reducing the opportunity to live with animals; Hunts 1974 study suggests that these demographic changes led to a significant change in reported occurrences of bestiality. The percentage of males who reported sexual interactions with animals in 1974 was 4.9% (1948: 8.3%), and in females in 1974 was 1.9% (1953: 3.6%). Miletski believes this is not due to a reduction in interest but merely a reduction in opportunity.Nancy Fridays 1973 book on female sexuality, My Secret Garden, comprised around 190 fantasies from different women; of these, 23 involve zoophilic activity.In one study, psychiatric patients were found to have a statistically significant higher prevalence rate (55 percent) of reported bestiality, both actual sexual contacts (45 percent) and sexual fantasy (30 percent) than the control groups of medical in-patients (10 percent) and psychiatric staff (15 percent). Crépault and Couture (1980) reported that 5.3 percent of the men they surveyed had fantasized about sexual activity with an animal during heterosexual intercourse. In a 2014 study, 3% of women and 2.2% of men reported fantasies about having sex with an animal. A 1982 study suggested that 7.5 percent of 186 university students had interacted sexually with an animal. A 2021 review estimated zoophilic behavior occurs in 2% of the general population.
Sexual arousal from watching animals mate is known as faunoiphilia.
Perspectives on zoophilia
Research perspectives
Zoophilia has been partly discussed by several sciences: psychology (the study of the human mind), sexology (a relatively new discipline primarily studying human sexuality), ethology (the study of animal behavior), and anthrozoology (the study of human–animal interactions and bonds).
In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), zoophilia is placed in the classification "other specified paraphilic disorder" ("paraphilias not otherwise specified" in the DSM-III and IV). The World Health Organization takes the same position, listing a sexual preference for animals in its ICD -10 as "other disorder of sexual preference". In the DSM-5, it rises to the level of a diagnosable disorder only when accompanied by distress or interference with normal functioning.Zoophilia may also be covered to some degree by other fields such as ethics, philosophy, law, animal rights and animal welfare. It may also be touched upon by sociology which looks both at zoosadism in examining patterns and issues related to sexual abuse and at non-sexual zoophilia in examining the role of animals as emotional support and companionship in human lives, and may fall within the scope of psychiatry if it becomes necessary to consider its significance in a clinical context.
The Journal of Forensic and Legal Medicine (Vol. 18, February 2011) states that sexual contact with animals is almost never a clinically significant problem by itself; it also states that there are several kinds of zoophiles:
Additionally, zoophiles in categories 2, 3, and 8 (romantic zoophiles, zoophilic fantasizers, and regular zoophiles) are the most common, while zoophiles found in categories 6 and 7 (sadistic bestials and opportunistic zoophiles) are the least common.Zoophilia may reflect childhood experimentation, sexual abuse or lack of other avenues of sexual expression. Exclusive desire for animals rather than humans is considered a rare paraphilia, and sufferers often have other paraphilias with which they present. Zoophiles will not usually seek help for their condition, and so do not come to the attention of psychiatrists for zoophilia itself.The first detailed studies of zoophilia date from prior to 1910. Peer reviewed research into zoophilia in its own right started around 1960. However, a number of the most oft-quoted studies, such as Miletski, were not published in peer-reviewed journals. There have been several significant modern books, from Masters (1962) to Beetz (2002); their research arrived at the following conclusions:
Most zoophiles have (or have also had) long term human relationships as well or at the same time as zoosexual ones, and that zoosexual partners are usually dogs and/or horses (Masters, Miletski, Beetz)
Zoophiles emotions and care for animals can be real, relational, authentic and (within animals abilities) reciprocal, and not just a substitute or means of expression. Beetz believes zoophilia is not an inclination which is chosen.
Society in general at present is considerably misinformed about zoophilia, its stereotypes, and its meaning. The distinction between zoophilia and zoosadism is a critical one to these researchers, and is highlighted by each of these studies. Masters (1962), Miletski (1999) and Weinberg (2003) each comment significantly on the social harm caused by misunderstandings regarding zoophilia: "This destroy[s] the lives of many citizens".Beetz also states the following:
The phenomenon of sexual contact with animals is starting to lose its taboo: it is appearing more often in scholarly publications, and the public are being confronted with it, too. ... Sexual contact with animals – in the form of bestiality or zoophilia – needs to be discussed more openly and investigated in more detail by scholars working in disciplines such as animal ethics, animal behavior, anthrozoology, psychology, mental health, sociology, and the law.
More recently, research has engaged three further directions: the speculation that at least some animals seem to enjoy a zoophilic relationship assuming sadism is not present, and can form an affectionate bond.Beetz described the phenomenon of zoophilia/bestiality as being somewhere between crime, paraphilia and love, although she says that most research has been based on criminological reports, so the cases have frequently involved violence and psychiatric illness. She says only a few recent studies have taken data from volunteers in the community. As with all volunteer surveys and sexual ones in particular, these studies have a potential for self-selection bias.Medical research suggests that some zoophiles only become aroused by a specific species (such as horses), some zoophiles become aroused by multiple species (which may or may not include humans), and some zoophiles are not attracted to humans at all.
Historical and cultural perspectives
Instances of this behavior have been found in the Bible. In a cave painting from at least 8000 BC in the Northern Italian Val Camonica a man is shown about to penetrate an animal. Raymond Christinger interprets that as a show of power of a tribal chief, and so we do not know if this practice was then more acceptable, and if the scene depicted was usual or unusual or whether it was symbolic or imaginary. The "Cambridge Illustrated History of Prehistoric Art" says the scene may be humorous, as the penetrating man seems to be waving cheerfully with his hand at the same time. Potters seem to have spent time depicting the practice, but this may be because they found the idea amusing. Dr "Jacobus X", said to be the pen name of a French author, said this was clearly "before any known taboos against sex with animals existed". Marc Epprecht states that authors such as Jacobus X do not deserve respect because their methodology is based on hearsay, and was designed for voyeuristic titillation of the reader. Masters said that since pre-historic man is prehistoric it goes without saying that we know little of his sexual behaviour; depictions in cave paintings may only show the artists subjective preoccupations or thoughts.
Pindar, Herodotus, and Plutarch claimed the Egyptians engaged in ritual congress with goats. Such claims about other cultures do not necessarily reflect anything about which the author had evidence, but may be a form of propaganda or xenophobia, similar to blood libel.Bestiality has been accepted in a few North American and Middle Eastern indigenous cultures.Several cultures built temples (Khajuraho, India) or other structures (Sagaholm, barrow, Sweden) with zoophilic carvings on the exterior, however at Khajuraho, these depictions are not on the interior, perhaps depicting that these are things that belong to the profane world rather than the spiritual world, and thus are to be left outside.In the Church-oriented culture of the Middle Ages, zoophilic activity was met with execution, typically burning, and death to the animals involved either the same way or by hanging, as "both a violation of Biblical edicts and a degradation of man as a spiritual being rather than one that is purely animal and carnal". Some witches were accused of having congress with the devil in the form of an animal. As with all accusations and confessions extracted under torture in the witch trials in Early Modern Europe, their validity cannot be ascertained.
Religious perspectives
Passages in Leviticus 18 (Lev 18:23: "And you shall not lie with any beast and defile yourself with it, neither shall any woman give herself to a beast to lie with it: it is a perversion." RSV) and 20:15–16 ("If a man lies with a beast, he shall be put to death; and you shall kill the beast. If a woman approaches any beast and lies with it, you shall kill the woman and the beast; they shall be put to death, their blood is upon them." RSV) are cited by Jewish, Christian, and Muslim theologians as categorical denunciation of bestiality. However, the teachings of the New Testament have been interpreted by some as not expressly forbidding bestiality.In Part II of his Summa Theologica, medieval philosopher Thomas Aquinas ranked various "unnatural vices" (sex acts resulting in "venereal pleasure" rather than procreation) by degrees of sinfulness, concluding that "the most grievous is the sin of bestiality". Some Christian theologians extend Matthews view that even having thoughts of adultery is sinful to imply that thoughts of committing bestial acts are likewise sinful.
There are a few references in Hindu scriptures to religious figures engaging in symbolic sexual activity with animals such as explicit depictions of people having sex with animals included amongst the thousands of sculptures of "Life events" on the exterior of the temple complex at Khajuraho. The depictions are largely symbolic depictions of the sexualization of some animals and are not meant to be taken literally. According to the Hindu tradition of erotic painting and sculpture, having sex with an animal is believed to be actually a human having sex with a god incarnated in the form of an animal. However, in some Hindu scriptures, such as the Bhagavata Purana and the Devi Bhagavata Purana, having sex with animals, especially the cow, leads one to hell, where one is tormented by having ones body rubbed on trees with razor-sharp thorns.
Legal status
In many jurisdictions, all acts of bestiality are prohibited; others outlaw only the mistreatment of animals, without specific mention of sexual activity. In the United Kingdom, Section 63 of the Criminal Justice and Immigration Act 2008 (also known as the Extreme Pornography Act) outlaws images of a person performing or appearing to perform an act of intercourse or oral sex with an animal (whether dead or alive). Despite the UK Ministry of Justices explanatory note on extreme images saying "It is not a question of the intentions of those who produced the image. Nor is it a question of the sexual arousal of the defendant", "it could be argued that a person might possess such an image for the purposes of satire, political commentary or simple grossness," according to The Independent.Many new laws banning sex with animals have been made recently, such as in New Hampshire, Ohio, Germany, Sweden, Iceland, Denmark, Thailand, Costa Rica, Bolivia, and Guatemala. The number of jurisdictions around the world banning it has grown in the 2000s and 2010s.
Germany legalized bestiality in 1969, but banned it again in 2013. The 2013 law was unsuccessfully challenged in 2015.Laws on bestiality are sometimes triggered by specific incidents. While some laws are very specific, others employ vague terms such as "sodomy" or "bestiality", which lack legal precision and leave it unclear exactly which acts are covered. In the past, some bestiality laws may have been made in the belief that sex with an animal could result in monstrous offspring, as well as offending the community. Current anti-cruelty laws focus more specifically on animal welfare while anti-bestiality laws are aimed only at offenses to community "standards".
Notable legal views include Sweden, where a 2005 report by the Swedish Animal Welfare Agency for the government expressed concern over the increase in reports of horse-ripping incidents. The agency believed current animal cruelty legislation was not sufficient in protecting animals from abuse and needed updating, but concluded that on balance it was not appropriate to call for a ban. In New Zealand, the 1989 Crimes Bill considered abolishing bestiality as a criminal offense, and instead viewing it as a mental health issue, but they did not, and people can still be prosecuted for it. Under Section 143 of the Crimes Act 1961, individuals can serve a sentence of seven years duration for animal sexual abuse and the offence is considered complete in the event of penetration.Copulating with a female alpaca is still specifically against the law in Peru.As of 2022, bestiality is illegal in 48 U.S. states. Most state bestiality laws were enacted between 1999 and 2022. Until 2005, there was a farm near Enumclaw, Washington that was described as an "animal brothel", where people paid to have sex with animals. After an incident on 2 July 2005, when a man was pronounced dead in the emergency room of the Enumclaw community hospital after his colon ruptured due to having had anal sex with a horse, the farm garnered police attention. The state legislature of the State of Washington, which had been one of the few states in the United States without a law against bestiality, within six months passed a bill making bestiality illegal. Arizona, Alaska, Florida, Alabama, New Jersey, New Hampshire, Ohio, Texas, Vermont, and Nevada have banned sex with animals between 2006 and the present, with the latter five all banning it in 2017. In 2021, Wyoming and Hawaii passed legislation banning bestiality. When such laws are proposed, they are never questioned or debated.Bestiality remains legal in two states (West Virginia and New Mexico), while 19 other states have statutes that date to the 19th century or even the Colonial period. These new statutes are distinct from older sodomy statutes in that they define the proscribed acts with precision.
Pornography
In the United States, zoophilic pornography would be considered obscene if it did not meet the standards of the Miller Test and therefore is not openly sold, mailed, distributed or imported across state boundaries or within states which prohibit it. Under U.S. law, distribution includes transmission across the Internet.
Similar restrictions apply in Germany (see above). In New Zealand the possession, making or distribution of material promoting bestiality is illegal.
The potential use of media for pornographic movies was seen from the start of the era of silent film. Polissons and Galipettes (re-released 2002 as "The Good Old Naughty Days") is a collection of early French silent films for brothel use, including some animal pornography, dating from around 1905 – 1930.
Material featuring sex with animals is widely available on the Internet. An early film to attain great infamy was "Animal Farm", smuggled into Great Britain around 1980 without details as to makers or provenance. The film was later traced to a crude juxtaposition of smuggled cuts from many of Bodil Joensens 1970s Danish movies.
Today, in Hungary, where production faces no legal limitations, zoophilic materials have become a substantial industry that produces a number of films and magazines, particularly for Dutch companies such as Topscore and Book & Film International, and the genre has stars such as "Hector", a Great Dane dog starring in several films.
In Japan, animal pornography is used to bypass censorship laws, often featuring models performing fellatio on animals, because oral penetration of a non-human penis is not in the scope of Japanese pixelization censorship. While primarily underground, there are a number of animal pornography actresses who specialize in bestiality movies.
In the United Kingdom, Section 63 of the Criminal Justice and Immigration Act 2008 criminalises possession of realistic pornographic images depicting sex with animals (see extreme pornography), including fake images and simulated acts, as well as images depicting sex with dead animals. The law provides for sentences of up to two years in prison; a sentence of 12 months was handed down in one case in 2011.
Zoophiles
Non-sexual zoophilia
The love of animals is not necessarily sexual in nature. In psychology and sociology the word "zoophilia" is sometimes used without sexual implications. Being fond of animals in general, or as pets, is accepted in Western society, and is usually respected or tolerated. However, the word zoophilia is used to mean a sexual preference towards animals, which makes it a paraphilia. Some zoophiles may not act on their sexual attraction to animals. People who identify as zoophiles may feel their love for animals is romantic rather than purely sexual, and say this makes them different from those committing entirely sexually motivated acts of bestiality.
Zoophile community
An online survey which recruited participants over the internet concluded that prior to the arrival of widespread computer networking, most zoophiles would not have known other zoophiles, and for the most part, zoophiles engaged in bestiality secretly, or told only trusted friends, family or partners. The internet and its predecessors made people able to search for information on topics which were not otherwise easily accessible and to communicate with relative safety and anonymity. Because of the diary-like intimacy of blogs and the anonymity of the internet, zoophiles had the ideal opportunity to "openly" express their sexuality. As with many other alternate lifestyles, broader networks began forming in the 1980s when participating in networked social groups became more common at home and elsewhere. Such developments in general were described by Markoff in 1990; the linking of computers meant that people thousands of miles apart could feel the intimacy akin to being in a small village together. The popular newsgroup alt.sex.bestiality, said to be in the top 1% of newsgroup interest (i.e. number 50 out of around 5000), – and reputedly started in humor – along with personal bulletin boards and talkers, chief among them Sleepys multiple worlds, Lintilla, and Planes of Existence, were among the first group media of this kind in the late 1980s and early 1990s. These groups rapidly drew together zoophiles, some of whom also created personal and social websites and Internet Forums. By around 1992–1994, the wide social net had evolved. This was initially centered around the above-mentioned newsgroup, alt.sex.bestiality, which during the six years following 1990 had matured into a discussion and support group. The newsgroup included information about health issues, laws governing zoophilia, bibliography relating to the subject, and community events.Weinberg and Williams observe that the internet can socially integrate an incredibly large number of people. In Kinseys day contacts between animal lovers were more localized and limited to male compatriots in a particular rural community. Further, while the farm boys Kinsey researched might have been part of a rural culture in which sex with animals was a part, the sex itself did not define the community. The zoophile community is not known to be particularly large compared to other subcultures which make use of the internet, so Weinberg and Williams surmised its aims and beliefs would likely change little as it grew. Those particularly active on the internet may not be aware of a wider subculture, as there is not much of a wider subculture, Weinberg and Williams felt the virtual zoophile group would lead the development of the subculture.Websites aim to provide support and social assistance to zoophiles (including resources to help and rescue abused or mistreated animals), but these are not usually well publicized. Such work is often undertaken as needed by individuals and friends, within social networks, and by word of mouth.Zoophiles tend to experience their first zoosexual feelings during adolescence, and tend to be secretive about it, hence limiting the ability for non-Internet communities to form.
See also
References and footnotes
External links
Encyclopedia of Human Sexuality entry for "Bestiality" at Sexology Department of Humboldt University, Berlin.
Zoophilia References Database Bestiality and zoosadism criminal executions.
Animal Abuse Crime Database search form for the U.S. and UK. |
Coronary artery aneurysm | Coronary artery aneurysm is an abnormal dilatation of part of the coronary artery. This rare disorder occurs in about 0.3–4.9% of patients who undergo coronary angiography.
Signs and symptoms
Causes
Acquired causes include atherosclerosis in adults, Kawasaki disease in children and coronary catheterization. With the invention of drug eluting stents, there has been more cases implying stents lead to coronary aneurysms. The pathophysiology, although not completely understood, might be comparable to that of aneurysms of larger vessels. This includes disruption of the arterial media, weakening of the arterial wall, increased wall strain and slow dilatation of the coronary artery portion.It can also be congenital. The following risk factors are thought to be associated with coronary artery aneurysms:
Individuals genetic make-up, especially in patients with congenital coronary artery aneurysms
Coronary artery disease (atherosclerosis)
Vasculitic and connective tissue diseases (Kawasaki and Marfan)
Intracoronary manipulation leading to local wall stress (stent placement, angioplasty, brachytherapy)
Post-infectious as a consequence of direct wall infiltration or immune complex deposition
Diagnosis
It is often found coincidentally on coronary angiography. Other modalities that can be used to diagnose a coronary artery aneurysm include echocardiography, magnetic resonance imaging and computerized tomography. Although coronary angiography remains to be the gold standard, the invasive procedure comes with its associated risks, is more expensive than other modalities and the size of the aneurysm might be miscalculated if there is a thrombus in place.
Treatment
Treatment for coronary artery aneurysm include medical management, surgery and percutaneous intervention. Underlying coronary artery risk factors should be addressed in patients with atherosclerosis and proper guideline-mediated medications should be started. In those with risk for embolism or thrombosis, anti-platelet or anticoagulation therapy should be contemplated.In patients with Kawasaki disease prompt administration of intravenous immunoglobulin (IVIG) therapy should be given to prevent complication of coronary artery aneurysm.
Prognosis
Generally, it has a good prognosis. In Kawasakis disease, untreated, there is a 1–2% death rate, from cardiac causes.The prognosis of coronary artery aneurysm is dependent on its diameter. The smaller the aneurysm the better the prognosis. There is less risk for ischemic myocardial damage and mortality with smaller aneurysms. Aneurysms with an internal diameter > 8 mm have poorer outcomes, since these aneurysms can be occluded and be associated with complications such as arrhythmias, myocardial infarction, or sudden death.
See also
Aneurysm
Coronary artery ectasia
References
== External links == |
Lebers hereditary optic neuropathy | Lebers hereditary optic neuropathy (LHON) is a mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; it predominantly affects young adult males. LHON is transmitted only through the mother, as it is primarily due to mutations in the mitochondrial (not nuclear) genome, and only the egg contributes mitochondria to the embryo. LHON is usually due to one of three pathogenic mitochondrial DNA (mtDNA) point mutations. These mutations are at nucleotide positions 11778 G to A, 3460 G to A and 14484 T to C, respectively in the ND4, ND1 and ND6 subunit genes of complex I of the oxidative phosphorylation chain in mitochondria. Men cannot pass on the disease to their offspring.
Signs and symptoms
Clinically, there is an acute onset of visual loss, first in one eye, and then a few weeks to months later in the other. Onset is usually young adulthood, but age range at onset from 7-75 is reported. The age of onset is slightly higher in females (range 19–55 years: mean 31.3 years) than males (range 15–53 years: mean 24.3). The male-to-female ratio varies between mutations: 3:1 for 3460 G>A, 6:1 for 11778 G>A and 8:1 for 14484 T>C.This typically evolves to very severe optic atrophy and a permanent decrease of visual acuity. Both eyes become affected either simultaneously (25% of cases) or sequentially (75% of cases) with a median inter-eye delay of 8 weeks. Rarely, only one eye is affected. In the acute stage, lasting a few weeks, the affected eye demonstrates an oedematous appearance of the nerve fiber layer, especially in the arcuate bundles and enlarged or telangiectatic and tortuous peripapillary vessels (microangiopathy). The main features are seen on fundus examination, just before or after the onset of visual loss. A pupillary defect may be visible in the acute stage as well. Examination reveals decreased visual acuity, loss of color vision and a cecocentral scotoma on visual field examination.
LHON with demyelinating lesions or LHON Plus
LHON Plus is a rare variant of the disorder with eye disease together with other conditions. Its symptoms include loss of the brains ability to control the movement of muscles, tremors, and cardiac arrhythmia. Many cases of LHON plus have been compared to multiple sclerosis because of the lack of muscular control and the presence of demyelinating lesions in the CNS. It is therefore a subtype of MS, according to McDonalds definition.
Genetics
Leber hereditary optic neuropathy is a condition related to changes in mitochondrial DNA. Although most DNA is packaged in chromosomes within the nucleus, mitochondria have a distinct mitochondrial genome composed of mtDNA.Mutations in the MT-ND1, MT-ND4, MT-ND4L, and MT-ND6 genes cause Leber hereditary optic neuropathy. These genes code for the NADH dehydrogenase protein involved in the normal mitochondrial function of oxidative phosphorylation. Oxidative phosphorylation uses a series of four large multienzyme complexes, all embedded in the inner mitochondrial membrane, to convert oxygen and simple sugars to energy. Mutations in any of the genes disrupt this process to cause a variety of syndromes depending on the type of mutation and other factors. It remains unclear how these genetic changes cause the death of cells in the optic nerve and lead to the specific features of Leber hereditary optic neuropathy.
Pathophysiology
The eye pathology is limited to the retinal ganglion cell layer, especially the maculopapillary bundle. Degeneration is evident from the retinal ganglion cell bodies to the axonal pathways leading to the lateral geniculate nuclei. Experimental evidence reveals impaired glutamate transport and increased reactive oxygen species (ROS) causing apoptosis of retinal ganglion cells. Also, experiments suggest that normal, non-LHON-affected retinal ganglion cells produce less of the potent superoxide radical than other normal central nervous system neurons. Viral vector experiments that augment superoxide dismutase 2 in LHON cybrids or LHON animal models or use of exogenous glutathione in LHON cybrids have been shown to rescue LHON-affected retinal ganglion cells from apoptotic death. These experiments may in part explain the death of LHON-affected retinal ganglion cells in preference to other central nervous system neurons that also carry LHON-affected mitochondria.
Diagnosis
Without a known family history of LHON the diagnosis usually requires a neuro-ophthalmological evaluation and blood testing for mitochondrial DNA assessment. It is important to exclude other possible causes of vision loss and associated syndromes such as heart electrical conduction system abnormalities.
Treatment
The prognosis for those left untreated is almost always continued significant visual loss in both eyes. Regular corrected visual acuity and perimetry checks are advised for affected people. There is beneficial treatment for some cases of LHON, especially for early-onset disease, and experimental treatment protocols are in progress. Genetic counseling should be offered. Health and lifestyle choices should be reassessed, particularly in light of toxic and nutritional theories of gene expression. Vision aids assistance and work rehabilitation should be used to assist in maintaining employment.For those who carry a LHON mutation, preclinical markers may be used to monitor progress. For example, fundus photography can monitor nerve fiber layer swelling. Optical coherence tomography can be used for more detailed study of retinal nerve fiber layer thickness. Red green color vision testing may detect losses. Contrast sensitivity may be diminished. There could be an abnormal electroretinogram or visual evoked potentials. Neuron-specific enolase and axonal heavy chain neurofilament blood markers may predict conversion to affected status.Cyanocobalamin (a form of B12) should be avoided as it may lead to blindness in LHON patients.Avoiding optic nerve toxins is generally advised, especially tobacco and alcohol. Certain prescription drugs are potential risks, so all drugs should be treated with suspicion and checked before use by those at risk. Ethambutol, in particular, has been implicated as triggering visual loss in carriers of LHON. In fact, toxic and nutritional optic neuropathies may have overlaps with LHON in symptoms, mitochondrial mechanisms of disease and management. And when a patient with LHON or toxic/nutritional optic neuropathy has a hypertensive crisis as a possible complication of the disease process, nitroprusside (trade name: Nipride) should not be used, due to increased risk of optic nerve ischemia in response to this anti-hypertensive.Idebenone has been shown in a small placebo-controlled trial to have modest benefit in about half of patients. People most likely to respond best were those treated early in onset.
α-Tocotrienol-quinone, a vitamin E metabolite, has had some success in small open-label trials in reversing early onset vision loss.Various treatment approaches have had early trials or been proposed, but so far none with convincing evidence of usefulness or safety for treatment or prevention, including brimonidine, minocycline, curcumin, glutathione, near infrared light treatment, and viral vector techniques."Three person in vitro fertilization" is a proof-of-concept research technique for preventing mitochondrial disease in developing human fetuses. So far, viable macaque monkeys have been produced. But ethical and knowledge hurdles remain before use of the technique in humans is established.
Idebenone
Idebenone is a short-chain benzoquinone that interacts with the mitochondrial electron transport chain to enhance cellular respiration. When used in people with LHON, it is believed to allow electrons to bypass the dysfunctional complex I. Successful treatment with idebenone was initially reported in a small number of patients.Two large-scale studies have demonstrated the benefits of idebenone. The Rescue of Hereditary Optic Disease Outpatient Study (RHODOS) evaluated the effects of idebenone in 85 patients with LHON who had lost vision within the prior five years. In this study, the group taking idebenone 900 mg per day for 24 weeks showed a slight improvement in visual acuity compared to the placebo group, though the difference was not statistically significant. But patients taking idebenone were protected from further vision loss, whereas the placebo group had a steady decline in visual acuity. Further, people taking idebenone demonstrated preservation of color vision and persistence of the effects of idebenone 30 months after discontinuing therapy. A retrospective analysis of 103 LHON patients by Carelli et al. builds upon these results. This study highlighted that 44 subjects who were treated with idebenone within one year of onset of vision loss had better outcomes, and that these improvements persisted for years.Idebenone, combined with avoidance of smoke and limitation of alcohol intake, is the preferred treatment protocol for people with LHON. Idebenone doses are prescribed to be taken spaced out throughout the day, rather than all at once. For example, to achieve a dose of 900 mg per day, patients take 300 mg three times daily with meals. Idebenone is fat-soluble, and may be taken with a moderate amount of dietary fat in each meal to promote absorption. It is recommended that patients on idebenone also take vitamin C 500 mg daily to keep idebenone in its reduced form, as it is most active in this state.
Estrogen Replacement Therapy
Estrogens have been shown to have a protective role in the pathogenesis of LHON. Experiments using LHON cybrids have demonstrated that the estrogen receptor localizes to the mitochondria where it directly mediates mitochondrial biogenesis. Estrogens upregulate the antioxidant enzyme superoxide dismutase 2 and mitochondrial DNA synthesis. These experiments helped to explain the mechanism behind the lower penetrance of disease among female carriers. While additional factors have been theorized, the protective role of estrogens appears to be a significant contributor.In addition to the experimental evidence, clinical data also points towards the protective role of estrogens. Penetrance among female carriers is substantially lower (between 3 and 8 to 1 male to female ratios depending on the mutation) while average age at onset is significantly higher. Multiple case series of various LHON pedigrees have described female carriers converting after menopause or cessation of hormone replacement therapies. Together, these form a shifting paradigm towards considering reduced estrogen states, such as menopause, as potential triggers of visual loss similar to smoking or excessive alcohol consumption.
Hormone replacement therapy (HRT) is emerging as an effective therapeutic target for female mutation carriers. In one recent case study where the affected female converted following cessation of HRT, idebenone, and HRT were given together. Visual acuity improved much faster than is typically expected. The patients vision returned to 20/40 and 20/60 from 20/60 and 20/200 in the right and left eyes respectively after only one month and was back normal by 8 months compared to the months to years timeframe seen in most cases. While the balance between risks and benefits of HRT remains controversial, the decision to start HRT requires an individualized approach based on the patients context. While not applicable for all post-menopausal women, prophylactic (and therapeutic) HRT should be considered in all female carriers of a known LHON mutation given the substantial risk of vision loss associated with menopause.
Epidemiology
In Northern European populations about one in 9,000 people carries one of the three primary LHON mutations. There is a prevalence of between 1:30,000 to 1:50,000 in Europe.
The LHON ND4 G11778A mutation is the primary mutation in most of the world, with 70% of Northern European cases and 90% of Asian cases. Due to a Founder effect, the LHON ND6 T14484C mutation accounts for 86% of LHON cases in Quebec, Canada.More than 50% of males with a mutation and more than 85% of females with a mutation never experience vision loss or related medical problems. The particular mutation type may predict the likelihood of penetrance, severity of illness and probability of vision recovery in the affected. As a rule of thumb, a woman who harbors a homoplasmic primary LHON mutation has a ~40% risk of having an affected son and a ~10% risk of having an affected daughter.Additional factors may determine whether a person develops the signs and symptoms of this disorder. Environmental factors such as smoking and alcohol use may be involved, though studies of these factors have produced conflicting results. Researchers are also investigating whether changes in additional genes, particularly genes on the X chromosome, contribute to the development of signs and symptoms. The degree of heteroplasmy, the percentage of mitochondria that have mutant alleles, may play a role. Patterns of mitochondrial alleles called haplogroup may also affect expression of mutations.
History
LHON was first described by the German ophthalmologist Theodor Leber (1840–1917) in 1871. In a paper, Leber described four families in which a number of young men had abrupt loss of vision in both eyes either simultaneously or sequentially. This disease was initially thought to be X-linked but was subsequently shown to be mitochondrial. The nature of the causative mutation was first identified in 1988 by Wallace et al. who discovered the guanine (G) to adenosine (A) mutation at nucleotide position 11778 in nine families. This mutation converts a highly conserved arginine to histidine at codon 340 in the NADH dehydrogenase subunit 4 of complex I of the mitochondrial respiratory chain. The other two mutations known to cause this condition were identified in 1991 (G to A point mutation at nucleotide position 3460) and 1992 (thymidine (T) to cytosine (C) mutation at nucleotide 14484). These three mutations account for over 95% of cases: the 11778 mutation accounts for 50-70% of cases, the 14484 mutation for 10-15% and the 3460 mutation for 8-25%.
Research
Human clinical trials are underway at GenSight Biologics (ClinicalTrials.gov # NCT02064569) and the University of Miami (ClinicalTrials.gov # NCT02161380) to examine the safety and efficacy of mitochondrial gene therapy in LHON. In these trials, participants affected by LHON with the G11778A mutation will have a virus expressing the functional version of ND4—the gene mutated in this variant of LHON—injected into one eye. A sham injection will be administered to the other eye for comparison. It is hypothesized that introduction of the viral vector may be able to rescue the function of the mutant gene. Preliminary results have demonstrated tolerability of the injections in a small number of subjects.Stealth BioTherapeutics is investigating the use of elamipretide (MTP-131), a mitochondrial protective agent, as a therapy for LHON. Elamipretide helps stabilize cardiolipin—an important component of mitochondrial inner membranes—and has been shown to reduce damaging reactive oxygen species in animal models.
See also
Amaurosis
Dominant optic atrophy
Glaucoma
Ischemic optic neuropathy
Optic atrophy
Toxic and nutritional optic neuropathy
References
Further reading
Lebers hereditary optic neuropathy at NLM Genetics Home Reference
Kerrison JB, Newman NJ (1997). "Clinical spectrum of Lebers hereditary optic neuropathy" (IFOND reprints). Clin. Neurosci. 4 (5): 295–301. PMID 9292259.
Carelli V, Ross-Cisneros FN, Sadun AA (January 2004). "Mitochondrial dysfunction as a cause of optic neuropathies". Prog Retin Eye Res. 23 (1): 53–89. doi:10.1016/j.preteyeres.2003.10.003. PMID 14766317. S2CID 15862778.
External links
NCBI Genetic Testing Registry |
Membranoproliferative glomerulonephritis | Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane (GBM) thickening, activating complement and damaging the glomeruli.
MPGN accounts for approximately 4% of primary renal causes of nephrotic syndrome in children and 7% in adults.It should not be confused with membranous glomerulonephritis, a condition in which the basement membrane is thickened, but the mesangium is not.
Type
There are three types of MPGN, but this classification is becoming obsolete as the causes of this pattern are becoming understood.
Type I
Type I, the most common by far, is caused by immune complexes depositing in the kidney. It is characterised by subendothelial and mesangial immune deposits.
It is believed to be associated with the classical complement pathway.
Type II
Also called recently as ‘C3 nephropathy’
The preferred name is "dense deposit disease." Most cases of dense deposit disease do not show a membranoproliferative pattern. A 2012 review considers DDD to be in a continuum with C3 glomerulonephritis, one reason the use of the type I to type III classification system is falling out of favour.Most cases are associated with the dysregulation of the alternative complement pathway.DDD is associated with deposition of complement C3 within the glomeruli with little or no staining for immunoglobulin. The presence of C3 without significant immunoglobulin suggested to early investigators that DDD was due to abnormal activation of the complement alternative pathway (AP). There is now strong evidence that DDD is caused by uncontrolled AP activation.Spontaneous remissions of MPGN II are rare; approximately half of those affected with MPGN II will progress to end stage renal disease within ten years.In many cases, people with MPGN II can develop drusen caused by deposits within Bruchs membrane beneath the retinal pigment epithelium of the eye. Over time, vision can deteriorate, and subretinal neovascular membranes, macular detachment, and central serous retinopathy can develop.
Type III
Type III is very rare, it is characterized by a mixture of subepithelial and subendothelial immune and/or complement deposits. These deposits elicit an immune response, causing damage to cells and structures within their vicinity. Has similar pathological findings of Type I disease.A candidate gene has been identified on chromosome 1.Complement component 3 is seen under immunofluorescence. it is associated with complement receptor 6 deficiency.
Pathology
Membranoproliferative glomerulonephritis involves deposits at the intraglomerular mesangium.
It is also the main hepatitis C associated nephropathy.
It also is related to a number of autoimmune diseases, prominently systemic lupus erythematosus (SLE), Class IV. Also found with Sjögren syndrome, rheumatoid arthritis, inherited complement deficiencies (esp C3 deficiency), scleroderma, Celiac disease.The histomorphologic differential diagnosis includes transplant glomerulopathy and thrombotic microangiopathies.
Diagnosis
The GBM is rebuilt on top of the deposits, causing a "tram tracking" appearance under the microscope. Mesangial cellularity is increased.
Treatment
Primary MPGN is treated with steroids, plasma exchange and other immunosuppressive drugs.
Secondary MPGN is treated by treating the associated infection, autoimmune disease or neoplasms. Pegylated interferon and ribavirin are useful in reducing viral load.
See also
Diffuse proliferative nephritis
References
External links
Glomerulonephritis, Membranoproliferative Types I, II, III at eMedicine
Corchado, Johnny Cruz, Smith, Richard JH (July 2007). "Dense Deposit Disease/Membranoproliferative Glomerulonephritis Type II". In Pagon RA, Bird TD, Dolan CR, et al. (eds.). GeneReviews. Seattle WA: University of Washington. PMID 20301598.
Membranoproliferative_GN at Nephropathology tutorial
MP GN Pathophysiology discusses the nephritic auto-antibodies/factors |
Cholinergic urticaria | Cholinergic urticaria (CU) presents with tiny very itchy wheals and small bumps on a reddish background.It is a type of physical urticaria (or hives) that appears when a person is sweating or their core body temperature increases.
Symptoms
Cholinergic urticaria typically presents with a number of small, short-lasting hives but may also involve cutaneous inflammation (wheals) and pain which develops usually in response to exercise, bathing, staying in a heated environment, or emotional stress. Although the symptoms subside rapidly, commonly within 1 hour, cholinergic urticaria may significantly impair quality of life, especially in relation to sporting activities.
Causes
Sweat hypersensitivity
Acquired anhidrosis and/or hypohidrosis
Idiopathic
Opioid use
Cholinesterase inhibitors
Subtypes
Sweat hypersensitivity
This subtype of CU refers to those who are hypersensitive to their own sweat.
Diagnosis
Diagnosis is made by injecting autologous (the persons own) sweat into the skin.
Features
The hives are observed to coincide with perspiration points of sweating.
Pathophysiology
Tanaka et al. found that the sweat hyper-sensitivities of CU and atopic dermatitis seem to be virtually the same, and therefore, the sweat-induced histamine release from basophils may also be mediated by a specific IgE for sweat in atopic dermatitis as well as CU.
Treatment
Proposed first-line treatment: Rapid desensitization protocol using autologous sweat.
Non-pharmacological treatment: Forced perspiration by excessive body warming (hot bath or exercise) used daily may reduce the symptoms through exhaustion of inflammatory mediators. This non-pharmacological treatment is contraindicated in those with CU as a result of hypohidrosis (see below).
Antihistamines are a commonly prescribed first-line treatment for conventional urticaria, but its effectiveness in the treatment of CU is rather limited in most cases. Some research suggests that first-generation antihistamines with anticholinergic properties such as diphenhydramine are most successful at treating CU.
Treatment(s) with mixed success: omalizumab (anti-IgE therapy), danazol (synthetic androgen), propranolol (beta blocker), zileuton (antileukotriene).
Acquired anhidrosis and/or hypohidrosis
This subtype of CU refers to those who have abnormally reduced sweating.
Diagnosis
Sweat is readily visualized by a topical indicator such as iodinated starch or sodium alizarin sulphonate. Both undergo a dramatic colour change when moistened by sweat. A thermoregulatory sweat test evaluates the bodys response to a thermal stimulus by inducing sweating through the use of a hot box ⁄ room, thermal blanket or exercise. Failure of the topical indicator to undergo a colour change during thermoregulatory sweat testing can indicate anhidrosis and/or hypohidrosis (see Minor test).A skin biopsy may reveal cellular infiltrates in sweat glands or ducts.
Features
Severe heat intolerance (e.g., nausea, dizziness, and headache), and tingling, pricking, pinchy or burning pain over the entire body on exposure to hot environments or prolonged exercise which improve after cooling the body. Occurs in the absence of any causative skin, metabolic, or neurological disorders.
Pathophysiology
The wheals, hypohidrosis, and pain seems to result from the low expression levels of acetylcholinesterase (AchE) and cholinergic receptor, muscarinic 3 (CHRM3) in the eccrine gland epithelial cells.
Elevated expression levels of CCL2/MCP-1, CCL5/RANTES and CCL17/TARC which result in chemoattracted CD4+ and CD8+ T cell populations to the surrounding area may be responsible for exerting a downmodulatory effect on the AchE and CHRM3 expressions.
Corticosteroid inhibits the expressions of CCL2/MCP-1, CCL5/RANTES and CCL17/TARC. This further support the notion that CCL2/MCP-1, CCL5/RANTES and CCL17/TARC play a crucial role.
Treatment
First-line treatment: H1RAs are first-line therapy for patients with CholU, but many patients show only a mild to moderate response to standard H1RA doses. The addition of an H2RA was reported to be effective in patients with refractory CholU that was unresponsive to up-dosing of an H1RA. Other studies have demonstrated the efficacy of scopolamine butylbromide (an anticholinergic agent); combinations of propranolol (a b2-adrenergic blocker), antihistamines, and montelukast; and treatment and injection with botulinum toxin.
Non-pharmacological treatment: In the absence of sweat, cold-water sprays and wet towels can be used to increase the evaporative loss of heat from the skin. Shifting to a cooler or air-conditioned environments when necessary can also reduce discomfort. In the event of severe hyperthermia (body temperature >106 °F/41 °C), drastic measures such as immersion in ice-cold water are necessary to prevent irreversible brain damage.
Idiopathic
Unknown or unclassified at this time. This represents those who do not fall under any of the above categories.
Prevalence
Though overall research is limited, various studies indicate that CU is relatively common across populations with prevalence rates reportedly ranging from 5% to 20% (depending on locale, race, and age). The condition is more common in young adults, and prevalence appears to peak in adults aged 26–28 (up to 20%). The vast majority of cases are reported to be mild, and proportionally few individuals seek medical attention regarding the condition.
History
Cholinergic urticaria was first described by Duke in 1924 as "urticaria calorica". The term cholinergic is derived from the finding that hives similar to those of CU can be evoked using cholinergic agonists (e.g. methacholine).
See also
Miliaria
Exercise-induced anaphylaxis
Idiopathic pure sudomotor failure
Hypohidrosis
Fabry disease
Aquagenic urticaria
References
== External links == |
Lichen ruber moniliformis | Lichen ruber moniliformis is a rare skin disease named for Fred Wise and Charles R. Rein.It is one of several diseases also known as Kaposis disease, based on its characterization in 1886 by Moritz Kaposi.It is thought to be a rare variety of lichen planus.It is also known as "Morbus moniliformis lichenoides".
Presentation
The disease causes numerous whitish punctiform papules and brownish macules arranged in a necklace-like pattern.
Diagnosis
Treatment
See also
Lichen planus
List of cutaneous conditions
References
== External links == |
Neurogenic shock | Neurogenic shock is a distributive type of shock resulting in hypotension (low blood pressure), often with bradycardia (slowed heart rate), caused by disruption of autonomic nervous system pathways. It can occur after damage to the central nervous system, such as spinal cord injury and traumatic brain injury. Low blood pressure occurs due to decreased systemic vascular resistance resulting from loss of sympathetic tone, which in turn causes blood pooling within the extremities rather than being available to circulate throughout the body. The slowed heart rate results from a vagal response unopposed by a sympathetic nervous system (SNS) response. Such cardiovascular instability is exacerbated by hypoxia, or treatment with endotracheal or endobronchial suction used to prevent pulmonary aspiration.Neurogenic shock is a potentially devastating complication, leading to organ dysfunction and death if not promptly recognized and treated.It is not to be confused with spinal shock, which is not circulatory in nature.
Signs and symptoms
Instantaneous hypotension due to sudden, massive vasodilation and decrease in blood oxygen saturation
Warm, flushed skin due to vasodilation and inability to constrict blood vessels.
Priapism, also due to vasodilation
The patient will be unable to mount a tachycardic response, and often becomes bradycardic
If the injury is below cervical vertebrae C5, the patient will exhibit diaphragmatic breathing due to loss of nervous control of the intercostal muscles (which are required for thoracic breathing).
If the injury is above C3, the patient will go into respiratory arrest immediately following the injury, due to loss of nervous control of the diaphragm.
Causes
Neurogenic shock can result from severe central nervous system damage (brain injury, cervical or high thoracic spinal cord). In simple terms, the trauma causes a sudden loss of background SNS stimulation to the blood vessels. This causes them to relax (vasodilation) resulting in a sudden decrease in blood pressure (secondary to a decrease in peripheral vascular resistance).
Neurogenic shock results from damage to the spinal cord above the level of the 6th thoracic vertebra. It is found in about half of people who have a spinal cord injury within the first 24 hours, and usually persists for one to three weeks.Neurogenic shock may be caused by severe brain injury. However, in case of increased intracranial pressure, according to the Cushing triad, blood pressure will be increased (unless decreased from hypovolemia), respirations will be irregular and bradycardia will also be a feature.
Pathophysiology
Neurogenic shock is diagnosed based on a persons symptoms and blood pressure levels.
Neurogenic shocks presentation includes:- warm and pink skin
- labored breathing
- low blood pressure
- dizziness
- anxiety
- history of trauma to head or upper spine.
- if the injury is to the head or neck, hoarseness or difficulty swallowing may occur.
Symptoms of neurogenic shock are differentiated from other forms of shock by the lack of signs of the compensatory mechanisms triggered by the SNS, usual in other forms of shock. This SNS response is effected via release of epinephrine and norepinephrine, and signs of these neurotransmitters activity are typically absent where shock is of neurogenic origin. Those signs - in non-neurogenic shock - would include: tachycardia (increased heart rate), tachypnea (increased breath rate), sweating, and adaptive vasoconstriction, which serves in other forms of shock to shunt blood away from the extremities and to the vital organs.
In neurogenic shock, the body loses its ability to activate the SNS so that only parasympathetic tone remains. The resulting loss of sympathetic tone, which plays a major role in other forms of shock, is responsible for the unique and atypical features mentioned above.<ref name=incidence>Mallek JT; Inaba K; et al. (2012). "The Incidence of Neurogenic Shock after Spinal Cord Injury in Patients Admitted to a High-Volume Level I Trauma Center". The American Surgeon. 78 (5): 623–626. doi:10.1177/000313481207800551. PMID 22546142. S2CID 12758597.</ref>
Treatment
Dopamine (Intropin) is often used in combination with other vasopressors. Dopamine is not the best first-line vasopressor as it increases the chance of arrhythmias.
Vasopressin (antidiuretic hormone, ADH) is another vasopressor often used in combination with norepinephrine
Certain vasopressors (ephedrine, norepinephrine). Norepinephrine(Levophed) is the most common first-line vasopressor for people who dont respond well to other hypotension treatments such as fluid resuscitation.
Atropine is administered for bradycardia. It acts on the vagus nerve so it its not effective in heart transplant patients as the vagus nerve is severed during the transplant
References
== External links == |
Megalencephalic leukoencephalopathy with subcortical cysts | Megalencephalic leukoencephalopathy with subcortical cysts (MLC, or Van der Knaap disease) is a form of hereditary CNS demyelinating disease. It belongs to a group of disorders called leukodystrophies. It is characterized by early-onset enlargement of the head (macrocephaly) as well as delayed-onset neurological deterioration to include spasticity, epilepsy, and lack of muscular coordination. MLC does not appear to be a disease that is fatal at birth or early in life despite its symptoms, although the number of patients throughout history known to have the disease is fairly limited.It belongs to a group of disorders called leukodystrophies. A series of cases with megalencephalic leukodystrophy were described by the Indian neurologist Bhim Sen Singhal (1933-) in 1991. However, it is sometimes referred to as Van der Knaap disease after the Dutch neurologist Marjo van der Knaap who described another series of cases with clinical and radiological features in 1995.There are three types of Megalencephalic leukoencephalopathy distinguished by the affected gene: Type 1 caused by autosomal recessive mutations on the MLC1 gene, Type 2A an autosomal recessive mutation on the HEPACAM gene, and Type 2B an autosomal dominant mutation on the HEPACAM gene.
Signs and Symptoms
Head
Macrocephaly
The disease is characterized by megalencephaly, the enlargement of the brain, which is followed by an increase in the size of the actual head.
Central Nervous System
Megalencephaly
The M in MLC stands for “megalencephaly”, the enlargement of the brain
Ataxia
Slow, progressive and early-onset cerebellar ataxia has been noted in many patients
Spasticity
Patients with MLC often have muscle spasms
Seizures
Delay in motor development
Mild mental retardation
Diffuse swelling of cerebral white matter
Large subcortical cysts in frontal and temporal lobes
Patients develop cysts on the tips of the temporal and subcortical area
Diffuse spongiform leukoencephalopathy
Vacuolizing myelinopathy
The protective myelin sheath on neurons pulls away from their cells forming small holes in nerve fibers – in turn affecting coordination and walking ability.
Genetics
It is associated with MLC1. The MLC1 gene is located in chromosome 22q13.33 and is in the genomic coordinates 22:50,059,390 – 50,085874. The gene contains 12 exons and that contain a start codon in exon 2 and an untranslated region in the 3’ end. The MLC1 gene product is a 377 amino acid protein highly expressed in the brain. The disease is caused by a homozygous or compound heterozygous mutation in the gene, MLC1. Previous research indicates that deficiency of cell surface protein expression of the MLC1 gene is the basis for the disorder. The mutant protein is expressed in intracellular compartments reducing the membrane surface expression when compared to the wild type.
Diagnosis
Diagnosis of Megalencephalic leukoencephalopathy with subcortical cysts is made with a combination of physical and clinical evaluations. The presence of frontal and temporal subcortical cysts is the main factor when diagnosing a patient with this disease. In the late stages of the disease, patients have been noted to develop impaired coordination, overresponsive reflexes, and even seizures. MRI testing is used to study and diagnose patients with this disease. A study conducted on four patients with this disease yielded similar MRI results despite their slightly differing symptoms. Genetic testing can show whether or not the individual has a mutation in the MLC1 gene, which accounts for 75% of all cases.
Management
There currently is not a known cure for this disease. However, there are treatment options to mitigate the effects of symptoms that come with this disease. The drug Carbamazepine is an anticonvulsant drug commonly used to treat seizures and nerve pain. A case with a 5-year-old girl indicated the ability of this drug to reduce the effects of seizures linked to this disease.
Epidemiology
Most of the cases were studied in Turkish families who were part of consanguineous marriages (getting married to relatives or the “same blood”). Nonetheless, Megalencephalic leukoencephalopathy with subcortical cysts does not show genetic heterogeneity which means that there are no mutations in other loci expressing similar phenotypes.
History
A series of cases with megalencephalic leukodystrophy were described by the Indian neurologist Bhim Sen Singhal (1933-)in 1991. However, it is sometimes referred to as Van der Knaap disease after the Dutch neurologist Marjo van der Knaap who described another series of cases with clinical and radiological features in 1995.
References
External links
GeneReview/NIH/UW entry on Megalencephalic Leukoencephalopathy with Subcortical Cysts |
Pilotto syndrome | Pilotto syndrome is a rare syndrome which affects the face, heart, and back. The syndrome can cause a cleft lip and palate, scoliosis, and mental retardation. The Office of Rare Diseases and National Institutes of Health have classified this syndrome as affecting less than 200,000 people in the United States.
References
== External links == |
Sphingolipidoses | Sphingolipidoses are a class of lipid storage disorders or degenerative storage disorders caused by deficiency of an enzyme that is required for the catabolism of lipids that contain ceramide, also relating to sphingolipid metabolism. The main members of this group are Niemann–Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay–Sachs disease and metachromatic leukodystrophy. They are generally inherited in an autosomal recessive fashion, but notably Fabry disease is X-linked recessive. Taken together, sphingolipidoses have an incidence of approximately 1 in 10,000, but substantially more in certain populations such as Ashkenazi Jews. Enzyme replacement therapy is available to treat mainly Fabry disease and Gaucher disease, and people with these types of sphingolipidoses may live well into adulthood. The other types are generally fatal by age 1 to 5 years for infantile forms, but progression may be mild for juvenile- or adult-onset forms.
Accumulated products
Gangliosides: Gangliosidosis
GM1 gangliosidoses
GM2 gangliosidoses
Tay–Sachs disease
Sandhoff disease
GM2-gangliosidosis, AB variant
Glycolipids
Fabrys disease
Krabbe disease
Metachromatic leukodystrophy
Glucocerebrosides
Gauchers disease
Comparison
Metabolic pathways
See also
Lipid storage disorder
References
External links
Sphingolipidoses at the US National Library of Medicine Medical Subject Headings (MeSH) |
Wasting | In medicine, wasting, also known as wasting syndrome, refers to the process by which a debilitating disease causes muscle and fat tissue to "waste" away. Wasting is sometimes referred to as "acute malnutrition" because it is believed that episodes of wasting have a short duration, in contrast to stunting, which is regarded as chronic malnutrition. An estimated 45 million children under 5 years of age (or 6.7%) were wasted in 2021.: 4 Prevalence is highest in Southern Asia, followed by Oceania (excluding Australia and New Zealand) and South-eastern Asia.: 14
Causes
Wasting can be caused by an extremely low energy intake (e.g., caused by famine), nutrient losses due to infection, or a combination of low intake and high loss. Infections and conditions associated with wasting include tuberculosis, chronic diarrhea, AIDS, and superior mesenteric artery syndrome. The mechanism may involve cachectin – also called tumor necrosis factor, a macrophage-secreted cytokine. Caretakers and health providers can sometimes contribute to wasting if the patient is placed on an improper diet. Voluntary weight loss and eating disorders are excluded as causes of wasting.
Classification
Children: Weight-for-height (WFH). In infants under 24 months, recumbent (supine) length is used. WFH as % of median reference value is calculated this way:
W
F
H
=
weight of a given child
median weight for a given child of that height
×
100
{\displaystyle \mathrm {WFH} ={\frac {\mbox{weight of a given child}}{\mbox{median weight for a given child of that height}}}\times 100}
Cutoff points may vary, but <80% (close to −2 Z-score) is often used.
Adults:
Body Mass Index (BMI) is the quotient between weight and height squared (kg/m2). An individual with a BMI < 18.5 is regarded as a case of wasting.
Percent of body weight lost (At Tufts, an unintentional loss of 6% or more in 6 months is regarded as wasting)
Treatment and prevention
Antiretrovirals and anabolic steroids have been used to treat HIV wasting syndrome. Additionally, an increase in protein-rich foods such as peanut butter and legumes (dried beans and peas) can assist in controlling the loss of muscle mass.
See also
Anorexia
Atrophy
Cachexia
Superior mesenteric artery syndrome
Weight loss
References
External links
Chronic Wasting Disease and Potential Transmission to Humans, Center for Disease Control and Prevention
Unintentional Weight Loss/Wasting, Tufts University Nutrition/Infection Unit |
Seal finger | Seal finger, also known as sealers finger and spekkfinger (from the Norwegian for "blubber"), is an infection that afflicts the fingers of seal hunters and other people who handle seals, as a result of bites or contact with exposed seal bones; it has also been contracted by exposure to untreated seal pelts. The State of Alaska Section of Epidemiology defines it as "a finger infection associated with bites, cuts, or scratches contaminated by the mouths, blood, or blubber of certain marine mammals".It can cause cellulitis, joint inflammation, and swelling of the bone marrow; untreated, the course of "seal finger" is slow and results often in thickened contracted joint. Historically, seal finger was treated by amputation of the affected digits once they became unusable. It was first described scientifically in 1907.The precise nature of the organism responsible for seal finger is unknown, as it has resisted culturing because most cases are promptly treated with antibiotics; however, as seal finger can be treated with tetracycline or similar antibiotics, the causative organism is most likely bacterial, or possibly fungal; in 1998, Baker, Ruoff, and Madoff showed that the organism is most likely a species of Mycoplasma called Mycoplasma phocacerebrale. This Mycoplasma was isolated in an epidemic of seal disease occurring in the Baltic Sea.
Notes
External links
Working with Marine Mammals and Your Health, NOAA brochure on zoonoses, including seal finger. (requires Acrobat Reader (via archive.org)) |
Palindromic rheumatism | Palindromic rheumatism (PR) is a syndrome characterised by recurrent, self-resolving inflammatory attacks in and around the joints, consists of arthritis or periarticular soft tissue inflammation. The course is often acute onset, with sudden and rapidly developing attacks or flares. There is pain, redness, swelling, and disability of one or multiple joints. The interval between recurrent palindromic attacks and the length of an attack is extremely variable from few hours to days. Attacks may become more frequent with time but there is no joint damage after attacks. It is thought to be an autoimmune disease, possibly an abortive form of rheumatoid arthritis.
Presentation
The exact prevalence of palindromic rheumatism in general population is unknown, and this condition is often considered a rare disease by nonrheumatologists. However, recent Canadian study showed that the incidence of PR in a cohort of incident arthritis was one case of PR for every 1.8 cases of rheumatoid arthritis (RA). The incidence of PR is less than that of RA but is not as rare as that was thought to be.
Palindromic rheumatism is a syndrome presented with inflammatory para-arthritis (soft tissue rheumatism) and inflammatory arthritis both of which cause sudden inflammation in one or several joints or soft tissue around joints. The flares usually present with mono- or oligo-articular involvement, which have onset over hours and last a few hours to a few days, and then go away completely. However episodes of recurrence form a pattern, with symptom-free periods between attacks lasting for weeks to months. The most commonly involved joints were knees, metacarpophalangeals and proximal interphalangeals. Constitutionally, there may or may not be a fever, and swelling of the joints. The soft tissues are involved with swelling of the periarticular tissues, especially heel pads and finger pads. Nodules may be found in the subcutaneous tissues. The frequency of attacks may be variable over the course but there is no joint damage after attacks.It typically affects people between the ages of 20 and 50. One study showed an average age of onset of 49.A population cohort study in Taiwan suggested that patients with PR had an increased risk of developing rheumatoid arthritis, systemic lupus erythematosus, Sjogrens syndrome, systemic sclerosis, and polymyositis.
Causes
Palindromic rheumatism is a disease of unknown cause. It has been suggested that it is an abortive form of rheumatoid arthritis (RA), since anti-cyclic citrullinated peptide antibodies (anti-CCP) and antikeratin antibodies (AKA) are present in a high proportion of patients, as is the case in rheumatoid arthritis. Unlike RA and some other forms of arthritis, palindromic rheumatism affects men and women equally. Palindromic rheumatism is frequently the presentation for Whipple disease which is caused by the infectious agent Tropheryma whipplei (formerly T. whippelii).
Diagnosis
Due to the symptoms of palindromic arthritis and the nature of the attacks, diagnosis can be difficult or take a long time. The symptoms can be similar to many other forms of arthritis or other autoimmune diseases. It is often a case of eliminating the other conditions before getting the correct diagnosis due to there being no specific test for PR diagnosis.
No single test can confirm a diagnosis. A doctor may make a diagnosis based on medical history and signs and symptoms. Palindromic rheumatism must be distinguished from acute gouty arthritis and an atypical, acute onset of rheumatoid arthritis (RA). Without specific tests (such as analysis of joint fluid), it may be difficult to distinguish palindromic rheumatism from other episodic joint problems. It is important to note that a person may experience more than one autoimmune disorder at the same time, as overlap syndrome. Laboratory findings are usually normal. Blood tests may show an elevation of the ESR and CRP, but are otherwise unremarkable. Rheumatoid factor may be present especially in the group that is likely to develop rheumatoid arthritis.
Proposed classification by Guerne and Weismann in 1992:
A 6-month history of brief sudden-onset and recurrent episodes of monoarthritis or rarely polyarthritis or of soft tissue inflammation.
Direct observation of one attack by a physician.
Three or more joints involved in different attacks.
No radiologic evidence of bone or joint erosion.
Exclusion of other arthritides, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or gout
Management
Treatment may include nonsteroidal anti-inflammatory drugs (NSAIDs) for acute attacks. Antimalarials, such as hydroxychloroquine, have been helpful in reducing the frequency and duration of attacks and may reduce the likelihood that palindromic rheumatism will progress to rheumatoid arthritis.
Etymology
Palindromic rheumatism derives its name from the Greek palindromos meaning to take the same road once again (palin, again + dromos, pathway) emphasizing how the illness begins and ends in a similar way. The term "palindrome" means a word that is spelled the same forward as backward (examples include "kayak" and "mum").
References
== External links == |
Craniometaphyseal dysplasia | Craniometaphyseal dysplasia is a rare skeletal disorder that results from a mutation in the ANKH or GJA1 genes. The condition is characterized abnormal facial features, impairment of cranial nerves, and malformation of the long bones in the limbs.
Signs and symptoms
Signs and symptoms include:
syndromic facies
hearing loss
facial paralysis
Genetics
The autosomal dominant form is caused by a mutation in ANKH on chromosome 5 (5p15.2-p14.1). The autosomal recessive form is caused by a mutation in a mutation in GJA1 on chromosome 6 (6q21-q22). The recessive form tends to be more severe than the dominant form.
Diagnosis
Craniometaphyseal dysplasia is diagnosed based on clinical and radiographic findings that include hyperostosis. Some things such as cranial base sclerosis and nasal sinuses obstruction can be seen during the beginning of the childs life. In radiographic findings the most common thing that will be found is the narrowing of foramen magnum and the widening of long bones. Once spotted treatment is soon suggested to prevent further compression of the foramen magnum and disabling conditions.
Treatment
The only treatment for this disorder is surgery to reduce the compression of cranial nerves and spinal cord. However, bone regrowth is common since the surgical procedure can be technically difficult. Genetic counseling is offered to the families of the people with this disorder.
References
== External links == |
Lymphocytic choriomeningitis | Lymphocytic choriomeningitis (LCM) is a rodent-borne viral infectious disease that presents as aseptic meningitis, encephalitis or meningoencephalitis. Its causative agent is lymphocytic choriomeningitis mammarenavirus (LCMV), a member of the family Arenaviridae. The name was coined by Charles Armstrong in 1934.Lymphocytic choriomeningitis (LCM) is "a viral infection of the membranes surrounding the brain and spinal cord and of the cerebrospinal fluid". The name is based on the tendency of an individual to have abnormally high levels of lymphocytes during infection. Choriomeningitis is "cerebral meningitis in which there is marked cellular infiltration of the meninges, often with a lymphocytic infiltration of the choroid plexuses".
Signs and symptoms
LCMV infection manifests itself in a wide range of clinical symptoms, and may even be asymptomatic for immunocompetent individuals. Onset typically occurs between one or two weeks after exposure to the virus and is followed by a biphasic febrile illness. During the initial or prodromal phase, which may last up to a week, common symptoms include fever, lack of appetite, headache, muscle aches, malaise, nausea, and/or vomiting. Less frequent symptoms include a sore throat and cough, as well as joint, chest, and parotid pain. The onset of the second phase occurs several days after recovery, and consists of symptoms of meningitis or encephalitis. Pathological findings during the first stage consist of leukopenia and thrombocytopenia. During the second phase, typical findings include elevated protein levels, increased leukocyte count, or a decrease in glucose levels of the cerebrospinal fluid).Occasionally, a patient improves for a few days, then relapses with aseptic meningitis, or very rarely, meningoencephalitis.
Patients with meningitis may have a stiff neck, fever, headache, myalgia, nausea and malaise. In some occasions, meningitis occurs without a prodromal syndrome. Meningoencephalitis is characterized by more profound neurological signs such as confusion, drowsiness, sensory abnormalities and motor signs. Under reported complications include myelitis, Guillain–Barré-type syndrome, cranial nerve palsies, transient or permanent hydrocephalus, sensorineural hearing loss, orchitis, arthritis and parotitis. LCMV infections have also been associated with pancreatitis, pneumonitis, myocarditis and pericarditis. The entire illness usually lasts 1 to 3 weeks, nonetheless, temporary or permanent neurological damage is possible in all central nervous system infections, especially in cases of meningoencephalitis. Chronic infections have not been reported in humans and deaths rarely occur.
Cause
Virus biology
There are several strains of LCM virus, among which the most widely used are LCMV Armstrong and LCMV Clone 13. Armstrong is the original virus strain which was isolated from the brain by Charles Armstrong in 1934. It triggers a vigorous cytotoxic T lymphocytes(CTL) response and thus, it is cleared rapidly by the host. This is referred to as acute (Armstrong) LCMV infection. On the other hand, Clone 13 is a variant of the Armstrong viral strain, isolated from the spleen and is consequently tropic for visceral organs. It was first isolated from mice which sustained a persistent LCMV infection from birth. This variant potentiates a less vigorous CTL response in the immune system, and thus can ultimately persist in the host organism indefinitely. The latter is referred to as chronic (Clone 13) LCMV infection.LCMV is a spherical enveloped virus with a diameter between 60 and 300 nm. The helical nucleocapsid contains an RNA genome consisting of two negative single-stranded RNA segments. The negative RNA strand, complementary to the necessary mRNA strand, indicates that it must first be transcribed into a positive mRNA strand before it can be translated into the required proteins. The L strand is ambisense RNA, encoding multiple proteins in opposite directions, separated by an intergenic region. It is approximately 7.2 kb in size and encodes a high-molecular-mass protein (L; 200 kDa) and an 11 kDa small polypeptide Z with unknown function and a ring finger motif. The viral RNA-dependent RNA polymerase is encoded by the L protein which contains conserved characteristic motifs throughout all the RNA-dependent, RNA-polymerases. The S strand is ambisense and approximately 3.4 kb in size. It encodes the two main structural proteins: nucleo-protein (NP) (63 kDa) and glycoprotein precursor complex (GPC) (75kDa). The latter undergoes posttranslational cleavage at two separate steps: first in the endoplasmic reticulum, where following translation on the membrane, the stable signal peptide region is cleaved by signal peptidase (SPase); notably, this signal peptide is retained, in contrast to other viruses. The second cleavage occurs at the Golgi apparatus, where GP1-GP2, having been trafficked to the Golgi, is cleaved into separate mature viral glycoproteins, GP1 and GP2 (with cleavage mediated by SK1-/PS1 or MTBPS1). The spikes present on the virion envelope are dictated by tetramer formation of GP-1 and GP-2.When LCMV attacks a cell, the process of replication starts by attachment of the virus to host receptors through its surface glycoproteins. It is then endocytosed into a vesicle inside the host cell and creates a fusion of the virus and vesicle membranes. The ribonucleocapsid is then released in the cytoplasm. The RNA-dependent, RNA-polymerase brought along with the virus initially binds to a promoter on the L and S segments and begins transcription from negative-stranded to a positive-stranded mRNA. The formation of a strong hairpin sequence at the end of each gene terminates transcription. The mRNA strands are capped by the RNA-dependent, RNA-polymerase in the cytoplasm and are then subsequently translated into the four proteins essential for LCMV assembly. The ribonucleocapsid interacts with the Z matrix protein and buds on the cell membrane, releasing the virion out from the infected cell.
The first arenavirus, Lymphocytic choriomeningitis mammarenavirus (LCMV), was isolated in 1933 by Charles Armstrong during a study of an epidemic in St. Louis. Although not the cause of the outbreak, LCMV was found to be a cause of nonbacterial or aseptic meningitis.In 1996, Peter Doherty and Rolf Zinkernagel shared the Nobel Prize in Medicine and Physiology, for their work with LCMV which led to a fundamental understanding of the adaptive immune response, MHC restriction. In the 1970s, studies concerning the importance of MHC locus were done exclusively in transplantation and tumor rejection. Taking this into consideration, Doherty and Zinkernagel were working on the response of mice to virus infections. They observed that T-cell receptors must recognise a complex of foreign antigen and an MHC antigen in order to destroy infected cells. Their key experiment involved harvesting of splenocytes containing LCMV-specific cytotoxic T lymphocytes(CTL) from an infected mouse strain A. These were then mixed in vitro with virus infected fibroblasts or macrophages from two different mouse strains, A and B. By the method of Cr-release cytotoxicity assay, thereby tagging the CTL with chromium-51 (Cr-51), the CTL destruction of infected cells was quantified by release of Cr-51. The results showed that CTL killed only the infected cells from strain A, and they did not lyse uninfected cells or infected cells from strain B. They concluded that these virus specific CTLs only lyse cells carrying the same molecules of the major histocompatibility site (MHC) as the CTLs themselves. Thus, the virus-specific CTLs are "MHC-restricted". This discovery lead to a greater understanding of an important aspect of the immune system.
Spread
LCMV is naturally spread by the common house mouse, Mus musculus. Once infected, these mice can become chronically infected by maintaining virus in their blood or persistently shedding virus in their urine.
Chronically infected female mice usually transmit infection to their offspring (vertical transmission), which in turn become chronically infected. Other modes of mouse-to-mouse transmission include nasal secretions, milk from infected dams, bites, and during social grooming within mouse communities. Airborne transmission also occurs.The virus seems to be relatively resistant to drying and therefore humans can become infected by inhaling infectious aerosolized particles of rodent urine, feces, or saliva, by ingesting food contaminated with virus, by contamination of mucous membranes with infected body fluids, or by directly exposing cuts or other open wounds to virus-infected blood. The only documented cases of transmission from animals have occurred between humans and mice or hamsters.Cases of lymphocytic choriomeningitis have been reported in North and South America, Europe, Australia, and Japan, particularly during the 1900s. However, infection may occur wherever an infected rodent host population exists. LCMV occurs worldwide and its natural host, the rodent, has become established on all continents, except Antarctica.Seroprevalence is approximately 5% (0.7–4.7%) of the US population. It tends to be more common among lower socio-economic groupings, probably reflecting more frequent and direct contacts with mice. However, obtaining an accurate sense of prevalence by geographic region is difficult due to underreporting.
Congenital infection
Lymphocytic choriomeningitis is a particular concern in obstetrics, as vertical transmission is known to occur. For immunocompetent mothers, there is no significant threat, but the virus has damaging effects upon the fetus. If infection occurs during the first trimester, LCMV results in an increased risk of spontaneous abortion. Later congenital infection may lead to malformations such as intracranial calcifications, hydrocephalus, microcephaly or macrocephaly, intellectual disabilities, and seizures. Other findings include chorioretinal scars, and optic atrophy. Chorioretinitis, which is followed by chorioretinal scarring, is the most common ocular lesion. Mortality among infants is approximately 30%. Among the survivors, two-thirds have lasting neurologic abnormalities.Other ocular defects including optic atrophy, microphthalmia, vitreitis, leukokoria and cataracts can also be seen. Most of the infants in one case series were of normal birth weight, although 30% were underweight. Aspiration pneumonia can be a fatal complication. Infants who survive may have severe neurological defects including epilepsy, impaired coordination, visual loss or blindness, spastic diplegia or quadriparesis/quadriplegia, delayed development and intellectual disability. Less severe cases with isolated cerebellar hypoplasia and symptoms of ataxia and jitteriness have been reported occasionally. There have also been rare cases with evidence of chorioretinitis but without neurological signs. Systemic signs seem to be rare, but hepatosplenomegaly, thrombocytopenia and hyperbilirubinemia have been documented in a few cases, and skin blisters were reported in one infant.If a woman has come into contact with a rodent during pregnancy and LCM symptoms are manifested, a blood test is available to determine previous or current infection. A history of infection does not pose a risk for future pregnancies.
Organ donation
Patients infected in solid organ transplants have developed a severe fatal illness, starting within weeks of the transplant. In all reported cases, the initial symptoms included fever, lethargy, anorexia and leukopenia, and quickly progressed to multisystem organ failure, hepatic insufficiency or severe hepatitis, dysfunction of the transplanted organ, coagulopathy, hypoxia, multiple bacteremias and shock. Localized rash and diarrhea were also seen in some patients. Nearly all cases have been fatal.In May 2005, four solid-organ transplant recipients contracted an illness that was later diagnosed as lymphocytic choriomeningitis. All received organs from a common donor, and within a month of transplantation, three of the four recipients had died as a result of the viral infection. Epidemiologic investigation traced the source to a pet hamster that the organ donor had recently purchased from a Rhode Island pet store. Similar cases occurred in Massachusetts in 2008, and Australia in 2013. There is not a LCMV infection test that is approved by the Food and Drug Administration for organ donor screening. The Morbidity and Mortality Weekly Report advises health-care providers to "consider LCMV infection in patients with aseptic meningitis and encephalitis and in organ transplant recipients with unexplained fever, hepatitis, or multisystem organ failure."
Diagnosis
Current or previous infection can be detected through a blood test. However, some authors note that such complement-fixation tests are insensitive and should not be used for diagnosis. Dr. Clare A. Dykewicz, et al. state,
Infection with LCMV should be considered in the differential diagnosis of any compatible, severe viral infection or aseptic meningitis, especially when there is a history of occupational exposure to laboratory rodents. Timeliness of diagnosis is important not only in expediting treatment of infected persons, but also in preventing further LCMV transmission to other workers and animals.Clinical diagnosis of LCM can be made by the history of prodrome symptoms and by considering the period of time before the onset of meningitis symptoms, typically 15–21 days for LCM.Pathological diagnosis of congenital infection is performed using either an immunofluorescent antibody (IFA) test or an enzyme immunoassay to detect specific antibody in blood or cerebrospinal fluid. A PCR assay has been recently developed which may be used in the future for prenatal diagnosis; however, the virus is not always present in the blood or CSF when the affected child is born." Diagnoses is subject to methodological shortcomings in regard to specificity and sensitivity of assays used. For this reason, LCMV may be more common than is realized.Another detection assay is the reverse transcription polymerase chain reaction (RT-PCR) tests which may detect nucleic acids in the blood and cerebrospinal fluid.(CSF) Virus isolation is not used for diagnosis in most cases but it can be isolated from the blood or nasopharyngeal fluid early in the course of the disease, or from CSF in patients with meningitis. LCMV can be grown in a variety of cell lines including BHK21, L and Vero cells, and it may be identified with immuno-fluorescence. A diagnosis can also be made by the intracerebral inoculation of blood or CSF into mice.
Prevention
LCMV is susceptible to most detergents and disinfectants including 1% sodium hypochlorite, 70%
ethanol, 2% glutaraldehyde and formaldehyde. The effectiveness of infection quickly declines below pH 5.5 and above pH 8.5. In addition, LCMV can also be inactivated by heat, ultraviolet light or gamma irradiation.Studies have indicated that human infection of the virus occurs primarily during the fall and winter months, presumably due to the movement of mice indoors. Several measures can be taken to prevent exposure to LCM from wild rodents in the home. A checklist of precautions is provided by the Centers for Disease Control and Prevention, providing tips for sealing the home to keep rodents out, using traps to eliminate existing rodents, and maintaining a clean, healthy home. New technology reflects a growing trend for more humane means of eliminating rodents. Products include devices that emit ultrasonic sound that allegedly irritates mice and drives them away, and more swift, painless means of death such as mini electrocution or gas chambers. However, the traditional snap trap remains an economic and popular option.
Treatment
Treatment is symptomatic and supportive. Children with hydrocephalus often need a ventriculoperitoneal shunt. Nucleoside analog ribavirin is used in some cases due to the inhibitory effect the agent has in vitro on arenaviruses. However, there is not sufficient evidence for efficacy in humans to support routine use. The only survivor of a transplant-associated LCMV infection was treated with ribavirin and simultaneous tapering of the immunosuppressive medications. Early and intravenous ribavirin treatment is required for maximal efficacy, and it can produce considerable side effects. Ribavirin has not been evaluated yet in controlled clinical trials.Use of ribavirin during pregnancy is generally not recommended, as some studies indicate the possibility of teratogenic effects. If aseptic meningitis, encephalitis, or meningoencephalitis develops in consequence to LCMV, hospitalization and supportive treatment may be required. In some circumstances, anti-inflammatory drugs may also be considered. In general, mortality is less than one percent.
Prognosis
Lymphocytic choriomeningitis is not a commonly reported infection in humans, though most infections are mild and are often never diagnosed. Serological surveys suggest that approximately 1–5% of the population in the U.S. and Europe has antibodies to LCMV. The prevalence varies with the living conditions and exposure to mice, and it has been higher in the past due to lower standards of living. The island of Vir in Croatia is one of the biggest described endemic places of origin of LCMV in the world, with IFA testing having found LCMV antibodies in 36% of the population. Individuals with the highest risk of infection are laboratory personnel who handle rodents or infected cells. Temperature and time of year is also a critical factor that contributes to the number of LCMV infections, particularly during fall and winter when mice tend to move indoors. Approximately 10–20% of the cases in immunocompetent individuals are thought to progress to neurological disease, mainly as aseptic meningitis. The overall case fatality rate is less than 1% and people with complications, including meningitis, almost always recover completely. Rare cases of meningoencephalitis have also been reported. More severe disease is likely to occur in people who are immunosuppressed.More than 50 infants with congenital LCMV infection have been reported worldwide. The probability that a woman will become infected after being exposed to rodents, the frequency with which LCMV crosses the placenta, and the likelihood of clinical signs among these infants are still poorly understood. In one study, antibodies to LCMV were detected in 0.8% of normal infants, 2.7% of infants with neurological signs and 30% of infants with hydrocephalus. In Argentina, no congenital LCMV infections were reported among 288 healthy mothers and their infants. However, one study found that two of 95 children in a home for people with severe mental disabilities had been infected with this virus. The prognosis for severely affected infants appears to be poor. In one series, 35% of infants diagnosed with congenital infections had died by the age of 21 months.Transplant-acquired lymphocytic choriomeningitis proves to have a very high morbidity and mortality rate. In the three clusters reported in the U.S. from 2005 to 2010, nine of the ten infected recipients died. One donor had been infected from a recently acquired pet hamster while the sources of the virus in the other cases were unknown.
Epidemiology
LCMV has been isolated from fleas, ticks, cockroaches, Culicoides and Aedes mosquitoes. Ticks, lice and mosquitoes have been shown to transmit this virus mechanically in the laboratory. The presence of LCMV in laboratories may cause serious long-term repercussions to worker safety. In 1989, an outbreak among humans occurred in a US cancer research institute that studied the effects of various therapeutic and diagnostic agents in animal models. Such agents had been developed in the animal care facility, which periodically screened sentinel animals for extraneous infection. Due to an oversight, no sentinel animals were monitored from August 1988 to March 1989. When testing resumed, LCMV antibodies were found in the oldest sentinel hamsters. Several workers reported symptoms consistent with LCMV infection, leading to an investigation. Blood samples were obtained and tested for LCMV antibodies. Of the 82 workers that were tested, seven had definite serologic evidence of past LCMV infection, and two were hospitalized for an acute febrile illness. All seven reported direct contact with the animals at the institute.An additional hazard associated with LCMV in laboratories misleading experimental results. Interference with research may involve:
[Inhibition of] tumor induction due to polyoma virus, and mammary tumor virus in the mouse, and [interference] with transplantable leukaemia in the guinea pig and the mouse. Infection is associated with depression of cellular immunity in the mouse. Rejection of cutaneous grafts or transplantable tumors may be delayed. In addition, infection will increase the sensitivity of the mouse to ectromelia virus and to bacterial endotoxins.Reported outbreaks have decreased, perhaps due to improved biohazard management in laboratories. However, it is possible that sporadic cases have been overlooked because of the wide range of clinical presentations. Clare A. Dykewicz, et al. recommend vigilant screening laboratory animals to be used in research facilities either through serum samples or cell line aliquots, as well as ensuring adequate ventilation in housing areas and use of appropriate sanitation products. Other practices to reduce cross-contamination in rodents include washing hands or changing gloves between animal care activities, thoroughly decontaminating cages before reusing them, and avoiding housing healthy rodents in the vicinity of potentially infected rodents.
Other animals
Although the house mouse (Mus musculus) is the primary reservoir host for LCMV, it is also often found in the wood mouse (Apodemus sylvaticus) and the yellow-necked mouse (Apodemus flavicollis). Hamster populations can act as reservoir hosts. Other rodents including guinea pigs, rats and chinchillas can be infected but do not appear to maintain the virus. LCMV has been shown to cause illness in New World primates such as macaques, marmosets and tamarins. Infections have also been reported in rabbits, dogs and pigs. After experimental inoculation, the incubation period in adult mice is 5 to 6 days. Congenitally or neonatally infected mice and hamsters do not become symptomatic for several months or longer.
Mice
A study conducted by John Hotchin and Heribert Weigand, of the New York State Department of Health, concluded, "The age of the mouse when first exposed to the virus determines its immune response." If LCMV infection occurs in utero or within the first few hours of life, during the immunologically unresponsive period, the mouse will develop immune tolerance. The virus will continue to proliferate for an indefinite time. However, if a mouse is infected after the neonatal period, when the immune system is responsive, the immune response is active. This immunological conflict can result in one of three ways; immunological paralysis, significant or complete suppression of virus with immunity to reinfection, or death. Mice that are infected after the neonatal period often pass through a "runt" stage, which may last for several weeks. Clinical symptoms include excitability, weight loss, and severe retardation of growth and hair development. In general, as the period of time between birth and inoculation decreases, less disease and mortality occurs.Post mortem lesions in mice show signs of hepatomegaly, splenomegaly, lymphadenopathy, and swollen or shrunken and pitted kidneys due to glomerulonephritis. Histological findings in persistently infected mice often show chronic glomerulonephritis. In these mice, and some hamsters, vasculitis and lymphocytic infiltrates in many organs and tissues including the liver, spleen, lung, kidneys, pancreas, blood vessels, meninges and brain are present.
Hamsters
Pathogenesis occurs in the same manner in hamsters as in mice. Symptoms in hamsters are highly variable, and typically indicate that the pet has been infected and shedding the virus for several months. Early signs may include inactivity, loss of appetite, and a rough coat. As the disease progresses, the animal may experience weight loss, hunched posture, inflammation around the eyes, and eventually death. Alternatively, some infected hamsters may be asymptomatic.
Rats
Experimental intracerebral infection of suckling rats results in microcephaly, retinitis and the destruction of several brain regions, leading to permanent abnormalities of movement, coordination, vision and behavior.
Primates
LCMV causes callitrichid hepatitis in New World primates. The onset of the infection is nonspecific and may include fever, anorexia, dyspnea, weakness and lethargy. Jaundice is characteristic and petechial hemorrhages may develop. Prostration and death usually follow.Necropsy lesions in primates with callitrichid hepatitis show signs of jaundice, hepatomegaly, splenomegaly, and subcutaneous and intramuscular hemorrhages. Pleural and pericardial effusion, sometimes sanguineous, has also been reported. On histology, multifocal necrosis with acidophilic bodies and mild inflammatory infiltrates are typically found in the liver.
Diagnosis
As in humans, the sensitivity of testing methods for rodents contributes to the accuracy of diagnosis. LCMV is typically identified through serology. However, in an endemically infected colony, more practical methods include MAP (mouse antibody production) and PCR testing. Another means of diagnosis is introducing a known naïve adult mouse to the suspect rodent colony. The introduced mouse will seroconvert, allowing use of immunofluorescence antibody (IFA), MFIA or ELISA to detect antibodies.
Treatment
Immunosuppressive therapy has been effective in halting the disease for laboratory animals.
Morbidity and mortality
LCMV infections are focal Estimates of its prevalence in wild mouse populations range from 0% to 60%, with an average prevalence of 9%. The incidence of LCMV in pet rodents is unknown, yet very few human cases have been associated with exposure to pets. In the transplant-associated cases linked to a pet hamster in 2005, two other hamsters and a guinea pig at the pet shop, and approximately 4% of the hamsters at the distributor, were also infected. Morbidity and mortality rates vary with the species of animal and its age at infection, as well as the strain of the virus and route of exposure. Neonatally and congenitally infected mice remain asymptomatic for many months, but the onset of glomerulonephritis reduces overall life expectancy. The morbidity rate in naturally infected post-neonatal mice is unknown; however, subclinical disease may be the most common form, as few natural outbreaks have been reported. In hamsters, approximately half of all congenitally infected animals clear the virus when they are approximately three months old and remain healthy; the remaining animals develop chronic disease. Hamsters infected as adults usually remain asymptomatic. Callitrichid hepatitis is reported to be highly fatal in naturally infected marmosets and tamarins in zoos. Since 1980, 12 outbreaks with 57 deaths have been reported in the U.S. In experimentally infected rhesusmacaques, three of four animals became fatally ill when inoculation was by the intravenous route. In contrast, inoculation by the intragastric route usually led to asymptomatic infections, with occasional disease and few deaths.
In pets
Pet rodents are not known to be natural reservoirs for lymphocytic choriomeningitis virus. However, pets can become vectors if they are exposed to wild house mice in a breeding facility, pet store, or home. Such infections are rare. To date, (January 2017) documented infections in humans have occurred only after introduction to infected mice, guinea pigs, and hamsters, with the majority of cases transmitted by mice. LCMV infection in other animals, including zoo animals |
Lymphocytic choriomeningitis | , may be possible.In choosing a pet, the CDC advises looking for general indications of health both in the prospective pet and others in the facility. The rodent of choice should be lively and alert, have a glossy coat, breathe normally and have no discharge from eyes or nose. If one of the animals in the facility looks ill, the others may have been exposed, and none of the rodents at that location should be purchased.Serologic testing is not recommended for pet rodents, as it has been unreliable in detecting antibodies in animals with active infections. For laboratory purposes, immunohistochemistry staining of tissues and virus isolation are used for more accurate testing, but this is unnecessary for the general house pet. The greatest risk of infection to humans occurs shortly after purchase of a pet, so that exposure to the virus, if present, has likely already occurred to existing pet owners. Continued ownership poses negligible additional risk.The National Center for Infectious Disease suggests the following precautions to reduce the risk of LCMV infection:
Wash hands with soap and water after handling pet rodents; use waterless alcohol-based hand rubs when soap is not available.
Keep rodent cages clean and free of soiled bedding.
Clean the cage in a well-ventilated area or outside.
Wash hands thoroughly with soap and water after cleaning up pet droppings. Closely supervise young children, especially those less than five years old, when cleaning cages, and make sure they wash their hands immediately after handling rodents and rodent caging or bedding.
Do not kiss pet rodents or hold them close to your face.Rodent owners who no longer wish to keep their pet should consult a veterinarian. Pets should not be released into the wild for humane, legal, and ecological reasons. After a rodent has been purchased, it should not be returned to the pet store as it may have been exposed to LCMV through house mice.
Research
LCM is the archetypal arenavirus, and was instrumental in research which uncovered the major pathogenetic mechanisms of all arenaviruses.The field of viral immunology will continue to be uncovered by the model system of LCMV. Specifically, the study of persistent viral infections as well as vaccine development, represent two essential areas. LCMV is already identified as the best model to examine the difference between acute and persistent infection in its natural host Mus musculus, the common house mouse. Conveniently, the mouse is also the most widely used genetic model for mammalian genetics. A major phenotypic difference results from only two nucleotide differences between acute LCMV, also known as Armstrong LCMV, and one of its variant, Clone 13, which leads to persistent LCMV infection. One of the nucleotide mutations is in the process of glycoprotein formation and affects tropism. The second base pair mutation affects the polymerase which influences replicative capacity. The mechanism by which these mutations cause acute versus chronic LCMV infection is not understood.
An important aspect of the present modern society is the thorough understanding of the burden of cancer. In many ways, this disease mirrors persistent viral infection, in the way that it evades and progresses despite the immune systems effort to eliminate it. The LCMV model will be a great path towards advancements in cancer studies. Furthermore, LCMV has been a widely used model system for understanding T cell memory and vaccine synthesis. It was the original model when first studied focused on CD-8 T cells response towards LCMV infection. In addition, a better understanding of CD-4 T cell memory is also a result of studies with LCMV and will continue to contribute to a more efficient mechanism of vaccine formation. Specifically, LCMV has been recently used to quantify the efficiency of a new hydrogen peroxide-based vaccine formation mechanism. The future enhancement of the field of vaccinology will greatly depend on the LCMV model system.LCMV is a prototype of more severe hemorrhagic fever viruses, especially Lassa virus with the greatest prevalence in sub-Saharan Africa. However, other strains of this virus (Junin and Machupo viruses) are present in parts of South America and other strains continue to significantly affect the southern African population. Since the modern society continue to become a more inter-connected world, the spread of these virus strains will continue to pose a severe threat around the globe. Understanding the biology of the LCMV model virus will help in advancing the understanding of this important class of viruses and more specifically will give insight into the biology of the Lassa virus which proves to be a growing threat around the world. Furthermore, the United States National Institute for Allergy and Infectious Diseases (NIAID) has appointed the family of arenaviridae to be "Category A Priority Pathogens". This translates to the highest level of importance for the high potential for morbidity and mortality from an infectious agent which is relatively easy to produce and transmit.
Footnotes
References
ICTVdB-The Universal Virus Database, version 4. [2]
Centers for Disease Control and Prevention. Lymphocytic Choriomeningitis Fact Sheet
CBWInfo (1999). "Safety Precautions for Lymphocytic Choriomeningitis Casualties". Archived from the original on 14 May 2006. Retrieved 11 May 2006.
"Rodent virus now linked to six deaths—PetSmart in Rhode Island testing animals for rare disease". NBC News. Microsoft. Associated Press. 25 May 2005. Retrieved 11 May 2006.
"Australian scientists discover new virus". The Age. Fairfax. Australian Associated Press. 22 April 2007. Retrieved 22 April 2007.
Marrie TJ, Saron MF (January 1998). "Seroprevalence of lymphocytic choriomeningitis virus in Nova Scotia". Am. J. Trop. Med. Hyg. 58 (1): 47–9. doi:10.4269/ajtmh.1998.58.47. PMID 9452291.
Bauers, Sandy. "House vs. Mouse: The Latest Ideas in Humanely Showing Our Disease-Ridden Fall Visitors the Door." Philadelphia Inquirer 10 Nov. 2006: n.p. Web.
"choriomeningitis." The American Heritage Medical Dictionary. 2009. Web.
Craighead, John E. MD. Pathology and Pathogenesis of Human Viral Disease. San Diego, California: Academic, 2000. Print.
Lasker, Jill S. "Lymphocytic choriomeningitis." The Gale Encyclopedia of Medicine. 2nd ed. 2002. Web.
"Lymphocytic Choriomeningitis Virus (LCMV)." Centers for Disease Control and Prevention. CDC, n.d. Web. 22 Sept. 2009
"Lymphocytic Choriomeningitis Virus." Charles River. Charles River Laboratories International, Inc, 2009. Web. 28 Oct 2009.
"Prevent LCMV from wild rodents." CDC Special Pathogens Branch. CDC. n.d. pdf. 22 Sept. 2009. https://web.archive.org/web/20130810131242/http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/lcmv/prevent.pdf
United States. National Center for Infectious Diseases. Lymphocytic Choriomeningitis Virus from Pet Rodents. CDC, n.d. Web. 22 Sept. 2009.
---. Lymphocytic Choriomeningitis Virus (LCMV) and Pregnancy: Facts and Prevention. CDC, 5 Oct. 2005. Web. 22 Sept. 2009.
United States. Special Pathogens Branch, Centers for Disease Control and Prevention. Information for Pet Owners: Reducing the Risk of Becoming Infected with LCMV from Pet Rodents. CDC. 6 Sept. 2005. Web. 26 Sept. 2009.
---. Lymphocytic choriomeningitis. CDC. 11 October 2007. Web. 26 Sept. 2009.
Vilches, Jose MD ed. Pam Mouser, MD. "Lymphocytic Choriomeningitis." Animal Disease Diagnostic Laboratory. Animal Disease Diagnostic Laboratory, Purdue University, 2007. Web. 23 September 2009.
Lee, KJ; Novella, IS; Teng, MN; Oldstone, MBA; de la Torre, JC (2000). "NP and L Proteins of Lymphocytic Choriomeningitis Virus (LCMV) Are Sufficient for Efficient Transcription and Replication of LCMV Genomic RNA Analog". Journal of Virology. 74 (8): 3470–7. doi:10.1128/jvi.74.8.3470-3477.2000. PMC 111854. PMID 10729120.
Swiss Institute of Bioinformatics. Viral Zone "Arenaviridae"
Zhou, X; Ramachaundran, S; Mann, M; Popkin, DL (2012). "Role of Lymphocytic Choriomeningitis virus(LCMV) in understanding viral immunology: Past, Present and Future". Viruses. 4 (11): 2650–69. doi:10.3390/v4112650. PMC 3509666. PMID 23202498.
Further reading
Palacios, Druce, Du, Tran, Birch, Briese, Conlan, Quan, Hui, Marshall, Simons, Egholm, Paddock, Shieh, Goldsmith, Zaki, Catton, Lipkin (2008). "A New Arenavirus in a Cluster of Fatal Transplant-Associated Diseases". The New England Journal of Medicine. 358 (10): 991–998. doi:10.1056/NEJMoa073785. PMID 18256387.{{cite journal}}: CS1 maint: multiple names: authors list (link)
External links
Virus Pathogen Database and Analysis Resource (ViPR): Arenaviridae |
Erotomania | Erotomania, also known as de Clérambaults Syndrome, named after French psychiatrist Gaëtan Gatian de Clérambault, is listed in the DSM-5 as a subtype of a delusional disorder. It is a relatively uncommon paranoid condition that is characterized by an individuals delusions of another person being infatuated with them. This disorder is most often seen (though not exclusively) in female patients who are shy, dependent and sexually inexperienced. The object of the delusion is typically a male who is unattainable due to high social or financial status, marriage or uninterest. The object of obsession may also be imaginary, deceased or someone the patient has never met. Delusions of reference are common, as the erotomanic individual often perceives that they are being sent messages from the secret admirer through innocuous events such as seeing license plates from specific states, but has no proof. Commonly, the onset of erotomania is sudden, and the course is chronic.
Presentation
Erotomania is more common in women, but men are more likely to exhibit violent and stalker-like behaviors. The core symptom of the disorder is that the individual holds an unshakable belief that another person is secretly in love with them. In some cases, the person with the condition may believe several people at once are "secret admirers". Most commonly, the individual has delusions of being loved by an unattainable person who is usually an acquaintance or someone the person has never met. They may also experience other types of delusions concurrently with erotomania, such as delusions of reference, wherein the perceived admirer secretly communicates their love by subtle methods such as body posture, arrangement of household objects, colors, license plates on cars from specific states, and other seemingly innocuous acts (or, if the person is a public figure, through clues in the media). Some delusions may be extreme such as the conception, birth, and kidnapping of children that never existed. The delusional objects may be replaced by others over time, and some may be chronic in fixed forms. Denial is characteristic with this disorder as the patients do not accept the fact that their object of delusion may be married, unavailable, or uninterested. The phantom lover may also be imaginary or deceased.
Erotomania has two forms: primary and secondary. Primary erotomania is also commonly referred to as de Clerambaults syndrome and Old Maids Insanity and it exists alone without comorbidities, has a sudden onset and a chronic outcome. The secondary form is found along with mental disorders like paranoid schizophrenia, often includes persecutory delusions, hallucinations, and grandiose ideas, and has a more gradual onset. Patients with a "fixed" condition are more seriously ill with constant delusions and are less responsive to treatment. These individuals are usually timid, dependent women that are often sexually inexperienced. In those with a more mild, recurrent condition, delusions are shorter-lived and the disorder can exist undetected by others for years. Problematic behaviors include actions like calling, sending letters and gifts, making unannounced house visits and other persistent stalking behaviors.
Cause
Erotomania may present as a primary mental disorder, or as a symptom of another psychiatric illness. With secondary erotomania, the erotomanic delusions are due to other mental disorders such as bipolar I disorder or schizophrenia. Symptoms may also be precipitated by alcoholism and the use of antidepressants. There may be a potential genetic component involved as family histories of first degree relatives with histories of psychiatric disorders are common. Sigmund Freud explained erotomania as a defense mechanism to ward off homosexual impulses which can lead to strong feelings of paranoia, denial, displacement and projection. Similarly, it has been explained as a way to cope with severe loneliness or ego deficit following a major loss. Erotomania may also be linked to unsatiated urges dealing with homosexuality or narcissism. Some research shows brain abnormalities occurring in patients with erotomania such as heightened temporal lobe asymmetry and greater volumes of lateral ventricles than those with no mental disorders.
Treatment
Prognosis differs from person to person, and the ideal treatment is not completely understood. Treatment for this disorder gains the best results when tailored specifically for each individual. To date, the mainline pharmacological treatments have been pimozide (a typical antipsychotic which was also approved for treating Tourettes Syndrome), and atypical antipsychotics like risperidone and clozapine. Non-pharmacologic treatments that have shown some degree of efficacy are electroconvulsive therapy (ECT), supportive psychotherapy, family and environment therapy, rehousing, risk management and treating underlying disorders in cases of secondary erotomania. ECT may provide temporary remission of delusional beliefs; antipsychotics help attenuate delusions and reduce agitation or associated dangerous behaviors, and SSRIs may be used to treat secondary depression. In delusional disorder there is some evidence that pimozide has superior efficacy compared with other antipsychotics. Psychosocial psychiatric interventions can enhance the quality of life through allowing some social functioning, and treating comorbid disorders is a priority for secondary erotomania. Family therapy, adjustment of socio-environmental factors, and replacing delusions with something positive may be beneficial to all. In most cases, harsh confrontation should be avoided. Structured risk assessment helps to manage risky behaviors in those individuals more likely to engage in actions that include violence, stalking, and crime. For particularly troublesome cases, neuroleptics and enforced separation may be moderately effective.
History
Early references to the condition can be found in the work of Hippocrates, Freud (1911), G.G. de Clérambault (1942), Erasistratus, Plutarch and Galen. Parisian physician, Bartholomy Pardoux (1545-1611) covered the topics of nymphomania and erotomania. In 1623, erotomania was referred to in a treatise by Jacques Ferrand (Maladie damour ou Mélancolie érotique) and has been called "erotic paranoia" and "erotic self-referent delusion" until the common usage of the terms erotomania and de Clérambaults syndrome. In 1971 and 1977, M.V. Seeman referred to the disorder as "phantom lover syndrome" and "psychotic erotic transference reaction and delusional loving". Emil Kraepelin and Bernard also wrote of erotomania and more recently, Winokur, Kendler, and Munro have contributed to knowledge on the disorder.G. E. Berrios and N. Kennedy outlined in Erotomania: a conceptual history (2002) several periods of history through which the definition of erotomania has changed considerably:
Classical times – early eighteenth century: General disease caused by unrequited love
Early eighteenth-beginning of nineteenth century: Practise of excess physical love (akin to nymphomania or satyriasis)
Early nineteenth century – beginning twentieth century: Unrequited love as a form of mental disease
Early twentieth century – present: Delusional belief of "being loved by someone else"In one case, erotomania was reported in a patient who had undergone surgery for a ruptured cerebral aneurysm.
Well-known cases
In his paper that described the syndrome, de Clérambault referenced a patient he had counselled who was obsessed with British monarch George V. She had stood outside Buckingham Palace for hours at a time, believing that the king was communicating his desire for her by moving the curtains.Parallels were drawn between this and a 2011 case where the body of a homeless American man was found on a secluded island in St James Park, within sight of Buckingham Palace. The man had sent hundreds of "strange and offensive" packages to Queen Elizabeth II over the previous fifteen years.The attempted assassination of United States president Ronald Reagan by John Hinckley Jr. has been reported to have been driven by an erotomaniac fixation on actress Jodie Foster, whom Hinckley was attempting to impress.
Late-night TV entertainer David Letterman and former astronaut Story Musgrave were both stalked by Margaret Mary Ray, who had erotomania.Michael David Barrett allegedly had erotomania, stalking ESPN correspondent Erin Andrews across the country, trying to see her and taking lewd videos.Many cases of obsession or stalking can be linked to erotomania but do not always necessarily go hand in hand.
In media
Nurse Betty (2000)
A main character in Orange Is the New Black, Lorna Morello, exhibits erotomanic behavior towards a man she has delusions of being engaged to.
He Loves Me... He Loves Me Not (2002)
A 2011 episode (Series 5, Episode 3) of the British TV series Lewis features a character with erotomania, referred to in the show as de Clérambaults syndrome.
Enduring Love (1997)
Criminal Minds Season 1, Episode 5: Broken Mirror.
Doc Martin Season 6, Episode 3: The Tameness of a Wolf
See also
Further reading
Remington GJ, Jeffries JJ (1994). "Erotomanic delusions and electroconvulsive therapy: a case series". J Clin Psychiatry. 55 (7): 306–8. PMID 8071292.
Anderson CA, Camp J, Filley CM (1998). "Erotomania after aneurysmal subarachnoid hemorrhage: case report and literature review". J Neuropsychiatry Clin Neurosci. 10 (3): 330–7. doi:10.1176/jnp.10.3.330. PMID 9706541.{{cite journal}}: CS1 maint: multiple names: authors list (link)
Frank Bruni, Behind the Jokes, a Life Of Pain and Delusion; For Letterman Stalker, Mental Illness Was Family Curse and Scarring Legacy, New York Times, November 22, 1998
Foster, David & Levinson, Arlene. Suicide on a railroad track ends a celebrity-stalkers inner agony Archived 2011-06-14 at the Wayback Machine., Associated Press, October 11, 1998
Berrios GE, Kennedy N (2002). "Erotomania: a conceptual history". Hist Psychiatry. 13 (52): 381–400. doi:10.1177/0957154X0201305202. PMID 12638595. S2CID 24663481.
Helen K. Gediman (14 December 2016). Stalker, Hacker, Voyeur, Spy: A Psychoanalytic Study of Erotomania, Voyeurism, Surveillance, and Invasions of Privacy. Karnac Books. pp. 21–34. ISBN 978-1-78181-706-3.
References
Notes
Bibliography
Anderson CA, Camp J, Filley CM (1998). "Erotomania after aneurysmal subarachnoid hemorrhage: case report and literature review". J Neuropsychiatry Clin Neurosci. 10 (3): 330–70. doi:10.1176/jnp.10.3.330. PMID 9706541.{{cite journal}}: CS1 maint: multiple names: authors list (link)
Berrios GE, Kennedy N (2002). "Erotomania: a conceptual history". History of Psychiatry. 13 (52): 381–400. doi:10.1177/0957154X0201305202. PMID 12638595. S2CID 24663481.
Helen K. Gediman (14 December 2016). Stalker, Hacker, Voyeur, Spy: A Psychoanalytic Study of Erotomania, Voyeurism, Surveillance, and Invasions of Privacy. Karnac Books. pp. 21–34. ISBN 978-1-78181-706-3.
Jordan H.W., Lockert E.W., Johnson-Warren M., Cabell C., Cooke T., Greer W., Howe G. (2006). "Erotomania revisisted: Thirty-four years later". Journal of the National Medical Association. 98 (5): 787–93. PMC 2569288. PMID 16749657.{{cite journal}}: CS1 maint: multiple names: authors list (link)
Kelly B.D. (2005). "Erotomania: Epidemiology and management". CNS Drugs. 19 (8): 657–669. doi:10.2165/00023210-200519080-00002. PMID 16097848.
McDonnell, Margaux, and Mike McPadden. "9 Stalkers That Make Us Glad Were Not Famous." CrimeFeed, 12 Nov. 2013, crimefeed.com/2013/10/9-stalkers-that-make-us-glad-were-not-famous/.
Oliveira C., Alves S., Ferreira C., Agostinho C., Avelino M.J. (2016). "Erotomania-A review of De Clerambaults Syndrome". The Journal of the European Psychiatric Association. 33: S664.{{cite journal}}: CS1 maint: multiple names: authors list (link)
Seeman M.V. (2016). "Erotomania and recommendations for treatment". Psychiatric Quarterly. 87 (2): 355–364. doi:10.1007/s11126-015-9392-0. PMID 26442945. S2CID 13059293.
Segal J.H. (1989). "Erotomania revisited: From Kraepelin to DSM-III-R". The American Journal of Psychiatry. 146 (10): 1261–6. doi:10.1176/ajp.146.10.1261. PMID 2675641. |
Neuroglycopenia | Neuroglycopenia is a shortage of glucose (glycopenia) in the brain, usually due to hypoglycemia. Glycopenia affects the function of neurons, and alters brain function and behavior. Prolonged or recurrent neuroglycopenia can result in loss of consciousness, damage to the brain, and eventual death.
Signs and symptoms
Abnormal mentation, impaired judgment
Nonspecific dysphoria, anxiety, moodiness, depression, crying, fear of dying, suicidal thoughts
Negativism, irritability, belligerence, combativeness, rage
Personality change, emotional lability
Fatigue, weakness, apathy, lethargy, daydreaming
Confusion, amnesia, dizziness, delirium
Staring, "glassy" look, blurred vision, double vision
Automatic behavior
Difficulty speaking, slurred speech
Ataxia, incoordination, sometimes mistaken for "drunkenness"
Focal or general motor deficit, paralysis, hemiparesis
Paresthesia, headache
Stupor, coma, abnormal breathing
Generalized or focal seizures
Plasma glucose 20 mg/dL (1.1 mmol/L) or lowerNot all of the above manifestations occur in every case of hypoglycemia. There is no consistent order to the appearance of the symptoms. Specific manifestations vary by age and by the severity of the hypoglycemia. In older children and adults, moderately severe hypoglycemia can resemble mania, mental illness, drug intoxication, or drunkenness. In the elderly, hypoglycemia can produce focal stroke-like effects or a hard-to-define malaise. The symptoms of a single person do tend to be similar from episode to episode.
In the large majority of cases, hypoglycemia severe enough to cause seizures or unconsciousness can be reversed without obvious harm to the brain. Cases of death or permanent neurological damage occurring with a single episode have usually involved prolonged, untreated unconsciousness, interference with breathing, severe concurrent disease, or some other type of vulnerability. Nevertheless, brain damage or death has occasionally resulted from severe hypoglycemia.
Metabolic responses
Most neurons have the ability to use other fuels besides glucose (e.g. lactic acid, ketones). Knowledge of the "switchover" process is incomplete. The most severe neuroglycopenic symptoms occur with hypoglycemia caused by excess insulin because insulin reduces the availability of other fuels by suppressing ketogenesis and gluconeogenesis.
A few types of specialized neurons, especially in the hypothalamus, act as glucose sensors, responding to changing levels of glucose by increasing or decreasing their firing rates. They can elicit a variety of hormonal, autonomic, and behavioral responses to neuroglycopenia. The hormonal and autonomic responses include release of counterregulatory hormones. There is some evidence that the autonomic nervous system can alter liver glucose metabolism independently of the counterregulatory hormones.
Adjustment of efficiency of transfer of glucose from blood across the blood–brain barrier into the central nervous system represents a third form of compensation which occurs more gradually. Levels of glucose within the central nervous system are normally lower than the blood, regulated by an incompletely understood transfer process. Chronic hypoglycemia or hyperglycemia seems to result in an increase or decrease in efficiency of transfer to maintain CNS levels of glucose within an optimal range.
In both young and old individuals, the brain may habituate to low glucose levels with a reduction of noticeable symptoms, sometimes despite neuroglycopenic impairment. In insulin-dependent diabetic patients this phenomenon is termed hypoglycemia unawareness and is a significant clinical problem when improved glycemic control is attempted. Another aspect of this phenomenon occurs in type I glycogenosis, when chronic hypoglycemia before diagnosis may be better tolerated than acute hypoglycemia after treatment is underway.
Neuroglycopenia without hypoglycemia
A rare metabolic disease of the blood-brain glucose transport system has been described in which severe neuroglycopenic effects occurred despite normal blood glucose levels. Low levels of glucose were discovered in the cerebrospinal fluid (CSF), a condition referred to as hypoglycorrhachia [or hypoglycorrhacia].
Hypoglycorrhachia is associated with Glucose transporter type 1 GLUT1 deficiency syndrome (GLUT1DS).Perhaps a much more common example of the same phenomenon occurs in the people with poorly controlled type 1 diabetes who develop symptoms of hypoglycemia at levels of blood glucose which are normal for most people.
== References == |
Pneumoperitoneum | Pneumoperitoneum is pneumatosis (abnormal presence of air or other gas) in the peritoneal cavity, a potential space within the abdominal cavity. The most common cause is a perforated abdominal organ, generally from a perforated peptic ulcer, although any part of the bowel may perforate from a benign ulcer, tumor or abdominal trauma. A perforated appendix seldom causes a pneumoperitoneum.
Spontaneous pneumoperitoneum is a rare case that is not caused by an abdominal organ rupture. This is also called an idiopathic spontaneous pneumoperitoneum when the cause is not known.
In the mid-twentieth century, an "artificial" pneumoperitoneum was sometimes intentionally administered as a treatment for a hiatal hernia. This was achieved by insufflating the abdomen with carbon dioxide. The practice is currently used by surgical teams in order to aid in performing laparoscopic surgery.
Causes
Perforated duodenal ulcer – The most common cause of rupture in the abdomen. Especially of the anterior aspect of the first part of the duodenum.
Perforated peptic ulcer
Bowel obstruction
Ruptured diverticulum
Penetrating trauma
Ruptured inflammatory bowel disease (e.g., megacolon)
Necrotising enterocolitis/pneumatosis coli
Bowel cancer
Ischemic bowel
Steroids
After laparotomy
After laparoscopy
Breakdown of a surgical anastomosis
Bowel injury after endoscopy
Peritoneal dialysis (PD), although the prevalence of pneumoperitoneum is estimated to be less than 4% among people with PD in a more recent study in the United Kingdom.
Vaginal insufflation (air enters via the fallopian tubes; e.g., water-skiing, oral sex)
Colonic or peritoneal infection
From chest (e.g., bronchopleural fistula)
Non-invasive PAP (positive airway pressure) can force air down duodenum as well as down trachea.
Spontaneous pneumoperitoneum
A spontaneous pneumoperitoneum is a rare case that is not caused by an abdominal organ rupture. This is also called an idiopathic spontaneous pneumoperitoneum when the cause is not known. Causes of a spontaneous pneumoperitoneum, with no peritonitis include a barotrauma due to mechanical ventilation, and a tracheal rupture following an emergency intubation. In the ventilation case, air had passed from the chest into the abdominal cavity through the diaphragm. In the tracheal rupture air had passed along the great vessels.
Diagnosis
When present, pneumoperitoneum can often be seen on projectional radiography, but small amounts are often missed, and CT scan is nowadays regarded as a criterion standard in the assessment of a pneumoperitoneum. CT can visualize quantities as small as 5 cm³ of air or gas.
Signs that can be seen on projectional radiography are shown below:
The double wall sign marks the presence of air on both sides of the intestine. However, a false double wall sign can result from two loops of bowel being in contact with one another. The sign is named after Leo George Rigler. It is not the same as Riglers triad.
The football sign is when the abdomen appears as a large oval radiolucency reminiscent of an American football on a supine projectional radiograph. The football sign is most frequently seen in infants with spontaneous or iatrogenic gastric perforation causing pneumoperitoneum. It is also seen in bowel obstruction with secondary perforation, as in Hirschprung disease, midgut volvulus, meconium ileus and intestinal atresia. Iatrogenic causes like endoscopic perforation may also give football sign.The Cupola sign is seen when air is accumulated under the central tendon of the diaphragm.
Differential diagnosis
As differential diagnoses, a subphrenic abscess, bowel interposed between diaphragm and liver (Chilaiditi syndrome), and linear atelectasis at the base of the lungs can simulate free air under the diaphragm on a chest X-ray.
Treatment
Treatment depends on the cause of the condition.
Terminology
Pneumoperitoneum can be described as peritoneal emphysema, just as pneumomediastinum can be called mediastinal emphysema, but pneumoperitoneum is the usual name.
See also
Cupola sign
Football sign
Pneumoretroperitoneum
Riglers sign
References
== External links == |
Larynx | The larynx (), commonly called the voice box, is an organ in the top of the neck involved in breathing, producing sound and protecting the trachea against food aspiration. The opening of larynx into pharynx known as the laryngeal inlet is about 4–5 centimeters in diameter. The larynx houses the vocal cords, and manipulates pitch and volume, which is essential for phonation. It is situated just below where the tract of the pharynx splits into the trachea and the esophagus. The word ʻlarynxʼ (plural ʻlaryngesʼ) comes from the Ancient Greek word lárunx ʻlarynx, gullet, throat.ʼ
Structure
The triangle-shaped larynx consists largely of cartilages that are attached to one another, and to surrounding structures, by muscles or by fibrous and elastic tissue components. The larynx is lined by a ciliated columnar epithelium except for the vocal folds. The cavity of the larynx extends from its triangle-shaped inlet, to the epiglottis, and to the circular outlet at the lower border of the cricoid cartilage, where it is continuous with the lumen of the trachea. The mucous membrane lining the larynx forms two pairs of lateral folds that project inward into its cavity. The upper folds are called the vestibular folds. They are also sometimes called the false vocal cords for the rather obvious reason that they play no part in vocalization. The lower pair of folds are known as the vocal cords, which produce sounds needed for speech and other vocalizations. The slit-like space between the left and right vocal cords, called the rima glottidis, is the narrowest part of the larynx. The vocal cords and the rima glottidis are together designated as the glottis. The laryngeal cavity above the vestibular folds is called the vestibule. The very middle portion of the cavity between the vestibular folds and the vocal cords is the ventricle of the larynx, or laryngeal ventricle. The infraglottic cavity is the open space below the glottis.
Location
In adult humans, the larynx is found in the anterior neck at the level of the cervical vertebrae C3–C6. It connects the inferior part of the pharynx (hypopharynx) with the trachea. The laryngeal skeleton consists of nine cartilages: three single (epiglottic, thyroid and cricoid) and three paired (arytenoid, corniculate, and cuneiform). The hyoid bone is not part of the larynx, though the larynx is suspended from the hyoid. The larynx extends vertically from the tip of the epiglottis to the inferior border of the cricoid cartilage. Its interior can be divided in supraglottis, glottis and subglottis.
Cartilages
There are nine cartilages, three unpaired and three paired (3 pairs=6), that support the mammalian larynx and form its skeleton.
Unpaired cartilages:
Thyroid cartilage: This forms the Adams apple (also called the laryngeal prominence). It is usually larger in males than in females. The thyrohyoid membrane is a ligament associated with the thyroid cartilage that connects it with the hyoid bone. It supports the front portion of the larynx.
Cricoid cartilage: A ring of hyaline cartilage that forms the inferior wall of the larynx. It is attached to the top of the trachea. The median cricothyroid ligament connects the cricoid cartilage to the thyroid cartilage.
Epiglottis: A large, spoon-shaped piece of elastic cartilage. During swallowing, the pharynx and larynx rise. Elevation of the pharynx widens it to receive food and drink; elevation of the larynx causes the epiglottis to move down and form a lid over the glottis, closing it off.Paired cartilages:
Arytenoid cartilages: Of the paired cartilages, the arytenoid cartilages are the most important because they influence the position and tension of the vocal cords. These are triangular pieces of mostly hyaline cartilage located at the posterosuperior border of the cricoid cartilage.
Corniculate cartilages: Horn-shaped pieces of elastic cartilage located at the apex of each arytenoid cartilage.
Cuneiform cartilages: Club-shaped pieces of elastic cartilage located anterior to the corniculate cartilages.
Muscles
The muscles of the larynx are divided into intrinsic and extrinsic muscles. The extrinsic muscles act on the region and pass between the larynx and parts around it but have their origin elsewhere; the intrinsic muscles are confined entirely within the larynx and have their origin and insertion there.The intrinsic muscles are divided into respiratory and the phonatory muscles (the muscles of phonation). The respiratory muscles move the vocal cords apart and serve breathing. The phonatory muscles move the vocal cords together and serve the production of voice. The main respiratory muscles are the posterior cricoarytenoid muscles. The phonatory muscles are divided into adductors (lateral cricoarytenoid muscles, arytenoid muscles) and tensors (cricothyroid muscles, thyroarytenoid muscles).
Intrinsic
The intrinsic laryngeal muscles are responsible for controlling sound production.
Cricothyroid muscle lengthen and tense the vocal cords.
Posterior cricoarytenoid muscles abduct and externally rotate the arytenoid cartilages, resulting in abducted vocal cords.
Lateral cricoarytenoid muscles adduct and internally rotate the arytenoid cartilages, increase medial compression.
Transverse arytenoid muscle adduct the arytenoid cartilages, resulting in adducted vocal cords.
Oblique arytenoid muscles narrow the laryngeal inlet by constricting the distance between the arytenoid cartilages.
Thyroarytenoid muscles narrow the laryngeal inlet, shortening the vocal cords, and lowering voice pitch. The internal thyroarytenoid is the portion of the thyroarytenoid that vibrates to produce sound.Notably the only muscle capable of separating the vocal cords for normal breathing is the posterior cricoarytenoid. If this muscle is incapacitated on both sides, the inability to pull the vocal cords apart (abduct) will cause difficulty breathing. Bilateral injury to the recurrent laryngeal nerve would cause this condition. It is also worth noting that all muscles are innervated by the recurrent laryngeal branch of the vagus except the cricothyroid muscle, which is innervated by the external laryngeal branch of the superior laryngeal nerve (a branch of the vagus).
Additionally, intrinsic laryngeal muscles present a constitutive Ca2+-buffering profile that predicts their better ability to handle calcium changes in comparison to other muscles. This profile is in agreement with their function as very fast muscles with a well-developed capacity for prolonged work. Studies suggests that mechanisms involved in the prompt sequestering of Ca2+ (sarcoplasmic reticulum Ca2+-reuptake proteins, plasma membrane pumps, and cytosolic Ca2+-buffering proteins) are particularly elevated in laryngeal muscles, indicating their importance for the myofiber function and protection against disease, such as Duchenne muscular dystrophy. Furthermore, different levels of Orai1 in rat intrinsic laryngeal muscles and extraocular muscles over the limb muscle suggests a role for store operated calcium entry channels in those muscles functional properties and signaling mechanisms.
Extrinsic
The extrinsic laryngeal muscles support and position the larynx within the mid-cervical cereal region.
thumb|Extrinsic laryngeal muscles
Sternothyroid muscles depress the larynx. (Innervated by ansa cervicalis)
Omohyoid muscles depress the larynx. (Ansa cervicalis)
Sternohyoid muscles depress the larynx. (Ansa cervicalis)
Inferior constrictor muscles. (CN X)
Thyrohyoid muscles elevates the larynx. (C1)
Digastric elevates the larynx. (CN V3, CN VII)
Stylohyoid elevates the larynx. (CN VII)
Mylohyoid elevates the larynx. (CN V3)
Geniohyoid elevates the larynx. (C1)
Hyoglossus elevates the larynx. (CN XII)
Genioglossus elevates the larynx. (CN XII)
Nerve supply
The larynx is innervated by branches of the vagus nerve on each side. Sensory innervation to the glottis and laryngeal vestibule is by the internal branch of the superior laryngeal nerve. The external branch of the superior laryngeal nerve innervates the cricothyroid muscle. Motor innervation to all other muscles of the larynx and sensory innervation to the subglottis is by the recurrent laryngeal nerve. While the sensory input described above is (general) visceral sensation (diffuse, poorly localized), the vocal cords also receives general somatic sensory innervation (proprioceptive and touch) by the superior laryngeal nerve.
Injury to the external branch of the superior laryngeal nerve causes weakened phonation because the vocal cords cannot be tightened. Injury to one of the recurrent laryngeal nerves produces hoarseness, if both are damaged the voice may or may not be preserved, but breathing becomes difficult.
Development
In newborn infants, the larynx is initially at the level of the C2–C3 vertebrae, and is further forward and higher relative to its position in the adult body. The larynx descends as the child grows.
Laryngeal cavity
The laryngeal cavity (cavity of the larynx) extends from the laryngeal inlet downwards to the lower border of the cricoid cartilage where it is continuous with that of the trachea.It is divided into two parts by the projection of the vocal folds, between which is a narrow triangular opening, the rima glottidis.
The portion of the cavity of the larynx above the vocal folds is called the laryngeal vestibule; it is wide and triangular in shape, its base or anterior wall presenting, however, about its center the backward projection of the tubercle of the epiglottis.
It contains the vestibular folds, and between these and the vocal folds are the laryngeal ventricles.
The portion below the vocal folds is called the infraglottic cavity. It is at first of an elliptical form, but lower down it widens out, assumes a circular form, and is continuous with the tube of the trachea.
Function
Sound generation
Sound is generated in the larynx, and that is where pitch and volume are manipulated. The strength of expiration from the lungs also contributes to loudness.
Manipulation of the larynx is used to generate a source sound with a particular fundamental frequency, or pitch. This source sound is altered as it travels through the vocal tract, configured differently based on the position of the tongue, lips, mouth, and pharynx. The process of altering a source sound as it passes through the filter of the vocal tract creates the many different vowel and consonant sounds of the worlds languages as well as tone, certain realizations of stress and other types of linguistic prosody. The larynx also has a similar function to the lungs in creating pressure differences required for sound production; a constricted larynx can be raised or lowered affecting the volume of the oral cavity as necessary in glottalic consonants.
The vocal cords can be held close together (by adducting the arytenoid cartilages) so that they vibrate (see phonation). The muscles attached to the arytenoid cartilages control the degree of opening. Vocal cord length and tension can be controlled by rocking the thyroid cartilage forward and backward on the cricoid cartilage (either directly by contracting the cricothyroids or indirectly by changing the vertical position of the larynx), by manipulating the tension of the muscles within the vocal cords, and by moving the arytenoids forward or backward. This causes the pitch produced during phonation to rise or fall. In most males the vocal cords are longer and have a greater mass than most females vocal cords, producing a lower pitch.
The vocal apparatus consists of two pairs of folds, the vestibular folds (false vocal cords) and the true vocal cords. The vestibular folds are covered by respiratory epithelium, while the vocal cords are covered by stratified squamous epithelium. The vestibular folds are not responsible for sound production, but rather for resonance. The exceptions to this are found in Tibetan chanting and Kargyraa, a style of Tuvan throat singing. Both make use of the vestibular folds to create an undertone. These false vocal cords do not contain muscle, while the true vocal cords do have skeletal muscle.
Other
The most important role of the larynx is its protective function, the prevention of foreign objects from entering the lungs by coughing and other reflexive actions. A cough is initiated by a deep inhalation through the vocal cords, followed by the elevation of the larynx and the tight adduction (closing) of the vocal cords. The forced expiration that follows, assisted by tissue recoil and the muscles of expiration, blows the vocal cords apart, and the high pressure expels the irritating object out of the throat. Throat clearing is less violent than coughing, but is a similar increased respiratory effort countered by the tightening of the laryngeal musculature. Both coughing and throat clearing are predictable and necessary actions because they clear the respiratory passageway, but both place the vocal cords under significant strain.Another important role of the larynx is abdominal fixation, a kind of Valsalva maneuver in which the lungs are filled with air in order to stiffen the thorax so that forces applied for lifting can be translated down to the legs. This is achieved by a deep inhalation followed by the adduction of the vocal cords. Grunting while lifting heavy objects is the result of some air escaping through the adducted vocal cords ready for phonation.Abduction of the vocal cords is important during physical exertion. The vocal cords are separated by about 8 mm (0.31 in) during normal respiration, but this width is doubled during forced respiration.During swallowing, elevation of the posterior portion of the tongue levers (inverts) the epiglottis over the glottis opening to prevent swallowed material from entering the larynx which leads to the lungs, and provides a path for a food or liquid bolus to "slide" into the esophagus; the hyo-laryngeal complex is also pulled upwards to assist this process. Stimulation of the larynx by aspirated food or liquid produces a strong cough reflex to protect the lungs.
In addition, intrinsic laryngeal muscles are spared from some muscle wasting disorders, such as Duchenne muscular dystrophy, may facilitate the development of novel strategies for the prevention and treatment of muscle wasting in a variety of clinical scenarios. ILM have a calcium regulation system profile suggestive of a better ability to handle calcium changes in comparison to other muscles, and this may provide a mechanistic insight for their unique pathophysiological properties
Clinical significance
Disorders
There are several things that can cause a larynx to not function properly. Some symptoms are hoarseness, loss of voice, pain in the throat or ears, and breathing difficulties.
Acute laryngitis is the sudden inflammation and swelling of the larynx. It is caused by the common cold or by excessive shouting. It is not serious. Chronic laryngitis is caused by smoking, dust, frequent yelling, or prolonged exposure to polluted air. It is much more serious than acute laryngitis.
Presbylarynx is a condition in which age-related atrophy of the soft tissues of the larynx results in weak voice and restricted vocal range and stamina. Bowing of the anterior portion of the vocal colds is found on laryngoscopy.
Ulcers may be caused by the prolonged presence of an endotracheal tube.
Polyps and vocal cord nodules are small bumps caused by prolonged exposure to tobacco smoke and vocal misuse, respectively.
Two related types of cancer of the larynx, namely squamous cell carcinoma and verrucous carcinoma, are strongly associated with repeated exposure to cigarette smoke and alcohol.
Vocal cord paresis is weakness of one or both vocal cords that can greatly impact daily life.
Idiopathic laryngeal spasm.
Laryngopharyngeal reflux is a condition in which acid from the stomach irritates and burns the larynx. Similar damage can occur with gastroesophageal reflux disease (GERD).
Laryngomalacia is a very common condition of infancy, in which the soft, immature cartilage of the upper larynx collapses inward during inhalation, causing airway obstruction.
Laryngeal perichondritis, the inflammation of the perichondrium of laryngeal cartilages, causing airway obstruction.
Laryngeal paralysis is a condition seen in some mammals (including dogs) in which the larynx no longer opens as wide as required for the passage of air, and impedes respiration. In mild cases it can lead to exaggerated or "raspy" breathing or panting, and in serious cases can pose a considerable need for treatment.
Duchenne muscular dystrophy, intrinsic laryngeal muscles (ILM) are spared from the lack of dystrophin and may serve as a useful model to study the mechanisms of muscle sparing in neuromuscular diseases. Dystrophic ILM presented a significant increase in the expression of calcium-binding proteins. The increase of calcium-binding proteins in dystrophic ILM may permit better maintenance of calcium homeostasis, with the consequent absence of myonecrosis. The results further support the concept that abnormal calcium buffering is involved in these neuromuscular diseases.
Treatments
Patients who have lost the use of their larynx are typically prescribed the use of an electrolarynx device. Larynx transplants are a rare procedure. The worlds first successful operation took place in 1998 at the Cleveland Clinic, and the second took place in October 2010 at the University of California Davis Medical Center in Sacramento.
Other animals
Pioneering work on the structure and evolution of the larynx was carried out in the 1920s by the British comparative anatomist Victor Negus, culminating in his monumental work The Mechanism of the Larynx (1929). Negus, however, pointed out that the descent of the larynx reflected the reshaping and descent of the human tongue into the pharynx. This process is not complete until age six to eight years. Some researchers, such as Philip Lieberman, Dennis Klatt, Bart de Boer and Kenneth Stevens using computer-modeling techniques have suggested that the species-specific human tongue allows the vocal tract (the airway above the larynx) to assume the shapes necessary to produce speech sounds that enhance the robustness of human speech. Sounds such as the vowels of the words ⟨see⟩ and ⟨do⟩, [i] and [u] (in phonetic notation), have been shown to be less subject to confusion in classic studies such as the 1950 Peterson and Barney investigation of the possibilities for computerized speech recognition.In contrast, though other species have low larynges, their tongues remain anchored in their mouths and their vocal tracts cannot produce the range of speech sounds of humans. The ability to lower the larynx transiently in some species extends the length of their vocal tract, which as Fitch showed creates the acoustic illusion that they are larger. Research at Haskins Laboratories in the 1960s showed that speech allows humans to achieve a vocal communication rate that exceeds the fusion frequency of the auditory system by fusing sounds together into syllables and words. The additional speech sounds that the human tongue enables us to produce, particularly [i], allow humans to unconsciously infer the length of the vocal tract of the person who is talking, a critical element in recovering the phonemes that make up a word.
Non-mammals
Most tetrapod species possess a larynx, but its structure is typically simpler than that found in mammals. The cartilages surrounding the larynx are apparently a remnant of the original gill arches in fish, and are a common feature, but not all are always present. For example, the thyroid cartilage is found only in mammals. Similarly, only mammals possess a true epiglottis, although a flap of non-cartilagenous mucosa is found in a similar position in many other groups. In modern amphibians, the laryngeal skeleton is considerably reduced; frogs have only the cricoid and arytenoid cartilages, while salamanders possess only the arytenoids.Vocal folds are found only in mammals, and a few lizards. As a result, many reptiles and amphibians are essentially voiceless; frogs use ridges in the trachea to modulate sound, while birds have a separate sound-producing organ, the syrinx.
History
The ancient Greek physician Galen first described the larynx, describing it as the "first and supremely most important instrument of the voice".
Additional images
See also
Articulatory phonetics
Electrolarynx
Histology of the vocal cords
Origin of speech
References
Notes
=== Sources === |
Subsets and Splits