page_title
stringlengths 1
91
| page_text
stringlengths 0
34.2k
|
|---|---|
Citrullinemia | Citrullinemia is an autosomal recessive urea cycle disorder that causes ammonia and other toxic substances to accumulate in the blood.Two forms of citrullinemia have been described, both having different signs and symptoms, and are caused by mutations in different genes. Citrullinemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of chemical reactions taking place in the liver. These reactions process excess nitrogen, generated when protein is used for energy by the body, to make urea, which is excreted by the kidneys.
Diagnosis
Type I
Type I citrullinemia (Online Mendelian Inheritance in Man (OMIM): 215700, also known as classic citrullinemia) usually becomes evident in the first few days of life. Affected infants typically appear normal at birth, but as ammonia builds up in the body, they develop a lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. These medical problems can be life-threatening in many cases. A milder form of type I citrullinemia is less common in childhood or adulthood. Some people with gene mutations that cause type I citrullinemia never experience signs and symptoms of the disorder.
Investigation for diagnosis of citrullinemia type l elevated citrulline .Type I citrullinemia is the most common form of the disorder, affecting about one in 57,000 births worldwide. Mutations in the ASS gene cause type I citrullinemia. The enzyme made by this gene, argininosuccinate synthetase (EC 6.3.4.5), is responsible for one step of the urea cycle. Mutations in the ASS gene reduce the activity of the enzyme, which disrupts the urea cycle and prevents the body from processing nitrogen effectively. Excess nitrogen, in the form of ammonia, and other byproducts of the urea cycle, accumulate in the bloodstream, leading to the characteristic features of type I citrullinemia.
Type II
The symptoms of type II citrullinemia (Online Mendelian Inheritance in Man (OMIM): 605814 and Online Mendelian Inheritance in Man (OMIM): 603471) usually appear during adulthood and mainly affect the central nervous system. Characteristic features include confusion, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma. Specific investigation like decrease citrulline level , increase ammonium ion . These symptoms can be life-threatening, and are known to be triggered by certain medications, infections, and alcohol intake in people with this type.Type II citrullinemia may also develop in people who had a liver disorder called neonatal cholestasis during infancy. This condition blocks the flow of bile and prevents the body from processing certain nutrients properly. In many cases, the symptoms resolve within a year. Years or even decades later, however, some of these people develop the characteristic features of adult type II citrullinemia.Type II citrullinemia is primarily found in the Japanese population, where it occurs in an estimated one in 100,000 to 230,000 individuals. Type II has also been reported in people from East Asian and Middle Eastern populations. Mutations in the SLC25A13 gene are responsible for type II citrullinemia. This gene makes a protein called citrin, which normally shuttles certain molecules in and out of mitochondria. These molecules are essential for the urea cycle and are also involved in making proteins and nucleotides. Mutations in SLC25A13 typically prevent the production of any functional citrin, which inhibits the urea cycle and disrupts the production of proteins and nucleotides. The resulting buildup of ammonia and other toxic substances leads to the symptoms of type II citrullinemia. Researchers have found many infants with neonatal intrahepatic cholestasis have the same mutations in the SLC25A13 gene as adults with type II citrullinemia.
Treatment
There are multiple treatment methods. Low protein diets, are intended to minimize production of ammonia. Arginine, sodium benzoate and sodium phenylacetate help to remove ammonia from the blood. Dialysis may be used to remove ammonia from the blood when it reaches critical levels.
In some cases, liver transplant has been successful.
See also
Hyperammonemia
Citrullinemia type I
References
Further reading
GeneReviews/NCBI/NIH/UW entry on Argininosuccinate Synthetase Deficiency; ASS Deficiency; Argininosuccinic Acid Synthetase Deficiency; CTLN1; Citrullinemia, Classic
GeneReviews/NIH/UW entry on Citrin deficiency and Citrullinemia Type II
The U.S. National Library of Medicine
== External links == |
Sixth nerve palsy | Sixth nerve palsy, or abducens nerve palsy, is a disorder associated with dysfunction of cranial nerve VI (the abducens nerve), which is responsible for causing contraction of the lateral rectus muscle to abduct (i.e., turn out) the eye. The inability of an eye to turn outward, results in a convergent strabismus or esotropia of which the primary symptom is diplopia (commonly known as double vision) in which the two images appear side-by-side. Thus, the diplopia is horizontal and worse in the distance. Diplopia is also increased on looking to the affected side and is partly caused by overaction of the medial rectus on the unaffected side as it tries to provide the extra innervation to the affected lateral rectus. These two muscles are synergists or "yoke muscles" as both attempt to move the eye over to the left or right. The condition is commonly unilateral but can also occur bilaterally.The unilateral abducens nerve palsy is the most common of the isolated ocular motor nerve palsies.
Signs and symptoms
The nerve dysfunction induces esotropia, a convergent squint on distance fixation. On near fixation the affected individual may have only a latent deviation and be able to maintain binocularity or have an esotropia of a smaller size. Patients sometimes adopt a face turned towards the side of the affected eye, moving the eye away from the field of action of the affected lateral rectus muscle, with the aim of controlling diplopia and maintaining binocular vision.
Diplopia is typically experienced by adults with VI nerve palsies, but children with the condition may not experience diplopia due to suppression. The neuroplasticity present in childhood allows the child to switch off the information coming from one eye (in this case the esotropic eye), thus relieving any diplopic symptoms. Whilst this is a positive adaptation in the short term, in the long term it can lead to a lack of appropriate development of the visual cortex giving rise to permanent visual loss in the suppressed eye; a condition known as amblyopia or Lazy eye.
Cause
Because the nerve emerges near the bottom of the brain, it is often the first nerve compressed when there is any rise in intracranial pressure. Different presentations of the condition, or associations with other conditions, can help to localize the site of the lesion along the VIth cranial nerve pathway.
The most common causes of VIth nerve palsy in adults are:
More common: Vasculopathic (diabetes, hypertension, atherosclerosis), trauma, idiopathic.
Less common: Increased intracranial pressure, giant cell arteritis, cavernous sinus mass (e.g. meningioma, Brain stem Glioblastoma aneurysm, metastasis), multiple sclerosis, sarcoidosis/vasculitis, postmyelography, lumbar puncture, stroke (usually not isolated), Chiari Malformation, hydrocephalus, intracranial hypertension, tuberculosis meningitis.In children, Harley reports typical causes as traumatic, neoplastic (most commonly brainstem glioma), as well as idiopathic. Sixth nerve palsy causes the eyes to deviate inward (see: Pathophysiology of strabismus). Vallee et al. report that benign and rapidly recovering isolated VIth nerve palsy can occur in childhood, sometimes precipitated by ear, nose and throat infections.
Pathophysiology
The pathophysiological mechanism of sixth nerve palsy with increased intracranial pressure has traditionally been said to be stretching of the nerve in its long intracranial course, or compression against the petrous ligament or the ridge of the petrous temporal bone. Collier, however, was "unable to accept this explanation", his view being that since the sixth nerve emerges straight forward from the brain stem, whereas other cranial nerves emerge obliquely or transversely, it is more liable to the mechanical effects of backward brain stem displacement by intracranial space occupying lesions.
Brainstem
Isolated lesions of the VI nerve nucleus will not give rise to an isolated VIth nerve palsy because paramedian pontine reticular formation fibers pass through the nucleus to the opposite IIIrd nerve nucleus. Thus, a nuclear lesion will give rise to an ipsilateral gaze palsy. In addition, fibers of the seventh cranial nerve wrap around the VIth nerve nucleus, and, if this is also affected, a VIth nerve palsy with ipsilateral facial palsy will result. In Millard–Gubler syndrome, a unilateral softening of the brain tissue arising from obstruction of the blood vessels of the pons involving sixth and seventh cranial nerves and the corticospinal tract, the VIth nerve palsy and ipsilateral facial paresis occur with a contralateral hemiparesis. Fovilles syndrome can also arise as a result of brainstem lesions which affect Vth, VIth and VIIth cranial nerves.
Subarachnoid space
As the VIth nerve passes through the subarachnoid space it lies adjacent to anterior inferior and posterior inferior cerebellar and basilar arteries and is therefore vulnerable to compression against the clivus. Typically palsies caused in this way will be associated with signs and symptoms of headache and/or a rise in ICP.
Petrous apex
The nerve passes adjacent to the mastoid sinus and is vulnerable to mastoiditis, leading to inflammation of the meninges, which can give rise to Gradenigos syndrome. This condition results in a VIth nerve palsy with an associated reduction in hearing ipsilaterally, plus facial pain and paralysis, and photophobia. Similar symptoms can also occur secondary to petrous fractures or to nasopharyngeal tumours.
Cavernous sinus/Superior orbital fissure
The nerve runs in the sinus body adjacent to the internal carotid artery and oculo-sympathetic fibres responsible for pupil control, thus, lesions here might be associated with pupillary dysfunctions such as Horners syndrome. In addition, III, IV, V1, and V2 involvement might also indicate a sinus lesion as all run toward the orbit in the sinus wall. Lesions in this area can arise as a result of vascular problems, inflammation, metastatic carcinomas and primary meningiomas.
Orbit
The VIth nerves course is short and lesions in the orbit rarely give rise to isolated VIth nerve palsies, but more typically involve one or more of the other extraocular muscle groups.
Diagnosis
Differential diagnoses
Differential diagnosis is rarely difficult in adults. Onset is typically sudden with symptoms of horizontal diplopia. Limitations of eye movements are confined to abduction of the affected eye (or abduction of both eyes if bilateral) and the size of the resulting convergent squint or esotropia is always larger on distance fixation - where the lateral recti are more active - than on near fixation - where the medial recti are dominant. Abduction limitations that mimic VIth nerve palsy may result secondary to surgery, to trauma or as a result of other conditions such as myasthenia gravis or thyroid eye disease.
In children, differential diagnosis is more difficult because of the problems inherent in getting infants to cooperate with a full eye movement investigation. Possible alternative diagnosis for an abduction deficit would include:
1. Mobius syndrome - a rare congenital disorder in which both VIth and VIIth nerves are bilaterally affected giving rise to a typically expressionless face.
2. Duane syndrome - A condition in which both abduction and adduction are affected arising as a result of partial innervation of the lateral rectus by branches from the IIIrd oculomotor cranial nerve.
3. Cross fixation which develops in the presence of infantile esotropia or nystagmus blockage syndrome and results in habitual weakness of lateral recti.
4. Iatrogenic injury. Abducens nerve palsy is also known to occur with halo orthosis placement. The resultant palsy is identified through loss of lateral gaze after application of the orthosis and is the most common cranial nerve injury associated with this device.
Management
The first aims of management should be to identify and treat the cause of the condition, where this is possible, and to relieve the patients symptoms, where present. In children, who rarely appreciate diplopia, the aim will be to maintain binocular vision and, thus, promote proper visual development.Thereafter, a period of observation of around 6 months is appropriate before any further intervention, as some palsies will recover without the need for surgery.
Symptom relief and/or binocular vision maintenance
This is most commonly achieved through the use of fresnel prisms. These slim flexible plastic prisms can be attached to the patients glasses, or to plano glasses if the patient has no refractive error, and serve to compensate for the inward misalignment of the affected eye. Unfortunately, the prism only correct for a fixed degree of misalignment and, because the affected individuals degree of misalignment will vary depending upon their direction of gaze, they may still experience diplopia when looking to the affected side. The prisms are available in different strengths and the most appropriate one can be selected for each patient. However, in patients with large deviations, the thickness of the prism required may reduce vision so much that binocularity is not achievable. In such cases it may be more appropriate simply to occlude one eye temporarily. Occlusion would never be used in infants though both because of the risk of inducing stimulus deprivation amblyopia and because they do not experience diplopia.Other management options at this initial stage include the use of botulinum toxin, which is injected into the ipsilateral medial rectus (botulinum toxin therapy of strabismus). The use of BT serves a number of purposes. Firstly, it helps to prevent the contracture of the medial rectus which might result from its acting unopposed for a long period. Secondly, by reducing the size of the deviation temporarily it might allow prismatic correction to be used where this was not previously possible, and, thirdly, by removing the pull of the medial rectus it may serve to reveal whether the palsy is partial or complete by allowing any residual movement capability of the lateral rectus to operate. Thus, the toxin works both therapeutically, by helping to reduce symptoms and enhancing the prospects for fuller ocular movements post-operatively, and diagnostically, by helping to determine the type of operation most appropriate for each patient.A Cochrane Review on interventions for eye movement disorders due to acquired brain injury, last updated June 2017, identified one study of botulinum toxin for acute sixth nerve palsy. The Cochrane review authors judged this to be low-certainty evidence; the study was not masked and the estimate of effect was imprecise.
Longer term management
If adequate recovery has not occurred after the 6-month period (during which observation, prism management, occlusion, or botulinum toxin may be considered), surgical treatment is often recommended.If the residual esotropia is small, or if the patient is unfit or unwilling to have surgery, prisms can be incorporated into their glasses to provide more permanent symptom relief. When the deviation is too large for prismatic correction to be effective, permanent occlusion may be the only option for those unfit or unwilling to have surgery.
Surgery
The procedure chosen will depend upon the degree to which any function remains in the affected lateral rectus. Where there is complete paralysis, the preferred option is to perform vertical muscle transposition procedures such as Jensens, Hummelheims or whole muscle transposition, with the aim of using the functioning inferior and superior recti to gain some degree of abduction. An alternative approach is to operate on both the lateral and medial recti of the affected eye, with the aim of stabilising it at the midline, thus giving single vision straight ahead but potentially diplopia on both far left and right gaze. This procedure is often most appropriate for those with total paralysis who, because of other health problems, are at increased risk of the anterior segment ischaemia associated with complex multi-muscle transposition procedures.
Where some function remains in the affected eye, the preferred procedure depends upon the degree of development of muscle sequelae. In a sixth nerve palsy one would expect that, over the 6 month observation period, most patients would show the following pattern of changes to their ocular muscle actions: firstly, an overaction of the medial rectus of the affected eye, then an overaction of the medial rectus of the contraletral eye and, finally, an underaction of the lateral rectus of the unaffected eye - something known as an inhibitional palsy. These changes serve to reduce the variation in the misalignment of the two eyes in different gaze positions (incomitance). Where this process has fully developed, the preferred option is a simple recession, or weakening, of the medial rectus of the affected eye, combined with a resection, or strengthening, of the lateral rectus of the same eye. However, where the inhibitional palsy of the contralateral lateral rectus has not developed, there will still be gross incomitance, with the disparity between the eye positions being markedly greater in the field of action of the affected muscle. In such cases recession of the medial rectus of the affected eye is accompanied by recession and/or posterior fixation (Fadenoperation) of the contraleral medial rectus.The same approaches are adopted bilaterally where both eyes have been affected.
See also
Congenital fourth nerve palsy
References
Further reading
== External links == |
Benign hereditary chorea | Benign hereditary chorea (BHC), also known as benign familial chorea, is a rare autosomal dominant neurogenetic syndrome. It typically presents itself in childhood with isolated chorea, with average to below average intelligence. Unlike other neurogenetic causes of chorea such as Huntingtons disease, BHC is not progressive, and not associated with cognitive decline or psychiatric problems in the vast majority of cases.The first description of BHC was reported in 1967 in an African American family from Mississippi. Two brothers reportedly had delayed motor development in childhood and were diagnosed with chorea.
These findings were reaffirmed by other families reporting similar traits and an autosomal dominant pattern of inheritance was suggested. However, heterogeneity in the presentations of the affected individuals made confirmation of these diagnoses of BHC difficult to prove. Features reported in these families, including dystonia, tremor, and myoclonus, led researchers to question whether BHC actually represents different diagnoses with similar phenotypes inappropriately grouped together.Further research in 2000 confirmed a connection between a Dutch family reporting similar characteristics of BHC and one of the original families. The investigators identified a linkage to a disease locus on the long arm of chromosome 14 from this connection.
Signs and Symptoms
Benign Hereditary Chorea is characterized by early onset of an abnormal gait, speech articulation difficulties, anxiety, and chorea.The clinical spectrum of symptoms resulting from BHC is vast, manifesting as thyroid agenesis to dysarthria to distress syndrome. As a result, genetic testing is the only way to confirm the syndrome.BHC is caused by a single-nucleotide substitution mutation in TITF1, which encodes thyroid transcription factor 1 (TTF-1) and is inherited in an autosomal dominant pattern. This gene is also known as NK2 homeobox 1 (NKX2-1) The single-nucleotide substitution mutation then ultimately has drastic effects on the maturation processes of TITF-1In some cases, additional developmental abnormalities of lung and thyroid tissue are found in BHC, leading to the suggested alternative name brain-lung-thyroid syndrome.
Genetics
Benign Hereditary Chorea is an autosomal dominant disorder. It is believed to be caused by a single-nucleotide substitution in TITF1, located on chromosome 14. A wide spectrum of mutations have been reported, drawing a potential association between amount of subsequently deleted nucleotides to severity of symptoms. These mutations lead to protein truncation, prevent DNA binding, and a loss-of-function. Mutations of the gene affect namely the lungs, brain, and thyroid. This is because during embryonic development, NKX2.1 plays a key role in binding to transcriptional regulatory elements and proteins within those respective organs.
Diagnosis
BHC begins showing symptoms during childhood, and is commonly a familial disorder. This is a disorder that is correlated with mutations in the thyroid transcription factor gene (TITF-1).
The disorder was discovered in the 1960s. During the time of its discovery, there were no tests that could be used to confirm a diagnosis of the disorder, and the phenotype was not easy to distinguish from other disorders. This resulted in the existence of the disorder being questioned. However, in 2002, the experimentally observed mutation of the gene leading to the BHC phenotype was identified, solidifying benign hereditary chorea as a disorder. In 1967, several families were examined and discovered to have movements that were abnormal and random since childhood. These random movements were not violent movements, and gave the person a "general appearance of restlessness." The movements occurred mostly in the hands and arms, and some also experienced them in their tongues, facial muscles, and lower body. Movements in the lower extremities, if severe enough, could cause changes in gait. The families were given a Wechsler Intelligence Scale test, scoring average relative to others in their community. Aside from the aforementioned symptoms, the peoples physical and neurological characteristics were normal. The observed symptoms were put in the category of chorea. Researchers made pedigrees of the families they studied and determined that BHC was an autosomal dominant disorder. By studying a Dutch family, the disorder was discovered to be linked to chromosome 14. In 2002, an Italian family was studied, and they had the same linkage to chromosome 14 as the Dutch family did. Looking closer at the region of the chromosome suspected of causing the disorder, researchers discovered that there was a 1.2 Mb deletion in the DNA that resulted in the loss of the TITF-1 gene. This meant that mutations in the TITF-1 gene were likely the reason behind the symptoms of BHC. Currently, BHC is diagnosed through the identification of the phenotypic symptoms with a genetic test to confirm the mutation in the TITF-1 gene.
Management
There are no cures for benign hereditary chorea, but there are several medications that have been shown to treat the symptoms of the disorder. Levodopa has been shown to improve the effects of chorea on a patients gait within 6 weeks of starting treatments. However, this medication did have the side effect of "dose-dependent dyskinesia." Methylphenidate has also been used to improve chorea symptoms. Steroids have been used to treat BHC, but due to the presence of dystonia, it is questionable whether these patients actually had BHC.
Epidemiology
In 1978, BHC was reported to have a frequency of 1:500,000 within a Welsh population, but due to how some symptoms are hard to distinguish, it was concluded that the number is underrespresentative of actual clinical cases. Results for correlation between sex and distribution of the disorder are inconclusive.
See also
Chorea
Huntingtons disease
References
== External links == |
Necrotizing sialometaplasia | Necrotizing sialometaplasia (NS) is a benign, ulcerative lesion, usually located towards the back of the hard palate. It is thought to be caused by ischemic necrosis (death of tissue due to lack of blood supply) of minor salivary glands in response to trauma. Often painless, the condition is self-limiting and should heal in 6–10 weeks.
Although entirely benign and requiring no treatment, due to its similar appearance to oral cancer, it is sometimes misdiagnosed as malignant. Therefore, it is considered an important condition, despite its rarity.
Signs and symptoms
The condition most commonly is located at the junction of the hard and soft palate. However, the condition may arise anywhere minor salivary glands are located. It has also been occasionally reported to involve the major salivary glands. It may be present only on one side, or both sides. The lesion typically is 1–4 cm in diameter.Initially, the lesion is a tender, erythematous (red) swelling. Later, in the ulcerated stage, the overlying mucosa breaks down to leave a deep, well-circumscribed ulcer which is yellow-gray in color and has a lobular base.There is usually only minor pain, and the condition is often entirely painless. There may be prodromal symptoms similar to flu before the appearance of the lesion.
Causes
The exact cause of the condition is unknown. There is most evidence to support vascular infarction and ischemic necrosis of salivary gland lobules as a mechanism for the condition. Experimentally, local anaesthetic injections and tying of the arteries is reported to trigger the development of tissue changes similar to NS in lab rats. Factors which are thought to cause this ischemia are listed below, however sometimes there is no evident predisposing factor or initiating event.
Trauma e.g. during intubation, or surgical procedures
Local anesthetic injection
Smoking
Alcohol
Diabetes mellitus
Vascular disease, (e.g. arteriosclerosis)
Pressure from a dental prosthesis
Allergy
Bulimia
Infection
Ionizing radiation
Diagnosis
Differentiation between this and SCC would be based on a history of recent trauma or dental treatment in the area.
Immunohistochemistry may aid the diagnosis. If the lesion is NS, there will be focal to absent immunoreactivity for p53, low immunoreactivity for MIB1 (Ki-67), and the presence of 4A4/p63- and calponin-positive myoepithelial cells.
Treatment
No surgery is required.
Prognosis
Healing is prolonged, and usually takes 6–10 weeks. The ulcer heals by secondary intention.
Epidemiology
The condition is rare.
The typical age range of those affected by the condition is about 23–66 years of age. It usually occurs in smokers. The male to female ratio has been reported as 1.95:1, and 2.31:1.
History
NS was first reported by Abrams et al. in 1973.
Notes
References
== External links == |
Familial hemiplegic migraine | Familial hemiplegic migraine (FHM) is an autosomal dominant type of hemiplegic migraine that typically includes weakness of half the body which can last for hours, days, or weeks. It can be accompanied by other symptoms, such as ataxia, coma, and paralysis. Migraine attacks may be provoked by minor head trauma. Some cases of minor head trauma in patients with hemiplegic migraine can develop into delayed cerebral edema, a life-threatening medical emergency. Clinical overlap occurs in some FHM patients with episodic ataxia type 2 and spinocerebellar ataxia type 6, benign familial infantile epilepsy, and alternating hemiplegia of childhood.
Three genetic loci for FHM are known. FHM1, which accounts for about 50% of FHM patients, is caused by mutations in a gene coding for the P/Q-type calcium channel α subunit, CACNA1A. FHM1 is also associated with cerebellar degeneration. FHM2, which accounts for less than 25% of cases, is caused by mutations in the Na+/K+-ATPase gene ATP1A2. FHM3 is a rare subtype of FHM and is caused by mutations in a sodium channel α-subunit coding gene, SCN1A. These three subtypes do not account for all cases of FHM, suggesting the existence of at least one other locus (FHM4).
Also, nonfamilial cases of hemiplegic migraine are seen, termed sporadic hemiplegic migraine. These cases seem to have the same causes as the familial cases and represent de novo mutations. Sporadic cases are also clinically identical to familial cases with the exception of a lack of known family history of attacks.
Signs and symptoms
FHM signs overlap significantly with those of migraine with aura. In short, FHM is typified by migraine with aura associated with hemiparesis, and in FHM1, cerebellar degeneration, which can result in episodic or progressive ataxia. FHM can also present with the same signs as benign familial infantile convulsions and alternating hemiplegia of childhood. Other symptoms are altered consciousness (in fact, some cases seem related to head trauma), gaze-evoked nystagmus, and coma. Aura symptoms, such as numbness and blurring of vision, typically persist for 30–60 minutes, but can last for weeks to months. An attack resembles a stroke, but unlike a stroke, it resolves in time. These signs typically first manifest themselves in the first or second decade of life.
Causes
See the equivalent section in the main migraine article.
FHM mutations are believed to lead to migraine susceptibility by lowering the threshold for cortical-spreading-depression generation. The FHM1 and FHM3 mutations occur in ion channels expressed in neurons. These mutations may lead to both the hyper- and hypoexcitable neurons that might underlie cortical-spreading-depression. How the mutations seen in FHM2 patients might lead to FHM symptoms is even less clear, as the gene mutated in FHM2 is expressed primarily in astrocytes. One proposal states that the depolarization of astrocytes caused by haploinsufficiency of the ATP1A2 Na+/K+-ATPase causes increased release of compounds such as adenosine from astrocytes. These compounds then interact with neighboring neurons, altering their excitability and leading to cortical-spreading-depression and migraine.
Pathophysiology
FHM1 (CACNA1A)
The first discovered FHM locus was the CACNA1A gene (originally named CACNL1A4), which encodes the P/Q-type calcium channel CaV2.1. Currently, 17 mutations in this channel are known (table 1), and these mutations are distributed throughout the channel. Some of these mutations result in patients with notable cerebellar degeneration or other dysfunction, including one mutation (S218L), which may be related to severe responses to mild concussion, up to and including delayed cerebral edema, coma, and death. Fifteen of these mutants have received at least some further analysis at the electrophysiological level to attempt to determine how they might lead to the FHM1 phenotype. Contradiction in the literature is increasing as to the end result of these mutations on channel kinetics and neuronal excitability.A good example of this contradiction can be seen in the literature regarding the R192Q mutation. The first investigation of this mutation, using the rabbit isoform of the channel expressed in oocytes, found that it did not alter any measured channel properties. A subsequent report, using human channels expressed in HEK293 cells, found a small, hyperpolarizing shift in the midpoint for activation, a result common among FHM1 mutants. This shift results in channels that open at more negative potentials, thus have a higher open probability than wild-type channels at most potentials. This report also found that the R192Q mutant produced almost twice as much whole-cell current compared to wild-type channels. This is not due to a change in single channel conductance, but to an equivalent increase in channel density. A subsequent group noticed that this mutation is in a region important for modulation by G protein-coupled receptors (GPCRs). GPCR activation leads to inhibition of wild-type CaV2.1 currents. R192Q mutant channel currents are also decreased by GPCR activation, but by a smaller amount. A more recent group has confirmed some of these results by creating a R192Q knock-in mouse. They confirmed that the R192Q mutant activates at more negative potentials and that neurons producing these channels have much larger whole-cell current. This resulted in a much larger quantal content (the number of neurotransmitter packets released per action potential) and generally enhanced neurotransmitter release in R192Q-expressing neurons versus wild-type. Consequently, these mutant mice were more susceptible to cortical-spreading-depression than their wild-type counterparts. The most recent experiments on this mutant, however, have contradicted some of these results. In CaV2.1 knockout neurons transfected with human channels, P/Q-type currents from mutant channels are actually smaller than their wild-type counterpart. They also found a significant decrease in calcium influx during depolarization, leading to decreased quantal content, in mutant versus wild-type expressing neurons. Neurons expressing mutant channels were also less able to mediate inhibitory input and have smaller inhibitory postsynaptic currents through P/Q-type channels. Further testing with this and other mutants is required to determine their end effect on human physiology.
FHM2 (ATP1A2)
The second subtype of familial hemiplegic migraine, FHM2, is caused by mutations in the gene ATP1A2 that encodes a Na+/K+-ATPase. This Na+/K+-ATPase is heavily expressed in astrocytes and helps to set and maintain their reversal potential. Twenty-nine known mutations in this gene are associated with FHM2 (table 2), many clustering in the large intracellular loop between membrane-spanning segments 4 and 5 (figure 1). Twelve of these mutations have been studied by expression in model cells. All but one have shown either complete loss of function or more complex decreases in ATPase activity or potassium sensitivity. Astrocytes expressing these mutant ion pumps will have much higher resting potentials and are believed to lead to disease through a poorly understood mechanism.
FHM3 (SCN1A)
The final known locus FHM3 is the SCN1A gene, which encodes a sodium channel α subunit. The only study so far that has found mutations in this gene discovered the same Q1489K mutation in three of 20 families (15%) with 11 other kindreds (55%) already having mutations in CACNA1A or ATP1A2. This mutation is located in a highly conserved region of an intracellular loop connecting domains three and four. This mutation results in a greatly hastened (two- to four-fold) recovery from inactivation compared to wild-type. As this channel is important for action potential generation in neurons, the Q1489K mutant is expected to result in hyperexcitable neurons.
FHM4 (1q31)
The final locus for FHM maps to the q-arm of chromosome 1. A number of attractive candidate genes occur in this area, though no mutations in them have yet been linked to FHM4.
Other genetic associations
A fourth gene associated with this condition is the proline-rich transmembrane protein 2 (PRRT2 gene) - an axonal protein associated with the exocytosis complex.A fifth gene associated with this condition is SLC4A4, which encodes the electrogenic NaHCO3 cotransporter NBCe1.
Diagnosis
Diagnosis of FHM is made according to these criteria:
Two attacks of each of:Aura with motor weakness accompanied by either reversible visual symptoms (flickering lights, spots, lines, etc.), reversible sensory symptoms (pins and needles, numbness, etc.) or speech symptoms
At least two occurrences of:One or more aura symptoms that develop over at least 5 minutes
These symptoms lasting more than 5 minutes and less than 24 hours
Headache beginning within 60 minutes of aura onset: These headaches can last 4–72 hours, occur on only one side of the head, pulsate, be of moderate to severe intensity, and may be aggravated by common physical activities such as walking. These headaches must also be accompanied by nausea/vomiting, phonophobia (avoidance of sound due to hypersensitivity), and/or photophobia (avoidance of light due to hypersensitivity).At least one close (first- or second-degree) relative with FHM
No other likely causeSporadic forms follow the same diagnostic criteria, with the exception of family history.
In all cases, family and patient histories are used for diagnosis. Brain-imaging techniques, such as MRI, CAT scan, and SPECT, are used to look for signs of other familial conditions such as CADASIL or mitochondrial disease, and for evidence of cerebellar degeneration. With the discovery of causative genes, genetic sequencing can also be used to verify diagnosis (though not all genetic loci are known).
Screening
Prenatal screening is not typically done for FHM, but it may be performed if requested. As penetrance is high, individuals found to carry mutations should be expected to develop signs of FHM at some point in life.
Management
See the equivalent section in the main migraine article.
People with FHM are encouraged to avoid activities that may trigger their attacks. Minor head trauma is a common attack precipitant, so FHM sufferers should avoid contact sports. Acetazolamide or standard drugs are often used to treat attacks, though those leading to vasoconstriction should be avoided due to the risk of stroke.
Epidemiology
Migraine itself is a very common disorder, occurring in 15–20% of the population. Hemiplegic migraine, be it familial or spontaneous, is less prevalent, at 0.01% prevalence according to one report. Women are three times more likely to be affected than males.
See also
Channelopathy
Childhood absence epilepsy
Hypokalemic periodic paralysis
Juvenile myoclonic epilepsy
Malignant hyperthermia
Timothy syndrome
References
External links
GeneReviews/NCBI/NIH/UW entry on Familial Hemiplegic Migraine
"The International Classification of Headache Disorders 2nd Edition". Cephalalgia. 24 (s1): 8–160. May 2004. ISSN 1468-2982. |
Congenital iodine deficiency syndrome | Congenital iodine deficiency syndrome is a medical condition present at birth marked by impaired physical and mental development, due to insufficient thyroid hormone (hypothyroidism) often caused by insufficient dietary iodine during pregnancy. It is one cause of underactive thyroid function at birth, called congenital hypothyroidism, historically referred to as cretinism (obsolete). If untreated, it results in impairment of both physical and mental development. Symptoms may include goiter, poor length growth in infants, reduced adult stature, thickened skin, hair loss, enlarged tongue, a protruding abdomen; delayed bone maturation and puberty in children; and mental deterioration, neurological impairment, impeded ovulation, and infertility in adults.In developed countries, thyroid function testing of newborns has assured that in those affected, treatment with the thyroid hormone thyroxine is begun promptly. This screening and treatment have virtually eliminated the consequences of the disease.
Signs and symptoms
Iodine deficiency causes gradual enlargement of the thyroid gland, referred to as a goiter. Poor length growth is apparent as early as the first year of life. Adult stature without treatment ranges from 100 to 160 cm (3 ft 3 in to 5 ft 3 in), depending on severity, sex, and other genetic factors. Other signs include thickened skin, hair loss, enlarged tongue, and a protruding abdomen. In children, bone maturation and puberty are severely delayed. In adults, ovulation is impeded and infertility is common.Mental deterioration is common. Neurological impairment may be mild, with reduced muscle tone and coordination, or so severe that the person cannot stand or walk. Cognitive impairment may also range from mild to so severe that the person is nonverbal and dependent on others for basic care. Thought and reflexes are slower.
Cause
Around the world, the most common cause of congenital iodine deficiency syndrome (endemic cretinism) is dietary iodine deficiency.
Iodine is an essential trace element, necessary for the synthesis of thyroid hormones. Iodine deficiency is the most common preventable cause of neonatal and childhood brain damage worldwide. Although iodine is found in many foods, it is not universally present in all soils in adequate amounts. Most iodine, in iodide form, is in the oceans, where the iodide ions are reduced to elemental iodine, which then enters the atmosphere and falls to earth in rain, introducing iodine to soils. Soil deficient in iodine is most common inland, in mountainous areas, and in areas of frequent flooding. It can also occur in coastal regions, where iodine might have been removed from the soil by glaciation, as well as leaching by snow, water and heavy rainfall. Plants and animals grown in iodine-deficient soils are correspondingly deficient. Populations living in those areas without outside food sources are most at risk of iodine deficiency diseases.
Diagnosis
Differential diagnosis
Dwarfism may also be caused by malnutrition or other hormonal deficiencies, such as insufficient growth hormone secretion, hypopituitarism, decreased secretion of growth hormone-releasing hormone, deficient growth hormone receptor activity and downstream causes, such as insulin-like growth factor 1 (IGF-1) deficiency.
Prevention
There are public health campaigns in many countries which involve iodine administration. As of December 2019, 122 countries have mandatory iodine food fortification programs.
Treatment
Congenital iodine deficiency has been almost eliminated in developed countries through iodine supplementation of food and by newborn screening utilizing a blood test for thyroid function.Treatment consists of lifelong administration of thyroxine (T4). Thyroxine must be dosed as tablets only, even to newborns, as the liquid oral suspensions and compounded forms cannot be depended on for reliable dosing. For infants, the T4 tablets are generally crushed and mixed with breast milk, formula milk or water. If the medication is mixed with formulas containing iron or soya products, larger doses may be required, as these substances may alter the absorption of thyroid hormone from the gut. Monitoring TSH blood levels every 2–3 weeks during the first months of life is recommended to ensure that affected infants are at the high end of normal range.
History
A goiter is the most specific clinical marker of either the direct or indirect insufficient intake of iodine in the human body. There is evidence of goiter, and its medical treatment with iodine-rich algae and burnt sponges, in Chinese, Egyptian, and Roman ancient medical texts. In 1848, King Carlo Alberto of Sardinia commissioned the first epidemiological study of congenital iodine deficiency syndrome, in northern Savoy where it was frequent. In past centuries, the well reported social diseases prevalent among the poorer social classes and farmers, caused by dietary and agricultural monocultures, were: pellagra, rickets, beriberi, scurvy in long-term sailors, and the endemic goiter caused by iodine deficiency. However, this disease was less mentioned in medical books because it was erroneously considered to be an aesthetic rather than a clinical disorder.Congenital iodine-deficiency syndrome was especially common in areas of southern Europe around the Alps and was often described by ancient Roman writers and depicted by artists. The earliest Alpine mountain climbers sometimes came upon whole villages affected by it. The prevalence of the condition was described from a medical perspective by several travellers and physicians in the late 18th and early 19th centuries. At that time the cause was not known and it was often attributed to "stagnant air" in mountain valleys or "bad water". The proportion of people affected varied markedly throughout southern Europe and even within very small areas, it might be common in one valley and not another. The number of severely affected persons was always a minority, and most persons were only affected to the extent of having a goitre and some degree of reduced cognition and growth. The majority of such cases were still socially functional in their pastoral villages.More mildly affected areas of Europe and North America in the 19th century were referred to as "goitre belts". The degree of iodine deficiency was milder and manifested primarily as thyroid enlargement rather than severe mental and physical impairment. In Switzerland, for example, where soil does not contain a large amount of iodine, cases of congenital iodine deficiency syndrome were very abundant and even considered genetically caused. As the variety of food sources dramatically increased in Europe and North America and the populations became less completely dependent on locally grown food, the prevalence of endemic goitre diminished. This is supported by a 1979 WHO publication which concluded that "changes in the origin of food supplies may account for the otherwise unexplained disappearance of endemic goitre from a number of localities during the past 50 years".The early 20th century saw the discovery of the relationships of neurological impairment with hypothyroidism due to iodine deficiency. Both have been largely eliminated in the developed world.
Terminology
The term cretin was originally used to describe a person affected by this condition, but, as with words such as spastic and lunatic, it underwent pejoration and is now considered derogatory and inappropriate. Cretin became a medical term in the 18th century, from an Occitan and an Alpine French expression, prevalent in a region where persons with such a condition were especially common (see below); it saw wide medical use in the 19th and early 20th centuries, and was a "tick box" category on Victorian-era census forms in the UK. The term spread more widely in popular English as a markedly derogatory term for a person who behaves stupidly. Because of its pejorative connotations in popular speech, current usage among health care professionals has abandoned the noun "cretin" referring to a person. The noun cretinism, referring to the condition, still occurs in medical literature and textbooks but its use is waning.The etymology of cretin is uncertain. Several hypotheses exist. The most common derivation provided in English dictionaries is from the Alpine French dialect pronunciation of the word Chrétien ("(a) Christian"), which was a greeting there. According to the Oxford English Dictionary, the translation of the French term into "human creature" implies that the label "Christian" is a reminder of the humanity of the affected, in contrast to brute beasts. Other sources suggest that Christian describes the persons "Christ-like" inability to sin, stemming, in such cases, from an incapacity to distinguish right from wrong.Other speculative etymologies have been offered:
From creta, Latin for chalk, because of the pallor of those affected.
From cretira, Grison-Romanche creature, from Latin creatus.
From cretine, French for alluvium (soil deposited by flowing water), an allusion to the conditions suspected origin in inadequate soil.
See also
Moron (psychology)
References
External links
Media related to Congenital iodine deficiency syndrome at Wikimedia Commons |
Ichthyosis with confetti | Ichthyosis en confetti, is a very rare form of congenital ichthyosis in which healthy patches of normal skin co-exist within the abnormal skin areas. The condition is caused by a frameshift mutation in the keratin 10 gene (KRT10); mutant keratin 10 accumulates in the nucleolus, a sub-nuclear structure, rather than within cellular intermediate filaments like the wild-type protein. Children with the condition exhibit red, flaky skin; however, for reasons not yet totally clear, wild type clonal patches of skin start to appear, in place of the red, flaky skin. Due to the clonal nature of the growth of the normal skin cells, it appears the patient is covered with confetti, hence the name of the condition. It has been hypothesized that this is the result of a combination of mitotic recombination and natural selection within the skin.
See also
List of cutaneous conditions caused by mutations in keratins
List of cutaneous conditions
References
== External links == |
Kidney stone disease | Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine stream. A small stone may pass without causing symptoms. If a stone grows to more than 5 millimeters (0.2 inches), it can cause blockage of the ureter, resulting in sharp and severe pain in the lower back or abdomen. A stone may also result in blood in the urine, vomiting, or painful urination. About half of people who have had a kidney stone will have another within ten years.Most stones form by a combination of genetics and environmental factors. Risk factors include high urine calcium levels, obesity, certain foods, some medications, calcium supplements, hyperparathyroidism, gout and not drinking enough fluids. Stones form in the kidney when minerals in urine are at high concentration. The diagnosis is usually based on symptoms, urine testing, and medical imaging. Blood tests may also be useful. Stones are typically classified by their location: nephrolithiasis (in the kidney), ureterolithiasis (in the ureter), cystolithiasis (in the bladder), or by what they are made of (calcium oxalate, uric acid, struvite, cystine).In those who have had stones, prevention is by drinking fluids such that more than two liters of urine are produced per day. If this is not effective enough, thiazide diuretic, citrate, or allopurinol may be taken. It is recommended that soft drinks containing phosphoric acid (typically colas) be avoided. When a stone causes no symptoms, no treatment is needed; otherwise, pain control is usually the first measure, using medications such as nonsteroidal anti-inflammatory drugs or opioids. Larger stones may be helped to pass with the medication tamsulosin or may require procedures such as extracorporeal shock wave lithotripsy, ureteroscopy, or percutaneous nephrolithotomy.Between 1% and 15% of people globally are affected by kidney stones at some point in their lives. In 2015, 22.1 million cases occurred, resulting in about 16,100 deaths. They have become more common in the Western world since the 1970s. Generally, more men are affected than women. Kidney stones have affected humans throughout history with descriptions of surgery to remove them dating from as early as 600 BC.
Signs and symptoms
The hallmark of a stone that obstructs the ureter or renal pelvis is excruciating, intermittent pain that radiates from the flank to the groin or to the inner thigh. This is due to the transfer of referred pain signals from the lower thoracic splanchnic nerves to the lumbar splanchnic nerves as the stone passes down from the kidney or proximal ureter to the distal ureter. This pain, known as renal colic, is often described as one of the strongest pain sensations known. Renal colic caused by kidney stones is commonly accompanied by urinary urgency, restlessness, hematuria, sweating, nausea, and vomiting. It typically comes in waves lasting 20 to 60 minutes caused by peristaltic contractions of the ureter as it attempts to expel the stone.The embryological link between the urinary tract, the genital system, and the gastrointestinal tract is the basis of the radiation of pain to the gonads, as well as the nausea and vomiting that are also common in urolithiasis. Postrenal azotemia and hydronephrosis can be observed following the obstruction of urine flow through one or both ureters.Pain in the lower-left quadrant can sometimes be confused with diverticulitis because the sigmoid colon overlaps the ureter, and the exact location of the pain may be difficult to isolate due to the proximity of these two structures.
Risk factors
Dehydration from low fluid intake is a major factor in stone formation. Individuals living in warm climates are at higher risk due to increased fluid loss. Obesity, immobility, and sedentary lifestyles are other leading risk factors.High dietary intake of animal protein, sodium, sugars including honey, refined sugars, fructose and high fructose corn syrup, and excessive consumption of fruit juices may increase the risk of kidney stone formation due to increased uric acid excretion and elevated urinary oxalate levels (whereas tea, coffee, wine and beer may decrease the risk).Kidney stones can result from an underlying metabolic condition, such as distal renal tubular acidosis, Dents disease, hyperparathyroidism, primary hyperoxaluria, or medullary sponge kidney. 3–20% of people who form kidney stones have medullary sponge kidney.Kidney stones are more common in people with Crohns disease; Crohns disease is associated with hyperoxaluria and malabsorption of magnesium.A person with recurrent kidney stones may be screened for such disorders. This is typically done with a 24-hour urine collection. The urine is analyzed for features that promote stone formation.
Calcium oxalate
Calcium is one component of the most common type of human kidney stones, calcium oxalate. Some studies suggest that people who take calcium or vitamin D as a dietary supplement have a higher risk of developing kidney stones. In the United States, kidney stone formation was used as an indicator of excess calcium intake by the Reference Daily Intake committee for calcium in adults.In the early 1990s, a study conducted for the Womens Health Initiative in the US found that postmenopausal women who consumed 1000 mg of supplemental calcium and 400 international units of vitamin D per day for seven years had a 17% higher risk of developing kidney stones than subjects taking a placebo. The Nurses Health Study also showed an association between supplemental calcium intake and kidney stone formation.Unlike supplemental calcium, high intakes of dietary calcium do not appear to cause kidney stones and may actually protect against their development. This is perhaps related to the role of calcium in binding ingested oxalate in the gastrointestinal tract. As the amount of calcium intake decreases, the amount of oxalate available for absorption into the bloodstream increases; this oxalate is then excreted in greater amounts into the urine by the kidneys. In the urine, oxalate is a very strong promoter of calcium oxalate precipitation—about 15 times stronger than calcium.
A 2004 study found that diets low in calcium are associated with a higher overall risk for kidney stone formation. For most individuals, other risk factors for kidney stones, such as high intakes of dietary oxalates and low fluid intake, play a greater role than calcium intake.
Other electrolytes
Calcium is not the only electrolyte that influences the formation of kidney stones. For example, by increasing urinary calcium excretion, high dietary sodium may increase the risk of stone formation.Drinking fluoridated tap water may increase the risk of kidney stone formation by a similar mechanism, though further epidemiologic studies are warranted to determine whether fluoride in drinking water is associated with an increased incidence of kidney stones. High dietary intake of potassium appears to reduce the risk of stone formation because potassium promotes the urinary excretion of citrate, an inhibitor of calcium crystal formation.Kidney stones are more likely to develop, and to grow larger, if a person has low dietary magnesium. Magnesium inhibits stone formation.
Animal protein
Diets in Western nations typically contain a large proportion of animal protein. Eating animal protein creates an acid load that increases urinary excretion of calcium and uric acid and reduced citrate. Urinary excretion of excess sulfurous amino acids (e.g., cysteine and methionine), uric acid, and other acidic metabolites from animal protein acidifies the urine, which promotes the formation of kidney stones. Low urinary-citrate excretion is also commonly found in those with a high dietary intake of animal protein, whereas vegetarians tend to have higher levels of citrate excretion. Low urinary citrate, too, promotes stone formation.
Vitamins
The evidence linking vitamin C supplements with an increased rate of kidney stones is inconclusive. The excess dietary intake of vitamin C might increase the risk of calcium-oxalate stone formation. The link between vitamin D intake and kidney stones is also tenuous.
Excessive vitamin D supplementation may increase the risk of stone formation by increasing the intestinal absorption of calcium; correction of a deficiency does not.
Pathophysiology
Supersaturation of urine
When the urine becomes supersaturated (when the urine solvent contains more solutes than it can hold in solution) with one or more calculogenic (crystal-forming) substances, a seed crystal may form through the process of nucleation. Heterogeneous nucleation (where there is a solid surface present on which a crystal can grow) proceeds more rapidly than homogeneous nucleation (where a crystal must grow in a liquid medium with no such surface), because it requires less energy. Adhering to cells on the surface of a renal papilla, a seed crystal can grow and aggregate into an organized mass. Depending on the chemical composition of the crystal, the stone-forming process may proceed more rapidly when the urine pH is unusually high or low.Supersaturation of the urine with respect to a calculogenic compound is pH-dependent. For example, at a pH of 7.0, the solubility of uric acid in urine is 158 mg/100 ml. Reducing the pH to 5.0 decreases the solubility of uric acid to less than 8 mg/100 ml. The formation of uric-acid stones requires a combination of hyperuricosuria (high urine uric-acid levels) and low urine pH; hyperuricosuria alone is not associated with uric-acid stone formation if the urine pH is alkaline. Supersaturation of the urine is a necessary, but not a sufficient, condition for the development of any urinary calculus. Supersaturation is likely the underlying cause of uric acid and cystine stones, but calcium-based stones (especially calcium oxalate stones) may have a more complex cause.
Randalls plaque
While supersaturation of urine may lead to crystalluria, it does not necessarily promote the formation of a kidney stone because the particle may not reach the sufficient size needed for renal attachment. On the other hand, Randalls plaques, which were first identified by Alexander Randall in 1937, are calcium phosphate deposits that form in the papillary interstitium and are thought to be the nidus required for stone development. In addition to Randalls plugs, which form in the Duct of Bellini, these structures can generate reactive oxygen species that further enhance stone formation.
Pathogenic bacteria
Some bacteria have roles in promoting stone formation. Specifically, urease-positive bacteria, such as Proteus mirabilis can produce the enzyme urease, which converts urea to ammonia and carbon dioxide. This increases the urinary pH and promotes struvite stone formation. Additionally, non-urease producing bacteria can provide bacteria components that can promote calcium oxalate crystallization, though this mechanism is poorly understood.
Inhibitors of stone formation
Normal urine contains chelating agents, such as citrate, that inhibit the nucleation, growth, and aggregation of calcium-containing crystals. Other endogenous inhibitors include calgranulin (an S-100 calcium-binding protein), Tamm–Horsfall protein, glycosaminoglycans, uropontin (a form of osteopontin), nephrocalcin (an acidic glycoprotein), prothrombin F1 peptide, and bikunin (uronic acid-rich protein). The biochemical mechanisms of action of these substances have not yet been thoroughly elucidated. However, when these substances fall below their normal proportions, stones can form from an aggregation of crystals.Sufficient dietary intake of magnesium and citrate inhibits the formation of calcium oxalate and calcium phosphate stones; in addition, magnesium and citrate operate synergistically to inhibit kidney stones. The efficacy of magnesium in subduing stone formation and growth is dose-dependent.
Hypocitraturia
Hypocitraturia or low urinary-citrate excretion (variably defined as less than 320 mg/day) can be a contributing cause of kidney stones in up to 2/3 of cases. The protective role of citrate is linked to several mechanisms; citrate reduces urinary supersaturation of calcium salts by forming soluble complexes with calcium ions and by inhibiting crystal growth and aggregation. Therapy with potassium citrate is commonly prescribed in clinical practice to increase urinary citrate and to reduce stone formation rates. Alkali citrate is also used to increase urine citrate levels. It can be prescribed or found over-the-counter in pill, liquid or powder form.
Diagnosis
Diagnosis of kidney stones is made on the basis of information obtained from the history, physical examination, urinalysis, and radiographic studies. Clinical diagnosis is usually made on the basis of the location and severity of the pain, which is typically colicky in nature (comes and goes in spasmodic waves). Pain in the back occurs when calculi produce an obstruction in the kidney. Physical examination may reveal fever and tenderness at the costovertebral angle on the affected side.
Imaging studies
Calcium-containing stones are relatively radiodense, and they can often be detected by a traditional radiograph of the abdomen that includes the kidneys, ureters, and bladder (KUB film). KUB radiograph, although useful in monitoring size of stone or passage of stone in stone formers, might not be useful in the acute setting due to low sensitivity. Some 60% of all renal stones are radiopaque. In general, calcium phosphate stones have the greatest density, followed by calcium oxalate and magnesium ammonium phosphate stones. Cystine calculi are only faintly radiodense, while uric acid stones are usually entirely radiolucent.In people with a history of stones, those who are less than 50 years of age and are presenting with the symptoms of stones without any concerning signs do not require helical CT scan imaging. A CT scan is also not typically recommended in children.Otherwise a noncontrast helical CT scan with 5 millimeters (0.2 in) sections is the diagnostic method to use to detect kidney stones and confirm the diagnosis of kidney stone disease. Near all stones are detectable on CT scans with the exception of those composed of certain drug residues in the urine, such as from indinavir.
Where a CT scan is unavailable, an intravenous pyelogram may be performed to help confirm the diagnosis of urolithiasis. This involves intravenous injection of a contrast agent followed by a KUB film. Uroliths present in the kidneys, ureters, or bladder may be better defined by the use of this contrast agent. Stones can also be detected by a retrograde pyelogram, where a similar contrast agent is injected directly into the distal ostium of the ureter (where the ureter terminates as it enters the bladder).Renal ultrasonography can sometimes be useful, because it gives details about the presence of hydronephrosis, suggesting that the stone is blocking the outflow of urine. Radiolucent stones, which do not appear on KUB, may show up on ultrasound imaging studies. Other advantages of renal ultrasonography include its low cost and absence of radiation exposure. Ultrasound imaging is useful for detecting stones in situations where X-rays or CT scans are discouraged, such as in children or pregnant women. Despite these advantages, renal ultrasonography in 2009 was not considered a substitute for noncontrast helical CT scan in the initial diagnostic evaluation of urolithiasis. The main reason for this is that, compared with CT, renal ultrasonography more often fails to detect small stones (especially ureteral stones) and other serious disorders that could be causing the symptoms.On the contrary, a 2014 study suggested that ultrasonography should be used as the initial diagnostic imaging test, with further imaging studies be performed at the discretion of the physician on the basis of clinical judgment, and using ultrasonography rather than CT as an initial diagnostic test results in less radiation exposure and equally good outcome.
Laboratory examination
Laboratory investigations typically carried out include
microscopic examination of the urine, which may show red blood cells, bacteria, leukocytes, urinary casts, and crystals;
urine culture to identify any infecting organisms present in the urinary tract and sensitivity to determine the susceptibility of these organisms to specific antibiotics;
complete blood count, looking for neutrophilia (increased neutrophil granulocyte count) suggestive of bacterial infection, as seen in the setting of struvite stones;
renal function tests to look for abnormally high blood calcium levels (hypercalcemia);
24 hour urine collection to measure total daily urinary volume, magnesium, sodium, uric acid, calcium, citrate, oxalate, and phosphate;
collection of stones (by urinating through a StoneScreen kidney stone collection cup or a simple tea strainer) is useful. Chemical analysis of collected stones can establish their composition, which in turn can help to guide future preventive and therapeutic management.
Composition
Calcium-containing stones
By far, the most common type of kidney stones worldwide contains calcium. For example, calcium-containing stones represent about 80% of all cases in the United States; these typically contain calcium oxalate either alone or in combination with calcium phosphate in the form of apatite or brushite. Factors that promote the precipitation of oxalate crystals in the urine, such as primary hyperoxaluria, are associated with the development of calcium oxalate stones. The formation of calcium phosphate stones is associated with conditions such as hyperparathyroidism and renal tubular acidosis.Oxaluria is increased in patients with certain gastrointestinal disorders including inflammatory bowel disease such as Crohns disease or in patients who have undergone resection of the small bowel or small-bowel bypass procedures. Oxaluria is also increased in patients who consume increased amounts of oxalate (found in vegetables and nuts). Primary hyperoxaluria is a rare autosomal recessive condition that usually presents in childhood.Calcium oxalate crystals can come in two varieties. Calcium oxalate monohydrate can appear as dumbbells or as long ovals that resemble the individual posts in a picket fence. Calcium oxalate dihydrate have a tetragonal “envelope” appearance.
Struvite stones
About 10–15% of urinary calculi are composed of struvite (ammonium magnesium phosphate, NH4MgPO4·6H2O). Struvite stones (also known as "infection stones," urease, or triple-phosphate stones) form most often in the presence of infection by urea-splitting bacteria. Using the enzyme urease, these organisms metabolize urea into ammonia and carbon dioxide. This alkalinizes the urine, resulting in favorable conditions for the formation of struvite stones. Proteus mirabilis, Proteus vulgaris, and Morganella morganii are the most common organisms isolated; less common organisms include Ureaplasma urealyticum and some species of Providencia, Klebsiella, Serratia, and Enterobacter. These infection stones are commonly observed in people who have factors that predispose them to urinary tract infections, such as those with spinal cord injury and other forms of neurogenic bladder, ileal conduit urinary diversion, vesicoureteral reflux, and obstructive uropathies. They are also commonly seen in people with underlying metabolic disorders, such as idiopathic hypercalciuria, hyperparathyroidism, and gout. Infection stones can grow rapidly, forming large calyceal staghorn (antler-shaped) calculi requiring invasive surgery such as percutaneous nephrolithotomy for definitive treatment.Struvite stones (triple-phosphate/magnesium ammonium phosphate) have a coffin lid morphology by microscopy.
Uric acid stones
About 5–10% of all stones are formed from uric acid. People with certain metabolic abnormalities, including obesity, may produce uric acid stones. They also may form in association with conditions that cause hyperuricosuria (an excessive amount of uric acid in the urine) with or without hyperuricemia (an excessive amount of uric acid in the serum). They may also form in association with disorders of acid/base metabolism where the urine is excessively acidic (low pH), resulting in precipitation of uric acid crystals. A diagnosis of uric acid urolithiasis is supported by the presence of a radiolucent stone in the face of persistent urine acidity, in conjunction with the finding of uric acid crystals in fresh urine samples.As noted above (section on calcium oxalate stones), people with inflammatory bowel disease (Crohns disease, ulcerative colitis) tend to have hyperoxaluria and form oxalate stones. They also have a tendency to form urate stones. Urate stones are especially common after colon resection.
Uric acid stones appear as pleomorphic crystals, usually diamond-shaped. They may also look like squares or rods which are polarizable.
Other types
People with certain rare inborn errors of metabolism have a propensity to accumulate crystal-forming substances in their urine. For example, those with cystinuria, cystinosis, and Fanconi syndrome may form stones composed of cystine. Cystine stone formation can be treated with urine alkalinization and dietary protein restriction. People affected by xanthinuria often produce stones composed of xanthine. People affected by adenine phosphoribosyltransferase deficiency may produce 2,8-dihydroxyadenine stones, alkaptonurics produce homogentisic acid stones, and iminoglycinurics produce stones of glycine, proline, and hydroxyproline. Urolithiasis has also been noted to occur in the setting of therapeutic drug use, with crystals of drug forming within the renal tract in some people currently being treated with agents such as indinavir, sulfadiazine, and triamterene.
Location
Urolithiasis refers to stones originating anywhere in the urinary system, including the kidneys and bladder. Nephrolithiasis refers to the presence of such stones in the kidneys. Calyceal calculi are aggregations in either the minor or major calyx, parts of the kidney that pass urine into the ureter (the tube connecting the kidneys to the urinary bladder). The condition is called ureterolithiasis when a calculus is located in the ureter. Stones may also form or pass into the bladder, a condition referred to as bladder stones.
Size
Stones less than 5 mm (0.2 in) in diameter pass spontaneously in up to 98% of cases, while those measuring 5 to 10 mm (0.2 to 0.4 in) in diameter pass spontaneously in less than 53% of cases.Stones that are large enough to fill out the renal calyces are called staghorn stones and are composed of struvite in a vast majority of cases, which forms only in the presence of urease-forming bacteria. Other forms that can possibly grow to become staghorn stones are those composed of cystine, calcium oxalate monohydrate, and uric acid.
Prevention
Preventative measures depend on the type of stones. In those with calcium stones, drinking plenty of fluids, thiazide diuretics and citrate are effective as is allopurinol in those with high uric acid levels in urine.
Dietary measures
Specific therapy should be tailored to the type of stones involved. Diet can have an effect on the development of kidney stones. Preventive strategies include some combination of dietary modifications and medications with the goal of reducing the excretory load of calculogenic compounds on the kidneys. Dietary recommendations to minimize the formation of kidney stones include
increasing total fluid intake to achieve more than two liters per day of urine output;
limiting cola, including sugar-sweetened soft drinks; to less than one liter per week.
limiting animal protein intake to no more than two meals daily (an association between animal protein and recurrence of kidney stones has been shown in men);
increasing citrate, or alkali intake, including from lemon and lime juice. However, citric acid does not alkalinize urine like alkali citrate, which is citrate bonded with sodium, potassium and magnesium. This is because when citrate is metabolized (mostly by liver and some by kidney), the protons in citric acid will neutralize the bicarbonate generated, so that no net effect on blood or urine pH will occur.
Reducing sodium intake is associated with a reduction in urine calcium excretion.Maintenance of dilute urine by means of vigorous fluid therapy is beneficial in all forms of kidney stones, so increasing urine volume is a key principle for the prevention of kidney stones. Fluid intake should be sufficient to maintain a urine output of at least 2 litres (68 US fl oz) per day. A high fluid intake may reduce the likelihood of kidney stone recurrence or may increase the time between stone development without unwanted effects.
Calcium binds with available oxalate in the gastrointestinal tract, thereby preventing its absorption into the bloodstream. Reducing oxalate absorption decreases kidney stone risk in susceptible people. Because of this, some doctors recommend increasing dairy intake so that its calcium content will serve as an oxalate binder. Taking calcium citrate tablets during or after meals containing high oxalate foods may be useful if dietary calcium cannot be increased by other means as in those with lactose intolerance. The preferred calcium supplement for people at risk of stone formation is calcium citrate, as opposed to calcium carbonate, because it helps to increase urinary citrate excretion.Aside from vigorous oral hydration and eating more dietary calcium, other prevention strategies include avoidance of higher doses of supplemental vitamin C (since ascorbate is metabolized to oxalate) and restriction of oxalate-rich foods such as leaf vegetables, rhubarb, soy products and chocolate. However, no randomized, controlled trial of oxalate restriction has been performed to test the hypothesis that oxalate restriction reduces stone formation. Some evidence indicates magnesium intake decreases the risk of symptomatic kidney stones.
Urine alkalinization
The mainstay for medical management of uric acid stones is alkalinization (increasing the pH) of the urine. Uric acid stones are among the few types amenable to dissolution therapy, referred to as chemolysis. Chemolysis is usually achieved through the use of oral medications, although in some cases, intravenous agents or even instillation of certain irrigating agents directly onto the stone can be performed, using antegrade nephrostomy or retrograde ureteral catheters. Acetazolamide is a medication that alkalinizes the urine. In addition to acetazolamide or as an alternative, certain dietary supplements are available that produce a similar alkalinization of the urine. These include alkali citrate, sodium bicarbonate, potassium citrate, magnesium citrate, and Bicitra (a combination of citric acid monohydrate and sodium citrate dihydrate). Aside from alkalinization of the urine, these supplements have the added advantage of increasing the urinary citrate level, which helps to reduce the aggregation of calcium oxalate stones.Increasing the urine pH to around 6.5 provides optimal conditions for dissolution of uric acid stones. Increasing the urine pH to a value higher than 7.0 may increase the risk of calcium phosphate stone formation, though this concept is controversial since citrate does inhibit calcium phosphate crystallization. Testing the urine periodically with nitrazine paper can help to ensure the urine pH remains in this optimal range. Using this approach, stone dissolution rate can be expected to be around 10 mm (0.4 in) of stone radius per month.
Slaked lime
It decreases urinary calcium when combined with food rich in oxalic acid such as green leafy vegetables.
Diuretics
One of the recognized medical therapies for prevention of stones is the thiazide and thiazide-like diuretics, such as chlorthalidone or indapamide. These drugs inhibit the formation of calcium-containing stones by reducing urinary calcium excretion. Sodium restriction is necessary for clinical effect of thiazides, as sodium excess promotes calcium excretion. Thiazides work best for renal leak hypercalciuria (high urine calcium levels), a condition in which high urinary calcium levels are caused by a primary kidney defect. Thiazides are useful for treating absorptive hypercalciuria, a condition in which high urinary calcium is a result of excess absorption from the gastrointestinal tract.
Allopurinol
For people with hyperuricosuria and calcium stones, allop |
Kidney stone disease | urinol is one of the few treatments that have been shown to reduce kidney stone recurrences. Allopurinol interferes with the production of uric acid in the liver. The drug is also used in people with gout or hyperuricemia (high serum uric acid levels). Dosage is adjusted to maintain a reduced urinary excretion of uric acid. Serum uric acid level at or below 6 mg/100 ml is often a therapeutic goal. Hyperuricemia is not necessary for the formation of uric acid stones; hyperuricosuria can occur in the presence of normal or even low serum uric acid. Some practitioners advocate adding allopurinol only in people in whom hyperuricosuria and hyperuricemia persist, despite the use of a urine-alkalinizing agent such as sodium bicarbonate or potassium citrate.
Treatment
Stone size influences the rate of spontaneous stone passage. For example, up to 98% of small stones (less than 5 mm (0.2 in) in diameter) may pass spontaneously through urination within four weeks of the onset of symptoms, but for larger stones (5 to 10 mm (0.2 to 0.4 in) in diameter), the rate of spontaneous passage decreases to less than 53%. Initial stone location also influences the likelihood of spontaneous stone passage. Rates increase from 48% for stones located in the proximal ureter to 79% for stones located at the vesicoureteric junction, regardless of stone size. Assuming no high-grade obstruction or associated infection is found in the urinary tract, and symptoms are relatively mild, various nonsurgical measures can be used to encourage the passage of a stone. Repeat stone formers benefit from more intense management, including proper fluid intake and use of certain medications, as well as careful monitoring.
Pain management
Management of pain often requires intravenous administration of NSAIDs or opioids. NSAIDs appear somewhat better than opioids or paracetamol in those with normal kidney function. Medications by mouth are often effective for less severe discomfort. The use of antispasmodics does not have further benefit.
Medical expulsive therapy
The use of medications to speed the spontaneous passage of stones in the ureter is referred to as medical expulsive therapy. Several agents, including alpha adrenergic blockers (such as tamsulosin) and calcium channel blockers (such as nifedipine), may be effective. Alpha-blockers likely result in more people passing their stones, and they may pass their stones in a shorter time. People taking alpha-blockers may also use less pain medication and may not need to visit the hospital. Alpha-blockers appear to be more effective for larger stones (over 5 mm in size) than smaller stones. However, use of alpha-blockers may be associated with a slight increase in serious, unwanted effects from this medication. A combination of tamsulosin and a corticosteroid may be better than tamsulosin alone. These treatments also appear to be useful in addition to lithotripsy.
Lithotripsy
Extracorporeal shock wave lithotripsy (ESWL) is a noninvasive technique for the removal of kidney stones. Most ESWL is carried out when the stone is present near the renal pelvis. ESWL involves the use of a lithotriptor machine to deliver externally applied, focused, high-intensity pulses of ultrasonic energy to cause fragmentation of a stone over a period of around 30–60 minutes. Following its introduction in the United States in February 1984, ESWL was rapidly and widely accepted as a treatment alternative for renal and ureteral stones. It is currently used in the treatment of uncomplicated stones located in the kidney and upper ureter, provided the aggregate stone burden (stone size and number) is less than 20 mm (0.8 in) and the anatomy of the involved kidney is normal.For a stone greater than 10 millimetres (0.39 in), ESWL may not help break the stone in one treatment; instead, two or three treatments may be needed. Some 80-85% of simple renal calculi can be effectively treated with ESWL. A number of factors can influence its efficacy, including chemical composition of the stone, presence of anomalous renal anatomy and the specific location of the stone within the kidney, presence of hydronephrosis, body mass index, and distance of the stone from the surface of the skin.Common adverse effects of ESWL include acute trauma, such as bruising at the site of shock administration, and damage to blood vessels of the kidney. In fact, the vast majority of people who are treated with a typical dose of shock waves using currently accepted treatment settings are likely to experience some degree of acute kidney injury. ESWL-induced acute kidney injury is dose-dependent (increases with the total number of shock waves administered and with the power setting of the lithotriptor) and can be severe, including internal bleeding and subcapsular hematomas. On rare occasions, such cases may require blood transfusion and even lead to acute kidney failure. Hematoma rates may be related to the type of lithotriptor used; hematoma rates of less than 1% and up to 13% have been reported for different lithotriptor machines. Recent studies show reduced acute tissue injury when the treatment protocol includes a brief pause following the initiation of treatment, and both improved stone breakage and a reduction in injury when ESWL is carried out at slow shock wave rate.In addition to the aforementioned potential for acute kidney injury, animal studies suggest these acute injuries may progress to scar formation, resulting in loss of functional renal volume. Recent prospective studies also indicate elderly people are at increased risk of developing new-onset hypertension following ESWL. In addition, a retrospective case-control study published by researchers from the Mayo Clinic in 2006 has found an increased risk of developing diabetes mellitus and hypertension in people who had undergone ESWL, compared with age and gender-matched people who had undergone nonsurgical treatment. Whether or not acute trauma progresses to long-term effects probably depends on multiple factors that include the shock wave dose (i.e., the number of shock waves delivered, rate of delivery, power setting, acoustic characteristics of the particular lithotriptor, and frequency of retreatment), as well as certain intrinsic predisposing pathophysiologic risk factors.To address these concerns, the American Urological Association established the Shock Wave Lithotripsy Task Force to provide an expert opinion on the safety and risk-benefit ratio of ESWL. The task force published a white paper outlining their conclusions in 2009. They concluded the risk-benefit ratio remains favorable for many people. The advantages of ESWL include its noninvasive nature, the fact that it is technically easy to treat most upper urinary tract calculi, and that, at least acutely, it is a well-tolerated, low-morbidity treatment for the vast majority of people. However, they recommended slowing the shock wave firing rate from 120 pulses per minute to 60 pulses per minute to reduce the risk of renal injury and increase the degree of stone fragmentation.Alpha-blockers are sometimes prescribed after shock wave lithotripsy to help the pieces of the stone leave the persons body. By relaxing muscles and helping to keep blood vessels open, alpha blockers may relax the ureter muscles to allow the kidney stone fragments to pass. When compared to usual care or placebo treatment, alpha blockers may lead to faster clearing of stones, a reduced need for extra treatment and fewer unwanted effects. They may also clear kidney stones in more adults than the standard shock wave lithotripsy procedure. The unwanted effects associated with alpha blockers are hospital emergency visits and return to hospital for stone-related issues, but these effects were more common in adults who did not receive alpha-blockers as a part of their treatment.
Surgery
Most stones under 5 mm (0.2 in) pass spontaneously. Prompt surgery may, nonetheless, be required in persons with only one working kidney, bilateral obstructing stones, a urinary tract infection and thus, it is presumed, an infected kidney, or intractable pain. Beginning in the mid-1980s, less invasive treatments such as extracorporeal shock wave lithotripsy, ureteroscopy, and percutaneous nephrolithotomy began to replace open surgery as the modalities of choice for the surgical management of urolithiasis. More recently, flexible ureteroscopy has been adapted to facilitate retrograde nephrostomy creation for percutaneous nephrolithotomy. This approach is still under investigation, though early results are favorable. Percutaneous nephrolithotomy or, rarely, anatrophic nephrolithotomy, is the treatment of choice for large or complicated stones (such as calyceal staghorn calculi) or stones that cannot be extracted using less invasive procedures.
Ureteroscopic surgery
Ureteroscopy has become increasingly popular as flexible and rigid fiberoptic ureteroscopes have become smaller. One ureteroscopic technique involves the placement of a ureteral stent (a small tube extending from the bladder, up the ureter and into the kidney) to provide immediate relief of an obstructed kidney. Stent placement can be useful for saving a kidney at risk for postrenal acute kidney failure due to the increased hydrostatic pressure, swelling and infection (pyelonephritis and pyonephrosis) caused by an obstructing stone. Ureteral stents vary in length from 24 to 30 cm (9.4 to 11.8 in) and most have a shape commonly referred to as a "double-J" or "double pigtail", because of the curl at both ends. They are designed to allow urine to flow past an obstruction in the ureter. They may be retained in the ureter for days to weeks as infections resolve and as stones are dissolved or fragmented by ESWL or by some other treatment. The stents dilate the ureters, which can facilitate instrumentation, and they also provide a clear landmark to aid in the visualization of the ureters and any associated stones on radiographic examinations. The presence of indwelling ureteral stents may cause minimal to moderate discomfort, frequency or urgency incontinence, and infection, which in general resolves on removal. Most ureteral stents can be removed cystoscopically during an office visit under topical anesthesia after resolution of urolithiasis. Research is currently uncertain if placing a temporary stent during ureteroscopy leads to different outcomes than not placing a stent in terms of number of hospital visits for post operative problems, short or long term pain, need for narcotic pain medication, risk of UTI, need for a repeat procedure or narrowing of the ureter from scarring.More definitive ureteroscopic techniques for stone extraction (rather than simply bypassing the obstruction) include basket extraction and ultrasound ureterolithotripsy. Laser lithotripsy is another technique, which involves the use of a holmium:yttrium aluminium garnet (Ho:YAG) laser to fragment stones in the bladder, ureters, and kidneys.Ureteroscopic techniques are generally more effective than ESWL for treating stones located in the lower ureter, with success rates of 93–100% using Ho:YAG laser lithotripsy. Although ESWL has been traditionally preferred by many practitioners for treating stones located in the upper ureter, more recent experience suggests ureteroscopic techniques offer distinct advantages in the treatment of upper ureteral stones. Specifically, the overall success rate is higher, fewer repeat interventions and postoperative visits are needed, and treatment costs are lower after ureteroscopic treatment when compared with ESWL. These advantages are especially apparent with stones greater than 10 mm (0.4 in) in diameter. However, because ureteroscopy of the upper ureter is much more challenging than ESWL, many urologists still prefer to use ESWL as a first-line treatment for stones of less than 10 mm, and ureteroscopy for those greater than 10 mm in diameter. Ureteroscopy is the preferred treatment in pregnant and morbidly obese people, as well as those with bleeding disorders.
Epidemiology
Kidney stones affect all geographical, cultural, and racial groups. The lifetime risk is about 10-15% in the developed world, but can be as high as 20-25% in the Middle East. The increased risk of dehydration in hot climates, coupled with a diet 50% lower in calcium and 250% higher in oxalates compared to Western diets, accounts for the higher net risk in the Middle East. In the Middle East, uric acid stones are more common than calcium-containing stones. The number of deaths due to kidney stones is estimated at 19,000 per year being fairly consistent between 1990 and 2010.In North America and Europe, the annual number of new cases per year of kidney stones is roughly 0.5%. In the United States, the frequency in the population of urolithiasis has increased from 3.2% to 5.2% from the mid-1970s to the mid-1990s. In the United States, about 9% of the population has had a kidney stone.The total cost for treating urolithiasis was US$2 billion in 2003. About 65–80% of those with kidney stones are men; most stones in women are due to either metabolic defects (such as cystinuria) or infections in the case of struvite stones. Urinary tract calculi disorders are more common in men than in women. Men most commonly experience their first episode between 30 and 40 years of age, whereas for women, the age at first presentation is somewhat later. The age of onset shows a bimodal distribution in women, with episodes peaking at 35 and 55 years. Recurrence rates are estimated at 50% over a 10-year and 75% over 20-year period, with some people experiencing ten or more episodes over the course of a lifetime.A 2010 review concluded that rates of disease are increasing.
History
The existence of kidney stones was first recorded thousands of years ago, with various explanations given; Joseph Glanvilles Saducismus Triumphatus, for example, gives a detailed description of Abraham Mechelburgs voiding of small stones through his penis virga, attributing the issue to witchcraft.In 1901, a stone discovered in the pelvis of an ancient Egyptian mummy was dated to 4,800 BC.
Medical texts from ancient Mesopotamia, India, China, Persia, Greece, and Rome all mentioned calculous disease. Part of the Hippocratic Oath suggests there were practicing surgeons in ancient Greece to whom physicians were to defer for lithotomies, or the surgical removal of stones. The Roman medical treatise De Medicina by Aulus Cornelius Celsus contained a description of lithotomy, and this work served as the basis for this procedure until the 18th century.Examples of people who had kidney stone disease include Napoleon I, Epicurus, Napoleon III, Peter the Great, Louis XIV, George IV, Oliver Cromwell, Lyndon B. Johnson, Benjamin Franklin, Michel de Montaigne, Francis Bacon, Isaac Newton, Samuel Pepys, William Harvey, Herman Boerhaave, and Antonio Scarpa.New techniques in lithotomy began to emerge starting in 1520, but the operation remained risky. After Henry Jacob Bigelow popularized the technique of litholapaxy in 1878, the mortality rate dropped from about 24% to 2.4%. However, other treatment techniques continued to produce a high level of mortality, especially among inexperienced urologists. In 1980, Dornier MedTech introduced extracorporeal shock wave lithotripsy for breaking up stones via acoustical pulses, and this technique has since come into widespread use.
Etymology
The term renal calculus is from the Latin rēnēs, meaning "kidneys", and calculus, meaning "pebble". Lithiasis (stone formation) in the kidneys is called nephrolithiasis (), from nephro-, meaning kidney, + -lith, meaning stone, and -iasis, meaning disorder. A distinction between nephrolithiasis and urolithiasis can be made because not all urinary stones (uroliths) form in the kidney; they can also form in the bladder. But the distinction is often clinically irrelevant (with similar disease process and treatment either way) and the words are thus often used loosely as synonyms.
Children
Although kidney stones do not often occur in children, the incidence is increasing. These stones are in the kidney in two thirds of reported cases, and in the ureter in the remaining cases. Older children are at greater risk independent of whether or not they are male or female.As with adults, most pediatric kidney stones are predominantly composed of calcium oxalate; struvite and calcium phosphate stones are less common. Calcium oxalate stones in children are associated with high amounts of calcium, oxalate, and magnesium in acidic urine.Treatment of kidney stones in children are similar to treatments for adults including: shock wave lithotripsy, medication, and treatment using scope through the bladder, kidney or skin. Of these treatments, research is uncertain if shock waves are more effective than medication or a scope through the bladder, but it is likely less successful than a scope through skin into the kidney. When going in with a scope through the kidney, a regular and a mini-sized scope likely have similar success rates of stone removal. Alpha-blockers, a type of medication, may increase the successful removal of kidney stones when compared with a placebo and without ibuprofen.
Research
Metabolic syndrome and its associated diseases of obesity and diabetes as general risk factors for kidney stone disease are under research to determine if urinary excretion of calcium, oxalate and urate are higher than in people with normal weight or underweight, and if diet and physical activity have roles. Dietary, fluid intake, and lifestyle factors remain major topics for research on prevention of kidney stones, as of 2017.
Gut microbiota
The gut microbiota has been explored as a contributing factor for stone disease, indicating that some bacteria may be different in people forming kidney stones. One bacterium, Oxalobacter formigenes, is potentially beneficial for mitigating calcium oxalate stones because of its ability to metabolize oxalate as its sole carbon source, but 2018 research suggests that it is instead part of a network of oxalate degrading bacteria. Additionally, one study found that oral antibiotic use, which alters the gut microbiota, can increase the odds of a person developing a kidney stone.
In animals
Among ruminants, uroliths more commonly cause problems in males than in females; the sigmoid flexure of the ruminant male urinary tract is more likely to obstruct passage. Early-castrated males are at greater risk, because of lesser urethral diameter.Low Ca:P intake ratio is conducive to phosphatic (e.g. struvite) urolith formation. Incidence among wether lambs can be minimized by maintaining a dietary Ca:P intake ratio of 2:1.Alkaline (higher) pH favors formation of carbonate and phosphate calculi. For domestic ruminants, dietary cation: anion balance is sometimes adjusted to assure a slightly acidic urine pH, for prevention of calculus formation.Differing generalizations regarding effects of pH on formation of silicate uroliths may be found. In this connection, it may be noted that under some circumstances, calcium carbonate accompanies silica in siliceous uroliths.Pelleted feeds may be conducive to formation of phosphate uroliths, because of increased urinary phosphorus excretion. This is attributable to lower saliva production where pelleted rations containing finely ground constituents are fed. With less blood phosphate partitioned into saliva, more tends to be excreted in urine. (Most saliva phosphate is fecally excreted.)
Oxalate uroliths can occur in ruminants, although such problems from oxalate ingestion may be relatively uncommon. Ruminant urolithiasis associated with oxalate ingestion has been reported. However, no renal tubular damage or visible deposition of calcium oxalate crystals in kidneys was found in yearling wether sheep fed diets containing soluble oxalate at 6.5 percent of dietary dry matter for about 100 days.Conditions limiting water intake can result in stone formation.Various surgical interventions, e.g. amputation of the urethral process at its base near the glans penis in male ruminants, perineal urethrostomy, or tube cystostomy may be considered for relief of obstructive urolithiasis.
See also
Nephrocalcinosis
Kidney disease
References
Notes
External links
Kidney stone disease at Curlie
Information from the European Urological Association
Kidney Stone Guide Book – University of Chicago Kidney Stone Program |
Intersex | Intersex people are individuals born with any of several sex characteristics including chromosome patterns, gonads, or genitals that, according to the Office of the United Nations High Commissioner for Human Rights, "do not fit typical binary notions of male or female bodies".Sex assignment at birth usually aligns with a childs anatomical sex and phenotype. The number of births with ambiguous genitals is in the range of 1:2000-1:4500 (0.022% - 0.05%). Other conditions involve atypical chromosomes, gonads, or hormones. Some persons may be assigned and raised as a girl or boy but then identify with another gender later in life, while most continue to identify with their assigned sex. The number of births where the baby is intersex has been reported differently depending on who reports and which definition of intersex is used. Anne Fausto-Sterling and her co-authors suggest that the prevalence of "nondimorphic sexual development" might be as high as 1.7%. A study published by Leonard Sax reports that this figure includes conditions such as Klinefelter syndrome (XXY) which most clinicians do not recognize as intersex, and that if the term is understood to mean only "conditions in which chromosomal sex is inconsistent with phenotypic sex, or in which the phenotype is not classifiable as either male or female", the prevalence of intersex is about 0.018%.Terms used to describe intersex people are contested, and change over time and place. Intersex people were previously referred to as "hermaphrodites" or "congenital eunuchs". In the 19th and 20th centuries, some medical experts devised new nomenclature in an attempt to classify the characteristics that they had observed, the first attempt to create a taxonomic classification system of intersex conditions. Intersex people were categorized as either having "true hermaphroditism", "female pseudohermaphroditism", or "male pseudohermaphroditism". These terms are no longer used, and terms including the word "hermaphrodite" are considered to be misleading, stigmatizing, and scientifically specious in reference to humans. In biology, the term "hermaphrodite" is used to describe an organism that can produce both male and female gametes. Some people with intersex traits use the term "intersex", and some prefer other language. In clinical settings, the term "disorders of sex development" (DSD) has been used since 2006, a shift in language considered controversial since its introduction.
Intersex people face stigmatization and discrimination from birth, or following the discovery of intersex traits at stages of development such as puberty. Intersex people may face infanticide, abandonment, and stigmatization from their families. Globally, some intersex infants and children, such as those with ambiguous outer genitalia, are surgically or hormonally altered to create more socially acceptable sex characteristics. However, this is considered controversial, with no firm evidence of favorable outcomes. Such treatments may involve sterilization. Adults, including elite female athletes, have also been subjects of such treatment. Increasingly, these issues are considered human rights abuses, with statements from international and national human rights and ethics institutions (see intersex human rights). Intersex organizations have also issued statements about human rights violations, including the 2013 Malta declaration of the third International Intersex Forum. In 2011, Christiane Völling became the first intersex person known to have successfully sued for damages in a case brought for non-consensual surgical intervention. In April 2015, Malta became the first country to outlaw non-consensual medical interventions to modify sex anatomy, including that of intersex people.
Terminology
There is no clear consensus definition of intersex and no clear delineation of which specific conditions qualify an individual as intersex. The World Health Organizations International Classification of Diseases (ICD), the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM), and many medical journals classify intersex traits or conditions among disorders of sex development (DSD).A common adjective for people with disorders of sex development (DSD) is "intersex".
Etymology and definitions
In 1917, Richard Goldschmidt created the term "intersexuality" to refer to a variety of physical sex ambiguities. However, according to The SAGE Encyclopedia of LGBTQ Studies, it wasnt until Anne Fausto Sterling published her article "The Five Sexes: Why Male and Female Are Not Enough" in 1993 that the term reached popularity.
According to the UN Office of the High Commissioner for Human Rights:
Intersex people are born with sex characteristics (including genitals, gonads and chromosome patterns) that do not fit typical binary notions of male or female bodies. Intersex is an umbrella term used to describe a wide range of natural bodily variations.
Attitudes towards the term
Some intersex organizations reference "intersex people" and "intersex variations or traits" while others use more medicalized language such as "people with intersex conditions", or people "with intersex conditions or DSDs (differences of sex development)" and "children born with variations of sex anatomy". In May 2016, interACT published a statement recognizing "increasing general understanding and acceptance of the term intersex".Australian sociological research on 272 "people born with atypical sex characteristics", published in 2016, found that 60% of respondents used the term "intersex" to self-describe their sex characteristics, including people identifying themselves as intersex, describing themselves as having an intersex variation or, in smaller numbers, having an intersex condition. Respondents also commonly used diagnostic labels and referred to their sex chromosomes, with word choices depending on audience.Research on 202 respondents by the Lurie Childrens Hospital, Chicago, and the AIS-DSD Support Group (now known as InterConnect Support Group) published in 2017 found that 80% of Support Group respondents "strongly liked, liked or felt neutral about intersex" as a term, while caregivers were less supportive. The hospital reported that the use of the term "disorders of sex development" may negatively affect care.Another study by a group of childrens hospitals in the United States found that 53% of 133 parent and adolescent participants recruited at five clinics did not like the term "intersex". Participants who were members of support groups were more likely to dislike the term. A "dsd-LIFE" study in 2020 found that around 43% of 179 participants thought the term "intersex" was bad, 20% felt neutral about the term, while the rest thought the term was good.
The term "hermaphrodite"
Historically, the term "hermaphrodite" was used in law to refer to people whose sex was in doubt. The 12th-century Decretum Gratiani states that "Whether an hermaphrodite may witness a testament, depends on which sex prevails" ("Hermafroditus an ad testamentum adhiberi possit, qualitas sexus incalescentis ostendit."). Similarly, the 17th-century English jurist and judge Edward Coke (Lord Coke), wrote in his Institutes of the Lawes of England on laws of succession stating, "Every heire is either a male, a female, or an hermaphrodite, that is both male and female. And an hermaphrodite (which is also called Androgynus) shall be heire, either as male or female, according to that kind of sexe which doth prevaile."During the Victorian era, medical authors attempted to ascertain whether or not humans could be hermaphrodites, adopting a precise biological definition for the term, and making distinctions between "male pseudohermaphrodite", "female pseudohermaphrodite" and especially "true hermaphrodite". These terms, which reflected histology (microscopic appearance) of the gonads, are no longer used. Until the mid-20th century, "hermaphrodite" was used synonymously with "intersex". Medical terminology shifted in the early 21st century, not only due to concerns about language, but also a shift to understandings based on genetics.The Intersex Society of North America has stated that hermaphrodites should not be confused with intersex people and that using "hermaphrodite" to refer to intersex individuals is considered to be stigmatizing and misleading.
Prevalence
Estimates of the number of people who are intersex vary, depending on which conditions are counted as intersex. The now-defunct Intersex Society of North America stated that:
If you ask experts at medical centers how often a child is born so noticeably atypical in terms of genitalia that a specialist in sex differentiation is called in, the number comes out to about 1 in 1500 to 1 in 2000 births [0.07–0.05%]. But a lot more people than that are born with subtler forms of sex anatomy variations, some of which wont show up until later in life.
Anne Fausto-Sterling and her co-authors broadly said in 2000 that "[a]dding the estimates of all known causes of nondimorphic sexual development suggests that approximately 1.7% of all live births do not conform to a Platonic ideal of absolute sex chromosome, gonadal, genital, and hormonal dimorphism"; these publications have been widely quoted by intersex activists. Of the 1.7 percent, 1.5 percentage points (88% of those considered "nondimorphic sexual development" in this figure) consist of individuals with late onset congenital adrenal hyperplasia (LOCAH) which may be asymptomatic but can present after puberty and cause infertility.In response to Fausto-Sterling, Leonard Sax estimated that the prevalence of intersex was about 0.018% of the worlds population, after discounting several conditions including LOCAH, Klinefelter syndrome (47,XXY), Turner syndrome (45,X), the chromosomal variants of 47,XYY and 47,XXX, and vaginal agenesis. Sax reasons that in these conditions chromosomal sex is consistent with phenotypic sex and phenotype is classifiable as either male or female.In a 2003 letter to the editor, political scientist Carrie Hull analyzed the data used by Fausto-Sterling and said the estimated intersex rate should instead have been 0.37%, due to many errors. In a response letter published simultaneously, Fausto-Sterling welcomed the additional analysis and said "I am not invested in a particular final estimate, only that there BE an estimate". A 2018 review reported that the number of births with ambiguous genitals is in the range of 0.02% to 0.05%.The figure of 1.7% is still maintained by Intersex Human Rights Australia "despite its flaws", stating both that the estimate "encapsulates the entire population of people who are stigmatized – or risk stigmatization – due to innate sex characteristics," and that Saxs definitions exclude individuals who experience such stigma and who have helped to establish the intersex movement.The following summarizes prevalences of traits that have been called intersex:
Prevalences of specific conditions can vary across regions. In the Dominican Republic, 5-alpha-reductase deficiency is not uncommon in the town of Las Salinas, resulting in social acceptance of the intersex trait. Men with the trait are called "güevedoces" (Spanish for "eggs at twelve"). 12 out of 13 families had one or more male family members that carried the gene. The overall incidence for the town was 1 in every 90 males were carriers, with other males either non-carriers or non-affected carriers.
History
From early history, societies have been aware of intersex people. Some of the earliest evidence is found in mythology: the Greek historian Diodorus Siculus wrote of the mythological Hermaphroditus in the first century BC, who was "born with a physical body which is a combination of that of a man and that of a woman", and reputedly possessed supernatural properties. He also recounted the lives of Diophantus of Abae and Callon of Epidaurus. Ardhanarishvara, an androgynous composite form of male deity Shiva and female deity Parvati, originated in Kushan culture as far back as the first century AD. A statue depicting Ardhanarishvara is included in Indias Meenakshi Temple; this statue clearly shows both male and female bodily elements.Hippocrates (c. 460 – c. 370 BC Greek physician) and Galen (129 – c. 200/216 AD Roman physician, surgeon and philosopher) both viewed sex as a spectrum between men and women, with "many shades in between, including hermaphrodites, a perfect balance of male and female". Pliny the Elder (AD 23/24–79) the Roman naturalist described "those who are born of both sexes, whom we call hermaphrodites, at one time androgyni" (from the Greek andr-, "man," and gyn-, "woman"). Augustine (354 – 28 August 430 AD) the influential Catholic theologian wrote in The Literal Meaning of Genesis that humans were created in two sexes, despite "as happens in some births, in the case of what we call androgynes".In medieval and early modern European societies, Roman law, post-classical canon law, and later common law, referred to a persons sex as male, female or hermaphrodite, with legal rights as male or female depending on the characteristics that appeared most dominant. The 12th century Decretum Gratiani states that "Whether an hermaphrodite may witness a testament, depends on which sex prevails". The foundation of common law, the 17th Century Institutes of the Lawes of England described how a hermaphrodite could inherit "either as male or female, according to that kind of sexe which doth prevaile." Legal cases have been described in canon law and elsewhere over the centuries.
Some non-European societies have sex or gender systems that recognize more than the two categories of male/man and female/woman. Some of these cultures, for instance the South-Asian Hijra communities, may include intersex people in a third gender category. Although–according to Morgan Holmes–early Western anthropologists categorized such cultures "primitive," Holmes has argued that analyses of these cultures have been simplistic or romanticized and fail to take account of the ways that subjects of all categories are treated.During the Victorian era, medical authors introduced the terms "true hermaphrodite" for an individual who has both ovarian and testicular tissue, "male pseudo-hermaphrodite" for a person with testicular tissue, but either female or ambiguous sexual anatomy, and "female pseudo-hermaphrodite" for a person with ovarian tissue, but either male or ambiguous sexual anatomy. Some later shifts in terminology have reflected advances in genetics, while other shifts are suggested to be due to pejorative associations.The term "intersexuality" was coined by Richard Goldschmidt in 1917. The first suggestion to replace the term "hermaphrodite" with "intersex" was made by Cawadias in the 1940s.Since the rise of modern medical science, some intersex people with ambiguous external genitalia have had their genitalia surgically modified to resemble either female or male genitals. Surgeons pinpointed intersex babies as a "social emergency" when born. An optimal gender policy, initially developed by John Money, stated that early intervention helped avoid gender identity confusion, but this lacks evidence. Early interventions have adverse consequences for psychological and physical health. Since advances in surgery have made it possible for intersex conditions to be concealed, many people are not aware of how frequently intersex conditions arise in human beings or that they occur at all.Dialogue between what were once antagonistic groups of activists and clinicians has led to only slight changes in medical policies and how intersex patients and their families are treated in some locations. In 2011, Christiane Völling became the first intersex person known to have successfully sued for damages in a case brought for non-consensual surgical intervention. In April 2015, Malta became the first country to outlaw non-consensual medical interventions to modify sex anatomy, including that of intersex people. Many civil society organizations and human rights institutions now call for an end to unnecessary "normalizing" interventions, including in the Malta declaration.
Human rights and legal issues
Human rights institutions are placing increasing scrutiny on harmful practices and issues of discrimination against intersex people. These issues have been addressed by a rapidly increasing number of international institutions including, in 2015, the Council of Europe, the United Nations Office of the United Nations High Commissioner for Human Rights and the World Health Organization (WHO). These developments have been accompanied by International Intersex Forums and increased cooperation amongst civil society organizations. However, the implementation, codification, and enforcement of intersex human rights in national legal systems remains slow.
Physical integrity and bodily autonomy
Stigmatization and discrimination from birth may include infanticide, abandonment, and the stigmatization of families. The birth of an intersex child was often viewed as a curse or a sign of a witch mother, especially in parts of Africa. Abandonments and infanticides have been reported in Uganda, Kenya, South Asia, and China.Infants, children and adolescents also experience "normalising" interventions on intersex persons that are medically unnecessary and the pathologisation of variations in sex characteristics. In countries where the human rights of intersex people have been studied, medical interventions to modify the sex characteristics of intersex people have still taken place without the consent of the intersex person. Interventions have been described by human rights defenders as a violation of many rights, including (but not limited to) bodily integrity, non-discrimination, privacy, and experimentation. These interventions have frequently been performed with the consent of the intersex persons parents, when the person is legally too young to consent. Such interventions have been criticized by the WHO, other UN bodies such as the Office of the High Commissioner for Human Rights, and an increasing number of regional and national institutions due to their adverse consequences, including trauma, impact on sexual function and sensation, and violation of rights to physical and mental integrity. The UN organizations decided that infant intervention should not be allowed, in favor of waiting for the child to mature enough to be a part of the decision-making – this allows for a decision to be made with total consent. In April 2015, Malta became the first country to outlaw surgical intervention without consent. In the same year, the Council of Europe became the first institution to state that intersex people have the right not to undergo sex affirmation interventions.
Anti-discrimination and equal treatment
People born with intersex bodies are seen as different. Intersex infants, children, adolescents and adults "are often stigmatized and subjected to multiple human rights violations", including discrimination in education, healthcare, employment, sport, and public services. Several countries have so far explicitly protected intersex people from discrimination, with landmarks including South Africa, Australia, and, most comprehensively, Malta.
Remedies and claims for compensation
Claims for compensation and remedies for human rights abuses include the 2011 case of Christiane Völling in Germany. A second case was adjudicated in Chile in 2012, involving a child and his parents. A further successful case in Germany, taken by Michaela Raab, was reported in 2015. In the United States, the Minor Child (M.C. v Aaronson) lawsuit was "a medical malpractice case related to the informed consent for a surgery performed on the Crawfords adopted child (known as M.C.) at [Medical University of South Carolina] in April 2006". The case was one of the first lawsuit of its kind to challenge "legal, ethical, and medical issues regarding genital-normalizing surgery" in minors, and was eventually settled out of court by the Medical University of South Carolina for $440,000 in 2017.
Information and support
Access to information, medical records, peer and other counselling and support. With the rise of modern medical science in Western societies, a secrecy-based model was also adopted, in the belief that this was necessary to ensure normal physical and psychosocial development.
Legal recognition
The Asia Pacific Forum of National Human Rights Institutions states that legal recognition is firstly "about intersex people who have been issued a male or a female birth certificate being able to enjoy the same legal rights as other men and women." In some regions, obtaining any form of birth certification may be an issue. A Kenyan court case in 2014 established the right of an intersex boy, "Baby A", to a birth certificate.Like all individuals, some intersex individuals may be raised as a certain sex (male or female) but then identify with another later in life, while most do not. Recognition of third sex or gender classifications occurs in several countries, However, it is controversial when it becomes assumed or coercive, as is the case with some German infants. Sociological research in Australia, a country with a third X sex classification, shows that 19% of people born with atypical sex characteristics selected an "X" or "other" option, while 75% of survey respondents self-described as male or female (52% as women, 23% as men), and 6% as unsure.
LGBT and LGBTI
Intersex conditions can be contrasted with transgender gender identities and the attached gender dysphoria a transgender person may feel, wherein their gender identity does not match their assigned sex. However, some people are both intersex and transgender; though intersex people by definition have variable sex characteristics that do not align with either typically male or female, this may be considered separate to an individuals assigned gender, the way they are raised and perceived, and their internal gender identity. A 2012 clinical review paper found that between 8.5% and 20% of people with intersex variations experienced gender dysphoria. In an analysis of the use of preimplantation genetic diagnosis to eliminate intersex traits, Behrmann and Ravitsky state: "Parental choice against intersex may... conceal biases against same-sex attractedness and gender nonconformity."The relationship of intersex people and communities to LGBTQ communities is complex, but intersex people are often added to the LGBT acronym, resulting in the acronym LGBTI. Emi Koyama describes how inclusion of intersex in LGBTI can fail to address intersex-specific human rights issues, including creating false impressions "that intersex peoples rights are protected" by laws protecting LGBT people, and failing to acknowledge that many intersex people are not LGBT. Organisation Intersex International Australia states that some intersex individuals are homosexual, and some are heterosexual, but "LGBTI activism has fought for the rights of people who fall outside of expected binary sex and gender norms." Julius Kaggwa of SIPD Uganda has written that, while the gay community "offers us a place of relative safety, it is also oblivious to our specific needs". Mauro Cabral has written that transgender people and organizations "need to stop approaching intersex issues as if they were trans issues", including use of intersex conditions and people as a means of explaining being transgender; "we can collaborate a lot with the intersex movement by making it clear how wrong that approach is".
In society
Fiction, literature and media
An intersex character is the narrator in Jeffrey Eugenides Pulitzer Prize-winning novel Middlesex.
The memoir, Born Both: An Intersex Life (Hachette Books, 2017), by intersex author and activist Hida Viloria, received strong praise from The New York Times Book Review, The Washington Post, Rolling Stone, People Magazine, and Psychology Today, was one of School Library Journals 2017 Top Ten Adult Books for Teens, and was a 2018 Lambda Literary Award nominee.
Television works about intersex and films about intersex are scarce. The Spanish-language film XXY won the Critics Week grand prize at the 2007 Cannes Film Festival and the ACID/CCAS Support Award. Faking It is notable for providing both the first intersex main character in a television show, and televisions first intersex character played by an intersex actor.
Civil society institutions
Intersex peer support and advocacy organizations have existed since at least 1985, with the establishment of the Androgen Insensitivity Syndrome Support Group Australia in 1985. The Androgen Insensitivity Syndrome Support Group (UK) was established in 1988. The Intersex Society of North America (ISNA) may have been one of the first intersex civil society organizations to have been open to people regardless of diagnosis; it was active from 1993 to 2008.
Events
Intersex Awareness Day is an internationally observed civil awareness day designed to highlight the challenges faced by intersex people, occurring annually on 26 October. It marks the first public demonstration by intersex people, which took place in Boston on 26 October 1996, outside a venue where the American Academy of Pediatrics was holding its annual conference.Intersex Day of Remembrance, also known as Intersex Solidarity Day, is an internationally observed civil awareness day designed to highlight issues faced by intersex people, occurring annually on 8 November. It marks the birthday of Herculine Barbin, a French intersex person whose memoirs were later published by Michel Foucault in Herculine Barbin: Being the Recently Discovered Memoirs of a Nineteenth-century French Hermaphrodite.
Flag
The intersex flag was created in July 2013 by Morgan Carpenter of Intersex Human Rights Australia to create a flag "that is not derivative, but is yet firmly grounded in meaning". The circle is described as "unbroken and unornamented, symbolising wholeness and completeness, and our potentialities. We are still fighting for bodily autonomy and genital integrity, and this symbolises the right to be who and how we want to be."
Religion
In Judaism, the Talmud contains extensive discussion concerning the status of two types of intersex people in Jewish law; namely, the androgynous, who exhibit both male and female external sexual organs, and the tumtum, who exhibit neither. In the 1970s and 1980s, the treatment of intersex babies started to be discussed in Orthodox Jewish medical halacha by prominent rabbinic leaders, such as Eliezer Waldenberg and Moshe Feinstein.
Sport
Erik Schinegger, Foekje Dillema, Maria José Martínez-Patiño and Santhi Soundarajan were subject to adverse sex verification testing resulting in ineligibility to compete in organised competitive competition. Stanisława Walasiewicz was posthumously ruled ineligible to have competed.The South African middle-distance runner Caster Semenya won gold at the World Championships in the womens 800 metres and won silver in the 2012 Summer Olympics. When Semenya won gold in the World Championships, the International Association of Athletics Federations (IAAF) requested sex verification tests. The results were not released. Semenya was ruled eligible to compete.Katrina Karkazis, Rebecca Jordan-Young, Georgiann Davis and Silvia Camporesi have claimed that IAAF policies on "hyperandrogenism" in female athletes are "significantly flawed", arguing that the policy does not protect against breaches of privacy, requires athletes to undergo unnecessary treatment in order to compete, and intensifies "gender policing", and recommended that athletes be able to compete in accordance with their legally-recognised gender.In April 2014, the BMJ reported that four elite women athletes with XY chromosomes and 5-ARD were subjected to sterilization and "partial clitoridectomies" in order to compete in sport. The authors noted that partial clitoridectomy was "not medically indicated" and "does not relate to real or perceived athletic advantage." Intersex advocates regarded this intervention as "a clearly coercive process". In 2016, the United Nations Special Rapporteur on health, Dainius Pūras, criticized "current and historic" sex verification policies, describing how "a number of athletes have undergone gonadectomy (removal of reproductive organs) and partial clitoridectomy (a form of female genital mutilation) in the absence of symptoms or health issues warranting those procedures."
Biology
The notion of intersex individuals can be understood in the context of sexual system biology that varies across different types of organisms. Most animal species (~95%, including humans) are gonochoric, in which individuals are of either a |
Intersex | female or male sex. Hermaphroditic species (some animals and most flowering plants) are represented by individuals that can express both sexes simultaneously or sequentially during their lifetimes. Intersex individuals in a number of gonochoric species, who express both female and male phenotypic characters to some degree, are known to exist at very low prevalences.
Although "hermaphrodite" and "intersex" have been used synonymously in humans, a hermaphrodite is specifically an individual capable of producing female and male gametes. While there are reports of individuals that seemed to have the potential to produce both types of gamete, in more recent years the term hermaphrodite as applied to humans has fallen out of favor, since female and male reproductive functions have not been observed together in the same individual.
Medical
Research in the late 20th century led to a growing medical consensus that diverse intersex bodies are normal, but relatively rare, forms of human biology. Clinician and researcher Milton Diamond stresses the importance of care in the selection of language related to intersex people:
Foremost, we advocate use of the terms "typical", "usual", or "most frequent" where it is more common to use the term "normal." When possible avoid expressions like maldeveloped or undeveloped, errors of development, defective genitals, abnormal, or mistakes of nature. Emphasize that all of these conditions are biologically understandable while they are statistically uncommon.
Medical classifications
Sexual differentiation
The common pathway of sexual differentiation, where a productive human female has an XX chromosome pair, and a productive male has an XY pair, is relevant to the development of intersex conditions.
During fertilization, the sperm adds either an X (female) or a Y (male) chromosome to the X in the ovum. This determines the genetic sex of the embryo. During the first weeks of development, genetic male and female fetuses are "anatomically indistinguishable", with primitive gonads beginning to develop during approximately the sixth week of gestation. The gonads, in a bipotential state, may develop into either testes (the male gonads) or ovaries (the female gonads), depending on the consequent events. Up until and including the seventh week, genetically female and genetically male fetuses appear identical.
At around eight weeks of gestation, the gonads of an XY embryo differentiate into functional testes, secreting testosterone. Ovarian differentiation, for XX embryos, does not occur until approximately week 12 of gestation. In typical female differentiation, the Müllerian duct system develops into the uterus, Fallopian tubes, and inner third of the vagina.
In males, the Müllerian duct-inhibiting hormone MIH causes this duct system to regress. Next, androgens cause the development of the Wolffian duct system, which develops into the vas deferens, seminal vesicles, and ejaculatory ducts.
By birth, the typical fetus has been completely sexed male or female, meaning that the genetic sex (XY-male or XX-female) corresponds with the phenotypical sex; that is to say, genetic sex corresponds with internal and external gonads, and external appearance of the genitals.
Signs
There are a variety of symptoms that can occur. Ambiguous genitalia is the most common sign. There can be micropenis, clitoromegaly, partial labial fusion, electrolyte abnormalities, delayed or absent puberty, unexpected changes at puberty, hypospadias, labial or inguinal (groin) masses (which may turn out to be testes) in girls and undescended testes (which may turn out to be ovaries) in boys.
Ambiguous genitalia
Ambiguous genitalia may appear as a large clitoris or as a small penis.
Because there is variation in all of the processes of the development of the sex organs, a child can be born with a sexual anatomy that is typically female or feminine in appearance with a larger-than-average clitoris (clitoral hypertrophy) or typically male or masculine in appearance with a smaller-than-average penis that is open along the underside. The appearance may be quite ambiguous, describable as female genitals with a very large clitoris and partially fused labia, or as male genitals with a very small penis, completely open along the midline ("hypospadic"), and empty scrotum. Fertility is variable.
Measurement systems for ambiguous genitalia
The orchidometer is a medical instrument to measure the volume of the testicles. It was developed by Swiss pediatric endocrinologist Andrea Prader. The Prader scale and Quigley scale are visual rating systems that measure genital appearance. These measurement systems were satirized in the Phall-O-Meter, created by the (now defunct) Intersex Society of North America.
Other signs
In order to help in classification, methods other than a genitalia inspection can be performed. For instance, a karyotype display of a tissue sample may determine which of the causes of intersex is prevalent in the case. Additionally, electrolyte tests, endoscopic exam, ultrasound and hormone stimulation tests can be done.
Causes
Intersex can be divided into four categories which are: 46, XX intersex; 46, XY intersex; true gonadal intersex; and complex or undetermined intersex.
46, XX intersex
This condition used to be called "female pseudohermaphroditism". Persons with this condition have female internal genitalia and karyotype (XX) and various degree of external genitalia virilization. External genitalia is masculinized congenitally when female fetus is exposed to excess androgenic environment. Hence, the chromosome of the person is of a woman, the ovaries of a woman, but external genitals that appear like a male. The labia fuse, and the clitoris enlarges to appear like a penis. The causes of this can be male hormones taken during pregnancy, congenital adrenal hyperplasia, male-hormone-producing tumors in the mother and aromatase deficiency.
46, XY intersex
This condition used to be called "male pseudohermaphroditism". This is defined as incomplete masculinization of the external genitalia. Thus, the person has the chromosomes of a man, but the external genitals are incompletely formed, ambiguous, or clearly female. This condition is also called 46, XY with undervirilization. 46, XY intersex has many possible causes, which can be problems with the testes and testosterone formation. Also, there can be problems with using testosterone. Some people lack the enzyme needed to convert testosterone to dihydrotestosterone, which is a cause of 5-alpha-reductase deficiency. Androgen insensitivity syndrome is the most common cause of 46, XY intersex.
True gonadal intersex
This condition used to be called "true hermaphroditism". This is defined as having asymmetrical gonads with ovarian and testicular differentiation on either sides separately or combined as ovotestis. In most cases, the cause of this condition is unknown.
Complex or undetermined intersex
This is the condition of having any chromosome configurations rather than 46, XX or 46, XY intersex. This condition does not result in an imbalance between internal and external genitalia. However, there may be problems with sex hormone levels, overall sexual development, and altered numbers of sex chromosomes.
Conditions
There are a variety of opinions on what conditions or traits are and are not intersex, dependent on the definition of intersex that is used. Current human rights based definitions stress a broad diversity of sex characteristics that differ from expectations for male or female bodies. During 2015, the Council of Europe, the European Union Agency for Fundamental Rights and Inter-American Commission on Human Rights have called for a review of medical classifications on the basis that they presently impede enjoyment of the right to health; the Council of Europe expressed concern that "the gap between the expectations of human rights organisations of intersex people and the development of medical classifications has possibly widened over the past decade".
Medical interventions
Rationales
Medical interventions take place to address physical health concerns and psychosocial risks. Both types of rationale are the subject of debate, particularly as the consequences of surgical (and many hormonal) interventions are lifelong and irreversible. Questions regarding physical health include accurately assessing risk levels, necessity, and timing. Psychosocial rationales are particularly susceptible to questions of necessity as they reflect social and cultural concerns.
There remains no clinical consensus about an evidence base, surgical timing, necessity, type of surgical intervention, and degree of difference warranting intervention. Such surgeries are the subject of significant contention due to consequences that include trauma, impact on sexual function and sensation, and violation of rights to physical and mental integrity. This includes community activism, and multiple reports by international human rights and health institutions and national ethics bodies.In the cases where gonads may pose a cancer risk, as in some cases of androgen insensitivity syndrome, concern has been expressed that treatment rationales and decision-making regarding cancer risk may encapsulate decisions around a desire for surgical "normalization".
Types
Feminizing and masculinizing surgeries: Surgical procedures depend on the diagnosis, and there is often a concern as to whether surgery should be performed at all. Typically, surgery is performed shortly after birth. Defenders of the practice argue that individuals must be clearly identified as male or female for them to function socially and develop "normally". Psychosocial reasons are often stated. This is criticised by many human rights institutions, and authors. Unlike other aesthetic surgical procedures performed on infants, such as corrective surgery for a cleft lip, genital surgery may lead to negative consequences for sexual functioning in later life, or feelings of freakishness and unacceptability.
Hormone treatment: There is widespread evidence of prenatal testing and hormone treatment to prevent or eliminate intersex traits, associated also with the problematization of sexual orientation and gender non-conformity.
Psychosocial support: All stakeholders support psychosocial support. A joint international statement by participants at the Third International Intersex Forum in 2013 sought, amongst other demands: "Recognition that medicalization and stigmatisation of intersex people result in significant trauma and mental health concerns. In view of ensuring the bodily integrity and well-being of intersex people, autonomous non-pathologising psycho-social and peer support be available to intersex people throughout their life (as self-required), as well as to parents and/or care providers."
Genetic selection and terminations: The ethics of preimplantation genetic diagnosis to select against intersex traits was the subject of 11 papers in the October 2013 issue of the American Journal of Bioethics. There is widespread evidence of pregnancy terminations arising from prenatal testing, as well as prenatal hormone treatment to prevent intersex traits. Behrmann and Ravitsky find social concepts of sex, gender and sexual orientation to be "intertwined on many levels. Parental choice against intersex may thus conceal biases against same-sex attractedness and gender nonconformity."
Medical display. Photographs of intersex childrens genitalia are circulated in medical communities for documentary purposes, and individuals with intersex traits may be subjected to repeated genital examinations and display to medical teams. Problems associated with experiences of medical photography of intersex children have been discussed along with their ethics, control and usage. "The experience of being photographed has exemplified for many people with intersex conditions the powerlessness and humiliation felt during medical investigations and interventions".
Gender dysphoria: The DSM-5 included a change from using gender identity disorder to gender dysphoria. This revised code now specifically includes intersex people who do not identify with their sex assigned at birth and experience clinically significant distress or impairment, using the language of disorders of sex development.
See also
Intersex Awareness Day
Intersex people and military service
Sexual differentiation in humans
Gynandromorphism
Endosex
True hermaphroditism
Androgyny
References
Bibliography
Asia Pacific Forum of National Human Rights Institutions (June 2016). Promoting and Protecting Human Rights in relation to Sexual Orientation, Gender Identity and Sex Characteristics. ISBN 978-0-9942513-7-4.
Blackless, Melanie; Charuvastra, Anthony; Derryck, Amanda; Fausto-Sterling, Anne; Lauzanne, Karl; Lee, Ellen (2000). "How sexually dimorphic are we? Review and synthesis". Am J Hum Biol. 12 (2): 151–166. doi:10.1002/(SICI)1520-6300(200003/04)12:2<151::AID-AJHB1>3.0.CO;2-F. PMID 11534012. S2CID 453278.
Council of Europe; Commissioner for Human Rights (April 2015), Human rights and intersex people, Issue Paper
Davis, Georgiann (2015). Contesting Intersex, The Dubious Diagnosis. NYU Press. New York. ISBN 978-1-4798-3786-1.
Elders, M Joycelyn; Satcher, David; Carmona, Richard (June 2017). "Re-Thinking Genital Surgeries on Intersex Infants" (PDF). Palm Center.
Fausto-Sterling, Anne (2000). Sexing the Body: Gender Politics and the Construction of Sexuality. Basic Books. ISBN 978-0-465-07714-4.
Ghattas, Dan Christian; Heinrich-Böll-Stiftung (2013). Human Rights between the Sexes: A preliminary study on the life situations of inter*individuals. Berlin: Heinrich-Böll-Stiftung. ISBN 978-3-86928-107-0.
Holmes, Morgan, ed. (2009). Critical intersex. Ashgate Publishing. Queer interventions. Burlington, VT. ISBN 978-0-7546-7311-8.
Hughes, I A; Houk, C; Ahmed, S F; Lee, P A; LWPES1/ESPE2 Consensus Group (June 2005). "Consensus statement on management of intersex disorders". Archives of Disease in Childhood. 91 (7): 554–563. doi:10.1136/adc.2006.098319. ISSN 0003-9888. PMC 2082839. PMID 16624884.
Human Rights Commission of the City and County of San Francisco; de María Arana, Marcus (2005). A Human Rights Investigation Into The Medical "Normalization" Of Intersex People. San Francisco.
Human Rights Watch; interACT (July 2017). I Want to Be Like Nature Made Me. ISBN 978-1-62313-502-7.
Jones, Tiffany; Hart, Bonnie; Carpenter, Morgan; Ansara, Gavi; Leonard, William; Lucke, Jayne (2016). Intersex: Stories and Statistics from Australia (PDF). Cambridge, UK: Open Book Publishers. ISBN 978-1-78374-208-0. Archived from the original (PDF) on 27 May 2018. Retrieved 2 February 2016.
Jones, Tiffany (2018). "Intersex Studies: A Systematic Review of International Health Literature". SAGE Open. 2018 (1): 1–22. doi:10.1177/2158244017745577.
Karkazis, Katrina (2008). Fixing Sex: Intersex, Medical Authority, and Lived Experience. Duke University Press. ISBN 978-0-8223-4318-9.
Lee, Peter A.; Nordenström, Anna; Houk, Christopher P.; Ahmed, S. Faisal; Auchus, Richard; Baratz, Arlene; Baratz Dalke, Katharine; Liao, Lih-Mei; Lin-Su, Karen; Looijenga, Leendert H.J.; Mazur, Tom; Meyer-Bahlburg, Heino F.L.; Mouriquand, Pierre; Quigley, Charmian A.; Sandberg, David E.; Vilain, Eric; Witchel, Selma; and the Global DSD Update Consortium (28 January 2016). "Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care". Hormone Research in Paediatrics. 85 (3): 158–180. doi:10.1159/000442975. ISSN 1663-2818. PMID 26820577.
National Advisory Commission on Biomedical Ethics, Switzerland (November 2012). On the management of differences of sex development. Ethical issues relating to "intersexuality".Opinion No. 20/2012 (PDF). 2012. Berne. Archived from the original (PDF) on 23 April 2015. Retrieved 20 October 2018.
Organisation Intersex International Australia; Carpenter, Morgan (April 2014). "Submission on the Review of Part B of the Ethical Guidelines for the Use of Assisted Reproductive Technology in Clinical Practice and Research, 2007". Sydney. Archived from the original on 6 October 2014. Retrieved 6 May 2014.
Regmi, Esan (2016). Stories of Intersex People from Nepal. Kathmandu. Archived from the original on 28 July 2017. Retrieved 19 March 2021.
Senate of Australia; Community Affairs References Committee (2013). Involuntary or coerced sterilisation of intersex people in Australia. Canberra. ISBN 978-1-74229-917-4.
Tamar-Mattis, Anne (2014). "Medical Treatment of People with Intersex Conditions as Torture and Cruel, Inhuman, or Degrading Treatment or Punishment". In Center for Human Rights & Humanitarian Law; Washington College of Law (eds.). Torture in Healthcare Settings: Reflections on the Special Rapporteur on Tortures 2013 Thematic Report. Washington, DC. pp. 91–104.
United Nations Office of the High Commissioner for Human Rights (2015). "Free & Equal Campaign Fact Sheet: Intersex" (PDF).
UN Committee against Torture; UN Committee on the Rights of the Child; UN Committee on the Rights of People with Disabilities; UN Subcommittee on Prevention of Torture and other Cruel, Inhuman or Degrading Treatment or Punishment; Juan Méndez; Dainius Pῡras; Dubravka Šimonoviæ; Marta Santos Pais; African Commission on Human and Peoples Rights; Council of Europe Commissioner for Human Rights; Inter-American Commission on Human Rights (24 October 2016), "Intersex Awareness Day – Wednesday 26 October. End violence and harmful medical practices on intersex children and adults, UN and regional experts urge", Office of the High Commissioner for Human Rights
World Health Organization; OHCHR; UN Women; UNAIDS; UNDP; UNFPA; UNICEF (2014). Eliminating forced, coercive and otherwise involuntary sterilization, An interagency statement (PDF). ISBN 978-92-4-150732-5.
Zwischengeschlecht (March 2014). "IGM – Historical Overview. Hermaphrodites in the Developed World: From Legal Self-Determination to IGM, Supplement 1" (PDF). NGO Report to the 2nd, 3rd and 4th Periodic Report of Switzerland on the Convention on the Rights of the Child (CRC) (2 ed.). pp. 49–62.
External links
Media related to Intersex at Wikimedia Commons |
Lissencephaly | Lissencephaly (, meaning "smooth brain") is a set of rare brain disorders whereby the whole or parts of the surface of the brain appear smooth. It is caused by defective neuronal migration during the 12th to 24th weeks of gestation resulting in a lack of development of brain folds (gyri) and grooves (sulci). It is a form of cephalic disorder. Terms such as agyria (no gyri) and pachygyria (broad gyri) are used to describe the appearance of the surface of the brain.
Children with lissencephaly generally have significant developmental delays, but these vary greatly from child to child depending on the degree of brain malformation and seizure control. Life expectancy can be shortened, generally due to respiratory problems.
Symptoms and signs
Affected children display severe psychomotor impairment, failure to thrive, seizures, and muscle spasticity or hypotonia. Other symptoms of the disorder may include unusual facial appearance, difficulty swallowing, and anomalies of the hands, fingers, or toes.
Symptoms of lissencephaly are detected via ultrasound at about twenty-three weeks and require confirmation from a prenatal MRI. It is characterised by absence or reduction of the sulci and gyri of the cerebral surface and a thickened cortex.There are anatomical symptoms that differ across the two main types of lissencephaly, Classical (Type I) and Cobble Stone (Type 2). In Classical lissencephaly the cortex becomes thickened and can be identified by four layers of the cerebral cortex rather than six.Cobblestone lissencephaly is named after the pebbled or cobblestone appearance of the cortical surface. This uneven cortical surface is due to incomplete organogenesis which leads to no distinguishable layers in the cerebral cortex. Cobblestone lissencephaly shows a reduction and abnormalities in the grey matter of the cerebral cortex.
Causes
Causes of lissencephaly can include viral infections of the uterus or the fetus during the first trimester, or insufficient blood supply to the fetal brain early in pregnancy. There are also a number of genetic causes of lissencephaly, including mutation of the reelin gene (on chromosome 7), as well as other genes on the X chromosome and on chromosome 17. Genetic counseling is usually offered if there is a risk of lissencephaly, coupled with genetic testing.
Neural migration
Folding of the cerebral cortex is important in the development of overall brain function and cognitive abilities. Neuronal migration is the process by which neurons migrate to the final position in the brain during the development of the nervous system. This development of the nervous system occurs between 12 and 16 weeks of gestation. The neurons are created at the ventricular zone. The neurons then extend along the radial glia to reach the cortical zone. It is the disruption of the radial and tangential migration that causes reduced or absence gyri that is known as lissencephaly.The lack of gyri causing a smooth appearance of the cerebral cortex is due to abnormal neuronal migration in the developmental stages of the nervous system. The cause of lissencephaly has been linked to both genetic and non-genetic factors. Three main types of lissencephaly have been identified and although all types display the similar symptoms the pathogenesis of each type varies.The genes associated with lissencephaly are still being discovered; however, due to advances in genetics individual genes are being identified as the cause of lissencephaly. Mutations in LIS1, DCX (doublecortin), ARX(aristaless related homeobox), RELN have all been identified to cause lissencephaly. Viral infections can also cause lissencephaly.The known genetic and viral causes are listed below:
LIS1
LIS1 (also known as PAFAH1B1) is the most widely studied. LIS1 is located on chromosome 17p13.3. LIS1 is integral in regulating the motor protein dynein which plays an important role in the movement of neuronal nuclei along microtubules. The mutation or deletion involving LIS1 is associated with both Isolated Lissencephaly Syndrome and Miller–Dieker syndrome. Miller-Dieker syndrome however, has additional deletions of adjacent genes on chromosome 17 causing facial and other congenital abnormalities and defects. This mutation full or deletion of chromosome 17p13.3 leads to inadequate neuronal migration due to LIS1 encoding for an enzyme that interacts with the microtubule protein dynein. LIS1 mutation or deletion is not inherited from a parent and thus recurrence is unlikely.A Chinese family with an autosomal dominant inheritance pattern and a mutation in this gene has been reported.
DCX
DCX or doublecortin encodes for the doublecortin protein which is similar to LIS1 as it encodes a microtubule associated protein that is related to microtubule function and transport in developing neuronal processes. DCX mutation causes the disorganisation of neocortical layering in the cerebral cortex leading to a reduced folding. DCX is localised to the X chromosome and thus this mutation may be inherited however it still can appear randomly. As it is an X chromosome linked abnormality males who inherit the gene are more likely to be severely affected. Females who inherit the DCX mutation have a more mild version of the syndrome.
ARX
The ARX gene encodes for the aristaless related homeobox genes which are active in the early embryonic development to control formation of many tissues and structure. ARX is involved in the development of the embryonic forebrain, migration and communication of neurons as well as migration and proliferation of interneurons. As ARX is expressed in the ganglionic eminences and the neocortical ventricular zone it can affect both radial and tangential migration. Similar to DCX, ARX is an X chromosome linked gene and is linked with other symptoms such as absence of portions of the brain, abnormal genitalia and severe epilepsy.
RELN
Reelin (RELN) is an extracellular matrix glycoproteins that is secreted to help with the regulation of neuronal migration. Lack of RELN in mice has shown deficiencies in migrating neurons. In reported cases, lissencephaly caused by RELN deficiency has been more severe in anterior brain regions with a very small cerebellum.
Viral infection
Lissencephaly has been recorded to have been caused by viruses and insufficient blood supply to the developing fetal brain. Cytomegalovirus (CMV) is a herpes related virus that can cause congenital defects. CMV has a high affinity for the developing germinal matrix of the brain. The severity of the infection is proportional to the time in gestation that the fetus was infected. It is early infection that leads to lissencephaly. This is because early infection disrupts the migration and development of neurons.
Diagnosis
The diagnosis of lissencephaly is usually made at birth or soon after by ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI). However, these results should be interpreted cautiously since even experienced radiologists can misdiagnose polymicrogyria, a different developmental malformation of the brain, as lissencephaly.
Before birth, complex ultrasounds performed routinely during pregnancy may indicate the presence of a cerebral abnormality, but this method of diagnosis should be complemented by other methods, such as genetic studies and NMR, and the examination is not recommended as part of routine ultrasound examinations, unless family medical history or other reasons for suspecting brain malformation are present. The earliest point during gestation when it is possible to observe abnormal development of the brain surface is approximately in week 20, although ultrasound examinations in week 25–30 are more common. Up to this time, the fetal brain normally has a smooth appearance. If lissencephaly is suspected, chorionic villus sampling can test for some lissencephaly variants, but only those with a known genetic mutation.
Classification
The spectrum of lissencephaly is only now becoming more defined as neuroimaging and genetics have provided more insights into migration disorders. There are around 20 types of lissencephaly that make up the spectrum. Other causes which have not yet been identified are likely as well.
Different systems for classifying lissencephaly exist. One major distinction is "classic" (type I) vs. "cobblestone" (type II), but some systems add additional forms that fit into neither of these categories.
Some types of lissencephaly are described below (OMIM numbers are included where available):
Treatment
Treatment for those with lissencephaly is symptomatic and depends on the severity and locations of the brain malformations. Treatment is tailored towards the symptoms of the individual. Therapies for lissencephaly are to deal with the symptoms as the syndrome is congenital. Supportive care may be needed to help with comfort and nursing needs. Seizures may be controlled with medication and hydrocephalus may require shunting. If feeding becomes difficult, a gastrostomy tube may be considered.
There are a number of organisations that raise awareness and funding for rare disabilities such as lissencephaly. They also seek to increase the quality of life for individuals living with related disabilities. In the United States, these organizations include Arc of the United States, National Organization for Rare Disorders, and March of Dimes.
Prognosis
The prognosis for children with lissencephaly varies depending on the malformation and severity of the syndrome. Many individuals remain at a 3–5 month developmental level. Life expectancy is short and many children with lissencephaly will die before the age of 10. Some children with lissencephaly will be able to roll over, sit, reach for objects, and smile socially. Aspiration and respiratory disease are the most common causes of illness or death. In the past, life expectancy was said to be around two years of age. However, with advances in seizure control, and treatments for respiratory illness, most children live well beyond that age. With other advances in therapy and the broader availability of services and equipment, some children with lissencephaly are able to walk with varying degrees of assistance and to perform other functions once thought too advanced.
See also
Gyrification
CEP85L - gene associated with posterior predominant lissencephaly in a 2020 study
References
External links
Lissencephaly at NINDS
GeneReviews/NCBI/NIH/UW entry on DCX-Related Disorders
OMIM entries on DCX-Related Disorders
GeneReview/NIH/UW entry on LIS1 Lissencephaly |
Bardet–Biedl syndrome | Bardet–Biedl syndrome (BBS) is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized by rod/cone dystrophy, polydactyly, central obesity, hypogonadism, and kidney dysfunction in some cases. Historically, slower mental processing has also been considered a principal symptom but is now not regarded as such.
Signs and symptoms
Bardet–Biedl syndrome is a pleiotropic disorder with variable expressivity and a wide range of clinical variability observed both within and between families. The most common clinical features are rod–cone dystrophy, with childhood-onset night-blindness followed by increasing visual loss; postaxial polydactyly; truncal obesity that manifests during infancy and remains problematic throughout adulthood; varying degrees of learning disabilities; male hypogenitalism and complex female genitourinary malformations; and renal dysfunction, a major cause of morbidity and mortality.There is a wide range of secondary features that are sometimes associated with BBS: 147–148 including: 153–154
Strabismus, cataracts, astigmatism, pigmentary retinopathy, poor visual acuity, low vision, and/or blindness caused by an impaired photoreceptor transport mechanism in the retina.
"Brachydactyly, syndactyly of both the hands and feet is common, as is partial syndactyl (most usually between the second and third toes)"
Polyuria/polydipsia (nephrogenic diabetes insipidus)
Ataxia/poor coordination/imbalance
Mild hypertonia (especially lower limbs)
Diabetes mellitus
Hepatic involvement
Anosmia
Auditory deficiencies
Hirschsprung disease and subsequent bowel obstruction has been described.
Hypertrophy of interventricular septum and left ventricle and dilated cardiomyopathy.
Hypogonadism, kidney failure, urogenital sinuses, ectopic urethra, uterus duplex, septate vagina, and hypoplasia of the uterus, ovaries, and fallopian tubes
Speech disorder/delay
Developmental delay, especially of fine and gross motor skills
Relation to other rare genetic disorders
Findings in genetic research published in 2006 have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely varying, phenotypically observed disorders. BBS is one such syndrome that has now been identified to be caused by defects in the cellular ciliary structure. Thus, BBS is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, polycystic kidney and liver disease, nephronophthisis, Alström syndrome, Meckel–Gruber syndrome and some forms of retinal degeneration.
Pathophysiology
The detailed biochemical mechanism that leads to BBS is still unclear.The gene products encoded by these BBS genes, called BBS proteins, are located in the basal body and cilia of the cell.Using the round worm C. elegans as a model system, biologists found that BBS proteins are involved in a process called intraflagellar transport (IFT), a bi-directional transportation activity within the cilia along the long axis of the ciliary shaft that is essential for ciliogenesis and the maintenance of cilia. Recent biochemical analysis of human BBS proteins revealed that BBS proteins are assembled into a multiple protein complex, called "BBSome". BBSome is proposed to be responsible for transporting intracellular vesicles to the base of the cilia and to play an important role in the ciliary function.Since abnormalities of cilia are known to be related to a wide range of disease symptoms including those commonly seen in BBS patients, it is now widely accepted that mutated BBS genes affect normal cilia function, which, in turn, causes BBS.A theory that photoreceptor cells are nourished by the IFT of retinal cilia now offers a potential explanation for the retinal dystrophy common in BBS patients after their early years of life.Genes involved include:
BBsome: BBS1, BBS2, ARL6/BBS3, BBS4, BBS5, BBS7, TTC8/BBS8, BBS10, TRIM32/BBS11 BBS12, CCDC28B, CEP290, TMEM67, MKS1, MKKS
chaperone: BBS6
Diagnosis
The diagnosis of BBS is established by clinical findings and family history. Molecular genetic testing can be used to confirm the diagnosis. Multigene panels offer the most effective approach in achieving molecular confirmation of BBS.
Eponym
The syndrome is named after Georges Bardet and Arthur Biedl. The first known case was reported by Laurence and Moon in 1866 at the Ophthalmic Hospital in South London. Laurence–Moon–Biedl–Bardet syndrome is no longer considered as valid terms in that patients of Laurence and Moon had paraplegia but no polydactyly or obesity, which are the key elements of the Bardet–Biedl syndrome. Laurence–Moon syndrome is usually considered a separate entity. However, some recent research suggests that the two conditions may not be distinct.As of 2012, 14
(or 15) different BBS genes had been identified.
References
External links
Overview at United States National Library of Medicine
Molecular diagnosis at NCBI |
Thymus hyperplasia | Thymus hyperplasia refers to an enlargement ("hyperplasia") of the thymus.It is not always a disease state. The size of the thymus usually peaks during adolescence and atrophies in the following decades. Before the immune function of the thymus was well understood, the enlargement was sometimes seen as a cause for alarm, and justification for surgical reduction. This approach is much less common today.
It can be associated with myasthenia gravis. Magnetic Resonance Imaging can be used to distinguish it from thymoma.
Thymic hyperplasia
Thymic hyperplasia can be divided into three groups namely, those without any pre-existing medical condition, those recovering from a pre-existing medical condition such as pneumonia, corticosteroid therapy, radiation therapy, chemotherapy, surgery, and burns, and those with other disorders such as hyperthyroidism, sarcoidosis, or pure red cell aplasia.
References
== External links == |
Aggressive infantile fibromatosis | Aggressive infantile fibromatosis is a locally recurring, non-metastasizing lesion, presenting with a single or multiple fast-growing masses that are present at birth or occur within the first year of life.: 607
See also
Infantile digital fibromatosis
Skin lesion
== References == |
Pustular psoriasis | The term pustular psoriasis is used for a heterogeneous group of diseases that share pustular skin characteristics.
Signs and symptoms
Characteristics may vary according to the subtype of pustular psoriasis. For example, it can be localized, commonly to the hands and feet (localized pustular psoriasis), or generalized with widespread patches appearing randomly on any part of the body (generalized pustular psoriasis). However, all forms of pustular psoriasis share in common the presence of red and tender blotchy skin covered with pustules.Pustular psoriasis can be localized, commonly to the hands and feet (palmoplantar pustulosis), or generalized with widespread patches occurring randomly on any part of the body. Acrodermatitis continua is a form of localized psoriasis limited to the fingers and toes that may spread to the hands and feet. Pustulosis palmaris et plantaris is another form of localized pustular psoriasis similar to acrodermatitis continua with pustules erupting from red, tender, scaly skin found on the palms of the hands and the soles of the feet.Generalized pustular psoriasis (GPP) is also known as (von Zumbusch) acute generalized pustular psoriasis in acute cases, and as impetigo herpetiformis during pregnancy. GPP is a rare and severe form of psoriasis that may require hospitalization. This form of psoriasis is characterized by an acute onset of numerous pustules on top of tender red skin. This skin eruption is often accompanied by a fever, muscle aches, nausea, and an elevated white blood cell count. Annular pustular psoriasis (APP), a rare form of GPP, is the most common type seen during childhood. APP tends to occur in women more frequently than in men, and is usually less severe than other forms of generalized pustular psoriasis such as impetigo herpetiformis. This form of psoriasis is characterized by ring-shaped plaques with pustules around the edges and yellow crusting. APP most often affects the torso, neck, arms, and legs.
Diagnosis
Classification
Pustular psoriasis is classified into two major forms: localized and generalized pustular psoriasis. Within these two categories there are several variants:
Management
injection of methotrexate
References
== External links == |
Lipoblastomatosis | Benign lipoblastomatosis is a tumor consisting of fetal-embryonal adipocytes, frequently confused with a liposarcoma, affecting exclusively infants and young children, with approximately 90% of cases occurring before 3 years of age.: 626 The term lipoblastomatosis was first used by Vellios et al. in 1958, at which point the tumor became generally accepted as a distinctive entity. Today Diffuse lipoblastoma is the preferred term for Lipoblastomatosis. The tumor is rare, accounting for less than 1% of all childhood neoplasm, and it has been found to be more common in males than females. It often presents as an asymptomatic rapidly enlarging mass, occurring more often in the soft tissues of the extremities.
See also
Myxoid lipoblastoma
List of cutaneous conditions
References
== External links == |
Transient lingual papillitis | Transient lingual papillitis are painful, hypertrophic, red and white lingual papillae on the tongue.
Cause
Transient lingual papillitis can affect males and females as early as 3 years of age. In many cases, the cause is unknown. Some dental professionals believe the inflammation is due to chronic irritation from teeth, fillings, or dental appliances. Stress, poor nutrition, smoking, and alcohol use may also be initiating factors.
== References == |
Vomiting | Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of ones stomach through the mouth and sometimes the nose.Vomiting can be the result of ailments like food poisoning, gastroenteritis, pregnancy, motion sickness, or hangover; or it can be an after effect of diseases such as brain tumors, elevated intracranial pressure, or overexposure to ionizing radiation. The feeling that one is about to vomit is called nausea; it often precedes, but does not always lead to vomiting. Impairment due to alcohol or anesthesia can cause inhalation of vomit, leading to suffocation. In severe cases, where dehydration develops, intravenous fluid may be required. Antiemetics are sometimes necessary to suppress nausea and vomiting. Self-induced vomiting can be a component of an eating disorder such as bulimia, and is itself now classified as an eating disorder on its own, purging disorder.
Complications
Aspiration
Vomiting is dangerous if gastric content enters the respiratory tract. Under normal circumstances the gag reflex and coughing prevent this from occurring; however, these protective reflexes are compromised in persons who are under the influence of certain substances (including alcohol) or even mildly anesthetized. The individual may choke and asphyxiate or develop aspiration pneumonia.
Dehydration and electrolyte imbalance
Prolonged and excessive vomiting depletes the body of water (dehydration), and may alter the electrolyte status. Gastric vomiting leads to the loss of acid (protons) and chloride directly. Combined with the resulting alkaline tide, this leads to hypochloremic metabolic alkalosis (low chloride levels together with high HCO−3 and CO2 and increased blood pH) and often hypokalemia (potassium depletion). The hypokalemia is an indirect result of the kidney compensating for the loss of acid. With the loss of intake of food the individual may eventually become cachectic. A less frequent occurrence results from a vomiting of intestinal contents, including bile acids and HCO−3, which can cause metabolic acidosis.
Mallory–Weiss tear
Repeated or profuse vomiting may cause erosions to the esophagus or small tears in the esophageal mucosa (Mallory–Weiss tear). This may become apparent if fresh red blood is mixed with vomit after several episodes.
Dentistry
Recurrent vomiting, such as observed in bulimia nervosa, may lead to the destruction of the tooth enamel due to the acidity of the vomit. Digestive enzymes can also have a negative effect on oral health, by degrading the tissue of the gums.
Pathophysiology
Receptors on the floor of the fourth ventricle of the brain represent a chemoreceptor trigger zone, known as the area postrema, stimulation of which can lead to vomiting. The area postrema is a circumventricular organ and as such lies outside the blood–brain barrier; it can therefore be stimulated by blood-borne drugs that can stimulate vomiting or inhibit it.There are various sources of input to the vomiting center:
The chemoreceptor trigger zone at the base of the fourth ventricle has numerous dopamine D2 receptors, serotonin 5-HT3 receptors, opioid receptors, acetylcholine receptors, and receptors for substance P. Stimulation of different receptors are involved in different pathways leading to emesis, in the final common pathway substance P appears involved.
The vestibular system, which sends information to the brain via cranial nerve VIII (vestibulocochlear nerve), plays a major role in motion sickness, and is rich in muscarinic receptors and histamine H1 receptors.
The cranial nerve X (vagus nerve) is activated when the pharynx is irritated, leading to a gag reflex.
The vagal and enteric nervous system inputs transmit information regarding the state of the gastrointestinal system. Irritation of the GI mucosa by chemotherapy, radiation, distention, or acute infectious gastroenteritis activates the 5-HT3 receptors of these inputs.
The CNS mediates vomiting that arises from psychiatric disorders and stress from higher brain centers.
The medulla plays an important role for triggering the vomiting act.The vomiting act encompasses three types of outputs initiated by the chemoreceptor trigger zone: Motor, parasympathetic nervous system (PNS), and sympathetic nervous system (SNS). They are as follows:
Increased salivation to protect tooth enamel from stomach acids. (Excessive vomiting leads to dental erosion.) This is part of the PNS output.
The body takes a deep breath to avoid aspirating vomit.
Retroperistalsis starts from the middle of the small intestine and sweeps up digestive tract contents into the stomach, through the relaxed pyloric sphincter.
Intrathoracic pressure lowers (by inspiration against a closed glottis), coupled with an increase in abdominal pressure as the abdominal muscles contract, propels stomach contents into the esophagus as the lower esophageal sphincter relaxes. The stomach itself does not contract in the process of vomiting except for at the angular notch, nor is there any retroperistalsis in the esophagus.
Vomiting is ordinarily preceded by retching.
Vomiting also initiates an SNS response causing both sweating and increased heart rate.
Phases
The vomiting act has two phases. In the retching phase, the abdominal muscles undergo a few rounds of coordinated contractions together with the diaphragm and the muscles used in respiratory inspiration. For this reason, an individual may confuse this phase with an episode of violent hiccups. In this retching phase, nothing has yet been expelled. In the next phase, also termed the expulsive phase, intense pressure is formed in the stomach brought about by enormous shifts in both the diaphragm and the abdomen. These shifts are, in essence, vigorous contractions of these muscles that last for extended periods of time—much longer than a normal period of muscular contraction. The pressure is then suddenly released when the upper esophageal sphincter relaxes resulting in the expulsion of gastric contents. Individuals who do not regularly exercise their abdominal muscles may experience pain in those muscles for a few days. The relief of pressure and the release of endorphins into the bloodstream after the expulsion causes the vomiter to feel better.
Contents
Gastric secretions and likewise vomit are highly acidic. Recent food intake appears in the gastric vomit. Irrespective of the content, vomit tends to be malodorous.The content of the vomitus (vomit) may be of medical interest. Fresh blood in the vomit is termed hematemesis ("blood vomiting"). Altered blood bears resemblance to coffee grounds (as the iron in the blood is oxidized) and, when this matter is identified, the term coffee-ground vomiting is used. Bile can enter the vomit during subsequent heaves due to duodenal contraction if the vomiting is severe. Fecal vomiting is often a consequence of intestinal obstruction or a gastrocolic fistula and is treated as a warning sign of this potentially serious problem (signum mali ominis).If the vomiting reflex continues for an extended period with no appreciable vomitus, the condition is known as non-productive emesis or "dry heaves", which can be painful and debilitating.
Color of vomitBright red in the vomit suggests bleeding from the esophagus
Dark red vomit with liver-like clots suggests profuse bleeding in the stomach, such as from a perforated ulcer
Coffee-ground-like vomit suggests less severe bleeding in the stomach because the gastric acid has had time to change the composition of the blood
Yellow vomit suggests bile, indicating that the pyloric valve is open and bile is flowing into the stomach from the duodenum (this is more common in older people)
Causes
Vomiting may be due to a large number of causes, and protracted vomiting has a long differential diagnosis.
Digestive tract
Causes in the digestive tract
Gastritis (inflammation of the gastric wall)
Gastroenteritis
Gastroesophageal reflux disease
Celiac disease
Non-celiac gluten sensitivity
Pyloric stenosis (in babies, this typically causes a very forceful "projectile vomiting" and is an indication for urgent surgery)
Bowel obstruction
Overeating (stomach too full)
Acute abdomen and/or peritonitis
Ileus
Food allergies (often in conjunction with hives or swelling)
Cholecystitis, pancreatitis, appendicitis, hepatitis
Food poisoning
In children, it can be caused by an allergic reaction to cows milk proteins (Milk allergy or lactose intolerance)
Sensory system and brain
Causes in the sensory system:
Movement leading to motion sickness (which is caused by overstimulation of the labyrinthine canals of the ear)
Ménières disease
VertigoCauses in the brain:
Concussion
Cerebral hemorrhage
Migraine
Brain tumors, which can cause the chemoreceptors to malfunction
Benign intracranial hypertension and hydrocephalusMetabolic disturbances (these may irritate both the stomach and the parts of the brain that coordinate vomiting):
Hypercalcemia (high calcium levels)
Uremia (urea accumulation, usually due to kidney failure)
Adrenal insufficiency
Hypoglycemia
HyperglycemiaPregnancy:
Hyperemesis, morning sicknessDrug reaction (vomiting may occur as an acute somatic response to):
Alcohol, which can be partially oxidized into acetaldehyde that causes the symptoms of hangover, including nausea, vomiting, shortness of breath, and fast heart rate.
Opioids
Selective serotonin reuptake inhibitors
Many chemotherapy drugs
Some entheogens (such as peyote or ayahuasca)Illness (sometimes colloquially known as "stomach flu"—a broad name that refers to gastric inflammation caused by a range of viruses and bacteria):
Norovirus (formerly Norwalk virus or Norwalk agent)
Swine influenzaPsychiatric/behavioral:
Bulimia nervosa
Purging disorder
Emetics
An emetic, such as syrup of ipecac, is a substance that induces vomiting when administered orally or by injection. An emetic is used medically when a substance has been ingested and must be expelled from the body immediately. (For this reason, many toxic and easily digestible products such as rat poison contain an emetic. This presents no problem for the effectiveness of the rodenticide as rodents are unable to vomit.) Inducing vomiting can remove the substance before it is absorbed into the body.
Emetics can be divided into two categories, those which produce their effect by acting on the vomiting center in the medulla, and those which act directly on the stomach itself. Some emetics, such as ipecac, fall into both categories; they initially act directly on the stomach, while their further and more vigorous effect occurs by stimulation of the medullary center.Salt water and mustard water, which act directly on the stomach, have been used since ancient times as emetics. Care must be taken with salt, as excessive intake can potentially be harmful.Copper sulfate was also used in the past as an emetic. It is now considered too toxic for this use.Hydrogen peroxide is used as an emetic in veterinary practice.
Self-induced
Eating disorders (anorexia nervosa or bulimia nervosa)
To eliminate an ingested poison (some poisons should not be vomited as they may be more toxic when inhaled or aspirated; it is better to ask for help before inducing vomiting)
Some people who engage in binge drinking induce vomiting to make room in their stomachs for more alcohol consumption.
Participants of the Milk challenge typically end up vomiting most of the milk they consume, as proteins in the ingested milk (such as casein) rapidly denature and unravel on contact with gastric acid and protease enzymes, rapidly filling the stomach. Once the stomach becomes full, stretch receptors in the stomach wall trigger signals to vomit to expel any further liquid the participant ingests.
People suffering from nausea may induce vomiting in hopes of feeling better.
Miscellaneous
After surgery (postoperative nausea and vomiting)
Disagreeable sights or disgust, smells, sounds or thoughts (such as decayed matter, others vomit, thinking of vomiting), etc.
Extreme pain, such as an intense headache or myocardial infarction (heart attack)
Extreme emotions
Cyclic vomiting syndrome (a poorly understood condition with attacks of vomiting)
Cannabinoid hyperemesis syndrome (similar to cyclic vomiting syndrome, but has cannabis use as its underlying cause).
High doses of ionizing radiation sometimes trigger a vomit reflex.
Violent fits of coughing, hiccups, or asthma
Anxiety
Depression
Overexertion (doing too much strenuous exercise can lead to vomiting shortly afterwards).
Rumination syndrome, an underdiagnosed and poorly understood disorder that causes patients to regurgitate food shortly after ingestion.
Other types
Projectile vomiting is vomiting that ejects the gastric contents with great force. It is a classic symptom of infantile hypertrophic pyloric stenosis, in which it typically follows feeding and can be so forceful that some material exits through the nose.
Treatment
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of medications such as opioids and chemotherapy.Antiemetics act by inhibiting the receptor sites associated with emesis. Hence, anticholinergics, antihistamines, dopamine antagonists, serotonin antagonists, and cannabinoids are used as antiemetics.Evidence to support the use of antiemetics for nausea and vomiting among adults in the emergency department is poor. It is unclear if any medication is better than another or better than no active treatment.
Epidemiology
Nausea and/or vomiting are the main complaints in 1.6% of visits to family physicians in Australia.
Society and culture
Herodotus, writing on the culture of the ancient Persians and highlighting the differences with those of the Greeks, notes that to vomit in the presence of others is prohibited among Persians.
Social cues
It is quite common that, when one person vomits, others nearby become nauseated, particularly when smelling the vomit of others, and often to the point of vomiting themselves. It is believed that this is an evolved trait among primates. Many primates in the wild tend to browse for food in small groups. Should one member of the party react adversely to some ingested food, it may be advantageous (in a survival sense) for other members of the party to also vomit. This tendency in human populations has been observed at drinking parties, where excessive consumption of alcoholic beverages may cause a number of party members to vomit nearly simultaneously, this being triggered by the initial vomiting of a single member of the party. This phenomenon has been touched on in popular culture: notorious instances appear in the films Monty Pythons The Meaning of Life (1983) and Stand By Me (1986).Intense vomiting in ayahuasca ceremonies is a common phenomenon. However, people who experience "la purga" after drinking ayahuasca, in general, regard the practise as both a physical and spiritual cleanse and often come to welcome it. It has been suggested that the consistent emetic effects of ayahuasca—in addition to its many other therapeutic properties—was of medicinal benefit to indigenous peoples of the Amazon, in helping to clear parasites from the gastrointestinal system.There have also been documented cases of a single ill and vomiting individual inadvertently causing others to vomit, when they are especially fearful of also becoming ill, through a form of mass hysteria.
Most people try to contain their vomit by vomiting into a sink, toilet, or trash can, as vomit is difficult and unpleasant to clean. On airplanes and boats, special bags are supplied for sick passengers to vomit into. A special disposable bag (leakproof, puncture-resistant, odorless) containing absorbent material that solidifies the vomit quickly is also available, making it convenient and safe to store until there is an opportunity to dispose of it conveniently.People who vomit chronically (e.g., as part of an eating disorder such as bulimia nervosa) may devise various ways to hide this disorder.An online study of peoples responses to "horrible sounds" found vomiting "the most disgusting". Professor Trevor Cox of the University of Salfords Acoustic Research Centre said, "We are pre-programmed to be repulsed by horrible things such as vomiting, as it is fundamental to staying alive to avoid nasty stuff." It is thought that disgust is triggered by the sound of vomiting to protect those nearby from possibly diseased food.
Psychology
Emetophilia is sexual arousal from vomiting, or watching others vomit. Emetophobia is a phobia that causes overwhelming, intense anxiety pertaining to vomiting.
See also
Bulimia nervosa
Emetophilia
Cancer and nausea
Emetophobia
Vasodilation
Diarrhea
Nose-blowing
Belching
Chyme
Notes
References
External links
Cyclical Vomiting Syndrome
"Emetics" . The American Cyclopædia. 1879. |
Mesoblastic nephroma | Congenital mesoblastic nephroma, while rare, is the most common kidney neoplasm diagnosed in the first three months of life and accounts for 3-5% of all childhood renal neoplasms. This neoplasm is generally non-aggressive and amenable to surgical removal. However, a readily identifiable subset of these kidney tumors has a more malignant potential and is capable of causing life-threatening metastases. Congenital mesoblastic nephroma was first named as such in 1967 but was recognized decades before this as fetal renal hamartoma or leiomyomatous renal hamartoma.
Presentation
Congenital mesoblastic nephroma typically (76% of cases) presents as an abdominal mass which is detected prenatally (16% of cases) by ultrasound or by clinical inspection (84% of cases) either at birth or by 3.8 years of age (median age ~1 month). The neoplasm shows a slight male preference. Concurrent findings include hypertension (19% of cases), polyhydramnios (i.e. excess of amniotic fluid in the amniotic sac) (15%), hematuria (11%), hypercalcemia (4%), and elevated serum levels of the kidney-secreted, hypertension-inducing enzyme, renin (1%). Congenital anomalies have been reported in 11 patients: 6 with genitourinary anomalies, 2 with gastrointestinal anomalies, 1 with hydrocephalus, and 1 with the Beckwith–Wiedemann syndrome. The vast majority of patients present with localized (i.e. non-metastatic) disease. Most patients disease is classified at presentation as stage I or II (i.e. localized), few patients present with stage III (i.e. locally advanced/infiltrating), and virtually no patients present with stage IV (metastases present or V (i.e. tumors in both kidneys) disease (see staging of renal cancer).
Tumor pathology
Congenital Mesoblastic nephroma is a malignant tumorous growth of the kidneys mesenchyme (i.e. connective tissue cells). Histologic examination of these tumors provides critical information on their prognoses. This examination divides congenital mesoblastic nephroma into three types:
1) The classic type occurs in ~39% of patients. Its tissues show interlaced spindle-shaped smooth muscle cells evidencing low mitotic activity with no evidence of tumor encapsulation; and infiltration into and entrapment of normal kidney tissue.
2) The cellular type occurs in ~42% of patients. Its tissues show densely packed fibrosarcoma-like cells evidencing high rates of mitosis, less infiltration of normal kidney tissue, and multiple areas of hemorrhage and cysts.
3) The mixed type occurs in ~19% of patients. It shows a mixture of the classic and cellular types in different areas of the neoplasm.
Genetics
A study conducted in 1998 found that congenital mesoblastic nephroma tissues taken from some patients contained an acquired mutation, the ETV6-NTRK3 fusion gene. This gene results from a translocation of genetic material from the ETV6 gene located on the short arm (designated p) of chromosome 12 at position p13.2 (i.e. 12p13.2) to the NTRK3 gene located on the long arm (designated q) of chromosome 15 at position q25.3 (i.e. 15q25.3). This ETV6-NTRK3 gene fusion is notated as t(12;15)(p13;q25) and consists of the 5 end of ETV6 fused to the 3 end of NTRK3. In consequence, the chimeric protein product of this gene lacks ETV6 proteins transcription factor activity while having NTRK3 proteins tyrosine kinase in an unregulated and continuously active form. Either event can drive the malignant growth of cells but in most cases the chimeric proteins tyrosine kinase activity appears responsible for doing so. Based on a limited number of genetic studies (a total of 65 patients), the ETY6-NTRK3 fusion gene appears to occur in most cases of the cellular and some cases of the mixed but no cases of the classical types of congenital mesolastic nephroma. However, a more recent study of 19 patients detected the fused gene in all 8 cases of cellular, 5 of 6 cases of mixed, and 0 of 5 cases of classic mesoblastic nephroma. This suggests that expression of this fused gene may be more common in cellar and mixed mesoblastic nephroma than previously appreciated.Trisomy, i.e. pathological presence of an extra chromosome, also occurs in these neoplasms. Trisomy of chromosome 11 (e.g. trisomy 11) appears to be the most commonly found trisomy in this disease, being detected in 7 of 13 genetically studied cases. Individual case reports have also found trisomy 8 (9 cases), 17 (4 cases), 20 (4 cases), 7 (3 cases), 10 (3 cases), 18 (2 cases), 2 (2 cases), and 9 (2 cases) associated with the disease. The contribution of these trisomies to the development of mesoblastic nephroma is unclear.
Diagnosis
Diagnosis of mesoblastic nephroma and its particular type (i.e. classic, mixed, or cellular) is made by histological examination of tissues obtained at surgery. Besides its histological appearance, various features of this disease aid in making a differential diagnosis that distinguish it from the following childhood neoplasms:
Wilms tumor is the most common childhood kidney neoplasm, representing some 85% of cases. Unlike mesoblastic nephroma, <2% of Wilms tumor patients present at under 3 months of age and most present in patients of >3 years of age. Bilateral kidney tumors, concurrent birth defects, and/or metastatic disease at presentation favor a diagnosis of Wilms tumor.
congenital infantile sarcoma is a rare aggressive sarcoma typically presenting in the lower extremities, head, or neck of infants during their first year of life. The histology, association with the ETV6-NRTK3 fusion gene along with certain chromosome trisomies, and the distribution of markers for cell type (i.e. cyclin D1 and Beta-catenin) within this tumor are the same as those found in cellular mesoblastic nephroma. Mesoblastic nephroma and congenital infantile sarcoma appear to be the same diseases with mesoblastic lymphoma originating in the kidney and congenital infantile sarcoma originating in non-renal tissues.
Rhabdoid tumor, which accounts for 5-10% of childhood kidney neoplasms, occurs predominantly in children from 1 to 2 years of age. Unlike mesoblastic nephroma, rhabdoid tumors may present with tumors in other tissues including in ~13% of cases, the brain. Rhabdoid tumors have a distinctive histology and abnormalities (i.e. loss of heterozygosity, single nucleotide polymorphism, and deletions) in chromosome 22.
Clear cell sarcoma of the kidney, which is responsible for 5-10% of childhood pediatric tumors, occurs predominantly in children from 2 to 3 years of age. Unlike mesoblastic nephroma, clear cell sarcoma of the kidney presents with metastasis, particularly to bone, in 5-6% of cases; it histology is diverse and has been mistaken for mesoblastic nephroma. One chromosomal translocations t,(10;17)(q22;p13), has been repeatedly reported to be associated with clear cell sarcoma of the kidney.
Infantile myofibromatosis is a fibrous tumor of infancy and childhood most commonly presenting during the first 2 years of life as a single subcutaneous nodule of the head and neck region or less commonly as multiple lesions of skin, muscle, bone, and in ~33% of these latter cases, visceral organs. All of these lesions have an excellent prognosis and can regress spontaneously except for those in which there is visceral involvement where the prognosis is poor. While infantile myofibromatosis and classic mesoblastic nephroma have been suggested to be the same diseases because of their very similar histology, studies on the distribution of cell-type markers (i.e. cyclin D1 and Beta-catenin) indicate that they have different cellular origins.
Treatment
Based on a survey of >800, surgical removal of the entire involved kidney plus the peri-renal fat appeared curative for the majority of all types of mesoblastic nephroma; the patient overall survival rate was 94%. Of the 4% of non-survivors, half were due to surgical or chemotherapeutic treatments. Another 4% of these patients suffered relapses, primarily in the local area of surgery rare cases of relapse due to lung or bone metastasis.. About 60% of these recurrent cases had a complete remission following further treatment. Recurrent disease was treated with a second surgery, radiation, and/or chemotherapy that often vincristine and actinomycin treatment. Removal of the entire afflicted kidney plus the peri-renal fat appears critical to avoiding local recurrences. In general, patients who were older than 3 months of age at diagnosis or had the cellular form of the disease, stage III disease, or involvement of renal lymph nodes had a higher recurrence rate. Among patients with these risk factors, only those with lymph node involvement are recommended for further therapy.It has been suggested that mesoblastic nephroma patients with lymph node involvement or recurrent disease might benefit by adding the ALK inhibitor, crizotinib, or a tyrosine kinase inhibitor, either larotrectinib or entrectinib, to surgical, radiation, and/or chemotherapy treatment regimens. These drugs inhibit NTRK3s tyrosine kinase activity. Crizotinib has proven useful in treating certain cases of acute lymphoblastic leukemia that are associated with the ETV6-NTRK3 fusion gene while larotrectinib and entrectinib have been useful in treating various cancers (e.g. a metastatic sarcoma, papillary thyroid cancer, non-small-cell lung carcinoma, gastrointestinal stromal tumor, mammary analog secretory carcinoma, and colorectal cancer) that are driven by mutated, overly active tyrosine kinases. Relevant to this issue, a 16-month-old girl with infantile fibrosarcoma harboring the ETV6–NTRK3 fusion gene was successfully treated with larotrectinib. The success of these drugs, however, will likely depend on the relative malignancy-promoting roles of ETV6-NTRK3 proteins tyrosine kinase activity, the lose of ETV6-related transcription activity accompanying formation of ETV6-NTRK3 protein, and the various trisomy chromosomes that populate mesoblastic nephroma.
References
External links
Congenital mesoblastic nephroma entry in the public domain NCI Dictionary of Cancer Terms This article incorporates public domain material from Dictionary of Cancer Terms. U.S. National Cancer Institute. |
Conjunctivitis | Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may occur. The affected eye may have increased tears or be "stuck shut" in the morning. Swelling of the white part of the eye may also occur. Itching is more common in cases due to allergies. Conjunctivitis can affect one or both eyes.The most common infectious causes are viral followed by bacterial. The viral infection may occur along with other symptoms of a common cold. Both viral and bacterial cases are easily spread between people. Allergies to pollen or animal hair are also a common cause. Diagnosis is often based on signs and symptoms. Occasionally, a sample of the discharge is sent for culture.Prevention is partly by handwashing. Treatment depends on the underlying cause. In the majority of viral cases, there is no specific treatment. Most cases due to a bacterial infection also resolve without treatment; however, antibiotics can shorten the illness. People who wear contact lenses and those whose infection is caused by gonorrhea or chlamydia should be treated. Allergic cases can be treated with antihistamines or mast cell inhibitor drops.About 3 to 6 million people get conjunctivitis each year in the United States. In adults, viral causes are more common, while in children, bacterial causes are more common. Typically, people get better in one or two weeks. If visual loss, significant pain, sensitivity to light, signs of herpes, or if symptoms do not improve after a week, further diagnosis and treatment may be required. Conjunctivitis in a newborn, known as neonatal conjunctivitis, may also require specific treatment.
Signs and symptoms
Red eye, swelling of the conjunctiva, and watering of the eyes are symptoms common to all forms of conjunctivitis. However, the pupils should be normally reactive, and the visual acuity normal.
Conjunctivitis is identified by inflammation of the conjunctiva, manifested by irritation and redness. Examination using a slit lamp (biomicroscope) may improve diagnostic accuracy. Examination of the palpebral conjunctiva, that overlying the inner aspects of the eyelids, is usually more diagnostic than examination of the bulbal conjunctiva, that overlying the sclera.
Viral
Between 65% and 90% of cases of viral conjunctivitis are caused by adenoviruses.
Viral conjunctivitis is often associated with an infection of the upper respiratory tract, a common cold, or a sore throat. Its symptoms include excessive watering and itching. The infection usually begins in one eye but may spread easily to the other eye.
Viral conjunctivitis manifests as a fine, diffuse pinkness of the conjunctiva which may be mistaken for iritis, but corroborative signs on microscopy, particularly numerous lymphoid follicles on the tarsal conjunctiva, and sometimes a punctate keratitis are seen.
Allergic
Allergic conjunctivitis is inflammation of the conjunctiva due to allergy. The specific allergens may differ among patients. Symptoms result from the release of histamine and other active substances by mast cells, and consist of redness (mainly due to vasodilation of the peripheral small blood vessels), swelling of the conjunctiva, itching, and increased production of tears.
Bacterial
Bacterial conjunctivitis causes the rapid onset of conjunctival redness, swelling of the eyelid, and a sticky discharge. Typically, symptoms develop first in one eye, but may spread to the other eye within 2–5 days. Conjunctivitis due to common pus-producing bacteria causes marked grittiness or irritation and a stringy, opaque, greyish or yellowish discharge that may cause the lids to stick together, especially after sleep. Severe crusting of the infected eye and the surrounding skin may also occur. The gritty or scratchy feeling is sometimes localized enough that patients may insist that they have a foreign body in the eye.Common bacteria responsible for nonacute bacterial conjunctivitis are Staphylococcus, Streptococcus, and Haemophilus species. Less commonly, Chlamydia spp. may be the cause.
Bacteria such as Chlamydia trachomatis or Moraxella spp. can cause a nonexudative but persistent conjunctivitis without much redness. Bacterial conjunctivitis may cause the production of membranes or pseudomembranes that cover the conjunctiva. Pseudomembranes consist of a combination of inflammatory cells and exudates and adhere loosely to the conjunctiva, while true membranes are more tightly adherent and cannot be easily peeled away. Cases of bacterial conjunctivitis that involve the production of membranes or pseudomembranes are associated with Neisseria gonorrhoeae, β-hemolytic streptococci, and Corynebacterium diphtheriae. C. diphtheriae causes membrane formation in conjunctiva of unimmunized children.
Chemical
Chemical eye injury may result when an acidic or alkaline substance gets in the eye. Alkali burns are typically worse than acidic burns. Mild burns produce conjunctivitis, while more severe burns may cause the cornea to turn white. Litmus paper may be used to test for chemical causes. When a chemical cause has been confirmed, the eye or eyes should be flushed until the pH is in the range 6–8. Anaesthetic eye drops can be used to decrease the pain.Irritant or toxic conjunctivitis is primarily marked by redness. If due to a chemical splash, it is often present in only the lower conjunctival sac. With some chemicals, above all with caustic alkalis such as sodium hydroxide, necrosis of the conjunctiva marked by a deceptively white eye due to vascular closure may occur, followed by sloughing off of the dead epithelium. A slit lamp examination is likely to show evidence of anterior uveitis.
Other
Inclusion conjunctivitis of the newborn is a conjunctivitis that may be caused by the bacterium Chlamydia trachomatis, and may lead to acute, purulent conjunctivitis. However, it is usually self-healing.
Causes
Infective conjunctivitis is most commonly caused by a virus. Bacterial infections, allergies, other irritants, and dryness are also common causes. Both bacterial and viral infections are contagious, passing from person to person or spread through contaminated objects or water. Contact with contaminated fingers is a common cause of conjunctivitis. Bacteria may also reach the conjunctiva from the edges of the eyelids and the surrounding skin, from the nasopharynx, from infected eye drops or contact lenses, from the genitals or the bloodstream. Infection by human adenovirus accounts for 65% to 90% of cases of viral conjunctivitis.
Viral
Adenoviruses are the most common cause of viral conjunctivitis (adenoviral keratoconjunctivitis). Herpetic keratoconjunctivitis, caused by herpes simplex viruses, can be serious and requires treatment with aciclovir. Acute hemorrhagic conjunctivitis is a highly contagious disease caused by one of two enteroviruses, enterovirus 70 and coxsackievirus A24. These were first identified in an outbreak in Ghana in 1969, and have spread worldwide since then, causing several epidemics.
Bacterial
The most common causes of acute bacterial conjunctivitis are Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. Though very rare, hyperacute cases are usually caused by Neisseria gonorrhoeae or Neisseria meningitidis. Chronic cases of bacterial conjunctivitis are those lasting longer than 3 weeks, and are typically caused by S. aureus, Moraxella lacunata, or Gram-negative enteric flora.
Allergic
Conjunctivitis may also be caused by allergens such as pollen, perfumes, cosmetics, smoke, dust mites, Balsam of Peru, or eye drops. The most frequent cause of conjunctivitis is allergic conjunctivitis and it affects 15% to 40% of the population. Allergic conjunctivitis accounts for 15% of eye related primary care consultations; most including seasonal exposures in the spring and summer or perpetual conditions.
Other
Computer vision syndrome
Dry eye syndrome
Reactive arthritis: Conjunctivitis is part of the triad of reactive arthritis, which is thought to be caused by autoimmune cross-reactivity following certain bacterial infections. Reactive arthritis is highly associated with HLA-B27. Conjunctivitis is associated with the autoimmune disease relapsing polychondritis.
Diagnosis
Cultures are not often taken or needed as most cases resolve either with time or typical antibiotics. If bacterial conjunctivitis is suspected, but no response to topical antibiotics is seen, swabs for bacterial culture should be taken and tested. Viral culture may be appropriate in epidemic case clusters.A patch test is used to identify the causative allergen in allergic conjunctivitis.Although conjunctival scrapes for cytology can be useful in detecting chlamydial and fungal infections, allergy, and dysplasia, they are rarely done because of the cost and the general dearth of laboratory staff experienced in handling ocular specimens. Conjunctival incisional biopsy is occasionally done when granulomatous diseases (e.g., sarcoidosis) or dysplasia are suspected.
Classification
Conjunctivitis may be classified either by cause or by extent of the inflamed area.
Causes
Allergy
Bacteria
Viruses
Chemicals
AutoimmuneNeonatal conjunctivitis is often grouped separately from bacterial conjunctivitis because it is caused by different bacteria than the more common cases of bacterial conjunctivitis.
By extent of involvement
Blepharoconjunctivitis is the dual combination of conjunctivitis with blepharitis (inflammation of the eyelids).
Keratoconjunctivitis is the combination of conjunctivitis and keratitis (corneal inflammation).
Blepharokeratoconjunctivitis is the combination of conjunctivitis with blepharitis and keratitis. It is clinically defined by changes of the lid margin, meibomian gland dysfunction, redness of the eye, conjunctival chemosis and inflammation of the cornea.
Differential diagnosis
Some more serious conditions can present with a red eye, such as infectious keratitis, angle-closure glaucoma, or iritis. These conditions require the urgent attention of an ophthalmologist. Signs of such conditions include decreased vision, significantly increased sensitivity to light, inability to keep the eye open, a pupil that does not respond to light, or a severe headache with nausea. Fluctuating blurring is common, due to tearing and mucoid discharge. Mild photophobia is common. However, if any of these symptoms is prominent, considering other diseases such as glaucoma, uveitis, keratitis, and even meningitis or carotico-cavernous fistula is important.A more comprehensive differential diagnosis for the red or painful eye includes:
Corneal abrasion
Subconjunctival hemorrhage
Pinguecula
Blepharitis
Dacryocystitis
Keratoconjunctivitis sicca (dry eye)
Keratitis
Herpes simplex
Herpes zoster
Episcleritis - an inflammatory condition that produces a similar appearance to conjunctivitis, but without discharge or tearing
Uveitis
Acute angle-closure glaucoma
Endophthalmitis
Orbital cellulitis
Prevention
The most effective prevention is good hygiene, especially avoiding rubbing the eyes with infected hands. Vaccination against adenovirus, Haemophilus influenzae, pneumococcus, and Neisseria meningitidis is also effective.Povidone-iodine eye solution has been found to prevent neonatal conjunctivitis. It is becoming more commonly used globally because of its low cost.
Management
Conjunctivitis resolves in 65% of cases without treatment, within 2–5 days. The prescription of antibiotics is not necessary in most cases.
Viral
Viral conjunctivitis usually resolves on its own and does not require any specific treatment. Antihistamines (e.g., diphenhydramine) or mast cell stabilizers (e.g., cromolyn) may be used to help with the symptoms. Povidone-iodine has been suggested as a treatment, but as of 2008, evidence to support it was poor.
Allergic
For allergic conjunctivitis, cool water poured over the face with the head inclined downward constricts capillaries, and artificial tears sometimes relieve discomfort in mild cases. In more severe cases, nonsteroidal anti-inflammatory medications and antihistamines may be prescribed. Persistent allergic conjunctivitis may also require topical steroid drops.
Bacterial
Bacterial conjunctivitis usually resolves without treatment. Topical antibiotics may be needed only if no improvement is observed after 3 days. No serious effects were noted either with or without treatment. Because antibiotics do speed healing in bacterial conjunctivitis, their use may be considered. Antibiotics are also recommended for those who wear contact lenses, are immunocompromised, have disease which is thought to be due to chlamydia or gonorrhea, have a fair bit of pain, or have copious discharge. Gonorrheal or chlamydial infections require both oral and topical antibiotics.The choice of antibiotic varies based on the strain or suspected strain of bacteria causing the infection. Fluoroquinolones, sodium sulfacetamide, or trimethoprim/polymyxin may be used, typically for 7–10 days. Cases of meningococcal conjunctivitis can also be treated with systemic penicillin, as long as the strain is sensitive to penicillin.When investigated as a treatment, povidone-iodine ophthalmic solution has also been observed to have some effectiveness against bacterial and chlamydial conjunctivitis, with a possible role suggested in locations where topical antibiotics are unavailable or costly.
Chemical
Conjunctivitis due to chemicals is treated via irrigation with Ringers lactate or saline solution. Chemical injuries, particularly alkali burns, are medical emergencies, as they can lead to severe scarring and intraocular damage. People with chemically induced conjunctivitis should not touch their eyes to avoid spreading the chemical.
Epidemiology
Conjunctivitis is the most common eye disease. Rates of disease is related to the underlying cause which varies by the age as well as the time of year. Acute conjunctivitis is most frequently found in infants, school-age children and the elderly. The most common cause of infectious conjunctivitis is viral conjunctivitis.It is estimated that acute conjunctivitis affects 6 million people annually in the United States.Some seasonal trends have been observed for the occurrence of different forms of conjunctivitis. The occurrence of bacterial conjunctivitis peaks from December to April, viral conjunctivitis peaks in the summer months and allergic conjunctivitis is more prevalent throughout the spring and summer.
History
An adenovirus was first isolated by Rowe et al. in 1953. Two years later, Jawetz et al. published on epidemic keratoconjunctivitis.: 437 "Madras eye" is a colloquial term that has been used in India for the disease.
Society and culture
Conjunctivitis imposes economic and social burdens. The cost of treating bacterial conjunctivitis in the United States was estimated to be $377 million to $857 million per year. Approximately 1% of all primary care office visits in the United States are related to conjunctivitis. Approximately 70% of all people with acute conjunctivitis present to primary care and urgent care.
See also
Conjunctival suffusion
Ophthalmia
References
External links
Conjunctivitis at Curlie
"Pink Eye". MedlinePlus. U.S. National Library of Medicine. |
Crossbite | Crossbite is a form of malocclusion where a tooth (or teeth) has a more buccal or lingual position (that is, the tooth is either closer to the cheek or to the tongue) than its corresponding antagonist tooth in the upper or lower dental arch. In other words, crossbite is a lateral misalignment of the dental arches.
Anterior crossbite
An anterior crossbite can be referred as negative overjet, and is typical of class III skeletal relations (prognathism).
Primary/mixed dentitions
An anterior crossbite in a child with baby teeth or mixed dentition may happen due to either dental misalignment or skeletal misalignment. Dental causes may be due to displacement of one or two teeth, where skeletal causes involve either mandibular hyperplasia, maxillary hypoplasia or combination of both.
Dental crossbite
An anterior crossbite due to dental component involves displacement of either maxillary central or lateral incisors lingual to their original erupting positions. This may happen due to delayed eruption of the primary teeth leading to permanent teeth moving lingual to their primary predecessors. This will lead to anterior crossbite where upon biting, upper teeth are behind the lower front teeth and may involve few or all frontal incisors. In this type of crossbite, the maxillary and mandibular proportions are normal to each other and to the cranial base. Another reason that may lead to a dental crossbite is crowding in the maxillary arch. Permanent teeth will tend to erupt lingual to the primary teeth in presence of crowding. Side-effects caused by dental crossbite can be increased recession on the buccal of lower incisors and higher chance of inflammation in the same area. Another term for an anterior crossbite due to dental interferences is Pseudo Class III Crossbite or Malocclusion.
Single tooth crossbite
Single tooth crossbites can occur due to uneruption of a primary teeth in a timely manner which causes permanent tooth to erupt in a different eruption pattern which is lingual to the primary tooth. Single tooth crossbites are often fixed by using a finger-spring based appliances. This type of spring can be attached to a removable appliance which is used by patient every day to correct the tooth position.
Skeletal crossbite
An anterior crossbite due to skeletal reasons will involve a deficient maxilla and a more hyperplastic or overgrown mandible. People with this type of crossbite will have dental compensation which involves proclined maxillary incisors and retroclined mandibular incisors. A proper diagnosis can be made by having a person bite into their centric relation will show mandibular incisors ahead of the maxillary incisors, which will show the skeletal discrepancy between the two jaws.
Posterior crossbite
Bjork defined posterior crossbite as a malocclusion where the buccal cusps of canine, premolar and molar of upper teeth occlude lingually to the buccal cusps of canine, premolar and molar of lower teeth. Posterior crossbite is often correlated to a narrow maxilla and upper dental arch. A posterior crossbite can be unilateral, bilateral, single-tooth or entire segment crossbite. Posterior crossbite has been reported to occur between 7–23% of the population. The most common type of posterior crossbite to occur is the unilateral crossbite which occurs in 80% to 97% of the posterior crossbite cases. Posterior crossbites also occur most commonly in primary and mixed dentition. This type of crossbite usually presents with a functional shift of the mandible towards the side of the crossbite. Posterior crossbite can occur due to either skeletal, dental or functional abnormalities. One of the common reasons for development of posterior crossbite is the size difference between maxilla and mandible, where maxilla is smaller than mandible. Posterior crossbite can result due to
Upper Airway Obstruction where people with "adenoid faces" who have trouble breathing through their nose. They have an open bite malocclusion and present with development of posterior crossbite.
Prolong digit or suckling habits which can lead to constriction of maxilla posteriorly
Prolong pacifier use (beyond age 4)
Unilateral posterior crossbite
Unilateral crossbite involves one side of the arch. The most common cause of unilateral crossbite is a narrow maxillary dental arch. This can happen due to habits such as digit sucking, prolonged use of pacifier or upper airway obstruction. Due to the discrepancy between the maxillary and mandibular arch, neuromuscular guidance of the mandible causes mandible to shift towards the side of the crossbite. This is also known as Functional mandibular shift. This shift can become structural if left untreated for a long time during growth, leading to skeletal asymmetries. Unilateral crossbites can present with following features in a child
Lower midline deviation to the crossbite side
Class 2 Subdivision relationships
Temporomandibular disorders
Treatment
A child with posterior crossbite should be treated immediately if the child shifts their mandible on closing, which is often seen in a unilateral crossbite as mentioned above. The best age to treat a child with crossbite is in their mixed dentition when their palatal sutures have not fused to each other. Palatal expansion allows more space in an arch to relieve crowding and correct posterior crossbite. The correction can include any type of palatal expanders that will expand the palate which resolves the narrow constriction of the maxilla. There are several therapies that can be used to correct a posterior crossbite: braces, Z spring or cantilever spring, quad helix, removable plates, clear aligner therapy, or a Delaire mask. The correct therapy should be decided by the orthodontist depending on the type and severity of the crossbite.
One of the keys in diagnosing the anterior crossbite due to skeletal vs dental causes is diagnosing a CR-CO shift in a patient. An adolescent presenting with anterior crossbite may be positioning their mandible forward into centric occlusion (CO) due to the dental interferences. Thus finding their occlusion in centric relation (CR) is key in diagnosis. For anterior crossbite, if their CO matches their CR then the patient truly has a skeletal component to their crossbite. If the CR shows a less severe class 3 malocclusion or teeth not in anterior crossbite, this may mean that their anterior crossbite results due to dental interferences.Goal to treat unilateral crossbites should definitely include removal of occlusal interferences and elimination of the functional shift. Treating posterior crossbites early may help prevent the occurrence of Temporomandibular joint pathology.Unilateral crossbites can also be diagnosed and treated properly by using a Deprogramming splint. This splint has flat occlusal surface which causes the muscles to deprogram themselves and establish new sensory engrams. When the splint is removed, a proper centric relation bite can be diagnosed from the bite.
Self-correction
Literature states that very few crossbites tend to self-correct which often justify the treatment approach of correcting these bites as early as possible. Only 0–9% of crossbites self-correct. Lindner et al. reported that in a 50% of crossbites were corrected in 76 four-year-old children.
See also
List of palatal expanders
Palatal expansion
Malocclusion
References
== External links == |
Necrotizing periodontal diseases | Necrotizing periodontal diseases is one of the seven categories of periodontitis as defined by the American Academy of Periodontology 1999 classification system and is one of the three classifications of periodontal diseases and conditions within the 2017 classification.
Necrotizing periodontal diseases are a type of inflammatory periodontal (gum) disease caused by bacteria (notably fusobacteria and spirochaete species). The diseases appear to represent different severities or stages of the same disease process, although this is not completely certain. These diseases usually have a sudden onset, and so the term acute is often added to the diagnosis. The mildest on the spectrum is necrotizing ulcerative gingivitis (NUG), followed by the successively more severe conditions necrotizing ulcerative periodontitis (NUP), necrotizing stomatitis and finally cancrum oris (noma), which is frequently fatal.
Necrotizing ulcerative gingivitis
Necrotizing ulcerative gingivitis, (NUG), or simply necrotizing gingivitis (NG), is a common, non-contagious infection of the gums. Acute necrotizing ulcerative gingivitis (ANUG) is the acute presentation of NUG, which is the usual course the disease takes. If improperly treated NUG may become chronic and/or recurrent. In developed countries, ANUG occurs mostly in young adults with predisposing factors such as psychological stress, sleep deprivation, poor oral hygiene, smoking, immunosuppression and/or malnutrition. In developing countries, ANUG occurs mostly in malnourished children. Due to shared predisposing factors in a population (e.g. students during a period of examinations, armed forces recruits) ANUG is known to occur in epidemic-type patterns. This has led to the popular belief that ANUG is contagious, but this is not the case. The main features of NUG are painful, bleeding gums and ulceration and necrosis of the interdental papilla. There may also be intra-oral halitosis, cervical lymphadenitis (swollen lymph nodes in the neck) and malaise. Treatment of the acute disease is by debridement and antibiotics, usually metronidazole. Poor oral hygiene and other predisposing factors may need to be corrected to prevent recurrence. ANUG is also known as trench mouth, as it was observed to occur in the mouths of front line soldiers during World War I.
Necrotizing ulcerative periodontitis
Necrotizing ulcerative periodontitis (NUP, or simply necrotizing periodontitis, NP) or acute necrotizing ulcerative periodontitis (ANUP) is where the infection leads to attachment loss (destruction of the ligaments anchoring teeth in their sockets), but involves only the gingiva, periodontal ligament and alveolar ligament. Usually this spectrum of diseases result in loss of attachment, and therefore many ANUG diagnoses may be technically termed NUP, although ANUG is the term in most common use. NUP may be an extension of NUG into the periodontal ligaments, although this is not completely proven. In the meantime, NUG and NUP are classified together under the term necrotizing periodontal diseases.
Necrotizing stomatitis
Progression of NUP into tissue beyond the mucogingival junction characterizes necrotizing stomatitis, which has many features in similar with cancrum oris.
Cancrum oris
Cancrum oris (also termed noma) is a necrotizing and destructive infection of the mouth and face, and therefore not strictly speaking a periodontal disease. In modern times, this condition usually occurs in malnourished children in developing countries. It may be disfiguring and is frequently fatal. It has been suggested that all cases of cancrum oris develop from pre-existing NUG, but this is not confirmed. Furthermore, the vast majority of cases of NUG and NUP will not progress to the more severe forms, even without treatment.
References
J Lindhe, NP Lang, T Karring (editors) (2008) "Clinical periodontology and implant dentistry" 5th edition, Blackwell Munksgaard, pp. 413,459
MG Newman, HH. Takei, PR Klokkevold, FA Carranza (editors) (2012) "Carranzas clinical periodontology" 11th edition, Elsevier/Saunders, p. 165 |
Fissure of the nipple | Fissure of the nipple, colloquially referred to as "joggers nipple", is a condition that is the result of chafing of one or both nipples. This can occur in both men and women during physical exercise such as long-distance running where there is prolonged friction between the nipple and clothing. The issue is also commonly seen in surfers who do not wear rash guards or wetsuits.
See also
Cracked nipple
List of cutaneous conditions
References
== External links == |
Xanthoma diabeticorum | Xanthoma diabeticorum is a cutaneous condition that may result in young persons who are unresponsive to insulin.: 534
See also
Xanthoma
Skin lesion
== References == |
Neuroferritinopathy | Neuroferritinopathy is a genetic neurodegenerative disorder characterized by the accumulation of iron in the basal ganglia, cerebellum, and motor cortex of the human brain. Symptoms, which are extrapyramidal in nature, progress slowly and generally do not become apparent until adulthood. These symptoms include chorea, dystonia, and cognitive deficits which worsen with age.This disorder is autosomal dominant and is caused by mutations in the gene encoding the light chain subunit of the ferritin protein. Wild type ferritin functions as a buffer for iron, sequestering it and controlling its release. Thus, mutations in the light chain of ferritin result in the accumulation of iron in the brain which can be imaged using MRI. Currently, neuroferritinopathy is the only neurodegenerative disease with an iron accumulation in the brain classified as an autosomal dominant syndrome.Treatment of neuroferritinopathy is focused on managing symptoms associated with chorea and dystonia using standard medications for each. The disorder is progressive and symptoms become worse with age. Fewer than 100 cases of neuroferritinopathy have been reported since its identification in 2001. Its incidence has been largely localized to Northeast England suggesting a founder effect. Due to its genetic nature, current research is focused on therapeutic management of the symptoms caused by the disorder.
Signs and symptoms
Neuroferritinopathy has several distinguishing signs and symptoms. These fall into two categories: diagnostic findings and physically visible symptoms.
Diagnostic findings
Symptoms categorized as medically tested and diagnosed include iron accumulation in the brain, basal ganglia cavitation, and neurodegeneration. Patients who are diagnosed with neuroferritinopathy have abnormal iron accumulation in the brain within the neurons and glia of the striatum and cerebellar cortices. Along with the accumulation of iron in the brain, neuroferritinopathy typically causes severe neuronal loss as well.
Secondary symptoms may also arise. It is possible that the initial iron accumulation will cause additional neuronal damage and neuronal death. The damaged neurons may be replaced by other cells in an effort to reverse the neurodegeneration. These cells often have a higher iron content. The breakdown of the blood brain barrier may also occur due to the loss of neurons and will subsequently allow more iron to access the brain and accumulate over time.Neuroferritinopathy is mainly seen in those who have reached late adulthood and is generally seen to slowly progress throughout many decades in a lifetime with the mean age of onset being 39 years old. A loss of cognition is generally only seen with late stages of the disease. Diagnosed patients are seen to retain most of their cognitive functioning until the most progressive stages of the illness sets in.
Physical symptoms
Symptoms categorized as physically visible symptoms include chorea, dystonia, spasticity, and rigidity, all physical symptoms of the body associated with movement disorders. The symptoms accompanying neuroferritinopathy affecting movement are also progressive, becoming more generalized with time. Usually during the first ten years of onset of the disease only one or two limbs are directly affected.
Distinctive symptoms of neuroferritinopathy are chorea, found in 50% of diagnosed patients, dystonia, found in 43% of patients, and parkinsonism, found in 7.5% of patients. Full control of upper limbs on the body generally remains until late onset of the disease. Over time, symptoms seen in a patient can change from one side of the body to the opposite side of the body, jumping from left to right or vice versa. Another route that the physically visible symptoms have been observed to take is the appearance, disappearance, and then reappearance once more of specific symptoms.While these symptoms are the classic indicators of neuroferritinopathy, symptoms will vary from patient to patient.
Causes
Neuroferritinopathy results from abnormal brain iron accumulation. This iron accumulation is due to mutations in the FTL polypeptide, which is responsible for encoding proteins involved in iron metabolism. Neuroferritinopathy is most commonly caused by a single insertion of the nucleotide adenine into the gene for L-chain ferritin which in turn, alters the carboxyl end of the entire protein chain. However, exact location of the insertion in the exon varies by family. Neuroferritinopathy may also be caused by the insertion of two extra nucleotide bases. The insertion of bases into the L-chain ferritin gene causes the chain to lengthen and alter the sequence of the amino acids found in the gene, also known as a frameshift mutation.These mutations result in decreased iron-binding ability. The oxidative damage caused by increased iron leads to apoptosis, or programmed cell death. Accumulation of iron in the brain is extremely dangerous as excess iron catalyzes the formation of free radicals, which have damaging effects to the brain. The iron accumulation characteristic of neuroferritinopathy particularly affects the cerebellum, basal ganglia, and motor cortex regions of the brain.
Mechanism
The protein ferritin functions to sequester and release iron, acting as an iron buffering system in cells. Iron is essential to brain function in oxygen transport and cellular metabolism for example. However, careful control of iron is important as increased brain iron levels catalyze the formation of free radicals that create oxidative molecules via the Fenton Reaction. These oxidative molecules can cause oxidative brain damage. Iron that is bound to ferritin in nonreactive.Fenton Reaction
(1) Fe2+ + H2O2 → Fe3+ + HO• + OH−(2) Fe3+ + H2O2 → Fe2+ + HOO• + H+The ferritin protein is made up of heavy chain (H) and light chain (L) subunits. In neuroferritinopathy, the gene encoding the light chain is mutated. Several different mutation variations have led to diagnosis as neuroferritinopathy; all of these mutations occur in the light chain. A mutated light chain is believed to inhibit ferritins ability to effectively sequester and hold iron. Without control of iron, it is free to cause oxidative brain damage as described above.The concentration of iron in a healthy brain varies greatly from region to region. The specific regions of the brain that are associated with motor functions appear to have larger accumulations of iron than non-motor-related regions. This observation of varying iron concentrations is a possible explanation for the correlation between movement disorders and the iron imbalance within the central nervous system.
Diagnosis
Neuroferritinopathy is primarily diagnosed in older adults, specifically in adults affected by Alzheimers disease or Parkinsons disease, as iron accumulates in the brain over long periods of time. Neuroferritinopathy is diagnosed using either neuroimaging techniques, physiological tests, or genetic testing.
Classification
Neuroferritinopathy was originally described with hallmark features of neurodegeneration and iron accumulation in the brain, leading it to be classified with other neurodegeneration with brain iron accumulation (NBIA) disorders which share similar symptoms and imaging findings. Over time single-gene causes have been found for many NBIA disorders, like neuroferritinopathy. Before the availability of genetic testing, all such disorders were considered together and known as Hallervorden-Spatz syndrome, a term which is no longer used due to the Nazi party ties of the namesakes. Brain iron disorders are now divided into three categories: genetic neurodegeneration with brain iron accumulation, genetic systemic iron accumulation with neurologic features, and acquired diseases associated with iron excess or iron deficiency. Neuroferritinopathy is classified under the first category. Neuroferritinopathy is classified as a late-onset basal ganglia disease and is a dominantly inherited neurodegenerative disease. Four different alleles are responsible for neuroferritinopathy. Three arise from nucleotide insertions in the ferritin light chain (FTL) polypeptide gene while the fourth arises from a missense mutation in the FTL gene.
Neuroimaging
Neuroferritinopathy is most commonly diagnosed using MRI and other neuroimaging techniques. MRIs help identify the iron deposits in the cerebellum, basal ganglia, and motor cortex common to neuroferritinopathy. MRIs of affected individuals also show mild cerebellar and cerebral atrophy, or tissue breakdown, and gas cavity formation in the putamen. Most importantly, the MRIs show misfolded ferritin proteins and iron deposits in the glial cells of the caudate, putamen, globus pallidus, cerebral cortex, thalamus, and purkinje cells, causing neuronal death in these areas.
Physiological testing
Blood tests usually come back normal in affected individuals, so they do not serve as a reliable means of diagnosis. Blood tests can show low serum ferritin levels. However, this is unreliable as method of diagnosis, as some patients show typical serum ferritin levels even at the latest stages of neuroferritinopathy. Cerebral spinal fluid tests also are typically normal.
Ferritin aggregates found in the skin, liver, kidney, and muscle tissues may help in diagnosing neuroferritinopathy. More cytochrome c oxidase-negative fibers are also often found in the muscle biopsies of affected individuals.
Genetic testing
Genetic testing can confirm a neuroferritinopathy diagnosis. A diagnosis can be made by analyzing the protein sequences of affected individuals and comparing them to known neuroferritinopathy sequences.
Treatment
Due to neuroferritinopathys genetic etiology, the disorder is not currently curable. Furthermore, progression of the disorder is unable to be effectively halted. Therefore, current treatment focuses on managing symptoms of the disorder.
No medication is available to treat all symptoms. Botox has been shown to help with focal dystonia. The dopamine depleter Tetrabenazine shown to help with involuntary movements. Symptoms affecting movement (dystonia) have also been treated with L-Dopa, orphenadrine, benzhexol, sulpiride, diazepam, clonazepam, and deanol. Parkinsonian symptoms were not decreased by L-Dopa. Iron supplements should be avoided.
Epidemiology
Neuroferritinopathy was first discovered in 2001, with its first case being reported in Cumbria from Northern England. The discovery of neuroferritinopathy was mediated by a study done on a large family suffering from a dominantly inherited basal ganglia disease. The disease was reported to be instigated by a mutation on the ferritin light chain polypeptide, (FTL1), and was found to cause iron accumulation in the brain and neurodegeneration. Following in suit of the location of the first case of Neuroferritinopathy, the majority of patients diagnosed with the disease have also been found in Northern and Northeast England. The localization of the majority of cases to Northern and Northeast England suggests that a common ancestor may be responsible for many or possibly all cases. Despite there being fewer than 100 cases reported and the diseases general location of Northern and Northeast England, multiple more cases of neuroferritinopathy have been diagnosed around the rest of the world in recent years.
Research
New potential treatment options being researched are Venesection (removing red blood cells), Iron chelation with deferiprone, and Coenzyme Q10 (ubiquinone).
References
== External links == |
Cholesterolosis of gallbladder | In surgical pathology, strawberry gallbladder, more formally cholesterolosis of the gallbladder and gallbladder cholesterolosis, is a change in the gallbladder wall due to excess cholesterol.The name strawberry gallbladder comes from the typically stippled appearance of the mucosal surface on gross examination, which resembles a strawberry. Cholesterolosis results from abnormal deposits of cholesterol esters in macrophages within the lamina propria (foam cells) and in mucosal epithelium. The gallbladder may be affected in a patchy localized form or in a diffuse form. The diffuse form macroscopically appears as a bright red mucosa with yellow mottling (due to lipid), hence the term strawberry gallbladder.
It is not tied to cholelithiasis (gallstones) or cholecystitis (inflammation of the gallbladder).
Additional images
See also
Cholecystectomy
Rokitansky-Aschoff sinuses
References
Further reading
Izzo L, Boschetto A, Brachini G, et al. (2001). "["Strawberry" gallbladder: review of the literature and our experience]". Il Giornale di Chirurgia (in Italian). 22 (1–2): 33–6. PMID 11272434.
== External links == |
Spiradenoma | Spiradenomas (SA) are rare, benign cutaneous adnexal tumors that may progress to become their malignant counterparts, i.e. spiradenocarcinomas (SAC). Cutaneous adnexal tumors are a group of skin tumors consisting of tissues that have differentiated (i.e. matured from stem cells) towards one of the four primary adnexal structures found in normal skin: hair follicles, sebaceous sweat glands, apocrine sweat glands, and eccrine sweat glands. SA and SAC tumors were regarded as eccrine gland tumors and termed eccrine spiradenomas and eccrine spiradenocarcinomas, respectively. However, more recent studies have found them to be hair follicle tumors and commonly term them spiradenomas and spiradenocarcinomas, respectively. Further confusing the situation, SA-like and SAC-like tumors are also 1) manifestations of the inherited disorder, CYLD cutaneous syndrome (CCS), and 2) have repeatedly been confused with an entirely different tumor, adenoid cystic carcinomas of the salivary gland. Here, SA and SAC are strictly defined as sporadic hair follicle tumors that do not include the hereditary CCS spiradenomas and heridtary spiradenocarcinoms of CCS or the adenoid cystic carcinomas.
SA tumors usually occur as slow-growing, single, small, nodular lesions located in the skin of the head, neck, or trunk. SAC tumors develop from benign SA tumors or in very rare cases begin as malignant tumors. SA and SAC tumors must be distinguished from the spiradenoma and spiradenocaricnoma tumors that develop in individuals afflicted with the CYLD cutaneous syndrome. CCS is an inherited disorder that commonly involves the development of multiple but on occasion a single or few tumors that closely resemble, and may be confused with, the sporadic SA and SAC tumors described here. CCS spiradenoma and CCS spiradenocarcinoma tumors must be distinguished form the sporadic SA and SAC tumors reviewed here in order to afford genetic counseling to individuals with CCS as well as to the close family members of these individuals.Currently, SA and SAC are usually treated by complete excision making sure that no tumor cells are left behind at the surgical site. This is particularly important in SAC where the incomplete surgical removal of all tumor cells may result in recurrence of the tumor at the surgical site and/or its metastasis to the local lymph nodes draining the surgical site and/or to distant tissues. In addition to surgical resection, some cases of SAC tumors have been treated with adjuvant therapy that includes radiotherapy and/or chemotherapy. It is not clear that these adjuvant treatments improve patient prognoses. Further studies are needed to determine the best treatment(s) for localize SA, localized SAC, and, in particular, metastatic SAC tumors.
Presentation
Spiradenoma tumors occur in individuals of various ages but tend to develop in middle-aged and elder adults (e.g. in a study of 27 patients, the median age at diagnosis was 62 years). However, cases have been reported in children as young as 2 years. These tumors usually present as a solitary, sometimes painful, slowly growing, 1–2 cm (i.e. centimeters), gray-to-pink nodules that lie underneath the skins epidermis in the head, neck, trunk, arms, or legs. However, these nodules have been reported to be as large as 6 cm and to occur in other hair follicle-containing cutaneious sites such as the vulva, breast, and breast nipple. Areas of the skin that do not have hair follicles (e.g. palms of the hands and soles of feet) do not develop these nodules. Less than 2% of cases present with more than one nodule; the multiple nodules in SA tend to array in a linear, blaschkoid (i.e. V-, U-, or inverted U-shaped), or zosteriform (i.e. belt- or girdle-shape tracking an area of skin served by a sensory nerve) patterns. Giant vascular eccrine spiradenomas are larger (> 2 cm) and more highly vascular variants of SA that usually develop at the same cutaneous sites as SA but have also been reported to occur in the abdomen and scrotum. No malignant giant vascular SA has been described in the literature to date (2021).A recent review of 182 cases reported that spiradenocarcinomas were diagnosed in individuals 8–89 years old (mean 57.4 years). These SAC tumors developed in SA tumors that had existed for 0–720 months (mean 168.5 months); 14.4% of individuals were diagnosed with multiple carcinoma lesions. (Multiple SAC lesions may appear as a nodule associated with smaller satellite nodules.) The lesions occurred on the trunk (32.3% of cases), limbs (31.3%), head or neck (30.7%), and genitalia (1.6%). These individuals presented with lesions that began to show abnormal growth (82.6% of cases), pain (47.7% of cases), and/or ulcerations (38.7% of cases). In earlier studies, SAC tumors were reported to varied in size with 40% being larger than 5 cm and the majority not having metastasized; the sites to which these lesions metastasized were most commonly to lymph nodes near to the SAC or, rarely, distant tissues such as the lung, liver, brain, spinal cord, bone, skin, and breast.
Pathology
As determined by the microscopic histopathological appearances of their hematoxylin and eosin-stained samples, spiradenomas are non-encapsulated nodular skin lesions that extend into the dermis. The lesions consist of a relatively disorganized and dense array of proliferating basophilic cells (i.e. cells appearing blue because of their abnormally large uptake of the hematoxylin stain). These cells are arranged as small cells with hyperchromatic nuclei and scant cytoplasm layered outside and larger cells with vesicular (i.e. vesicle-containing) nuclei layered inside of intertwining strips. Lymphocytes commonly populate these lesions. Some lesions may merge the histopathological features of spiroadenomas with those of cylindromas. Cylindromas are hair follicle tumors that consist of basal cells (i.e. small, round cells similar to those seen in the lowest layer of the skins epidermis) which are arranged in ("jigsaw-like" cylindrical patterns separated by thickened basement membranes. The cylindroma tissues may also contain disorganized, dense arrays of proliferating basophilic cells.Spiradenocarcinoma tumors almost always derive from SA tumors and have areas of SA architecture abruptly transitioning to areas of SAC architecture. The SAC component of these lesions consists of cells that, along with their nuclei and cytoplasm, vary greatly in size and shape. The cells may be rapidly proliferating, have atypical mitosis figures, and may be invading nearby neural or lymphovascular structures; they do not arrange into intertwining strips of small and large cells. High-grade SAC tissues show a more severely disturbed architecture, more marked variation in cell, nuclei, and cytoplasm sizes and shapes, and more rapidly proliferating cells than low-grade SAC tissues. SAC tumor tissues may show various other features, e.g. they may closely resemble sarcomas. In rare cases, SAC has been reported to apparently arise de novo, i.e. begin as malignant lesions.
Gene abnormalities
Studies indicate that a minority of SA and SAC cases have one of two potentially disease-causing mutations in their tumor cells: loss-of-function (i.e. gene-inactivating) mutations in the CYLD gene in 5 of 17 SA and 2 of 24 SAC cases or gain-of-function (i.e. gene-activating) mutations in the ALPK1 gene in 7 of 16 SA and 4 of 14 SAC cases. The two mutations are mutually exclusive, i.e. do not occur together in any individuals tumor(s). Both mutations result in blocking the actions pf NF-κB. NF-κB is a transcription factor which acts indirectly to stimulate the expression of various genes that trigger cell death by apoptosis and necroptosis and also inhibit cell proliferation (see CYLD genes mechanism of action). It is proposed that the blockade of NF-κBs actions prolongs cell survival, stimulates high rates of cell growth, and perhaps has other effects which contribute to the formation and/or progression of SA and SAC tumors.
Diagnosis
SA and SAC tumors have been confused with leiomyoma, angiolipoma, granular cell tumor, basal cell carcinoma, squamous cell carcinoma, metastatic adenocarcinoma, and adenoid cystic carcinoma tumors; the giant vascular SA form of these tumors has been mistaken for a hemangioma, angiolipoma, calcifying epithelioma, neuroma, malignant melanoma, angiosarcoma, vascular malformation, and venous thrombosis. CT scans, FDG-positron emission tomography, and magnetic resonance imaging to detect 1) the shape and local invasiveness of these tumors and 2) the presence of metastases and 2) the clinical presentation of individuals of these tumors often suggest the correct diagnosis. However, definitive separation of SA, SAC, and giant vascular SA from the just cited lesions requires histopathological examinations. The diagnosis of SA versus SAC tumors is often suggested by their clinical presentations, e.g. rapid enlargement or onset of pain in a long-standing SA tumor strongly suggests that it has become a SAC. Findings that a known SA or undiagnosed tumor has areas of SA histology transitioning to SAC histology (see above Pathology section) is virtually diagnostic for SAC.The sporadic SA and SAC tumors reviewed here must also be distinguished from the very similar appearing SA-like and SAC-like tumors in individuals afflicted with the CYLD cutaneous syndrome. CCS is a familial disease uniformly associated with the inheritance of inactivating mutations in the CYLD gene. Individuals with CCS commonly develop an increasingly large number of skin tumors, including SA and SAC, over time. Usually, these individuals are readily distinguished from sporadic SA and SAC by their family history of the disease and the presence of large numbers of tumors. The rare cases of CCS that present with one or a few tumors are distinguished form CCS by testing for the CYLD gene: all individuals with CCS carry a mutated CYLD gene in their tumor as well as other tissues such as blood leucocytes while individuals with sporadic SA or SAC carry the mutated CYLD gene in their tumor but not other tissues (see Genetics of CCS). It is important to afford individuals with CCS and the close family members of these individuals access to in depth genetic counselling.
Treatments
There is no consensus on the best treatment(s) for SA and SAC tumors. Further research, including meta-analysis comparisons of different treatment regimens, is needed to define the best treatment(s) for these tumors. In all cases, however, regular follow-ups of individuals with SA and SAC are strongly recommended in order to detect as early as possible: the formation of new tumors; changes in old tumors that suggest their progression to more aggressive or malignant formss; local recurrences of surgically removed tumors; and the development of local or distant metastases. One recommended follow-up strategy prescribes patients to have check-ups ever three months in the first year after treatment, every six months in the second year after treatment, and annually thereafter. Each check-up should incorporate the examination of the patients regional lymph nodes and on a case-by-case basis annual chest X-rays and liver function tests.
Spiradenomas
The currently preferred treatment for sporadic SA tumors (including giant vascular eccrine SA) in almost all cases is surgical excision. Many studies recommend wide local surgical excision of these tumors with surgical margins of ≥1 cm in order to ensure that all tumor cells are removed: local lymph node resections are usually reserved for those cases suspected of having lymph node metastases. Mohs micrographic surgery has been used as an alternative to surgical excision for the complete removal of these tumors. Since SA tumors may contain unidentified areas of malignancy and therefore have high recurrence rates, may metastasize to local lymph nodes and/or distant tissues, and can result in overall poor survival times, adjuvant radiation therapy has been used to minimize these aggressive events in SA tumors with equivocal signs of malignancy. However, the effectiveness of these adjuvant therapies has not been established. Adjuvant CO2 laser treatments have been used on occasion to remove these tumors in cases with multiple tumors. Some trials have using botulinum toxin A and triamcinolone injections directly into SA tumors but these trials have had limited success.
Spiradenocarcinomas
With only 117 malignant cases reported in the literature as of 2022, there are no standard guidelines for the treatment of SAC tumors. Localized (i.e. no evidence of metastases) SAC tumors and SAC tumors that have metastasized to local lymph nodes are commonly treated by surgical removal (with ≥1 cm margins) of the tumor plus surgical resection (i.e. removal) of the local lymph nodes. Individuals presenting with lymph node metastasis have also been treated with one or both of theses regimens plus, where possible and indicated, adjuvant radiation therapy to the areas of the removed tumors and lymph nodes. Chemotherapeutic agents such as methotrexate, cisplatin, etoposide, and 5-fluorouracil have been used to treat SAC with distant tissue metastases but the success of these drug treatments has been limited.
Prognoses
In the only meta-analysis study reported on the treatment of SA and SAC tumors to date, 35 individuals with SA tumors and no evidence of local or distant metastasis who were treated with local resection (3 of these individuals underwent additional lymph node resections after removal of their primary tumor) all 35 were disease-free with a mean follow-up period of 33 months. Among individuals with SAC tumors that had metastasized to lymph nodes but not distant tissues, 3 individuals who had surgical excisions of their tumors but not their involved lymph nodes died of metastatic disease (range 39–49 months, mean survival range 45 months); one individual was alive with disease 24 months after lymph node dissection; and 8 individuals (6 of whom had lymph node dissection) lacked evidence of recurrent disease (observation times 2 to 97 months, mean observation time 47 months). In a review of 136 reported cases treated for SA or SAC: 1) 4.4% and 14.7% of individuals with SA and SAC tumors, respectively, had died (time between treatment and death was not reported); 2) patients who presented with metastasis to distant tissues had a median survival time of 16 months (11 of these patients were treated with adjuvant therapy in addition to surgery [adjuvant treatments included 5 patients treated with radiotherapy, 3 treated with chemotherapy, and 2 treated with both radiotherapy and chemotherapy]); and 3) Surgery with adjuvant therapy yielded a median survival time of 20 months (this survival time did not significantly differ from that found in individuals treated with surgery alone).
See also
Malignant acrospiroma
List of cutaneous conditions
Dermal cylindroma
Trichoepithelioma
CYLD cutaneous syndrome
List of cutaneous neoplasms associated with systemic syndromes
References
== External links == |
Cigarette burns | Cigarette burns are usually deliberate injuries caused by pressing a lit cigarette to the skin. They are a common form of child abuse and torture. They are typically round and about 1 centimetre (0.4 in) in diameter, with a hypopigmented center and hyperpigmented periphery.
== References == |
Aniridia | Aniridia is the absence of the iris, a muscular structure that opens and closes the pupil to allow light into the eye. It is also responsible for eye color. Without it the central eye appears all black. It can be congenital, in which both eyes are usually involved, or caused by a penetrant injury. Isolated aniridia is a congenital disorder which is not limited to a defect in iris development, but is a panocular condition with macular and optic nerve hypoplasia, cataract, and corneal changes. Vision may be severely compromised and the disorder is frequently associated with a number of ocular complications: nystagmus, amblyopia, buphthalmos, and cataract. Aniridia in some individuals occurs as part of a syndrome, such as WAGR syndrome (kidney nephroblastoma (Wilms tumour), genitourinary anomalies and intellectual disability), or Gillespie syndrome (cerebellar ataxia).
PAX6
The AN2 region of the short arm of chromosome 11 (11p13) includes the PAX6 gene (named for its PAired boX status), whose gene product helps regulate a cascade of other genetic processes involved in the development of the eye (as well as other non-ocular structures). This PAX6 gene is around 95% similar to the pax gene found in zebrafish, a creature whose ancestors diverged from human evolutionary development around 400 million years ago. Thus the PAX6 gene is highly conserved across evolutionary lineages.
Defects in the PAX6 gene cause aniridia-like ocular defects in mice (as well as Drosophila). Aniridia is a heterozygous disorder, meaning that only one of the two chromosome 11 copies is affected. When both copies are altered (homozygous condition), the result is a uniformly fatal condition with near complete failure of entire eye formation. In 2001, two cases of homozygous aniridia patients were reported; the fetuses died prior to birth and had severe brain damage. In mice, homozygous small eye defect (mouse Pax-6) leads to loss of the eyes and nose and the murine fetuses sustain severe brain damage.
Types
Aniridia may be broadly divided into hereditary and sporadic forms. Hereditary aniridia is usually transmitted in an autosomal dominant manner (each offspring has a 50% chance of being affected), although rare autosomal recessive forms (such as Gillespie syndrome) have also been reported. Sporadic aniridia mutations may affect the WT1 region adjacent to the AN2 aniridia region, causing a kidney cancer called nephroblastoma (Wilms tumor). These patients often also have genitourinary abnormalities and intellectual disability (WAGR syndrome).
Several different mutations may affect the PAX6 gene. Some mutations appear to inhibit gene function more than others, with subsequent variability in the severity of the disease. Thus, some aniridic individuals are only missing a relatively small amount of iris, do not have foveal hypoplasia, and retain relatively normal vision. Presumably, the genetic defect in these individuals causes less "heterozygous insufficiency," meaning they retain enough gene function to yield a milder phenotype.
Online Mendelian Inheritance in Man (OMIM): 106210 AN
Online Mendelian Inheritance in Man (OMIM): 106220 Aniridia and absent patella
Online Mendelian Inheritance in Man (OMIM): 106230 Aniridia, microcornea, and spontaneously reabsorbed cataract
Online Mendelian Inheritance in Man (OMIM): 206700 Aniridia, cerebellar ataxia, and mental deficiency (Gillespie syndrome)
Mutational analysis
Molecular (DNA) testing for PAX6 gene mutations (by sequencing of the entire coding region and deletion/duplication analysis) is available for isolated aniridia and the Gillespie syndrome. For the WAGR syndrome, high-resolution cytogenetic analysis and fluorescence in situ hybridization (FISH) can be utilized to identify deletions within chromosome band 11p13, where both the PAX6 and WT1 genes are located.
Symptoms
Aniridia can cause many symptoms, such as:
Poor vision (not always present)
More sensitivity to light
Fast, uncontrolled, shaking "to and from" eye movements (nystagmus)
Eyes dont line up (strabismus)
Treatment
In May 2018, the U.S. Food and Drug Administration approved the CustomFlex Artificial Iris, the first synthetic iris for use in adults and children with congenital aniridia or iris defects related to other conditions, such as albinism, traumatic injury, or surgical removal due to ocular melanoma. The artificial iris is a surgically implanted device made of thin, foldable, medical-grade silicone and is custom-sized and colored for each individual patient. The prosthetic iris is held in place by the anatomical structures of the eye or, if needed, by sutures.
See also
WAGR syndrome
Scleral lenses
References
External links
GeneReviews/NCBI/NIH/UW entry on Aniridia
NCBI/Molecular diagnosis of aniridia
OMIM entries on Aniridia
GeneReviews/NIH/NCBI/UW entry on Wilms Tumor Overview |
Monostotic fibrous dysplasia | Monostotic fibrous dysplasia is a form of fibrous dysplasia where only one bone is involved. It comprises a majority of the cases of fibrous dysplasia (approximately 70–80%).It is a rare bone disease characterized by the replacement of normal elements of the bone by fibrous connective tissue, which can cause very painful swellings and bone deformities, and make bone abnormally fragile and prone to fracture.A congenital, noninherited, benign anomaly of bone development in a single bone, it consists of the replacement of normal marrow and cancellous bone by immature bone with fibrous stroma. Monostotic fibrous dysplasia occurs with equal frequency in both sexes and normally develops early in life, with lesions frequently identified late in the first and early second decades. Most patients are asymptomatic, with the diagnosis often established after an incidental finding or with pain, swelling, or fracture. Lesions usually enlarge in proportion to skeletal growth and the abnormal replacement remain active only until skeletal maturity.Monostotic fibrous dysplasia does not convert into the polyostotic type. When symptoms are present, they often are nonspecific, including pain, swelling, or pathologic fracture. It most often affects the ribs (28%), proximal femur (23%), tibia, craniofacial bones (10-25%) and humerus (10-25%).
See also
Polyostotic fibrous dysplasia
References
== External links == |
Obsessive–compulsive personality disorder | Obsessive–compulsive personality disorder (OCPD) is a cluster C personality disorder marked by an excessive need for orderliness and neatness. Symptoms are usually present by the time a person reaches adulthood, and are visible in a variety of situations. The cause of OCPD is thought to involve a combination of genetic and environmental factors, namely problems with attachment.This is a distinct disorder from obsessive–compulsive disorder (OCD), and the relation between the two is contentious. Some studies have found high comorbidity rates between the two disorders but others have shown little comorbidity. Both disorders may share outside similarities, such as rigid and ritual-like behaviors. Attitudes toward these behaviors differ between people affected with either of the disorders: for people with OCD, these behaviors are egodystonic, unwanted and involuntary, being the product of anxiety-inducing and involuntary thoughts. On the other hand, for people with OCPD, they are egosyntonic; the person perceives them as rational and wanted, being the result of, for example, strong adherence to routines, a desire for control, or a need for perfection. OCPD is highly comorbid with other personality disorders, autism spectrum, eating disorders, anxiety, mood disorders, and substance use disorders.The disorder is the most common personality disorder in the United States, and is diagnosed twice as often in males as in females, however, there is evidence to suggest the prevalence between men and women is equal.
Signs and symptoms
Obsessive–compulsive personality disorder (OCPD) is marked by an excessive obsession with rules, lists, schedules, and order; a need for perfectionism that interferes with efficiency and the ability to complete tasks; a devotion to productivity that hinders interpersonal relationships and leisure time; rigidity and zealousness on matters of morality and ethics; an inability to delegate responsibilities or work to others; restricted functioning in interpersonal relationships; restricted expression of emotion and affect; and a need for control over ones environment and self.Some of OCPDs symptoms are persistent and stable, whilst others are unstable. The obsession with perfectionism, reluctance to delegate tasks to others, and rigidity and stubbornness are stable symptoms. On the other hand, the symptoms that were most likely to change over time were the miserly spending style and the excessive devotion to productivity. This discrepancy in the stability of symptoms may lead to mixed results in terms of the course of the disorder, with some studies showing a remission rate of 58% after a 12-month period, whilst others suggesting that the symptoms are stable and may worsen with age.
Attention to order and perfection
People with OCPD tend to be obsessed with controlling their environments; to satisfy this need for control, they become preoccupied with trivial details, lists, procedures, rules, and schedules.This preoccupation with details and rules makes the person unable to delegate tasks and responsibilities to other people unless they submit to their exact way of completing a task because they believe that there is only one correct way of doing something. They stubbornly insist that a task or job must be completed their way, and only their way, and may micromanage people when they are assigned a group task. They are frustrated when other people suggest alternative methods. A person with this disorder may reject help even when they desperately need it as they believe that only they can do something correctly.People with OCPD are obsessed with maintaining perfection. The perfectionism and the extremely high standards that they establish are to their detriment and may cause delays and failures to complete objectives and tasks. Every mistake is thought of as a major catastrophe that will soil their reputation for life. For example, a person may write an essay for a college, and then believe that it fell short of "perfection", so they continue rewriting it until they miss the deadline. They may never complete the essay due to the self-imposed high standards. They are unaware that other people may become frustrated and annoyed by the repeated delays and hassles that this behavior causes. Work relationships may then become a source of tension.
Devotion to productivity
Individuals with OCPD devote themselves to work and productivity at the expense of interpersonal relationships and recreation. Economic necessity, such as poverty, cannot account for this behavior. They may believe that they do not have sufficient time to relax because they have to prioritize their work above all. They may refuse to spend time with friends and family because of that. They may find it difficult to go on a vacation, and even if they book a vacation, they may keep postponing it until it never happens. They may feel uncomfortable when they do go on a vacation and will take something along with them so they can work. They choose hobbies that are organized and structured, and they approach them as a serious task requiring work to perfect. The devotion to productivity in OCPD, however, is distinct from work addiction. OCPD is controlled and egosyntonic, whereas work addiction is uncontrolled and egodystonic, and the affected person may display signs of withdrawal.
Rigidity
Individuals with OCPD are overconscientious, scrupulous and rigid, and inflexible on matters of morality, ethics and other areas of life. They may force themselves and others to follow rigid moral principles and strict standards of performance. They are self-critical and harsh about their mistakes. These symptoms should not be accounted for or caused by a persons culture or religion. Their view of the world is polarised and dichotomous; there is no grey area between what is right and what is wrong. Whenever this dichotomous view of the world cannot be applied to a situation, this causes internal conflict as the persons perfectionist tendencies are challenged.People with this disorder are so obsessed with doing everything the "right and correct" way that they have a hard time understanding and appreciating the ideas, beliefs, and values of other people, and are reluctant to change their views, especially on matters of morality and politics.
Restricted emotions and interpersonal functioning
Individuals with this disorder may display little affection and warmth; their relationships and speech tend to have a formal and professional approach, and not much affection is expressed even to loved ones, such as greeting or hugging a significant other at an airport or train station.They are extremely careful in their interpersonal interactions. They have little spontaneity when interacting with others, and ensure that their speech follows rigid and austere standards by excessively scrutinising it. They filter their speech for embarrassing or imperfect articulation, and they have a low bar for what they consider to be such. They lower their bar even further when they are communicating with their superiors or with a person of high status. Communication becomes a time-consuming and exhausting effort, and they start avoiding it altogether. Others regard them as cold and detached as a result.Their need for restricting affection is a defense mechanism used to control their emotions. They may expunge emotions from their memories and organize them as a library of facts and data; the memories are intellectualized and rationalized, not experiences that they can feel. This helps them avoid unexpected emotions and feelings and allows them to remain in control. They view self-exploration as a waste of time and have a patronising attitude towards emotional people.
Interpersonal control
Individuals with OCPD are at one extreme of the conscientiousness continuum. While conscientiousness is a desirable trait generally, its extreme presentation for those with OCPD leads to interpersonal problems. OCPD individuals present as over-controlled and this extends to the relationships they have with other people. Individuals with OCPD are referential to authority and rules. OCPD individuals may therefore punish those who violate their strict standards. The inability to accept differences in belief or behaviors from others often leads to high conflict and controlling relationships with coworkers, spouses, and children.
Cause
The cause of OCPD is thought to involve a combination of genetic and environmental factors. There is clear evidence to support the theory that OCPD is genetically inherited, however, the relevance and impact of genetic factors vary with studies placing it somewhere between 27% and 78%.Other studies have found links between attachment theory and the development of OCPD. According to this hypothesis, those with OCPD have never developed a secure attachment style, had overbearing parents, were shown little care, and were unable to develop empathetically and emotionally.
Diagnosis
DSM-5
The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, a widely used manual for diagnosing mental disorders, places obsessive-compulsive personality disorder under section II, under the "personality disorders" chapter, and defines it as: "a pervasive pattern of preoccupation with orderliness, perfectionism, and mental and interpersonal control, at the expense of flexibility, openness, and efficiency, beginning by early adulthood and present in a variety of contexts". A diagnosis of OCPD is only received when four out of the eight criteria are met.The eight criteria of OCPD described in the DSM-5 (of which four are required to be present in a patient for a diagnosis) are:
Preoccupation with details
Perfectionism interfering with task completion
Rigidity and stubbornness
Reluctance to delegate
Excessive conscientiousness and pedantry (excessive concern with minor details and rules)
Workaholic behavior
Miserliness (excessive desire to save money)
Unable to discard worn-out or worthless objectsThe list of criteria for the ICD-10 is similar, but does not include the last three criteria in the above list, and additionally includes the symptoms "intrusive thoughts" and "excessive doubt and caution" as criteria for diagnosis.
Alternative model for diagnosis
The DSM-5 also includes an alternative set of diagnostic criteria as per the dimensional model of conceptualizing personality disorders. Under the proposed set of criteria, a person only receives a diagnosis when there is an impairment in two out of four areas of ones personality functioning, and when there are three out of four pathological traits, one of which must be rigid perfectionism.
The patient must also meet the general criteria C through G for a personality disorder, which state that the traits and symptoms being displayed by the patient must be stable and unchanging over time with an onset of at least adolescence or early adulthood, visible in a variety of situations, not caused by another mental disorder, not caused by a substance or medical condition, and abnormal in comparison to a persons developmental stage and culture/religion.
Differential diagnosis
There are several mental disorders in the DSM-5 that are listed as differential diagnoses for OCPD. They are as follows:
Obsessive–compulsive disorder. OCD and OCPD have a similar name which may cause confusion; however, OCD can be easily distinguished from OCPD: OCPD is not characterized by true obsessions or compulsions.
Hoarding disorder. A diagnosis of hoarding disorder is only considered when the hoarding behavior exhibited is causing severe impairment in the functioning of the person, such as an inability to access rooms in a house due to excessive hoarding.
Narcissistic personality disorder. Individuals with a narcissistic personality disorder usually believe that they have achieved perfection (especially compared to other people) and cannot get better, whereas those with OCPD do not believe that they have achieved perfection, and are self-critical. Those with NPD tend to be stingy and lack generosity; however, they are usually generous when spending on themselves, unlike those with OCPD who hoard money and are miserly on themselves and others.
Antisocial personality disorder. Similarly, individuals with antisocial personality disorder are not generous, but miserly around others, although they usually over-indulge themselves and are sometimes reckless in spending.
Schizoid personality disorder. Schizoid personality disorder and obsessive-compulsive personality disorder may both display restricted affectivity and coldness; however, in OCPD, this is usually due to a controlling attitude, whereas, in SPD, it occurs due to a lack of ability to experience emotion and display affection.
Other personality traits. Obsessive-compulsive personality traits may be particularly useful and helpful, especially in productive environments. Only when these traits become extreme, maladaptive, and cause clinically significant impairment in several aspects of ones life should a diagnosis of OCPD be considered.
Personality change due to another medical condition. Obsessive–compulsive personality disorder must be differentiated from a personality change due to a medical condition, which affects the central nervous system, and may cause changes in behavior and traits.
Substance use disorders. Substance use may cause the advent of obsessive-compulsive traits. It is necessary that this is distinguished from underlying and persistent behavior, which must occur when a person is not under influence of a substance.
ICD-10
The World Health Organizations ICD-10 uses the term anankastic personality disorder (F60.5). At least four of the following must be present:
Feelings of doubt
Perfectionism
Excessive conscientiousness
Checking and preoccupation with details
Stubbornness
Caution
Rigidity
Insistent and unwelcome thoughts or impulses that do not attain the severity of an obsessive-compulsive disorder.
Millons subtypes
In his book, Personality Disorders in Modern Life, Theodore Millon describes 5 types of obsessive–compulsive personality disorder, which he shortened to compulsive personality disorder.
Comorbidity
Obsessive–compulsive disorder
OCPD is often confused with obsessive-compulsive disorder (OCD). Despite the similar names, they are two distinct disorders. Some OCPD individuals do have OCD, and the two can be found in the same family, sometimes along with eating disorders.The rate of comorbidity of OCPD in patients with OCD is estimated to be around 15–28%. However, due to the addition of the hoarding disorder diagnosis in the DSM-5, and studies showing that hoarding may not be a symptom of OCPD, the true rate of comorbidity may be much lower.There is significant similarity in the symptoms of OCD and OCPD, which can lead to complexity in distinguishing them clinically. For example, perfectionism is an OCPD criterion and a symptom of OCD if it involves the need for tidiness, symmetry, and organization. Hoarding is also considered both a compulsion found in OCD and a criterion for OCPD in the DSM-5. Even though OCD and OCPD are seemingly separate disorders there are obvious redundancies between the two concerning several symptoms.Regardless of similarities between the OCPD criteria and the obsessions and compulsions found in OCD, there are discrete qualitative dissimilarities between these disorders, predominantly in the functional part of symptoms. Unlike OCPD, OCD is described as invasive, and stressful. Time-consuming obsessions and habits are aimed at reducing obsession-related stress. OCD symptoms are at times regarded as egodystonic because they are experienced as alien and repulsive to the person. Therefore, there is a greater mental anxiety associated with OCD.In contrast, the symptoms seen in OCPD, although repetitive, are not linked with repulsive thoughts, images, or urges. OCPD characteristics and behaviors are known as ego-syntonic, as people with this disorder view them as suitable and correct. On the other hand, the main features of perfectionism and inflexibility can result in considerable suffering in an individual with OCPD as a result of the associated need for control.The presence of OCPD in patients with OCD has been linked to a worse prognosis of OCD, especially when cognitive behavioral therapy was used. This may be due to the ego-syntonic nature of OCPD which may lead to the obsessions becoming aligned with ones personal values. In contrast, the trait of perfectionism may improve the outcome of treatment as patients are likely to complete homework assigned to them with determination. The findings with regards to pharmacological treatment has also been mixed, with some studies showing a lower reception to SRIs in OCD patients with comorbid OCPD, with others showing no relationship.Comorbidity between OCD and OCPD has been linked to a more severe presentation of symptoms, a younger age of onset, more significant impairment in functioning, poorer insight, and higher comorbidity of depression and anxiety.
Autism spectrum disorder
There are considerable similarities and overlap between autism spectrum disorder (ASD) and OCPD, such as list-making, inflexible adherence to rules, and obsessive aspects of ASD, although the latter may be distinguished from OCPD especially regarding affective behaviors, worse social skills, difficulties with Theory of Mind and intense intellectual interests, e.g. an ability to recall every aspect of a hobby. A 2009 study involving adult autistic people found that 32% of those diagnosed with ASD met the diagnostic requirements for a comorbid OCPD diagnosis.
Eating disorders
Perfectionism has been linked with Anorexia Nervosa in research for decades. A researcher in 1949 described the behavior of the average "anorexic girl" as being "rigid" and "hyperconscious", observing a tendency to "[n]eatness, meticulosity, and a mulish stubbornness not amenable to reason [which] make her a rank perfectionist". So common are such traits as perfectionism and rigidity among anorectics, that they have been referred to in clinical literature as "classical childhood features of patients with anorexia nervosa" or classical premorbid personality descriptors of anorexia nervosa".Regardless of the prevalence of the full-fledged OCPD among eating disordered samples, the presence of this personality disorder or its traits, such as perfectionism, has been found to be positively correlated with a range of complications in eating disorders and a negative outcome, as opposed to impulsive features—those linked with histrionic personality disorder, for example—which predict a better outcome from treatment. OCPD predicts more severe symptoms of Anorexia Nervosa, and worse remission rates, however, OCPD and perfectionistic traits predicted a higher acceptance of treatment, which was defined as undergoing 5 weeks of treatment.People with Anorexia Nervosa who exercise excessively display a higher prevalence of several OCPD traits when compared to their counterparts who did not exercise excessively. The traits included self-imposed perfectionism, and the childhood OCPD traits of being rule-bound and cautious. It may be that people with OCPD traits are more likely to use exercise alongside restricting food intake in order to mitigate fears of increased weight, reduce anxiety, or reduce obsessions related to weight gain. Samples that had the childhood traits of rigidity, extreme cautiousness, and perfectionism endured more severe food restriction and higher levels of exercise and underwent longer periods of underweight status. It may be that OCPD traits are an indicator of a more severe manifestation of AN which is harder to treat.
Gambling Disorder
A majority of those with lifelong gambling disorder have some sort of personality disorder, and the most common personality disorder amongst them is obsessive compulsive personality disorder. OCPD has a strong comorbidity with individuals who have gambling disorder. A study of data collected in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions looked at pathological gambling and psychiatric conditions as defined by the DSM-IV. Of the surveyed population consistent with gambling disorder, 60.8% also had a personality disorder, with OCPD appearing most frequently at 30%. About 300,000 U.S citizens have both a gambling disorder and obsessive compulsive personality disorder; and yet, there is little research on the comorbidity of the two disorders. Those with gambling disorders and OCPD do, indeed, exhibit different behavioral patterns than those with gambling disorders alone. More research on the relationship between the disorders is thought to help uncover causes and develop treatments for patients.
Mental Fatigue
Recently, in 2020, the connection between mental fatigue and OCPD was published for the first time, even though mental fatigue has been previously associated with identified characteristics of OCPD such as workaholic behavior and perfectionism.
Other disorders and conditions
A diagnosis of OCPD is common with anxiety disorders, substance use disorders, and mood disorders. OCPD is also highly comorbid with Cluster A personality disorders,[4]
especially paranoid and schizotypal personality disorders.OCPD is also linked to hypochondriasis, with some studies estimating a rate of co-occurrence as high as 55.7%.Moreover, OCPD has been found to be very common among some medical conditions, including Parkinsons disease and the hypermobile subtype of Ehler-Danlos syndrome. The latter may be explained by the need for control that arises from musculoskeletal problems and the associated features that arise early in life, whilst the former can be explained by dysfunctions in the fronto-basal ganglia circuitry.
Treatment
The best-validated treatment for OCPD is cognitive therapy (CT) or cognitive behavioral therapy (CBT), with studies showing an improvement in areas of personality impairment, and reduced levels of anxiety and depression. Group CBT is also associated with an increase in extraversion and agreeableness and reduced neuroticism. Interpersonal psychotherapy has been linked to even better results when it came to reducing depressive symptoms.
Epidemiology
Estimates for the prevalence of OCPD in the general population are 3%, making it the most common personality disorder. Current evidence is inconclusive as to whether OCPD is more common in men than women, or in equal rates among sexes. It is estimated to occur in 8.7% of psychiatric outpatient settings.A study of data collected in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions looked specifically for seven personality disorders as defined by the DSM-IV. The study concluded the most prevalent personality disorder of the surveys population to be OCPD, at 7.88%. This study also concluded there were no gender differences in prevalence and that OCPD was not a predicter of disability.
History
In 1908, Sigmund Freud named what is now known as obsessive–compulsive or anankastic personality disorder "anal retentive character". He identified the main strands of the personality type as a preoccupation with orderliness, parsimony (frugality), and obstinacy (rigidity and stubbornness). The concept fits his theory of psychosexual development. Freud believed that the anal retentive character faced difficulties regulating the control of defecation, leading to repercussions by the parents, and it is the latter that would cause the anal retentive character.Aubrey Lewis, in his 1936 book Problems of Obsessional Illness, suggests that anal-erotic characteristics are found in patients without obsessive thoughts, and proposed two types of obsessional personality, one melancholy and stubborn, the other uncertain and indecisive.In the book Contributions to the theory of the anal character, Karl Abraham noted that the core feature of the anal character is being perfectionistic, and he believed that these traits will help an individual in becoming industrious and productive, whilst hindering their social and interpersonal functioning, such as working with others.OCPD was included in the first edition of the Diagnostic and Statistical Manual of Mental Disorders in 1952 by the American Psychiatric Association under the name "compulsive personality". It was defined as a chronic and excessive preoccupation with adherence to rules and standards of conscience. Other symptoms included rigidity, over-conscientiousness, and a reduced ability to relax.The DSM-II (1968) changed the name to "obsessive-compulsive personality", and also suggested the term "anankastic personality" in order to reduce confusion between OCPD and OCD, but the proposed name was removed from later editions. The symptoms described in the DSM-II closely resembled those in the original DSM.In 1980, the DSM-III was released, and it renamed the disorder back to "compulsive personality disorder", and also included new symptoms of the disorder: a restricted expression of affect, and an inability to delegate tasks. Devotion to productivity, perfectionism, and indecisiveness were the other symptoms included. The DSM-III-R (1987) renamed the disorder again to "obsessive-compulsive personality disorder" and the name has remained since then. A diagnosis of OCPD was given when 5 of the 9 symptoms were met, and the 9 symptoms included perfectionism, preoccupation with details, an insistence that others submit to ones way, indecisiveness, devotion to work, restricted expression of affect, excessive conscientiousness, lack of generosity, and hoarding.With DSM-IV, OCPD was classified as a Cluster C personality disorder. There was a dispute about the categorization of OCPD as an Axis II anxiety disorder. Although the DSM-IV attempted to distinguish between OCPD and OCD by focusing on the absence of obsessions and compulsions in OCPD, OC personality traits are easily mistaken for abnormal cognitions or values considered to underpin OCD. The disorder is a neglected and understudied area of research.
See also
Analysis paralysis
Anal retentiveness
Authoritarian personality
Compulsive hoarding
Germaphobia
Jobsworth
Pedantic
Scrupulosity
References
Further reading
Grant, John E., Obsessive-Compulsive Personality Disorder (2019). American Psychiatric Association Publishing. ISBN 978-1-61537-280-5
External links
MedlinePlus Encyclopedia: Obsessive–compulsive personality disorder |
Endolymphatic sac tumor | An endolymphatic sac tumor (ELST) is a very uncommon papillary epithelial neoplasm arising within the endolymphatic sac or endolymphatic duct. This tumor shows a very high association with Von Hippel–Lindau syndrome (VHL).
Classification
The ELST has been referred to as adenocarcinoma of endolymphatic sac, Heffner tumor, papillary adenomatous tumor, aggressive papillary adenoma, invasive papillary cystadenoma, and papillary tumor of temporal bone. However, these names are not encouraged as they do not accurately classify the current understanding of the tumor.
Signs and symptoms
Patients with ELST may present clinically with progressive or fluctuating, one sided sensorineural hearing loss which may mimick Ménières disease due to the development of tumor associated endolymphatic hydrops. Patients may also experience tinnitus, vertigo, and loss of vestibular function (ataxia). Alternatively, symptom onset may be sudden, due to intralabyrinthine hemorrhage. Patients may also present with other symptoms related to von Hippel–Lindau syndrome in other anatomic sites, which will result in imaging evaluation of the head.
Imaging findings
Imaging studies help to identify the tumor and the specific anatomic site of involvement. Magnetic resonance images show a hyperintensity (hypervascularity) of a heterogeneous mass by T1 weighted images. Computed tomography shows a multilocular, lytic destructive temporal bone mass, centered on the vestibular aqueduct (between internal auditory canal and sigmoid sinus).
Pathogenesis
The von Hippel–Lindau tumor suppressor gene generally has a germline mutation. This suppressor gene is also called elongin binding protein and G7 protein. The VHL protein is involved in up-regulation of hypoxic response via the [[hypoxia inducible factor [HIF]-1 alpha]]. Mutations generally prevent the production of any functional VHL protein or result in a change of structure of VHL protein. This genetic disorder shows an autosomal dominant inheritance pattern, with about 20% of patients possessing a new mutation. There are usually several other tumors which are part of the syndrome, including tumors of the central nervous system, kidneys, pancreas, adrenal glands, epididymis, broad ligament, along with the endolymphatic sac. The vast majority of patients with an endolymphatic sac tumor have von Hippel-Lindau syndrome.
Pathology findings
Tumors range from several millimeters up to 10 cm, with larger tumors more frequently seen in older patients. If the tumor is bilateral, it is almost always seen in a VHL patient. The tumor destroys the mastoid air spaces and extends into the middle ear and/or posterior cranial fossa.
The microscopic appearance shows an unencapsulated, destructive growth, remodeling and invading bone. The tumor is arranged as simple, broad, non-complex papillary projections without large cystic spaces. The spaces are often fluid filled, have extravasated erythrocytes and/or inspissated material. The cells are cuboidal, usually single layered along the papillary structures, showing indistinct cell borders. The nuclei are round and hyperchromatic.
Immunohistochemistry
The neoplastic cells are reactive with keratin, CK7, and Epithelial membrane antigen, but negative with TTF-1 and CK20.
Cytogenetics
The germline mutations of VHL tumor suppressor gene will be found on 3p25-26 (short arm of chromosome 3), usually between base pair 10,158,318 to 10,168,761.
Differential diagnosis
The clinical and pathology differential are different. From a pathology perspective, an endolymphatic sac tumor needs to be separated from metastatic renal cell carcinoma, metastatic thyroid papillary carcinoma, middle ear adenoma, paraganglioma, choroid plexus papilloma, middle ear adenocarcinoma, and ceruminous adenoma.
Management
Wide excision is the treatment of choice, although attempting to preserve hearing. Based on the anatomic site, it is difficult to completely remove, and so while there is a good prognosis, recurrences or persistence may be seen. There is no metastatic potential. Patients who succumb to the disease, usually do so because of other tumors within the von Hippel-Lindau complex rather than from this tumor. Surgery is the primary treatment modality, but in some rare instances adjuvant radiation therapy may be used.
Epidemiology
This is a very rare tumor, since only about 1 in 35,000 to 40,000 people have VHL, of whom about 10% have endolymphatic sac tumors. Patients usually present in the 4th to 5th decades without an gender predilection. The tumor involves the endolymphatic sac, a portion of the intraosseous inner ear of the posterior petrous bone.
References
Further reading
Lester D. R. Thompson; Bruce M. Wenig (2011). Diagnostic Pathology: Head and Neck: Published by Amirsys. Hagerstown, MD: Lippincott Williams & Wilkins. pp. 7:64–67. ISBN 978-1-931884-61-7. |
Phoenix abscess | A phoenix abscess is an acute exacerbation of a chronic periapical lesion. It is a dental abscess that can occur immediately following root canal treatment. Another cause is due to untreated necrotic pulp (chronic apical periodontitis). It is also the result of inadequate debridement during the endodontic procedure. Risk of occurrence of a phoenix abscess is minimised by correct identification and instrumentation of the entire root canal, ensuring no missed anatomy.
Treatment involves repeating the endodontic treatment with improved debridement, or tooth extraction. Antibiotics might be indicated to control a spreading or systemic infection.
Causes
Phoenix abscesses are believed to be due to a changing internal environment of the root canal system during the instrumentation stage of root canal treatment, causing a sudden worsening of the symptoms of chronic periradicular periodontitis. This instrumentation is thought to stimulate the residual microbes in the root canal space to cause an inflammatory reaction. These microbes are predominantly facultative anaerobic gram-positive bacteria, such as Streptococcus, Enterococcus and Actinomyces species. Another cause of a phoenix abscess is a decrease in a patients resistance to these bacteria and their products.
Signs & Symptoms
Clinical Features
PainA common clinical feature is exacerbated and exaggerated pain. There may or may not be associated with pus & suppuration. The signs & symptoms are similar to that of an acute periradicular abscess, but with a periradicular radiolucency present as well.
Loss of VitalityThe problematic tooth will have a non-vital pulp with no previous symptoms. Vitality of teeth can be assessed through various means. Common tests would include ethyl chloride test or electric pulp test. Other examples of tests would be laser doppler flowmetry (LDF), pulse oximetry etc.
Tender to TouchThe tooth is extremely tender to touch, and it may be high on occlusion as it may be extruded from the socket.
MobileMobility may be observed.
Radiographic Features
Radiographically, there will be a periapical lesion associated with the tooth. This lesion is normally existent prior to this episode. Widened periodontal ligament (PDL) space is visible.
Treatment
For most situations urgent treatment is required to eliminate the pain and swelling.
1) Further Endodontic Treatment
Further root canal treatment is often the best option. Firstly, the tooth should be accessed and thoroughly irrigated using sodium hypochlorite. Following this the canals should be dried using paper points. The tooth should then be debrided, and drainage established.
2) Medications
i) Antibiotics
In certain circumstances it may be necessary to provide an antibiotic. These circumstances include the presence of a diffuse swelling or cellulitis, when immediate drainage cannot be achieved, or the patient has systemic involvement.
ii) Analgesics
Analgesics may also be advised for pain control.
3) Extraction
If the tooth is unrestorable then extraction may also be an option.
4) Bite Adjustment
Adjusting the bite may provide some relief but this will not be a permanent solution to the problem.
== References == |
Hypodontia | Hypodontia is defined as the developmental absence of one or more teeth excluding the third molars. It is one of the most common dental anomalies, and can have a negative impact on function, and also appearance. It rarely occurs in primary teeth (also known as deciduous, milk, first and baby teeth) and the most commonly affected are the adult second premolars and the upper lateral incisors. It usually occurs as part of a syndrome that involves other abnormalities and requires multidisciplinary treatment.
The phenomenon can be subdivided into the following according to the number of teeth concerned:
Hypodontia: one to six missing teeth excluding the third molars
Oligodontia: six or more missing permanent teeth excluding the third molars
Anodontia: complete absence of teeth
Signs and symptoms
Typically, all baby teeth will be present by the age of three. As for all adult teeth, they erupt between the ages 6 to 14, with the exception of the third molar, also known as the wisdom teeth which normally erupt between 17 and 25 years of age. If the tooth has yet to erupt by an appropriate age, panoramic x-rays are taken.
Dental features
Microdontia may be present in one or more of the other teeth. This means that the teeth appear smaller than normal, may be observed in both the primary and permanent dentition. This condition can be genetically-linked and in severe cases, may present themselves in the form of ectodermal dysplasia, cleft lip or palate or Down Syndrome. A delay in tooth development may also serve as an indication, whereby the absence of an adult successor slows down the normal resorption of the roots of the baby teeth, which is the progressive loss of parts of the tooth.
Misplaced (ectopic) positioning of the adult teeth may be discovered upon examination or a radiograph. One of the consequences may be an adult tooth intercepting with a baby tooth, causing premature loss or wrong positioning. This can be due to either the absence of neighboring teeth acting as a guide during eruption or the lack of space in the jaw for them to erupt into because of malocclusion.
Skeletal features
Several studies have discovered that anteriorly missing teeth can accompany retrognathic maxilla, also known as an underbite, prognathic mandible, where the lower jaw protrudes out more than normal, and smaller posterior cranial base length. Occurrence of hypodontia can be associated with reduced anterior lower facial height and lip protrusion. This can be linked to lower maxillary to mandibular plane angles.
A more acute mandibular angle and flatter chin may develop as a result. These characteristics become more prominent as the condition becomes progressively severe, particularly when more than one tooth is missing.
Other dental and radiographic features
Data derived from principal component analysis of radiographic images show that children with mild hypodontia may display significant increase of the interincisal angle and decrease in the maxillary and mandibular incisor angles.
Cephalometric tracing is commonly used to study a patients dentofacial proportions in the craniofacial complex. This can aid in predicting growth changes, allowing dentists, especially orthodontists, to develop a suitable treatment plan. Coupled with that, findings consistent among individuals include:
Anterior hypodontia associated with hyper divergent craniofacial pattern;
A tendency toward a class III malocclusion identified in maxillary hypodontia, and;
Reduced lower posterior facial height in children with posterior and mandibular hypodontia.
Associated anomalies
Reduction in coronal or radical dimensions
Retained primary teeth
Ectopic canine eruption
Abnormal morphology such as peg-shaped maxillary lateral incisors and taurodontism, characterized by an enlarged tooth body and roots that are reduced in size
Extracted teeth
Cause
Several theories regarding the aetiology of hypodontia have been proposed in existing literature. There have been various theories mostly looking into genetic and environmental aspects and how they may both be involved. However, the exact cause remains unclear. The extent of individual influences of genetic and environmental factors is still widely debated.Theories regarding the mechanism through which hypodontia occurs can be categorised into evolutional or anatomical.Preliminary studies focused on an evolutionary approach which suggested shortening of the intermaxillary complex and thus shorter arches may contribute to a decrease in number of teeth. This was also suggested in 1945 by Dahlberg using Butlers Field Theory that focused on evolution and development of mammalian teeth into human dentition in an attempt to analyse different of agenesis. In each jaw, four morphological sites were identified (incisors, canines, premolars and molars). The tooth at the end of each region was less genetically stable and hence more prone to absence. In contrast, the tooth most mesial in each region seemed to be more genetically stable. A subsequent theory hypothesised the teeth at the end of each region were possibly "vestigial bodies" that became obsolete during the evolutionary process. At present, it has been theorised that evolutionary change is working to decrease the human dentition by the loss of an incisor, premolar and molar in each quadrant. According to Vastardis (2000), the size of jaws and number of teeth seem to decrease along with human evolution.Theories focusing on anatomical principle, hypothesised that specific areas of the dental lamina are especially prone to environmental effects during tooth maturation. Svinhufvud et al. (1988) suggested that teeth that were more prone to absence developed in areas of initial fusion of the jaw. For instance, maxillary lateral incisors originate where the lateral maxillae and medial nasal bone processes fuse. In contrast, Kjaer et al. (1994) suggested regions where innervation developed were more sensitive than areas of fusion. Commonly affected regions were found to undergo innervation last, this might imply the developmental relationship between nerve and hard tissue. It is thought to be local nerve development that affects tooth agenesis rather than global development, as brainstem anomalies have not been seen to affect tooth development.Presently, the role of polygenic and environmental factors on hypodontia is recognised in most theories.
Environmental factors
Environmental factors can be classified into two main groups, invasive and non-invasive. These factors act additively or independently, ultimately affecting positioning and physical development of the tooth.Invasive environmental factors potentially affect tooth development and positioning leading to hypodontia and impaction. Examples include jaw fractures, surgical procedures and extraction of the preceding deciduous tooth. Treatment such as irradiation has been shown to have severe effects on developing teeth. In a smaller capacity, chemotherapy was also found to have a similar effect. Thalidomide (N-phthaloylglutamine) was also discovered to have a causative effect on mothers who took the drug during pregnancy, resulting in congenitally missing teeth in their children. A link was found between systemic diseases, endocrine disruption (i.e. idiopathic hypoparathyroidism and pseudohypoparathyroidism) and ectodermal dysplasia. However, a definite etiological relationship has yet to be established. Examples of infections include rubella and candida. Exposure to PCBs (such as dioxin), allergies, and toxic epidermal necrolysis folloeing a drug reaction may also be contributing factors.
In a recent study assessing environmental risk factors for hypodontia, it was established that maternal smoking does play a causative role in hypodontia. Passive smoking and caffeine were also assessed but showed no statistical significance.The Journal of the American Dental Association published preliminary data suggesting a statistical association between hypodontia of the permanent teeth and epithelial ovarian cancer (EOC). The study shows that women with EOC are 8.1 times more likely to have hypodontia than are women without EOC. The suggestion therefore is that hypodontia can serve as a "marker" for potential risk of EOC in women.
Genetics
Genetic causes also involve the genes MSX1 and PAX9.Genetic associations for selective tooth agenesis ("STHAG") include:
Failure of tooth formation due to disturbances during the early stages of development could be the cause of congenital missing teeth; this is also known as tooth agenesis. A variety of studies show that missing teeth are commonly associated with genetic and environmental factors. Some literature also shows that a combination of both factors may contribute to the occurrence of hypodontia.Most craniofacial characteristics are influenced by both genetic and environmental factors through complex interactions. The variable expressivity of traits can be either completely genetically determined, environmentally determined, or both. That genetics plays an important role in hypodontia is shown in many different cases. There are hundreds of genes expressed and involved in regulating tooth morphogenesis. Although a single gene defect may contribute to hypodontia, more studies propose that hypodontia is the result of one or more points of closely linked genetic mutations, or polygenic defects.The pattern of congenitally missing teeth seen in monozygotic twins is different, suggesting an underlying epigenetic factor, which may be due to the simultaneous occurrence of two anomalies. This multifactorial aetiology involves environmental factors which trigger the genetic anomalies, resulting in the occurrence of dental agenesis. Common environmental factors include infection, trauma and drugs which predispose to the condition. In hereditary cases, evidence of dental germ developing after surrounding tissues have closed the space required for development may be a large contributing factor, as well as such genetic disorders as Down syndrome, ectodermal dysplasia, cleidocranial dysplasia, and cleft lip and cleft palate.
MSX1
MSX1 (muscle segment homeobox 1) is involved in condensation of ectomesenchyme in the tooth germ. Among the members of homeobox genes, MSX1 and MSX2 are crucial in mediating direct epithelial-mesenchymal interactions during tooth development by expressing in regions of condensing ectomesenchyme in the tooth germ. MSX1 mutations have been identified as a contributing factor in missing second premolars, third molars, and a small percentage of first molars. MSX1 is less likely to cause anterior agenesis.Heterozygous mutations in PAX9 (paired box gene 9) could arrest tooth morphogenesis as it plays a role of transcription the gene expressed in tooth mesenchyme at the bud stage during tooth development. A study showed that single nucleotide polymorphisms in PAX9 were highly associated with missing upper lateral incisors.
AXIN2
The AXIN2 (AXIS inhibition protein 2) gene is a negative regulator of the Wnt signalling pathway, which is important in regulating cell fate, proliferation, differentiation and apoptosis. Its polymorphic variant may be associated with hypodontia such as missing lower incisors or in a more severe form of agenesis like oligontia (lack of six or more permanent teeth).
EDA
EDA provides instructions for making a protein called ectodysplasin A. It encodes transmembrane protein that is part of TNF (tumour necrosis factor) family of ligands. EDA gene defects cause ectodermal dysplasia, which is also known as X-linked hypohidrotic ectodermal dysplasia. Common dental features of ectodermal dysplasia are multiple missing teeth and microdontia.PAX9 and TGFA are involved in regulating between MSX1 and PAX9, causing hypodontia of the molars.Hypodontia can be found in isolated cases too. The familiar or sporadic type of isolations are more frequently reported than the syndromic type. Isolated cases of autosomal dominant, autosomal recessive, or X-linked inheritance patterns may have an impact on the isolation conditions in expressing variation of both penetration and expressivity of traits. Mutations in MSX, PAX9 and TGFA genes are known to cause congenitally missing teeth in some racial groups.
Research
In the 1960s and 1970s, several studies were conducted sponsored by the U.S. Atomic Energy Commission, with the aim of finding a link between genetics and hypodontia.
Impact
There are numerous studies and research reports on the prevalence, aetiology, and treatment of hypodontia and the dentoskeletal effect of hypodontia. A few studies have investigated Oral Health-related Quality of Life (OHRQoL) in individuals with hypodontia and provided some evidence that hypodotia may have an impact on quality of life.
Psychosocial
Cosmetic dentistry has become more notable and prevalent in modern society. Interpersonal relationships and perceived qualities, such as intelligence, friendliness, social class, and popularity can be affected by dentofacial appearance. Some studies have shown that the extent of complaints made by patients was associated with the severity of the condition and the number of missing permanent teeth.Meta-analyses and theoretical reviews have demonstrated that attractive children are seen by others as more intelligent and exhibit more positive social behaviour and traits, other than receiving much more positive treatment than their less attractive counterparts. Therefore, a divergence from perceived ideal dentofacial aesthetic, particularly in children, might adversely affect self-esteem and self-confidence besides attracting mockery from peers.It is therefore reasonable to theorize that deviations from "normal" or "ideal" dentofacial aesthetic could be destructive to an individuals psychosocial and emotional well-being, which brings upon some psychosocial distress in that individual as a result of their condition.
Functional
Individuals with hypodontia tend to have deeper bites and spaces. Further deepening of the bite can also be seen on individuals with missing posterior teeth. Apart from that, hypodontia may lead to non-working interferences, poor gingival contours and over-eruptions of the opposing teeth.It has been found that individuals with hypodontia experience more difficulty during mastication or functioning movements due to smaller occlusal table available. A recent cross-sectional study showed that hypodontia patients have more difficulties in chewing, especially if the deciduous teeth associated with the missing permanent teeth had been exfoliated. Despite currently limited evidence to support this statement, it is plausible that hypodontia may pose functional limitations, which eventually affect that individuals general well-being and quality of life.Hypodontia can indeed pose limitations on the chewing ability of a patient. The condition can be associated with split in the upper lips – a condition known as oral cleft. Hypodontia can have impacts on speech, aesthetics and function of muscles in the mouth. As a result, hypodontia can have negative impacts on the quality of life, although the condition can be well managed and treated by dentists and orthodontists. To manage the condition, the patient will need to have long-term orthodontic treatment.
Financial
Patient with hypodontia requires careful treatment plan due to complex case in order to ensure the best treatment outcomes. Such treatment plans require multi-disciplinary approach, which usually come at a financial cost to both patient and possibly their family. Due to this reason, a team consists of different dental specialties is involved in the patient care.
Management
Hypodontia is a condition that can present in various ways with differing severities. This results in a wide range of treatment methods available. Those affected should be allowed to consider and select the most suitable option for themselves. Early diagnosis of hypodontia is critical for treatment success. The treatment of hypodontia involves specialists in departments such as oral and maxillofacial surgery, operative dentistry, pediatric dentistry, orthodontics and prosthodontics.Before determining a treatment plan, the following should be determined:
Evaluate the number of teeth missing
The size and number of remaining teeth in both arches
Malocclusion
Facial profile
Bone volume
Age: Definitive treatment for hypodontia only commences once all permanent teeth erupt, or upon the completion of orthodontic treatment
Primary teeth condition
Patients motivation towards treatmentTraditionally, the management of hypodontia has involved replacing missing teeth. By replacing the missing teeth, it can prevent neighbouring teeth tilting or drifting and also prevents the overeruption of opposing teeth which could then impact on occlusion and temporo-mandibular joint dysfunction and impact the patients susceptibility to gum disease, tooth wear and tooth fractures. However, studies have suggested that a stable occlusion can be achieved even with a shortened arch of 10 occluding pairs of teeth. The findings support the concept that a healthy and stable occlusion can exist despite missing teeth as long as an acceptable number of teeth are in occlusion. However, this management technique may not be suitable for those with gum disease, parafunctioning activity (tooth grinding or clenching) or malocclusion.It should also be noted that spaces within the dental arch should be monitored, especially in younger patients, as teeth are more likely to drift, tilt or over-erupt. To do this, study models and clinical photographs could be taken in order to record baseline records. If tooth movement was to occur, another form of management may be required depending on the severity and nature.The following below are the methods used to manage hypodontia:
Accept spacing
This is a method suitable to individuals if the space from a missing tooth is not deemed to be an aesthetic concern. Appearance may not be a problem in some cases, for example, when spacing present behind the canines may not be particularly visible, depending on the individual.
Management of retained primary teeth
When there is a case of hypodontia of the permanent premolar teeth, the primary molar teeth would often remain in the mouth beyond the time they are meant to be lost. Therefore, with a presence of healthy primary teeth in the absence of a permanent successor, retaining the primary teeth can be a feasible management of hypodontia.
The primary molars present also functions as a space maintainer, prevent alveolar bone resorption and delays future prosthodontic space replacement by acting as a semi permanent solution going into adulthood Previous studies also shown a good prognosis of retained primary molars going into adulthood. However, leaving the primary teeth in place may run the risk of tooth infraocclusion where the occlusal surface is below that of adjacent teeth.Despite this, the retention of primary teeth, particularly molars, are more susceptible to occlusal wear, over-eruption of opposing teeth and the loss of inter-occlusal space.
Orthodontic space closure
Orthodontic space closure is a way of using orthodontics in order to close spaces in the mouth where the teeth are missing. The ideal age for definitive orthodontic treatment is early adolescence but it is important to consider the patients age, severity of hypodontia, patient expectations and their commitment to treatment. It can be an option for hypodontia management in the case of missing maxillary lateral incisors through the reshaping, and mesial re-positioning of the adjacent canine. This management is indicated in hypodontia cases of Class I molar relationship with severe crowding in the mandibular anterior region where the extraction of lower premolar leads to a predictable outcome, and Class II molar relationship in the absence of crowding and protrusion of the mandibular anterior dentition.When moving the canine into the space of the lateral incisor, the dimensions of the canine, root position and gingival position differ from a lateral incisor and therefore preparation of the canine is necessary in order for it to mimic the incisor. This may involve:
Reduction of the incisal tip and addition of composite on the incisal edge to create a straight contour and a rounded disto-incisal corner
Reduction of the mesial and distal surfaces to reduce the width of the tooth
Flattening of the labial surface to reduce bulbosity. However, removal of enamel by expose the darker coloured dentine and therefore further restoration may be required.
Preparation of the palatal surface of the canine to reduce its bulk.The use of veneers can also be used instead of composite however, these are more expensive and more time-consuming.
There have been several studies which showed the advantages of orthodontic space closure without prosthodontic space replacements. The main advantage mentioned is the early completion of the treatment during early adolescence and the long lasting result of the treatment outcome. In individuals with a high smile line, the mesial re-positioning of canine maintains the normal soft tissue architecture is important in maintaining the aesthetic appearance. This option also negates the risks and costs that comes with prosthodontic treatment and the impression that there is no missing tooth.Some factors need to be considered when making a decision whether to undergo space closure. These include facial profile, size and dimension of canine, the shade of colour of the teeth and the gingival contour and height. Group function occlusion is usually present as a result of the mesial movement of the canine. In order to maintain the stability of the closed space, direct-bonded lingual retainers are usually required.
Orthodontic space opening prior to prosthodontic treatment
The need for orthodontic space opening prior to prosthodontic management depends on the amount of edentulous space available in relation to adjacent teeth, occlusion and aesthetic concerns. To determine the amount of space needed, three methods in the literature can be used which are the golden proportion, the Bolton Analysis and comparing the edentulous space with the contralateral tooth size if present.Space opening and prosthodontic treatment is indicated where there is a Class I molar relationships in the absence of malocclusion Class III molar relationships presenting with a concave facial profile. However, the alteration in appearance during orthodontic treatment (e.g. creating diastema for placement of prostheses) before the filling up the space, although temporary, can negatively impact the oral health-related quality of life in adolescents.
Removable partial dentures
Removable partial dentures are known to be an effective interim method for maintaining functional and aesthetic demands in a growing patient, where definitive fixed restorations are not suitable yet. Removable dentures act as a space maintainer and also prevent the migration of adjacent or opposing teeth, thereby preserving the face height. They are also easy to adjust or add on to in the event of further tooth eruption. However, it may be difficult for young individuals to adhere with wearing removable dentures, due to their bulk. Some patients also find the idea of dentures functionally and socially unacceptable, making them unwilling to comply. Removable prosthetic devices are also known to cause damage to the remaining teeth if worn over a long period of time.
Conventional crown and bridgework
Fixed restorative options are generally preferred over removable ones.
Resin-bonded bridges: Due to its minimal preparation required, this method of replacing teeth is more suited to young adults. It is a definitive restoration with the ability to fill up one or two tooth spaces. Research has reflected a survival rate of 80% over a period of 6 years or longer, and that cantilever resin-bonded bridges are at least as good as conventional fixed-fixed bridges. Restoring teeth with this method can only be done after orthodontic treatment and will need an element of retention to ensure that tooth contacts are not misplaced.
Conventional bridges: Teeth tend to be prepared for conventional bridgework if there are large restorations present, thus being more commonly done on adult patients with hypodontia. Treatment with conventional bridgework will require significant reduction of tooth structure, which will put the tooth at risk of biological damage i.e. loss of vitality. This risk is especially high in young patients with large pulp chambers.
Tooth autotransplantation
Autotransplantation involves the removal of a tooth from one socket and relocating to another socket in the same individual. If done successfully, it is able to ensure stable alveolar bone volume as there is continuous stimulation of the periodontal ligament.
Implant supported tooth replacement
Placing dental implants has proven to be a predictable and reliable method of treating hypodontia, along with bringing excellent aesthetic results. Implant placement should be delayed until jaw growth in an individual is complete. One limitation of implant placement would be the need for a sufficient amount of bone volume, which if not met, may affect the positioning of the implant. However, bone grafting can be carried out to overcome this.
Epidemiology
Hypodontia is less common in the primary dentition, with reported prevalence rates ranging from 0.5% in the Icelandic population to 2.4% in the Japanese population. In the primary dentition the teeth reported as most likely to be missing are the lateral incisors, both maxillary and mandibular. If a deciduous tooth is missing this will increase the risk of an absent successor.In the permanent dentition third molars are most commonly absent, and one study found prevalence rates of between 20–22%. When third molars are ignored the prevalence rate for each tooth varies from study to study. In Caucasian studies mandibular second premolars and maxillary lateral incisors are most often absent. Several UK studies have found the lower second premolar to be most commonly absent. Studies from Asian populations report that the mandibular incisor is most commonly absent.A higher prevalence of hypodontia in females has been reported. The most extensive studies have been in Caucasian populations and suggest a prevalence of 4–6%.One study looked at 33 previous studies with a sample size of 127,000, and concluded that the prevalence of hypodontia in the permanent dentition varied between continents, racial groups and genders. In the white European population they suggested a prevalence of 4.6% in males and 6.3% in females. In an African-American sample they found this to be 3.2% in males and 4.6% in females. The same study found that in the permanent dentition the most likely teeth to be missing and the frequency of these missing teeth was:
Mandibular second premolar 3%
Maxillary lateral incisor 1.7%
Maxillary second premolar 1.5%
Mandibular central incisor 0.3%
References
== External links == |
Vaginal vault | The vaginal vault is the expanded region of the vaginal canal at the internal end of the vagina.
Prolapse
The vaginal vault may prolapse after a hysterectomy, as there is no uterus supporting the interior end of the vagina.
Colposacropexy is often used for treating vaginal vault prolapse. A Cochrane Collaboration review[needs update] found that limited data are available on optimal surgical approaches, including the use of transvaginal surgical mesh devices, in the form of a patch or sling, similar to its implementation for abdominal hernia. However, the use of a transvaginal mesh in treating vaginal prolapses is associated with side effects including pain, infection, and organ perforation. According to the FDA, serious complications are "not rare." A number of class action lawsuits have been filed and settled against several manufacturers of TVM devices.
See also
Vagina
Hysterectomy
References
External links
Dictionary definition of "Vaginal vault" from TheFreeDictionary.com |
Krukenberg tumor | A Krukenberg tumor refers to a malignancy in the ovary that metastasized from a primary site, classically the gastrointestinal tract, although it can arise in other tissues such as the breast. Gastric adenocarcinoma, especially at the pylorus, is the most common source. Krukenberg tumors are often (over 80%) found in both ovaries, consistent with its metastatic nature.
Signs and symptoms
Krukenberg tumors often come to the attention when they cause abdominal or pelvic pain, bloating, ascites, or pain during sexual intercourse. Krukenberg tumors can occasionally provoke a reaction of the ovarian stroma which leads to hormone production, that results in vaginal bleeding, a change in menstrual habits, or hirsutism, or occasionally virilization as a main symptom. In rare cases the disease can manifest with hydronephrosis and hydroureter.All these symptoms are non-specific and can also arise with a range of problems other than cancer, and a diagnosis can only be made following confirmatory investigations such as computed tomography (CT) scans, laparotomy and/or a biopsy of the ovary.
Cause and incidence
Krukenberg tumors can be seen in all age groups, with an average age of 45 years. In most countries, cancer that has metastasized to the ovary accounts for only about 1 to 2% of ovarian cancer; in the remainder, the ovary itself is the primary cancer site. However, in Japan they represent a much higher percentage of malignancies in the ovary (almost 20%) due to the increased prevalence of gastric cancer.Krukenberg tumors account for about 15% of metastatic cancers that initially appear to have arisen in the ovary, and as such is less common than metastasis arising from ovarian epithelial and germ-cell tumors.In people who have had nongynecologic malignancy, approximately 20% of adnexal masses are malignant, and 60% of these are Krukenberg tumors.
Pathogenesis
There has been debate over the exact mechanism of metastasis of the tumor cells from the stomach, appendix or colon to the ovaries. Classically it was thought that direct seeding across the abdominal cavity accounted for the spread of this tumor, but spread by way of the lymphatic is considered more likely. Retrograde lymphatics are thought to be more important in the pathogenesis of Krukenberg tumour, since the ovaries in Krukenberg tumour do not show capsular invasion or a breech of the epithelium lining the surface. The average age of diagnosis of Krukenberg tumors may partly relate to the relatively increased vascularity of the ovaries.Microscopically, Krukenberg tumors are often characterized by mucin-secreting signet-ring cells in the tissue of the ovary; when the primary tumor is discovered, the same signet-ring cells are typically found. However, other microscopic features can predominate. Krukenberg tumors are most commonly metastases from gastric cancer, particularly adenocarcinoma, or breast cancer particularly invasive lobular breast carcinoma, but they can arise in the appendix, colon, small intestine, rectum, gallbladder, and urinary bladder or gallbladder, biliary tract, pancreas, ampulla of Vater or uterine cervix.Immunohistochemistry may help in diagnosing Krukenberg tumors from primary ovarian neoplasms but needs to be applied with discretion. For example, tumors that are immunoreactive to CEA or cytokeratin 20 (CK20) and negative for cytokeratin 7 (CK7) may be more likely to be of colorectal origin.
Treatment and prognosis
Since Krukenberg tumors are secondary (metastatic), management might logically be driven by identifying and treating the primary cancer. The optimal treatment of Krukenberg tumors is unclear. The role of surgical resection has not been adequately addressed but if metastasis is limited to the ovaries, surgery may improve survival. The role of chemotherapy and/or radiotherapy is uncertain but may sometimes be beneficial.
History
Krukenberg tumors are named after Friedrich Ernst Krukenberg (1871–1946), who reported what he thought was a new type of primary ovarian malignancy in 1896; six years later these were shown to be of metastatic gastrointestinal tract origin. However, Paget had described the process in 1854.
References
External links
00498 at CHORUS |
Constriction ring syndrome | Constriction ring syndrome (CRS) is a congenital disorder with unknown cause. Because of the unknown cause there are many different, and sometimes incorrect names. It is a malformation due to intrauterine bands or rings that give deep grooves in, most commonly, distal extremities like fingers and toes. In rare cases the constriction ring can form around other parts of the fetus and cause amputation or even intrauterine death. The anatomy proximal to the site of constriction (or amputation) is developmentally normal.
CRS can be associated with other malformations with club foot being most common.
The precise configuration of the bands, lymphedema, and character of the amputations are not predictable and vary with each individual patient. Also more than one extremity is usually affected, and it is rare for only one ring to present as an isolated malformation with no other manifestation of this syndrome.
Signs and symptoms
The constriction of appendages by amniotic bands may result in:
Constriction rings around the digits, arms, and legs
Swelling of the extremities distal to the point of constriction (congenital lymphedema)
Amputation of digits, arms, and legs (congenital amputation)
Cause
There are three different theories to the cause of the constriction ring syndrome.
The first is the intrinsic theory, which was proposed by Streeter in 1930, implicates an anomaly in germ plasm resulting in the defects. This theory is reinforced by the clinical presentation of the constriction rings with other internal visceral and systematic anomalies. Because of these other anomalies the names "Constriction Ring Syndrome", "Constriction Band Syndrome", and "Streeter Bands" are given to this defect/disease. This is sometimes attributed to vascular disruption shared between cleft palate and other forms of cleft defects occurring together with ABS; this co-occurrence suggests an "intrinsic" defect of the blood circulation.The second theory postulates the involvement of an intrauterine disruption during pregnancy followed by a cascade of events involving amniotic rupture. When spontaneous rupture of the amnion occurs early in the second trimester, the separation of amnion from chorion produces many small, thin strands that can become entangled within digits and toes. Later, as the fetus grows but the bands do not, the bands become constricting. This constriction reduces blood circulation, hence causes congenital abnormalities. In some cases a complete "natural" amputation of a digit(s) or limb may occur before birth or the digit(s) or limbs may be necrotic (dead) and require surgical amputation following birth. The names "Amniotic Band Syndrome" (ABS), "Amniotic Disruption Complex", and "Amniochorionic Mesoblastic Fibrous Strings" are based on this theory.
The third theory postulates the involvement of intrauterine trauma. Intrauterine trauma could be something like amniocentesis, or something like a fetal surgery. An intrauterine trauma could result in hemorrhage leading to acrosyndactyly. One study also showed the presence of bands as confirmed by sonography after fetal surgery.Because of these different theories, there are many names for this syndrome. For a long time people believed the second theory about the amniotic rupture and strands. In the research cases not every child had a real (amniotic) strand. It could be that there has to be another explanation for the development of these anomalies.
Diagnosis
The diagnosis of constriction ring syndrome can be confirmed with an ultrasonography. The clinical manifestations can be extremely variable. It could be a single or multiple manifestation. This can be confirmed at the end of the first trimester or at the beginning of the second trimester. But not every patient will be diagnosed at that moment, most will get this diagnosis at birth.Individual strands are small and hard to see on ultrasound, so bands are detected indirectly because of the constrictions and swelling upon limbs or digits. Misdiagnosis is also common, so if there are any signs of amniotic bands, further detailed ultrasound tests should be done to assess the severity. 3D ultrasound and MRI can be used for more detailed and accurate diagnosis of bands and the resulting damage/danger to the fetus.
Decreased fetal movement could be a sign of a serious problem which may include ABS. It is rare but possible for the membrane to become wrapped around the placenta or the neck of the baby in the womb causing strangulation and death.
There is a strong relationship between ABS and clubfoot (also called "talipes"). 31.5% of clubfoot cases can be correlated with ABS, with 20% occurring bilaterally. Other abnormalities found with ABS include: clubhands, cleft lip, and/or cleft palate, and hemangioma.
Differential diagnosis
The differential diagnosis includes:
Symbrachydactyly
Congenital amputations
Hypoplasias of hand, digit, thumb
Adams–Oliver syndrome
ADAM complexADAM Complex; CRS is sometimes mislabeled as ADAM complex. ADAM is an abbreviation for Amniotic Deformity, Adhesions Mutilations. CRS is the malformation due to a constriction ring around mostly a limb. ADAM-complex is the association of limb defects (caused by constriction rings) and certain craniofacial clefts"Adams–Oliver syndrome is often mislabeled as CRS and consists of cutis aplasia of the scalp in which a longitudinal defect can vary in size and can often be associated with full-thickness skullcap loss. The distal digital or toe hypoplasia-aplasia is often confused with CRS. Constriction rings with or without edema are not present. The digital or toe hypoplasia-aplasia usually contains diminutive nails or nail folds".
Classification
The constriction ring syndrome is a complex collection of asymmetric congenital anomalies, in which no two cases are exactly alike. This is why a classification is difficult to make.
The most widely used classification system was proposed by Patterson. This classification system is based on the severity of the syndrome and is useful because, the different types require different treatments. Other clinicians have amended this scheme by separating the depth of the ring into mild, moderate, severe, and amputation and by further defining the presence or absence of lymphedema or soft tissue loss distal to the ring. Expanding over subdivision in depth of the clefts for every classification is not necessary because the principles of treatment and technique for correction are the same.There are four categories:
simple constriction rings
constriction rings associated with deformity of the distal part with or without lymphedema
constriction rings associated with acrosyndactyly
uterine amputationPatterson divided the constriction ring associated with acrosyndactyly into three types:
Type I: conjoined fingertips with well-formed webs of the proper depth
Type II: the tips of the digits are joined, but web formation is not complete
Type III: joined tips, sinus tracts between digits and absent websPatterson IThere are simple constriction rings which are strands most commonly around the distal extremities as fingers and toes. In general, the thumb is not likely to be affected by a constriction ring because the fetus typically holds the thumb in tight adduction flexion, making entanglement with strands less likely. These malformations need to be surgically removed which must be executed in different stages and can done by different techniques (see also treatment).
Patterson IIThe CRS involves strands which obstruct the lymphatic vessels and thus causing fluid retention, distal of the affected extremity. This utters itself with swollen parts distal of the constriction.
Patterson IIIIn this form there is a complex form of syndactyly named acrosyndactyly, the fingers (or toes) were initially separated but due to the constriction they are formed back together. Sometimes multiple fingers can be involved. The distal fusion between digits or toes never initially involves a skeletal coalition. The digits are usually hypoplastic if multiple digits are involved. When the constriction cuts off the blood supply to the fingers, the fingers can form a peak with the most palmar digit being the index finger. Normal neurovascular bundles are not present in the distal parts. Hands with fused fingers need to be released in phases to preserve the distal blood supply.
Paterson IVOne of the most severe consequence of constriction strains is probably intrauterine amputations, this is where the constriction goes as deep as the bone and cuts off the blood supply of the proximal extremity. The result will be that the developing toe or finger will become ischemic and fall off. Because the result is a transverse amputation that cuts off the vascular supply to the developing extremity, the actual constriction ring is not seen.
This can result in different outcomes:
complete resorption; this is the most common form of amputation. In this form the amputated digit is completely resorbed during intrauterine development and therefore the amputated digit cant be found.
recovery of the digit; the digit is recovered with the placenta during delivery.
engraftment elsewhere; the amputated digit can be, in rare cases, engrafted somewhere on the fetus.Intrauterine deathIn extremely rare cases a strain can form around the umbilical cord and cut off the blood supply to the fetus which will result in intrauterine death.
Malformation associated with constriction ring syndromeThe percentage of associated anomalies varies from 40% to as high as 80%
Constriction ring deformities are as common on the lower extremity as on the upper, almost all of these involve the musculoskeletal system, with clubbed feet being the most common in up to 30% of reported cases.
Large reported series reveal an incidence between 5% and 15% of craniofacial malformations with clefting of the lip or palate.
Prevention
Amniotic band syndrome is considered an accidental event and it does not appear to be genetic or hereditary, so the likelihood of it occurring in another pregnancy is remote. The cause of amnion tearing is unknown and as such there are no known preventative measures.
Treatment
Surgical correction is recommended when a constriction ring results in a limb contour deformity, with or without lymphedema.
Surgical technique
At the beginning of the surgery a tourniquet will be applied to the limb. A tourniquet compresses and controls local arterial and venous circulation for about 2 hours. The constriction band must be dissected very carefully to avoid damaging the underlying neurovasculature. When the constriction band is excised, there will be a direct closure. This allows the fatty tissue to naturally reposition itself under the skin."With complete circumferential constriction bands, it is recommended that a two-stage correction approach be used. At the first operation, one-half of the circumference is excised and the other one-half can be excised after three to six months. This will avoid any problems to the distal circulation in the limb, which may already be compromised. Lymphedema, when present, will significantly improve within a few weeks of the first surgery."For the direct closure of the defect after dissecting a constriction band there are two techniques:
Triangular flaps; For this technique the circumference between the two borders must be measured. Depending on the difference the number of triangular flaps can be decided. With a triangular flap you can create more skin.
Z-plasty or W-plasty; "Z-plasty is a plastic surgery technique that is used to improve the functional and cosmetic appearance of scars. It can elongate a contracted scar or rotate the scar tension line. The middle line of the Z-shaped incision (the central element) is made along the line of greatest tension or contraction, and triangular flaps are raised on opposite sides of the two ends and then transposed."In rare cases, if diagnosed in utero, fetal surgery may be considered to save a limb that is in danger of amputation or other deformity. This operation has been successfully performed on fetuses as young as 22 weeks. The Melbournes Monash Medical Centre in Australia, as well as multiple facilities in the United States of America, have performed successful amniotic band release surgery.
Reconstructions and prosthetics
Treatment usually occurs after birth and where plastic and reconstructive surgery is considered to treat the resulting deformity. Plastic surgery ranges from simple to complex depending on the extent of the deformity. Physical and occupational therapy may be needed long term.Prosthetics may help some people with ABS to live more functional lives. The price and complexity of these prosthetics vary dramatically, but advances in 3-D printing have helped to increase the availability of artificial fingers while reducing their cost of production.
Prognosis
The prognosis depends on the location and severity of the constricting bands. Every case is different and multiple bands may be entangled around the fetus.
Bands which wrap around fingers and toes can result in syndactyly or amputations of the digits. In other instances, bands can wrap around limbs causing restriction of movement resulting in clubbed feet. In more severe cases, the bands can constrict the limb causing decreased blood supply and amputation. Amniotic bands can also sometimes attach to the face or neck causing deformities such as cleft lip and palate. If the bands become wrapped around the head or umbilical cord it can be life-threatening for the fetus.
The number of cases of miscarriage that can be attributed to ABS is unknown, although it has been reported that it may be the cause of 178 in 10,000 miscarriages. Up to 50% of cases have other congenital anomalies including cleft lip, cleft palate, and clubfoot deformity. Hand and finger anomalies occur in up to 80%.
Epidemiology
The reported incidence of constriction ring syndrome varies from 1/1200 and 1/15000 live births. The prevalence is equally in male and female.Fetomaternal factors like prematurity, maternal illness, low birth weight, and maternal drug exposure are predisposing factors for the constriction ring syndrome.No positive relationship between CRS and genetic inheritance has been reported.
Society
Notable people living with ABS include:
Sophie Wells, British member Paralympics dressage team
Gina Casillas, US volleyball player
Ian T. Jamison, US artist
Anna Johannes, US Paralympic swimmer
Jean-Jacques Machado, 7th degree red-and-black belt in Brazilian Jiu-Jitsu
Monica Price, a case study of a young woman born with amniotic band syndrome
Kingsley McGowan, U.S. Mens Rugby Player
Troy Fumagalli, University of Wisconsin Football Player (2017 Cotton Bowl Offensive MVP)
Lyric Mariah Heard U.S. model
Shaquem Griffin, Miami Dolphins Football Player (2016 AAC Defensive Player of the Year)
Jennifer Bricker, acrobat and aerialist
Sarah Herron, The Bachelor Season 17 contestant, Bachelor in Paradise Seasons 1 and 3 contestant, founder of "She Lift" for girls with disabilities.
Victoria Canal, Cuban-American singer and songwriter
See also
List of skin conditions
Ainhum, auto-amputation of the fifth toe in adults
References
Further reading
Walter JH, Goss LR, Lazzara AT (1998). "Amniotic band syndrome". The Journal of Foot and Ankle Surgery. 37 (4): 325–33. doi:10.1016/s1067-2516(98)80070-7. PMID 9710786.
Light TR, Ogden JA (1993). "Congenital constriction band syndrome. Pathophysiology and treatment". The Yale Journal of Biology and Medicine. 66 (3): 143–55. PMC 2588858. PMID 8209551.
== External links == |
Pneumatosis | Pneumatosis is the abnormal presence of air or other gas within tissues.In the lungs, emphysema involves enlargement of the distal airspaces, and is a major feature of chronic obstructive pulmonary disease (COPD). Other pneumatoses in the lungs are focal (localized) blebs and bullae, pulmonary cysts and cavities.
Pneumoperitoneum (or peritoneal emphysema) is air or gas in the abdominal cavity, and is most commonly caused by gastrointestinal perforation, often the result of surgery.
Pneumarthrosis, the presence of air in a joint, is rarely a serious sign.
Lung cysts
A lung cyst, or pulmonary cyst, encloses a small volume of air, and has a wall thickness of up to 4 mm. A minimum wall thickness of 1 mm has been suggested, but thin-walled pockets may be included in the definition as well. Pulmonary cysts are not associated with either smoking or emphysema.A lung cavity has a wall thickness of more than 4 mm.
Other thoracic
Pneumothorax, air or gas in the pleural space
Pneumomediastinum, air or gas in the mediastinum
Also called mediastinal emphysema or pneumatosis/emphysema of the mediastinum
Abdominal
Pneumoperitoneum (or peritoneal emphysema), air or gas in the abdominal cavity. The most common cause is a perforated abdominal viscus, generally a perforated peptic ulcer, although any part of the bowel may perforate from a benign ulcer, tumor or abdominal trauma.
Pneumatosis intestinalis, air or gas cysts in the bowel wall
Gastric pneumatosis (or gastric emphysema) is air or gas cysts in the stomach wall
Joints
Pneumarthrosis is the presence of air in a joint. Its presentation on radiography is a radiolucent cleft often called a vacuum phenomenon, or vacuum sign. Pneumarthrosis is associated with osteoarthritis and spondylosis.Pneumarthrosis is a common normal finding in shoulders as well as in sternoclavicular joints. It is believed to be a cause of the sounds of joint cracking. It is also a common normal post-operative finding at least after spinal surgery. Pneumarthrosis is extremely rare in conjunction with fluid or pus in a joint, and its presence can therefore practically exclude infection.
Other
Subcutaneous emphysema is found in the deepest layer of the skin. Emphysematous cystitis is a condition of gas in the bladder wall. On occasion this may give rise to secondary subcutaneous emphysema which has a poor prognosis.Pneumoparotitis is the presence of air in the parotid gland caused by raised air pressure in the mouth often as a result of playing wind instruments. In rare cases air may escape from the gland and give rise to subcutaneous emphysema in the face, neck, or mediastinum.
Terminology
The term pneumatosis has word roots of pneumat- + -osis, meaning "air problem/injury".
References
== External links == |
Mixed receptive-expressive language disorder | Mixed receptive-expressive language disorder (DSM-IV 315.32) is a communication disorder in which both the receptive and expressive areas of communication may be affected in any degree, from mild to severe. Children with this disorder have difficulty understanding words and sentences. This impairment is classified by deficiencies in expressive and receptive language development that is not attributed to sensory deficits, nonverbal intellectual deficits, a neurological condition, environmental deprivation or psychiatric impairments. Research illustrates that 2% to 4% of five year olds have mixed receptive-expressive language disorder. This distinction is made when children have issues in expressive language skills, the production of language, and when children also have issues in receptive language skills, the understanding of language. Those with mixed receptive-language disorder have a normal left-right anatomical asymmetry of the planum temporale and parietale. This is attributed to a reduced left hemisphere functional specialization for language. Taken from a measure of cerebral blood flow (SPECT) in phonemic discrimination tasks, children with mixed receptive-expressive language disorder do not exhibit the expected predominant left hemisphere activation. Mixed receptive-expressive language disorder is also known as receptive-expressive language impairment (RELI) or receptive language disorder.
Classification
If assessed on the Wechsler Adult Intelligence Scale, for instance, symptoms of mixed receptive-expressive language disorder may show as relatively low scores for Information, Vocabulary and Comprehension (perhaps below the 25th percentile). If a person has difficulty with specific types of concepts, for example spatial terms, such as over, under, here and there, they may also have difficulties with arithmetic, understanding word problems and instructions, or difficulties using words at all.
They may also have a more general problem with words or sentences, both comprehension and orally. Some children will have issues with pragmatics – the use of language in social contexts as well; and therefore, will have difficulty with inferring meaning. Furthermore, they have severe impairment of spontaneous language production and for this reason, they have difficulty in formulating questions. Generally, children will have trouble with morphosyntax, which is word inflections. These children have difficulty understanding and applying grammatical rules, such as endings that mark verb tenses (e.g. -ed), third-person singular verbs (e.g. I think, he thinks), plurals (e.g. -s), auxiliary verbs that denote tenses (e.g. was running, is running), and with determiners (the, a). Moreover, children with mixed receptive-expressive language disorders have deficits in completing two cognitive operations at the same time and learning new words or morphemes under time pressure or when processing demands are high. These children also have auditory processing deficits in which they process auditory information at a slower rate and as a result, require more time for processing.
Presentation
Related disorders
Studies show that low receptive and expressive language at young ages was correlated to increased autism symptom severity in children in their early school years. Below is a chart depicting language deficits of children on the autistic spectrum. This table indicates the lower levels of language processing, receptive/expressive disorders, which is more severe in children with autism. When autistic children speak, they are often difficult to understand, their language is sparse and dysfluent, they speak in single, uninflected words or short phrases, and their supply of words is severely depleted. This leads to limited vocabulary while also having deficits in verbal short-term memory.
Management
Children who demonstrate deficiencies early in their speech and language development are at risk for continued speech and language issues throughout later childhood. Similarly, even if these speech and language problems have been resolved, children with early language delay are more at risk for difficulties in phonological awareness, reading, and writing throughout their lives. Children with mixed receptive-expressive language disorder are often likely to have long-term implications for language development, literacy, behavior, social development, and even mental health problems. If suspected of having a mixed receptive-expressive language disorder, treatment is available from a speech therapist or pathologist. Most treatments are short term, and rely upon accommodations made within the environment, in order to minimize interfering with work or school. Programs that involve intervention planning that link verbal short-term memory with visual/nonverbal information may be helpful for these children. In addition, approaches such as parent training for language stimulation and monitoring language through the "watch and see" method are recommended. The watch-and-see technique advises children with mixed receptive-expressive language disorder who come from stable, middle-class homes without any other behavioral, medical, or hearing problems should be vigilantly monitored rather than receive intervention. It is often the case that children do not meet the eligibility criteria established through a comprehensive oral language evaluation; and as a result, are not best suited for early intervention programs and require a different approach besides the "one size fits all" model.
See also
Expressive language disorder
References
External links
Language disorder - children - Medline plus |
Dicheirus | Dicheirus is a genus of beetles in the family Carabidae, containing the following species:
Dicheirus dilatatus Dejean, 1829
Dicheirus obtusus LeConte, 1852
Dicheirus piceus Menetries, 1845
Dicheirus pilosus G. Horn, 1880
Dicheirus strenuus G. Horn, 1868
== References == |
Communication disorder | A communication disorder is any disorder that affects an individuals ability to comprehend, detect, or apply language and speech to engage in dialogue effectively with others. The delays and disorders can range from simple sound substitution to the inability to understand or use ones native language.
Diagnosis
Disorders and tendencies included and excluded under the category of communication disorders may vary by source. For example, the definitions offered by the American Speech–Language–Hearing Association differ from those of the Diagnostic Statistical Manual 4th edition (DSM-IV).Gleanson (2001) defines a communication disorder as a speech and language disorder which refers to problems in communication and in related areas such as oral motor function. The delays and disorders can range from simple sound substitution to the inability to understand or use ones native language. In general, communication disorders commonly refer to problems in speech (comprehension and/or expression) that significantly interfere with an individuals achievement and/or quality of life. Knowing the operational definition of the agency performing an assessment or giving a diagnosis may help.Persons who speak more than one language or are considered to have an accent in their location of residence do not have a speech disorder if they are speaking in a manner consistent with their home environment or that is a blending of their home and foreign environment.
DSM-IV
According to the DSM-IV-TR, communication disorders are usually first diagnosed in childhood or adolescence, though they are not limited as childhood disorders and may persist into adulthood. They may also occur with other disorders.
Diagnosis involves testing and evaluation during which it is determined if the scores/performance are "substantially below" developmental expectations and if they "significantly" interfere with academic achievement, social interactions, and daily living. This assessment may also determine if the characteristic is deviant or delayed. Therefore, it may be possible for an individual to have communication challenges but not meet the criteria of being "substantially below" criteria of the DSM IV-TR.
The DSM diagnoses do not comprise a complete list of all communication disorders, for example, auditory processing disorder is not classified under the DSM or ICD-10.
The following diagnoses are included as communication disorders:
Expressive language disorder – characterized by difficulty expressing oneself beyond simple sentences and a limited vocabulary. Individuals can better understand than use language; they may have a lot to say, but have more difficulty organizing and retrieving the words than expected for their developmental stage.
Mixed receptive-expressive language disorder – problems comprehending the commands of others.
Stuttering – a speech disorder characterized by a break in fluency, where sounds, syllables, or words may be repeated or prolonged.
Phonological disorder – a speech sound disorder characterized by problems in making patterns of sound errors (e.g., "dat" for "that").
Communication disorder NOS (not otherwise specified) – the DSM-IV diagnosis in which disorders that do not meet the specific criteria for the disorder listed above may be classified.
DSM-5
The DSM-5 diagnoses for communication disorders completely rework the ones stated above. The diagnoses are made more general in order to capture the various aspects of communications disorders in a way that emphasizes their childhood onset and differentiate these communications disorders from those associated with other disorders (e.g. autism spectrum disorders).
Language disorder – the important characteristics of a language disorder are difficulties in learning and using language, which is caused by problems with vocabulary, with grammar, and with putting sentences together in a proper manner. Problems can both be receptive (understanding language) and expressive (producing language).
Speech sound disorder – previously called phonological disorder, for those with problems with pronunciation and articulation of their native language.
Childhood-Onset Fluency Disorder (Stuttering) - standard fluency and rhythm of speech is interrupted, often causing the repetition of whole words and syllables. May also include the prolongation of words and syllables; pauses within a word; and/or the avoidance of pronouncing difficult words and replacing them with easier words that the individual is better able to pronounce. This disorder causes many communication problems for the individual and may interfere with social communication and performance in work and/or school settings where communication is essential.
Social (pragmatic) communication disorder – this diagnosis described difficulties in the social uses of verbal and nonverbal communication in naturalistic contexts, which affects the development of social relationships and dialogue comprehension. The difference between this diagnosis and autism spectrum disorder is that in the latter there is also a restricted or repetitive pattern of behavior.
Unspecified communication disorder – for those who have symptoms of a communication disorder but who do not meet all criteria, and whose symptoms cause distress or impairment.
Examples
Examples of disorders that may include or create challenges in language and communication and/or may co-occur with the above disorders:
autism spectrum disorders - autistic disorder, pervasive developmental disorder not otherwise specified (PDDNOS), and Asperger disorder – developmental disorders that affect the brains normal development of social and communication skills.
expressive language disorder – affects speaking and understanding where there is no delay in non-verbal intelligence.
mixed receptive-expressive language disorder – affects speaking, understanding, reading and writing where there is no delay in non-verbal intelligence.
specific language impairment – a language disorder that delays the mastery of language skills in children who have no hearing loss or other developmental delays. SLI is also called developmental language disorder, language delay, or developmental dysphasia.
Sensory impairments
Blindness – A link between communication skills and visual impairment with children who are blind is currently being investigated.
Deafness/frequent ear infections – Trouble with hearing during language acquisition may lead to spoken language problems. Children with frequent ear infections may temporarily develop problems pronouncing words correctly. Some of the above communication disorders can occur with people who use sign language. The inability to hear is not in itself a communication disorder.
Aphasia
Aphasia is loss of the ability to produce or comprehend language. There are acute aphasias which result from stroke or brain injury, and primary progressive aphasias caused by progressive illnesses such as dementia.
Acute aphasias
Expressive aphasia also known as Brocas aphasia, expressive aphasia is a non-fluent aphasia that is characterized by damage to the frontal lobe region of the brain. A person with expressive aphasia usually speaks in short sentences that make sense but take great effort to produce. Also, a person with expressive aphasia understands another persons speech but has trouble responding quickly.
Receptive aphasia also known as Wernickes aphasia, receptive aphasia is a fluent aphasia that is categorized by damage to the temporal lobe region of the brain. A person with receptive aphasia usually speaks in long sentences that have no meaning or content. People with this type of aphasia often have trouble understanding others speech and generally do not realize that they are not making any sense.
Conduction aphasia
Anomic aphasia
Global aphasia
Primary progressive aphasias
Progressive nonfluent aphasia
Semantic dementia
Logopenic progressive aphasia
Learning disability
Dyscalculia – an impairment in the systems used in communicating numbers
Dyslexia – an impairment in systems used in reading
Dysgraphia – an impairment in the systems used in writing
Speech disorders
cluttering - a syndrome characterized by a speech delivery rate which is either abnormally fast, irregular, or both.
dysarthria - a condition that occurs when problems with the muscles that helps a person to talk make it difficult to pronounce words.
esophageal voice - involves the patient injecting or swallowing air into the esophagus. Usually learnt and used by patients who cannot use their larynges to speak. Once the patient has forced the air into their esophagus, the air vibrates a muscle and creates esophageal voice. Esophageal voice tends to be difficult to learn and patients are often only able to talk in short phrases with a quiet voice.
lisp - a speech impairment that is also known as sigmatism.
speech sound disorder - Speech-sound disorders (SSD) involve impairments in speech-sound production and range from mild articulation issues involving a limited number of speech sounds to more severe phonologic disorders involving multiple errors in speech-sound production and reduced intelligibility.
stuttering - a speech disorder in which sounds, syllables, or words are repeated or last longer than normal. These problems cause a break in the flow of speech (called disfluency).
See also
References
Further reading
Cherney LR, Gardner P, Logemann JA, et al. (2010). "The role of speech-language pathology and audiology in the optimal management of the service member returning from Iraq or Afghanistan with a blast-related head injury: position of the Communication Sciences and Disorders Clinical Trials Research Group". J Head Trauma Rehabil. 25 (3): 219–24. doi:10.1097/HTR.0b013e3181dc82c1. PMID 20473095. S2CID 8929365.
Wong PC, Perrachione TK, Gunasekera G, Chandrasekaran B (August 2009). "Communication disorders in speakers of tone languages: etiological bases and clinical considerations". Semin Speech Lang. 30 (3): 162–73. doi:10.1055/s-0029-1225953. PMC 2805066. PMID 19711234.
External links
Communication Disorders
Aphasia - National Institute on Deafness and Other Communication Disorders (NIDCD)
Dysgraphia - National Institute on Deafness and Other Communication Disorders Archived 2016-12-02 at the Wayback Machine
Voice and Speech Disorder Online Community (VoiceMatters.net)
List of communication disorder related links
Child Language Disorders |
Vascular access steal syndrome | In nephrology, vascular access steal syndrome is a syndrome caused by ischemia (not enough blood flow) resulting from a vascular access device (such as an arteriovenous fistula or synthetic vascular graft–AV fistula) that was installed to provide access for the inflow and outflow of blood during hemodialysis.
Signs
Pallor
Diminished pulses (distal to the fistula)
Necrosis
Decreased wrist-brachial index (ratio of blood pressure measured in the wrist and the blood pressure measured in the upper arm), especially if below 0.6
Symptoms
Pain distal to the fistula.Symptoms are graded by their severity:
Grade 0: No symptoms of steal
Grade 1: Mild - cool extremity, improvement in hand pulse with access occlusion
Grade 2: Moderate - Ischemic symptoms during dialysis
Grade 3: Severe - Ischemic hand pain outside of dialysis; Ulcers or gangrene of the fingers
Diagnosis
History and physical exam - relief of symptoms with compression of the fistula on exam is highly suggestive of steal
Arteriography
Duplex ultrasound
Treatment
The fistula flow can be restricted through banding, or modulated through surgical revision.
Revascularization techniques
Distal Revascularization and Interval Ligation (DRIL) procedure
PAI (Proximalization of the Arterial Inflow)
RUDI (Revision Using Distal Inflow)
Banding techniques
Narrowing suture
Plication
Minimally invasive MILLER banding
Tapering
Surgical bandingIf the above methods fail, the fistula is ligated, and a new fistula is created in a more proximal location in the same limb, or in the contralateral limb.
Incidence
DASS occurs in about 1% of AV fistulas and 2.7-8% of PTFE grafts.
Terminology
Within the contexts of nephrology and dialysis, vascular access steal syndrome is also less precisely just called steal syndrome (for short), but in wider contexts that term is ambiguous because it can refer to other steal syndromes, such as subclavian steal syndrome or coronary steal syndrome.
See also
Terms for anatomical location
== References == |
Dhat syndrome | Dhat syndrome (Sanskrit: धातु दोष, IAST: Dhātu doṣa) is a condition found in the cultures of South Asia (including Pakistan, India, Bangladesh, Nepal, and Sri Lanka) in which male patients report that they suffer from premature ejaculation or impotence, and believe that they are passing semen in their urine. The condition has no known organic cause.In traditional Hindu spirituality, semen is described as a "vital fluid". The discharge of this "vital fluid", either through sex or masturbation, is associated with marked feelings of anxiety and dysphoria. Often the patient describes the loss of a whitish fluid while passing urine. At other times, marked feelings of guilt associated with what the patient assumes is "excessive" masturbation are noted.
Many doctors view dhat as a folk diagnostic term used in South Asia to refer to anxiety and hypochondriacal concerns associated with the discharge of semen, with discoloration of the urine, and feelings of weakness and exhaustion.
Dhat is thought to be a culture-bound syndrome similar to jiryan (South-East Asia), prameha (Sri Lanka), and
shenkui (China). Dhat syndrome might be related to other post-orgasmic diseases, such as post-coital tristesse (PCT), postorgasmic illness syndrome (POIS), and sexual headache.
Signs and symptoms
Young males are most often affected, though similar symptoms have been reported in females with excessive vaginal discharge or leucorrhea, which is also considered a "vital fluid". In addition, there are symptoms of fatigue and weakness. Patients with Dhat condition most normally ascribe their semen misfortune (secretion of semen in urine) to reasons like inordinate masturbation, sensual dreams, and unreasonable sexual longing. Nocturnal emission and secretion of semen in urine are considered to be the most widely recognized symptoms of semen misfortune. Patients with Dhat condition frequently dread the result of semen misfortune and regularly have the conviction that it will lead to decrease in sexual performance. The most widely recognized side effects in patients with Dhat condition are shortcoming of the body, sluggishness, low energy, and low temperament. Premature ejaculation and impotence are commonly seen. Other somatic symptoms like weakness, easy fatiguability, palpitations, insomnia, low mood, guilt and anxiety are often present. Males sometimes report a subjective feeling that their penises have shortened. These symptoms are usually associated with an anxious and dysphoric mood state. Another sign of this syndrome is white discharge. According to Ayurvedic, an Indian medical system, men who have experienced this have shown signs of anxiety issues. This disease is a culture bound syndrome. Semen loss is generally viewed as taboo and harmful. It is also associated with a lower socioeconomic class. Being able to produce semen is viewed as longevity of ones health and certain powers. In Indian culture, it is important for a man to produce semen.
Treatment
Cognitive behavioral therapy is the mainstay of treatment. At other times counseling, anti-anxiety and antidepressant medications have been shown to be of use. Doctors have found that antidepressant (PDE-5 inhibitors) medicines have shown positive results in controlling the Dhat syndromes psychological causes."
Epidemiology
Dhat syndrome has been reported throughout South Asia in several communities."
History
The term Dhat gets its origin from the Sanskrit word Dhatu (धातु), which, according to the Sushruta Samhita, means "elixir that constitutes the body". Indian doctor Narendra Wig coined the term Dhat syndrome in 1960 and described it as being characterized by vague psychosomatic symptoms of fatigue, weakness, anxiety, loss of appetite, guilt, and sexual dysfunction, attributed by the patient to loss of semen in nocturnal emission, through urine or masturbation. Literature describing semen as a vital constituent of the human body dates back to 1500 BC. The disorders of Dhatus have been elucidated in the Charaka Samhita, which describes a disorder called Shukrameha (शुक्रमेह) in which there is a passage of semen in the urine. In China, various names such as (Shen Kuei), Sri Lanka (Prameha) and other parts of South East Asia (Jiryan) symptoms and conditions are similar to dhatus. The International Classification of diseases ICD-10 classifies Dhat syndrome as both a neurotic disorder (code F48.8) and a culture-specific disorder (Annexe 2) caused by "undue concern about the debilitating effects of the passage of semen".
Society and culture
Some doctors believe Dhat syndrome to be either a culture-bound presentation of clinical depression, as a somatized set of symptoms, or a result of Western doctors misinterpretation of patients descriptions of their condition.Dhat syndrome is very common in Nepali culture as well. Most of them come with the complaints of "drops" and become extremely anxious about it and see it as loss of "male power". It is often related with obsessive ruminations and somatoform symptoms. Others see it as a distinct clinical entity which is less culture-bound than these critics assert, and describe it as one form of a syndrome of "semen-loss anxiety" which also occurs in other Eastern cultures as jiryan and shen-kuei, as well as in Western cultures.
Chlamydia infection might also be related to it because of similar symptoms in case of infection of the urethra (urethritis), which is usually symptomatic, causing a white discharge from the penis with or without pain on urinating (dysuria).
See also
Cross-cultural psychiatry
Koro
Shenkui
References
== External links == |
Follicular cyst of ovary | The follicular cyst of the ovary is a type of functional simple cyst, and is the most common type of ovarian cyst.
Signs and symptoms
Its rupture can create sharp, severe pain on the side of the ovary on which the cyst appears. This sharp pain (sometimes called mittelschmerz) occurs in the middle of the menstrual cycle, during ovulation. About a fourth of women with this type of cyst experience pain.Usually, these cysts produce no symptoms and disappear by themselves within a few months.
Pathophysiology
This type can form when ovulation doesnt occur, and a follicle doesnt rupture or release its egg but instead grows until it becomes a cyst, or when a mature follicle involutes (collapses on itself). It usually forms during ovulation, and can grow to about 7 cm in diameter. It is thin-walled, lined by one or more layers of granulosa cell, and filled with clear fluid.
Diagnosis
Ultrasound is the primary tool used to document the follicular cyst. A doctor monitors these to make sure they disappear, and looks at treatment options if they do not.
References
== External links == |
Polioencephalitis | Polioencephalitis is a viral infection of the brain, causing inflammation within the grey matter of the brain stem. The virus has an affinity for neuronal cell bodies and has been found to affect mostly the midbrain, pons, medulla and cerebellum of most infected patients. The infection can reach up through the thalamus and hypothalamus and possibly reach the cerebral hemispheres. The infection is caused by the poliomyelitis virus which is a single-stranded, positive sense RNA virus surrounded by a non-enveloped capsid. Humans are the only known natural hosts of this virus. The disease has been eliminated from the U.S. since the mid-twentieth century, but is still found in certain areas of the world such as Africa.
Signs and symptoms
Signs and symptoms may vary and some individuals may not experience any symptoms at all. The most common reported symptom of polioencephalitis is fatigue. Fatigue is associated with difficulty in attention, cognition, and maintaining wakefulness Some individuals experience psychiatric symptoms that include anxious mood, pain, insomnia, and depressed mood. Confusion and disorientation of time and space have also been reported. Motor symptoms vary more from patient to patient, but can include incoordination and tremors, nystagmus, loss of conjugate eye movements, rigidity and hemiparesis.
Mechanism
The poliomyelitis virus is an enterovirus that enters through the mouth and multiplies in the throat and epithelial cells of the gastrointestinal tract. It will then move to the bloodstream and is carried to the central nervous system. Once in the CNS, the virus will attach to a host cell by binding with a cell surface receptor. The host cell surface receptor is a glycoprotein that has been recently identified as CD155. Once the virus has bound to the host cell, it will penetrate the host cell membrane and begin the replication of its genome. Many cells contain the surface receptor CD155; however, manifestation of this disease does not occur in all cells. The reason for incidence of the disease in only certain areas of the brain such as the brainstem is unknown. Once areas of the brain have been invaded by the virus, inflammation will occur. During inflammation, the brain’s tissues become swollen due to the body’s immune system response to the infection. Fluid, white blood cells, dead cellular debris and inactivated viruses resulting from the actions of the immune response can significantly alter the fluid surrounding healthy neurons. The function of these healthy neurons can decline due to disruptions in the cell membrane affecting electrical properties of the neuron or by interfering with the blood supply causing anoxic cellular damage. Depending on which neurons are damaged will result in a variety of different symptoms.
Diagnosis
If someone is suspected of having polioencephalitis a sample of throat secretions, stool or cerebrospinal fluid is checked for the virus. Blood tests can be done to detect antibodies against viral antigens and foreign proteins. Virus isolation is the most sensitive method and it is most likely to be isolated from stool samples. Once isolated, RT-PCR is used to differentiate naturally occurring strains from vaccine-like strains.
Prevention
The virus is most often spread by person to person contact with the stool or saliva of the infected person. Two types of vaccines have been developed to prevent the occurrence and spread of the poliomyelitis virus. The first is an inactivated, or killed, form of the virus and the second is an attenuated, or weakened, form of the virus. The development of vaccines has successfully eliminated the disease from the United States. There are continued vaccination efforts in the U.S. to maintain this success rate as this disease still occurs in some areas of the world.
Treatment
There is no cure for polioencephalitis so prevention is essential. Many people that become infected will not develop symptoms and their prognosis is excellent. However, the prognosis is dependent on the amount of cellular damage done by the virus and the area of the brain affected. Many people that develop more severe symptoms can have lifelong disabilities or it can lead to death. Supportive treatments include bed rest, pain relievers, and a nutritious diet. Many drugs have been used to treat psychiatric symptoms such as Clonazepam for insomnia and Desvenlafaxine or Citalopram for depressed mood.
Recent research
Research into the mechanism of this disease stalled with the development of the vaccines in the mid-twentieth century. However, with the recent identification of the cell surface receptor CD155 new interest has resurfaced in this disease. Experiments on transgenic mice are investigating the initial sites of viral replication in the host and how the virus moves from the bloodstream into the central nervous system. Research into the host range of the virus has also been of interest. The host range of a virus is determined by the interaction of the virus with host cellular receptors such as CD155. Comparison of the amino acid sequence in the binding domain of the host cell receptor is highly variable among mammalian species. Rapid changes in the sequence of the binding domain have restricted the host range of the poliovirus. Targeting of the brain and spinal cord have also come under investigation. The restricted tropism maybe due to organ specific differences in the initiation of translation by the virus internal ribosome entry site.
== References == |
Pathological jealousy | Pathological jealousy, also known as morbid jealousy, Othello syndrome or delusional jealousy, is a psychological disorder in which a person is preoccupied with the thought that their spouse or sexual partner is being unfaithful without having any real proof, along with socially unacceptable or abnormal behaviour related to these thoughts. The most common cited forms of psychopathology in morbid jealousy are delusions and obsessions. It is considered a subtype of delusional disorder.Overvaluing an idea, which is defined as “an acceptable, comprehensible idea pursued by the patient beyond the bounds of reason. The idea is not resisted and, although it is not a delusion, the patient characteristically attaches utmost importance to investigating and maintaining the partner’s fidelity at great personal disadvantage and to the distress of the partner”. Overvalued ideas are characterized by being existent in the individuals own thoughts, being egosyntonic; meaning that the ideas project the behaviors, values, and feelings that are aligned with the desires and aims of the individuals ego, or consistent with the individuals ideal self-image, the ideas are also amenable to reason but are not resisted.
Definition
This disorder occurs when a person typically makes repeated accusations that their spouse or sexual partner is being unfaithful, based on insignificant, minimal, or no evidence, often citing seemingly normal or everyday events or material to back up their claims.
Unlike other delusional disorders, people who suffer from this disorder have a strong association with stalking, cyberstalking, sabotage, or even violence. It can be found in the context of schizophrenia and delusional disorder, such as bipolar disorder, but is also associated with alcoholism and sexual dysfunction and has been reported after neurological illness (i.e. Parkinsons).
The name "Othello Syndrome" comes from the character in Shakespeares play Othello, who murders his wife as a result of a false belief that she has been unfaithful. Recently, some psychologists and psychiatrists have asserted that Othello was deceived rather than deluded about Desdemonas alleged infidelity and thus did not have ‘the Othello Syndrome’.
Psychiatric history
Presenting difficulties: neurotic or psychotic jealousy
Past psychiatric history: neurotic or psychotic disorders, deliberate self-harm and attempted suicide
Family history: mental illness including pathological jealousy
Relationship history: incorporating both the current and previous relationship and taking account of the quality of the relationships and the difficulties experienced
Forensic history: previous and pending charges and convictions as well as deviant behavior which was not reported or did not result in a charge or conviction (including aggressive behavior and stalking)
Medical history: organic causes which may be responsible for the morbid jealousy (i.e. Parkinsons)
Forms
Obsessions: the individuals own thoughts are egodystonic; they are acknowledged to be senseless, and usually resisted. Jealous thoughts are experienced as intrusive and excessive, and compulsive behavior such as checking up on their partner may follow. Egodystonicity (the distress caused by thoughts that are unwanted and viewed as contrary to conscious wishes) generally varies a large amount between patients and “a continuum from obsessional to delusional, which morbid jealousy has been suggested” (Insel & Akiskal 1986).
Extreme obsessions: much time is taken up by jealous concerns, and there is a great difficulty in putting the concerns out of the mind. Impairment of the relationship, limitation of the partners freedom and checking on the partners behavior may occur. Although a distinction was occasionally difficult to make, the categories of ‘psychotic’ (delusional) and ‘neurotic’ jealousy contained similar proportions (each between one-third and one-half).
Delusions: the individuals own thoughts are egosyntonic; they are regarded as true, and not resisted. Some authors compare morbid jealousy to a delusional state (e.g. Enoch & Trethowan, 1979). Beliefs may include the morbidly jealous subjects suspicion that: 1. he or she is being poisoned or given some substance(s) to decrease sexual potency by the partner, 2. that the partner has contracted a sexually transmitted disease from a third party 3. is engaging in sexual intercourse with a third party while the subject sleeps.
Causes
Psychological
There are many psychological causes that go along with morbid jealousy. Some people equate morbid jealousy with a delusional state. “Delusions of infidelity exist without any other psychopathology and may be considered to be morbid jealousy in its ‘purest’ form” (Kingham and Gordon). For morbid jealousy to occur ones memories are subconsciously changed and their partners actions are misinterpreted as well to the extent that the person is absolutely convinced of betrayal from the partner. It is thought that even some brain disorders might eventually lead to delusions of betrayal. It has also been recorded by Cobb (1979) “that morbid jealousy may be present with all types of cerebral insult or injury.” "It has been suggested that morbid jealousy may potentially arise in response to reduced sexual function”. Cobb (1979) drew attention to the elderly man whose waning sexual powers were insufficient to satisfy a younger wife.
Mullen (1990) considered morbid jealousy to be associated with four features:
An underlying mental disorder emerges before or with the jealousy
The features of the underlying disorder coexist with the jealousy
The course of morbid jealousy closely relates to that of the underlying disorder
The jealousy has no basis in reality
Personality
People who are very insecure, or even fearful, are more likely to become anxious, or question their partners commitment to them. “Insecure attachment style correlates strongly with borderline personality disorder” (Kingham and Gordon).
Environmental
Some people even believe that someone who is morbidly jealous might suspect that he or she is being drugged or given some kind of substance that might decrease their sexual potency, or they might even be under the impression that their significant other has somehow received a sexually transmitted disease from another person while the subject is unaware.
Epidemiology
There is no known prevalence of morbid jealousy; currently there is no community survey tracking its existence in individuals. As of late, it is considered to be a rare occurrence. Still, many counselors encounter cases of morbid jealousy. Some clinicians may never be able to treat this condition due to other dominating psychopathologies present within the jealous person that call for more attention.
Men and women differ dramatically when it comes to morbid jealousy. Men who suffer from morbid jealousy are more likely than women to use violence and also are more likely to harm or kill with their hands rather than a blunt object. Women on the other hand, when using violence, tend to use a blunt object or knife. Men focus on the rivals status and resources when it comes to the threat of jealousy they fear. Women tend to become more jealous of a potential threat on their rivals youth and physical attractiveness.
Triggers
For men the strongest trigger is sexual infidelity and with women the strongest trigger is emotional infidelity. If partner-related violence does not stop infidelity from happening, the male mate will sometimes resort to suicide instead. The final resort to stopping infidelity inside of morbid jealousy is to commit partner murder. Women are much less likely to kill their partner, unless it is in self-defense. Morbid jealousy can occur in a number of conditions such as chronic alcoholism, addiction to substances other than alcohol (i.e. cocaine, amphetamines, marijuana.), organic brain disorders (i.e. Parkinsons, Huntingtons), schizophrenia, neurosis, affective disturbances or personality disorders.
Associated drug and alcohol use
Alcohol and drug misuse has a well-recognized association with morbid jealousy. “In two studies, morbid jealousy was present in 27% and 34% respectively of men recruited from alcohol treatment services” (Shrestha et al., 1985; Michael et al., 1995). Amphetamine and cocaine increase the possibility of a delusion of infidelity that can continue after intoxication stops. (Shepherd, 1961).
Assessment
In an attempt to counsel or treat the morbid jealousy of an individual, proper and thorough assessment must be employed. This approach is broad in nature, but necessary so as to provide adequate information that will aid in the possible reparation of a dynamic containing a morbidly jealous person. To begin, a careful history should be taken of both partners if possible; separate and together. It is imperative that a full and detailed psychiatric history and mental state examination be recorded for the jealous partner; doing so may enable one to distinguish whether the jealousy is obsessional or delusional in nature. It is also possible that the jealousy may be the result of a thought that has been given too much importance. Considering that jealousy is a very delicate issue, any reference made to it should be approached carefully and with tact. It must be kept in mind that the jealous individual may be displacing blame for their issues onto their partner and their alleged infidelity as opposed to their own behavior. If there is any history of relevant or related mental illness and substance misuse it should be noted as it may possibly be a contributing or aiding factor. In order to get the best grasp on the issues and begin positive progression, multiple interviews should be held to assess the marital relationship.After completing the assessment, it is best to deliver information about risk with both individuals in the relationship. Due to confidentiality, the patient should give consent for this information to be shared unless there is a risk to another individual and it is serious and immediate. This is the only case in which confidentiality is invalid. The professional should ensure that all necessary steps are taken to guarantee the safety of a potential victim, keeping in mind that it is possible that authorities may have to be alerted regarding the matter. If the professional has reason to believe that there is a high risk of harm to themselves or another person, the individual who is morbidly jealous should be admitted to hospital as soon as possible to prevent any negative outcomes for any parties involved.
Management
Morbid jealousy encompasses various psychiatric states and the best way to approach treatment depends on the symptoms that are observed in the individual. Therefore, prognosis and outcomes vary from person to person and depends on the situation and the complexities of the interpersonal relationships being observed. Also, other issues that may exacerbate the negative aspects of the environment created by jealous behavior need to be addressed in order to begin reparations. For example, if alcoholism plays a role in the behavior of the morbidly jealous individual, treatment of their addiction can positively affect their progress in trying to change their jealous nature. While psychotherapy can be an effective method of treating morbidly jealous persons, it is not sufficient when the nature of their illness is more serious. It is not possible to say that there is one form of treatment that is superior over all those that are currently available. Even though this may be true, cognitive behavioral therapy is the treatment that has proven to be most effective.Medical
Treatment of the primary psychiatric condition
Antipsychotic medication
Antidepressant medicationPsychological
Psycho education for the affected person and the partner
Behavioral therapy
Cognitive therapy
Individual psychotherapy
Insight oriented psychotherapies
Family therapy
Couple therapySocial
Geographical separation of the partners
Social work involvement for child protection issues
Alcohol and substance misuse treatment
Risks associated
Confirmatory behaviors
When suspicions of the partners fidelity arise, they quickly become all that is thought about. Certain behaviors, such as interrogation of the partner, repeated telephone calls to work and surprise visits, stalking behavior, setting up recording devices in the home or work, or hiring a private detective to follow the partner, are all common in trying to determine if there is truly infidelity or if it is just perceived. Individuals that are jealous may take drastic measures, such as searching the partners clothing and belongings, look through diaries and other communication methods (email, text messaging), or examining bed sheets, undergarments and even genitalia for evidence of sexual activity.
Harm to self
Suicidal thoughts are common in morbid jealousy, especially because of its association with depression and substance abuse.
Risk to others
Violence can occur in any relationship tainted with jealousy, either normal or morbid jealousy. In a recent study of jealousy by Mullen & Martin in 1994, 15% of both men and women reported that at some time they had been “subjected to physical violence at the hands of a jealous partner.” Culturally, jealousy may be even used to “justify violence towards partners.” Victims in a homicide case are most likely to be current or ex-partners in both female and male perpetrators.
When a partner repeatedly denies infidelity, this may provoke anger and extreme violence. On the other hand, the partner that is suffering may give up and give a false confession, which in turn most likely will provoke rage in the jealous individual. In the U.S. a sample was taken of 20 participants with delusional jealousy. 19 were male and Silva (1998) found that 13 had threatened to kill their spouse because of their perceived infidelity. Of the 13 males, nine actually attacked their spouse. Out of the 20, a weapon was used by three of them, and 12 had harmed their spouse.
A presence of paranoid delusions and hallucinations of injury to the spouse were most often associated with violence. This suggests that individuals that suffer from delusional jealousy that partake in violence may be solely driven by psychotic phenomena. A higher risk of assault was associated with alcohol consumption.
Risk to children
Children that live in a household with a parent that suffers from morbid jealousy may suffer emotional and/or physical abuse as a direct result of the actions made by the parent. Children may also accidentally overhear arguments or witness physical violence between their parents. They could even be potentially accidentally injured during assaults. The morbidly jealous parent may employ a child or more than one to spy on the other parent. It is not out of the question for a child to witness a homicide or suicide where their parent is the victim.
See also
References
Sources
Enoch, D. & Ball, H. (2001) The Othello Syndrome. In Enoch, D. & Ball, H. Uncommon psychiatric syndromes (fourth edition) pp50–73. London: Arnold. ISBN 0-340-76388-4
Further reading
Easton, J.A.; Shackelford, T.K.; Schipper, L.D. (2008). "Delusional Disorder--Jealous Type: How Inclusive are the DSM-IV Diagnostic Criteria?" (PDF). Journal of Clinical Psychology. 64 (3): 264–275. doi:10.1002/jclp.20442. PMID 18257054.
Easton, J. A.; Schipper, L. D.; Shackelford, T. K. (2007). "Morbid jealousy from an evolutionary psychological perspective" (PDF). Evolution and Human Behavior. 28 (6): 399–402. doi:10.1016/j.evolhumbehav.2007.05.005. Archived from the original (PDF) on 2008-12-02. |
Traumatic spondylopathy | Traumatic spondylopathy is a form of dorsopathy.
References
== External links == |
Spinocerebellar ataxia type 1 | Spinocerebellar ataxia type 1 (SCA1) is a rare autosomal dominant disorder, which, like other spinocerebellar ataxias, is characterized by neurological symptoms including dysarthria, hypermetric saccades, and ataxia of gait and stance. This cerebellar dysfunction is progressive and permanent. First onset of symptoms is normally between 30 and 40 years of age, though juvenile onset can occur. Death typically occurs within 10 to 30 years from onset.
SCA1 is typically inherited from the parents in an autosomal dominant regime; the children of a person with the disease have a 50% chance of inheriting it themselves, and new mutations can occur in some cases. It is caused by an expanded number of trinucleotide repeats in the polyglutamine tract of the ATXN1 gene, which encodes the ataxin 1 protein. This expansion results in a larger than normal number of repeats of the nucleotide sequence cytosine, adenine, guanine, or CAG, in the gene which, in turn, results in a larger than normal number of consecutive glutamine amino acid residues in the protein. This mutant protein causes degradation in certain types of neurons, like Purkinje neurons, which are common in the cerebellum, spinal cord, and related parts of the brain. While the mechanism is not fully understood, it is suspected that changes in the interactions between ataxin 1 and other proteins result in a toxic gain of function.
The mutation can be detected before or after the onset of symptoms by genetic testing. Currently, no cure for SCA1 is known, so treatment of the disease focuses primarily on management of symptoms to maintain quality of life, focusing on physical therapy to retrain and replace lost functions. Research to develop treatments is ongoing and in addition to conventional pharmaceutical treatment, SCA1 has been the subject of research into more advanced treatment options such as gene therapy and stem cell therapy. Worldwide, an expected 1 to 2 people in 100,000 have spinocerebellar ataxia type 1, however, the prevalence varies between populations and is often linked to the founders effect.
Ataxia as a symptom has been known since the mid 19th century and the heterogeneous group of diseases now known as spinocerebellar ataxias was the subject of extensive research in the latter part of that century. Advances in molecular genetics in the 20th century allowed distinct causes of these diseases to be identified. In the early 1990s the gene causing SCA1 was localized to the human leukocyte antigen complex on chromosome 6 and by 1993, ataxin 1 was identified as the causative gene. It was the first spinocerebellar ataxia-causing gene to be localized and identified.
Signs and symptoms
Ataxia refers to a lack of coordinated muscle movements that include gait abnormality and is the cerebellar sign that typifies all spinocerebellar ataxia (SCA) types, though individuals with SCA1 also develop pyramidal and bulbar signs as the disease progresses. The average age of onset is between 30 and 40 years of age, though exceptions exist. From the first symptoms, duration is typically between one and three decades, where earlier onset correlates with faster progression.Spinocerebellar ataxia 1, like other SCAs, often causes dysarthria, a motor disorder of speech often manifest as slurring of words; pathological nystagmus, a disorder in which eyes drift involuntarily affecting vision; and gait and balance issues. SCA1 is also commonly present with dysphagia, a swallowing disorder that can cause choking while eating and drinking; and hypermetric saccades, where the eye tends to move faster or further than intended as it tracks an object or moves from one focus to another. As the disease progresses, more severe neurologic symptoms can appear like dysmetria, where limb movements consistently overshoot the desired position; dysdiadochokinesia, where repeated body movements become uncoordinated; or hypotonia, where muscles atrophy. While new symptoms appear as SCA1 progresses, nystagmus may disappear as eye movements and saccades slow down. Fatality may ultimately be caused by loss of bulbar functions, but complications from symptoms, such as pneumonia from swallowing problems, or trauma from falls, can be fatal as well. The severity and exact phenotype of these symptoms may vary between types of SCA. SCA 1 dysarthria may vary in severity depending on the task and is often associated with more strained, strangled or harsh sounding vocalization than that of other disorders.Because of the significant variance between cases of SCA1, typical signs and symptoms may appear alongside more subtle or rare symptoms. Maculopathy has been reported in rare cases, and may be linked effects from the mutation on the ATXN1 locus on genes in neighboring loci. Task specific dystonias have been reported in individual cases, often in the form of writers cramps or cervical dystonia.SCAs can also be detected before serious atrophy with electrophysiologic techniques, using electrodes on the scalp to detect changes in electric potential within the brain in response to sensations or movements. Individuals with SCA1 often exhibit abnormal brainstem auditory evoked potential, including prolonged latency and absent or poorly defined waveforms, with one study reporting 73.3% of test subjects exhibiting abnormalities. The same study also found abnormalities in visual evoked potential and median somatosensory evoked potential in some SCA1 persons. These results were similar to those exhibited in other SCAs and differences between the SCAs were not statistically significant, so electrophysiologic techniques cannot replace genetic testing for specific diagnoses of SCAs.All SCAs cause atrophy in various neural tissues that are detectable using magnetic resonance imaging, computed tomography, or other imaging techniques. In SCA1 some degradation in the grey matter of the cerebellum and brain stem can sometimes be detected in presymptomatic individuals with the expansion in ATXN1. Typically, grey matter loss can be observed in cerebellar vermis in all lobules of the cerebellum and in the paramedian portions of both hemispheres. White matter loss can also be observed in the middle cerebellar peduncles. The volume loss can be correlated to severity and duration.An estimated 77% of cases of progressive cerebellar disease are reported to have one or more mental health disorders, and 19% exhibit cognitive disorders. These estimates are consistently higher than the portion with mental health disorders in the general population, but still follow other general patterns, like correlations between depression frequency and sex or age. It is unclear if depression can be linked causally to cerebellar degeneration; one study reports data consistent with depression primarily being a response to the disability, not a symptom of it, while another reports evidence that depression may have a causal link; prevalence of depression varies differently between SCA types than does the rate of progression of disability.
Genetics
Spinocerebellar ataxia type 1 is caused by a mutation in the ATXN1 gene. This mutation is passed down through an autosomal dominant inheritance pattern, meaning that the disease does not skip generations, at least one parent must have the disease for the children to inherit it, and that the odds of any given child inheriting SCA 1, regardless of gender or other phenotypes, is 50% if the affected parent is heterozygous.: 26 The ATXN1 gene on chromosome 6 encodes the ataxin 1 protein, which is used in signaling pathways and gene regulation, and is heavily expressed in Purkinje neurons. The coding region for Ataxin 1 (6p22.3) contains a polyglutamine tract of variable length. SCA1 is present in individuals where the region on at least one copy of chromosome 6 contains 39 or more continuous repeats of glutamine in which more repeats are correlated to earlier onset and faster progression. Histidine interruptions in the polygluatamine tract can mitigate or prevent SCA1.SCA1 is known to exhibit genetic anticipation, where one generation with the disease may exhibit earlier onset and faster progression than the previous generation. This is typically caused by expansions in the polyglutamine tract between generations and is more common in cases of patrilineal inheritance. This non-Mendelian inheritance is similar to that observed in Huntingtons disease and is believed to be caused by differences in various mechanisms in gamete production between the sexes that result in increased mosaicism in the male germline. DNA with CAG repeats are prone to forming secondary structures, including hairpin loops and R-loops, which can result in mutations and mosaicism if DNA repair mechanisms fail. These secondary structures cause somatic mosaicism by lagging DNA polymerase in Okazaki fragments and by disrupting DNA mismatch repair, base excision repair, nucleotide excision repair and double strand break repair mechanisms. The mechanism for germline expansions is not well understood, but it is believed that only mismatch repair pathways effect germline instability and the MSH2 repair protein has been linked to expansions in male gametes in mice models.
Pathophysiology
Normal ataxin 1 is intimately involved in a number of signaling pathways, in protein ubiquitination, RNA metabolism, in transcription regulation, protein transformation, and protein stabilization.: 149–165 Among other interactions, it forms a transcription complex with Retinoid-related Orphan nuclear-receptor transcription factor α (RORα) following interactions with an activator, Histone acetyltransferase KAT5, sometimes referred to as TIP60, and it is in the signaling mediated by metabotropic glutamate receptor 1 (mGluR1). Resonant Recognition Modeling of the ataxin 1 protein has shown possible binding sites for growth factor independent transcription repressor 1 (Gfi-1). The predictions of this computational model reveal an interaction that could play a role in SCA1 pathology, because the Gfi-1 protein is known to cause selective degradation of Purkinje cells.: 149–165 It is the extensive involvement of ataxin 1 in many different functions that make understanding the biochemical pathophysiology of its mutant form difficult to identify and understand.: 15 The mechanism by which expanded CAG repeat regions in ataxin 1 cause neuronal degeneration is unclear. It was historically believed to be caused by aggregation and deposition of the affected protein similar to other polyglutamine expansion diseases, however rodent model studies have shown significantly later formation of nuclear inclusions of mutant proteins in cerebellum and spinal cord neurons than in cortical and hippocampal neurons, which typically show only mild degeneration in SCA1 persons, suggesting a more complicated mechanism. Ataxin-null mice are shown to exhibit reduced motor and spatial learning, suggesting ataxin 1 plays a role in synaptic plasticity and interactions between the motor neurons and the hippocampus. However mice lacking both copies of ataxin 1 do not develop progressive neurological symptoms or show signs of atrophy, suggesting that toxicity of the mutated protein, not loss of function, is the main mechanism for SCA1 pathology. A comparison of mRNA between ataxin null mice and mice with ataxin1154Q/+ shows that there are common changes in gene expression, including upregulation of genes known to be repressed by an ataxin 1/CIC complex. This suggest that, while not the primary mechanism, a loss of ataxin 1 function contributes to the pathogenesis of SCA1. While the ataxin 1/CIC complex losses some of its regulatory function with expanded ataxin 1, CIC knockout mice do not show degeneration, suggesting interactions between ataxin 1 and CIC mediate most of the toxic effects. Mutant ataxin-1 also known to alter the neural circuitry of the developing cerebellum, which may lead to later vulnerability of Purkinje cells and suggests the existence of non-cell autonomous toxicity.The various interactions of ataxin 1 lead to many possible factors that can exasperate or moderate toxicity of its mutant form. Wild type ataxin 1 is quickly degraded in the cytoplasm, but can be stabilized by phosphorylation and 14-3-3 binding as needed by the cell. SCA1 positive mice haplodeficient in 14-3-3ε+/- were shown not to exhibit cerebellar degeneration but still exhibited lethal bulbar degeneration, suggesting that cerebellar atrophy may be related to increased stability of the expanded ataxin 1 protein and that there may be different pathogenic mechanisms for different regions of the brain. The site of phosphorylation is the serine at the 776th residue in ataxin 1. Similar to those that lack 14-3-3 proteins, mice with this residue replaced with alanine do not exhibit cerebellar syndrome. Similarly, removal of the AXH domain from ataxin 1 prevents aberrant interactions with growth factor independent transcription repressor 1 that leads to GFI1 degradation in the proteasome. The expanded polyglutamine region results in increased affinity of the ataxin 1 AXH domain for certain transcription factors, and this effect is believed to play a significant role in ataxin 1 toxicity. Another protein shown to have significant interactions with ataxin 1 is the leucine-rich acidic nuclear protein or LANP. Its function is unknown, but it is predominately expressed in the same neurons as ataxin 1 and has been shown to localize in the nuclei of these neurons at the same substructures as ataxin 1. LANP only interacts with the polyglutamine region of ataxin 1, and its interactions are stronger as the number of glutamine residues increases, so the two proteins are likely vital to each others functions in neurons and LANP may also facilitate pathology of mutant ataxin 1 proteins. Ataxin 1 like, also called Brother of Ataxin 1 or Boat, has significant interactions with ataxin-1 and many associated proteins, like N-CoR. Ataxin 1 like has reduced expression in transgenic mice models and has been shown to moderate cytotoxicity of ataxin-1.Toxicity from the mutated protein causes degradation in neural tissues. This includes loss of dendritic aborization, or branching, early in disease progression and eventual atrophy of brain tissues in later stages. SCA1 causes moderate degradation of a variety of tissues, including both hemispheres of the cerebellum, the cerebellar vermis, the pons, and the brain stem. It also causes mild atrophy in cerebral cortical tissue. A recent study also found significant atrophy of the spinal cord and flattening of the posterior column and found a correlation between cord area, CAG repeats, and SARA scores in SCA1. Central nervous system tissues, unlike that of bone, muscle, or skin, lacks mechanisms for endogenously generating and differentiating new cells and for restoring long distance patterns and connections as they are lost, so as degeneration progresses the losses are permanent.
Diagnosis and evaluation
Most SCAs and other ataxic disorders are clinically heterogeneous, meaning clinical signs and symptoms are similar between diseases and distinguishing between diseases with a neurologic exam alone is difficult. In symptomatic persons, diagnosis of ataxia related disorders often requires a neurological exam, evaluation of neurological and family history, and molecular genetic testing. Absence of a family history does not exclude hereditary causes like spinocerebellar ataxia type 1 because family history may not have been collected or may be unavailable for certain individuals and new cases may originate from anticipation in an allele with a mutable number of repeats.: 2–4 To establish a diagnosis, molecular genetic testing is currently commercially available for 14 SCA types, including SCA1. In cases where SCAs are not present in family history or where family history is unavailable, testing for the 4 most common SCAs will return positive results for 50% of suspected SCA cases.: 11 Individuals who are at risk of inheriting SCA1 but are currently presymptomatic can also be screened with molecular genetic testing.
Genetic testing
Genetic testing is the only definitive way to differentiate between spinocerebellar ataxia types because of the similarity between clinical characteristics of these diseases and the large variance between cases. Genetic testing is available for many SCA types, including the relatively common types SCA1, 2, 3, 6, and 7; and the less common SCA8, 10, 12, 14, and 17. However, genetic testing is high in cost and has a low diagnostic yield, with positive diagnoses being found in only 24% of tests ordered by a subspecialist and 10% overall.Genetic testing can be administered at various stages of disease progression. When genetic testing is administered after the onset of symptoms, the test is said to be diagnostic; in adults prior to onset of symptoms it is presymptomatic, and the test can be performed for prenatal or preimplantation diagnoses. The European Molecular Quality Genetics Network (EMQN) recommends criteria for each type, which must be met before testing can begin. The EQMN recommends that labs receive a written clinical evaluation of symptoms by a neurologist and a disclosure of family history, or lack of history, before initiating diagnostic genetic testing. Because no preventative or curative treatments are known for SCAs, genetic testing for at risk individuals is not recommended for all cases, and is typically issued on an individual basis. Presymptomatic, prenatal, and preimplantation testing are typically requested through a genetic counsellor and require existing family history and documentation of informed consent of the consultand. Spinocerebellar ataxia type 1 was one of the first late onset diseases for which presymptomatic testing was demonstrated effective and predictive; prior to the development of testing for SCA1, Huntingtons disease was the only similar disease for which presymptomatic testing was available.Molecular genetic testing of SCAs must be able to differentiate samples with the pathogenic allele from those without and be able to accurately measure the number of repeats in repeat expansion disorders. Capillary electrophoresis (CE) is one method that has met these criteria and is recommended by the EMQN. Another method that is common is polyacrylamide gel electrophoresis (PAGE). Both methods require amplification of all loci of interest for a given test. Amplification is done using polymerase chain reactions or PCR. The choice of primers can allow either for a single gene to be amplified or for many genes to amplified for use in a multiplex assay which can save time in cases where a panel of many tests may be required. PAGE and CE both use timed cycles of electricity to draw pieces of DNA through a porous polymer, separating analytes by a combination of ionic mobility, size and mass. CE is advantageous over PAGE in that molecular weight measurements like mass spectrometry can be used with analytes, whereas PAGE requires the use of Southern blot to allow comparison to a sequencing ladder. For repeat lengths within the range where interruptions are relevant, assays like CE and PAGE will not determine if the strain is pathogenic and additional testing will be required.
Clinical
No formal diagnostic criteria exist for most SCAs, and genetic testing is the only certain diagnostic method, but clinical examination of signs and symptoms may be vital to distinguishing SCAs from non-genetic ataxias, and from other types of genetic ataxias. Clinical examination can also help distinguish between SCA types to some extent, so genetic tests for certain types can be prioritized over others. Diagnosis of SCAs often begins with the detection of symptoms that suggest a cerebellar disorder, like progressive ataxia or dysarthria, or with recognition of similar symptoms to a case identified in the individuals family history, especially in first or second degree relatives. Many laboratory studies can be used to further narrow the potential cause of ataxia; imaging of brain and spinal cord and various electrophysiology exams may be useful for identifying disease phenotypes and blood and urine studies may rule out acquired causes.: 4 When evaluating ataxic disorders and their treatments, there are numerous tests that a neurologist may perform. Tests may be evaluated individually or follow a scale for evaluating the ataxia. A cerebellar exam may include saying phrases with many consonants to detect scanning speech, detecting horizontal gaze nystagmus by following a finger with the eyes, performing rapid alternating movements like rotating a hand from palm to back repeatedly, testing the Holmes rebound phenomenon, and testing patellar reflex for hypotonia or hypertonia. Common scales include the International Cooperative Ataxia Rating Scale (ICARS) and Scale for the Assessment and Rating of Ataxic Disorders (SARA) for evaluating the severity of ataxia as a symptom. ICARS measures on a 100 scale, where 0 is normal function and 100 is the highest possible impairment, assigning different point values for different tests. The tests are divided into categories evaluating posture and gait, kinetic functions, speech, and oculomotor functions. While these categories create useful categorization to assess which areas need to be focused on in therapies, this redundancy results in a longer test time, which can skew results of tests performed at the end of a session; and can result in contradictory scores. SARA is a shorter exam, evaluated on a scale of 0 to 40, where again zero is normal function and 40 is highest possible impairment. It comprises eight tests: gait, stance, finger chase, finger-to-nose test, fast alternating hand movements, heel-shin slide, and three limb kinectic function tests.
Differential diagnosis
Differential diagnosis of SCAs by clinical methods is difficult because these diseases are clinically heterogenous and there is significant variance between the expression of individual cases. Using clinical information for differential diagnosis is used to prioritize genetic testing not as a stand-alone diagnosis. Many potential differentiating symptoms have been found, and methods of assessing many symptoms and their progression to guide genetic testing have been developed. Even if a specific type of spinocerebellar ataxia cannot be immediately determined clinical history, family history, clinical examination can help distinguish between other ataxias and can help reduce the number of genetic tests needed to identify a type of SCA. Examination of relatives of individuals thought to have sporadic ataxia can often reveal enough family history to identify a transmission mode.There are some common trends that may be useful to discriminate SCAs. SCA1 tends to progress faster than SCA2, 3, and 6, with greater annual change in SARA scores and earlier loss of functions after onset. In the diagnostics of clinical ataxia, imaging may not be useful to distinguish SCA1 from other SCAs as there is significant variance between individual cases and significant overlap between diseases. Vestibulo-ocular reflex can be tested using a video recorded head impulse test or vHIT. In this test, SCA1 typically has normal reflex latency, and does not consistently show a deficit in VOR function, distinguishing it from SCA3 and Friedreichs ataxia. Certain patterns in ocular motor disorders, detectable with video-oculography, appear to typify certain SCA types. While SCA1 was not significantly correlated with a unique pattern, other possible SCAs can be linked and absence of a vertical nystagmus following horizontal head shaking reduces the likelihood of an SCA6 diagnosis, while the absence of a square wave pattern during fixation reduces the likelihood of SCA3.One possible system for the differential diagnosis of SCA types is to record the progression of symptoms and use Bayesian probability to build a predictive model, or a Bayesian classifier, that compares the observed data to trends like those described above to find the likelihood of each diagnosis to be correct. One such Bayesian classifier was shown to accurately predict 78% of SCA cases out of a cohort with known types of SCA. The sensitivity and specificity for SCA1 within this model was 76.9% and 98.2% respectively. Regional variance in prevalence, symptoms and clinical assessment might still limit the use of this system on large scales, though the system may implemented by individual clinics using their own regional data.
Management
There is currently no cure for Spinocerebellar ataxia type 1. However, some of its symptoms may be managed with physical, occupational or speech therapies, lifestyle and dietary changes, or with medications. Managing symptoms will not prevent the disease from progressing but can be important for maintaining quality of life.: 48 It is important to note, however, that many disorders that cause ataxia and related symptoms exist, and that management strategies that work for some, such as vitamin E supplements for certain acquired ataxias, will not work for hereditary ataxias like SCA1 and can be dangerous to a persons health.: 52 Small cohort studies have shown that individuals with cerebellar disorders recover coordination and have lower SARA scores regardless of stage or severity of their ataxia before therapy when they are regularly participating in physiotherapy or exergaming over individuals who are not. These studies suggest that multidomain physical therapy, more focused coordinative training, and exergaming routines all produced improvements in SARA scores equivalent to at least one year of normal progression, 2.2 points or more on average, over the course of several weeks. While these results are promising, larger scale studies may be necessary to validate these results. Overall, physical therapy for individuals with ataxia has modest evidence supporting its efficaciousness, but current practice uses custom treatments without a standard decision making procedure between clinics, which limits the ability to reproducibly assess the quality of routines in literature. Among the earliest developed neurorehabilitation practices is Frenkel exercises, which was developed by Heinrich Frenkel in the mid nineteenth century; these exercises were drawn from contemporary physical medicine and rehabilitation techniques, called medical gymnastics, and from everyday activities, like standing up from a chair, to find exercises which are closely related to the pathology of ataxia and rely on slow practice and on the individuals perseverance to relearn key motor skills, replacing lost proprioception with visual feedback. There are exercises for lower limbs, like extending the legs, and upper limbs, like placing pegs in boards, and depending on the severity of the ataxia can be performed laying down, sitting, or standing up. All exercises often start with simple movements and become progressively more difficult to emulate real world movements affected by the disorder.Common recommendations for persons with dysphagia, or swallowing problems, include pureeing food, replacing difficult to eat foods in the diet, or changing posture during eating. When swallowing problems become severe enough that aspiration pneumonias are frequent or dietary changes fail to prevent weight loss, a feeding tube may be considered.: 82–86 Typically these are percutaneous endoscopic gastrostomy jejunal tubes (PEG-Js), however these do not necessarily lead to a decreased incidence of aspiration, as clogs may result in gastroesphageal reflux which can be aspirated. Direct PEG-Js seem to cause less frequent reflux and have lower incidence of aspiration pneumonia compared to the standard PEG-J procedure. Numerous strategies for treating dysphagia have been investigated including physical exercises like modified Valsalva maneuvers, pharmaceutical treatments focused on treating spasticity, and compensatory practices including adjusting posture and longer chewing. These strategies, like the treatment of many symptoms hereditary ataxias, have small scale evidence for their usefulness but are not yet established by large studies.As with all hereditary diseases, concerns about the impact on family members, especially children, are often very important. Individuals diagnosed with SCA 1 may seek genetic counseling to aid in family planning, developing coping skills, and planning for the future. Persons with SCA 1 may consider in vitro fertilization with preimplantation testing to prevent passing the disease on to their children.
Prognosis
Penetrance for SCA1 is 100% for most alleles, so almost all individuals who have at least one copy of the mutated gene will eventually develop symptoms. At least one case has been reported where penetrance may have been incomplete in a woman with 44 glutamine repeats with histidine interruptions whose father had exhibited symptoms, but herself had not shown symptoms at the age of 66. Individuals with a low number of repeats, around 39 to 55, typically live past reproductive age and can pass on the disease to their children, while high repeats may express juvenile onset and fatality.
Epidemiology
The National Institute of Health reports that SCA1 has a prevalence of approximately 1 or |
Spinocerebellar ataxia type 1 | 2 per 100,000 however a review of literature has shown that these estimates vary significantly from study to study and can be less than 1 per 100,000 or as high as 6 per 100,000. Among all types of SCA, SCA1 is among the most common and the portion accounted for by SCA1 varies between geographic regions, with percentages as high as 40% of all SCA diagnoses in populations in Russia and South Africa being SCA1. In the United States SCA1 accounts for 6% of SCA diagnoses. Overall, SCA1 accounts for 6-27% of all cases dominant ataxias.: 6 Because of its late onset, often appearing after reproductive age, SCA1 exerts low selection intensity, ranking about 0.19 on the Crows index, but intensity may vary with time within a population or family, as anticipation increases the number of CAG repeats. One implication of this is that SCA1 is unlikely to disappear from a population by natural selection alone.Prevalence of each type of SCA varies with geographic region and ethnicity, possibly because of founder effects and historic migration patterns. High prevalence regions include central Poland, where 68% of autosomal dominant cerebellar disorders are SCA1; communities in Tamil Nadu, where up to 7.2% of the population has SCA1 in some small villages; the Tohoku region on the northern portion of Honshu Island, with 24.8% of cases being SCA1; and among Yakut populations in eastern Siberia, with a prevalence 46 per 100,000 in rural populations.
History
Ataxia as a symptom was first described by French neurologist Duchenne de Boulogne in a subject with tabes dorsalis. By the late 19th and early 20th centuries, extensive research into the characterization, cause, and diagnostics of hereditary cerebellar ataxias was underway with the work of several prominent neurologists, including Jean-Martin Charcot, Pierre Marie, Nikolaus Friedreich, Adolph Strümpell, and others. Marie described a number of cases of hereditary, adult onset disease he thought to be clinically distinct from Friedreichs ataxia, spastic paraplegia, and other known types of ataxia, calling the syndrome hereditary cerebellar ataxia, though it became known Maries ataxia.While the hereditary patterns were clearly distinct, there was on-going debate well into the 1940s over whether Maries ataxia was really distinct from Freidreichs ataxia and Strümpells paraplegia and if these categorys themselves represented a single disease or many. This was because of the heterogenous nature of hereditary ataxias, the similarity of symptoms, and the lack of understood biochemical mechanisms. Further frustration with the ambiguity of terms introduced by Marie and Friedreich resulted in the creation of other systems to classify ataxias. Gordon Morgan Holmes and Godwin Greenfield each developed systems of categorizing ataxias, giving rise to categories called olivopontocerebellar atrophy and spinocerebellar degradation, though little consensus between the systems was achieved, and many terms are used interchangeably.In the depression era United States, the Schut family in Minnesota was one family known to carry a hereditary ataxia. Several members of the family actively participated in research and the family consented to post mortem examinations of the brains of several deceased relatives. The disease in the Schut family was found to have an autosomal dominant inheritance pattern, and afflicted the spinocerebellar tract. In 1945, John Schut received free medical school education for his service with the United States Army during the second world war and began his own efforts researching hereditary ataxia.: 90–91 Schut developed ataxia like many of his relatives. In 1957, when Schuts ataxia progressed to a point where he was unable to continue work in regular medical practice, he founded the National Ataxia Foundation with lab space donated by Glenwood Hills Hospital in Minneapolis.: 131 John Schuts nephew, Lawerence Schut, also became an ataxia researcher and contributed to localizing a spinocerebellar ataxia gene to the human leukocyte antigen complex in chromosome 6. The success in linking one of these class of diseases to a locus showed that the classification systems in use were unable to distinguish between diseases with many different causes. Many ataxic disorders which were historically identified as Maries ataxia, olivopontocerebellar atrophy or other names were now reclassified as types of spinocerebellar ataxia, each type numbered in order as a new locus was found. In 1993, the gene and a mutation causing spinocerebellar ataxia type 1 was identified. It was the first genetic defect found known to cause an ataxic disorder.
Research directions
Treatment and mitigation of neurodegenerative disorders is of particular interest to researchers, and several potential options for SCA1 are under investigation. As the pathology of SCA1 is complex, there are several possible approaches to treatment, which include clearance of expanded ataxin 1 proteins, reducing the toxicity of expanded ataxin 1 proteins, suppressing production of ataxin 1, multiple gene therapies, and replacing lost brain cells. Because many SCAs, including SCA1, are polyglutamine diseases and operate by similar mechanisms to Huntingtons disease many promising treatments for Huntingtons disease are being investigated for SCAs as well.
Gene downregulation and silencing
Because spinocerebellar ataxias are often linked to a mutation on a single gene, modifying how the gene is expressed can modify the phenotype. There are several approaches to modifying the expression of mutant proteins, including techniques that completely stop expression, known as gene silencing. In SCA1, pathogenesis requires constant expression of the mutant ATXN1 gene, and silencing has been shown to halt further progression of the disease, clear nuclear inclusions and aggregates and lead to partial recovery of motor functions in rodent models with conditional expression of the gene. The conditional expression of ATXN1 in mice models differs from how the gene would be silenced therapeutically but the results indicate that therapeutic methods of gene silencing may be viable for treatment and management of SCA1. The process that turns coded information in DNA into proteins requires two steps: transcription, in which DNA is used to generate a complementary RNA strand by RNA polymerase, and translation, in which RNA is used to produce a protein by ribosomes. Disrupting either step can slow or prevent the expression of a mutant gene.
Ataxin 1 is involved in a number of signaling pathways and its expression is controlled by signaling pathways. The MAPK/ERK pathway has been shown to activate ataxin 1 expression, and MSK1 also phosphorylates ataxin 1, controlling its localization and degradation. Inhibitors of key proteins in this pathway may be used in combination therapy to potentially decrease expression and lower steady state concentrations of ataxin 1.One technique for disrupting translation, antisense oligonucleotide therapy, which uses single strands of RNA complementary to the target to prevent the target from binding to a ribosome and trigger the degradation of the target, has already begun clinical trials in other neurodegenerative disorders with many different delivery mechanisms. A similar technique is RNA interference or RNAi. Instead of complementary antisense strands of RNA, RNAi uses very small double stranded segments of RNA called small interfering RNA which triggers degradation of the target before it can be translated. Studies using RNAi agents delivered by adeno associated viruses (AAV) has been shown to halt progression of disease and lead to some recovery of function with treatment applied to only the deep cerebellar nuclei in mice and rhesus macaques. Both of these techniques are difficult to apply to polyglutamine diseases because targeting the polyglutamine tract may cause normal genes to be downregulated as well. SCA1 has also shown to be difficult to target reliably with single-nucleotide polymorphisms limiting the number of ways RNAi and antisense therapy techniques can be designed to treat SCA1.
Reducing toxicity and increasing cell survival
Because of the numerous interactions ataxin-1 has with other proteins, techniques for reducing toxicity of the mutant ataxin-1 protein often change the expression of related proteins. For example, ataxin-1-like has many common domains with ataxin-1 and overexpression of ataxin-1-like compete with ataxin-1 and prevent its integration into other complexes, reducing toxicity. This effect was replicated in mice models using AAVs, and shown to be about as effective as RNAi techniques at slowing the progression of symptoms. Similarly, the drug baclofen, which is used to help reduce spasticity in persons with multiple sclerosis and related diseases, operates as an agonist of γ-aminobutyric acid type B receptors (GABABR). This pathway crosstalks with the mGluR1 pathway, which interacts with the ataxin 1 protein and proteins responsible for localization and degradation of ataxin 1, suggesting that baclofen may be a viable treatment for SCA 1 treatment.Molecular chaperones are introduced proteins that may have interactions with the mutant protein that reduce toxicity by various mechanisms. Studies in both mice models and Drosophila models have shown that heat shock proteins 40 and 70 may reduce toxicity of expanded ataxin 1 proteins and slow progression of SCA1.While there is currently no known method for exclusively promoting polyglutamine contractions in vivo, techniques using programmable nucleases have shown some promise in causing these changes in vitro. Programmable nucleases are proteins that can break DNA strands near sequences that can be specified by scientists before use. This includes CRISPR/Cas9, which uses a protein found in bacteria and guide strand of RNA, and zinc finger nucleases, which use engineered proteins with special recurring DNA binding domains to guide an attached nuclease. A study reports that both CRISPR and Zinc fingers nucleases that rely on double strand breaks trigger contractions and expansions with nearly equal frequency, while CRISPR using a mutant variation of Cas9, Cas9 D10A or Cas9 nickase, which causes only single strand breaks, produced mainly contractions.In mice, mitochondrial impairments contribute to SCA1 progression. Prominent alterations in Purkinje cell mitochondrial proteins coincide with the symptomatic phase of the disease. Purkinje cells in SCA1 mice also undergo age-dependent alterations in mitochondrial morphology. In addition, Purkinje cells of SCA1 mice have impaired electron transport complexes and decreased ATPase activity. The SCA1 mice experience increased oxidative stress and increased oxidative DNA damage. The mitochondrial targeted antioxidant MitoQ was found to slow down the appearance of SCA1-linked neuropathologies such as lack of motor coordination. MitoQ also prevented oxidative stress induced DNA damage and Purkinje cell loss.
Cell replacement therapies
One treatment option being investigated is stem cell therapy, which attempts to replace dead tissue by transplanting stem cells into affected region and either stimulating them to differentiate into the desired cell types or allowing them to stimulate endogenous regenerative mechanisms. These techniques are of interest to researchers as a possible treatment for neurodegenerative diseases, but currently are of limited success in animal models, and in in-vitro cell culture studies. The ability for grafted cells to integrate into the desired tissue and adjust for the unique pathologies of different neurodegenerative disorders can be a severe limitation on the development of stem cell based treatments. Further, the tissues in the brain often rely on intricate and complicated arrangements of neurons; regions of the brain that do not require precision in these patterns to function, like the striatum affected by Parkinsons disease which uses paracrine signaling, tend to have better results in stem cell therapies than systems that require precision, like the cerebellum and pons. Stem cell therapies can be especially difficult in replacing Purkinje neuron loss as unaffected granule cells can prevent axons reaching the deep cerebellar nuclei with which Purkinje cells interface. Despite these difficulties, grafted neural precursor cells have been shown to be viable and to successfully migrate into desired location in SCA1 transgenic mice models and mesenchymal stem cells have been shown to mitigate loss of dendritic arborization SCA1 mice. Positive results have been found in mice models using both stem cells from fetal neuroectoderm and adult stem cells from the lateral ventricles and the dentate gyrus.: 177–188 Using harvested stem cells in stem cell therapies require immunosuppression to prevent the host from rejecting the transplants; creating induced pluripotent stem cells from the hosts own cells would mitigate this risk and has had some testing in other neurodegenerative diseases.: 177–188
== References == |
Gray platelet syndrome | Gray platelet syndrome (GPS), or platelet alpha-granule deficiency, is a rare congenital autosomal recessive bleeding disorder caused by a reduction or absence of alpha-granules in blood platelets, and the release of proteins normally contained in these granules into the marrow, causing myelofibrosis. The name derives from the initial observation of gray appearance of platelets with a paucity of granules on blood films from a patient with a lifelong bleeding disorder.
Signs and symptoms
Signs of GPS typically arise at birth or in childhood, these signs and symptoms include thrombocytopenia, bruising susceptibility, and epistaxis. Typically, the observed low platelet count in individuals is progressive, this can result in fatal hemorrhages later in life. Additionally, females who are affected may experience irregular menstrual cycles and heavy menstrual bleeding. Another common effect of GPS is myelofibrosis, where scar tissue builds up in the bone marrow causing it to be unable to produce a sufficient amount of blood cells. To compensate, other organs such as the spleen start to produce more blood cells which can lead to splenomegaly.
Genetics
GPS is primarily inherited in an autosomal recessive manner. The gene that is mutated in GPS has been mapped to chromosome 3p and identified as NBEAL2. The location is 3p21.31. This is caused by a homozygous or compound heterozygous mutations in the NBEAL2 gene. NBEAL2 encodes a protein containing a BEACH domain that is predicted to be involved in vesicular trafficking. It is expressed in platelets and megakaryocytes and is required for the development of platelet alpha-granules. NBEAL2 expression is also required for the development of thrombocytes in zebrafish.In Japan, GPS was found in 24 affected patients in a single family. There was at least 1 instance of male-to-male transmission, consistent with autosomal dominant inheritance.A study reported of 14 families with GPS, 11 families had clear autosomal recessive inheritance. This was evidenced by consanguinity or multiple affected siblings with unaffected parents. The families had various backgrounds, including Bedouin, Turkish, Mennonite, French, German, Somali, African American, and mixed Northern and Southern European.GPS is characterized by "thrombocytopenia, and abnormally large agranular platelets in peripheral blood smears." The defect in GPS is the failure of megakaryocytes to package secretory proteins into alpha-granules. Patients with the GPS are affected by mild to moderate bleeding tendencies. Usually these are not major bleeds but there has been some life-threatening cases. Affected women will tend to have heavy, irregular periods. Myelofibrosis is a condition that usually comes with GPS.
Diagnosis
GPS is diagnosed based on clinical findings and requires demonstration of absence or marked reduction of alpha-granules by electron microscopy (EM). High serum vitamin B12 levels are common in patients diagnosed with GPS. Bone marrow sampling, though not required for diagnosis of GPS, might be necessary to evaluate myelofibrosis occurring in GPS and to exclude other disorders.
Management
There is no specific treatment for GPS, but it can be managed by anticipating and preventing the risks of bleeding. The treatment options include desmopressin. Splenectomy can be used to increase the platelet counts in those whose platelet counts decrease to approximately 30,000/microliter. Prognosis is generally good early in life when thrombocytopenia is mild.
Epidemiology
Currently, only 60 cases have been recorded worldwide. While the prevalence of this syndrome is not known, it was found that it affects males and females equally.
See also
Pseudo gray platelet syndrome
Giant platelet disorder
References
External links
Gray platelet syndrome at NIHs Office of Rare Diseases |
Juvenile plantar dermatosis | Juvenile plantar dermatosis is a condition usually seen in children between the ages of 3 and 14, and involves the cracking and peeling of weight bearing areas of the soles of the feet. One of the earliest descriptions was made by British dermatologist Darrell Wilkinson.
See also
Sulzberger–Garbe syndrome
List of cutaneous conditions
References
== External links == |
Blau syndrome | Blau syndrome is an autosomal dominant genetic inflammatory disorder which affects the skin, eyes, and joints. It is caused by a mutation in the NOD2 (CARD15) gene. Symptoms usually begin before the age of four, and the disease manifests as early onset cutaneous sarcoidosis, granulomatous arthritis, and uveitis.
Presentation
Cause
The elucidation that the gene defect in Blau syndrome (BS) involves the CARD15/NOD2 gene has stimulated many investigators to define how this gene operates as part of the innate immune system. The innate immune system recognizes pathogen-associated molecular patterns (PMAPs), including bacterial polysaccharides such as muramyl dipeptide, via its pattern recognition receptors (PRRs), such as NOD2, to induce signaling pathways that activate cytokine responses and protect the organism. In BS the genetic defect seems to lead to over activation and poor control of the inflammatory response leading to widespread granulomatous inflammation and tissue damage.
Diagnosis
Treatment
Treatment has included the usual anti-inflammatory drugs such as adrenal glucocorticoids, anti-metabolites and also biological agents such as anti-TNF and infliximab all with varying degrees of success.
History
In 1981, Malleson et al. reported a family that had autosomal dominant synovitis, camptodactyly, and iridocyclitis. One member died of granulomatous arteritis of the heart and aorta.
In 1982, Rotenstein reported a family with granulomatous arteritis, rash, iritis, and arthritis transmitted as an autosomal dominant trait over three generations.In 1985, Edward Blau, a pediatrician in Marshfield, Wisconsin, reported a family that over four generations had granulomatous inflammation of the skin, eyes and joints. The condition was transmitted as an autosomal dominant trait. In the same year Jabs et al. reported a family that over two generations had granulomatous synovitis, uveitis and cranial neuropathies. The condition was transmitted in an autosomal dominant fashion.Then in 1990 Pastores et al. reported a kindred with a phenotype very similar to what Blau described and suggested that the condition be called Blau Syndrome (BS). They also pointed out the similarities in the families noted above to BS but also pointed out the significant differences in the phenotypes.In 1996 Tromp et al. conducted a genome wide search using affected and non affected members of the original family. A marker, D16S298, gave a maximum logarithm of odds (LOD) score of 3.75 and put the BS susceptibility locus within the 16p12-q21 interval. Hugot et al. found a susceptibility locus for Crohn disease, a granulomatous inflammation of the bowel, on chromosome 16 close to the locus for BS. Based on the above information Blau suggested in 1998 that the genetic defect in BS and Crohn Disease might be the same or similar.
Finally in 2001 Miceli-Richard et al. found the defect in BS to be in the nucleotide-binding domain of CARD15/NOD2. They commented in their article that mutations in CARD15 had also been found in Crohns disease. Confirmation of the defect in BS being in the CARD15 gene was made by Wang et al. in 2002 using the BS family and others. With that information the diagnosis of BS was not only determined by phenotype but now by genotype.Early onset sarcoidosis is BS without a family history, BS has been diagnosed in patients who have not only the classic triad but granuloma in multiple organs.
See also
List of cutaneous conditions
References
Further reading
Wouters CH, Maes A, Foley KP, Bertin J, and Rose CD: Blau Syndrome, the prototypic auto-inflammatory granulomatous disease. Pediatric Rheumatology 2014;12:33. PMID 25136265. PMC 4136643. doi:10.1186/1546-0096-12-33.
Blau EB : Familial Granulomatous Arthritis, Iritis, and Rash. The Journal of Pediatrics 1985; 107: 689-693. PMID 4056967. doi:10.1016/s0022-3476(85)80394-2.
Jabs DA, Houk JL, Bias WB, and Arnett FC: Familial Granulomatous Synovitis, Uveitis, and Cranial Neuropathies. The American Journal of Medicine 1985; 78: 801–804. PMID 3993660. doi:10.1016/0002-9343(85)90286-4.
Malleson P, Schaller JG, Dega F, Cassidy SB, and Pagon RA : Familial Arthritis and Camplodactyly. Arthritis and Rheumatism 1981; 24: 1199–1204. PMID 7306244. doi:10.1002/art.1780240915.
Rotenstein D, Gibbas DL, Majmudar B, and Chastain EA: Familial Granulomatous Arteritis with Polyarthritis of Juvenile Onset. The New England Journal of Medicine 1982; 306: 85–90. PMID 7053492. doi:10.1056/NEJM198201143060208.
Pastores GM, Michels VV, Stickler GB, Su WP, Nelson AM, and Bovenmyer DA: Autosomal dominant granulomatous arthritis, uveitis, skin rash, and synovial cysts. The Journal of Pediatrics 1990; 117: 403–408. PMID 2391595. doi:10.1016/s0022-3476(05)81080-7.
Tromp G, Kuivaniemi H, Raphael S, et al.: Genetic Linkage of Familial Granulomatous Inflammatory Arthritis, Skin Rash, and Uveitis to Chromosome 16. The American Journal of Human Genetics 1996; 59: 1097-1107. PMID 8900239. PMC 1914842.
Hugot JP, Chamaillard M, Zouali H, et al.: Association of NOD2 leucine-rich repeat variants with susceptibility to Crohns disease. Nature 2001; 411:599-603. PMID 11385576. doi:10.1038/35079107.
Blau EB : Autosomal dominant granulomatous disease of childhood: The naming of things. The Journal of Pediatrics 1998; 133: 322–323. PMID 9738710. doi:10.1016/s0022-3476(98)70263-x.
Miceli-Richard C, Lesage S, Rybojad M, Prieur A-M, Manouvrier-Hanu S, Häfner R, Chamaillard M, Zouali H, Thomas G, and Hugot J-P: CARD15 mutations in Blau syndrome. Nature Genetics 2001; 29: 19-20. PMID 11528384. doi:10.1038/ng720.
Wang X, Kuivaniemi H, Bonavita G, Mutkus L, Mau U, Blau E, Inohara N, Nunez G, Tromp G, and Williams CJ: CARD15 Mutations in Familial Granulomatous Syndromes: A Study of the Original Blau Syndrome Kindred and Other Families with Large-Vessel Arteritis and Cranial Neuropathy. Arthritis and Rheumatism 2002; 46: 3041-3045. PMID 12428248. doi:10.1002/art.10618.
Caso F, Galozzi P, Costa L, Sfriso P, Cantarini L, and Punzi L; Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohns disease. RMD Open 2015; 1: e000097. PMID 26509073. PMC 4612691. doi:10.1136/rmdopen-2015-000097.
External links
Blau Syndrome in Orpha website |
Bagassosis | Bagassosis, an interstitial lung disease, is a type of hypersensitivity pneumonitis attributed to exposure to moldy molasses or bagasse dust.
Signs and symptoms
Some symptoms and signs of Bagassosis include breathlessness, cough, haemoptysis, slight fever. Acute diffuse bronchiolitis may also occur. An xray may show mottling of lungs or a shadow.
Cause
Bagassosis has been shown to be due to a thermophilic actinomycetes for which the name thermoactinomycetes sacchari was suggested.
Prevention
The following are precautionary measures that can be taken to avoid the spread of bagassosis:
Dust control-prevention /suppression of dust such as wet process, enclosed apparatus, exhaust ventilation etc. should be used
Personal protection- masks/ respirators
Medical control- initial medical examination & periodical checkups of workers
Bagasse control- keep moisture content above 20% and spray bagasse with 2% propionic acid
History
Bagassosis was first reported in India by Ganguly and Pal in 1955, in a cardboard manufacturing plant near Kolkata. India has a large cane sugar industry. The sugarcane fibre which, until recently, went to waste, is now utilised in the manufacture of cardboard, paper and rayon.
References
== External links == |
Growth hormone deficiency | Growth hormone deficiency (GHD), or human growth hormone deficiency, is a medical condition resulting from not enough growth hormone (GH). Generally the most noticeable symptom is that an individual attains a short height. Newborns may also present low blood sugar or a small penis size. In adults there may be decreased muscle mass, high cholesterol levels, or poor bone density.GHD can be present at birth or develop later in life. Causes may include genetics, trauma, infections, tumors, or radiation therapy. Genes that may be involved include GH1, GHRHR, or BTK. In a third of cases no cause is apparent. The underlying mechanism generally involves problems with the pituitary gland. Some cases are associated with a lack of other pituitary hormones, in which case it is known as combined pituitary hormone deficiency. Diagnosis involves blood tests to measure growth hormone levels.Treatment is by growth hormone replacement using synthetic human growth hormone. The frequency of the condition is unclear. Most cases are initially noticed in children. The genetic forms of this disease are estimated to affect about 1 in 7,000 people. Most types occur equally in males and females though males are more often diagnosed.
Signs and symptoms
Child
Severe prenatal deficiency of GH, as occurs in congenital hypopituitarism, has little effect on fetal growth. However, prenatal and congenital deficiency can reduce the size of a males penis, especially when gonadotropins are also deficient. Besides micropenis in males, additional consequences of severe deficiency in the first days of life can include hypoglycemia and exaggerated jaundice (both direct and indirect hyperbilirubinemia).Even congenital GH deficiency does not usually impair length growth until after the first few months of life. From late in the first year until mid-teens, poor growth and/or shortness is the hallmark of childhood GH deficiency. Growth is not as severely affected in GH deficiency as in untreated hypothyroidism, but growth at about half the usual velocity for age is typical. It tends to be accompanied by delayed physical maturation so that bone maturation and puberty may be several years delayed. When severe GH deficiency is present from birth and never treated, adult heights can be as short as 48-65 inches (122–165 cm).Severe GH deficiency in early childhood also results in slower muscular development, so that gross motor milestones such as standing, walking, and jumping may be delayed. Body composition (i.e., the relative amounts of bone, muscle, and fat) is affected in many children with severe deficiency, so that mild to moderate chubbiness is common (though GH deficiency alone rarely causes severe obesity). Some severely GH-deficient children have recognizable, cherubic facial features characterized by maxillary hypoplasia and forehead prominence.Other side effects in children include sparse hair growth and frontal recession, and pili torti and trichorrhexis nodosa are also sometimes present.: 501
Adults
Recognised effects include:
Increased 5-alpha-reductase
Reduced sex hormone-binding globulin (SHBG)
Reduced muscle mass and strength
Baldness in men
Reduced bone mass and osteoporosis (Decreased bone density)
Reduced energy
Impaired concentration and memory loss
Increased body fat, particularly around the waistline
Lipid abnormalities, particularly raised LDL cholesterol
Increased levels of fibrinogen and plasminogen activator inhibitor
Cardiac dysfunction, including a thickened intima media
Lack of well-being
Depression and anxiety
Social isolation
Fibromyalgia syndrome
Neuromuscular dysfunction
Central adiposity
Decreased muscle mass
Insulin resistance
Accelerated atherogenesis
Prothrombotic state
Decreased sweating and thermoregulation.
Causes
Growth hormone deficiency in childhood commonly has no identifiable cause (idiopathic), and adult-onset GHD is commonly due to pituitary tumours and their treatment or to cranial irradiation. A more complete list of causes includes:
mutations of specific genes (e.g., GHRHR, GH1)
congenital diseases such as Prader-Willi syndrome, Turner syndrome, or short-stature homeobox gene deficiency
congenital malformations involving the pituitary (e.g., septo-optic dysplasia, posterior pituitary ectopia)
chronic kidney disease
intracranial tumors in or near the sella turcica, especially craniopharyngioma
damage to the pituitary from radiation therapy to the head (e.g. for leukemia or brain tumors), from surgery, from trauma, or from intracranial disease (e.g. hydrocephalus)
autoimmune inflammation (hypophysitis)
ischemic or hemorrhagic infarction from low blood pressure (Sheehan syndrome) or hemorrhage pituitary apoplexyThere are a variety of rare diseases that resemble GH deficiency, including the childhood growth failure, facial appearance, delayed bone age, and low insulin-like growth factor-1 (IGF-1) levels. However, GH testing elicits normal or high levels of GH in the blood, demonstrating that the problem is not due to a deficiency of GH but rather to a reduced sensitivity to its action. Insensitivity to GH is traditionally termed Laron dwarfism, but over the last 15 years many different types of GH resistance have been identified, primarily involving mutations of the GH binding protein or receptors.Familial isolated growth hormone deficiency (IGHD) can be inherited as an autosomal recessive (type I), autosomal dominant (type II), or X-linked (type III) characteristic.
Pathophysiology
As an adult ages, it is normal for the pituitary to produce diminishing amounts of GH and many other hormones, particularly the sex steroids. Physicians, therefore, distinguish between the natural reduction in GH levels which comes with age, and the much lower levels of "true" deficiency. Such deficiency almost always has an identifiable cause, with adult-onset GHD without a definable cause ("idiopathic GH deficiency") extremely rare. GH does function in adulthood to maintain muscle and bone mass and strength, and has poorly understood effects on cognition and mood.
Diagnosis
Although GH can be readily measured in a blood sample, testing for GH deficiency is constrained by the fact that levels are nearly undetectable for most of the day. This makes simple measurement of GH in a single blood sample useless for detecting deficiency. Physicians, therefore use a combination of indirect and direct criteria in assessing GHD, including:
Auxologic criteria (defined by body measurements)
Indirect hormonal criteria (IGF levels from a single blood sample)
Direct hormonal criteria (measurement of GH in multiple blood samples to determine secretory patterns or responses to provocative testing), in particular:
Subnormal frequency and amplitude of GH secretory peaks when sampled over several hours
Subnormal GH secretion in response to at least two provocative stimuli
Increased IGF1 levels after a few days of GH treatment
Response to GH treatment
Corroborative evidence of pituitary dysfunction"Provocative tests" involve giving a dose of an agent that will normally provoke a pituitary to release a burst of growth hormone. An intravenous line is established, the agent is given, and small amounts of blood are drawn at 15-minute intervals over the next hour to determine if a rise of GH was provoked. Agents which have been used clinically to stimulate and assess GH secretion are arginine, levodopa, clonidine, epinephrine and propranolol, glucagon, and insulin. An insulin tolerance test has been shown to be reproducible, age-independent, and able to distinguish between GHD and normal adults, and so is the test of choice.
Severe GH deficiency in childhood additionally has the following measurable characteristics:
Proportional stature well below that expected for family heights, although this characteristic may not be present in the case of familial-linked GH deficiency
Below-normal velocity of growth
Delayed physical maturation
Delayed bone age
Low levels of IGF1, IGF2, IGF binding protein 3
Increased growth velocity after a few months of GH treatmentIn childhood and adulthood, the diagnosing doctor will look for these features accompanied by corroboratory evidence of hypopituitarism such as deficiency of other pituitary hormones, a structurally abnormal pituitary, or a history of damage to the pituitary. This would confirm the diagnosis; in the absence of pituitary pathology, further testing would be required.
Classification
Growth hormone deficiency can be congenital or acquired in childhood or adult life. It can be partial or complete. It is usually permanent, but sometimes transient. It may be an isolated deficiency or occur in association with deficiencies of other pituitary hormones.The term hypopituitarism is often used interchangeably with GH deficiency but more often denotes GH deficiency plus deficiency of at least one other anterior pituitary hormone. When GH deficiency (usually with other anterior pituitary deficiencies) is associated with posterior pituitary hormone deficiency (usually diabetes insipidus), the condition is termed panhypopituitarism.
Treatment
GH deficiency is treated by replacing GH with daily injections under the skin or into muscle. Until 1985, growth hormone for treatment was obtained by extraction from human pituitary glands collected at autopsy. Since 1985, recombinant human growth hormone (rHGH) is a recombinant form of human GH produced by genetically engineered bacteria, manufactured by recombinant DNA technology. In both children and adults, costs of treatment in terms of money, effort, and the impact on day-to-day life, are substantial.
Child
GH treatment is not recommended for children who are not growing despite having normal levels of growth hormone, and in the UK it is not licensed for this use. Children requiring treatment usually receive daily injections of growth hormone. Most pediatric endocrinologists monitor growth and adjust dose every 3–6 months and many of these visits involve blood tests and x-rays. Treatment is usually extended as long as the child is growing, and lifelong continuation may be recommended for those most severely deficient. Nearly painless insulin syringes, pen injectors, or a needle-free delivery system reduce the discomfort. Injection sites include the biceps, thigh, buttocks, and stomach. Injection sites should be rotated daily to avoid lipoatrophy. Treatment is expensive, costing as much as US$10,000 to $40,000 a year in the US.
Adults
GH supplementation is not recommended medically for the physiologic age-related decline in GH/IGF secretion. It may be appropriate in diagnosed adult-onset deficiency, where a weekly dose of approximately 25% of that given to children is given. Lower doses again are called for in the elderly to reduce the incidence of side effects and maintain age-dependent normal levels of IGF-1.In many countries, including the UK, the majority view among endocrinologists is that the failure of treatment to provide any demonstrable, measurable benefits in terms of outcomes means treatment is not recommended for all adults with severe GHD, and national guidelines in the UK as set out by NICE suggest three criteria which all need to be met for treatment to be indicated:
Severe GH deficiency, defined as a peak GH response of <9mU/litre during an insulin tolerance test
Perceived impairment of quality of life, as assessed by questionnaire
They are already treated for other pituitary hormone disordersWhere treatment is indicated, duration is dependent upon indication.
Cost of adult treatment in the UK is 3000-4000 GBP annually.
Side effects
Headaches
Joint pain and muscle pain
Fluid retention, and carpal tunnel syndrome
Mild hypertension
Visual problems
Nausea and vomiting
Paraesthesiae
Antibody formation
Reactions at the injection site
Rarely, benign intracranial hypertension.
Prognosis
Child
When treated with GH, a severely deficient child will begin to grow faster within months. In the first year of treatment, the rate of growth may increase from half as fast as other children are growing to twice as fast (e.g., from 1 inch a year to 4 inches, or 2.5 cm to 10). Growth typically slows in subsequent years, but usually remains above normal so that over several years a child who had fallen far behind in his height may grow into the normal height range. Excess adipose tissue may be reduced.
Adults
GH treatment can confer a number of measurable benefits to severely GH-deficient adults, such as enhanced energy and strength, and improved bone density. Muscle mass may increase at the expense of adipose tissue. Although adults with hypopituitarism have been shown to have a reduced life expectancy, and a cardiovascular mortality rate of more than double controls, treatment has not been shown to improve mortality, although blood lipid levels do improve. Similarly, although measurements of bone density improve with treatment, rates of fractures have not been shown to improve.Effects on quality of life are unproven, with a number of studies finding that adults with GHD had near-normal indicators of QoL at baseline (giving little scope for improvement), and many using outdated dosing strategies. However, it may be that those adults with poor QoL at the start of treatment do benefit.
Epidemiology
The incidence of idiopathic GHD in infants is about 1 in every 3800 live births, and rates in older children are rising as more children survive childhood cancers which are treated with radiotherapy, although exact rates are hard to obtain. The incidence of genuine adult-onset GHD, normally due to pituitary tumours, is estimated at 10 per million.
History
Like many other 19th century medical terms which lost precise meaning as they gained wider currency, "midget" as a term for someone with severe proportional shortness acquired pejorative connotations and is no longer used in a medical context.Notable modern pop cultural figures with growth hormone deficiency include actor and comedian Andy Milonakis, who has the appearance and voice of an adolescent boy despite being in his 40s. Argentine footballer Lionel Messi was diagnosed at age 10 with growth hormone deficiency and was subsequently treated.
See also
Hypothalamic–pituitary–somatic axis
References
External links
Am Assoc Clinical Endocrinologists - practice guidelines and recommendations for diagnosis and treatment of GH deficiency, reflecting standard practice among U.S. endocrinologists |
Maffucci syndrome | Maffucci syndrome is a very rare disorder in which multiple benign tumors of cartilage develop within the bones (such tumors are known as enchondromas). The tumors most commonly appear in the bones of the hands, feet, and limbs, causing bone deformities and short limbs.It is named for the Italian pathologist Angelo Maffucci who described it in 1881. Fewer than 200 cases of this syndrome have been reported.
Signs and symptoms
Patients are normal at birth and the syndrome manifests during childhood and puberty.The enchondromas affect the extremities and their distribution is asymmetrical. The most common sites of enchondromas are the metacarpal bones and phalanges of the hands. The feet are less commonly affected.
Disfigurations of the extremities are a result. Pathological fractures can arise in affected metaphyses and diaphyses of the long bones and are common (26%).
The risk for sarcomatous degeneration of enchondromas, hemangiomas, or lymphangiomas is 15–30% in the setting of Maffucci syndrome. Maffucci syndrome is associated with a higher risk of CNS, pancreatic, and ovarian malignancies. Multiple enchondromas may present in three disorders: Ollier disease, Maffucci syndrome, and metachondromatosis. It is important to make the distinction between these diseases, particularly Ollier disease and Maffucci syndrome. Ollier disease is more common than Maffucci syndrome, and presents with multiple enchondromas often in a unilateral distribution. However, hemangiomas and lymphangiomas are not seen in Ollier disease. Metachondromatosis demonstrates autosomal-dominant transmission and presents with both multiple osteochondromas and enchondromas.It is associated with multiple cavernous hemangioma and phlebolith. Lymphangiomas may also be apparent.
Cause
Maffucci syndrome is most commonly caused by mutations in the IDH1 or IDH2 gene.
Diagnosis
Differential diagnosis
In Ollier disease isolated enchondromas are present without the presence of hemangiomas.
Management
Management entails careful examination and monitoring for malignant degenerations. Surgical interventions can correct or minimize deformities.
See also
Ollier disease
Njolstad syndrome
List of cutaneous conditions
List of radiographic findings associated with cutaneous conditions
References
External links
Malfucci syndrome at Genetics Home Reference
Gupta N, Kabra M (February 2007). "Maffucci syndrome" (PDF). Indian Pediatr. 44 (2): 149–50. PMID 17351310. |
Eumycetoma | Eumycetoma, also known as Madura foot, is a persistent fungal infection of the skin and the tissues just under the skin, affecting most commonly the feet, although it can occur in hands and other body parts. It starts as a painless wet nodule, which may be present for years before ulceration, swelling, grainy discharge and weeping from sinuses and fistulae, followed by bone deformity.Several fungi can cause eumycetoma, including: Madurella mycetomatis, Madurella grisea, Leptosphaeria senegalensis, Curvularia lunata, Scedosporium apiospermum, Neotestudina rosatii, and Acremonium and Fusarium species. Diagnosis is by biopsy, visualising the fungi under the microscope and culture. Medical imaging may reveal extent of bone involvement. Other tests include ELISA, immunodiffusion, and DNA Barcoding.Treatment includes surgical removal of affected tissue and antifungal medicines. After treatment, recurrence is common. Sometimes, amputation is required.The infection occurs generally in the tropics, and is endemic in Sub-Saharan Africa, especially Sudan, India, parts of South America and Mexico. Few cases have been reported across North African. Mycetoma is probably low-endemic to Egypt with predilection for eumycetoma. In 2016, the World Health Organization recognised eumycetoma as a neglected tropical disease.
Signs and symptoms
The initial lesion is a small swelling under the skin following minor trauma. It appears as a painless wet nodule, which may be present for years before ulceration, swelling and weeping from sinuses, followed by bone deformity. The sinuses discharge a grainy liquid of fungal colonies. These grains are usually black or white. Destruction of deeper tissues, and deformity and loss of function in the affected limbs may occur in later stages. It tends to occur in one foot. Mycetoma due to bacteria has similar clinical features.
Causes
Eumycetoma is a type of mycetoma caused by fungi. Mycetoma caused by bacteria from the phylum Actinomycetes is different. Both have similar clinical features.The most common fungi causing white discharge is Pseudallescheria boydii. Other causative agents of non-black grain eumycetoma include Acremonium and Fusarium species.Black discharge tends to be caused by species from the genera Madurella, Pyrenochaeta, Exophiala, Leptosphaeria and Curvularia. The most common species are Madurella mycetomatis and Trematospheria grisea (previously called Madurella grisea).
Mechanism
The disease is acquired by entry of the fungal spores from the soil through a breach in the skin produced by minor trauma like a thorn prick. The disease then spreads to deeper tissues and also forms sinus tracts leading to skin surface. Mature lesions are characterised by a grainy discharge from these sinuses. These discharges contain fungal colonies and are infective. Spread of infection internally through blood or lymph is uncommon.Infections that produce a black discharge mainly spread subcutaneously. In the red and yellow varieties deep spread occurs early, infiltrating muscles and bones but sparing nerves and tendons, which are highly resistant to the invasion.Botryomycosis, also known as bacterial pseudomycosis, produces a similar clinical picture and is caused usually by Staphylococcus aureus. Other bacteria may also cause botryomycosis.
Diagnosis
Diagnosis is by biopsy, visualising the fungi under the microscope and culture, which show characteristic fungal filaments and vesicles characteristic of the fungi. Other tests include ELISA, immunodiffusion, and PCR with DNA sequencing (so-called DNA barcoding).X rays and ultrasonography may be carried out to assess the extent of the disease. X rays findings are extremely variable. The disease is most often observed at an advanced stage that exhibits extensive destruction of all bones of the foot. Rarely, a single lesion may be seen in the tibia where the picture is identical with chronic osteomyelitis. Cytology of fine needle aspirate or pus from the lesion, and tissue biopsy may be undertaken sometimes. Some publications have claimed a "dot in a circle sign" as a characteristic MRI feature for this condition (this feature has also been described on ultrasound).
Differential diagnosis
The following clinical conditions may be considered before diagnosing a patient with mycetoma:
Tuberculous ulcer
Kaposis sarcoma, a vascular tumour of skin usually seen in AIDS.
Leprosy
Syphilis
Malignant neoplasm
Tropical ulcer
Botryomycosis, a skin infection usually caused by the bacteria Staphylococcus aureus.
Prevention
No vaccine is available. Simple hygienic precautions like wearing shoes or sandals while working in fields, and washing hands and feet at regular intervals may help prevent the disease.
Treatment
Surgery combined with itraconazole may be given for up to year when the grains are black. Posaconazole is another option. Voriconazole can be used for infections caused by Fusarium species.Ketoconazole has been used to treat eumycetoma but has many side effects. Actinomycetes usually respond well to medical treatment, but eukaryotic infections are generally resistant and may require surgical interventions including salvage procedures as bone resection or even the more radical amputation.
Epidemiology
The disease is more common in males aged 20–40 years who work as labourers, farmers and herders, and in travellers to tropical regions, where the condition is endemic.
History
Madura foot or maduromycosis or maduramycosis is described in ancient writings of India as Padavalmika, which, translated means Foot anthill. The first modern description of Madura foot was made in 1842 from Madurai (the city after which the disease was named Madura-mycosis) in India, by Gill. The fungal cause of the disease was established in 1860 by Carter.
Society and culture
In 2016, the World Health Organization recognised eumycetoma as a neglected tropical disease. Traditionally occurring in regions where resources are scarce, medicines may be expensive and diagnosis is frequently made late, when more invasive treatment may be required.
References
== External links == |
Histrionic personality disorder | Histrionic personality disorder (HPD) is defined by the American Psychiatric Association as a personality disorder characterized by a pattern of excessive attention-seeking behaviors, usually beginning in early childhood, including inappropriate seduction and an excessive desire for approval. People diagnosed with the disorder are said to be lively, dramatic, vivacious, enthusiastic, extroverted and flirtatious.
HPD lies in the dramatic cluster of personality disorders. People with HPD have a high desire for attention, make loud and inappropriate appearances, exaggerate their behaviors and emotions, and crave stimulation. They may exhibit sexually provocative behavior, express strong emotions with an impressionistic style, and can be easily influenced by others. Associated features include egocentrism, self-indulgence, continuous longing for appreciation, and persistent manipulative behavior to achieve their own wants.
Signs and symptoms
People diagnosed with HPD may be dramatic. They often fail to see their own personal situation realistically, instead dramatizing and exaggerating their difficulties. Patients with this disorder can have rapidly shifting emotions and a decreased ability to recognize others emotions. Their emotions may appear superficial or exaggerated to others. This disorder is associated with extraversion, a lower tolerance for frustration or delayed gratification, and openness to new experiences. People with HPD may have little self-doubt and often appear egocentric.Research has also shown those with histrionic personality have a greater desire for social approval and reassurance and will constantly seek it out, making those with HPD more vulnerable to social media addiction. People with this disorder often display excessive sensitivity to criticism or disapproval. They will work hard to get others to pay attention to them, possibly as a method of testing the stability of relationships. They may enjoy situations in which they can be the center of attention, and may feel uncomfortable when people are not paying attention to them. It is common for people with this disorder to wear flamboyant clothing, try body modifications, and fake medical conditions in an attempt to draw others attention. They may display inappropriately sexually provocative, flirtatious, or exploitative behavior. Sexting and exhibitionist behavior are also behaviors people with this condition sometimes exhibit. Some people with histrionic traits or personality disorder change their seduction technique into a more maternal or paternal style as they age. When their desire for attention is not met, it can heighten the severity of their symptoms. They tend to be impressionable and easily manipulatable, especially by those they respect.Patients with HPD are usually high-functioning, both socially and professionally. They usually have good social skills, despite tending to use them to make themselves the center of attention. HPD may also affect a persons social and romantic relationships, as well as their ability to cope with losses or failures. People with HPD tend to consider relationships closer than they usually are. They may seek treatment for clinical depression when romantic (or other close personal) relationships end. Substance disorders, such as Alcohol Use Disorder or Opioid use disorder, are all common in patients with Histrionic Personality Disorder. They are also at higher risks of suicide, body dysmorphia, and divorce. They may go through frequent job changes, as they become easily bored and may prefer withdrawing from frustration (instead of facing it). Because they tend to crave novelty and excitement, they may place themselves in risky situations. All of these factors may lead to greater risk of developing clinical depression. People with this condition can have an impressionistic and undetailed style of speech.Despite these traits they can be prideful of their own personality, and may be unwilling to change, viewing any change as a threat. They may even blame their personal failures or disappointments on others.
Causes
Little research has been done to find evidence of what causes histrionic personality disorder. Although direct causes are inconclusive, various theories and studies suggest multiple possible causes, of a neurochemical, genetic, psychoanalytic, or environmental nature. Traits such as extravagance, vanity, and seductiveness of hysteria have similar qualities to women diagnosed with HPD. HPD symptoms typically do not fully develop until the age of 15, while the onset of treatment only occurs, on average, at approximately 40 years of age.
Neurochemical/physiological
Studies have shown that there is a strong correlation between the function of neurotransmitters and the Cluster B personality disorders such as HPD. Individuals diagnosed with HPD have a highly responsive noradrenergic system, which is responsible for the synthesis, storage, and release of the neurotransmitter norepinephrine. High levels of norepinephrine lead to anxiety-proneness, dependency, and high sociability.
Genetic
Twin studies have aided in breaking down the genetic vs. environment debate. A twin study conducted by the Department of Psychology at Oslo University attempted to establish a correlation between genetics and Cluster B personality disorders. With a test sample of 221 twins, 92 monozygotic and 129 dizygotic, researchers interviewed the subjects using the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) and concluded that there was a correlation of 0.67 that histrionic personality disorder is hereditary.
Psychoanalytic theory
Though criticised as being unsupported by scientific evidence, psychoanalytic theories incriminate authoritarian or distant attitudes by one (mainly the mother) or both parents, along with conditional love based on expectations the child can never fully meet. Using psychoanalysis, Freud believed that lustfulness was a projection of the patients lack of ability to love unconditionally and develop cognitively to maturity, and that such patients were overall emotionally shallow. He believed the reason for being unable to love could have resulted from a traumatic experience, such as the death of a close relative during childhood or divorce of ones parents, which gave the wrong impression of committed relationships. Exposure to one or multiple traumatic occurrences of a close friend or family members leaving (via abandonment or mortality) would make the person unable to form true and affectionate attachments towards other people.
HPD and antisocial personality disorder
Another theory suggests a possible relationship between histrionic personality disorder and antisocial personality disorder. Research has found 2/3 of patients diagnosed with histrionic personality disorder also meet criteria similar to those of the antisocial personality disorder, which suggests both disorders based towards sex-type expressions may have the same underlying cause.
Some family history studies have found that histrionic personality disorder, as well as borderline and antisocial personality disorders, tend to run in families, but it is unclear how much is due to genetic versus environmental factors. Both examples suggest that predisposition could be a factor as to why certain people are diagnosed with histrionic personality disorder, however little is known about whether or not the disorder is influenced by any biological compound or is genetically inheritable. Little research has been conducted to determine the biological sources, if any, of this disorder.
Diagnosis
The persons appearance, behavior and history, along with a psychological evaluation, are usually sufficient to establish a diagnosis. There is no test to confirm this diagnosis. Because the criteria are subjective, some people may be wrongly diagnosed.
DSM 5
The current edition of the Diagnostic and Statistical Manual of Mental Disorders, DSM 5, defines histrionic personality disorder (in Cluster B) as:
A pervasive pattern of excessive emotionality and attention-seeking, beginning by early adulthood and present in a variety of contexts, as indicated by five (or more) of the following:
is uncomfortable in situations in which he or she is not the center of attention
interaction with others is often characterized by inappropriate sexually seductive or provocative behavior
displays rapidly shifting and shallow expression of emotions
consistently uses physical appearance to draw attention to self
has a style of speech that is excessively impressionistic and lacking in detail
shows self-dramatization, theatricality, and exaggerated expression of emotion
is suggestible, i.e., easily influenced by others or circumstances
considers relationships to be more intimate than they actually are
The DSM 5 requires that a diagnosis for any specific personality disorder also satisfies a set of general personality disorder criteria.
ICD-10
The World Health Organizations ICD-10 lists histrionic personality disorder as:
A personality disorder characterized by:
shallow and labile affectivity,
self-dramatization,
theatricality,
exaggerated expression of emotions,
suggestibility,
egocentricity,
self-indulgence,
lack of consideration for others,
easily hurt feelings, and
continuous seeking for appreciation, excitement and attention.
It is a requirement of ICD-10 that a diagnosis of any specific personality disorder also satisfies a set of general personality disorder criteria.
Comorbidity
Most histrionics also have other mental disorders. Comorbid conditions include: antisocial, dependent, borderline, and narcissistic personality disorders, as well as depression, anxiety disorders, panic disorder, somatoform disorders, anorexia nervosa, substance use disorder and attachment disorders, including reactive attachment disorder.
Millons subtypes
Theodore Millon identified six subtypes of histrionic personality disorder. Any individual histrionic may exhibit one or more of the following:
Treatment
Treatment is often prompted by depression associated with dissolved romantic relationships. Medication does little to affect the personality disorder, but may be helpful with symptoms such as depression. Treatment for HPD itself involves psychotherapy, including cognitive therapy.
Interviews and self-report methods
In general clinical practice with assessment of personality disorders, one form of interview is the most popular: an unstructured interview. The actual preferred method is a semi-structured interview but there is reluctance to use this type of interview because they can seem impractical or superficial. The reason that a semi-structured interview is preferred over an unstructured interview is that semi-structured interviews tend to be more objective, systematic, replicable, and comprehensive. Unstructured interviews, despite their popularity, tend to have problems with unreliability and are susceptible to errors leading to false assumptions of the patient.One of the single most successful methods for assessing personality disorders by researchers of normal personality functioning is the self-report inventory following up with a semi-structured interview. There are some disadvantages with the self-report inventory method that with histrionic personality disorder there is a distortion in character, self-presentation, and self-image. This cannot be assessed simply by asking most clients if they match the criteria for the disorder. Most projective testing depend less on the ability or willingness of the person to provide an accurate description of the self, but there is currently limited empirical evidence on projective testing to assess histrionic personality disorder.
Functional analytic psychotherapy
Another way to treat histrionic personality disorder after identification is through functional analytic psychotherapy. The job of a Functional Analytic Psychotherapist is to identify the interpersonal problems with the patient as they happen in session or out of session. Initial goals of functional analytic psychotherapy are set by the therapist and include behaviors that fit the clients needs for improvement. Functional analytic psychotherapy differs from the traditional psychotherapy due to the fact that the therapist directly addresses the patterns of behavior as they occur in-session.The in-session behaviors of the patient or client are considered to be examples of their patterns of poor interpersonal communication and to adjust their neurotic defenses. To do this, the therapist must act on the clients behavior as it happens in real time and give feedback on how the clients behavior is affecting their relationship during therapy. The therapist also helps the client with histrionic personality disorder by denoting behaviors that happen outside of treatment; these behaviors are termed "Outside Problems" and "Outside Improvements". This allows the therapist to assist in problems and improvements outside of session and to verbally support the client and condition optimal patterns of behavior". This then can reflect on how they are advancing in-session and outside of session by generalizing their behaviors over time for changes or improvement".
Coding client and therapist behaviors
In these sessions there is a certain set of dialogue or script that can be forced by the therapist for the client to give insight on their behaviors and reasoning". Here is an example from" the conversation is hypothetical. T = therapist C = Client This coded dialogue can be transcribed as:
ECRB – Evoking clinically relevant behavior
T: Tell me how you feel coming in here today (CRB2) C: Well, to be honest, I was nervous. Sometimes I feel worried about how things will go, but I am really glad I am here.
CRB1 – In-session problems
C: Whatever, you always say that. (becomes quiet). I dont know what I am doing talking so much.
CRB2 – In-session improvements
TCRB1 – Clinically relevant response to client problems
T: Now you seem to be withdrawing from me. That makes it hard for me to give you what you might need from me right now. What do you think you want from me as we are talking right now?".
TCRB2 – Responses to client improvement
T: Thats great. I am glad youre here, too. I look forward to talking to you.
Functional ideographic assessment template
Another example of treatment besides coding is functional ideographic assessment template. The functional ideographic assessment template, also known as FIAT, was used as a way to generalize the clinical processes of functional analytic psychotherapy. The template was made by a combined effort of therapists and can be used to represent the behaviors that are a focus for this treatment. Using the FIAT therapists can create a common language to get stable and accurate communication results through functional analytic psychotherapy at the ease of the client; as well as the therapist.
Epidemiology
The survey data from the National epidemiological survey from 2001 to 2002 suggests a prevalence of HPD of 1.84 percent. Major character traits may be inherited, while other traits may be due to a combination of genetics and environment, including childhood experiences. This personality is seen more often in women than in men. Approximately 65% of HPD diagnoses are women while 35% are men. In Marcie Kaplans A Womens View of DSM-III, she argues that women are overdiagnosed due to potential biases and expresses that even healthy women are often automatically diagnosed with HPD. It has also been argued due to diagnostic bias that prevalence rates are equal among women and men.Many symptoms representing HPD in the DSM are exaggerations of traditional feminine behaviors. In a peer and self-review study, it showed that femininity was correlated with histrionic, dependent and narcissistic personality disorders. Although two thirds of HPD diagnoses are female, there have been a few exceptions. Whether or not the rate will be significantly higher than the rate of women within a particular clinical setting depends upon many factors that are mostly independent of the differential sex prevalence for HPD. Those with HPD are more likely to look for multiple people for attention, which leads to marital problems due to jealousy and lack of trust from the other party. This makes them more likely to become divorced or separated once married. With few studies done to find direct causations between HPD and culture, cultural and social aspects play a role in inhibiting and exhibiting HPD behaviors.
See also
Acting out
References
== External links == |
Lepromatous leprosy | Lepromatous leprosy is a form of leprosy characterized by pale macules in the skin.: 346 It results from the failure of Th1 cell activation which is necessary to eradicate the mycobacteria (Th1 response is required to activate macrophages that engulf and contain the disease). In lepromatous leprosy, TH2 response is turned on, and because of reciprocal inhibition (IL-4; IL-10), the cell-mediated response (TH1) is depressed. Lepromatous leprosy, in contrast to the tuberculoid form of leprosy, is characterized by the absence of epithelioid cells in the lesions. In this form of leprosy Mycobacterium leprae are found in lesion in large numbers. This is the most unfavorable clinical variant of leprosy.This debilitating form of leprosy begins to spread causing the eyebrows to disappear and spongy tumor like swellings appear on the face and body. The disease attacks the internal organs, bones, joints and marrow of the body resulting in physical degeneration. The result is deformity with loss of feeling in the fingers and toes which eventually fall off. Contrary to popular belief, both forms of leprosy are curable, with the lepromatous form classically treated with antibiotics dapsone, rifampin and clofazimine for as long as 2–5 years, but if left untreated the person may die up to 20 or 30 years from its inception.Early detection of the disease is of utmost importance, since severe physical and neurological damage are irreversible even if cured (e.g. blindness, loss of digits/limbs/sensation). Early infection is characterized by a well demarcated, usually pale, skin lesion which has lost its hair, and there may be many of these lesions if the infection is more severe (most commonly found on the cooler parts of the body such as the elbows, knees, fingers, or scrotum, as the bacteria thrive in cooler environments). This early presentation is the same for both tuberculous and lepromatous forms of leprosy as they are a spectrum of the same disease (lepromatous being the more contagious and severe form in patients with impaired Th1 response). Disease progression is extremely slow, and signs of infection may not appear for years.Family members of those with the disease, and especially children, are most at risk. The disease is believed to be spread through respiratory droplets in close quarters like its relative Mycobacterium tuberculosis, and similarly requires extended exposure to an individual in most situations, so outsiders and healthcare workers are normally not infected (except with the most infective individuals such as those in the most progressed lepromatous forms, as those patients have the highest bacterial loads).
See also
Tuberculoid leprosy
Diffuse leprosy of Lucio and Latapí
References
== External links == |
Reactive perforating collagenosis | Reactive perforating collagenosis is a rare, familial, nonpuritic skin disorder characterized by papules that grow in a diameter of 4 to 6mm and develop a central area of umbilication to which keratinous material is lodged. The cause of reactive perforating collagenosis is unknown.
Clinical Features
Inherited form
Keratotic papules measuring 1 to 6 mm develop on the extensor surface of the hands, the elbows, and the knees following superficial trauma. These lesions are painless. They appear as pin-sized lesions that grow to a papule of about 6mm in the following 3–5 weeks. They undergo spontaneous resolution in about 6–8 weeks leaving residual scarring. Lesions may recur throughout life. Cold weather is one of the factors known to trigger recurrences.
Acquired form
In this form, keratotic papules develop on the trunk and extremities. These are commonly associated with pruritus. Lesions may or may not be related to superficial trauma.
See also
Elastosis perforans serpiginosa
List of cutaneous conditions
References
== External links == |
Bone fracture | A bone fracture (abbreviated FRX or Fx, Fx, or #) is a medical condition in which there is a partial or complete break in the continuity of a bone. In more severe cases, the bone may be broken into several fragments, known as a comminuted fracture. A bone fracture may be the result of high force impact or stress, or a minimal trauma injury as a result of certain medical conditions that weaken the bones, such as osteoporosis, osteopenia, bone cancer, or osteogenesis imperfecta, where the fracture is then properly termed a pathologic fracture.
Signs and symptoms
Although bone tissue contains no pain receptors, a bone fracture is painful for several reasons:
Breaking in the continuity of the periosteum, with or without similar discontinuity in endosteum, as both contain multiple pain receptors.
Edema and hematoma of nearby soft tissues caused by ruptured bone marrow evokes pressure pain.
Involuntary muscle spasms trying to hold bone fragments in place.Damage to adjacent structures such as nerves, muscles or blood vessels, spinal cord, and nerve roots (for spine fractures), or cranial contents (for skull fractures) may cause other specific signs and symptoms.
Complications
Some fractures may lead to serious complications including a condition known as compartment syndrome. If not treated, eventually, compartment syndrome may require amputation of the affected limb. Other complications may include non-union, where the fractured bone fails to heal or mal-union, where the fractured bone heals in a deformed manner. One form of malunion is the malrotation of a bone, which is especially common after femoral and tibial fractures.
Complications of fractures may be classified into three broad groups, depending upon their time of occurrence. These are as follows –
Immediate complications – occurs at the time of the fracture.
Early complications – occurring in the initial few days after the fracture.
Late complications – occurring a long time after the fracture.
Pathophysiology
The natural process of healing a fracture starts when the injured bone and surrounding tissues bleed, forming a fracture hematoma. The blood coagulates to form a blood clot situated between the broken fragments. Within a few days, blood vessels grow into the jelly-like matrix of the blood clot. The new blood vessels bring phagocytes to the area, which gradually removes the non-viable material. The blood vessels also bring fibroblasts in the walls of the vessels and these multiply and produce collagen fibres. In this way, the blood clot is replaced by a matrix of collagen. Collagens rubbery consistency allows bone fragments to move only a small amount unless severe or persistent force is applied.At this stage, some of the fibroblasts begin to lay down bone matrix in the form of collagen monomers. These monomers spontaneously assemble to form the bone matrix, for which bone crystals (calcium hydroxyapatite) are deposited in amongst, in the form of insoluble crystals. This mineralization of the collagen matrix stiffens it and transforms it into bone. In fact, bone is a mineralized collagen matrix; if the mineral is dissolved out of bone, it becomes rubbery. Healing bone callus on average is sufficiently mineralized to show up on X-ray within 6 weeks in adults and less in children. This initial "woven" bone does not have the strong mechanical properties of mature bone. By a process of remodelling, the woven bone is replaced by mature "lamellar" bone. The whole process may take up to 18 months, but in adults, the strength of the healing bone is usually 80% of normal by 3 months after the injury.Several factors may help or hinder the bone healing process. For example, tobacco smoking hinders the process of bone healing, and adequate nutrition (including calcium intake) will help the bone healing process. Weight-bearing stress on bone, after the bone has healed sufficiently to bear the weight, also builds bone strength.
Although there are theoretical concerns about NSAIDs slowing the rate of healing, there is not enough evidence to warrant withholding the use of this type analgesic in simple fractures.
Effects of smoking
Smokers generally have lower bone density than non-smokers, so they have a much higher risk of fractures. There is also evidence that smoking delays bone healing.
Diagnosis
A bone fracture may be diagnosed based on the history given and the physical examination performed. Radiographic imaging often is performed to confirm the diagnosis. Under certain circumstances, radiographic examination of the nearby joints is indicated in order to exclude dislocations and fracture-dislocations. In situations where projectional radiography alone is insufficient, Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) may be indicated.
Classification
In orthopedic medicine, fractures are classified in various ways. Historically they are named after the physician who first described the fracture conditions, however, there are more systematic classifications as well.They may be divided into stable versus unstable depending on the likelihood that they may shift further.
Mechanism
Traumatic fracture – a fracture due to sustained trauma. e.g., fractures caused by a fall, road traffic accident, fight, etc.
Pathologic fracture – a fracture through a bone that has been made weak by some underlying disease is called pathological fracture. e.g., a fracture through a bone weakened by metastasis. Osteoporosis is the most common cause of pathological fracture.
Periprosthetic fracture – a fracture at the point of mechanical weakness at the end of an implant
Soft-tissue involvement
Closed/simple fractures are those in which the overlying skin is intact
Open/compound fractures involve wounds that communicate with the fracture, or where fracture hematoma is exposed, and may thus expose bone to contamination. Open injuries carry a higher risk of infection. Reports indicate an incidence of infection after internal fixation of closed fracture of 1-2%, rising to 30% in open fractures.Clean fracture
Contaminated fracture
Displacement
Non-displaced
Displaced
Translated, or ad latus, with sideways displacement.
Angulated
Rotated
Shortened, a reduction in overall bone length when displaced fracture fragments overlap
Fracture pattern
Linear fracture – a fracture that is parallel to the bones long axis
Transverse fracture – a fracture that is at a right angle to the bones long axis
Oblique fracture – a fracture that is diagonal to a bones long axis (more than 30°)
Spiral fracture – a fracture where at least one part of the bone has been twisted
Compression fracture/wedge fracture – usually occurs in the vertebrae, for example when the front portion of a vertebra in the spine collapses due to osteoporosis (a medical condition which causes bones to become brittle and susceptible to fracture, with or without trauma)
Impacted fracture – a fracture caused when bone fragments are driven into each other
Avulsion fracture – a fracture where a fragment of bone is separated from the main mass
Fragments
Incomplete fracture – a fracture in which the bone fragments are still partially joined, in such cases, there is a crack in the osseous tissue that does not completely traverse the width of the bone.
Complete fracture – a fracture in which bone fragments separate completely.
Comminuted fracture – a fracture in which the bone has broken into several pieces.
Anatomical location
An anatomical classification may begin with specifying the involved body part, such as the head or arm, followed by more specific localization. Fractures that have additional definition criteria than merely localization often may be classified as subtypes of fractures, such as a Holstein-Lewis fracture being a subtype of a humerus fracture. Most typical examples in an orthopaedic classification given in the previous section cannot be classified appropriately into any specific part of an anatomical classification, however, as they may apply to multiple anatomical fracture sites.
Skull fracture
Basilar skull fracture
Blowout fracture – a fracture of the walls or floor of the orbit
Mandibular fracture
Nasal fracture
Le Fort fracture of skull – facial fractures involving the maxillary bone and surrounding structures in a usually bilateral and either horizontal, pyramidal, or transverse way.
Spinal fracture
Cervical fracture
Fracture of C1, including Jefferson fracture
Fracture of C2, including Hangmans fracture
Flexion teardrop fracture – a fracture of the anteroinferior aspect of a cervical vertebral
Clay-shoveler fracture – fracture through the spinous process of a vertebra occurring at any of the lower cervical or upper thoracic vertebrae
Burst fracture – in which a vertebra breaks from a high-energy axial load
Compression fracture – a collapse of a vertebra, often in the form of wedge fractures due to larger compression anteriorly
Chance fracture – compression injury to the anterior portion of a vertebral body with concomitant distraction injury to posterior elements
Holdsworth fracture – an unstable fracture dislocation of the thoraco lumbar junction of the spine
Rib fracture
Sternal fracture
Shoulder fracture
Clavicle fracture
Scapular fracture
Arm fracture
Humerus fracture (fracture of upper arm)
Supracondylar fracture
Holstein-Lewis fracture – a fracture of the distal third of the humerus resulting in entrapment of the radial nerve
Forearm fracture
Ulnar fracture
Monteggia fracture – a fracture of the proximal third of the ulna with the dislocation of the head of the radius
Hume fracture – a fracture of the olecranon with an associated anterior dislocation of the radial head
Radius fracture
Essex-Lopresti fracture – a fracture of the radial head with concomitant dislocation of the distal radio-ulnar joint with disruption of the interosseous membrane
Distal radius fracture
Galeazzi fracture – a fracture of the radius with dislocation of the distal radioulnar joint
Colles fracture – a distal fracture of the radius with dorsal (posterior) displacement of the wrist and hand
Smiths fracture – a distal fracture of the radius with volar (ventral) displacement of the wrist and hand
Bartons fracture – an intra-articular fracture of the distal radius with dislocation of the radiocarpal joint
Hand fracture
Scaphoid fracture
Rolando fracture – a comminuted intra-articular fracture through the base of the first metacarpal bone
Bennetts fracture – a fracture of the base of the first metacarpal bone which extends into the carpometacarpal (CMC) joint
Boxers fracture – a fracture at the neck of a metacarpal
Broken finger – a fracture of the carpal phalanges
Pelvic fracture
Fracture of the hip bone
Duverney fracture – an isolated pelvic fracture involving only the iliac wing
Femoral fracture
Hip fracture (anatomically a fracture of the femur bone and not the hip bone)
Patella fracture
Crus fracture
Tibia fracture
Pilon fracture
Tibial plateau fracture
Bumper fracture – a fracture of the lateral tibial plateau caused by a forced valgus applied to the knee
Segond fracture – an avulsion fracture of the lateral tibial condyle
Gosselin fracture – a fractures of the tibial plafond into anterior and posterior fragments
Toddlers fracture – an undisplaced and spiral fracture of the distal third to distal half of the tibia
Fibular fracture
Maisonneuve fracture – a spiral fracture of the proximal third of the fibula associated with a tear of the distal tibiofibular syndesmosis and the interosseous membrane
Le Fort fracture of ankle – a vertical fracture of the antero-medial part of the distal fibula with avulsion of the anterior tibiofibular ligament
Bosworth fracture – a fracture with an associated fixed posterior dislocation of the distal fibular fragment that becomes trapped behind the posterior tibial tubercle; the injury is caused by severe external rotation of the ankle
Combined tibia and fibula fracture
Trimalleolar fracture – involving the lateral malleolus, medial malleolus, and the distal posterior aspect of the tibia
Bimalleolar fracture – involving the lateral malleolus and the medial malleolus
Potts fracture
Foot fracture
Lisfranc fracture – in which one or all of the metatarsals are displaced from the tarsus
Jones fracture – a fracture of the proximal end of the fifth metatarsal
March fracture – a fracture of the distal third of one of the metatarsals occurring because of recurrent stress
Cuneiform fracture – a fracture of one of the three cuneiform bones typically due to direct blow, axial load, or avulsion
Calcaneal fracture – a fracture of the calcaneus (heel bone)
Broken toe – a fracture of the pedal phalanges
OTA/AO classification
The Orthopaedic Trauma Association Committee for Coding and Classification published its classification system in 1996, adopting a similar system to the 1987 AO Foundation system. In 2007, they extended their system, unifying the two systems regarding wrist, hand, foot, and ankle fractures.
Classifications named after people
A number of classifications are named after the person (eponymous) who developed it.
"Denis classification" for spinal fractures
"Frykman classification" for forearm fractures (fractures of radius and ulna)
"Gustilo open fracture classification"
"Letournel and Judet Classification" for Acetabular fractures
"Neer classification" for humerus fractures
Seinsheimer classification, Evans-Jensen classification, Pipkin classification, and Garden classification for hip fractures
Prevention
Both high- and low-force trauma can cause bone fracture injuries. Preventive efforts to reduce motor vehicle crashes, the most common cause of high-force trauma, include reducing distractions while driving. Common distractions are driving under the influence and texting or calling while driving, both of which lead to an approximate 6-fold increase in crashes. Wearing a seatbelt can also reduce the likelihood of injury in a collision. 30 km/h or 20 mph speed limits (as opposed to the more common intracity 50 km/h / 30 mph) also drastically reduce the risk of accident, serious injury and even death in crashes between motor vehicles and humans. Vision Zero aims to reduce traffic deaths to zero through better traffic design and other measures and to drastically reduce traffic injuries which would prevent many bone fractures.
A common cause of low-force trauma is an at-home fall. When considering preventative efforts, the National Institute of Health (NIH) examines ways to reduce the likelihood of falling, the force of the fall, and bone fragility. To prevent at-home falls they suggest keeping cords out of high-traffic areas where someone could trip, installing handrails and keeping stairways well-lit, and installing an assistive bar near the bathtub in the washroom for support. To reduce the impact of a fall the NIH recommends to try falling straight down on your buttocks or onto your hands.Some sports have a relatively high risk of bone fractures as a common sports injury. Preventive measures depend to some extent on the specific sport, but learning proper technique, wearing protective gear and having a realistic estimation of ones own capabilities and limitations can all help reduce the risk of bone fracture. In contact sports rules have been put in place to protect athlete health, such as the prohibition of unnecessary roughness in American football.
Taking calcium and vitamin D supplements can help strengthen your bones. Vitamin D supplements combined with additional calcium marginally reduces the risk of hip fractures and other types of fracture in older adults; however, vitamin D supplementation alone did not reduce the risk of fractures.
Patterns
Treatment
Treatment of bone fractures are broadly classified as surgical or conservative, the latter basically referring to any non-surgical procedure, such as pain management, immobilization or other non-surgical stabilization. A similar classification is open versus closed treatment, in which open treatment refers to any treatment in which the fracture site is opened surgically, regardless of whether the fracture is an open or closed fracture.
Pain management
In arm fractures in children, ibuprofen has been found to be as effective as a combination of paracetamol and codeine. In the ems setting it might be applicable to administer 1mg/kg of iv ketamine to achieve a dissociated state.
Immobilization
Since bone healing is a natural process that will occur most often, fracture treatment aims to ensure the best possible function of the injured part after healing. Bone fractures typically are treated by restoring the fractured pieces of bone to their natural positions (if necessary), and maintaining those positions while the bone heals. Often, aligning the bone, called reduction, in a good position and verifying the improved alignment with an X-ray is all that is needed. This process is extremely painful without anaesthesia, about as painful as breaking the bone itself. To this end, a fractured limb usually is immobilized with a plaster or fibreglass cast or splint that holds the bones in position and immobilizes the joints above and below the fracture. When the initial post-fracture oedema or swelling goes down, the fracture may be placed in a removable brace or orthosis. If being treated with surgery, surgical nails, screws, plates, and wires are used to hold the fractured bone together more directly. Alternatively, fractured bones may be treated by the Ilizarov method which is a form of an external fixator.
Occasionally smaller bones, such as phalanges of the toes and fingers, may be treated without the cast, by buddy wrapping them, which serves a similar function to making a cast. A device called a Suzuki frame may be used in cases of deep, complex intra-articular digit fractures. By allowing only limited movement, immobilization helps preserve anatomical alignment while enabling callus formation, toward the target of achieving union.
Splinting results in the same outcome as casting in children who have a distal radius fracture with little shifting.
Surgery
Surgical methods of treating fractures have their own risks and benefits, but usually, surgery is performed only if conservative treatment has failed, is very likely to fail, or is likely to result in a poor functional outcome. With some fractures such as hip fractures (usually caused by osteoporosis), surgery is offered routinely because non-operative treatment results in prolonged immobilisation, which commonly results in complications including chest infections, pressure sores, deconditioning, deep vein thrombosis (DVT), and pulmonary embolism, which are more dangerous than surgery. When a joint surface is damaged by a fracture, surgery is also commonly recommended to make an accurate anatomical reduction and restore the smoothness of the joint.
Infection is especially dangerous in bones, due to the recrudescent nature of bone infections. Bone tissue is predominantly extracellular matrix, rather than living cells, and the few blood vessels needed to support this low metabolism are only able to bring a limited number of immune cells to an injury to fight infection. For this reason, open fractures and osteotomies call for very careful antiseptic procedures and prophylactic use of antibiotics.
Occasionally, bone grafting is used to treat a fracture.Sometimes bones are reinforced with metal. These implants must be designed and installed with care. Stress shielding occurs when plates or screws carry too large of a portion of the bones load, causing atrophy. This problem is reduced, but not eliminated, by the use of low-modulus materials, including titanium and its alloys. The heat generated by the friction of installing hardware can accumulate easily and damage bone tissue, reducing the strength of the connections. If dissimilar metals are installed in contact with one another (i.e., a titanium plate with cobalt-chromium alloy or stainless steel screws), galvanic corrosion will result. The metal ions produced can damage the bone locally and may cause systemic effects as well.
Other
A Cochrane review of low-intensity pulsed ultrasound to speed healing in newly broken bones found insufficient evidence to justify routine use. Other reviews have found tentative evidence of benefit. It may be an alternative to surgery for established nonunions.
Children
In children, whose bones are still developing, there are risks of either a growth plate injury or a greenstick fracture.
A greenstick fracture occurs due to mechanical failure on the tension side. That is since the bone is not so brittle as it would be in an adult, it does not completely fracture, but rather exhibits bowing without complete disruption of the bones cortex in the surface opposite the applied force.
Growth plate injuries, as in Salter-Harris fractures, require careful treatment and accurate reduction to make sure that the bone continues to grow normally.
Plastic deformation of the bone, in which the bone permanently bends, but does not break, also is possible in children. These injuries may require an osteotomy (bone cut) to realign the bone if it is fixed and cannot be realigned by closed methods.
Certain fractures mainly occur in children, including fracture of the clavicle and supracondylar fracture of the humerus.
See also
Stress fracture
Distraction osteogenesis
Rickets
Catagmatic
H. Winnett Orr, U.S. Army surgeon who developed Orthopedic plaster casts
References
External links
Authoritative information in orthopaedic surgery American Association of Orthopedic Surgeons (AAOS)
Radiographic Atlas of Fracture |
Siti | Siti or SITI may refer to:
People
Siti (given name), a common Malay female given name
Siti Kassim (born 1961), Comorian politician
Siti Mwinyi (born 1932), Tanzanian first lady
Beáta Siti (born 1973), Hungarian handball player and coach
Eszter Siti (born 1977), Hungarian handball player
Walid Siti (born 1952), Kurdish artist
Siti Badriah (born 1991), musical artist Dancedhut at the Productions Nagaswara
Places
Siti Hydroelectric Power Station (disambiguation)
Other
Siti, character in Opera Jawa
Saratoga International Theater Institute, theater company in New York, United States
SITI: An Iconic Exhibition of Dato Siti Nurhaliza
Siti (film), 2014 Indonesian film
Siti Networks
Siti language
Stevens Institute of Technology International, former private university in Dominican Republic
See also
All pages with titles containing Siti
All pages with titles beginning with Siti |
Aggressive angiomyxoma | Angiomyxoma is a myxoid tumor involving the blood vessels.
It can affect the vulva and other parts of the pelvis. The characteristic feature of this tumor is its frequent local recurrence and it is currently regarded as a non-metastasizing benign tumor.
Genetics
HMGA2 rearrangement
by translocation t(12;21)(q15;q21.1)
by translocation t(11;12)(q23;q15)
by translocation t(8;12)(p12;q15)
t(5;8)(p15;q22)
Pathology
Microscopy
Vascular appearance of tumor
Hypocellular mesenchymal lesion
Spindled and stellate cells with an ill-defined cytoplasm
Cells loosely scattered in a myxoid stroma
No evidence of nuclear atypia and mitosis
Numerous, thin-to-thick wall vessels of different sizes
Myxoid, hypocellular background
Bland cytological appearance of spindle cells
Microscopical views
Immunochemistry
Immunohistochemical studies show strong staining for desmin, estrogen receptors, and progesterone receptors. Staining for actin, CD34 and smooth muscle actin are intermediate. Staining for S-100 protein is negative.
Diagnosis
Differential diagnosis
Myxoid tumors
Angiomyofibroblastoma
Treatment
Prognosis
Although it is a benign tumour and does not invade neighbouring tissues, it has a tendency to recur after surgical excision so it is termed "aggressive". Recurrence can occur as early as six months from initial resection. Patients frequently present at tertiary medical centers with a history of labial mass (sometimes misdiagnosed as Gartners cyst), with multiple surgical excisions from several surgeons. There is no standard medical therapy; agents reported to be effective in case reports include systemic hormonal therapy with SERMs such as tamoxifen or LHRH agonists (leuprolide), and cytotoxic ("traditional") chemotherapy, as well as radiation therapy especially for recurrent disease.
History
Aggressive angiomyxoma was originally described in 1983, but the term "angiomyxoma" dates back to at least 1952.
See also
Myxoma
Cutaneous myxoma (Superficial angiomyxoma)
References
== External links == |
Trigger finger | Trigger finger, also known as stenosing tenosynovitis, is a disorder characterized by catching or locking of the involved finger in full or near full flexion, typically with force. There may be tenderness in the palm of the hand near the last skin crease (distal palmar crease). The name "trigger finger" may refer to the motion of "catching" like a trigger on a gun. The ring finger and thumb are most commonly affected.The problem is generally idiopathic (no known cause). There may be an association with diabetes. The pathophysiology is enlargement of the flexor tendon and the A1 pulley of the tendon sheath. While often referred to as a type of stenosing tenosynovitis (which implies inflammation) the pathology is mucoid degeneration. Mucoid degeneration is when fibrous tissue such as tendon has less organized collagen, more abundant extra-cellular matrix, and changes in the cells (fibrocytes) to act and look more like cartilage cells (chondroid metaplasia). Diagnosis is typically based on symptoms and signs after excluding other possible causes.Trigger digits can resolve without treatment. Treatment options that are disease modifying include steroid injections and surgery. Splinting immobilization of the finger may or may not be disease modifying.
Signs and symptoms
Symptoms include catching or locking of the involved finger when it is forcefully flexed. There may be tenderness in the palm of the hand near the last skin crease (distal palmar crease). Often a nodule can be felt in this area. There is some evidence that idiopathic trigger finger behaves differently in people with diabetes.
Causes
It is important to distinguish association and causation. The vast majority of trigger digits are idiopathic, meaning there is no known cause.
Some speculate that repetitive forceful use of a digit leads to narrowing of the fibrous digital sheath in which it runs, but there is little scientific data to support this theory. The relationship of trigger finger to work activities is debatable and there are arguments for and against a relationship to hand use with no experimental evidence supporting a relationship.
Diagnosis
Diagnosis is made on interview and physical examination. More than one finger may be affected at a time. It is most common in the thumb and ring finger. The triggering more often occurs while gripping an object firmly or during sleep when the palm of the subject’s hand remains closed for an extended period of time. Upon waking, the affected person may have to force the triggered fingers open with their other hand. In some, this can be a daily occurrence.
Treatment
Corticosteroid injections can cure trigger digits.
Treatment consists of injection of a corticosteroid such as methylprednisolone often combined with a local anesthetic (lidocaine) at the A1 pulley in the palm. The infiltration of the affected site is straightforward using standard anatomic landmarks. There is evidence that the steroid does not need to enter the sheath. The role of sonographic guidance is therefore debatable.
Injection of the tendon sheath with a corticosteroid is effective over weeks to months in more than half of people. Steroid injection is not effective in people with Type 1 diabetes. If triggering persists 2 months after injection, a second injection can be considered. Most specialists recommend no more than 3 injections because corticosteroids can weaken the tendon and there is a possibility of tendon rupture.
Triggering is predictably resolved by a relatively simple surgical procedure under local anesthesia. The surgeon will cut the sheath that is restricting the tendon. The patient should be awake in order to confirm adequate release. On occasion, triggering does not resolve until a slip of the FDS (Flexor digitorum superficialis) tendon is resected.
One study suggests that the most cost-effective treatment is up to two corticosteroid injections followed by open release of the first annular pulley. Choosing surgery immediately is an option and can be affordable if done in the office under local anesthesia.
Surgery
Trigger digits can be released percutaneously using a needle. This is not used for the thumb where the digital reves are at greater risk.
References
External links
Video of Trigger Finger Release Surgery on YouTube
American Academy of Orthopaedic Surgeons information on trigger finger
Information from the Mayo Clinic |
Epiretinal membrane | Epiretinal membrane or macular pucker is a disease of the eye in response to changes in the vitreous humor or more rarely, diabetes. Sometimes, as a result of immune system response to protect the retina, cells converge in the macular area as the vitreous ages and pulls away in posterior vitreous detachment (PVD). PVD can create minor damage to the retina, stimulating exudate, inflammation, and leucocyte response. These cells can form a transparent layer gradually and, like all scar tissue, tighten to create tension on the retina which may bulge and pucker, or even cause swelling or macular edema. Often this results in distortions of vision that are clearly visible as bowing and blurring when looking at lines on chart paper (or an Amsler grid) within the macular area, or central 1.0 degree of visual arc. Usually it occurs in one eye first, and may cause binocular diplopia or double vision if the image from one eye is too different from the image of the other eye. The distortions can make objects look different in size (usually larger = macropsia), especially in the central portion of the visual field, creating a localized or field dependent aniseikonia that cannot be fully corrected optically with glasses. Partial correction often improves the binocular vision considerably though. In the young (under 50 years of age), these cells occasionally pull free and disintegrate on their own; but in the majority of those affected (over 60 years of age) the condition is permanent. The underlying photoreceptor cells, rod cells and cone cells, are usually not damaged unless the membrane becomes quite thick and hard; so usually there is no macular degeneration.
Cause
The source of the cells in epiretinal membranes (ERM) has been found to comprise glial cells, retinal pigment epithelial (RPE) cells, macrophages, fibrocytes, and collagen cells. These cells are found in varying proportions. Those from retinal breaks, previous retinal detachments, or cryopexy are composed mainly of dispersed RPE cells, while cells of glial origin predominate in idiopathic pathology. Laminocytes are the fundamental cell type in idiopathic ERMs. These cells are frequently found in small and dispersed numbers in eyes containing a PVD. The presence of retinal pigment cells invariably indicates proliferative retinopathy and is only seen in association with a retinal detachment or tear.
The incidence of associated PVD range from 75 to 93%, and PVD is present in virtually all eyes with retinal breaks or retinal detachments and subsequent ERM formation. PVD can lead to retinal breaks that may liberate RPE cells that initiate membrane formation. Small breaks in the internal limiting membrane (ILM) after PVD also may provide retinal astrocytes access to the vitreous cavity, where they may subsequently proliferate. Many ERM also have ILM fragments that may be peeled separately. Finally, vitreous hemorrhage, inflammation, or both associated with a PVD also may stimulate ERM formation.
Both sexes appear to be affected equally frequently.
Diagnosis
Epiretinal membrane is typically diagnosed by appearance with optical coherence tomography (OCT) of the macula. Features include a thickening of the nerve fiber layer, a serrated appearance to the surface of the retina just beneath a thickened layer of glial tissue at the retinal-vitreous interface.
Prevention
There is no good evidence for any preventive actions, since it appears this is a natural response to aging changes in the vitreous. It has been estimated that Posterior vitreous detachment (PVD) occurs in over 75 percent of the population over age 65, that PVD is essentially a harmless condition (although with some disturbing symptoms), and that it does not normally threaten sight. However, since epiretinal membrane appears to be a protective response to PVD, where inflammation, exudative fluid, and scar tissue is formed, it is possible that NSAIDs may reduce the inflammation response. Usually there are flashing light experiences and the emergence of floaters in the eye that herald changes in the vitreous before the epiretinal membrane forms.
Treatment
Surgeons can remove or peel the membrane through the sclera and improve vision by 2 or more Snellen lines. Usually the vitreous is replaced at the same time with clear (BSS) fluid, in a vitrectomy. Surgery is not usually recommended unless the distortions are severe enough to interfere with daily living, since there are the usual hazards of surgery, infections, and a possibility of retinal detachment. More common complications are high intraocular pressure, bleeding in the eye, and cataracts, which are the most frequent complication of vitrectomy surgery. Many patients will develop a cataract within the first few years after surgery. In fact, the visual distortions and diplopia created by cataracts may sometimes be confused with epiretinal membrane.
Epidemiology
This ocular pathology was first described by Iwanoff in 1865, and it has been shown to occur in about 7% of the population. It can occur more frequently in the older population with postmortem studies showing it in 2% of those aged 50 years and 20% in those aged 75 years.
Culture
In 1996, Spalding Gray (June 5, 1941 – ca. January 10, 2004), an American actor, screenwriter and playwright, released Grays Anatomy, a film monologue describing his experiences dealing with a macular pucker and his decision to undergo surgery.
In the 2011 film Paul, Ruth had Epiretinal membrane complicated by macular edema in her left vitreous cavity.
See also
Eye surgery
References
Additional references
de Wit GC (2007). "Retinally-induced aniseikonia". Binocul Vis Strabismus Q. 22 (2): 96–101. PMID 17688418.
Benson WE, Brown GC, Tasman W, McNamara JA (1988). "Complications of vitrectomy for non-clearing vitreous hemorrhage in diabetic patients". Ophthalmic Surg. 19 (12): 862–4. PMID 3231410.
Suami M, Mizota A, Hotta Y, Tanaka M (2007). "Pattern VEPs before and after idiopathic epiretinal membrane removal". Doc Ophthalmol. 114 (2): 67–73. doi:10.1007/s10633-006-9039-4. PMID 17216518. S2CID 22039065.
Dev S, Mieler WF, Pulido JS, Mittra RA (1999). "Visual outcomes after pars plana vitrectomy for epiretinal membranes associated with pars planitis". Ophthalmology. 106 (6): 1086–90. doi:10.1016/S0161-6420(99)90247-6. PMID 10366075.
Johnson MW (2005). "Perifoveal vitreous detachment and its macular complications". Trans Am Ophthalmol Soc. 103: 537–67. PMC 1447588. PMID 17057817.
External links
Macular Pucker Resource Guide from the National Eye Institute (NEI). |
Combined malonic and methylmalonic aciduria | Combined malonic and methylmalonic aciduria (CMAMMA), also called combined malonic and methylmalonic acidemia is an inherited metabolic disease characterized by elevated levels of malonic acid and methylmalonic acid. Some researchers have hypothesized that CMAMMA might be one of the most common forms of methylmalonic acidemia, and possibly one of the most common inborn errors of metabolism. Due to being infrequently diagnosed, it most often goes undetected.
Symptoms and signs
The clinical phenotypes of CMAMMA are highly heterogeneous and range from asymptomatic, mild to severe symptoms. The underlying pathophysiology is not yet understood. The following symptoms are reported in the literature:
metabolic acidosis
coma
hypoglycemia
seizures
gastrointestinal disease
developmental delay
speech delay
failure to thrive
psychiatric disease
memory problems
cognitive decline
encephalopathy
cardiomyopathy
dysmorphic featuresWhen the first symptoms appear in childhood, they are more likely to be intermediary metabolic disorders, whereas in adults they are usually neurological symptoms.
Causes
CMAMMA can be divided by causation into two separate inherited disorders: one is a deficiency of the mitochondrial enzyme acyl-CoA synthetase family member 3, encoded by the ACSF3 gene (OMIM#614265); the other disorder is a malonyl-CoA decarboxylase deficiency encoded by the MLYCD gene (OMIM#248360).
ACSF3 deficiency
CMAMMA due to ACSF3 is inherited in an autosomal recessive manner. The ACSF3 gene is located on chromosome 16 locus q24.3 and consists of 11 exons and encodes a 576-amino-acid protein. CMAMMA can be caused by homozygous or compound heterozygous variants in the ACSF3 gene. Based on minor allele frequency (MAF), a population incidence of ~ 1: 30 000 can be predicted for CMAMMA due to ACSF3.
Malonyl-CoA decarboxylase deficiency
CMAMMA due to malonyl-CoA decarboxylase is also inherited in an autosomal recessive manner. The MLYCD gene is located on chromosome 16 locus q23.3.
Pathophysiology
ACSF3
ACSF3 encodes an acyl-CoA synthetase, which is localized in the mitochondria and has a high specificity for malonic acid and methylmalonic acid. Thus, the synthetase catalyzes the synthesis of malonyl-CoA as well as methylmalonyl-CoA.
Malonic acid
The conversion of malonic acid to malonyl-CoA by acyl-CoA synthetase represents the first step in the mitochondrial fatty acid synthesis (mtFASII) pathway, which plays an important role in the regulation of energy metabolism and which should not be confused with the more familiar fatty acid synthesis that occurs in the cytoplasm. The dysfunctional mtFASII pathway leads to an accumulation of malonic acid, which has a competitive inhibitory effect on complex II, and also leads to a deficiency of malonyl-CoA. These deficiencies can be continued to the end-product of the mtFASII pathway, octanoyl-ACP. The consequences of this are diminished oxidative phosphorylation and major alterations in complex lipids, such as increased levels of sphingomyelins and cardiolipins and lower levels of phosphatidylcholines, phosphatidylglycerol and ceramides. Since octanoyl-ACP is the direct precursor in lipoic acid synthesis, this results in diminished lipoylation, since lipoic acid acts as an essential cofactor for several mitochondrial multienzyme complexes, such as pyruvate dehydrogenase complex (PDHC) and α-ketoglutarate dehydrogenase complex (α-KGDHC), among others. This diminished lipoylation also leads to a reduced glycolytic flux. To likely compensate for the cells energy demand, an upregulation of fatty acid β-oxidation and a decreased concentration of certain amino acids that feed anaplerotically into the citrate cycle, such as glutamine (via the fifth site of the citrate cycle), leucine, isoleucine, threonine (all via the sixth site of the citrate cycle) and aspartate (via the 10th site of the citrate cycle), could be detected. In summary, this reduced mitochondrial respiration and glycolytic flux results in impaired mitochondrial flexibility with a large dependence on fatty acid β-oxidation.However, neurons, with the exception of hypothalamic neurons, are not capable of satisfying their large energy demands by degrading fatty acids. It is speculated that an upregulation of β-oxidation also occurs in brain cells due to the hypofunctional mtFASII pathway. The consequence would be an increased risk for hypoxia and oxidative stress, which may contribute to neurological symptoms in the long term.
Methylmalonic acid
Methylmalonic acid is formed from the essential amino acids valine, methionine, threonine and isoleucine, from odd-chained fatty acids, from propionate and from cholesterol side chain, on the degradation path into the citrate cycle. In this process, the last intermediate methylmalony-CoA can be converted to methymalonic acid by a deacylase before incorporation at the succinyl-CoA site of the citrate cycle. At this point, the acyl-CoA synthease encoded by ACSF3 could convert the methylmalonic acid back to methylmalonyl-CoA and then feed it to the citrate cycle with the help of the methylmalonyl-CoA mutase and its cofactor vitamin B12. However, intracellular esterases are also capable of cleaving the methyl group of methylmalonic acid and generating the parent molecule malonic acid.Bacterial fermentation in the gut is a quantitatively significant source of propionate, which is a precursor for methylmalonic acid. Alongside this, propionic acid is also absorbed through the diet, as it is naturally present in certain foods or is added as a preservative by the food industry, especially in baked goods and dairy products. In addition, methylmalonate is formed during catabolism of thymine.In a study with fibroblasts, increased accumulations of triglycerides, an altered profile of fatty acid chain length and the presence of odd chain fatty acids were detected. A partial degradation due to accumulated methylmalonic acid and the use of propionyl-CoA as a starter unit for fatty acid synthesis is suggested as a possible cause, supported by the observation of a higher expression of CD36, which imports fatty acids into the cell.In vitro, a connection between free methylmalonic acid and malonic acid to neurotoxicity could be established.
Malonyl-CoA decarboxylase deficiency
Malonyl-CoA decarboxylase acts as a catalyst in the conversion of malonyl-CoA to acetyl-CoA and CO2. It is speculated that in MCD deficiency, the excess of mitochondrial malonyl-CoA increases methylmalonic acid levels, as a result of an inhibitory effect on methylmalonyl-CoA mutase. In the cytoplasm, malonyl-CoA acts as an inhibitor of the mitochondrial outer membrane enzyme carnitine palmitoyltransferase I (CPT1), which consequently inhibits fatty acid oxidation. The inhibitory effect of cytoplastic malonyl-CoA on CPT1 varies, so it inhibits roughly 100-fold greater in cardiac and skeletal muscles than in the liver.
Diagnosis
Due to a wide range of clinical symptoms and largely slipping through newborn screening programs, CMAMMA is thought to be an under-recognized condition.
Newborn screening programs
Because CMAMMA due to ACSF3 does not result in accumulation of methylmalonyl-CoA, malonyl-CoA, or propionyl-CoA, nor are abnormalities seen in the acylcarnitine profile, CMAMMA is not detected by standard blood-based newborn screening programs.A special case is the province of Quebec, which, in addition to the blood test, also screens urine on the 21st day after birth with the Quebec Neonatal Blood and Urine Screening Program. This makes Quebec province interesting for CMAMMA research, as it represents the only patient cohort in the world without selection bias. Between 1975 and 2010, an estimated 2 695 000 newborns were thus screened, with 3 detections of CMAMMA due to ACSF3. However, based on this lower detection rate to the predicted rate by heterozygous frequencies, it is likely that not all newborns with this biochemical phenotype were detected by the screening program. A 2019 study then identified as many as 25 CMAMMA due to ACSF3 patients in the province of Quebec. All but one came to clinical attention through the Provincial Neonatal Urine Screening Program, 20 of them directly and 4 after the diagnosis of an older sibling.
Malonic acid to methylmalonic acid ratio
The use of plasma rather than urine is recommended for determining the ratio of malonic acid to methylmalonic acid. Since even with an increase in sensitivity for malonic acid (MA), concentrations in urine samples can be so subtle that they are easily missed. In contrast, if only urinary methylmalonic acid (MAA) is used as the sole matrix, then CMAMMA due to ACSF3 may be misdiagnosed as classic methylmalonic acidemia. Also the calculation of the MA/MAA ratio in urine is not useful, because due to overlapping, healthy individuals cannot be clearly distinguished from CMAMMA affected individuals. Whereas, by calculating the MA/MMA ratio in plasma, a CMAMMA can be clearly distinguished from a classic methylmalonic acidemia. This is true for both, vitamin B12 responders and non-responders in methylmalonic acidemia.In CMAMMA due to ACSF3, methylamlonic acid levels exceed those of malonic acid. In contrast, in CMAMMA due to malonyl-CoA deficiency, the MMA/MA ratio is less than 1.
Genetic testing
Extended carrier screening (ECS) in the course of fertility treatment can also identify carriers of mutations in the ACSF3 gene.
Treatments
Dietary
One approach to reduce the accumulating amount of malonic acid and methylmalonic acid is diet. Here, a diet high in carbohydrate and low in protein has been shown to be best. Changes in malonic acid and methylmalonic acid excretion can be seen as early as 24-36 h after a change in diet.
Bacteria-reducing measures
Another quantitatively significant source of malonic acid and methylmalonic acid, in addition to dietary protein intake, is bacterial fermentation. This leads to treatment measures such as the administration of antibiotics and laxatives.
Vitamin B12
Since some forms of methylmalonic acidemia respond to vitamin B12, treatment attempts in CMAMMA due to ACSF3 with vitamin B12 have been made, also in the form of hydroxocobalamin injections, which, however did not lead to any clinical or biochemical effects.
L-Carnitin
One study also mentions treatment with L-carnitine in patients with CMAMMA due to ACSF3, but only retrospectively and without mentioning results.
messenger RNA
Preclinical proof of concept studies in animal models have shown that messenger RNA (mRNA) therapy is also suitable for use in rare metabolic diseases. In this regard, the phase 1/2 study (mRNA-3704 & mRNA-3705) for the treatment of isolated methylmalonic acidemia, which has been ongoing since 2019 by the biotechnology company Moderna, is worth mentioning.
Research
In 1984, CMAMMA (due to malonyl-CoA decarboxylase deficiency) was described for the first time in a scientific study. Further studies on this form of CMAMMA followed until 1994, when another form of CMAMMA with normal malonyl-CoA decarboxylase activity was discovered. In 2011, genetic research through exome sequencing identified the ACSF3 gene as a cause of CMAMMA with normal malonyl-CoA decarboxylase. With a study published in 2016, calculation of the MA/MAA ratio in plasma presented a new possibility for rapid, metabolic diagnosis of CMAMMA.
See also
Methylmalonic acidemia
Organic acidemia
Notes
The term combined malonic and methylmalonic aciduria with the suffix -uria (from Greek ouron, urine) has become established in the scientific literature in contrast to the other term combined malonic and methylmalonic acedemia with the suffix -emia (from Greek aima, blood). However, in the context of CMAMMA, no clear distinction is made, since malonic acid and methylmalonic acid are elevated in both blood and urine.
References
External links
Combined malonic and methylmalonic acidemia at Orphanet |
Adult polyglucosan body disease | Adult polyglucosan body disease (APBD) is a rare genetic glycogen storage disorder caused by an inborn error of metabolism. Symptoms can emerge any time after the age of 30; early symptoms include trouble controlling urination, trouble walking, and lack of sensation in the legs. People eventually develop dementia.
A person inherits loss-of-function mutations in the GBE1 gene from each parent, and the lack of glycogen branching enzyme (the protein encoded by GBE1) leads to buildup of unbranched glycogen in cells, which harms neurons more than other kinds of cells.
Most people first go to the doctor due to trouble with urination. The condition is diagnosed by gathering symptoms, a neurological examination, laboratory tests including genetic testing, and medical imaging. As of 2015 there was no cure or treatment, but the symptoms could be managed. People diagnosed with APBD can live a long time after diagnosis, but will probably die earlier than people without the condition.
Signs and symptoms
Adult polyglucosan body disease is a condition that affects the nervous system. People with this condition have problems walking due to reduced sensation in their legs (peripheral neuropathy) and progressive muscle weakness and stiffness (spasticity). Damage to the nerves that control bladder function (neurogenic bladder) causes progressive difficulty in controlling the flow of urine. About half of people with adult polyglucosan body disease experience dementia. Most people with the condition first complain of bladder issues.People with adult polyglucosan body disease typically first experience signs and symptoms related to the condition between ages 30 and 60.
Causes
APBD is an autosomal recessive disorder that is caused when a person inherits genes from both parents containing one or more loss-of-function mutations in the gene GBE1 which encodes for glycogen branching enzyme, also called 1,4-alpha-glucan-branching enzyme.
Mechanism
The GBE1 gene provides instructions for making the glycogen branching enzyme. This enzyme is involved in the production of a complex sugar called glycogen, which is a major source of stored energy in the body. Most GBE1 gene mutations result in a shortage (deficiency) of the glycogen branching enzyme, which leads to the production of abnormal glycogen molecules. These abnormal glycogen molecules, called polyglucosan bodies, accumulate within cells and cause damage. Neurons appear to be particularly vulnerable to the accumulation of polyglucosan bodies in people with this disorder, leading to impaired neuronal function.Some mutations in the GBE1 gene that cause adult polyglucosan body disease do not result in a shortage of glycogen branching enzyme. In people with these mutations, the activity of this enzyme is normal. How mutations cause the disease in these individuals is unclear. Other people with adult polyglucosan body disease do not have identified mutations in the GBE1 gene. In these individuals, the cause of the disease is unknown.
Diagnosis
Along with evaluation of the symptoms and a neurological examination, a diagnosis can be made based on genetic testing. Whether or not a person is making sufficient amounts of functional glycogen branching enzyme can be determined by taking a skin biopsy and testing for activity of the enzyme. Examination of tissue biopsied from the sural nerve under a microscope can reveal the presence of polyglucosan bodies. There will also be white matter changes visible in a magnetic resonance imaging scans.
Classification
Adult polyglucosan body disease is an orphan disease and a glycogen storage disorder that is caused by an inborn error of metabolism, that affects the central and peripheral nervous systems.The condition in newborns caused by the same mutations is called glycogen storage disease type IV.
Prevention
APBD can only be prevented if parents undergo genetic screening to understand their risk of producing a child with the condition; if in vitro fertilization is used, then preimplantation genetic diagnosis can be done to identify fertilized eggs that do not carry two copies of mutated GBE1.
Management
As of 2015 there was no cure for APDB, instead symptoms are managed. There are various approaches to managing neurogenic bladder dysfunction, physical therapy and mobility aids to help with walking, and dementia can be managed with occupational therapy, counseling and drugs. Presently a number of promising research initiatives are underway in universities and hospitals in the United States, Canada, and Israel. These studies are in need of funding but due to the small number of known cases both research funding and participation is small. It is estimated that there are upwards of 12,000 cases in the United States, most of which are undiagnosed.
Outcomes
The rate of progression varies significantly from person to person.There is not good data on outcomes; it appears that APBD likely leads to earlier death, but people with APBD can live many years after diagnosis with relatively good quality of life.
Epidemiology
The prevalence is unknown; about 70 cases had been reported in the medical literature as of 2016. As of 2016 the largest set of case studies included 50 people; about 70% of them were of Ashkenazic Jewish descent.
Society and culture
A person with APBD named Gregory Weiss created a foundation, the Adult Polyglucosan Body Disease Research Foundation, to fund research into the disease and its management.
Research directions
In 2015 the first transgenic mouse that appeared to be a useful model organism for studying APBD was published.
References
This article incorporates public domain material from Adult polyglucosan body disease. United States Department of Health and Human Services.
== External links == |
Bezoar | A bezoar is a mass often found trapped in the gastrointestinal system, though it can occur in other locations. A pseudobezoar is an indigestible object introduced intentionally into the digestive system.There are several varieties of bezoar, some of which have inorganic constituents and others organic. The term has both a modern (medical, scientific) and traditional usage.
Types
By content
Food boluses (or boli; singular bolus) have the archaic and positive meaning of bezoar, and are composed of loose aggregates of food items such as seeds, fruit pith, or pits, as well as other types of items such as shellac, bubble gum, soil, and concretions of some medications.
Lactobezoars are a specific type of food bezoar comprising inspissated milk. It is most commonly seen in premature infants receiving formula foods.
Pharmacobezoars (or medication bezoars) are mostly tablets or semiliquid masses of drugs, normally found following overdose of sustained-release medications.
Phytobezoars are composed of indigestible plant material (e.g., cellulose), and are frequently reported in patients with impaired digestion and decreased gastric motility.
Diospyrobezoar is a type of phytobezoar formed from unripe persimmons. Coca-Cola has been used to treat them.
Trichobezoar is a bezoar formed from hair – an extreme form of hairball. Humans who frequently consume hair sometimes require these to be removed. In cases of Rapunzel syndrome, surgery may be required.
By location
A bezoar in the esophagus is common in young children and in horses; in horses, it is known as choke.
A bezoar in the large intestine is known as a fecalith.
A bezoar in the trachea is called a tracheobezoar.
Cause
Esophageal bezoars discovered in nasogastrically fed patients on mechanical ventilation and sedation are reported to be due to precipitation of certain food types rich in casein, which are precipitated with gastric acid reflux to form esophageal bezoars. Bezoars can also be caused by gastroparesis due to the slowing of gastric emptying, which allows food to form a bolus.
History
The word bezoar is derived from the Persian pād-zahr (پادزهر), literally "antidote". The myth of the bezoar as an antidote was introduced to Europe from the Middle East in the 11th century and remained popular until the 18th century. It was believed to have the power of a universal antidote, would work against any poison, and that a drinking glass which contained a bezoar could neutralize any poison poured into it.
Ox bezoars are used in Chinese herbology, also known as niu-huang (牛黃) or calculus bovis. They are gallstones or gallstone substitutes created from ox or cattle bile. In some products, they claim to remove toxins from the body.
The Andalusian physician Ibn Zuhr (d. 1161), known in the West as Avenzoar, is thought to have made the earliest description of bezoar stones as medicinal items. Extensive reference to bezoars also appears in the Picatrix.
In 1567, French surgeon Ambroise Paré did not believe that it was possible for the bezoar to cure the effects of any poison, and described an experiment to test the properties of the stone. A cook in the Kings court was sentenced to death, and chose to be poisoned. Paré administered the bezoar stone to the cook, but it had no effect, and the cook died in agony seven hours after taking the poison, proving that contrary to popular belief, the bezoar could not cure all poisons.Modern examinations of the properties of bezoars by Gustaf Arrhenius and Andrew A. Benson of the Scripps Institution of Oceanography show that when bezoars are immersed in an arsenic-laced solution, they can remove the poison. The toxic compounds in arsenic are arsenate and arsenite; each is acted upon differently by the bezoars: arsenate is removed by being exchanged for phosphate in brushite found in the stones, while arsenite is bound to sulfur compounds in the protein of degraded hair, which is a key component in bezoars.A famous case in the common law of England (Chandelor v Lopus, 79 Eng Rep. 3, Cro. Jac. 4, Eng. Ct. Exch. 1603) announced the rule of caveat emptor ("let the buyer beware") if the goods they purchased are not in fact genuine and effective. The case concerned a purchaser who sued for the return of the purchase price of an allegedly fraudulent bezoar.
Bezoars were important objects in cabinets of curiosity and natural history collections, mainly for their use in early modern pharmacy and the study of animal health.The Merck Manual of Diagnosis and Therapy notes that consumption of unripened persimmons has been identified as the main cause of epidemics of intestinal bezoars, and that up to 90 percent of bezoars that occur from excessive consumption require surgery for removal.A 2013 review of three databases identified 24 publications presenting 46 patients treated with Coca-Cola for phytobezoars. The cola was administered in doses of 500 ml (18 imp fl oz; 17 US fl oz) to up to 3,000 ml (110 imp fl oz; 100 US fl oz) over 24 hours, orally or by gastric lavage. A total of 91.3% of patients had complete resolution after treatment with Coca-Cola: 50% after a single treatment, with others requiring the cola plus endoscopic removal. Doctors resorted to surgical removal in four cases.
See also
Bezoardicum
Coca-Cola treatment of phytobezoars
Enterolith
Fecalith
Gastrolith
Goa stone
Gorochana
List of English words of Persian origin
Regurgitalith
Snake-stones
Toadstone
References
Bibliography
Barry Levine. 1999. Principles of Forensic Toxicology. Amer. Assoc. for Clinical Chemistry. ISBN 1-890883-87-5.
Martín-Gil FJ, Blanco-Ávarez JI, Barrio-Arredondo MT, Ramos-Sanchez MC, Martin-Gil J. Jejunal bezoar caused by a piece of apple peel – Presse Med, 1995 Feb. 11; 24(6):326.
The Poison Sleuths: Arsenic – The King of Poisons. Retrieved March 10, 2007. (This webpage is a reprint by the author of an article originally published in the 1997 issue of Science Reporter, published by the National Institute of Science Communication (CSIR) in India.) at archive.today (archived December 5, 2012)
This article incorporates text from a publication now in the public domain: Chambers, Ephraim (ed.). "Bezoar". Cyclopædia, or an Universal Dictionary of Arts and Sciences. James and John Knapton, et al.
Further reading
Borschberg, Peter, "The Euro-Asian Trade in Bezoar Stones (approx. 1500–1700)", Artistic and Cultural Exchanges between Europe and Asia, 1400–1900: Rethinking Markets, Workshops and Collections, ed. Thomas DaCosta Kaufmann and Michael North, Aldershot: Ashgate, 2010, pp. 29–43. https://www.academia.edu/4311591
Borschberg, Peter, "The Trade, Forgery and Medicinal Use of Porcupine Bezoars in the Early Modern Period (c.1500–1750)", ed. Carla Alferes Pinto, Oriente, vol. 14, Lisbon: Fundação Oriente, 2006.
== External links == |
Salpingitis | Salpingitis is an infection causing inflammation in the Fallopian tubes (also called salpinges). It is often included in the umbrella term of pelvic inflammatory disease (PID), along with endometritis, oophoritis, myometritis, parametritis, and peritonitis.
Signs and symptoms
The symptoms usually appear after a menstrual period. The most common are:
an abnormal smell and colour of vaginal discharge, fever, nausea, vomiting, bloating, and frequent urination.
Pain may be felt during ovulation, during periods, during sexual intercourse, on both sides of the abdomen, and lower back.
Causes
The infection usually has its origin in the vagina and ascends to the Fallopian tube from there. Because the infection can spread via the lymph vessels, infection in one Fallopian tube usually leads to infection of the other.
Risk factors
Its been theorized that retrograde menstrual flow and the cervix opening during menstruation allows the infection to reach the Fallopian tubes.
Other risk factors include surgical procedures that break the cervical barrier, such as:
endometrial biopsy
curettage
hysteroscopyAnother risk is factors that alter the microenvironment in the vagina and cervix, allowing infecting organisms to proliferate and eventually ascend to the Fallopian tube:
antibiotic treatment
ovulation
menstruation
sexually transmitted disease (STD)Finally, sexual intercourse may facilitate the spread of disease from the vagina to the Fallopian tube. Coital risk factors are:
Uterine contractions
Sperm, carrying organisms upward
Bacterial species
The bacteria most associated with salpingitis are:
N. gonorrhoeae
Chlamydia trachomatis
Mycoplasma
Staphylococcus
StreptococcusHowever, salpingitis is usually polymicrobial, involving many kinds of pathogens such as Ureaplasma urealyticum, and anaerobic and aerobic bacteria.
Diagnosis
Salpingitis may be diagnosed by pelvic examination, blood tests, and/or a vaginal or cervical swab.
Types
Salpingitis can be acute, chronic, or subclinical.
Epidemiology
Approximately one in fourteen untreated Chlamydia infections will result in salpingitis.Over one million cases of acute salpingitis are reported every year in the US, but the number of incidents is probably larger, due to incomplete and untimely reporting methods and that many cases are reported first when the illness has gone so far that it has developed chronic complications. For women age 16–25, salpingitis is the most common serious infection. It affects approximately 11% of females of reproductive age.Salpingitis has a higher incidence among members of lower socioeconomic classes. However, this is thought of being an effect of earlier sexual debut, multiple partners, and decreased ability to receive proper health care rather than any independent risk factor for salpingitis.
As an effect of an increased risk due to multiple partners, the prevalence of salpingitis is highest for people age 15–24 years. Decreased awareness of symptoms and less will to use contraceptives are also common in this group, raising the occurrence of salpingitis.
Complications
For those affected, 20% need hospitalization. For those aged 15–44 years, 0.29 per 100,000 die from salpingitis.One in six cases of salpingitis will lead to infertility. Salpingitis can also lead to tubal factor infertility because the eggs released in ovulation cannot make contact with the sperm. Approximately 75,000-225,000 cases of infertility in the US are caused by salpingitis. The more times one has the infection, the greater the risk of infertility. With one episode of salpingitis, the risk of infertility is 8-17%. With 3 episodes of salpingitis, the risk is 40-60%, although the exact risk depends on the severity of each episode.Damaged oviducts from salpingitis increase the risk of an ectopic pregnancy by 7-10 fold. Half of ectopic pregnancies are due to a salpingitis infection.Other complications are:
Infection of ovaries and uterus
Infection of sex partners
An abscess on the ovary
Internal scars resulting in Fitz-Hugh–Curtis syndrome of the liver
Treatment
Salpingitis is most commonly caused by bacteria and typically treated with antibiotics.
In other animals
E. coli, Gallibacterium and other bacteria can cause salpingitis in chickens and other poultry. This can result in lower egg production. Dairy cows can also have salpingitis.
References
== External links == |
Progressive rubella panencephalitis | Progressive rubella panencephalitis (PRP) is a neurological disorder which may occur in a child with congenital rubella. It is a slow viral infection of the brain characterized by chronic encephalitis, usually manifesting between 8–19 years of age.
It is believed to be due to a persistence or reactivation of rubella virus infection.
Cause
It develops 6 months to 4 years after the primary rubella infection, which in most cases is a congenital rubella.
In children with congenital rubella infection the deficits remain stable; neurological deterioration after the
first few years of life is not believed to occur.Progression of the disease can be divided into two stages:
1st stage: Behavioural Changes
insidious onset
subtle changes in behaviour and declining school work
2nd stage: Neurological Changes
seizures – sometimes myoclonic
cerebellar ataxia
spastic weakness
retinopathy, optic atrophy
frank dementia leading to coma
spasticity and brainstem involvement with death in 2–5 years
Diagnosis
The diagnosis is considered when a child with congenital rubella develops progressive spasticity, ataxia, mental deterioration, and seizures. Testing involves at least CSF examination and serology. Elevated CSF total protein and globulin and elevated rubella antibody titers in CSF and serum occur. CT may show ventricular enlargement due to cerebellar atrophy and white matter disease. Brain biopsy may be necessary to exclude other causes of encephalitis or encephalopathy. Rubella virus cannot usually be recovered by viral culture or immunohistologic testing.
Treatment
Although no specific treatment exists, the disease can be managed with anticonvulsants, physiotherapy, etc.
Incidence
PRP is very rare and similar to SSPE but without intracellular inclusion bodies.
Only 20 patients have been identified since first recognized in 1974.
See also
Subacute sclerosing panencephalitis
References
== Further reading == |
Sandifer syndrome | Sandifer syndrome (or Sandifers syndrome) is an eponymous paediatric medical disorder, characterised by gastrointestinal symptoms and associated neurological features. There is a significant correlation between the syndrome and gastro-oesophageal reflux disease (GORD); however, it is estimated to occur in less than 1% of children with reflux.
Symptoms and signs
Onset is usually confined to infancy and early childhood, with peak prevalence at 18–36 months. In rare cases, particularly where the child is severely mentally impaired, onset may extend to adolescence.The classical symptoms of the syndrome are spasmodic torticollis and dystonia. Nodding and rotation of the head, neck extension, gurgling, writhing movements of the limbs, and severe hypotonia have also been noted.Spasms may last for 1–3 minutes and may occur up to 10 times a day. Ingestion of food is often associated with occurrence of symptoms; this may result in reluctance to feed. Associated symptoms, such as epigastric discomfort, vomiting (which may involve blood) and abnormal eye movements have been reported. Clinical signs may also include anaemia.
Diagnosis
Diagnosis is made on the basis of the association of gastro-oesophageal reflux with the characteristic movement disorder. Neurological examination is usually normal. Misdiagnosis as benign infantile spasms or epileptic seizures is common, particularly where clear signs or symptoms of gastro-oesophageal reflux are not apparent. Early diagnosis is critical, as treatment is simple and leads to prompt resolution of the movement disorder.
Treatment
Successful treatment of the associated underlying disorder, such as GORD or hiatus hernia, may provide relief.
Prognosis
Sandifer syndrome is not typically life-threatening and the prognosis is typically good.
History
Sandifer syndrome was first described in 1964 by Austrian neurologist Marcel Kinsbourne in The Lancet. Kinsbourne named the syndrome after his mentor, British neurologist Paul Sandifer, who had initially cared for the patients described in Kinsbournes case reports.
See also
List of eponymously named diseases
References
== External links == |
Paranoia | Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself (i.e. "Everyone is out to get me"). Paranoia is distinct from phobias, which also involve irrational fear, but usually no blame.
Making false accusations and the general distrust of other people also frequently accompany paranoia. For example, a paranoid person might believe an incident was intentional when most people would view it as an accident or coincidence. Paranoia is a central symptom of psychosis.
Signs and symptoms
A common symptom of paranoia is the attribution bias. These individuals typically have a biased perception of reality, often exhibiting more hostile beliefs. A paranoid person may view someone elses accidental behavior as though it is with intent or threatening.
An investigation of a non-clinical paranoid population found that feeling powerless and depressed, isolating oneself, and relinquishing activities are characteristics that could be associated with those exhibiting more frequent paranoia.
Some scientists have created different subtypes for the various symptoms of paranoia including erotic, persecutory, litigious, and exalted.Due to the suspicious and troublesome personality traits of paranoia, it is unlikely that someone with paranoia will thrive in interpersonal relationships. Most commonly paranoid individuals tend to be of a single status.According to some research there is a hierarchy for paranoia. The least common types of paranoia at the very top of the hierarchy would be those involving more serious threats. Social anxiety is at the bottom of this hierarchy as the most frequently exhibited level of paranoia.
Causes
Social and environmental
Social circumstances appear to be highly influential in paranoid beliefs. Based on data collected by means of a mental health survey distributed to residents of Ciudad Juárez, Chihuahua (in Mexico) and El Paso, Texas (in the United States), paranoid beliefs seem to be associated with feelings of powerlessness and victimization, enhanced by social situations. Potential causes of these effects included a sense of believing in external control, and mistrust which can be strengthened by lower socioeconomic status. Those living in a lower socioeconomic status may feel less in control of their own lives. In addition, this study explains that females have the tendency to believe in external control at a higher rate than males, potentially making females more susceptible to mistrust and the effects of socioeconomic status on paranoia.Emanuel Messinger reports that surveys have revealed that paranoia can develop from parental relationships and untrustworthy environments. These environments could include being very disciplinary, stringent, and unstable. It was even noted that, "indulging and pampering (thereby impressing the child that they are something special and warrants special privileges)," can be contributing backgrounds. Experiences likely to enhance or manifest the symptoms of paranoia include increased rates of disappointment, stress, and a hopeless state of mind.Discrimination has also been reported as a potential predictor of paranoid delusions. Such reports that paranoia seemed to appear more in older patients who had experienced higher levels of discrimination throughout their lives. In addition to this it has been noted that immigrants are quite susceptible to forms of psychosis. This could be due to the aforementioned effects of discriminatory events and humiliation.
Psychological
Many more mood-based symptoms, grandiosity and guilt, may underlie functional paranoia.Colby (1981) defined paranoid cognition in terms of persecutory delusions and false beliefs whose propositional content clusters around ideas of being harassed, threatened, harmed, subjugated, persecuted, accused, mistreated, wronged, tormented, disparaged, vilified, and so on, by malevolent others, either specific individuals or groups (p. 518).
Three components of paranoid cognition have been identified by Robins & Post: a) suspicions without enough basis that others are exploiting, harming, or deceiving them; b) preoccupation with unjustified doubts about the loyalty, or trustworthiness, of friends or associates; c) reluctance to confide in others because of unwarranted fear that the information will be used maliciously against them (1997, p. 3).
Paranoid cognition has been conceptualized by clinical psychology almost exclusively in terms of psychodynamic constructs and dispositional variables. From this point of view, paranoid cognition is a manifestation of an intra-psychic conflict or disturbance. For instance, Colby (1981) suggested that the biases of blaming others for ones problems serve to alleviate the distress produced by the feeling of being humiliated, and helps to repudiate the belief that the self is to blame for such incompetence. This intra-psychic perspective emphasizes that the cause of paranoid cognitions is inside the head of the people (social perceiver), and dismisses the possibility that paranoid cognition may be related to the social context in which such cognitions are embedded. This point is extremely relevant because when origins of distrust and suspicion (two components of paranoid cognition) are studied many researchers have accentuated the importance of social interaction, particularly when social interaction has gone awry. Even more, a model of trust development pointed out that trust increases or decreases as a function of the cumulative history of interaction between two or more persons.Another relevant difference can be discerned among "pathological and non-pathological forms of trust and distrust". According to Deutsch, the main difference is that non-pathological forms are flexible and responsive to changing circumstances. Pathological forms reflect exaggerated perceptual biases and judgmental predispositions that can arise and perpetuate them, are reflexively caused errors similar to a self-fulfilling prophecy.
It has been suggested that a "hierarchy" of paranoia exists, extending from mild social evaluative concerns, through ideas of social reference, to persecutory beliefs concerning mild, moderate, and severe threats.
Physical
A paranoid reaction may be caused from a decline in brain circulation as a result of high blood pressure or hardening of the arterial walls.Drug-induced paranoia, associated with cannabis, amphetamines, methamphetamine and similar stimulants has much in common with schizophrenic paranoia; the relationship has been under investigation since 2012. Drug-induced paranoia has a better prognosis than schizophrenic paranoia once the drug has been removed. For further information, see stimulant psychosis and substance-induced psychosis.
Based on data obtained by the Dutch NEMESIS project in 2005, there was an association between impaired hearing and the onset of symptoms of psychosis, which was based on a five-year follow up. Some older studies have actually declared that a state of paranoia can be produced in patients that were under a hypnotic state of deafness. This idea however generated much skepticism during its time.
Diagnosis
In the DSM-IV-TR, paranoia is diagnosed in the form of:
Paranoid personality disorder (F60.0)
Paranoid schizophrenia (a subtype of schizophrenia) (F20.0)
The persecutory type of delusional disorder, which is also called "querulous paranoia" when the focus is to remedy some injustice by legal action (F22.8)According to clinical psychologist P. J. McKenna, "As a noun, paranoia denotes a disorder which has been argued in and out of existence, and whose clinical features, course, boundaries, and virtually every other aspect of which is controversial. Employed as an adjective, paranoid has become attached to a diverse set of presentations, from paranoid schizophrenia, through paranoid depression, to paranoid personality—not to mention a motley collection of paranoid psychoses, reactions, and states—and this is to restrict discussion to functional disorders. Even when abbreviated down to the prefix para-, the term crops up causing trouble as the contentious but stubbornly persistent concept of paraphrenia".At least 50% of the diagnosed cases of schizophrenia experience delusions of reference and delusions of persecution. Paranoia perceptions and behavior may be part of many mental illnesses, such as depression and dementia, but they are more prevalent in three mental disorders: paranoid schizophrenia, delusional disorder (persecutory type), and paranoid personality disorder.
Treatment
Paranoid delusions are often treated with antipsychotic medication, which exert a medium effect size. Cognitive behavioral therapy (CBT) improves paranoid delusions relative to control conditions according to a meta-analysis. A meta-analysis of 43 studies reported that metacognitive training (MCT) reduces (paranoid) delusions at a medium to large effect size relative to control conditions.
History
The word paranoia comes from the Greek παράνοια (paranoia), "madness", and that from παρά (para), "beside, by" and νόος (noos), "mind". The term was used to describe a mental illness in which a delusional belief is the sole or most prominent feature. In this definition, the belief does not have to be persecutory to be classified as paranoid, so any number of delusional beliefs can be classified as paranoia. For example, a person who has the sole delusional belief that they are an important religious figure would be classified by Kraepelin as having pure paranoia. The word “paranoia” is associated from the Greek word “para-noeo”. Its meaning was "derangement", or "departure from the normal". However, the word was used strictly and other words were used such as "insanity" or "crazy", as these words were introduced by Aurelius Cornelius Celsus. The term “paranoia” first made an appearance during plays of Greek tragedians, and was also used by sufficient individuals such as Plato and Hippocrates. Nevertheless, the word “paranoia” was the equivalent of “delirium” or “high fever”. Eventually, the term made its way out of everyday language for two millennia. “Paranoia” was soon revived as it made an appearance in the writings of the nosologists. It began to take appearance in France, with the writings of Rudolph August Vogel (1772) and Francois Boissier de Sauvage (1759).According to Michael Phelan, Padraig Wright, and Julian Stern (2000), paranoia and paraphrenia are debated entities that were detached from dementia praecox by Kraepelin, who explained paranoia as a continuous systematized delusion arising much later in life with no presence of either hallucinations or a deteriorating course, paraphrenia as an identical syndrome to paranoia but with hallucinations. Even at the present time, a delusion need not be suspicious or fearful to be classified as paranoid. A person might be diagnosed with paranoid schizophrenia without delusions of persecution, simply because their delusions refer mainly to themselves.
Relations to violence
It has generally been agreed upon that individuals with paranoid delusions will have the tendency to take action based on their beliefs. More research is needed on the particular types of actions that are pursued based on paranoid delusions. Some researchers have made attempts to distinguish the different variations of actions brought on as a result of delusions. Wessely et al. (1993) did just this by studying individuals with delusions of which more than half had reportedly taken action or behaved as a result of these delusions. However, the overall actions were not of a violent nature in most of the informants. The authors note that other studies such as one by Taylor (1985), have shown that violent behaviors were more common in certain types of paranoid individuals, mainly those considered to be offensive such as prisoners.Other researchers have found associations between childhood abusive behaviors and the appearance of violent behaviors in psychotic individuals. This could be a result of their inability to cope with aggression as well as other people, especially when constantly attending to potential threats in their environment. The attention to threat itself has been proposed as one of the major contributors of violent actions in paranoid people, although there has been much deliberation about this as well. Other studies have shown that there may only be certain types of delusions that promote any violent behaviors, persecutory delusions seem to be one of these.Having resentful emotions towards others and the inability to understand what other people are feeling seem to have an association with violence in paranoid individuals. This was based on a study of paranoid schizophrenics (one of the common mental disorders that exhibit paranoid symptoms) theories of mind capabilities in relation to empathy. The results of this study revealed specifically that although the violent patients were more successful at the higher level theory of mind tasks, they were not as able to interpret others emotions or claims.
Paranoid social cognition
Social psychological research has proposed a mild form of paranoid cognition, paranoid social cognition, that has its origins in social determinants more than intra-psychic conflict. This perspective states that in milder forms, paranoid cognitions may be very common among normal individuals. For instance, it is not strange that people may exhibit in their daily life, self-centered thought such as they are being talked about, suspiciousness about other’ intentions, and assumptions of ill-will or hostility (i.e. people may feel as if everything is going against them). According to Kramer, (1998) these milder forms of paranoid cognition may be considered as an adaptive response to cope with or make sense of a disturbing and threatening social environment.
Paranoid cognition captures the idea that dysphoric self-consciousness may be related with the position that people occupy within a social system. This self-consciousness conduces to a hypervigilant and ruminative mode to process social information that finally will stimulate a variety of paranoid-like forms of social misperception and misjudgment. This model identifies four components that are essential to understanding paranoid social cognition: situational antecedents, dysphoric self-consciousness, hypervigilance and rumination, and judgmental biases.
Situational antecedents
Perceived social distinctiveness, perceived evaluative scrutiny and uncertainty about the social standing.
Perceived social distinctiveness: According to the social identity theory, people categorize themselves in terms of characteristics that made them unique or different from others under certain circumstances. Gender, ethnicity, age, or experience may become extremely relevant to explain peoples behavior when these attributes make them unique in a social group. This distinctive attribute may have influence not only in how people are perceived, but may also affect the way they perceive themselves.
Perceived evaluative scrutiny: According to this model, dysphoric self-consciousness may increase when people feel under moderate or intensive evaluative social scrutiny such as when an asymmetric relationship is analyzed. For example, when asked about their relationships, doctoral students remembered events that they interpreted as significant to their degree of trust in their advisors when compared with their advisors. This suggests that students are more willing to pay more attention to their advisor than their advisor is motivated to pay attention to them. Also students spent more time ruminating about the behaviors, events, and their relationship in general.
Uncertainty about social standing: The knowledge about the social standing is another factor that may induce paranoid social cognition. Many researchers have argued that experiencing uncertainty about a social position in a social system constitutes an adverse psychological state, one which people are highly motivated to reduce.
Dysphoric self-consciousness
Refers to an aversive form of heightened public self-consciousness characterized by the feelings that one is under intensive evaluation or scrutiny. Becoming self-tormenting will increase the odds of interpreting others behaviors in a self-referential way.
Hypervigilance and rumination
Self-consciousness was characterized as an aversive psychological state. According to this model, people experiencing self-consciousness will be highly motivated to reduce it, trying to make sense of what they are experiencing. These attempts promote hypervigilance and rumination in a circular relationship: more hypervigilance generates more rumination, whereupon more rumination generates more hypervigilance. Hypervigilance can be thought of as a way to appraise threatening social information, but in contrast to adaptive vigilance, hypervigilance will produce elevated levels of arousal, fear, anxiety, and threat perception. Rumination is another possible response to threatening social information. Rumination can be related to the paranoid social cognition because it can increase negative thinking about negative events, and evoke a pessimistic explanatory style.
Judgmental and cognitive biases
Three main judgmental consequences have been identified:
The sinister attribution error: This bias captures the tendency that social perceivers have to overattribute lack of trustworthiness to others.
The overly personalistic construal of social interaction: Refers to the inclination that paranoid perceiver has to interpret others’ action in a disproportional self-referential way, increasing the belief that they are the target of others’ thoughts and actions. A special kind of bias in the biased punctuation of social interaction, which entail an overperception of causal linking among independent events.
The exaggerated perception of conspiracy: Refers to the disposition that the paranoid perceiver has to overattribute social coherence and coordination to others’ actions.Meta-analyses have confirmed that individuals with paranoia tend to jump to conclusions and are incorrigible in their judgements, even for delusion-neutral scenarios.
Research
A study suggests that combining cognitive behavioral therapy (CBT) with SlowMo, an app that helps notice their "unhelpful fast-thinking" might be more effective for treating paranoia in people with psychosis than CBT alone.
See also
References
Sources
Further reading
American Psychiatric Association (1994). Diagnostic and statistical manual of mental health disorders (4th ed). Washington DC: Author.
Arnold, K. & Vakhrusheva, J. (2015). "Resist the negation reflex: Minimizing reactance in psychotherapy of delusions" (PDF). Psychosis. 8 (2): 1–10. doi:10.1080/17522439.2015.1095229. S2CID 146386637.
Canneti, Elias (1962). Crowds and Power. Translated from the German by Carol Stewart. Gollancz, London. 1962.
Colby, K. (1981). Modeling a paranoid mind. The Behavioral and Brain Sciences, 4, 515 - 560.
Deutsch, M. (1958). Trust and suspicion. Journal of Conflict Resolution, 2, 265 - 279.
Messinger, Emanuel (1963). "Paranoia". In Deutsch, Albert; Fishman, Helen (eds.). The encyclopedia of mental health, Vol IV. The Encyclopedia of Mental Health. Vol. IV. New York, NY, US: Franklin Watts. pp. 1407–1420. doi:10.1037/11547-024. Retrieved April 4, 2014.
Farrell, John (2006). Paranoia and Modernity: Cervantes to Rousseau. Cornell University Press.
Freeman, D. & Garety, P. A. (2004). Paranoia: The Psychology of Persecutory Delusions. Hove: Psychology Press. ISBN 1-84169-522-X
Igmade (Stephan Trüby et al., eds.), 5 Codes: Architecture, Paranoia and Risk in Times of Terror, Birkhäuser 2006. ISBN 3-7643-7598-1
Kantor, Martin (2004). Understanding Paranoia: A Guide for Professionals, Families, and Sufferers. Westport: Praeger Press. ISBN 0-275-98152-5
Munro, A. (1999). Delusional disorder. Cambridge: Cambridge University Press. ISBN 0-521-58180-X
Mura, Andrea (2016). "National Finitude and the Paranoid Style of the One" (PDF). Contemporary Political Theory. 15: 58–79. doi:10.1057/cpt.2015.23. S2CID 53724373.
Robins, R., & Post, J. (1997). Political paranoia: The politics of hatred. New Haven, CT: Yale University Press.
Sant, P. (2005). Delusional disorder. Punjab: Panjab University Chandigarh. ISBN 0-521-58180-X
Sims, A. (2002). Symptoms in the mind: An introduction to descriptive psychopathology (3rd edition). Edinburgh: Elsevier Science Ltd. ISBN 0-7020-2627-1
Siegel, Ronald K. (1994). Whispers: The Voices of Paranoia. New York: Crown. ISBN 978-0-684-80285-5.
External links
The dictionary definition of paranoia at Wiktionary
Media related to Paranoia at Wikimedia Commons
Quotations related to Paranoia at Wikiquote |
Mandibular fracture | Mandibular fracture, also known as fracture of the jaw, is a break through the mandibular bone. In about 60% of cases the break occurs in two places. It may result in a decreased ability to fully open the mouth. Often the teeth will not feel properly aligned or there may be bleeding of the gums. Mandibular fractures occur most commonly among males in their 30s.Mandibular fractures are typically the result of trauma. This can include a fall onto the chin or a hit from the side. Rarely they may be due to osteonecrosis or tumors in the bone. The most common area of fracture is at the condyle (36%), body (21%), angle (20%) and symphysis (14%). While a diagnosis can occasionally be made with plain X-ray, modern CT scans are more accurate.Immediate surgery is not necessarily required. Occasionally people may go home and follow up for surgery in the next few days. A number of surgical techniques may be used including maxillomandibular fixation and open reduction internal fixation (ORIF). People are often put on antibiotics such as penicillin for a brief period of time. The evidence to support this practice; however, is poor.
Signs and symptoms
General
By far, the two most common symptoms described are pain and the feeling that teeth no longer correctly meet (traumatic malocclusion, or disocclusion). The teeth are very sensitive to pressure (proprioception), so even a small change in the location of the teeth will generate this sensation. People will also be very sensitive to touching the area of the jaw that is broken, or in the case of condylar fracture the area just in front of the tragus of the ear.Other symptoms may include loose teeth (teeth on either side of the fracture will feel loose because the fracture is mobile), numbness (because the inferior alveolar nerve runs along the jaw and can be compressed by a fracture) and trismus (difficulty opening the mouth).Outside the mouth, signs of swelling, bruising and deformity can all be seen. Condylar fractures are deep, so it is rare to see significant swelling although, the trauma can cause fracture of the bone on the anterior aspect of the external auditory meatus so bruising or bleeding can sometimes be seen in the ear canal. Mouth opening can be diminished (less than 3 cm). There can be numbness or altered sensation (anesthesia/paraesthesia in the chin and lower lip (the distribution of the mental nerve).Intraorally, if the fracture occurs in the tooth bearing area, a step may seen between the teeth on either side of the fracture or a space can be seen (often mistaken for a lost tooth) and bleeding from the gingiva in the area. There can be an open bite where the lower teeth, no longer meet the upper teeth. In the case of a unilateral condylar fracture the back teeth on the side of the fracture will meet and the open bite will get progressively greater towards the other side of the mouth.Sometimes bruising will develop in the floor of the mouth (sublingual eccymosis) and the fracture can be moved by moving either side of the fracture segment up and down. For fractures that occur in the non-tooth bearing area (condyle, ramus, and sometimes the angle) an open bite is an important clinical feature since little else, other than swelling, may be apparent.: page number needed
Condylar
This type of fractured mandible can involve one condyle (unilateral) or both (bilateral). Unilateral condylar fracture may cause restricted and painful jaw movement. There may be swelling over the temporomandibular joint region and bleeding from the ear because of lacerations to the external auditory meatus. The hematoma may spread downwards and backwards behind the ear, which may be confused with Battles sign (a sign of a base of skull fracture), although this is an uncommon finding so if present, intra-cranial injury must be ruled out. If the bones fracture and overlie each other there may be shortening of the height of the ramus. This results in gagging of the teeth on the fractured side (the teeth meet too soon on the fractured side, and not on the non fractured side, i.e. "open bite" that becomes progressively worse to the unaffected side). When the mouth is opened, there may be deviation of the mandible towards the fractured side. Bilateral condylar fractures may cause the above signs and symptoms, but on both sides. Malocclusion and restricted jaw movement are usually more severe. Bilateral body or parasymphysis fractures are sometimes termed "flail mandible", and can cause involuntary posterior movement of the tongue with subsequent obstruction of the upper airway. Displacement of the condyle through the roof of the glenoid fossa and into the middle cranial fossa is rare. Other rare complications of mandibular trauma include internal carotid artery injury, and obliteration of the ear canal due to posterior condylar dislocation. Bilateral condylar fractures combined with a symphyseal fracture is sometimes termed a guardsmans fracture. The name comes from this injury occurring in soldiers who faint on parade grounds and strike the floor with their chin.
Diagnosis
Plain film radiography
Traditionally, plain films of the mandible would be exposed but had lower sensitivity and specificity owing to overlap of structures. Views included AP (for parasymphsis), lateral oblique (body, ramus, angle, coronoid process) and Townes (condyle) views. Condylar fractures can be especially difficult to identify, depending on the direction of condylar displacement or dislocation so multiple views of it are usually examined with two views at perpendicular angles.
Panoramic radiography
Panoramic radiographs are tomograms where the mandible is in the focal trough and show a flat image of the mandible. Because the curve of the mandible appears in a 2-dimensional image, fractures are easier to spot leading to an accuracy similar to CT except in the condyle region. In addition, broken, missing or malaligned teeth can often be appreciated on a panoramic image which is frequently lost in plain films. Medial/lateral displacement of the fracture segments and especially the condyle are difficult to gauge so the view is sometimes augmented with plain film radiography or computed tomography for more complex mandible fractures.
Computed tomography
Computed tomography is the most sensitive and specific of the imaging techniques. The facial bones can be visualized as slices through the skeletal in either the axial, coronal or sagittal planes. Images can be reconstructed into a 3-dimensional view, to give a better sense of the displacement of various fragments. 3D reconstruction, however, can mask smaller fractures owing to volume averaging, scatter artifact and surrounding structures simply blocking the view of underlying areas.Research has shown that panoramic radiography is similar to computed tomography in its diagnostic accuracy for mandible fractures and both are more accurate than plain film radiograph. The indications to use CT for mandible fracture vary by region, but it does not seem to add to diagnosis or treatment planning except for comminuted or avulsive type fractures, although, there is better clinician agreement on the location and absence of fractures with CT compared to panoramic radiography.
Classification
There are various classification systems of mandibular fractures in use.
Location
This is the most useful classification, because both the signs and symptoms, and also the treatment are dependent upon the location of the fracture. The mandible is usually divided into the following zones for the purpose of describing the location of a fracture (see diagram): condylar, coronoid process, ramus, angle of mandible, body (molar and premolar areas), parasymphysis and symphysis.
Alveolar
This type of fracture involves the alveolus, also termed the alveolar process of the mandible.
Condylar
Condylar fractures are classified by location compared to the capsule of ligaments that hold the temporomandibular joint (intracapsular or extracapsular), dislocation (whether or not the condylar head has come out of the socket (glenoid fossa) as the muscles (lateral pterygoid) tend to pull the condyle anterior and medial) and neck of the condyle fractures. E.g. extracapsular, non-displaced, neck fracture. Pediatric condylar fractures have special protocols for management.
Coronoid
Because the coronoid process of the mandible lies deep to many structures, including the zygomatic complex (ZMC), it is rare to be broken in isolation. It usually occurs with other mandibular fractures or with fracture of the zygomatic complex or arch. Isolated fractures of the coronoid process should be viewed with suspicion and fracture of the ZMC should be ruled out.
Ramus
Ramus fractures are said to involve a region inferiorly bounded by an oblique line extending from the lower third molar (wisdom tooth) region to the posteroinferior attachment of the masseter muscle, and which could not be better classified as either condylar or coronoid fractures.
Angle
The angle of the mandible refers to the angle created by the arrangement of the body of the mandible and the ramus. Angle fractures are defined as those that involve a triangular region bounded by the anterior border of masseter muscle and an oblique line extending from the lower third molar (wisdom tooth) region to the posteroinferior attachment of the masseter muscle.
Body
Fractures of the mandibular body are defined as those that involve a region bounded anteriorly by the parasymphysis (defined as a vertical line just distal to the canine tooth) and posteriorly by the anterior border of the masseter muscle.
Parasymphysis
Parasymphyseal fractures are defined as mandibular fractures that involve a region bounded bilaterally by vertical lines just distal to the canine tooth.
Symphysis
Symphyseal fractures are a linear fractures that run in the midline of the mandible (the symphysis).
Fracture type
Mandibular fractures are also classified according to categories that describe the condition of the bone fragments at the fracture site and also the presence of communication with the external environment.
Greenstick
Greenstick fractures are incomplete fractures of flexible bone, and for this reason typically occur only in children. This type of fracture generally has limited mobility.
Simple
A simple fracture describes a complete transection of the bone with minimal fragmentation at the fracture site.
Comminuted
The opposite of a simple fracture is a comminuted fracture, where the bone has been shattered into fragments, or there are secondary fractures along the main fracture lines. High velocity injuries (e.g. those caused by bullets, improvised explosive devices, etc...) will frequently cause comminuted fractures.
Compound
A compound fracture is one that communicates with the external environment. In the case of mandibular fractures, communication may occur through the skin of the face or with the oral cavity. Mandibular fractures that involve the tooth-bearing portion of the jaw are by definition compound fractures, because there is at least a communication via the periodontal ligament with the oral cavity and with more displaced fractures there may be frank tearing of the gingival and alveolar mucosa.
Involvement of teeth
When a fracture occurs in the tooth bearing portion of the mandible, whether or not it is dentate or edentulous will affect treatment. Wiring of the teeth helps stabilize the fracture (either during placement of osteosynthesis or as a treatment by itself), so the lack of teeth will guide treatment. When an edentulous mandible (no teeth) is less than 1 cm in height (as measured on panoramic radiograph or CT scan) additional risks apply because the blood flow from the marrow (endosseous) is minimal and the healing bone must rely on blood supply from the periosteum surrounding the bone. If a fracture occurs in a child with mixed dentition different treatment protocols are needed.Other fractures of the body, are classified as open or closed. Because fractures that involve the teeth, by definition, communicate with the mouth this distinction is largely lost in mandible fractures. Condylar, ramus, and coronoid process fractures are generally closed whereas angle, body and parasymphsis fractures are generally open.
Displacement
The degree to which the segments are separated. The larger the separation, the more difficult it is to bring them back together (approximate the segments)
Favourability
For angle and posterior body fractures, when the angle of the fracture line is angled back (more posterior at the top of the jaw and more anterior at the bottom of the jaw) the muscles tend to bring the fracture segments together. This is called favorable. When the angle of the fractures is pointing to the front, it is unfavorable.
Age of the fracture
While mandible fractures have similar complication rates whether treated immediately or days later, older fractures are believed to have higher non-union and infection rates although the data on this makes it difficult to draw firm conclusions.
Treatment
Like all fractures, consideration has to be given to other illnesses that might jeopardize the patient, then to reduction and fixation of the fracture itself. Except in avulsive type injuries, or those where there might be airway compromise, a several day delay in the treatment of mandible fractures seems to have little impact on the outcome or complication rates.
General considerations
Since mandible fractures are usually the result of blunt force trauma to the head and face, other injuries need to be considered before the mandible fracture. First and foremost is compromise of the airway. While rare, bilateral mandible fractures that are unstable can cause the tongue to fall back and block the airway. Fractures such as a symphyseal or bilateral parasymphyseal may lead to mobility of the central portion of the mandible where genioglossus attaches, and allow the tongue to fall backwards and block the airway. In larger fractures, or those from high velocity injuries, soft tissue swelling can block the airway.In addition to the potential for airway compromise, the force delivered to break the jaw can be great enough to either fracture the cervical spine or cause intra-cranial injury (head injury). It is common for both to be assessed with facial fractures.Finally, vascular injury can result (with particular attention to the internal carotid and jugular) from high velocity injuries or severely displaced mandible fractures.
Loss of consciousness combined with aspiration of tooth fragments, blood and possibly dentures mean that the airway may be threatened.
Reduction
Reduction refers to approximating the ends of the bones edges that are broken. This is done with either an open technique, where an incision is made, the fracture is found and is physically manipulated into place, or closed technique where no incision is made.The mouth is unique, in that the teeth are well secured to the bone ends but come through epithelium (mucosa). A leg or wrist, for instance, has no such structure to help with a closed reduction. In addition, when the fracture happens to be in a tooth bearing area of the jaws, aligning the teeth well usually results in alignment of the fracture segments.To align the teeth, circumdental wiring is often used where wire strands (typically 24 gauge or 26 gauge) are wrapped around each tooth then attached to a stainless steel arch bar. When the maxillary (top) and mandibular (bottom) teeth are aligned together, this brings the fracture segments into place. Higher tech solutions are also available, to help reduce the segments with arch bars using bonding technology.
Fixation
Simple fractures are usually treated with closed reduction and indirect skeletal fixation, more commonly referred to as maxillo-mandibular fixation (MMF). The closed reduction is explained above. The indirect skeletal fixation is accomplished by placing an arch bar, secured to the teeth on the maxillary and mandibular dentition, then securing the top and bottom arch bars with wire loops.Many alternatives exist to secure the maxillary and mandibular dentition including resin bonded arch bars, Ivy loops (small eyelets of wires), orthodontic bands and MMF bone screws where titanium screws with holes in the head of them are screwed into the basal bone of the jaws then secured with wire.Closed reduction with direct skeletal fixation follows the same premise as MMF except that wires are passed through the skin and around the bottom jaw in the mandibule and through the piriform rim or zygomatic buttresses of the maxilla then joined to secure the jaws. The option is sometimes used when a patient is edentulous (has no teeth) and rigid internal fixation cannot be used.Open reduction with direct skeletal fixation allows the bones to be directly mandibulated through an incision so that the fractured ends meet, then they can be secured together either rigidly (with screws or plates and screws) or non-rigidly (with transosseous wires). There are a multitude of various plate and screw combinations including compression plates, non-compression plates, lag-screws, mini-plates and biodegradable plates.External fixation, which can be used with either open or closed reduction uses a pin system, where long screws are passed through the skin and into either side of a fracture segment (typically 2 pins per side) then secured in place using an external fixator. This is a more common approach when the bone is heavily comminuted (shattered into small pieces, for instance in a bullet wound) and when the bone is infected (osteomyelitis).
Regardless of the method of fixation, the bone need to remain relatively stable for a period of 3–6 weeks. On average, the bone gains 80% of its strength by 3 weeks and 90% of it by 4 weeks. There is great variation depending on the severity of injury, health of the wound, and age of the patient.
Current clinical evidence
A 2013 Cochrane review assessed clinical studies on surgical (open reduction) and non-surgical (closed reduction) management of mandible fractures that do not involve the condyle. The review found insufficient evidence to recommend the effectiveness of any single intervention.
Special considerations
Condyle
The best treatment for condylar fractures is controversial. There are two main options, namely closed reduction or open reduction and fixation. Closed reduction may involve intermaxillary fixation, where the jaws are splinted together in the correct position for a period of weeks. Open reduction involves surgical exposure of the fracture site, which can be carried out via incisions within the mouth or incisions outside the mouth over the area of the condyle. Open reduction is sometimes combined with use of an endoscope to aid visualization of fracture site. Although closed reduction carries a risk of the bone healing out of position, with consequent alteration of the bite or the creation of facial asymmetry, it does not risk temporary damage to the facial nerve or result in any facial scar that accompanies open reduction. A systematic review was unable to find sufficient evidence of the superiority of one method over another in the management of condylar fractures. Paediatric condylar fractures are especially problematic, owing to the remaining growth potential and possibility of ankylosis of the joint. Early mobilization is often recommended as in the Walker protocol.
Edentulous mandible
A broken jaw that has no teeth in it faces two additional issues. First, the lack of teeth makes reduction and fixation using MMF difficult. Instead of placing circumdental wires around the teeth, existing dentures can be left in (or Gunning splints, a type of temporary denture) and the mandible fixated to the maxilla using skeletal fixation (circummandibular and circumzygomatic wires) or using MMF bone screws. More commonly, open reduction and rigid internal fixation is placed.When the width of the mandible is less than 1 cm, the jaw loses its endosteal blood supply. Instead, the blood supply comes largely from the periosteum. Open reduction (which normally strips the periosteum during the dissection) can lead to avascular necrosis. In these cases, oral surgeons sometimes opt for external fixation, closed reduction, supraperiosteal dissection or other techniques to maintain the periosteal blood flow.
High velocity injuries
In high velocity injuries, the soft tissue can be severely damaged far from the bullet wound itself due to hydrostatic shock. Because of this the airway must be carefully managed and vessels well examined. Because the jaw can be highly comminuted, MMF and rigid internal fixation can be difficult. Instead, external fixation is often used,.
Pathologic fracture
Fractures where large cysts or tumours are in the area (and weaken the jaw), where there is an area of osteomyelitis or where osteonecrosis exist cause special challenges to fixation and healing. Cysts and tumours can limit effective bone to bone contact and osteomyelitis or osteonecrosis compromise blood supply to the bone. In all of the situations, healing will be delayed and sometimes, resection is the only alternative to treatment.
Prognosis
The healing time for a routine mandible fractures is 4–6 weeks whether MMF or rigid internal fixation (RIF) is used. For comparable fractures, patients who received MMF will lose more weight and take longer to regain mouth opening, whereas, those who receive RIF have higher infection rates.The most common long-term complications are loss of sensation in the mandibular nerve, malocclusion and loss of teeth in the line of fracture. The more complicated the fracture (infection, comminution, displacement) the higher the risk of fracture.Condylar fractures have higher rates of malocclusion which in turn are dependent on the degree of displacement and/or dislocation. When the fracture is intracapsular there is a higher rate of late-term osteoarthritis and the potential for ankylosis although the later is a rare complication as long as mobilization is early. Pediatric condylar fractures have higher rates of ankylosis and the potential for growth disturbance.,Rarely, mandibular fracture can lead to Freys syndrome.
Epidemiology
Mandible fracture causes vary by the time period and the region studied. In North America, blunt force trauma (a punch) is the leading cause of mandible fracture whereas in India, motor vehicle collisions are now a leading cause. On battle grounds, it is more likely to be high velocity injuries (bullets and shrapnel). Prior to the routine use of seat belts, airbags and modern safety measures, motor vehicle collisions were a leading cause of facial trauma. The relationship to blunt force trauma explains why 80% of all mandible fractures occur in males. Mandibular fracture is a rare complication of third molar removal, and may occur during the procedure or afterwards. With respect to trauma patients, roughly 10% have some sort of facial fracture, the majority of which come from motor vehicle collisions. When the person is unrestrained in a car, the risk of fracture rises 50% and when an unhelmeted motorcyclist the risk rises 4-fold.
History
Management of mandible fractures has been mentioned as early as 1700 B.C. in the Edwin Smith Papyrus and later by Hippocrates in 460 B.C., "Displaced but incomplete fractures of the mandible where continuity of the bone is preserved should be reduced by pressing the lingual surface with the fingers...". Open reduction was described as early as 1869. Since the late 19th century, modern techniques including MMF (see above) have been described with titanium based rigid internal fixation becoming commonplace since the 1970s and biodegradable plates and screws being available since the 1980s.
References
== External links == |
Tubo-ovarian abscess | A tubo-ovarian abscess (TOA) is one of the late complications of pelvic inflammatory disease (PID) and can be life-threatening if the abscess ruptures and results in sepsis. It consists of an encapsulated or confined pocket of pus with defined boundaries that forms during an infection of a fallopian tube and ovary. These abscesses are found most commonly in reproductive age women and typically result from upper genital tract infection. It is an inflammatory mass involving the fallopian tube, ovary and, occasionally, other adjacent pelvic organs. A TOA can also develop as a complication of a hysterectomy.: 103 Symptoms typically include fever, an elevated white blood cell count, lower abdominal-pelvic pain, and/or vaginal discharge. Fever and leukocytosis may be absent. TOAs are often polymicrobial with a high percentage of anaerobic bacteria. The cost of treatment in the United States is approximately $2,000 per patient, which equals about $1.5 billion annually. Though rare, TOA can occur without a preceding episode of PID or sexual activity.
Signs and symptoms
The signs and symptoms of tubo-ovarian abscess (TOA) are the same as with pelvic inflammatory disease (PID) with the exception that the abscess can be found with magnetic resonance imaging (MRI), sonography and x-ray. It also differs from PID in that it can create symptoms of acute-onset pelvic pain. Typically this disease is found in sexually active women. Tubo-ovarian abscess can mimic abdominal tumours.
Complications
Complications of TOA are related to the possible removal of one or both ovaries and fallopian tubes. Without these reproductive structures, fertility can be affected. Surgical complications can develop and include:
Allergic shock due to anesthetics
A paradoxical reaction to a drug
Infection
Cause
The development of TOA is thought to begin with the pathogens spreading from the cervix to the endometrium, through the salpinx, into the peritoneal cavity and forming the tubo-ovarian abscess with (in some cases) pelvic peritonitis. TOA can develop from the lymphatic system with infection of the parametrium from an intrauterine device (IUD). Bacteria recovered from TOAs are Escherichia coli, Bacteroides fragilis, other Bacteroides species, Peptostreptococcus, Peptococcus, and aerobic streptococci. Long term IUD use is associated with TOA. Actinomyces is also recovered from TOA.
Diagnosis
Laparoscopy and other imaging tools can visualize the abscess. Physicians are able to make the diagnosis if the abscess ruptures when the woman begins to have lower abdominal pain that then begins to spread. The symptoms then become the same as the symptoms for peritonitis. Sepsis occurs, if left untreated.: 103 Ultrasonography is a sensitive enough imaging tool that it can accurately differentiate between pregnancy, hemorrhagic ovarian cysts, endometriosis, ovarian torsion, and tubo-ovarian abscess. Its availability, the relative advancement in the training of its use, its low cost, and because it does not expose the woman (or fetus) to ionizing radiation, ultrasonography an ideal imaging procedure for women of reproductive age.
Prevention
Risk factors have been identified which indicate what women will be more likely to develop TOA. These are: increased age, IUD insertion, chlamydia infection, and increased levels of certain proteins (CRP and CA-125) and will alert clinicians to follow up on unresolved symptoms of PID.
Treatment
Treatment for TOA differs from PID in that some clinicians recommend patients with tubo-ovarian abscesses have at least 24 hours of inpatient parenteral treatment with antibiotics, and that they may require surgery. If surgery becomes necessary, pre-operative administration of broad-spectrum antibiotics is started and removal of the abscess, the affected ovary and fallopian tube is done. After discharge from the hospital, oral antibiotics are continued for the length of time prescribed by the physician.: 103 Treatment is different if the TOA is discovered before it ruptures and can be treated with IV antibiotics. During this treatment, IV antibiotics are usually replaced with oral antibiotics on an outpatient basis. Patients are usually seen three days after hospital discharge and then again one to two weeks later to confirm that the infection has cleared.: 103 Ampicillin/sulbactam plus doxycycline is effective against C. trachomatis, N. gonorrhoeae, and anaerobes in women with tubo-ovarian abscess. Parenteral Regimens described by the Centers for Disease Control and prevention are Ampicillin/Sulbactam 3 g IV every 6 hours and Doxycycline 200 mg orally or IV every 24 hours, though other regiments that are used for pelvic inflammatory disease have been effective.
Epidemiology
The epidemiology of TOA is closely related to that of pelvic inflammatory disease which is estimated to one million people yearly.
References
== External links == |
Cobalt poisoning | Cobalt poisoning is intoxication caused by excessive levels of cobalt in the body. Cobalt is an essential element for health in animals in minute amounts as a component of Vitamin B12. A deficiency of cobalt, which is very rare, is also potentially lethal, leading to pernicious anemia.Exposure to cobalt metal dust is most common in the fabrication of tungsten carbide. Another source is from wear and tear of certain metal-on-metal hip prostheses.Per the International Agency for Research on Cancer (IARC), cobalt metal with tungsten carbide is "probably carcinogenic to humans" (IARC Group 2A Agent), whereas cobalt metal without tungsten carbide is "possibly carcinogenic to humans" (IARC Group 2B Agent).
Cobalt salts
The LD50 value for soluble cobalt salts has been estimated to be between 150 and 500 mg/kg. Thus, for a 100 kg person the LD50 would be about 20 grams.Soluble cobalt(II) salts are "possibly carcinogenic to humans" (IARC Group 2B Agents).
Beer drinkers cardiomyopathy
In August 1965, a person presented to a hospital in Quebec City with symptoms suggestive of alcoholic cardiomyopathy. Over the next eight months, fifty more cases with similar findings appeared in the same area with twenty of these being fatal. It was noted that all were heavy drinkers who mostly drank beer and preferred the Dow brand; thirty out of those drank more than 6 litres (12 pints) of beer per day. Epidemiological studies found that Dow had been adding cobalt sulfate to the beer for foam stability since July 1965 and that the concentration added in the Quebec city brewery was ten times that of the same beer brewed in Montreal where there were no reported cases. A 1972 paper noted that several dozen cases were also identified over a similar time period in Omaha, Nebraska; Minneapolis, Minnesota; and Belgium.
Cobalt in the environment
Plants, animals, and humans can all be affected by high cobalt concentrations in the environment. For plants, the uptake and distribution of cobalt is entirely species-specific. In some species of plants, the overaccumulation of cobalt can lead to an iron deficiency. This in turn leads to poor growth of the plant as well as leaf loss which overall decreases the amount of oxygen produced by plants during photosynthesis. Eventually the deficiency would lead to plant death. One such example was seen in an experiment involving the effects of increased cobalt concentration on tomato plants. As the dosage of cobalt in the soil surrounding the plants increased, so too did the rate of necrosis of the leaves of the tomato plant. Over time this led to an inability of the plant to produce fruit and eventually the plant died.
References
== External links == |
Cadmium poisoning | Cadmium is a naturally occurring toxic metal with common exposure in industrial workplaces, plant soils, and from smoking. Due to its low permissible exposure in humans, overexposure may occur even in situations where trace quantities of cadmium are found. Cadmium is used extensively in electroplating, although the nature of the operation does not generally lead to overexposure. Cadmium is also found in some industrial paints and may represent a hazard when sprayed. Operations involving removal of cadmium paints by scraping or blasting may pose a significant hazard. The primary use of cadmium is in the manufacturing of NiCd rechargeable batteries. The primary source for cadmium is as a byproduct of refining zinc metal. Exposures to cadmium are addressed in specific standards for the general industry, shipyard employment, the construction industry, and the agricultural industry.
Signs and symptoms
Acute
Acute exposure to cadmium fumes may cause flu-like symptoms including chills, fever, and muscle ache sometimes referred to as "the cadmium blues." Symptoms may resolve after a week if there is no respiratory damage. More severe exposures can cause tracheobronchitis, pneumonitis, and pulmonary edema. Symptoms of inflammation may start hours after the exposure and include cough, dryness and irritation of the nose and throat, headache, dizziness, weakness, fever, chills, and chest pain.
Chronic
Complications of cadmium poisoning include cough, anemia, and kidney failure (possibly leading to death). Cadmium exposure increases ones chances of developing cancer. Similar to zinc, long-term exposure to cadmium fumes can cause life long anosmia.
Bone and joints
One of the main effects of cadmium poisoning is weak and brittle bones. The bones become soft (osteomalacia), lose bone mineral density (osteoporosis), and become weaker. This results in joint and back pain, and increases the risk of fractures. Spinal and leg pain is common, and a waddling gait often develops due to bone deformities caused by the long-term cadmium exposure. The pain eventually becomes debilitating, with fractures becoming more common as the bone weakens. Permanent deformation in bones can occur. In extreme cases of cadmium poisoning, more body weight causes a fracture.
Renal
The kidney damage inflicted by cadmium poisoning is irreversible. The kidneys can shrink up to 30 percent. The kidneys lose their function to remove acids from the blood in proximal renal tubular dysfunction. The proximal renal tubular dysfunction causes hypophosphatemia, leading to muscle weakness and sometimes coma. Hyperchloremia also occurs. Kidney dysfunction also causes gout, a form of arthritis due to the accumulation of uric acid crystals in the joints because of high acidity of the blood (hyperuricemia). Cadmium exposure is also associated with the development of kidney stones.
Sources of exposure
Smoking is a significant source of cadmium exposure. Even small amounts of cadmium from smoking are highly toxic to humans, as the lungs absorb cadmium more efficiently than the stomach. Cadmium is emitted to the electronic cigarette (EC) aerosol but, on currently available data, the lifetime cancer risk (LCR) calculated doesn’t exceed the acceptable risk limit.
Environmental
Buildup of cadmium levels in the water, air, and soil has been occurring particularly in industrial areas. Environmental exposure to cadmium has been particularly problematic in Japan where many people have consumed rice that was grown in cadmium-contaminated irrigation water. This phenomenon is known as itai-itai disease.People who live near hazardous waste sites or factories that release cadmium into the air have the potential for exposure to cadmium in air. However, numerous state and federal regulations in the United States control the amount of cadmium that can be released to the air from waste sites and incinerators so that properly regulated sites are not hazardous. The general population and people living near hazardous waste sites may be exposed to cadmium in contaminated food, dust, or water from unregulated or accidental releases. Numerous regulations and use of pollution controls are enforced to prevent such releases.Some sources of phosphate in fertilizers contain cadmium in amounts of up to 100 mg/kg, which can lead to an increase in the concentration of cadmium in soil (for example in New Zealand). Cadmium can be removed from soil using nanopolymers.
Food
Food is another source of cadmium. Plants may contain small or moderate amounts in non-industrial areas, but high levels may be found in the liver and kidneys of adult animals. The daily intake of cadmium through food varies by geographic region. Intake is reported to be approximately 8 to 30μg in Europe and the United States versus 59 to 113 μg in various areas of Japan.
Occupational exposure
In the 1950s and 1960s industrial exposure to cadmium was high, but as the toxic effects of cadmium became apparent, industrial limits on cadmium exposure have been reduced in most industrialized nations and many policy makers agree on the need to reduce exposure further. While working with cadmium it is important to do so under a fume hood to protect against dangerous fumes. Brazing fillers which contain cadmium should be handled with care. Serious toxicity problems have resulted from long-term exposure to cadmium plating baths.
Workers can be exposed to cadmium in air from the smelting and refining of metals, or from the air in plants that make cadmium products such as batteries, coatings, or plastics. Workers can also be exposed when soldering or welding metal that contains cadmium. Approximately 512,000 workers in the United States are in environments each year where cadmium exposure may occur. Regulations that set permissible levels of exposure, however, are enforced to protect workers and to make sure that levels of cadmium in the air are considerably below levels thought to result in harmful effects.Artists who work with cadmium pigments, which are commonly used in strong oranges, reds, and yellows, can easily accidentally ingest dangerous amounts, particularly if they use the pigments in dry form, as with chalk pastels, or in mixing their own paints.
Consumer products
Cadmium is used in nickel-cadmium batteries; these are some of the most popular and most common cadmium-based products.
In February 2010, cadmium was found in an entire line of Wal-Mart exclusive Miley Cyrus jewelry. The charms were tested at the behest of the Associated Press and were found to contain high levels of cadmium. Wal-Mart did not stop selling the jewelry until May 12 because "it would be too difficult to test products already on its shelves". On June 4 cadmium was detected in the paint used on promotional drinking glasses for the movie Shrek Forever After, sold by McDonalds Restaurants, triggering a recall of 12 million glasses.
Toxicology
Cadmium is an extremely toxic industrial and environmental pollutant classified as a human carcinogen: Group 1, according to the International Agency for Research on Cancer; Group 2a, according to Environmental Protection Agency (EPA); and a 1B carcinogen as classified by European Chemical Agency.
Toxicodynamics
Cellular toxicology
Inside cells, cadmium ions act as a catalytic hydrogen peroxide generator. This sudden surge of cytosolic hydrogen peroxide causes increased lipid peroxidation and additionally depletes ascorbate and glutathione stores. Hydrogen peroxide can also convert thiol groups on proteins into nonfunctional sulfonic acids and is also capable of directly attacking nuclear DNA. This oxidative stress causes the afflicted cell to manufacture large amounts of inflammatory cytokines.
Toxicokinetics
Inhaling cadmium-laden dust quickly leads to respiratory tract and kidney problems which can be fatal (often from kidney failure). Ingestion of any significant amount of cadmium causes immediate poisoning and damage to the liver and the kidneys. Compounds containing cadmium are also carcinogenic.
Diagnosis
Biomarkers of excessive exposure
Increased concentrations of urinary beta-2 microglobulin can be an early indicator of kidney dysfunction in persons chronically exposed to low but excessive levels of environmental cadmium. The urinary beta-2 microglobulin test is an indirect method of measuring cadmium exposure. Under some circumstances, the Occupational Health and Safety Administration requires screening for kidney damage in workers with long-term exposure to high levels of cadmium. Blood or urine cadmium concentrations provide a better index of excessive exposure in industrial situations or following acute poisoning, whereas organ tissue (lung, liver, kidney) cadmium concentrations may be useful in fatalities resulting from either acute or chronic poisoning. Cadmium concentrations in healthy persons without excessive cadmium exposure are generally less than 1 μg/L in either blood or urine. The ACGIH biological exposure indices for blood and urine cadmium levels are 5 μg/L and 5 μg/g creatinine, respectively, in random specimens. Persons who have sustained kidney damage due to chronic cadmium exposure often have blood or urine cadmium levels in a range of 25-50 μg/L or 25-75 μg/g creatinine, respectively. These ranges are usually 1000-3000 μg/L and 100-400 μg/g, respectively, in survivors of acute poisoning and may be substantially higher in fatal cases.
Treatment
Any person with cadmium poisoning must seek immediate medical attention. For a single exposure by ingestion, gastric decontamination by emesis or gastric lavage may be beneficial soon after exposure. Administration of activated charcoal has not been proven effective.Chelation therapies to remove cadmium are not effective, so the most important action is to prevent additional exposure. Detoxification of Cadmium (Cd) with EDTA and other chelators is possible. Clinically available chelators include EDTA, DMPS, DMSA, and British Anti-Lewisite (BAL). BAL is more toxic than its derivatives, DMPS and DMSA, and is seldom used clinically. EDTA, DMPS, and DMSA increase urinary excretion of Cd. Studies in vitro and in vivo suggest that EDTA is superior to DMSA in mobilizing intracellular Cd. As EDTA is approved by the FDA for lead and other heavy metals, and has a long history of safe use, it is most widely accepted for clinical use. Use of such chelators as has been seen as therapeutically beneficial to humans and animals when done using established protocols.
Epidemiology
In a mass cadmium poisoning in Japan, a marked prevalence for skeletal complications has been noted for older, postmenopausal women, however, the cause of the phenomenon is not fully understood, and is under investigation. Cadmium poisoning in postmenopausal women may result in an increased risk for osteoporosis. Current research has pointed to general malnourishment, as well as poor calcium metabolism relating to the womens age. Studies are pointing to damage of the mitochondria of kidney cells by cadmium as a key factor of the disease.
History
An experiment during the early 1960s involving the spraying of cadmium over Norwich was declassified in 2005 by the UK government, as documented in a BBC News article.
See also
Cobalt poisoning
Itai-itai disease
References
Footnotes
Shannon M. Heavy Metal Poisoning, in Haddad LM, Shannon M, Winchester JF(editors): Clinical Management of Poisoning and Drug Overdose, Third Edition, 1998.
"Cadmium and you" (PDF). Redgrave Court, Merton Road, Bootle, Merseyside, L20 7HS, United Kingdom: Health and Safety Executive. March 2010. Retrieved January 29, 2011.{{cite web}}: CS1 maint: location (link)
Hartwig, Andrea (2013). "Cadmium and Cancer". Cadmium: From Toxicity to Essentiality. Metal Ions in Life Sciences. Vol. 11. pp. 491–507. doi:10.1007/978-94-007-5179-8_15. ISBN 978-94-007-5178-1. PMID 23430782.
External links
ATSDR Case Studies in Environmental Medicine: Cadmium Toxicity U.S. Department of Health and Human Services
CDC - Cadmium - NIOSH Workplace Safety and Health Topic U.S. Department of Health and Human Services
National Pollutant Inventory - Cadmium and compounds
http://www.canoshweb.org/odp/html/cadmium.htm Archived 2021-03-09 at the Wayback Machine |
Spinal enthesopathy | Spinal enthesopathy is a form of enthesopathy affecting the spine.
References
== External links == |
Autoimmune progesterone dermatitis | Autoimmune progesterone dermatitis may appear as urticarial papules, deep gyrate lesions, papulovesicular lesions, an eczematous eruption, or as targetoid lesions.: 82 Autoimmune progesterone dermatitis initially manifests with eye symptoms, e.g. burning, and progresses into rashes. Its relapsing-remitting pattern in women correspond to the progesterone levels during the menstrual cycle, which spike twice a month. It is an extremely rare disease.
See also
Skin lesion
References
== External links == |
Infantile acne | Infantile acne is a form of acneiform eruption that occurs in infants from 6 weeks to 1 year of age. Typical symptoms include inflammatory and noninflammatory lesions, papules and pustules most commonly present on the face. No cause of infantile acne has been established but it may be caused by increased sebaceous gland secretions due to elevated androgens, genetics and the fetal adrenal gland causing increased sebum production. Infantile acne can resolve by itself by age 1 or 2 however treatment options include topical benzyl peroxide, topical retinoids and topical antibiotics in most cases.
Signs and symptoms
Infantile acne has a later onset and is less commonly seen than neonatal acne, occurring between 6 weeks to 1 year of age. It is also more commonly seen in boys rather than girls. Infantile acne tends to be more inflammatory and wide spread than neonatal acne. It presents with both open and closed comedones, papules and pustules. Cystic lesions are uncommon. Scarring can occur in severe cases. Very rarely, facial conglobate acne, a severe form of acne that involves extensive inflammation and nodule formation can develop and lead to extensive scarring. Lesions occur most commonly on the cheeks but can also appear on the chest and back. More severe occurrences may lead to development of more severe forms of acne in adolescence.
Causes
The cause of infantile acne is not known for certain. Research into higher occurrence in boys rather than girls imply that higher than normal levels of testicular androgens can cause increased sebaceous gland secretions. During the first 6–12 months of age, there is increased sebum production stimulated by luteinizing hormone (LH) and testosterone of testicular origin that stops after this period until adrenarche. Girls do not experience this.Genetics and family history play a role in influencing sebaceous gland size and activity, pore size and inflammation that can increase risk of onset and presentation of infantile acne.It is suggested that the fetal adrenal gland along with testicular androgen could be the cause of infantile acne. During the neonatal period, there is increased sebum production through an enlarged zona reticularis (an androgen producing area) on the fetal adrenal gland that gradually decreases to very low levels at around 1 years of age, coinciding with when infantile acne tends to resolve. The fetal adrenal gland produces androgens such as dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) that stimulate sebaceous glands.
Diagnosis
Diagnosis is based on presentation of comedones primarily on the face of an infant of 6–12 months of age. Severity can be mild, moderate or severe and can be determined from the presence and distribution of comedones and inflammatory lesions such as papules and nodules. A physical may be followed up next with particular attention paid to signs of an endocrine disorder including normal growth and weight, testicular growth, breast development, hirsutism or growth of pubic hair. Hormonal workup may not be necessary unless one of these abnormalities is present, then work up of testosterone, DHEA, DHEAS, LH and FSH or referral to a pediatric endocrinologist specialist may be recommended.
Differential diagnosis
It is important to differentiate infantile acne from other forms of acneiform eruptions. Acne venenata infantum is a form of acne characterized by comedone formation and induced by chemical irritants on the skin. This can include comedogenic products such as lotions, ointments, creams and oils. Upon discontinuation of these products, lesions will heal within 6–8 weeks.Other conditions that should be considered include periorificial dermatitis, keratosis pilaris, sebaceous hyperplasia and infections. Pyodermas and panniculitis should be considered in severe cases of inflammatory acne or in cases of acne conglobata while hyperandrogenism should be ruled out in cases of persistent infantile acne.
Treatment
Infantile acne is a self-limiting condition that resolves by itself within 6–12 months of occurrence or occasionally by ages 4–5 and does not require treatment in most cases but topical therapies can be used, especially in more severe cases.The goals of treatment are to reduce sebum production, prevent formation of microcomedones, suppress the growth of bacteria and reduce inflammation. As there are no US FDA approved medications for treatment of infantile acne due to lack of high quality trials in patients under 9, recommendations for treatment is based on observations in adult and adolescent populations.
Benzoyl peroxide
Benzoyl peroxide (BPO) is first line for mild cases of infantile acne due to its safety and effectiveness. BPO concentrates within cells of sebaceous follicles where it generates free radicals to oxidize proteins in bacteria such as P. acnes. This leads to bacterial death. It additionally works as a mild comedolytic and anti-inflammatory. No bacterial resistance has been reported from BPO usage and in fact it can help limit resistance to antibiotics. Common side effects include burning, stinging, scaling and dryness at the sight of application and can be managed by reducing quantity applied, frequency of application, using a less potent product and use of non-comedogenic moisturizers.
Retinoids
Topical retinoids both alone and in combination are also first line for treating mild to moderate cases of acne. Safety and efficacy has been demonstrated in individuals 12–18 years of age. Retinoids prevent formation of comedones and promote comedolysis by binding to retinoic receptors and normalizing growth of keratinocytes. Tretinoin and adapalene have demonstrated efficacy in reducing inflammation. Adapalene as a newer retinoid is thought to be more effective and better tolerated than others in this class. As a topical product, it has similar side effects to topical BPO of burning, stinging, drying and scaling which can be managed much the same way. Reducing the potency of initial treatment, using a non-comedogenic moisturizers, and applying a small amount on the whole face rather than spot-treating may reduce severity of side effects.In severe cases, oral isotretinoin may be recommended to prevent scarring. Dosing ranges from 0.2 mg/kg/day to 2 mg/kg/day for several months to over a year with careful monitoring. Monitoring may include complete blood count with differential and baseline liver function and lipids tests followed by routine liver function and lipid tests while on treatment.
Antibiotics
Topical antibiotics
Topical antibiotics are often used in cases of inflammatory infantile acne in combination with another topical treatment to prevent emergence of antibiotic resistance especially for periods longer than a few weeks. Clindamycin and erythromycin are the most commonly prescribed topical antibiotics for acne with coverage for S. aureus and P. acnes. These bacteriostatic antibiotics interfere with bacterial protein synthesis, preventing formation of free fatty acids by these bacteria that cause inflammation.
Oral antibiotics
In severe cases of infantile acne, especially with the presence of nodules and cysts with risks of scarring, oral antibiotics may be used. First line therapy is erythromycin with sulfamethoxazole-trimethoprim as a secondary choice in cases of P. acnes resistance. It is suggested not to use tetracyclines due to risks of permanently staining teeth in children under the age of 7. Side effects of erythromycin include gastrointestinal upset. There has however been concerns about resistant P. acnes due to widespread usage of antibiotics, and therefore steps taken to minimize resistance such as use in combination with BPO is highly recommended by experts.
Epidemiology
Infantile acne effects around 2% of children with a higher occurrence in males rather than females. Of around 9.2 million visits to outpatient care for pediatric acne, 3% or 276,000 visits, were due to neonatal and pediatric acne in the United States from 2000 to 2010.
See also
List of cutaneous conditions
Neonatal acne
References
== External links == |
Ovarian vein syndrome | In medicine, ovarian vein syndrome is a rare (possibly not uncommon, certainly under-diagnosed) condition in which a dilated ovarian vein compresses the ureter (the tube that brings the urine from the kidney to the bladder). This causes chronic or colicky abdominal pain, back pain and/or pelvic pain. The pain can worsen on lying down or between ovulation and menstruation. There can also be an increased tendency towards urinary tract infection or pyelonephritis (kidney infection). The right ovarian vein is most commonly involved, although the disease can be left-sided or affect both sides. It is currently classified as a form of pelvic congestion syndrome.
Mechanism
Normally, the ovarian vein crosses over the ureter at the level of the fourth or fifth lumbar vertebral bone. The ureter itself courses over the external iliac artery and vein. Thus, these vessels can impinge on the ureter causing obstruction. The left ovarian vein ends in the renal vein whereas the right ovarian vein normally enters into the inferior vena cava. In the case of right ovarian vein syndrome, the vein often ends in the renal vein. This is thought to contribute to venous engorgement, in analogy to what is seen in varicoceles, which arise more commonly on the left side. The straight angle between the ovarian vein (or testicular vein in males in the case of varicocoele) and the renal vein has been proposed as a cause of decreased blood return.A related diagnosis is "Nutcraker Syndrome" where the left renal vein is described as being compressed between the aorta and the superior mesenteric artery. This is reported to cause collateral flow paths to open up to drain the left kidney i.e. reversed flow (reflux caudally) in the left renal vein. Pelvic Congestion Syndrome, vaginal and vulval varices, lower limb varices are clinical sequelae. Virtually all such patient are female and have been pregnant, often multiply.
The ovarian vein often displays incompetent valves. This has been observed more often in women with a higher number of previous pregnancies. Pressure from the baby might hinder the return of blood through the ovarian vein. It has to be noted however that dilation of the urinary tract is a normal observation in pregnancy, due to mechanical compression and the hormonal action of progesterone. Ovarian vein dilatation might also follow venous thrombosis (clotting inside the vein).
Another proposed mechanism of obstruction is when the ovarian vein and ureter both run through a sheath of fibrous tissue, following a local inflammation. This could be seen as a localised form of retroperitoneal fibrosis.Following obstruction, the ureter displays an abnormal peristalsis (contractions) towards the kidney instead of towards the bladder. This is thought to cause the colicky pain (similar to renal colic), and it is relieved after surgical decompression.
Diagnosis
Since it is a rare disease, it remains a diagnosis of exclusion of other conditions with similar symptoms. The diagnosis is supported by the results of imaging studies such as computed tomography or magnetic resonance imaging, ultrasound of the abdomen (with or without doppler imaging) or intravenous urography.Specialist vascular ultrasonographers should routinely look for left ovarian vein reflux in patients with lower limb varices especially if not associated with long or short saphenous reflux. The clinical pattern of varices differs between the two types of lower limb varices.
CT scanning is used to exclude abdominal or pelvic pathology. CT-Angiography/Venography can often demonstrate left ovarian vein reflux and image an enlarged left ovarian vein but is less sensitive and much more expensive than duplex Doppler ultrasound examination. Ultrasound requires that the ultrasonographer be experienced in venous vascular ultrasound and so is not always readily available. A second specialist ultrasound exam remains preferable to a CT scan.As a wide range of pelvic and abdominal pathology can cause symptoms consistent with those symptoms due to left ovarian vein reflux, prior to embolisation of the left ovarian vein, a careful search for such diagnoses is essential. Consultation with general surgeons, gynaecologists, and possibly CT scanning should always be considered.
Treatment
Treatment consists of painkillers and surgical ablation of the dilated vein. This can be accomplished with open abdominal surgery (laparotomy) or keyhole surgery (laparoscopy). Recently, the first robot-assisted surgery was described.Another approach to treatment involves catheter-based embolisation, often preceded by phlebography to visualise the vein on X-ray fluoroscopy.Ovarian vein coil embolisation is an effective and safe treatment for pelvic congestion syndrome and lower limb varices of pelvic origin. Many patients with lower limb varices of pelvic origin respond to local treatment i.e. ultrasound guided sclerotherapy. In those cases, ovarian vein coil embolisation should be considered second line treatment to be used if veins recur in a short time period i.e. 1–3 years. This approach allows further pregnancies to proceed if desired. Bilateral coil embolisation is not advised if a future pregnancy is possible. This treatment has largely superseded operative options.Coil embolisation requires exclusion of other pelvic pathology, expertise in endovascular surgery, correct placement of appropriate sized coils in the pelvis and also in the upper left ovarian vein, careful pre- and post-procedure specialist vascular ultrasound imaging, a full discussion of the procedure with the patient i.e. informed consent. Complications, such as coil migration, are rare but reported. Their sequelae are usually minor.If a Nutcracker compression (see below) is discovered, operative relocation of the renal vein should be considered before embolization of the ovarian vein. Stenting is not advised. Reducing outflow obstruction should always be the main objective.
History
The entity was first described by Clark in 1964. Following initial scepticism and lively discussion in the medical literature, it is now recognised by many authors.
== References == |
Autoimmune polyendocrine syndrome type 3 | Autoimmune polyendocrine syndromes (APS) occur when more than one autoimmune disease occurs in endocrine glands. These syndromes are also called Polyendocrine Autoimmune Disorders. In Type 3, autoimmune thyroiditis and another endocrine autoimmune disease are present, but the adrenal cortex is not involved.
References
== External links == |
Queensland tick typhus | Queensland tick typhus is a zoonotic disease caused by the bacterium Rickettsia australis.
It is transmitted by the ticks Ixodes holocyclus and Ixodes tasmani.
Signs and symptoms
Queensland tick typhus is a tick-borne disease. Onset of the illness is variable; there is an incubation period of 2 to 14 days after being bitten by the infected tick. The clinical features of this illness include fever, headache, an eschar at the site of the tick bite, erythematous eruption and satellite lymphadenopathy. Queensland tick typhus symptomatically resembles Rocky Mountain spotted fever, a less severe tick-borne disease. If left untreated for longer than one to two weeks, the disease can take longer to recover from and pose a heightened risk of pneumonitis, encephalitis, septic shock, or even death. In some cases, even after the initial rash is cleared, the person may still experience prolonged lethargy or fatigue, which is common in such rickettsial infections.
Causes
Queensland tick typhus is caused by the bacteria Rickettsia australis from the genus Rickettsia.
Tick life cycle
The tick life cycle consists of four stages: egg, larva, nymph, and adult. An adult female tick can lay over a thousand eggs in her lifetime. Once a tick hatches from an egg, it enters the larvae stage, where it must attach to any available host and begin feeding. After it has fed, it detaches and molts, entering the larger nymph stage. In this stage it must reattach to a larger host and feed again, whereupon it detaches and molts again. This results in the adult stage, where it feeds one last time and is able to sexually reproduce.The stage when ticks are most able to transmit this disease is the nymph stage. They are also the most dangerous in this stage since they are usually less than two millimeters in size and can stay virtually undetected until they are done feeding.
Transmission
Queensland tick typhus is transmitted primarily by two types of tick: Ixodes holocyclus and Ixodes tasmani. After the initial attachment to a host, depending on the species and life stage of the tick, it takes anywhere from 10 minutes to 2 hours for it to begin to feed. Once a tick attaches, it can stay on a host for about 12 to 18 hours and then falls off when full. A tick must be attached for a long period of time to transmit bacteria. A tick that appears flat and small probably has not eaten yet.
Pathogenesis
After transmission from the infected tick, the bacterium Rickettsia australias enters the body via the bloodstream. The first sign of disease is damage to the skins microcirculation, which results in a rash. From there, the damage continues further into vital organs and can ultimately result in sepsis with multi-organ failure if left untreated.
Diagnosis
This disease can be challenging to diagnose because the initial signs are non-descript and relatively common. Analyzing recent travel history can be vital in the beginning stages of treatment. Serological assays are the best means of diagnosing this disease, with the indirect microimmunofluorescence assay (IFA) being considered the best tool. However, underlying illnesses, such as rheumatologic and other immune-mediated disorders, can lead to false positives. To combat these limitations, a PCR test may also be used; this test looks for rickettsial DNA. It can sensitively detect the target DNA in a sample taken from an eschar or blood during the first few days of infection.
Prevention
There is no vaccine available for this disease, so to prevent infection, the US CDC recommends taking personal safety measures when venturing out into areas known to harbour ticks.
Before going into these areas, the following preparations should be followed:
Wear protective clothing that will cover your arms and legs, with closed-toed shoes. Wearing long socks that you can tuck your pants into will provide an extra layer of safety, especially if you are walking in areas with tall grass for an extended period of time.
Use strong insect repellent such as DEET on your body and Permethrin on your clothes
If you are taking a pet with you, they should also be updated on all preventative medications, and a veterinarian should be consulted for any extra precautions.After you return from these areas, the following precautions should be taken to prevent ticks from entering your home:
Check clothes and gear used for any ticks. Dry clothes should be put into a dryer on high heat for 10 minutes to effectively kill any small ticks that may not be visible to the naked eye. If the clothes are wet, then they should be washed with hot water then dried on high heat.
Each individual should shower within two hours of returning home since this can help wash off any unattached ticks.
Finally, a full-body check should be performed to ensure that there is no attached tick.
If a pet was taken with you, they should receive a bath and a full-body tick check as well to ensure that they are not carrying anything into the home.
Treatment
Early treatment for Queensland tick typhus is relatively simple. It includes a course of oral antibiotics such as doxycycline or chloramphenicol. If a patient cannot take the medication orally, then the antibiotics are given intravenously by a medical professional.
Epidemiology
Queensland tick typhus is endemic to Australia. Since there is no compulsory reporting of rickettsial infections in Australia, it can be difficult to monitor the geographical distribution of this disease and have an accurate count of the number of cases occurring each year. The disease is most common along the east coast of Australia, coinciding with the geographic range of its tick vectors.
History
This disease was noted during World War II among Australian soldiers undergoing basic training on the Atherton Tableland in Queensland. It is most common along the east coast of Australia, including that of Queensland.
See also
Typhus
North Asian tick typhus
Rocky Mountain spotted fever
List of cutaneous conditions
References
== External links == |
Giant platelet disorder | Giant platelet disorders, also known as macrothrombocytopenia, are rare disorders featuring abnormally large platelets, thrombocytopenia and a tendency to bleeding. Giant platelets cannot stick adequately to an injured blood vessel walls, resulting in abnormal bleeding when injured. Giant platelet disorder occurs for inherited diseases like Bernard–Soulier syndrome, gray platelet syndrome and May–Hegglin anomaly.
Signs and symptoms
Symptoms usually present from the period of birth to early childhood as: nose bleeds, bruising, and/or gum bleeding. Problems later in life may arise from anything that can cause internal bleeding such as: stomach ulcers, surgery, trauma, or menstruation. Abnormality of the abdomen, nosebleeds, heavy menstrual bleeding, purpura, too few platelets circulating in the blood, and prolonged bleeding time have also been listed as symptoms of various giant platelet disorders.
Genetics
Many of the further classifications of giant platelet disorder occur as a result of being genetically passed down through families as an autosomal recessive disorder, such as in Bernard-Soulier syndrome and gray platelet syndrome.
Diagnosis
People may be diagnosed after prolonged and/or recurring bleeding episodes. Children and adults may also be diagnosed after profuse bleeding after a trauma or tooth extraction. Ultimately, a laboratory diagnosis is usually required. This would utilize platelet aggregation studies and flow cytometry.
Classification
Giant platelet disorders can be further categorized:
caused by auto-immune disorders, for example Immune thrombocytopenic purpura (ITP), and characterized by low platelet count, but high MPV (mean platelet volume).
Caused by glycoprotein abnormalities: Bernard–Soulier syndrome, velocardiofacial syndrome
Caused by calpain defect: Montreal platelet syndrome
Caused by alpha granules defect: gray platelet syndrome
Characterized by abnormal neutrophil inclusions: May–Hegglin anomaly, Sebastian syndrome
With systemic manifestations: Hereditary macrothrombocytopenia with hearing loss, Epstein syndrome, Fechtner syndrome
With no specific abnormalities: Mediterranean macrothrombocytopenia
Harris platelet syndrome
Treatment
There has been no general recommendation for treatment of patients with giant platelet disorders, as there are many different specific classifications to further categorize this disorder which each need differing treatments. Platelet transfusion is the main treatment for people presenting with bleeding symptoms. There have been experiments with DDAVP (1-deamino-8-arginine vasopressin) and splenectomy on people with giant platelet disorders with mixed results, making this type of treatment contentious.
References
== External links == |
Tetrasomy 18p | Tetrasomy 18p is a genetic condition that is caused by the presence of an isochromosome composed of two copies of the short arm of chromosome 18 in addition to the two normal copies of the chromosome. It is characterized by multiple medical and developmental concerns.
Signs and symptoms
Tetrasomy 18p causes a wide range of medical and developmental problems.
Congenital anomalies
Cardiac anomalies are the most common congenital malformation in individuals with tetrasomy 18p. However, there is no pathognomatic heart defect associated with the condition. Patent ductus arteriosus is the most common defect. Septal defects (ventricular septal defects and atrial septal defects) are also common, as are patent foramina ovalia. Other cardiac anomalies include mitral valve regurgitation, mitral valve prolapse, bicuspid pulmonary valve, hypoplastic transverse aortic arch, tricuspid valve regurgitation, right ventricular hypertrophy, and pulmonic stenosis.
In males, cryptorchidism is common. Abnormal genitalia in females is not a common feature. Renal abnormalities have been reported in a minority of patients. Horseshoe kidney and bladder diverticuli have been reported. Other abdominal malformations, including pyloric stenosis and hernias, have also been reported, though they are present in only a minority of patients.Orthopedic anomalies also occur relatively frequently, with hip dysplasia being the most common orthopedic issue. Clubfoot and rocker bottom feet have also been reported.Myelomeningocele is another known feature associated with tetrasomy 18p.
Neonatal complications
Neonatal complications (apart from congenital anomalies) are common. In a paper published in 2010, 41 of 42 individuals had some type medical problem in the first days of life, the most common being feeding difficulties. Respiratory difficulty and jaundice are also relatively frequent.
ENT
Recurrent otitis media is common, and many patients required the placement of PE tubes. Small ear canals are also fairly common, but not as much as in 18q-.
Gastrointestinal
The most common gastrointestinal abnormality is chronic constipation, though gastrointestinal reflux was also common.
Endocrine
Growth hormone deficiency is present in about 20% of people with tetrasomy 18p.
Neurologic
Hypotonia and/or hypertonia are present in nearly all individuals with tetrasomy 18p. Approximately 25% have a seizure disorder.
Growth
Short stature is common, with ~50% being at or below the 25th centile and 20% being at or below the 3rd centile. Microcephaly is present in about 40% of patients.
Development
All reported cases of tetrasomy 18p have some degree of intellectual disability. Most individuals score in the moderate range of intellectual disability based on standardized testing.
Genetics
Tetrasomy 18p is caused by the presence of an additional isochromosome composed of two copies of the p arm of chromosome 18. This extra chromosome is classified as a small supernumerary marker chromosome that forms de novo in a parents egg or sperm or, in rare cases, is directly inherited from a parent carrier of the intact small supernumerary marker chromosome. It has been reported in both the non-mosaic as well as the mosaic state. (The phrase "mosaicism" in this context means that some cells carry the genetic change while others do not.) In the grand majority of cases, the isochromosome is de novo. Although there has been some speculation that tetrasomy 18p may occur with a higher frequency in children of older mothers, there is not enough evidence to say that this is definitively the case.
Diagnosis
Suspicion of a chromosome abnormality is typically raised due to the presence of developmental delays or congenital malformations. Diagnosis of tetrasomy 18p is typically made via a routine chromosome analysis from a blood sample. The diagnosis can also be made prenatally by chorionic villus sampling or amniocentesis.
Severity of tetrasomy 18p is variable. Individuals with mosaicism are typically less severely affected than non-mosaic individuals.
Management
At present, treatment for tetrasomy 18p is symptomatic, meaning that the focus is on treating the signs and symptoms of the conditions as they arise. The Chromosome 18 Clinical Research Center has published a list of recommended screening and evaluations:
Research
Current research is focusing on clearly defining the phenotype associated with tetrasomy 18p and identifying which genes cause medical and developmental problems when present in four copies.
References
== External links == |
Congenital myasthenic syndrome | Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder caused by defects of several types at the neuromuscular junction. The effects of the disease are similar to Lambert-Eaton Syndrome and myasthenia gravis, the difference being that CMS is not an autoimmune disorder. There are only 600 known family cases of this disorder and it is estimated that its overall frequency in the human population is 1 in 200,000.
Types
The types of CMS are classified into three categories: presynaptic, postsynaptic, and synaptic.
Presynaptic symptoms include brief stops in breathing, weakness of the eye, mouth, and throat muscles. These symptoms often result in double vision and difficulty chewing and swallowing.
Postsynaptic symptoms in infants include severe muscle weakness, feeding and respiratory problems, and delays in the ability to sit, crawl, and walk.
Synaptic symptoms include early childhood feeding and respiratory problems, reduced mobility, curvature of the spine, and weakness, which causes a delay in motor milestones.
Presentation
The onset of symptoms for all ages may include droopy eyelids. A particular form of postsynaptic CMS (slow-channel CMS) includes severe weakness beginning in infancy or childhood that progresses to respiratory problems, and leads to loss of mobility in adolescence or later life.
Mechanisms
Postsynaptic CMS
CMS is associated with genetic defects that affect proteins of the neuromuscular junction. Postsynaptic defects are the most frequent cause of CMS and often result in abnormalities in the acetylcholine receptor (AChR). In the neuromuscular junction there is a vital pathway that maintains synaptic structure and results in the aggregation and localization of AChR on the postsynaptic folds. This pathway consists of agrin, muscle-specific tyrosine kinase (MuSK), acetylcholine receptors (AChRs) and the AChR-clustering protein rapsyn, encoded by the RAPSN gene. The vast majority of mutations causing CMS are found in the AChR subunits and rapsyn genes.Out of all mutations associated with CMS, more than half are mutations in one of the four genes encoding the adult acetylcholine receptor (AChR) subunits. Mutations of the AChR often result in endplate deficiency. Most of the mutations of the AChR are mutations of the CHRNE gene. The CHRNE gene codes for the epsilon subunit of the AChR. Most mutations are autosomal recessive loss-of-function mutations and as a result there is endplate AChR deficiency. CHRNE is associated with changing the kinetic properties of the AChR. One type of mutation of the epsilon subunit of the AChR introduces an Arginine into the binding site at the α/ε subunit interface of the receptor. The addition of a cationic Arg into the anionic environment of the AChR binding site greatly reduces the kinetic properties of the receptor. The result of the newly introduced Arg is a 30-fold reduction of agonist affinity, 75-fold reduction of gating efficiency, and an extremely weakened channel opening probability. This type of mutation results in an extremely fatal form of CMS.Another common underlying mechanism of CMS is the mutation of the rapsyn protein, coded by the RAPSN gene. Rapsyn interacts directly with the AChRs and plays a vital role in agrin-induced clustering of the AChR. Without rapsyn, functional synapses cannot be created, as the membrane folds do not form properly. Patients with CMS-related mutations of the rapsyn protein typically are either homozygous for N88K or heterozygous for N88K and a second mutation. The major effect of the mutation N88K in rapsyn is to reduce the stability of AChR clusters. The second mutation can be a determining factor in the severity of the disease.Studies have shown that most patients with CMS that have rapsyn mutations carry the common mutation N88K on at least one allele. However, research has revealed that there is a small population of patients who do not carry the N88K mutation on either of their alleles, but instead have different mutations of the RAPSN gene that codes for rapsyn on both of their alleles. Two novel missense mutations that have been found are R164C and L283P; the result is a decrease in co-clustering of AChR with raspyn. A third mutation is the intronic base alteration IVS1-15C>A, which causes abnormal splicing of RAPSN RNA. These results show that diagnostic screening for CMS mutations of the RAPSN gene cannot be based exclusively on the detection of N88K mutationsDok-7 is a postsynaptic protein that binds and activates MuSK protein, which then leads to AChR clustering and typical folding of the postsynaptic membrane. Mutations of Dok-7 are yrt another underlying mechanism of postsynaptic CMS.
Diagnosis
Congenital myasthenic syndrome (CMS) is "often difficult to diagnose because of a broad differential diagnosis and lack of specific laboratory findings. Identification of the underlying mutation is critical, as certain mutations lead to treatment-responsive conditions while others do not." Whole exome sequencing (WES) is often used as a diagnostic tool that allows for the "initiation of specific treatment".
Management
Treatment depends on the form (category) of the disease. Although symptoms are similar to myasthenia gravis, treatments used in MG are not useful in CMS. MG is treated with immunosuppressants, but CMS is not an autoimmune disorder. Instead, CMS is genetic and responds to other forms of drug treatments. A form of presynaptic CMS is caused by an insufficient release of acetylcholine (ACh) and is treated with cholinesterase inhibitors.Postsynaptic fast-channel CMS, in which ACh receptors do not stay open long enough, is treated with cholinesterase inhibitors and 3,4-diaminopyridine. In the U.S., the more stable phosphate salt formulation of 3,4-diaminopyridine (amifampyridine phosphate) is under development as an orphan drug for CMS and is available to eligible patients at no cost under an expanded access program.
Postsynaptic slow-channel CMS is treated with quinidine or fluoxetine, which blocks the ACh receptor.Ephedrine, a β(2)-adrenergic receptor agonist with alpha activity, has been tested on patients in clinical trials and appears to be an effective treatment for DOK7 CMS. Most patients tolerate this type of treatment and improvements in strength can be substantial. The effect of ephedrine is delayed and the improvement occurs over a period of months.Salbutamol, a selective β(2)-adrenergic receptor agonist, has been found, in adults, to have fewer side effects than Ephedrine and to be more easily obtained in some countries. It has been trialed in children with positive resultsAs of 2022, the standard of care for DOK7 CMS is either ephedrine or salbutamol.
People
Two brothers with apparent myasthenic syndrome with a seemingly circadian off/on cycle, living near Quetta, Pakistan were nicknamed the solar kids, because their condition resulted in an inability to move from approximately sunset to sunrise, while their daytime motor abilities were seemingly normal. Doctors observed that some "factor" seemed to become exhausted in the course of normal diurnal activities, and was "recharged" over the period of inertia and sleep. The father first sought help from spiritual healers, then turned to Western medicine. A younger brother of the two had also begun to manifest the same symptoms. The family had other children, two daughters and one son, who were unaffected. The "solar kids" condition, despite extensive testing, was said to be undiagnosed as of 2016, and assumed to be genetic, as their parents were cousins. Samples of their genetic material were to be sent to the UK for analysis.
See also
Congenital disorder
Myasthenia gravis
Lambert-Eaton syndrome
References
External links
Congenital Myasthenic Syndromes
About Congenital Myasthenic Syndrome From the Mayo Clinic
Treatment for Congenital Myasthenic Syndromes From the Mayo Clinic |
Hydrocephalus | Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased pressure inside the skull. Older people may have headaches, double vision, poor balance, urinary incontinence, personality changes, or mental impairment. In babies, it may be seen as a rapid increase in head size. Other symptoms may include vomiting, sleepiness, seizures, and downward pointing of the eyes.Hydrocephalus can occur due to birth defects or be acquired later in life. Associated birth defects include neural tube defects and those that result in aqueductal stenosis. Other causes include meningitis, brain tumors, traumatic brain injury, intraventricular hemorrhage, and subarachnoid hemorrhage. The four types of hydrocephalus are communicating, noncommunicating, ex vacuo, and normal pressure. Diagnosis is typically made by physical examination and medical imaging.Hydrocephalus is typically treated by the surgical placement of a shunt system. A procedure called a third ventriculostomy is an option in some people. Complications from shunts may include overdrainage, underdrainage, mechanical failure, infection, or obstruction. This may require replacement. Outcomes are variable, but many people with shunts live normal lives. Without treatment, death or permanent disability may occur.About one to two per 1,000 newborns have hydrocephalus. Rates in the developing world may be higher. Normal pressure hydrocephalus is estimated to affect about 5 per 100,000 people, with rates increasing with age. Description of hydrocephalus by Hippocrates dates back more than 2,000 years. The word hydrocephalus is from the Greek ὕδωρ, hydōr, meaning water and κεφαλή, kephalē, meaning head.
Signs and symptoms
The clinical presentation of hydrocephalus varies with chronicity. Acute dilatation of the ventricular system is more likely to manifest with the nonspecific signs and symptoms of increased intracranial pressure (ICP). By contrast, chronic dilatation (especially in the elderly population) may have a more insidious onset presenting, for instance, with Hakims triad (Adams triad).Symptoms of increased ICP may include headaches, vomiting, nausea, papilledema, sleepiness, or coma. With increased levels of CSF, there have been cases of hearing loss due to CSF creating pressure on the auditory pathways or disrupting the communication of inner ear fluid. Elevated ICP of different etiologies have been linked to sensorineural hearing loss (SNHL). Transient SNHL has been reported after the loss of CSF with shunt surgeries. Hearing loss is a rare but well-known sequela of procedures resulting in CSF loss. Elevated ICP may result in uncal or tonsillar herniation, with resulting life-threatening brain stem compression.Hakims triad of gait instability, urinary incontinence, and dementia is a relatively typical manifestation of the distinct entity normal-pressure hydrocephalus. Focal neurological deficits may also occur, such as abducens nerve palsy and vertical gaze palsy (Parinaud syndrome due to compression of the quadrigeminal plate, where the neural centers coordinating the conjugated vertical eye movement are located). The symptoms depend on the cause of the blockage, the persons age, and how much brain tissue has been damaged by the swelling.In infants with hydrocephalus, CSF builds up in the central nervous system (CNS), causing the fontanelle (soft spot) to bulge and the head to be larger than expected. Early symptoms may also include:
Eyes that appear to gaze downward
Irritability
Seizures
Separated sutures
Sleepiness
VomitingSymptoms that may occur in older children can include:
Brief, shrill, high-pitched cry
Changes in personality, memory, or the ability to reason or think
Changes in facial appearance and eye spacing (craniofacial disproportion)
Crossed eyes or uncontrolled eye movements
Difficulty feeding
Excessive sleepiness
Headaches
Irritability, poor temper control
Loss of bladder control (urinary incontinence)
Loss of coordination and trouble walking
Muscle spasticity (spasm)
Slow growth (child 0–5 years)
Delayed milestones
Failure to thrive
Slow or restricted movement
VomitingBecause hydrocephalus can injure the brain, thought and behavior may be adversely affected. Learning disabilities, including short-term memory loss, are common among those with hydrocephalus, who tend to score better on verbal IQ than on performance IQ, which is thought to reflect the distribution of nerve damage to the brain. Hydrocephalus that is present from birth can cause long-term complications with speech and language. Children can have issues such as nonverbal learning disorder, difficulty understanding complex and abstract concepts, difficulty retrieving stored information, and spatial/perceptual disorders. Children with hydrocephalus are often known in having the difficulty in understanding the concepts within conversation and tend to use words they know or have heard. However, the severity of hydrocephalus can differ considerably between individuals, and some are of average or above-average intelligence. Someone with hydrocephalus may have coordination and visual problems, or clumsiness. They may reach puberty earlier than the average child (this is called precocious puberty). About one in four develops epilepsy.
Cause
Congenital
Congenital hydrocephalus is present in the infant prior to birth, meaning the fetus developed hydrocephalus in utero during fetal development. The most common cause of congenital hydrocephalus is aqueductal stenosis, which occurs when the narrow passage between the third and fourth ventricles in the brain is blocked or too narrow to allow sufficient cerebral spinal fluid to drain. Fluid accumulates in the upper ventricles, causing hydrocephalus.Other causes of congenital hydrocephalus include neural-tube defects, arachnoid cysts, Dandy–Walker syndrome, and Arnold–Chiari malformation.
The cranial bones fuse by the end of the third year of life. For head enlargement to occur, hydrocephalus must occur before then. The causes are usually genetic, but can also be acquired and usually occur within the first few months of life, which include intraventricular matrix hemorrhages in premature infants, infections, type II Arnold-Chiari malformation, aqueduct atresia and stenosis, and Dandy-Walker malformation. Hydrocephalus has also been seen in cases of congenital syphilis.In newborns and toddlers with hydrocephalus, the head circumference is enlarged rapidly and soon surpasses the 97th percentile. Since the skull bones have not yet firmly joined, bulging, firm anterior and posterior fontanelles may be present even when the person is in an upright position.The infant exhibits fretfulness, poor feeding, and frequent vomiting. As the hydrocephalus progresses, torpor sets in, and infants show lack of interest in their surroundings. Later on, their upper eyelids become retracted and their eyes are turned downwards ("sunset eyes") (due to hydrocephalic pressure on the mesencephalic tegmentum and paralysis of upward gaze). Movements become weak and the arms may become tremulous. Papilledema is absent, but vision may be reduced. The head becomes so enlarged that they eventually may be bedridden.About 80–90% of fetuses or newborn infants with spina bifida—often associated with meningocele or myelomeningocele—develop hydrocephalus.
Acquired
This condition is acquired as a consequence of CNS infections, meningitis, brain tumors, head trauma, toxoplasmosis, or intracranial hemorrhage (subarachnoid or intraparenchymal), and is usually painful.
Type
The cause of hydrocephalus is not known with certainty and is probably multifactorial. It may be caused by impaired CSF flow, reabsorption, or excessive CSF production.
Obstruction to CSF flow hinders its free passage through the ventricular system and subarachnoid space (e.g., stenosis of the cerebral aqueduct or obstruction of the interventricular foramina secondary to tumors, hemorrhages, infections or congenital malformations) and can cause increases in ICP.
Hydrocephalus can also be caused by overproduction of CSF (relative obstruction) (e.g., choroid plexus papilloma, villous hypertrophy).
Bilateral ureteric obstruction is a rare, but reported, cause of hydrocephalus.Hydrocephalus can be classified into communicating and noncommunicating (obstructive). Both forms can be either congenital or acquired.
Communicating
Communicating hydrocephalus, also known as nonobstructive hydrocephalus, is caused by impaired CSF reabsorption in the absence of any obstruction of CSF flow between the ventricles and subarachnoid space. This may be due to functional impairment of the arachnoidal granulations (also called arachnoid granulations or Pacchionis granulations), which are located along the superior sagittal sinus, and is the site of CSF reabsorption back into the venous system. Various neurologic conditions may result in communicating hydrocephalus, including subarachnoid/intraventricular hemorrhage, meningitis, and congenital absence of arachnoid villi. Scarring and fibrosis of the subarachnoid space following infectious, inflammatory, or hemorrhagic events can also prevent reabsorption of CSF, causing diffuse ventricular dilatation.
Noncommunicating
Noncommunicating hydrocephalus, or obstructive hydrocephalus, is caused by an obstruction to the flow of CSF.
Foramen of Monro obstruction may lead to dilation of one, or if large enough (e.g., in colloid cyst), both lateral ventricles.
The aqueduct of Sylvius, normally narrow, may be obstructed by a number of genetic or acquired lesions (e.g., atresia, ependymitis, hemorrhage, or tumor) and lead to dilation of both lateral ventricles, as well as the third ventricle.
Fourth ventricle obstruction leads to dilatation of the aqueduct, as well as the lateral and third ventricles (e.g., Chiari malformation).
The foramina of Luschka and foramen of Magendie may be obstructed due to congenital malformation (e.g., Dandy–Walker malformation).
Other
Normal pressure hydrocephalus (NPH) is a particular form of chronic communicating hydrocephalus, characterized by enlarged cerebral ventricles, with only intermittently elevated cerebrospinal fluid pressure. Characteristic triad of symptoms are; dementia, apraxic gait and urinary incontinence. The diagnosis of NPH can be established only with the help of continuous intraventricular pressure recordings (over 24 hours or even longer), since more often than not instant measurements yield normal pressure values. Dynamic compliance studies may be also helpful. Altered compliance (elasticity) of the ventricular walls, as well as increased viscosity of the cerebrospinal fluid, may play a role in the pathogenesis.
Hydrocephalus ex vacuo also refers to an enlargement of cerebral ventricles and subarachnoid spaces, and is usually due to brain atrophy (as it occurs in dementias), post-traumatic brain injuries, and even in some psychiatric disorders, such as schizophrenia. As opposed to hydrocephalus, this is a compensatory enlargement of the CSF-spaces in response to brain parenchyma loss; it is not the result of increased CSF pressure.
Mechanism
Hydrocephalus is usually due to blockage of CSF outflow in the ventricles or in the subarachnoid space over the brain. In a person without hydrocephalus, CSF continuously circulates through the brain, its ventricles and the spinal cord and is continuously drained away into the circulatory system. Alternatively, the condition may result from an overproduction of the CSF, from a congenital malformation blocking normal drainage of the fluid, or from complications of head injuries or infections.Compression of the brain by the accumulating fluid eventually may cause neurological symptoms such as convulsions, intellectual disability, and epileptic seizures. These signs occur sooner in adults, whose skulls are no longer able to expand to accommodate the increasing fluid volume within. Fetuses, infants, and young children with hydrocephalus typically have an abnormally large head, excluding the face, because the pressure of the fluid causes the individual skull bones—which have yet to fuse—to bulge outward at their juncture points. Another medical sign, in infants, is a characteristic fixed downward gaze with whites of the eyes showing above the iris, as though the infant were trying to examine its own lower eyelids.The elevated ICP may cause compression of the brain, leading to brain damage and other complications. A complication often overlooked is the possibility of hearing loss due to ICP. The mechanism of ICP on hearing loss is presumed that the transmission of CSF pressure to and from the Perilymphatic space through a patent cochlear aqueduct. The cochlear aqueduct connects the Perilymphatic space of the inner ear with the subarachnoid space of the posterior cranial fossa. A loss of CSF pressure can induce Perilymphatic loss or endolymphatic hydrops resembling the clinical presentation of Ménières disease associated hearing loss in the low frequencies.CSF can accumulate within the ventricles, this condition is called internal hydrocephalus and may result in increased CSF pressure. The production of CSF continues, even when the passages that normally allow it to exit the brain are blocked. Consequently, fluid builds inside the brain, causing pressure that dilates the ventricles and compresses the nervous tissue. Compression of the nervous tissue usually results in irreversible brain damage. If the skull bones are not completely ossified when the hydrocephalus occurs, the pressure may also severely enlarge the head. The cerebral aqueduct may be blocked at the time of birth or may become blocked later in life because of a tumor growing in the brainstem.
Treatments
Procedures
Hydrocephalus treatment is surgical, creating a way for the excess fluid to drain away. In the short term, an external ventricular drain (EVD), also known as an extraventricular drain or ventriculostomy, provides relief. In the long term, some people will need any of various types of cerebral shunt. It involves the placement of a ventricular catheter (a tube made of silastic) into the cerebral ventricles to bypass the flow obstruction/malfunctioning arachnoidal granulations and drain the excess fluid into other body cavities, from where it can be resorbed. Most shunts drain the fluid into the peritoneal cavity (ventriculoperitoneal shunt), but alternative sites include the right atrium (ventriculoatrial shunt), pleural cavity (ventriculopleural shunt), and gallbladder. A shunt system can also be placed in the lumbar space of the spine and have the CSF redirected to the peritoneal cavity (lumbar-peritoneal shunt). An alternative treatment for obstructive hydrocephalus in selected people is the endoscopic third ventriculostomy (ETV), whereby a surgically created opening in the floor of the third ventricle allows the CSF to flow directly to the basal cisterns, thereby shortcutting any obstruction, as in aqueductal stenosis. This may or may not be appropriate based on individual anatomy. For infants, ETV is sometimes combined with choroid plexus cauterization, which reduces the amount of cerebrospinal fluid produced by the brain. The technique, known as ETV/CPC, was pioneered in Uganda by neurosurgeon Benjamin Warf and is now in use in several U.S. hospitals. Hydrocephalus can be successfully treated by placing a drainage tube (shunt) between the brain ventricles and abdominal cavity. Some risk exists of infection being introduced into the brain through these shunts, however, and the shunts must be replaced as the person grows.
External hydrocephalus
External hydrocephalus is a condition generally seen in infants which involves enlarged fluid spaces or subarachnoid spaces around the outside of the brain. This condition is generally benign, and resolves spontaneously by two years of age and therefore usually does not require insertion of a shunt. Imaging studies and a good medical history can help to differentiate external hydrocephalus from subdural hemorrhages or symptomatic chronic extra-axial fluid collections which are accompanied by vomiting, headaches, and seizures.
Shunt complications
Examples of possible complications include shunt malfunction, shunt failure, and shunt infection, along with infection of the shunt tract following surgery (the most common reason for shunt failure is infection of the shunt tract). Although a shunt generally works well, it may stop working if it disconnects, becomes blocked (clogged) or infected, or it is outgrown. If this happens, the CSF begins to accumulate again and a number of physical symptoms develop (headaches, nausea, vomiting, photophobia/light sensitivity), some extremely serious, such as seizures. The shunt failure rate is also relatively high (of the 40,000 surgeries performed annually to treat hydrocephalus, only 30% are a persons first surgery) and people not uncommonly have multiple shunt revisions within their lifetimes.Another complication can occur when CSF drains more rapidly than it is produced by the choroid plexus, causing symptoms of listlessness, severe headaches, irritability, light sensitivity, auditory hyperesthesia (sound sensitivity), hearing loss, nausea, vomiting, dizziness, vertigo, migraines, seizures, a change in personality, weakness in the arms or legs, strabismus, and double vision to appear when the person is vertical. If the person lies down, the symptoms usually vanish quickly. A CT scan may or may not show any change in ventricle size, particularly if the person has a history of slit-like ventricles. Difficulty in diagnosing over-drainage can make treatment of this complication particularly frustrating for people and their families. Resistance to traditional analgesic pharmacological therapy may also be a sign of shunt overdrainage or failure.Following placement of a ventriculoperitoneal shunt there have been cases of a decrease in post-surgery hearing. It is presumed that the cochlea aqueduct is responsible for the decrease in hearing thresholds. The cochlea aqueduct has been considered as a probable channel where CSF pressure can be transmitted. Therefore, the reduced CSF pressure could cause a decrease in Perilymphatic pressure and cause secondary endolymphatic hydrops. In addition to the increased hearing loss, there have also been findings of resolved hearing loss after ventriculoperitoneal shunt placement, where there is a release of CSF pressure on the auditory pathways.The diagnosis of CSF buildup is complex and requires specialist expertise. Diagnosis of the particular complication usually depends on when the symptoms appear, that is, whether symptoms occur when the person is upright or in a prone position, with the head at roughly the same level as the feet.Standardized protocols for inserting cerebral shunts have been shown to reduce shunt infections. There is tentative evidence that preventative antibiotics may decrease the risk of shunt infections.
Epidemiology
The hydrocephalus disease burden are concentrated in the developing world while North America and Canada has the least number of cases. A systematic review in 2019 estimated that there are 180,000 childhood hydrocephalus cases from African continent alone per year, followed by 90,000 cases from Southeast Asia and Western Pacific. Latin America also has high prevalence of hydrocephalus. However, data on hydrocephalus disease burden in adults are lacking.
History
In the pre-historic area, there were various paintings or artifacts depicting children or adults with macrocephaly (large head) or clinical findings of hydrocephalus. However, due to lack of writing, it was unknown how the people thought of the disorder at that time and the ways to treat the disease.References to hydrocephalic skulls can be found in ancient Egyptian medical literature from 2,500 BC to 500 AD. Hydrocephalus was described more clearly by the ancient Greek physician Hippocrates in the fourth century BC, while a more accurate description was later given by the Roman physician Galen in the second century AD.The first clinical description of an operative procedure for hydrocephalus appears in the Al-Tasrif (1,000 AD) by the Arab surgeon Abulcasis, who clearly described the evacuation of superficial intracranial fluid in hydrocephalic children. He described it in his chapter on neurosurgical disease, describing infantile hydrocephalus as being caused by mechanical compression. He wrote:
The skull of a newborn baby is often full of liquid, either because the matron has compressed it excessively or for other, unknown reasons. The volume of the skull then increases daily, so that the bones of the skull fail to close. In this case, we must open the middle of the skull in three places, make the liquid flow out, then close the wound and tighten the skull with a bandage.
In 1881, a few years after the landmark study of Retzius and Key, Carl Wernicke pioneered sterile ventricular puncture and external drainage of CSF for the treatment of hydrocephalus. It remained an intractable condition until the 20th century, when cerebral shunt and other neurosurgical treatment modalities were developed.It is a lesser-known medical condition; relatively little research is conducted to improve treatment, and still no cure has been found. In developing countries, the condition often goes untreated at birth. Before birth, the condition is difficult to diagnose, and access to medical treatment is limited. However, when head swelling is prominent, children are taken at great expense for treatment. By then, brain tissue is undeveloped and neurosurgery is rare and difficult. Children more commonly live with undeveloped brain tissue and consequential intellectual disabilities and restrictions.
Society and culture
Name
The word hydrocephalus is from the Greek ὕδωρ, hydōr meaning water and κεφαλή, kephalē meaning head. Other names for hydrocephalus include "water on the brain", a historical name, and "water baby syndrome".
Awareness campaign
September was designated National Hydrocephalus Awareness Month in July 2009 by the U.S. Congress in H.Res. 373. The resolution campaign is due in part to the advocacy work of the Pediatric Hydrocephalus Foundation. Prior to July 2009, no awareness month for this condition had been designated. Many hydrocephalus organizations, such as the One Small Voice Foundation, promote awareness and fundraising activities.
Exceptional case
One case of hydrocephalus was a man whose brain shrank to a thin sheet of tissue, due to a buildup of cerebrospinal fluid in his skull. As a child, the man had a shunt, but it was removed when he was 14. In July 2007, at age 44, he went to a hospital due to mild weakness in his left leg. When doctors learned of the mans medical history, they performed a CT and MRI scan, and were astonished to see "massive enlargement" of the lateral ventricles in the skull. Dr. Lionel Feuillet of Hôpital de la Timone in Marseille said, "The images were most unusual... the brain was virtually absent." Intelligence tests showed the person had an IQ of 75, considered "Borderline intellectual functioning", just above what would be officially classified as intectually disabled.The person was a married father of two children, and worked as a civil servant, leading an at least superficially normal life, despite having enlarged ventricles with a decreased volume of brain tissue. "What I find amazing to this day is how the brain can deal with something which you think should not be compatible with life", commented Dr. Max Muenke, a pediatric brain-defect specialist at the National Human Genome Research Institute. "If something happens very slowly over quite some time, maybe over decades, the different parts of the brain take up functions that would normally be done by the part that is pushed to the side."
Notable cases
Ice hockey player Colby Cave had acute obstructive hydrocephalus due to a colloid cyst.
Author Sherman Alexie, born with the condition, wrote about it in his semi-autobiographical junior fiction novel The Absolutely True Diary of a Part-Time Indian.
Prince William, Duke of Gloucester (1689–1700), probably contracted meningitis at birth, which resulted in this condition.
Emperor Ferdinand I of Austria (1793–1875) became emperor in 1835 despite various health issues including hydrocephalus and epilepsy.
In the American folklore of the states of Ohio, Michigan, and Connecticut, an urban legend exists about the melon heads, the inbred descendants of families of people born with hydrocephaly.
References
External links
Hydrocephalus at Curlie
Guidelines for pediatric hydrocephalus |
Xanthinuria | Xanthinuria, also known as xanthine oxidase deficiency, is a rare genetic disorder causing the accumulation of xanthine. It is caused by a deficiency of the enzyme xanthine oxidase.
It was first formally characterized in 1954.
Presentation
Sufferers have unusually high concentrations of xanthine in their blood and urine, which can lead to health problems such as renal failure and xanthine kidney stones, one of the rarest types of kidney stones.
Causes
Type I xanthinuria can be caused by a deficiency of xanthine oxidase, which is an enzyme necessary for converting xanthine to uric acid. Type II xanthinuria and molybdenum cofactor deficiency lack one or two other enzyme activities in addition to xanthine oxidase.
Treatment
There is no specific treatment beyond maintaining a high fluid intake and avoiding foods that are high in purine.
References
External links
Xanthinuria at NIHs Office of Rare Diseases |
Hospital-acquired pneumonia | Hospital-acquired pneumonia (HAP) or nosocomial pneumonia refers to any pneumonia contracted by a patient in a hospital at least 48–72 hours after being admitted. It is thus distinguished from community-acquired pneumonia. It is usually caused by a bacterial infection, rather than a virus.HAP is the second most common nosocomial infection (after urinary tract infections) and accounts for 15–20% of the total. It is the most common cause of death among nosocomial infections and is the primary cause of death in intensive care units.HAP typically lengthens a hospital stay by 1–2 weeks.
Signs and symptoms
New or progressive infiltrate on the chest X-ray with one of the following:
Fever > 37.8 °C (100 °F)
Purulent sputum
Leukocytosis > 10,000 cells/μlIn an elderly person, the first sign of hospital-acquired pneumonia may be mental changes or confusion.
Other symptoms may include:
A cough with greenish or pus-like phlegm (sputum)
Fever and chills
General discomfort, uneasiness, or ill feeling (malaise)
Loss of appetite
Nausea and vomiting
Sharp chest pain that gets worse with deep breathing or coughing
Shortness of breath
Decreased blood pressure and fast heart rate
Types
Bacterial pneumonia: The majority of cases related to various rod shaped gram-negative organisms (52%) and Staphylococcus aureus (19%), usually of the MRSA type. Others are Haemophilus spp. (5%). In the ICU results were S. aureus (17.4%), Pseudomonas aeruginosa (17.4%), Klebsiella pneumoniae and Enterobacter spp. (18.1%), and Haemophilus influenzae (4.9%).
Viral pneumonia: influenza and respiratory syncytial virus and, in the immunocompromised host, cytomegalovirus – cause 10–20% of infections.
Ventilator-associated pneumonia
Ventilator-associated pneumonia (VAP) is a sub-type of hospital-acquired pneumonia (HAP) which occurs in people who are receiving mechanical ventilation. VAP is not characterized by the causative agents; rather, as its name implies, definition of VAP is restricted to patients undergoing mechanical ventilation while in a hospital. A positive culture after intubation is indicative of ventilator-associated pneumonia and is diagnosed as such. In order to appropriately categorize the causative agent or mechanism it is usually recommended to obtain a culture prior to initiating mechanical ventilation as a reference.
Healthcare-associated pneumonia (HCAP)
HCAP is a condition in patients who can come from the community, but have frequent contact with the healthcare environment. Historically, the etiology and prognosis of nursing home pneumonia appeared to differ from other types of community acquired pneumonia, with studies reporting a worse prognosis and higher incidence of multi drug resistant organisms as etiology agents. The definition criteria which has been used is the same as the one which has been previously used to identify bloodstream healthcare associated infections.
HCAP is no longer recognized as a clinically independent entity. This is due to increasing evidence from a growing number of studies that many patients defined as having HCAP are not at high risk for MDR pathogens. As a result, 2016 IDSA guidelines removed consideration of HCAP as a separate clinical entity.
Definition
Healthcare-associated pneumonia can be defined as pneumonia in a patient with at least one of the following risk factors:
hospitalization in an acute care hospital for two or more days in the last 90 days;
residence in a nursing home or long-term care facility in the last 30 days
receiving outpatient intravenous therapy (like antibiotics or chemotherapy) within the past 30 days
receiving home wound care within the past 30 days
attending a hospital clinic or dialysis center in the last 30 days
having a family member with known multi-drug resistant pathogens
Causes
In some studies, the bacteria found in patients with HCAP were more similar to HAP than to CAP; compared to CAP, they could have higher rates of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa, and less Streptococcus pneumoniae and Haemophilus influenzae. In European and Asian studies, the etiology of HCAP was similar to that of CAP, and rates of multi drug resistant pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa were not as high as seen in North American studies. It is well known that nursing home residents have high rates of colonization with MRSA. However, not all studies have found high rates of S. aureus and gram-negative bacteria. One factor responsible for these differences is the reliance on sputum samples and the strictness of the criteria to discriminate
between colonising or disease-causing bacteria. Moreover, sputum samples might be less frequently obtained in the elderly. Aspiration (both of microscopic drops and macroscopic amounts of nose and throat secretions) is thought to be the most important cause of HCAP. Dental plaque might also be a reservoir for bacteria in HCAP.
Bacteria have been the most commonly isolated pathogens, although viral and fungal pathogens are potentially found in immunocompromised hosts (patients on chronic immunosuppressed medications, solid organ and bone marrow transplant recipients). In general, the distribution of microbial pathogens varies among institutions, partly because of differences in patient population and local patterns of anti microbial resistance in hospitals and critical care units Common bacterial pathogens include aerobic GNB, such as Pseudomonas aeruginosa, Acinetobacter baumanii, Klebsiella pneumoniae, Escherichia coli as well as gram-positive organisms such as Staphylococcus aureus. In patients with an early onset pneumonia (within 5 days of hospitalization), they are usually due to anti microbial-sensitive bacteria such as Enterobacter spp, E. coli, Klebsiella spp, Proteus spp, Serratia mare scans, community pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, and methicillin-sensitive S. aureus should also be considered.
Pneumonia that starts in the hospital tends to be more serious than other lung infections because: people in the hospital are often very sick and cannot fight off germs. The types of germs present in a hospital are often more dangerous and more resistant to treatment than those outside in the community. Pneumonia occurs more often in people who are using a respirator. This machine helps them breathe. Hospital-acquired pneumonia can also be spread by health care workers, who can pass germs from their hands or clothes from one person to another. This is why hand-washing, wearing gloves, and using other safety measures is so important in the hospital.
Treatment
Patients with HCAP are more likely than those with community-acquired pneumonia to receive inappropriate antibiotics that do not target the bacteria causing their disease.In 2002, an expert panel made recommendations about the evaluation and treatment of probable nursing home-acquired pneumonia. They defined probably pneumonia, emphasized expedite antibiotic treatment (which is known to improve survival) and drafted criteria for the hospitalization of willing patients.
For initial treatment in the nursing home, a fluoroquinolone antibiotic suitable for respiratory infections (moxifloxacin, for example), or amoxicillin with clavulanic acid plus a macrolide has been suggested. In a hospital setting, injected (parenteral) fluoroquinolones or a second- or third-generation cephalosporin plus a macrolide could be used. Other factors that need to be taken into account are recent antibiotic therapy (because of possible resistance caused by recent exposure), known carrier state or risk factors for resistant organisms (for example, known carrier of MRSA or presence of bronchiectasis predisposing to Pseudomonas aeruginosa), or suspicion of possible Legionella pneumophila infection (legionnaires disease).In 2005, the American Thoracic Society and Infectious Diseases Society of America have published guidelines suggesting antibiotics specifically for HCAP. The guidelines recommend combination therapy with an agent from each of the following groups to cover for both Pseudomonas aeruginosa and MRSA. This is based on studies using sputum samples and intensive care patients, in whom these bacteria were commonly found.
cefepime, ceftazidime, imipenem, meropenem or piperacillin–tazobactam; plus
ciprofloxacin, levofloxacin, amikacin, gentamicin, or tobramycin; plus
linezolid or vancomycinIn one observational study, empirical antibiotic treatment that was not according to international treatment guidelines was an independent predictor of worse outcome among HCAP patients.Guidelines from Canada suggest that HCAP can be treated like community-acquired pneumonia with antibiotics targeting Streptococcus pneumoniae, based on studies using blood cultures in different settings which have not found high rates of MRSA or Pseudomonas.Besides prompt antibiotic treatment, supportive measure for organ failure (such as cardiac decompensation) are also important. Another consideration goes to hospital referral; although more severe pneumonia requires admission to an acute care facility, this also predisposes to hazards of hospitalization such as delirium, urinary incontinence, depression, falls, restraint use, functional decline, adverse drug effects and hospital infections. Therefore, mild pneumonia might be better dealt with inside the long-term care facility. In patients with a limited life expectancy (for example, those with advanced dementia), end-of-life pneumonia also requires recognition and appropriate, palliative care.
Prognosis
Healthcare-associated pneumonia seems to have fatality rates similar to hospital-acquired pneumonia, worse than community-acquired pneumonia but less severe than pneumonia in ventilated patients. Besides clinical markers like tachypnea (fast breathing) or a high white cell count (leukocytosis), the prognosis seems to be influenced by the underlying associated diseases (comorbidities) and functional capacities (for example, the ADL score). Many patients have a decreased health condition after the episode.
Epidemiology
Several studies found that healthcare-associated pneumonia is the second most common type of pneumonia, occurring less commonly than community-acquired pneumonia but more frequently than hospital-acquired pneumonia and ventilator-associated pneumonia. In a recent observational study, the rates for CAP, HCAP and HAP were 60%, 25% and 15% respectively. Patients with HCAP are older and more commonly have simultaneous health problems (such as previous stroke, heart failure and diabetes).The number of residents in long-term care facilities is expected to rise dramatically over the next 30 years. These older adults are known to develop pneumonia 10 times more than their community-dwelling peers, and hospital admittance rates are 30 times higher.
Nursing home-acquired pneumonia
Nursing home-acquired pneumonia is an important subgroup of HCAP. Residents of long-term care facilities may become infected through their contacts with the healthcare system; as such, the microbes responsible for their pneumonias may be different from those traditionally seen in community-dwelling patients, requiring therapy with different antibiotics. Other groups include patients who are admitted as a day case for regular hemodialysis or intravenous infusion (for example, chemotherapy). Especially in the very old and in demented patients, HCAP is likely to present with atypical symptoms.
Risk factors
Among the factors contributing to contracting HAP are mechanical ventilation (ventilator-associated pneumonia), old age, decreased filtration of inspired air, intrinsic respiratory, neurologic, or other disease states that result in respiratory tract obstruction, trauma, (abdominal) surgery, medications, diminished lung volumes, or decreased clearance of secretions may diminish the defenses of the lung. Also, poor hand-washing and inadequate disinfection of respiratory devices cause cross-infection and are important factors.
Pathogenesis
Most nosocomial respiratory infections are caused by so-called microaspiration of upper airway secretions, through inapparent aspiration, into the lower respiratory tract. Also, "macroaspirations" of esophageal or gastric material is known to result in HAP. Since it results from aspiration either type is called aspiration pneumonia.Although gram-negative bacilli are a common cause they are rarely found in the respiratory tract of people without pneumonia, which has led to speculation of the mouth and throat as origin of the infection.
Diagnosis
In hospitalised patients who develop respiratory symptoms and fever, one should consider the diagnosis. The likelihood increases when upon investigation symptoms are found of respiratory insufficiency, purulent secretions, newly developed infiltrate on the chest X-Ray, and increasing leucocyte count. If pneumonia is suspected material from sputum or tracheal aspirates are sent to the microbiology department for cultures. In case of pleural effusion, thoracentesis is performed for examination of pleural fluid. In suspected ventilator-associated pneumonia it has been suggested that bronchoscopy or bronchoalveolar lavage is necessary because of the risks of incorrect clinical diagnoses.
Differential diagnosis
Atelectasis
Congestive heart failure
Pulmonary embolism
Treatment
Usually initial therapy is empirical. If sufficient reason to suspect influenza, one might consider oseltamivir. In case of legionellosis, erythromycin or fluoroquinolone.A third generation cephalosporin (ceftazidime) + carbapenems (imipenem) + beta lactam & beta lactamase inhibitors (piperacillin/tazobactam)
References
Further reading
Carratalà J, Garcia-Vidal C (2008). "What is healthcare-associated pneumonia and how is it managed?". Curr. Opin. Infect. Dis. 21 (2): 168–173. doi:10.1097/QCO.0b013e3282f4f248. PMID 18317041. S2CID 3060658.
Morrow L. Critical Decisions for the Treatment of Health-care-Associated Pneumonia in the ICU.
External links
Hospital-Acquired, Health Care Associated, and Ventilator-Associated Pneumonia from the Cleveland Clinic
Cecil Textbook of Medicine |
Central sleep apnea | Central sleep apnea (CSA) or central sleep apnea syndrome (CSAS) is a sleep-related disorder in which the effort to breathe is diminished or absent, typically for 10 to 30 seconds either intermittently or in cycles, and is usually associated with a reduction in blood oxygen saturation. CSA is usually due to an instability in the bodys feedback mechanisms that control respiration. Central sleep apnea can also be an indicator of Arnold–Chiari malformation.
Signs and symptoms
In a healthy person during sleep, breathing is regular so oxygen levels and carbon dioxide levels in the bloodstream stay fairly constant: After exhalation, the blood level of oxygen decreases and that of carbon dioxide increases. Exchange of gases with a lungful of fresh air is necessary to replenish oxygen and rid the bloodstream of built-up carbon dioxide. Oxygen and carbon dioxide receptors in the body (called chemoreceptors) send nerve impulses to the brain, which then signals for reflexive opening of the larynx (enlarging the opening between the vocal cords) and movements of the rib cage muscles and diaphragm. These muscles expand the thorax (chest cavity) so that a partial vacuum is made within the lungs and air rushes in to fill it. In the absence of central apnea, any sudden drop in oxygen or excess of carbon dioxide, even if small, strongly stimulates the brains respiratory centers to breathe; the respiratory drive is so strong that even conscious efforts to hold ones breath do not overcome it.In pure central sleep apnea, the brains respiratory control centers, located in the region of the human brain known as the pre-Botzinger complex, are imbalanced during sleep and fail to give the signal to inhale, causing the individual to miss one or more cycles of breathing. The neurological feedback mechanism that monitors blood levels of carbon dioxide and in turn stimulates respiration fails to react quickly enough to maintain an even respiratory rate, allowing the entire respiratory system to cycle between apnea and hyperpnea, even for a brief time following an awakening during a breathing pause. The sleeper stops breathing for up to two minutes and then starts again. There is no effort made to breathe during the pause in breathing: there are no chest movements and no muscular struggling, although when awakening occurs in the middle of a pause, the inability to immediately operate the breathing muscles often results in cognitive struggle accompanied by a feeling of panic exacerbated by the feeling associated with excessive blood CO2 levels. Even in severe cases of central sleep apnea, however, the effects almost always result in pauses that make breathing irregular rather than cause the total cessation of breathing over the medium term. After the episode of apnea, breathing may be faster and/or more intense (hyperpnea) for a period of time, a compensatory mechanism to blow off retained waste gases, absorb more oxygen, and, when voluntary, enable a return to normal instinctive breathing patterns by restoring oxygen to the breathing muscles themselves.
Secondary effects
The conditions of hypoxia and hypercapnia, whether caused by apnea or not, trigger additional effects on the body. The immediate effects of central sleep apnea on the body depend on how long the failure to breathe endures, how short is the interval between failures to breathe, and the presence or absence of independent conditions whose effects amplify those of an apneic episode.
Brain cells need constant oxygen to live, and if the level of blood oxygen remains low enough for long enough, brain damage and even death will occur. These effects, however, are rarely a result of central sleep apnea, which is a chronic condition whose effects are usually much milder.
Drops in blood oxygen levels that are severe but not severe enough to trigger brain-cell or overall death may trigger seizures even in the absence of epilepsy.
In severe cases of sleep apnea, the more translucent areas of the body will show a bluish or dusky cast from cyanosis, the change in hue ("turning blue") produced by the deoxygenation of blood in vessels near the skin.
Compounding effects of independent conditions:In persons with epilepsy, the hypoxia caused by apnea may be powerful enough to trigger seizures even in the presence of medication that otherwise controls those seizures well.
In adults with coronary artery disease, a severe drop in blood oxygen level can cause angina, arrhythmias, or heart attacks (myocardial infarction).
Longstanding and recurrent episodes of apnea may, over months and years, have the cumulative effect of increasing blood carbon-dioxide levels to the point that enough carbon dioxide dissolves in the blood to form carbonic acid in overall proportions sufficient to cause respiratory acidosis.
In persons who have either or both forms of sleep apnea, breathing irregularities during sleep can be dangerously aggravated by taking respiration-depressing drugs, especially sedative drugs that operate by depressing the central nervous system generally; respiratory depressants include opiates, barbiturates, benzodiazepines, and, in large quantities, alcohol, the last three of which are broad-spectrum CNS depressants. Quantities that are normally considered safe may cause the person with chronic sleep apnea to stop breathing altogether. Should these individuals have general anaesthesia, for example, they require prolonged monitoring after initial recovery, as compared against a person with no history of sleep apnea, because apnea is likely to occur with even low levels of the drugs in their system.
Sudden infant death syndrome is sometimes theorized to be attributable to sleep apnea; the recommendation, prevalent since the mid-1980s, of placing infants on their backs rather than their stomachs for sleep represents an attempt to prevent those instances of breathing cessation that are attributable to compressive obstruction.
Premature infants with immature brains and reflex systems are at high risk for central sleep apnea syndrome, even if these babies are otherwise healthy. Premature babies who have the syndrome will generally outgrow it as they mature, provided that they receive careful enough monitoring and supportive care during infancy to survive. Because of premature infants propensity toward central apnea, medications that can cause respiratory drive depression are either not given to them or administered to them only under careful monitoring, with equipment for resuscitation immediately available. Such precautions are routinely taken for premature infants after general anesthesia; administration of caffeine has been found not only to aid in maintenance of respiratory function after general anaesthesia but to reduce apnea for preterm infants regardless of context.
Diagnosis
A diagnosis of sleep apnea requires determination by a physician. The examination may require a study of an individual in a sleep lab, although the AAST has said a two belt IHT (In Home Test) will replace a PSG for diagnosing obstructive apnea. There, the patient will be monitored while at rest, and the periods when breathing ceases will be measured with respect to length and frequency. During a PSG (polysomnography) (a sleep study), a person with sleep apnea shows breathing interruptions followed by drops/reductions in blood oxygen and increases in blood carbon dioxide level.
In adults, a pause must last 10 seconds to be scored as an apnea. However, in young children, who normally breathe at a much faster rate than adults, shorter pauses may still be considered apneas.
Hypopneas in adults are defined as a 30% reduction in air flow for more than ten seconds, followed by oxygen-saturation declines of at least 3% or 4% per the AASM standards. and/or EEG arousal. The Apnea-Hypopnea Index (AHI) is expressed as the number of apneas or hypopneas per hour of sleep.As noted above, in central sleep apnea, the cessation of airflow is associated with the absence of physical attempts to breathe; specifically, polysomnograms reveal correlation between absence of rib cage and abdominal movements and cessation of airflow at the nose and lips. By contrast, in obstructive sleep apnea, pauses are not correlated with the absence of attempts to breathe and may even be correlated with more effortful breathing in an instinctive attempt to overcome the pressure on the affected persons airway. If the majority of a sleep-apnea patients apneas/hypopneas are central, their condition is classified as central; likewise, if the majority are obstructive, their condition is classified as obstructive.
Criteria
CSA is divided in 6 categories, Primary CSA, Cheyne–Stokes respiration, High-altitude periodic breathing, CSA due to a medical condition without CSB, Central sleep apnea due to a medication or substance and Treatment Emergent Central Apnea (also called Complex Sleep Apnea). The following symptoms are present in the Primary CSA: excessive daytime sleepiness, frequent arousals and awakenings during sleep or insomnia complaints, awakening short of breath, snoring, witness apneas. His polysomnography shows ≥5 central apneas and/or central hypopneas per hour of sleep, representing at least 50% of total respiratory events in the apnea-hypopnea index. CSA with Cheyne-Stokes breathing is characterized by at least one of the criteria of Primary CSA or the presence of atrial fibrillation/flutter, CHF, or a neurologic disorder. His polysomnography looks like the Primary CSA polysomnography with the addition of a ventilatory pattern compatible with CSB. High-Altitude Periodic Breathing requires that the patient has recently been at least 2500 meters. In the CSA due to a medication or substance, opioid or respiratory depressants must had been taken. For the CSA due to a medical condition without CSB, the criteria are the same as Primary CSA, but the symptoms are caused by a disease. In the Treatment Emergent Central Apnea, there was firstly some obstructive respiratory events but after their disappearance, the CSA has appeared.
Differential diagnosis
Although central and obstructive sleep apnea have some signs and symptoms in common, others are present in one but absent in another, enabling differential diagnosis as between the two types:Signs and symptoms of sleep apnea generally
Signs:Observed breathing pauses during sleep
High carbon-dioxide saturation of blood, especially just before awakenings during which a patient experiences urgent need to breathe (see "Symptoms" below)
Low oxygen saturation of blood
Heart rate increase (response to both hypercapnia and hypoxemia/hypoxia), unless there also exist problems with the heart muscle itself or the autonomic nervous system severe enough to make this compensatory increase impossibleSymptoms:High frequency of urgent need to breathe upon awakening (symptom created by hypercapnia), especially among subset of awakenings occurring at times other than normal for an individuals sleep schedule and circadian rhythmsSigns and symptoms of central sleep apnea
Signs:Lack of abdominal and thoracic movement for 10 seconds or longer during sleep and coincident with breathing pausesSymptoms:Inability, either complete or without excessive effort, to voluntarily operate diaphragm and other thoracic muscles upon awakeningThe combination of this symptom with a high frequency of urgent need to breathe upon awakening is especially specific in that the co-presence of the latter symptom differentiates central sleep apneas presentation from that of sleep paralysis generally.Signs and symptoms of and conditions associated with obstructive sleep apnea
Signs:Observably ineffective respiratory movements (observable lack of air flow despite observable muscle movements indicating efforts to breathe)
Snoring (high-sensitivity but low-specificity)
Observably dry mouth or throat (high-sensitivity but low-specificity)Symptoms:Sleepiness, fatigue, or tiredness, often rising to the level of excessive daytime sleepiness
Frequent feelings of choking (airway and/or lung compression), as distinguished from mere feeling of suffocation nonspecific with respect to presence/absence of pressure, upon awakeningAssociated conditions:Opioid medication use
Large neck circumference (>16" for females, > 17" for males) (frequent causal factor and possible indirect symptom; see "Obesity" below)
Obesity (frequent causal factor and possible, albeit low-specificity, sign both direct and indirect): Obesity frequently involves accumulation of fat below the chin and around the neck, depressing the trachea when one is in the supine position, and central obesity can, depending on an individuals fat distribution, lead to increased direct pressure on the thoracic cavity and/or compressive anterior (headward) displacement of the abdominal organs, in the second case reducing space for and increasing difficulty of the motion of the diaphragm. Poor breathing during sleep a] reduces oxygen available for metabolism and may therefore depress basal metabolic rate during sleep, increasing the difference between supply of food energy and demand for it during that time and thereby promoting weight gain, and b] reduces sleep quality and recovery per time unit of sleep, resulting in sleepiness or fatigue that may prompt affected people to eat more in an attempt to increase short-term energy levels.
Correlation with cardiac disorders:Atrial fibrillation (AF): A study in the medical journal Sleep found that the prevalence of atrial fibrillation among patients with idiopathic central sleep apnea was significantly higher than the prevalence among patients with obstructive sleep apnea or no sleep apnea (27%, 1.7%, and 3.3%, respectively). The study was based on 180 subjects with 60 people in each of the 3 groups. Possible explanations for the association between CSA and AF include a causal relationship in one direction or the other between the two conditions or a common cause involving an abnormality of central cardiorespiratory regulation.
Adults with congestive heart failure are at risk for a form of central apnea called Cheyne-Stokes respiration, which manifests itself both during sleep and during waking hours. Cheyne-Stokes respiration is characterized by periodic breathing featuring recurrent episodes of apnea alternating with episodes of rapid breathing. There is good evidence that replacement of the failing heart (heart transplant) cures central apnea in these patients. Temporary measures (e.g., those taken pending the availability of an organ donor) include the administration of drugs whose effects include respiratory stimulation, although these drugs are not universally effective in reducing the severity of Cheyne-Stokes apneas.
Congenital central hypoventilation syndrome
Congenital central hypoventilation syndrome (CCHS), often referred to by its older name "Ondines curse," is a rare and very severe inborn form of abnormal interruption and reduction in breathing during sleep. This condition involves a specific homeobox gene, PHOX2B, which guides maturation of the autonomic nervous system; certain loss-of-function mutations interfere with the brains development of the ability to effectively control breathing. There may be a recognizable pattern of facial features among individuals affected by this syndrome.Once almost uniformly fatal, CCHS is now treatable. Children who have it must have tracheotomies and access to mechanical ventilation on respirators while sleeping, but most do not need to use a respirator while awake. The use of a diaphragmatic pacemaker may offer an alternative for some patients. When pacemakers have enabled some children to sleep without the use of a mechanical respirator, reported cases still required the tracheotomy to remain in place because the vocal cords did not move apart with inhalation.Persons with the syndrome who survive to adulthood are strongly instructed to avoid certain condition-aggravating factors, such as alcohol use, which can easily prove lethal.
Treatment
After a patient receives a diagnosis, the diagnosing physician can provide different options for treatment. If central sleep apnea is medication-induced (e.g., opioids), reducing the dose or eventual withdrawal of the offending medication often improves CSA.
The FDA has recently approved a pacemaker-like implantable device called the remedē System for adult patients with moderate to severe central sleep apnea. After a commonly performed procedure, the device stimulates a nerve in the chest (phrenic nerve) to send signals to the large muscle that controls breathing (the diaphragm). It monitors respiratory signals during sleep and helps restore normal breathing patterns. The device is silent, activates automatically during the night, and does not require the patient to wear a mask.
Mechanical regulation of airflow and/or airway pressure:Treatment for central sleep apnea differs in that the device is set not at one constant optimal pressure but rather at two different settings, one for inhalation (IPAP) and for exhalation (EPAP), maintaining normal breathing rhythm by inflating the patients lungs at regular intervals whose specifics, such as the breathing rate and the duration of a single breath, can be programmed. Devices tailored to this purpose are known as BiPAP ("bilevel positive airway pressure") devices.
Both CPAP and BiPAP devices can be connected to a humidifier to humidify and heat the inhaled air, thus reducing unpleasant symptoms such as a sore throat or blocked nose that can result from inhaling cold, dry air.
CPAP and BiPAP devices can trigger central Apneas in those with obstructive sleep apnea requiring the use of an ASV (adaptive servo ventilation) device, which is also the proper machine for those who have central sleep apnea or mixed/complex apnea.
Epidemiology
Central sleep apnea is less prevalent than obstructive sleep apnea. In one study, CSA is stated to have a prevalence of 0.9% in comparison to OSA.There are many factors that increase the risk of developing CSA. Chronic opioid use produces a mean prevalence in central sleep apnea development of 24%. An estimate of 10% of chronic kidney disease (CKD) patients have a CSA diagnosis. Cohort studies of stroke patients show a 70% development rate of CSA within 72 hours of the stroke event, although CSA was detected in less than 17% after 3 months of follow-up. Another cohort study from the Sleep Heart Healthy study showed incidence of CSA in heart failure patients to be 0.9%.
Infancy
Central sleep apnea is common in preterm, newborn, and infancy stages but a decrease in risk is found with aging and maturity of the central nervous system. Underlying neurological disorders are the most common cause of CSA in full term infants. Of the apnea related events in preterm infants born at less than 29 weeks, 25% are central in origin.
Childhood
CSA is less common after 2 years of age. The prevalence of CSA in healthy children aging 10 to 18 years is 30%. Children with underlying medical conditions fall under a prevalence rate of 4-6%. For children diagnosed with Prader-Willi syndrome (PWS), CSA is more common and can occur in up to 53% of cases.
Adulthood
Research shows that rates of sleep apnea are higher in adults over the age of 65 years, due to older individuals having higher risks of developing CSA due to pre-existing medical conditions. Recorded prevalence in a cohort study of 2,911 men over the age of 65 was 7.5%. There is reduced risk of CSA in women, and a higher incidence in men. One study showed the incidence of CSA in men was 7.8% and 0.3% in women, stating a difference in hormones have an effect on the apneic threshold (AT) for apnea.
References
Further reading
== External links == |
Birthmark | A birthmark is a congenital, benign irregularity on the skin which is present at birth or appears shortly after birth—usually in the first month. They can occur anywhere on the skin. Birthmarks are caused by overgrowth of blood vessels, melanocytes, smooth muscle, fat, fibroblasts, or keratinocytes.
Dermatologists divide birthmarks into two types: pigmented birthmarks and vascular birthmarks. Pigmented birthmarks caused by excess skin pigment cells include: moles, café au lait spots, and Mongolian spots. Vascular birthmarks, also called red birthmarks, are caused by increased blood vessels and include macular stains (salmon patches), hemangiomas, and port-wine stains. A little over 1 in 10 babies have a vascular birthmark present by age 1. Several birthmark types are part of the group of skin lesions known as nevi or naevi, which is Latin for "birthmarks".
Birthmarks occur as a result of a localized imbalance in factors controlling the development and migration of skin cells. In addition, it is known that vascular birthmarks are not hereditary.
Pigmented types
Mole
Congenital melanocytic nevus is a type of melanocytic nevus, the medical term for what is colloquially called a "mole", found in infants at birth. Occurring in about 1% of infants in the United States, it is located in the area of the head and neck 15% of the time, but may occur anywhere on the body. It may appear as light brown in fair-skinned people, to almost black in people with darker skin. Coming in a variety of sizes and appearances, they may be irregular in shape and flat, or raised and lumpy in appearance and feel. Such naevi can also manifest themselves as beauty marks, which most commonly appear on the face, neck or arms.
Café au lait spot
Café au lait spot macules may occur anywhere on the body. They are most commonly oval in shape and light brown, or milk coffee, in color. These birthmarks may be present at birth, or appear in early childhood, and do not fade much with age. One or two on an individual is common; however, four or more may be an indicator of neurofibromatosis. In the event of weight gain, the birthmark can stretch with the skin and become larger.
Mongolian spot
A Mongolian blue spot (dermal melanocytosis) is a benign flat congenital birthmark with wavy borders and irregular shape, most common among East Asians and Turkic people (excluding Turks of Asia Minor), and named after Mongolians. It is also extremely prevalent among East Africans and Native Americans. It normally disappears three to five years after birth and almost always by puberty. The most common color is blue, although they can be blue-gray, blue-black or even deep brown.
The Mongolian spot is a congenital developmental condition exclusively involving the skin. The blue colour is caused by melanocytes, melanin-containing cells, that are deep under the skin. Usually, as multiple spots or one large patch, it covers one or more of the lumbosacral area (lower back), the buttocks, sides, and shoulders. It results from the entrapment of melanocytes in the dermis during their migration from the neural crest to the epidermis during embryonic development.Among those who are not aware of the background of the Mongolian spots, it may sometimes be mistaken for a bruise indicative of child abuse.
Vascular types
Stork bite
Colloquially called a "stork bite", "angels kiss" or "salmon patch", telangiectatic nevus appears as a pink or tanned, flat, irregularly shaped mark on the knee, back of the neck, and/or the forehead, eyelids and, sometimes, the top lip. The skin is not thickened and feels no different from anywhere else on the body; the only difference is in appearance. Nearly half of all babies have such a birthmark.
Strawberry mark
An infantile hemangioma, colloquially called a strawberry mark, is a benign self-involuting tumor (swelling or growth) of endothelial cells, the cells that line blood vessels. It usually appears during the first weeks of life and resolves by age 10. It is the most common tumor of infancy.PHACES Syndrome, a rare condition that often involves brain, heart, and arterial abnormalities, is generally accompanied by the presence of large facial hemangiomas. In such cases, what appears to be a small bruise or birthmark may grow rapidly and take on a puffy appearance in the first days or weeks of life.
Port-wine stain
Port-wine stains, also known as nevus flammeus and sometimes mistaken for strawberry marks, are present at birth and range from a pale pink in color, to a deep wine-red. Irregular in appearance, they are usually quite large, and caused by a deficiency or absence in the nerve supply to blood vessels. This causes vasodilation, the dilation of blood vessels, causing blood to pool or collect in the affected area. Over time, port-wine stains may become thick or develop small ridges or bumps, and do not fade with age. Such birthmarks may have emotional or social repercussions. Port-wine stains occur in 0.3% of the population, equally among males and females. They frequently express unilaterally, i.e., on only one side, not crossing the midline of the body. Often on the face, marks on the upper eyelid or forehead may be indicative of a condition called Sturge–Weber syndrome. Additionally, port-wine stains in these locations may be associated with glaucoma and seizures.
Treatment
Most birthmarks are harmless and do not require treatment. Pigmented marks can resolve on their own over time in some cases. Vascular birthmarks may require reduction or removal for cosmetic reasons. Treatments include administering oral or injected steroids, dermatological lasers to reduce size and/or color, or dermatologic surgery.
Historical Explanations
Many explanations were given to explain the origin of birthmarks. Occasionally, it was said that children could be marked or imprinted upon by scares or frights given to the mother during the pregnancy. Children are also said to be marked by some sudden fright or unpleasant experience of the mother, and I have myself seen a pop-eyed, big-mouthed idiot whose condition is ascribed to the fact that his mother stepped on a toad several months before his birth. In another case, a large red mark on a baby’s cheek was caused by the mother seeing a man shot down at her side, when the discharge of the gun threw some of the blood and brains into her face.Other explanations claimed that birthmarks shaped like food were the direct result of the mothers pregnancy cravings, or the mother touching a certain part of her body during a solar eclipse - her childs birthmark will be in the same location.
References
External links
Birthmarks via the Cleveland Clinic
Vascular Birthmarks Foundation
Birthmarks via MedlinePlus |
Toxic anterior segment syndrome | Toxic anterior segment syndrome is an acute, sterile anterior segment inflammation following generally uneventful cataract and anterior segment surgery.One of the main factors in differentiating toxic anterior segment syndrome from an infectious endophthalmitis is the rapid onset. Most patients with toxic anterior segment syndrome will develop symptoms within 12 to 24 hours of the surgery. Common findings on anterior segment slit lamp examination include increased cell and flare with associated fibrin and possible hypopyon formation. Patients may show signs of diffuse corneal edema, and they may also show signs of iris atrophy with pupillary abnormalities and eventual increased intraocular pressure.
It is important to differentiate sterile postoperative inflammation from infectious endophthalmitis because the treatments of these patients are markedly different. Patients with toxic anterior segment syndrome will often respond rapidly to treatment with topical corticosteroids, while infectious endophthalmitis must be treated with antibiotics. It is important that the patients be evaluated often to ensure that the inflammation is clearing and that the patients intraocular pressure is under control. The clearing of the inflammation and eventual patient outcome is related to the severity of the toxic insult at the time of surgery. Most patients reported to date are in the category of a moderate toxic inflammation.
Toxic anterior segment syndrome may be related to problems with any irrigating solution or other solution placed in the patients eye during surgery, including balanced salt solution or anything added to solutions. Material placed in the eye during surgery such as anesthetics, ophthalmic viscoelastic devices, antibiotics, or other medications has been associated with toxic anterior segment syndrome. Problems related to the cleaning and sterilization of instruments for cataract surgery have been found to be a cause.
References
== External links == |
Dermatosis papulosa nigra | Dermatosis papulosa nigra (DPN) is a condition of many small, benign skin lesions on the face, a condition generally presenting on dark-skinned individuals.: 638–9 DPN is extremely common, affecting up to 30% of Black people in the US. From a histological perspective, DPN resembles seborrheic keratoses. The condition may be cosmetically undesirable to some.
They should not be confused for Leser-Trélat sign, a sudden explosion of lesions due to a growing tumor.
Pathophysiology
The pathophysiology of DPN is unknown. Evidence of family history may suggest a genetic propensity.
Treatment
DPN lesions are benign and no treatment generally is indicated unless lesions are cosmetically undesirable. Surgical options including curettage, cryotherapy and laser therapy are options. Scarring, postoperative skin discoloration or keloid formation are potential complications. Therefore, conservative DPN treatment is advisable.
Prognosis
DPN is not a pre-malignant condition nor is it associated with any underlying systemic disease. DPN lesions show no tendency to regress spontaneously, and often increase in size and number as an individual ages.
Epidemiology
DPN affects up to 35% of the African American population in the USA. Insufficient data is available on the international frequency of DPN. Lesions generally emerge during puberty, increasing steadily in number and size as an individual ages. The incidence of DPN lesions increases with age. Black people with a fair complexion have the lowest frequency of involvement. DPN also occurs among Asians and Polynesians, although the exact incidence is unknown. Females are affected more frequently than males. Dermatosis papulosa nigra generally emerges in adolescence and is rarely in persons younger than 7 years.
See also
List of cutaneous conditions
References
External links
eMedicine.com article on DPN |
Fanconi anemia | Fanconi anaemia (FA) is a rare genetic disease resulting in impaired response to DNA damage. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected, the majority develop cancer, most often acute myelogenous leukemia (AML), and 90% develop aplastic anemia (the inability to produce blood cells) by age 40. About 60–75% have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% have some form of endocrine problem, with varying degrees of severity.
FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair via homologous recombination.Treatment with androgens and hematopoietic (blood cell) growth factors can help bone marrow failure temporarily, but the long-term treatment is bone marrow transplant if a donor is available. Because of the genetic defect in DNA repair, cells from people with FA are sensitive to drugs that treat cancer by DNA crosslinking, such as mitomycin C. The typical age of death was 30 years in 2000.FA occurs in about one per 130,000 births, with a higher frequency in Ashkenazi Jews and Afrikaners in South Africa. The disease is named after the Swiss pediatrician who originally described this disorder, Guido Fanconi. It should not be confused with Fanconi syndrome, a kidney disorder also named after Fanconi.
Signs and symptoms
FA is characterized by bone marrow failure, AML, solid tumors, and developmental abnormalities. Classic features include abnormal thumbs, absent radii, short stature, skin hyperpigmentation, including café au lait spots, abnormal facial features (triangular face, microcephaly), abnormal kidneys, and decreased fertility. Many FA patients (about 30%) do not have any of the classic physical findings, but diepoxybutane chromosome fragility assay showing increased chromosomal breaks can make the diagnosis. About 80% of FA will develop bone marrow failure by age 20.The first sign of a hematologic problem is usually petechiae and bruises, with later onset of pale appearance, feeling tired, and infections. Because macrocytosis usually precedes a low platelet count, patients with typical congenital anomalies associated with FA should be evaluated for an elevated red blood cell mean corpuscular volume.
Genetics
FA is primarily an autosomal recessive genetic disorder. This means that two mutated alleles (one from each parent) are required to cause the disease. The risk is 25% that each subsequent child will have FA. About 2% of FA cases are X-linked recessive, which means that if the mother carries one mutated Fanconi anemia allele on one X chromosome, a 50% chance exists that male offspring will present with Fanconi anemia.Scientists have identified 21 FA or FA-like genes: FANCA, FANCB, FANCC, FANCD1 (BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (BRIP1), FANCL, FANCM, FANCN (PALB2), FANCO (RAD51C), FANCP (SLX4), FANCQ (XPF), FANCS (BRCA1), FANCT (UBE2T), FANCU (XRCC2), FANCV (REV7), and FANCW (RFWD3). FANCB is the one exception to FA being autosomal recessive, as this gene is on the X chromosome. These genes are involved in DNA repair.The carrier frequency in the Ashkenazi Jewish population is about one in 90. Genetic counseling and genetic testing are recommended for families who may be carriers of Fanconi anemia.Because of the failure of hematologic components—white blood cells, red blood cells, and platelets—to develop, the bodys capabilities to fight infection, deliver oxygen, and form clots are all diminished.
Pathogenesis
Clinically, hematological abnormalities are the most serious symptoms in FA. By the age of 40, 98% of FA patients will have developed some type of hematological abnormality. However, a few cases have occurred in which older patients have died without ever developing them. Symptoms appear progressively, and often lead to complete bone marrow failure. While at birth, blood count is usually normal, macrocytosis/megaloblastic anemia, defined as unusually large red blood cells, is the first detected abnormality, often within the first decade of life (median age of onset is 7 years). Within the next 10 years, over 50% of patients presenting haematological abnormalities will have developed pancytopenia, defined as abnormalities in two or more blood cell lineages. This is in contrast to Diamond–Blackfan anemia, which affects only erythrocytes, and Shwachman–Diamond syndrome, which primarily causes neutropenia. Most commonly, a low platelet count (thrombocytopenia) precedes a low neutrophil count (neutropenia), with both appearing with relative equal frequencies. The deficiencies cause increased risk of hemorrhage and recurrent infections, respectively.As FA is now known to affect DNA repair, specifically homologous recombination, and given the current knowledge about dynamic cell division in the bone marrow, patients are consequently more likely to develop bone marrow failure, myelodysplastic syndromes, and acute myeloid leukemia (AML).
Myelodysplastic syndromes
MDSs, formerly known as preleukemia, are a group of bone marrow neoplastic diseases that share many of the morphologic features of AML, with some important differences. First, the percentage of undifferentiated progenitor cells, blast cells, is always less than 20%, with considerably more dysplasia, defined as cytoplasmic and nuclear morphologic changes in erythroid, granulocytic, and megakaryocytic precursors, than what is usually seen in cases of AML. These changes reflect delayed apoptosis or a failure of programmed cell death. When left untreated, MDS can lead to AML in about 30% of cases. Due to the nature of the FA pathology, MDS diagnosis cannot be made solely through cytogenetic analysis of the marrow. Indeed, it is only when morphologic analysis of marrow cells is performed, that a diagnosis of MDS can be ascertained. Upon examination, MDS-affected FA patients will show many clonal variations, appearing either prior or subsequent to the MDS. Furthermore, cells will show chromosomal aberrations, the most frequent being monosomy 7 and partial trisomies of chromosome 3q 15. Observation of monosomy 7 within the marrow is well correlated with an increased risk of developing AML and with a very poor prognosis, death generally ensuing within 2 years (unless prompt allogeneic hematopoietic progenitor cell transplant is an option).
Acute myeloid leukemia
FA patients are at elevated risk for the development of AML defined as presence of 20% or more of myeloid blasts in the marrow or 5 to 20% myeloid blasts in the blood. All of the subtypes of AML can occur in FA with the exception of promyelocytic. However, myelomonocytic and acute monocytic are the most common subtypes observed. Many MDS patients diseases evolve into AML if they survive long enough. Furthermore, the risk of developing AML increases with the onset of bone-marrow failure.Although risk of developing either MDS or AML before the age of 20 is only 27%, this risk increases to 43% by the age of 30 and 52% by the age of 40. Historically, even with a marrow transplant, about a quarter of FA patients diagnosed with MDS/ALS have died from MDS/ALS-related causes within two years, although more recent published evidence suggests that earlier allogeneic hematopoietic progenitor cell transplantation in children with FA is leading to better outcomes over time.
Bone marrow failure
The last major haematological complication associated with FA is bone marrow failure, defined as inadequate blood cell production. Several types of failure are observed in FA patients, and generally precede MDS and AML. Detection of decreasing blood count is generally the first sign used to assess necessity of treatment and possible transplant. While most FA patients are initially responsive to androgen therapy and haemopoietic growth factors, these have been shown to promote leukemia, especially in patients with clonal cytogenetic abnormalities, and have severe side effects, including hepatic adenomas and adenocarcinomas. The only treatment left would be bone marrow transplant; however, such an operation has a relatively low success rate in FA patients when the donor is unrelated (30% 5-year survival). It is, therefore, imperative to transplant from an HLA-identical sibling. Furthermore, due to the increased susceptibility of FA patients to chromosomal damage, pretransplant conditioning cannot include high doses of radiation or immunosuppressants, thus increased chances of patients developing graft-versus-host disease. If all precautions are taken, and the marrow transplant is performed within the first decade of life, two-year probability of survival can be as high as 89%. However, if the transplant is performed at ages older than 10, two-year survival rates drop to 54%.A recent report by Zhang et al. investigates the mechanism of bone marrow failure in FANCC-/- cells. They hypothesize and successfully demonstrate that continuous cycles of hypoxia-reoxygenation, such as those seen by haemopoietic and progenitor cells as they migrate between hyperoxic blood and hypoxic marrow tissues, leads to premature cellular senescence and therefore inhibition of haemopoietic function. Senescence, together with apoptosis, may constitute a major mechanism of haemopoietic cell depletion occurred in bone marrow failure.
Molecular basis
There are 19 genes responsible for FA, one of them being the breast-cancer susceptibility gene BRCA2. They are involved in the recognition and repair of damaged DNA; genetic defects leave them unable to repair DNA. The FA core complex of 8 proteins is normally activated when DNA stops replicating because of damage. The core complex adds ubiquitin, a small protein that combines with BRCA2 in another cluster to repair DNA (see Figure Recombinational repair of DNA double-strand damage). At the end of the process, ubiquitin is removed.Recent studies have shown that eight of these proteins, FANCA, -B, -C, -E, -F, -G, -L and -M, assemble to form a core protein complex in the nucleus. According to current models, the complex moves from the cytoplasm into the nucleus following nuclear localization signals on FANCA and FANCE. Assembly is activated by replicative stress, particularly DNA damage caused by cross-linking agents (such as mitomycin C or cisplatin) or reactive oxygen species (ROS) that is detected by the FANCM protein.Following assembly, the protein core complex activates FANCL protein which acts as an E3 ubiquitin-ligase and monoubiquitinates FANCD2.Monoubiquitinated FANCD2, also known as FANCD2-L, then goes on to interact with a BRCA1/BRCA2 complex (see Figure Recombinational repair of DNA double-strand damage). Details are not known, but similar complexes are involved in genome surveillance and associated with a variety of proteins implicated in DNA repair and chromosomal stability. With a crippling mutation in any FA protein in the complex, DNA repair is much less effective, as shown by its response to damage caused by cross-linking agents such as cisplatin, diepoxybutane and Mitomycin C. Bone marrow is particularly sensitive to this defect.
In another pathway responding to ionizing radiation, FANCD2 is thought to be phosphorylated by protein complex ATM/ATR activated by double-strand DNA breaks, and takes part in S-phase checkpoint control. This pathway was proven by the presence of radioresistant DNA synthesis, the hallmark of a defect in the S phase checkpoint, in patients with FA-D1 or FA-D2. Such a defect readily leads to uncontrollable replication of cells and might also explain the increase frequency of AML in these patients.
Spermatogenesis
In humans, infertility is one of the characteristics of individuals with mutational defects in the FANC genes. In mice, spermatogonia, preleptotene spermatocytes, and spermatocytes in the meiotic stages of leptotene, zygotene and early pachytene are enriched for FANC proteins. This finding suggests that recombinational repair processes mediated by the FANC proteins are active during germ cell development, particularly during meiosis, and that defects in this activity can lead to infertility.
Neural stem cell homeostasis
Microphthalmia and microcephaly are frequent congenital defects in FA patients. The loss of FANCA and FANCG in mice causes neural progenitor apoptosis both during early developmental neurogenesis and later during adult neurogenesis. This leads to depletion of the neural stem cell pool with aging. Much of the Fanconi anemia phenotype might be interpreted as a reflection of premature aging of stem cells.
Treatment
The first line of therapy is androgens and hematopoietic growth factors, but only 50–75% of patients respond. A more permanent cure is hematopoietic stem cell transplantation. If no potential donors exist, a savior sibling can be conceived by preimplantation genetic diagnosis (PGD) to match the recipients HLA type.
Prognosis
Many patients eventually develop acute myelogenous leukemia (AML). Older patients are extremely likely to develop head and neck, esophageal, gastrointestinal, vulvar and anal cancers. Patients who have had a successful bone marrow transplant and, thus, are cured of the blood problem associated with FA still must have regular examinations to watch for signs of cancer. Many patients do not reach adulthood.The overarching medical challenge that Fanconi patients face is a failure of their bone marrow to produce blood cells. In addition, Fanconi patients normally are born with a variety of birth defects. A significant number of Fanconi patients have kidney problems, trouble with their eyes, developmental delay and other serious defects, such as microcephaly (small head).
References
External links
Fanconi Anemia Research Fund
GeneReviews/NCBI/NIH/UW entry on Fanconi Anemia
OMIM entries on Fanconi Anemia
Fanconi anemia at Curlie
Fanconis Anaemia on patient.info |
Syndesmophyte | A syndesmophyte is a bony growth originating inside a ligament, commonly seen in the ligaments of the spine, specifically the ligaments in the intervertebral joints leading to fusion of vertebrae. Syndesmophytes are pathologically similar to osteophytes. Ankylosing spondylitis patients are particularly prone to developing syndesmophytes. They are also commonly seen in patients who have had back surgery or other chronic stresses on the ligaments of their spine. Syndesmophytes indicate spine degeneration, similar to osteophytes of spine; however, they bridge across the joint as compared to osteophytes which are non-bridging.
== References == |
Transient acantholytic dermatosis | Grovers disease (GD) is a polymorphic, pruritic, papulovesicular dermatosis characterized histologically by acantholysis: 529 with or without dyskeratosis. Once confirmed, most cases of Grovers disease last six to twelve months, which is why it was originally called "transient". However it may last much longer. Nevertheless, it is not to be confused with relapsing linear acantholytic dermatosis.
Signs and symptoms
Grovers disease often starts quite suddenly. There are intensely itchy spots on the central back, mid chest and occasionally elsewhere. Frequently, it follows sweating or some unexpected heat stress.
The itchy eruption lasts an average of 10–12 months. It is characterized by papules and papulovesicles with excoriations occurring on the chest, back, lower sternum, arms, and thighs. The papules are most commonly found on the mid chest.
Sometimes the features of Grovers are found in people who do not itch or have a conspicuous rash. Most of the people with Grovers who visit a dermatologist, however, itch a lot.
Cause
The cause of Grovers disease is unknown. Suspected triggers of disease activity include heat and sweating, sunlight, and adverse reaction to medications: 24 as well as ionizing radiation, end-stage renal disease/hemodialysis, and mechanical irritation or prolonged bed rest.
Some cases of Grovers disease have been associated with medications such as sulfadoxine-pyrimethamine, ribavirin, cetuximab, and interleukin-4 [1,8-15]. One series of 300 patients with Grovers disease reported an association with other coexisting dermatoses including atopic dermatitis, contact dermatitis, and xerosis cutis. Finally, smaller series have detailed an association with pyoderma gangrenosum, bacterial and viral infections, and occasionally, malignancies.
Diagnosis
Grovers may be suspected by its appearance, but since it has such a characteristic appearance under the microscope a shave skin or punch biopsy is often performed.
Treatment
Sweating causes lesions to form, but lesions aggravated by sweat usually return to "normal" fairly quickly—avoiding sweat is not considered a reason to avoid exercise. Minor outbreaks can be controlled with prescription strength topical cortisone creams. More severe eruptions usually clear up after treatment for one to three months with Accutane or tetracycline. If these fail or the outbreak is severe, PUVA phototherapy treatments, antifungal medication and cortisone injections are alternatives.Some research has suggested a correlation of Grovers disease with mercury toxicity in which case Dimercaptosuccinic acid might help.
Epidemiology
The prevalence and incidence of Grovers disease have not been firmly established. In a study from Switzerland, Grovers disease was diagnosed in just 24 of more than 30,000 skin biopsies. Grovers disease is mainly seen in males over the age of forty.Grovers disease affects chiefly white adults in the fifth decade or later, and appears to be around 1.6 to 2.1 times more common in men than in women. Grovers disease appears less commonly in darker-skinned individuals.
History
This condition was first reported in 1975 by the American dermatopathologist, Ralph Wier Grover (1920–2008) while working at Franklin Hospital in New York. He described and examined around 40 patients having the characteristic signs of the disease, which now bears his name.
References
External links
Media related to Transient acantholytic dermatosis at Wikimedia Commons |
Trichoblastoma | Trichoblastomas are a skin condition characterized by benign neoplasms of the follicular germinative cells known as trichoblasts.: 673 Trichoblastic fibroma is a term used to describe small nodular trichoblastomas that contain a conspicuous fibrocytic component, sometimes constituting over 50% of the lesion.
Image at left shows a trichoblastoma from a 68-year-old Caucasian male. It shows a pseudo-encapsulated, multinodular, basaloid tumor with fibrocellular stroma spanning the reticular dermis extending into subcutaneous fat (A). No epidermal connection or retraction artifact was noted. Tumor lobules were arranged as monomorphous basaloid cells in a cribriform pattern with peripheral palisading some resembling abortive hair follicles (B, F). Focally, tumor lobules exhibited squamous eddies, papillary mesenchymal bodies, and a germinative component comprising basaloid cells admixed with distinct pales cells (Zellballen) (C–E, D is an enlargement of boxed area in C).
See also
Trichoepithelioma
Basal cell carcinoma#Pathophysiology (trichoblastic carcinoma is a rare malignant lesion that can sometimes resemble trichoblastoma)
Skin lesion
List of cutaneous conditions
List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer
References
== External links == |
Pacman dysplasia | Pacman dysplasia is a lethal autosomal recessive skeletal dysplasia. The dysplasia is present during fetal development.
References
Wilcox WR, Wenger DA, Lachman RS, Rimoin DL (2005). "Distinguishing Pacman dysplasia from mucolipidosis II: comment on Saul et al. [2005]". Am J Med Genet A. 135 (3): 333. doi:10.1002/ajmg.a.30717. PMID 15887286. S2CID 38848656.
Saul RA, Proud V, Taylor HA, Leroy JG, Spranger J (2005). "Prenatal mucolipidosis type II (I-cell disease) can present as Pacman dysplasia". Am J Med Genet A. 135 (3): 328–32. doi:10.1002/ajmg.a.30716. PMID 15887289. S2CID 2151584.
Wilcox WR, Lucas BC, Loebel B, Bachman RP, Lachman RS, Rimoin DL (1998). "Pacman dysplasia: report of two affected sibs". Am J Med Genet. 77 (4): 272–6. doi:10.1002/(SICI)1096-8628(19980526)77:4<272::AID-AJMG4>3.0.CO;2-P. PMID 9600734.
Shohat M, Rimoin DL, Gruber HE, Lachman R (1993). "New epiphyseal stippling syndrome with osteoclastic hyperplasia". Am J Med Genet. 45 (5): 558–61. doi:10.1002/ajmg.1320450506. PMID 8456823.
Miller SF, Proud VK, Werner AL, Field FM, Wilcox WF, Lachman RS, Rimoin DL (2003). "Pacman dysplasia: a lethal skeletal dysplasia with variable radiographic features". Pediatr Radiol. 33 (4): 256–60. doi:10.1007/s00247-002-0859-4. PMID 12709756. S2CID 185059.
External links
Online Mendelian Inheritance in Man (OMIM): 167220 |
Axillary lymphadenopathy | Axillary lymphadenopathy is lymphadenopathy of the axillary lymph nodes.
Causes
Cat scratch fever
Brucellosis
Lymphoma
Rheumatoid arthritis
Diagnosis
To diagnose this condition, scans or other imaging tests are used. Enlarged nodes in the vicinity of cancer areas could potentially contain cancer.
Probable patients are observed for few weeks until the cause of lymphadenopathy becomes obvious and they are instructed to return to the doctor if there is increase in node size. Biopsy should be performed in case tests suggest malignancy.
Treatment
== References == |
Radial neuropathy | Radial neuropathy is a type of mononeuropathy which results from acute trauma to the radial nerve that extends the length of the arm. It is known as transient paresthesia when sensation is temporarily abnormal.
Signs and symptoms
Symptoms of radial neuropathy vary depending on the severity of the trauma; however, common symptoms may include wrist drop, numbness on the back of the hand and wrist, and inability to voluntarily straighten the fingers. Loss of wrist extension is due to loss of the ability to move of the posterior compartment of forearm muscles. In the event of lacerations to the wrist area the symptom would therefore be sensory. Additionally, depending on the type of trauma, other nerves may be affected such as the median nerve and axillary nerves.
Causes
There are many ways to acquire radial nerve neuropathy, including:
Upper arm - a fracture of the bone
Elbow - entrapment of the nerve
Wrist - elbow deformity and soft-tissue masses
Axilla - here the most common cause is compression. However, a dislocation of the humerus is a possible factor as well. It could also be due to brachial plexus compression.
Mechanism
The mechanism of radial neuropathy is such that it can cause focal demyelination and axonal degeneration. These would be caused via laceration or compression of the nerve in question.
Diagnosis
Radial neuropathy may be diagnosed using MRI, ultrasound, nerve conduction study or electromyography (EMG).
Treatment
The treatment and management of radial neuropathy can be achieved via the following methods:
Physical therapy or occupational therapy
Surgery (depending on the specific area and extent of damage)Tendon transfer (the origin remains the same but insertion is moved)Splinting
Prognosis
Radial neuropathy is not necessarily permanent, though there could be partial loss of movement or sensation. Complications include deformity of the hand in some individuals. If the injury is axonal (the underlying nerve fiber itself is damaged), recovery may take months or years and full recovery may never occur. EMG and nerve conduction studies are typically performed to diagnose the extent and distribution of the damage, and to help with prognosis for recovery.
Culture and society
There are a number of terms used to describe radial nerve injuries, which are dependent on the causation factor such as:
Honeymoon palsy from another individual sleeping on and compressing ones arm overnight.
Saturday night palsy from falling asleep with ones arm hanging over the arm rest of a chair, compressing the radial nerve.
Squash palsy, from traction forces associated with the sport squash, happens to squash players during periods between matches.
See also
Crutch paralysis
Peripheral neuropathy
References
Further reading
Cartwright, Michael S.; Yoon, Joon Shik; Lee, Kyu Ho; Deal, Nicole; Walker, Francis O. (1 April 2011). "Diagnostic Ultrasound for Traumatic Radial Neuropathy". American Journal of Physical Medicine & Rehabilitation. 90 (4): 342–343. doi:10.1097/PHM.0b013e3181e29daa. ISSN 0894-9115. PMC 2964388. PMID 20531154.
Tuncel, Umut; Turan, Aydin; Kostakoglu, Naci (1 January 2011). "Acute closed radial nerve injury". Asian Journal of Neurosurgery. 6 (2): 106–109. doi:10.4103/1793-5482.92175. ISSN 1793-5482. PMC 3277063. PMID 22347334.
== External links == |
Uncombable hair syndrome | Uncombable hair syndrome (UHS) is a rare structural anomaly of the hair with a variable degree of effect. It is characterized by hair that is silvery, dry, frizzy, wiry, and impossible to comb. It was first reported in the early 20th century. It typically becomes apparent between the ages of 3 months and 12 years. UHS has several names, including "pili trianguli et canaliculi," "cheveux incoiffables," and "spun-glass hair." This disorder is believed to be autosomal recessive in most instances, but there are a few documented cases where multiple family members display the trait in an autosomal dominant fashion. Based on the current scientific studies related to the disorder, the three genes that have been causally linked to UHS are PADI3, TGM3, and TCHH. These genes encode proteins important for hair shaft formation. Clinical symptoms of the disorder arise between 3 months and 12 years of age. The quantity of hair on the head does not change, but hair starts to grow more slowly and becomes increasingly "uncombable." To be clinically apparent, 50% of all scalp hair shafts must be affected by UHS. This syndrome only affects the hair shaft of the scalp and does not influence hair growth in terms of quantity, textural feel, or appearance on the rest of the body.
Presentation
The hair is normal in quantity and is usually silvery-blond or straw-colored. It is disorderly, stands out from the scalp, and cannot be combed flat, but it can be controlled by braiding methods. This is caused by mutations in one of three possible genes; PADI3, TGM, or TCHH. These genes code for proteins involved in hair shaft formation and improvement often occurs in later childhood. Uncombable hair syndrome is mainly autosomal recessive, but it can also be autosomal dominant because there are other involved genes that have yet to be identified.By early adulthood, phenotypic symptoms of UHS spontaneously improve or disappear. The hair of people with UHS may eventually lie flat and appear near normal in texture by adolescence or early adulthood for unknown reasons. Basmanav et al. have suggested that either different, non-mutated isoforms of the hair-forming enzymes are produced as we age, or that aging-related mechanistic changes in hair such as greater diameter and length help resolve UHS.
Symptoms
Coarse hair
Trichodysplasia
White hair
Woolly hair
Patchy baldness
Cause
As one would expect from the name, individuals affected by this disorder have difficulty managing and grooming their hair. Affected individuals usually possess blonde or silver hair that may be present at birth or develop over time. The hair is wiry, frizzy, and stands straight out from the scalp. It is often dry but not fragile or brittle. This is due to several structural abnormalities in the hair shaft. A cross-section of the hair shaft from affected individuals reveals a kidney bean, triangular, or oval diameter, unlike the circular shaft shape displayed in straight hair. This irregularity in the diameter of the hair shaft prevents the hair from lying neatly against adjacent hair fibers. Trichohyalin (TCHH) is a structural protein responsible for the proper cylindrical fiber topology of the hair shaft. TCHH binds other TCHH and keratin-intermediate filaments creating the proper cross-links and cylindrical shape of the hair shaft. PADI3 and TGM3 are two enzymes responsible for post-translational modification of TCHH important for cross-linking of TCHH within the hair. In Uncombable Hair Syndrome mutations in TCHH, PADI3, or TGM3 result in improper cross-linking and the resulting irregular shape of the hair shaft.The particular defect in TCHH as a structural component of hair may be a defect of deimination. Deimination converts the amino acid arginine to the amino acid citrulline. This conversion is done by calcium-dependent enzymes known as peptidylarginine deiminases (PADs). PADI3 is a member of this enzyme class. One study reported PAD involvement in skin and skin-related diseases, particularly at the hair follicle. Alterations to PAD activity resulted in the development of Uncombable Hair Syndrome. Another study examined the transglutaminase (TG) family of enzymes and their involvement in UHS. This family of enzymes includes TGM3, which is expressed in epidermal cells. Mutations in TGM3 may therefore reduce or alter the intermolecular cross-linking important for hair shaft formation, leading to Uncombable Hair Syndrome.Another molecular mechanism of UHS was proposed by Ralph Trueb in 2003. He suggested that premature keratinization of the inner hair root forms a rigid sheath that alters the shape of a hair strand as it grows out of the root.
Uncombable Hair Syndrome 1
Uncombable Hair Syndrome 1 is caused by a defect in the Trichohyalin gene (TCHH) found in hair follicles and some parts of hair strands. It serves as a scaffold protein, with involucrin, in cell envelope organization. The trichohyalin gene is produced and changed by other proteins and to molecules such as keratin intermediate filaments to form organized cross-links. These networks provide the hair shaft with its cylindrical form. This, in turn, leads to frizzy hair, resulting in uncombable hair. The chromosomal location for this TCHH gene is located on chromosome 1. The condition usually improves over time, and will have better hair structure once it reaches adolescence.It is still being decided whether TCHH is autosomal dominant, or autosomal recessive. In an experiment, they identified the causative mutations of UHS in 3 genes; PADI3, TGM3, and TCHH in 11 children. These children carried homozygous/heterozygous mutations in those 3 genes, which resulted in autosomal recessive inheritance. Because it was identified as autosomal recessive inheritance, scanning electron microscopy was performed in order to rule out autosomal dominance since this type of gene can also be autosomal dominant to a certain extent.
Uncombable Hair Syndrome 2
Uncombable Hair Syndrome 2 is caused by a defect in Transglutaminase 3 (TGM3) gene. This gene helps provide instructions for creating an enzyme known as Transglutaminase 3. This gene is found in skin cells known as keratinocytes and corneocytes. This helps frame the scalp, root, and strands of hair. It helps the molecules bind
proteins. The cross-links help provide strength and structure to the cells skin and hair cells. Chromosomal location of Transglutaminase 3 is located on chromosome 20.An experiment was done where Transglutaminase 3 reduced in esophageal cancer. They used western blot analysis and polymerase chain reaction. With the 58 pairs of tissues that were sampled, it was confirmed that Transglutaminase 3 is closely related to growth proliferation and migration. However, the over-expression of this gene induces cell proliferation, migration, and invasion, and promotes programmed cell death. This came to show that Transglutaminse 3 will be a candidate growth and could function as a helpful biomarker and a therapeutic target to esophageal cancer treatment.
Uncombable Hair Syndrome 3
Uncombable Hair Syndrome 3 is caused by a defect in the PADI3 gene (peptidylarginine-deiminase 3) and is located on chromosome 1. This defect apparently is the most common cause of UHS. The PADI3 gene provides instructions for creating an enzyme called peptidylargine deiminase 3. PADI3 is found within the skins extreme external surface, inside cells called karinocytes. The protein also contributes to hair follicles that are specialized structures within the skin where development happens. In these hair follicles, the PADI3 gene adjusts proteins that are giving structure to the hair strand. The PADI3 gene also involves a process called deimination. This process modifies the proteins intuitive with other proteins.An experiment was performed in where the PADI3 is found in central centrifugal cicatricial alopecia which is mostly found in African women that suggests an autosomal dominant trait to occur. With this experiment, they performed a process called immunoblotting and immunofluorescence. With immunoblotting, it appeared that the transfected cells had a marginally lower expression of the mutant compared to the wild-type. With immunofluorescence it resulted in an irregular intracellular location of the protein. Therefore, it helped conclude that there was a reduction in enzymatic action that encodes a protein to hair shaft arrangement, which relates to central centrifugal cicatricial alopecia(CCCA).
Diagnosis
Differential diagnosis
Other syndromes with hair abnormalities may also show features of uncombable hair syndrome such as Rapp–Hodgkin ectodermal dysplasia syndrome, loose anagen syndrome, EEC syndrome (ectodermal dysplasia, ectrodactyly and cleft lip/palate) and familial tricho-odonto-onychial ectodermal dysplasia with syndactyly. However, unlike these conditions, uncombable hair syndrome alone is not associated with physical, neurologic, or mental abnormalities.According to the U.S. National Institute of Health, the condition tends to develop in childhood (age 3-12) and resolve by adolescence.Another observation that can be made when detecting uncombable hair syndrome in individuals is by observing the hair shaft under a special microscope. When individual hair strands are being viewed, the hair is triangular or kidney-shaped and has a longitudinal groove on one or two faces.Clinical diagnosis of UHS can be confirmed molecularly by performing high-resolution microscopy on hair shafts using scanning electron microscopy (SEM). SEM allows for the visualization of hair shaft cross-sections, which can appear triangular, heart-shaped, kidney-shaped, flat, or longitudinally grooved. Interestingly, multiple different cross sections can appear on a single shaft of hair. An alternative method for confirming a UHS diagnosis molecularly is by embedding UHS hairs into paraffin. Due to the atypical shape of the hair shafts in UHS, UHS hair will refract light differently than typical hair, causing a glistening effect.
Treatment
Although it tends to regress naturally later in childhood, there is no definitive treatment for Uncombable Hair Syndrome. The only recommended treatment is using soft brushes and gentle conditioners. It is also recommended to avoid hair treatments that can be harsh on hair (excessive brushing, blow drying, perms, or coloring hair). Biotin supplements have also been used as a treatment, due to their historical utility in controlling nail fragility and improving hair growth after 4 months of supplementation.
Epidemiology
While UHS is thought to be extremely rare, its precise frequency and prevalence is unknown. As of 2016, there were ~100 case studies of UHS in the scientific literature, and as of 2020, there are a few more documented case studies.UHS has been found in patients who also have diseases such as ectodermal dysplasia and loose anagen hair syndrome. While sometimes observed with other disorders, it is believed that Uncombable Hair Syndrome is an isolated disease.
History
The syndromes name comes directly from its abnormal, frizzy appearance that “totally resists any effort to control it with brush or comb.” A possible case of uncombable hair syndrome was reported in 1912 by A.F. Le Double and F. Houssay. The syndrome was described in 1973 by A. Dupré, P. Rochiccioli, and J.L. Bonafé, who named it "cheveux incoiffables". Later that year it was independently described as "spun-glass hair" by J.D. Stroud and A.H. Mehregan. The currently used term was coined in the early 1980s. However, the UHS phenotype was recorded well before the first literature report in 1973. A children’s story published in Germany in 1845 detailed a character named “Struwwelpeter” or “Shockheaded Peter,” presumably to describe the frizzy nature of a patient’s hair with UHS. This children’s story was later translated by Mark Twain and the character was instead called “Slovenly Peter.”Evidence of familial transmission of UHS prior to 1973 also comes from case studies. In 1983, Garty et al. described the case of a 2-year-old boy whose father, grandfather, and great-grandfather were all said to have the same condition at a young age—difficulty combing their hair. In 1993, Zanca and Zanca found a book from 1912 that details the observations, made by Le Double and Houssay (in their book “Les Velus”), of people with “mop hair” that does not tolerate combing.
Current research
The American Hair Research Society studies hair growth disorders and possible treatments for them. In addition to UHS, these disorders include alopecia areata, telogen effluvium, cicatricial alopecia, female and male pattern hair loss, trichotillomania, and hair shaft defects. The society was founded in 1989 by a group of dermatologists and has grown to include general physicians, scientific researchers, and other collaborative partners to advance research on human hair. It is one of the only non-profit research centers on hair disorders in the Americas. Current clinical trials and research opportunities can be found on their website.
See also
List of cutaneous conditions
TGM3
PADI3
Trichohyalin
References
External links
Uncombable hair syndrome at NIHs Office of Rare Diseases |
Subsets and Splits
No saved queries yet
Save your SQL queries to embed, download, and access them later. Queries will appear here once saved.