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Pyonephrosis | Pyonephrosis (Greek pyon "pus" + nephros "kidney") is an infection of the kidneys collecting system. Pus collects in the renal pelvis and causes distension of the kidney. It can cause kidney failure.
Cause
Pyonephrosis is sometimes a complication of kidney stones, which can be a source of persisting infection. It may also occur spontaneously. It can occur as a complication of hydronephrosis or pyelonephritis.
Diagnosis
CECT is investigation of choice.
Treatment
This requires drainage, best performed by ureteral stent placement or nephrostomy.
Surgery - Nephrectomy, if the ureter affects - Nephroureterectomy.
If the second kidney is not healthy, only drainage of the kidney or puncture nephrostomy is performed.
See also
Pyelonephritis
Nephrotic syndrome
References
== External links == |
Aase syndrome | Aase syndrome or Aase–Smith syndrome is a rare inherited disorder characterized by anemia with some joint and skeletal deformities. Aase syndrome is thought to be an autosomal dominant inherited disorder. The genetic basis of the disease is not known. The anemia is caused by underdevelopment of the bone marrow, which is where blood cells are formed.
It is named after the American paediatricians Jon Morton Aase and David Weyhe Smith, who characterized it in 1968.
Signs and symptoms
Among the presentation are:
Mildly slowed growth
Pale skin
Delayed closure of fontanelles (soft spots)
Narrow shoulders
Triple jointed thumbs, absent or small knuckles, decreased skin creases at finger joints
Inability to fully extend the joints from birth (congenital contractures)
Cleft palate
Deformed ears
Droopy eyelids
Complications
Complications related to anemia include weakness, fatigue, and decreased oxygenation of the blood.
Decreased white blood cells alter the bodys ability to fight infection.
If a heart defect exists, it may cause multiple complications (depending on the specific defect).
Severe cases have been associated with still birth or early death.
Cause
Some cases of Aase syndrome (45%) have been shown to be inherited, and are due to a change in one gene which makes ribosomal proteins. However, many cases are not inherited and occur without a known cause.
Diagnosis
A CBC (complete blood count) will show anemia and a decrease in the white blood cell count.
An echocardiogram may reveal heart defects (ventricular septal defect is most common).
X-rays will show skeletal abnormalities as described above.
A bone marrow biopsy may be performed.
Prevention
As with most genetic diseases there is no way to prevent the entire disease. With prompt recognition and treatment of infections in childhood, the complications of low white blood cell counts may be limited.
Treatment
Frequent blood transfusions are given in the first year of life to treat anemia. Prednisone may be given, although this should be avoided in infancy because of side effects on growth and brain development. A bone marrow transplant may be necessary if other treatment fails.
Prognosis
Anemia usually resolves over the years.
References
== External links == |
Lattice corneal dystrophy | Lattice corneal dystrophy type is a rare form of corneal dystrophy. It has no systemic manifestations, unlike the other type of the dystrophy, Lattice corneal dystrophy type II. Lattice corneal dystrophy was first described by Swiss ophthalmologist Hugo Biber in 1890.Lattice dystrophy gets its name from an accumulation of amyloid deposits, or abnormal protein fibers, throughout the middle and anterior stroma.
Presentation
Filamentous opacities appear in the cornea with intertwining delicate branching processes. During an eye examination, the doctor sees these deposits in the stroma as clear, comma-shaped overlapping dots and branching filaments, creating a lattice effect. Over time, the lattice lines will grow opaque and involve more of the stroma. They will also gradually converge, giving the cornea a cloudiness that may also reduce vision. The disease is bilateral, usually noted before the end of the first decade of life. Although lattice dystrophy can occur at any time in life, the condition usually arises in children between the ages of two and seven.In some people, these abnormal protein fibers can accumulate under the corneas outer layer—the epithelium. This can cause erosion of the epithelium. This condition is known as recurrent epithelial erosion. These erosions alter the corneas normal curvature, resulting in temporary vision problems, and expose the nerves that line the cornea, causing severe pain. Even the involuntary act of blinking can be painful.
In systemic cases, kidney failure, heart failure and neuropathy such as facial nerve palsy, laxity of the skin may be noted.
Genetics
Lattice corneal dystrophy has three types:
type I: with no systemic association. It is caused by mutations in TGFBI gene encoding keratoepithelin, which maps to chromosome 5q.
type II or Finnish type amyloidosis: associated with manifestations of systemic amyloidosis due to accumulation of gelsolin. Associated conditions may include cutis laxa and ataxia.
type III is also described which has an onset at age 70 to 90 years and is not associated with systemic amyloidosis.
Diagnosis
In the examination of biomicroscopy, it appears as branches spread on the corneal stroma in the appearance of ghost vessels. diagnosis can also be confirmed with anterior segment OCT (Visante OCT, spectral domain OCT).The interwoven linear opaque filaments have some resemblance to NERVES, but may not be observed in all affected members of families with the condition. Recurrent corneal erosions may precede the corneal opacities and even appear in individuals lacking recognizable stromal disease. Amyloid deposits are found throughout the corneal stroma. Linear and other shaped opaque areas accumulate particularly within the central corneal stroma, while the peripheral cornea remains relatively transparent.
Treatment
In case of corneal erosion, a doctor may prescribe eye drops and ointments to reduce the friction on the eroded cornea. In some cases, an eye patch may be used to immobilize the eyelids. With effective care, these erosions usually heal within three to seven days, although occasional sensations of pain may occur for the next six-to-eight weeks. As patients with LCD suffer with dry eyes as a result of erosion, a new technique involving the insertion of punctal plugs (both upper and lower) can reduce the amount of drops used a day, aiding ocular stability.By about age 40, some people with lattice dystrophy will have scarring under the epithelium, resulting in a haze on the cornea that can greatly obscure vision. In this case, a corneal transplantation may be needed. There have been many cases in which teenage patients have had the procedure, which accounts for the change in severity of the condition from person to person.Although people with lattice dystrophy have an excellent chance for a successful corneal transplantation, the disease may also arise in the donor cornea in as little as three years. In one study, about half of the transplant patients with lattice dystrophy had a recurrence of the disease between two and 26 years after the operation. Of these, 15 percent required a second corneal transplant. Early lattice and recurrent lattice arising in the donor cornea responds well to treatment with the excimer laser.
Phototherapeutic keratectomy (PTK) using [Excimer laser] can restore and preserve useful visual function for a significant period of time in patients with anterior corneal dystrophies.
References
== External links == |
Black palm | Black palm is a common name for several species of plants in the family Arecaceae, including:
Astrocaryum standleyanum, native to Central and South America
Borassus flabellifer
Normanbya normanbyi (Queensland black palm) |
Multifocal fibrosclerosis | Multifocal fibrosclerosis and idiopathic fibrosclerosis are disorders of unknown aetiology, characterised by fibrous lesions (co-)occurring at a variety of sites. Known manifestations include retroperitoneal fibrosis, mediastinal fibrosis and Riedels thyroiditis.They are now considered to be manifestations of IgG4-related disease.
References
== External links == |
Amelogenesis imperfecta | Amelogenesis imperfecta (AI) is a congenital disorder which presents with a rare abnormal formation of the enamel or external layer of the crown of teeth, unrelated to any systemic or generalized conditions. Enamel is composed mostly of mineral, that is formed and regulated by the proteins in it. Amelogenesis imperfecta is due to the malfunction of the proteins in the enamel (ameloblastin, enamelin, tuftelin and amelogenin) as a result of abnormal enamel formation via amelogenesis.People with amelogenesis imperfecta may have teeth with abnormal color: yellow, brown or grey; this disorder can affect any number of teeth of both dentitions. Enamel hypoplasia manifests in a variety of ways depending on the type of AI an individual has (see below), with pitting and plane-form defects common. The teeth have a higher risk for dental cavities and are hypersensitive to temperature changes as well as rapid attrition, excessive calculus deposition, and gingival hyperplasia. The earliest known case of AI is in an extinct hominid species called Paranthropus robustus, with over a third of individuals displaying this condition.
Genetics
Several gene expression is needed for enamel formation where the relevant matrix proteins & proteinases are transcribed for regular crystal growth & enamel mineralization.Mutations in the AMELX, ENAM, MMP20, KLK-4, FAM83H, WDR72, C4orf26, SLC24A4 LAMB3 and ITGB6 genes have been found to cause amelogenesis imperfecta (non-syndromic form). AMELX and ENAM encode extracellular matrix proteins of the developing tooth enamel and KLK-4 and MMP20 encode proteases that help degrade organic matter from the enamel matrix during the maturation stage of amelogenesis. SLC24A4 encodes a calcium transporter that mediates calcium transport to developing enamel during tooth development. Less is known about the function of other genes implicated in amelogenesis imperfecta.Researchers expect that mutations in further genes are likely to be identified as causes of amelogenesis imperfecta. Types include:
Amelogenesis imperfecta can have different inheritance patterns depending on the gene that is altered. Mutations in the ENAM gene are the most frequent known cause and are most commonly inherited in an autosomal dominant pattern. This type of inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder.Amelogenesis imperfecta is also inherited in an autosomal recessive pattern; this form of the disorder can result from mutations in the ENAM, MMP20, KLK4, FAM20A, C4orf26 or SLC24A4 genes. Autosomal recessive inheritance means two copies of the gene in each cell are altered.About 5% of amelogenesis imperfecta cases are caused by mutations in the AMELX gene and are inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In most cases, males with an X-linked form of this condition experience more severe dental abnormalities than affected females. Recent genetic studies suggest that the cause of a significant proportion of amelogenesis imperfecta cases remains to be discovered.
Diagnosis
AI can be classified according to their clinical appearances:
Type 1 - Hypoplastic
Enamel of abnormal thickness due to malfunction in enamel matrix formation. Enamel is very thin but hard & translucent, and may have random pits & grooves. Condition is of autosomal dominant, autosomal recessive, or x-linked pattern. Enamel differs in appearance from dentine radiographically as normal functional enamel.
Type 2 - Hypomaturation
Enamel has sound thickness, with a pitted appearance. It is less hard compared to normal enamel, and are prone to rapid wear, although not as intense as Type 3 AI. Condition is of autosomal dominant, autosomal recessive, or x-linked pattern. Enamel appears to be comparable to dentine in its radiodensity on radiographs.
Type 3 - Hypocalcified
Enamel defect due to malfunction of enamel calcification, therefore enamel is of normal thickness but is extremely brittle, with an opaque/chalky presentation. Teeth are prone to staining and rapid wear, exposing dentine. Condition is of autosomal dominant and autosomal recessive pattern. Enamel appears less radioopaque compared to dentine on radiographs.
Type 4 - Hypomature hypoplastic enamel with taurodontism
Enamel has a variation in appearance, with mixed features from Type 1 and Type 2 AI. All Type 4 AI has taurodontism in common. Condition is of autosomal dominant pattern. Other common features may include an anterior open bite, taurodontism, sensitivity of teeth.Differential diagnosis would include dental fluorosis, molar-incisor hypomineralization, chronological disorders of tooth development.
Treatment
Preventive and restorative dental care is very important as well as considerations for esthetic issues since the crown are yellow from exposure of dentin due to enamel loss. The main objectives of treatment is pain relief, preserving patients remaining dentition, and to treat and preserve the patients occlusal vertical height.Many factors are to be considered to decide on treatment options such as the classification and severity of AI, the patients social history, clinical findings etc. There are many classifications of AI but the general management of this condition is similar.Full-coverage crowns are sometimes being used to compensate for the abraded enamel in adults, tackling the sensitivity the patient experiences. Usually stainless steel crowns are used in children which may be replaced by porcelain once they reach adulthood. These aid with maintaining occlusal vertical dimension.
Aesthetics may be addressed via placement of composite or porcelain veneers, depending on patient factors e.g. age. If the patient has primary or mixed dentition, lab-made composite veneers may be provided temporarily, to be replaced by permanent porcelain veneers once the patient has stabilized permanent dentition. The patients oral hygiene and diet should be controlled as well as they play a factor in the success of retaining future restorations.In the worst-case scenario, the teeth may have to be extracted and implants or dentures are required. Loss of nerves in the affected teeth may occur.
Epidemiology
The exact incidence of amelogenesis imperfecta is uncertain. Estimates vary widely, from 1 in 700 people in northern Sweden to 1 in 14,000 people in the United States. The prevalence of amelogenesis imperfecta in non-human animals has not been explored, however its presence has been noted.This condition is neither caused by nor the equivalent of dental fluorosis. A manifestation of amelogenesis imperfecta known as "snow capping" is confined to the outer prismless enamel layer. It may superficially resemble dental fluorosis, and indeed "snow capping" may be used as a descriptive term in some incidents of dental fluorosis.
References
Further reading
== External links == |
Bicipital tenosynovitis | Bicipital tenosynovitis is tendinitis or inflammation of the tendon and sheath lining of the biceps muscle. It is often the result of many years of small tears or other degenerative changes in the tendon first manifesting in middle age, but can be due to a sudden injury. Calcification of the tendon, and osteophytes ("bone spurs") in the intertubercular groove can be apparent on x-rays. The condition (which can also occur in dogs) is commonly treated with physical therapy and cortisone
== References == |
Cushing reflex | Cushing reflex (also referred to as the vasopressor response, the Cushing effect, the Cushing reaction, the Cushing phenomenon, the Cushing response, or Cushings Law) is a physiological nervous system response to increased intracranial pressure (ICP) that results in Cushings triad of increased blood pressure, irregular breathing, and bradycardia. It is usually seen in the terminal stages of acute head injury and may indicate imminent brain herniation. It can also be seen after the intravenous administration of epinephrine and similar drugs. It was first described in detail by American neurosurgeon Harvey Cushing in 1901.
Definition
The Cushing reflex classically presents as an increase in systolic and pulse pressure, reduction of the heart rate (bradycardia), and irregular respiration. It is caused by increased pressure inside the skull. These symptoms can be indicative of insufficient blood flow to the brain (ischemia) as well as compression of arterioles.In response to rising intracranial pressure (ICP), respiratory cycles change in regularity and rate. Different patterns indicate a different location of the brain where the injury occurred. The increase in ventilation is exhibited as an increase in rate rather than depth of ventilation, so the Cushing reflex is often associated with slow, irregular breathing. As a result of the now defective regulation of heart rate and blood pressure, the physiologic response is decreased blood flow peripherally, which can present as Mayer waves. These are simply pathologic waves seen in HR tracings (i.e., arterial lines, electrocardiograph (ECG, etc.), which reflect decreased intravascular blood flow. This decreased flow often causes a reflexive HTN, or hypertension (increase in blood pressure) despite the actual decrease in intravascular volume.
Differential diagnosis
Whenever a Cushing reflex occurs, there is a high probability of death in seconds to minutes. As a result, a Cushing reflex indicates a need for immediate care. Since its presence is a good detector of high ICP, it is often useful in the medical field, particularly during surgery. During any neurosurgery being performed on the brain, there is always a likelihood that raised intracranial pressure may occur. Early recognition of this is crucial to the well being of the patient. Although direct measurement of ICP is possible, it is not always accurate. In the past, physicians and nurses have relied on hemodynamic changes or bradycardia, the late phase of the reflex, to identify the ICP increase. Once the initial stage of the Cushing reflex (bradycardia combined with hypertension) was discovered, it offered a much more reliable and swift warning sign of high ICP. It was found that hypertension and bradycardia occurred 93% of the time when cerebral perfusion pressure (CPP) dropped below 15 mmHg due to raised ICP. Also, the Cushing reflex is known to arise only from acute prolonged raises in ICP. Thus, it can be used as a tool by physicians to differentiate acute and chronic rises in ICP.It has also been reported that the presence of a Cushing reflex due to an ICP increase could allow one to conclude that ischemia has occurred in the posterior cranial fossa. Finally, the Cushing reflex may be one of many ways to identify if a patient has rejected a transplanted organ. Aside from the innate autoimmune response, ischemia in the cranial region has been detected with a transplanted organ that is being rejected. As such, the presence of a Cushing reflex due to ICP can indicate that ischemia may be occurring due to foreign organ rejection.As first postulated by Harvey Cushing, raised intracranial pressure is the primary cause of the Cushing reflex. Furthermore, continued moderate increases in cranial pressure allows for the Cushing reflex to occur. In contrast, rapid and dramatic pressure rises do not allow for the mechanism of the reflex to sufficiently take place. Elevated intracranial pressure can result from numerous pathways of brain impairment, including: subarachnoid hemorrhages, ischemia, meningitis, trauma, including concussions, hypoxia, tumors, and stroke. In one study, it was confirmed that raised ICP due to subarachnoid hemorrhaging causes mechanical distortion of the brainstem, specifically the medulla. Due to the mechanism of the Cushing reflex, brainstem distortion is then swiftly followed by sympathetic nervous system over activity. In addition, during typical neurosurgical procedures on patients, especially those involving neuroendoscopic techniques, frequent washing of the ventricles have been known to cause high intracranial pressure. The Cushing reflex can also result from low CPP, specifically below 15 mmHg. CPP normally falls between 70-90 mmHg in an adult human, and 60-90 mmHg in children.Brain plateau wave changes are also associated with the Cushing reflex. These waves are characterized by acute rises of the ICP, and are accompanied by a decrease of the cerebral perfusion pressure. It has been found that if a Cushing reflex occurs, brain plateau wave changes can be erased due to disappearance of high ICP.
Mechanism
The Cushing reflex is complex and seemingly paradoxical. The reflex begins when some event causes increased intracranial pressure (ICP). Since cerebrospinal fluid is located in an area surrounded by the skull, increased ICP consequently increases the pressure in the fluid itself. The pressure in the cerebral spinal fluid eventually rises to the point that it meets and gradually exceeds the mean arterial blood pressure (MAP). When the ICP exceeds the MAP, arterioles located in the brains cerebrum become compressed. Compression then results in diminished blood supply to the brain, a condition known as cerebral ischemia.During the increase in ICP, both the sympathetic nervous system and the parasympathetic nervous system are activated. In the first stage of the reflex, sympathetic nervous system stimulation is much greater than parasympathetic stimulation. The sympathetic response activates alpha-1 adrenergic receptors, causing constriction of the bodys arteries. This constriction raises the total resistance of blood flow, elevating blood pressure to high levels, which is known as hypertension. The bodys induced hypertension is an attempt to restore blood flow to the ischemic brain. The sympathetic stimulation also increases the rate of heart contractions and cardiac output. Increased heart rate is also known as tachycardia. This combined with hypertension is the first stage of the Cushing reflex.Meanwhile, baroreceptors in the aortic arch detect the increase in blood pressure and trigger a parasympathetic response via the vagus nerve. This induces bradycardia, or slowed heart rate, and signifies the second stage of the reflex. Bradycardia may also be caused by increased ICP due to direct mechanical distortion of the vagus nerve and subsequent parasympathetic response. Furthermore, this reflexive increase in parasympathetic activity is thought to contribute to the formation of Cushing ulcers in the stomach, due to uncontrolled activation of the parietal cells. The blood pressure can be expected to remain higher than the pressure of the raised cerebral spinal fluid to continue to allow blood to flow to the brain. The pressure rises to the point where it overcomes the resisting pressure of the compressed artery, and blood is allowed through, providing oxygen to the hypoxic area of the brain. If the increase in blood pressure is not sufficient to compensate for the compression on the artery, infarction occurs.Raised ICP, tachycardia, or some other endogenous stimulus can result in distortion and/or increased pressure on the brainstem. Since the brainstem controls involuntary breathing, changes in its homeostasis often results in irregular respiratory pattern and/or apnea. This is the third and final stage of the reflex.
The role of the central chemoreceptors in the Cushing reflex is unclear. In most normal pressure responses the chemoreceptors and baroreceptors work together to increase or decrease blood pressure. In the Cushing reflex, the central chemoreceptors are likely involved in the detection of ischemia, contributing to the sympathetic surge and hypertension in the first phase of the reflex, and work in opposition to the baroreceptors, contributing to the combined high sympathetic and parasympathetic activation.
Function
Raised intracranial pressure can ultimately result in the shifting or crushing of brain tissue, which is detrimental to the physiological well-being of patients. As a result, the Cushing reflex is a last-ditch effort by the body to maintain homeostasis in the brain. It is widely accepted that the Cushing reflex acts as a baroreflex, or homeostatic mechanism for the maintenance of blood pressure, in the cranial region. Specifically, the reflex mechanism can maintain normal cerebral blood flow and pressure under stressful situations such as ischemia or subarachnoid hemorrhages. A case report of a patient who underwent a spontaneous subarachnoid hemorrhage demonstrated that the Cushing reflex played a part in maintaining cerebral perfusion pressure (CPP) and cerebral blood flow. Eventually, the ICP drops to a level range where a state of induced hypertension in the form of the Cushing reflex is no longer required. The Cushing reflex was then aborted, and CPP was maintained. It has also been shown that an increase in mean arterial pressure due to hypertension, characteristic of the reflex, can cause the normalization of CPP. This effect is protective, especially during increased intracranial pressure, which creates a drop in CPP.
Cushings triad
Cushings triad is a clinical triad variably defined as having:
Irregular, decreased respirations (caused by impaired brainstem function)
Bradycardia
Systolic hypertension (widening pulse pressure)
History
Cushings reflex is named after Harvey Williams Cushing (1869–1939), an American neurosurgeon. Cushing began his research in Bern, Switzerland studying abroad with Emil Theodor Kocher. A month into his trip, Cushing received a formal proposition from Emil Theodor Kocher to begin testing how compression of the brain affected blood vessels. Cushing also enlisted the aid of Hugo Kronecker, a known blood pressure researcher. Utilizing Kroeneckers assistance and resources, Cushing began his research. Cushing left Bern in 1901 to work in Turin, Italy with Angelo Mosso, a previous student of Kroenecker. He continued to work on the same research project, while also simultaneously improving his methods of recording coincidence of blood pressure and ICP. In June 1901 Cushing published his first paper through Johns Hopkins Hospital Bulletin entitled "Concerning a definite regulatory mechanism of the vasomotor centre which controls blood pressure during cerebral compression". Between 1901 and 1903, Cushing published five papers pertaining to his research on the vasopressor response. These papers were published in German and English, and one was authored by Emil Theodor Kocher.
Experimental setup and results
Cushing began experimenting once he obtained approval from Kocher. His experimental setup was a modified version of Leonard Hills model to similarly test the effects of brain pressure on sinus pressure, cerebrospinal fluid pressure, arterial and venous blood pressure. Like Hill, Cushing used dogs for his experiments. To begin, Cushing monitored the caliber and color of cortical vessels by fitting a glass window into the skull of the dog. Intracranial pressure was raised by filling an intracranial, soft, rubber bag with mercury. Cushing recorded the intracranial pressure along with blood pressure, pulse rate, and respiratory rate simultaneously. This three part effect is commonly referred to as Cushings triad. In later experiments performed by Mosso, intracranial pressure was induced by injecting physiological saline into the subarachnoid space rather than increasing mercury content of an intracranial bag.This research clearly displayed the cause and effect relationship between intracranial pressure and cerebral compression. Cushing noted this relationship in his subsequent publications. He also noted that there must exist a specific regulatory mechanism that increased blood pressure to a high enough point such that it did not create anemic conditions. Cushings publications contain his observations and no statistical analysis. The sample size of the experiment is also not known.
Other researchers
Several notable figures in the medical field, including Ernst von Bergmann, Henri Duret, Friedrich Jolly, and others experimented with intracranial pressure similarly to Cushing. Some of these researchers published similar findings concerning the relationship of intracranial pressure to arterial blood pressure before Cushing had begun experimenting. Cushing studied this relationship more carefully and offered an improved explanation of the relationship.Some controversy concerning plagiarism does surround some of Cushings research. Bernhard Naunyn, a German pathologist and contemporary of Cushing, made remarks claiming that Cushing neither cited him in Cushings research nor expanded on any of the results that he had found in his original experiments.
Research directions
Although a lot of progress has been made since 1901 when Harvey Cushing first expanded knowledge of what is now known as the Cushing reflex, there are still many aspects of the research that remain to be seen. The exact pathogenesis of the disease remains undetermined. The possibility that intracranial pressure (ICP) may not be the sole cause of the Cushing reflex per se came from an occurrence of Cushing blood pressure response occurring before increased ICP. Some research observed symptoms of Cushing reflex, without the usual increased ICP and medullary anemia, suggesting other causes that still require research. Axial brain stem distortion could be the pathogenesis of Cushing reflex.The nature of receptors mediating the Cushing response is also unknown. Some research suggests the existence of intracranial baroreceptors to trigger specific Cushing baroreceptor reflex. Experiments by Schmidt and his fellow researchers showed that the Cushing reflex is directed by autonomic nervous system, since its physiological change has to do with the balance of the sympathetic nervous system and parasympathetic nervous system. However, the specific relation between the autonomic nervous system response and the Cushing reflex and its symptoms has yet to be identified.It has been determined that rate of respiration is affected by the Cushing reflex, though the respiratory changes induced are still an area that needs more research. Some researchers have reported apnea, while others have reported increased respiratory rates. Other researchers have found that increases in respiratory rate follow ICP decreases, while others say it is a response to ICP increase. One must also take into account the use of anesthetics in early experimentation. Research was initially performed on animals or patients under anesthesia. The anesthesia used in experiments have led to respiratory depression, which might have had effect on the results. Early experiments also put animal subjects under artificial ventilation, only allowing for limited conclusions about respiration in the Cushing reflex. The use of anesthetics proposes ideas for future research, since the creation of the Cushing response has been difficult to create under basal conditions or without anesthesia.Some researchers have also suggested a long-term effect of the Cushing reflex. Thus far it has only been observed as an immediate acute response, but there has been some evidence to suggest that its effects could be prolonged, such as a long-term raise in blood pressure. Heightened sensitivity of neurological response systems leading to arterial hypertension is also possible, but has not been examined.Although the Cushing reflex was primarily identified as a physiological response when blood flow has almost ceased, its activity has also been seen in fetal life. This activity has not been thoroughly investigated, so there is a need for more research in this area.
The underlying mechanisms of the reflex on a cellular level are yet to be discovered, and will likely be the next area of research if scientists and or doctors chose to do so.
See also
Traumatic brain injury
Bainbridge reflex
== References == |
Pectus excavatum | Pectus excavatum is a structural deformity of the anterior thoracic wall in which the sternum and rib cage are shaped abnormally. This produces a caved-in or sunken appearance of the chest. It can either be present at birth or develop after puberty.
Pectus excavatum can impair cardiac and respiratory function and cause pain in the chest and back.
People with the condition may experience severe negative psychosocial effects and avoid activities that expose the chest.
Signs and symptoms
The hallmark of the condition is a sunken appearance of the sternum. The most common form is a cup-shaped concavity, involving the lower end of the sternum; a broader concavity involving the upper costal cartilages is possible. The lower-most ribs may protrude ("flared ribs"). Pectus excavatum defects may be symmetric or asymmetric.
People may also experience chest and back pain, which is usually of musculoskeletal origin.In mild cases, cardiorespiratory function is normal, although the heart can be displaced and/or rotated. In severe cases, the right atrium may be compressed, mitral valve prolapse may be present, and physical capability may be limited due to base lung capacity being decreased.Psychological symptoms manifest with feelings of embarrassment, social anxiety, shame, limited capacity for activities and communication, negativity, intolerance, frustration, and even depression.
Causes
Researchers are unsure of the cause of pectus excavatum. Some researchers take the stance that it is a congenital disorder (birth defect), but not genetic. Others assume that there is some genetic component. A small sample size test found that in at least some cases, 37% of individuals have an affected first degree family member. As of 2012, a number of genetic markers for pectus excavatum have also been discovered.It was believed for decades that pectus excavatum is caused by an overgrowth of costal cartilage, however people with pectus excavatum actually tend to have shorter, not longer, costal cartilage relative to rib length.Pectus excavatum can be present in other conditions too, including Noonan syndrome, Marfan syndrome and Loeys–Dietz syndrome as well as other connective tissue disorders such as Ehlers–Danlos syndrome. Many children with spinal muscular atrophy develop pectus excavatum due to their diaphragmatic breathing.
Pathophysiology
Physiologically, increased pressure in utero, rickets and increased traction on the sternum due to abnormalities of the diaphragm have been postulated as specific mechanisms. Because the heart is located behind the sternum, and because individuals with pectus excavatum have been shown to have visible deformities of the heart seen both on radiological imaging and after autopsies, it has been hypothesized that there is impairment of the function of the cardiovascular system in individuals with pectus excavatum. While some studies have demonstrated decreased cardiovascular function, no consensus has been reached based on newer physiological tests such as echocardiography of the presence or degree of impairment in cardiovascular function. However, a 2016 meta-analysis found significant evidence that surgical correction of pectus excavatum improves patient cardiac performance.
Diagnosis
Pectus excavatum is initially suspected from visual examination of the anterior chest. Auscultation of the chest can reveal displaced heart beat and valve prolapse. There can be a heart murmur occurring during systole caused by proximity between the sternum and the pulmonary artery.
Lung sounds are usually clear yet diminished due to decreased base lung capacity.Many scales have been developed to determine the degree of deformity in the chest wall. Most of these are variants on the distance between the sternum and the spine. One such index is the Backer ratio which grades severity of deformity based on the ratio between the diameter of the vertebral body nearest to xiphosternal junction and the distance between the xiphosternal junction and the nearest vertebral body. More recently the Haller index has been used based on CT scan measurements. An index over 3.25 is often defined as severe. The Haller index is the ratio between the horizontal distance of the inside of the ribcage and the shortest distance between the vertebrae and sternum.
Chest x-rays are also useful in the diagnosis. The chest x-ray in pectus excavatum can show an opacity in the right lung area that can be mistaken for an infiltrate (such as that seen with pneumonia). Some studies also suggest that the Haller index can be calculated based on chest x-ray as opposed to CT scanning in individuals who have no limitation in their function.Pectus excavatum is differentiated from other disorders by a series of elimination of signs and symptoms. Pectus carinatum is excluded by the simple observation of a collapsing of the sternum rather than a protrusion. Kyphoscoliosis is excluded by diagnostic imaging of the spine, wherein pectus excavatum the spine usually appears normal in structure.
Treatment
Pectus excavatum requires no corrective procedures in mild cases. Treatment of severe cases can involve either invasive or non-invasive techniques or a combination of both. Before an operation proceeds several tests are usually performed. These include, but are not limited to, a CT scan, pulmonary function tests, and cardiology exams (such as auscultation and ECGs). After a CT scan is taken, the Haller index is measured. The patients Haller is calculated by obtaining the ratio of the transverse diameter (the horizontal distance of the inside of the ribcage) and the anteroposterior diameter (the shortest distance between the vertebrae and sternum). A Haller Index of greater than 3.25 is generally considered severe, while normal chest has an index of 2.5. The cardiopulmonary tests are used to determine the lung capacity and to check for heart murmurs.
Conservative treatment
The chest wall is elastic, gradually stiffening with age. Non-surgical treatments have been developed that aim at gradually alleviating the pectus excavatum condition, making use of the elasticity of the chest wall, including the costal cartilages, in particular in young cases.
Exercise
Physical exercise has an important role in conservative pectus excavatum treatment though is not seen as a means to resolve the condition on its own. It is used in order to halt or slow the progression of mild or moderate excavatum conditions and as supplementary treatment to improve a poor posture, to prevent secondary complications, and to prevent relapse after treatment.Exercises are aimed at improving posture, strengthening back and chest muscles, and enhancing exercise capacity, ideally also increasing chest expansion. Pectus exercises include deep breathing and breath holding exercises, as well as strength training for the back and chest muscles. Additionally, aerobic exercises to improve cardiopulmonary function are employed.
Vacuum bell
An alternative to surgery, the vacuum bell, was described in 2006; the procedure is also referred to as treatment by cup suction. It consists of a bowl shaped device which fits over the caved-in area; the air is then removed by the use of a hand pump. The vacuum created by this lifts the sternum upwards, lessening the severity of the deformity. It has been proposed as an alternative to surgery in less severe cases. Once the defect visually disappears, two additional years of use of the vacuum bell is required to make what may be a permanent correction. The treatment, in combination with physiotherapy exercises, has been judged by some as "a promising useful alternative" to surgery provided the thorax is flexible; the duration of treatment that is required has been found to be "directly linked to age, severity and the frequency of use". Long-term results are still lacking.A single-center study reported in the Journal of Pediatric Surgery found that use of vacuum bell therapy resulted in an excellent correction in twenty percent of patients, but "is not a substitute for the Nuss procedure which can achieve an excellent result in 90% of patients". Variables predictive of an excellent outcome include age ≤ 11 years, chest wall depth ≤ 1.5 cm, chest wall flexibility, and vacuum bell use over 12 consecutive months.In an article by Interactive Cardiovascular and Thoracic Surgery, the results found that vacuum bell treatment is safe for correcting the deformity non-surgically. The treatment has been shown to have higher success rates in patients who present earlier, have a mild and/or symmetrical deformity, a flexible chest wall and lack of costal flaring.The vacuum bell can also be used in preparation to surgery.
Orthoses
Brazilian orthopedist Sydney Haje developed a non-surgical protocol for treating pectus carinatum as well as pectus excavatum. The method involves wearing a compressive orthosis and adhering to an exercise protocol.Mild cases have also reportedly been treated with corset-like orthopedic support vests and exercise.
Thoracic surgery
There has been controversy as to the best surgical approach for correction of pectus excavatum. It is important for the surgeon to select the appropriate operative approach based on each individuals characteristics.
Surgical correction has been shown to repair any functional symptoms that may occur in the condition, such as respiratory problems or heart murmurs, provided that permanent damage has not already arisen from an extremely severe case. Surgical correction of the pectus excavatum has been shown to significantly improve cardiovascular function; there is inconclusive evidence so far as to whether it might also improve pulmonary function. One of the most popular techniques for repair of pectus excavatum today is the minimally invasive operation, also known as MIRPE or Nuss technique.
Magnetic mini-mover procedure
The magnetic mini-mover procedure (3MP) is a minimally invasive procedure used to correct pectus excavatum by using two magnets to realign the sternum with the rest of the chest and ribcage. One magnet is inserted 1 cm into the patients body on the lower end of the sternum, the other is placed externally onto a custom fitted brace. These two magnets generate around 0.04 tesla (T) in order to slowly move the sternum outwards over a number of years. The maximum magnetic field that can be applied to the body safely is around 4 T, making this technique safe from a magnetic viewpoint. The 3MP techniques main advantages are that it is more cost-effective than major surgical approaches such as the Nuss procedure and it is considerably less painful postoperatively.
Its effectiveness is limited to younger children in early- to mid-puberty because older individuals have less compliant (flexible) chest walls. One potential adverse interaction with other medical devices is possible inactivation of artificial pacemakers if present.
Ravitch technique
The Ravitch technique is an invasive surgery that was introduced in 1949 and developed in the 1950s. It involves creating an incision along the chest through which the cartilage is removed and the sternum detached. A small bar is inserted underneath the sternum to hold it up in the desired position. The bar is left implanted until the cartilage grows back, typically about six months. The bar is subsequently removed in a simple outpatient procedure; this technique is thus a two-stage procedure.The Ravitch technique is not widely practiced because it is so invasive. It is more often used in older individuals, where the sternum has calcified when the deformity is asymmetrical, or when the less invasive Nuss procedure has proven unsuccessful.
Nuss procedure
In 1987, Donald Nuss, based at Childrens Hospital of The Kings Daughters in Norfolk, Virginia, performed the first minimally invasive repair of pectus excavatum (MIRPE) and presented it much later at a conference in 1997.His procedure, widely known as the Nuss procedure, involves slipping in one or more concave steel bars into the chest, underneath the sternum. The bar is flipped to a convex position so as to push outward on the sternum, correcting the deformity. The bar usually stays in the body for about two years, although many surgeons are now moving toward leaving them in for up to five years. When the bones have solidified into place, the bar is removed through outpatient surgery. Although initially designed to be performed in younger children (less than 10 years of age) whose sternum and cartilage is more flexible, there are successful series of Nuss treatment in patients well into their teens and twenties.
The Nuss procedure is a two-stage procedure.
Robicsek technique
In 1965, Francis Robicsek, based at Charlotte Memorial Hospital, now named Carolinas Medical Center in Charlotte, North Carolina, developed the Robicsek procedure. Each time the procedure is performed, it is individually tailored based on the extent and location of the deformity in the patient. The operation begins with an incision, no more than 4–6 centimeters, to the sternum. The pectoralis major muscles are then detached from the sternum. Using the upper limit of the sternal depression as a guide, the deformed cartilages are removed one by one, using sharp and blunt dissection. The lower tip of the sternum is then grabbed with a towel-clip and, using blunt dissection, is freed of tissue connections with the pericardium and the pleura. The sternum is then forcefully bent forward into a corrected position. To keep the sternum elevated, a piece of mesh is placed under the mobilized sternum and sutured under moderate tension bilaterally to the stumps of the ribs. The pectoralis muscles are united in front of the sternum and the wound is closed. The Robicsek procedure is a single-stage procedure (one surgery only).The purported advantage of this technique is that it is less invasive than the Ravitch technique, but critics have suggested that the relapse rate may be high due to cartilage and bone displaying memory phenomenon.
Taulinoplasty
In 2016, Carlos Bardají, a Barcelona-based pediatric surgeon, together with Lluís Cassou, a biomedical engineer, published a paper describing an extra-thoracic surgical procedure for the correction of pectus excavatum called taulinoplasty. A specially designed implant and traction hardware were developed specifically for the procedure.
In taulinoplasty, a small hole is drilled into the sternum at the deepest point of defect, and a double screw is driven into the hole. Then, a stainless steel implant is placed underneath the skin on top of the sternum and ribs, centered over the double screw. Traction tools are then used to lift the sternum up by the double screw using the implant and ribs for traction. Additional screws are then used to secure the implant onto the sternum holding the sternum in the desired position. Optionally, stainless steel wire may be wrapped around the implant and ribs to further secure the implant in place.
Like the Nuss procedure, taulinoplasty requires follow-up surgery several years later to remove the implanted hardware once the sternum has permanently assumed its new position.
The implant and related hardware used in taulinoplasty is a proprietary product of Ventura Medical Technologies and is marketed as a surgical kit under the brand name Pectus UP.Taulinoplasty was developed to be an alternative to the Nuss procedure that eliminates the risks and drawbacks of entering the thorax. In particular, patients usually have shorter operating and recovery times, and less post-operative pain than with the Nuss procedure.
Plastic surgery
Implants
The implant allows pectus excavatum to be treated from a purely morphological perspective. Today it is used as a benchmark procedure as it is simple, reliable, and minimally intrusive while offering aesthetically pleasing results. This procedure does not, however, claim to correct existing cardiac and respiratory problems which, in very rare cases, can be triggered by the pectus excavatum condition. For female patients, the potential resulting breast asymmetry can be partially or completely corrected by this procedure.The process of creating a plaster-cast model, directly on the skin of the patients thorax, can be used in the design of the implants. The evolution of medical imaging and CAD (computer-aided design) now allows customised 3D implants to be designed directly from the ribcage, therefore being much more precise, easier to place sub-pectorally and perfectly adapted to the shape of each patient. The implants are made of medical silicon rubber which is age-resistant and unbreakable (different to the silicon gel used in breast implants). They will last for life (apart from the case of adverse reactions) and are not visible externally.
The surgery is performed under general anesthesia and takes about an hour. The surgeon makes an incision of approximately seven centimetres, prepares the customised space in the chest, inserts the implant deep beneath the muscle, then closes the incision. Post-operative hospitalization is typically around three days.The recovery after the surgery typically requires only mild pain relief. Post-operatively, a surgical dressing is required for several days and compression vest for a month following the procedure. A check-up appointment is carried out after a week for puncture of seroma. If the surgery has minimal complications, the patient can resume normal activities quickly, returning to work after 15 days and participating in any sporting activities after three months.
Lipofilling
The "lipofilling" technique consists of sucking fat from the patient using a syringe with a large gauge needle (usually from the abdomen or the outer thighs), then after centrifugation, the fat cells are re-injected beneath the skin into whichever hollow it is needed to fill. This technique is primarily used to correct small defects which may persist after conventional surgical treatment.
Epidemiology
Pectus excavatum occurs in an estimated 1 in 150 to 1 in 1000 births, with male predominance (male-to-female ratio of 3:1). In 35% to 45% of cases family members are affected.
Etymology
Pectus excavatum is from Latin meaning hollowed chest. It is sometimes referred to as sunken chest syndrome, cobblers chest or funnel chest.
Society
American Olympic swimmer Cody Miller (born 1992) opted not to have treatment for pectus excavatum, even though it limited his lung capacity. He earned a gold medal in 2016.
Actor Joel Kinnaman underwent surgery prior to the filming of Altered Carbon, inserting two metal bars to push the sternum outward in order to correct the deformity. English comedian and presenter Josh Widdicombe and YouTuber/streamer Ludwig Ahgren are known to have this condition. Zachary Woods is another popular American actor that has pectus excavatum, which is noticeable in his shirtless scene in an episode of The Office (Season 8, episode 12).
In animals
Pectus excavatum is also known to occur in animals, e.g. the Munchkin breed of cat. Some procedures used to treat the condition in animals have not been used in human treatments, such as the use of a cast with sutures wrapped around the sternum and the use of internal and external splints. These techniques are generally used in immature animals with flexible cartilage.
See also
Pectus carinatum
References
Further reading
Tocchioni F, Ghionzoli M, Messineo A, Romagnoli P (2013). "Pectus excavatum and heritable disorders of the connective tissue". Pediatric Reports (Review). 5 (3): e15. doi:10.4081/pr.2013.e15. PMC 3812532. PMID 24198927.
Jaroszewski D, Notrica D, McMahon L, Steidley DE, Deschamps C (2010). "Current management of pectus excavatum: a review and update of therapy and treatment recommendations". Journal of the American Board of Family Medicine (Review). 23 (2): 230–9. doi:10.3122/jabfm.2010.02.090234. PMID 20207934.
www.ctds.info Archived 2019-03-27 at the Wayback Machine
External links
Pectus excavatum at Curlie |
Childhood disintegrative disorder | Childhood disintegrative disorder (CDD), also known as Hellers syndrome and disintegrative psychosis, is a rare condition characterized by late onset of developmental delays—or severe and sudden reversals—in language, social function, and motor skills. Researchers have not been successful in finding a cause for the disorder. CDD has some similarity to autism and is sometimes considered a low-functioning form of it. In May 2013, CDD, along with other sub-types of PDD (Aspergers syndrome, autism, and PDD-NOS), was fused into a single diagnostic term called "autism spectrum disorder" under the new DSM-5 manual.CDD was originally described by Austrian educator Theodor Heller (1869–1938) in 1908, 35 years before Leo Kanner and Hans Asperger described autism. Heller had previously used the name dementia infantilis for the syndrome.An apparent period of fairly normal development is often noted before a regression in skills or a series of regressions in skills. The age at which this regression can occur varies, after three years of normal development is typical. The regression, known as a ‘prodrome,’ can be so dramatic that the child may be aware of it, and may in its beginning even ask, vocally, what is happening to them. Some children describe or appear to be reacting to hallucinations, but the most obvious symptom is that skills apparently attained are lost.Many children are already somewhat delayed when the disorder becomes apparent, but these delays are not always obvious in young children. This has been described by many writers as a devastating condition, affecting both the family and the individuals future. As is the case with all pervasive developmental disorder categories, there is considerable controversy about the right treatment for CDD.
Signs and symptoms
CDD is a rare condition, with only 1.7 cases per 100,000.A child affected with childhood disintegrative disorder shows normal development. Up until this point, the child has developed normally in the areas of language skills, social skills, comprehension skills, and has maintained those skills for about two years. However, between the ages of two and 10, skills acquired are lost almost completely in at least two of the following six functional areas:
Expressive language skills (being able to produce speech and communicate a message)
Receptive language skills (comprehension of language – listening and understanding what is communicated)
Social skills and self care skills
Control over bowel and bladder
Play skills
Motor skillsLack of normal function or impairment also occurs in at least two of the following three areas:
Social interaction
Communication
Repetitive behavior and interest patternsIn her book, Thinking in Pictures, Temple Grandin argues that compared to "Kanners classic autism" and to Asperger syndrome, CDD is characterized with more severe sensory processing disorder but less severe cognitive problems. She also argues that compared to most autistic individuals, persons with CDD have more severe speech pathology and they usually do not respond well to stimulants.
Causes
All of the causes of childhood disintegrative disorder are still unknown. Sometimes CDD surfaces abruptly within days or weeks, while in other cases it develops over a longer period of time. A Mayo Clinic report indicates: "Comprehensive medical and neurological examinations in children diagnosed with childhood disintegrative disorder seldom uncover an underlying medical or neurological cause. Although the occurrence of epilepsy is higher in children with childhood disintegrative disorder, experts dont know whether epilepsy plays a role in causing the disorder."CDD, especially in cases of later age of onset, has also been associated with certain other conditions, particularly the following:
Lipid storage diseases: In this condition, a toxic buildup of excess fats (lipids) takes place in the brain and nervous system.
Subacute sclerosing panencephalitis: Chronic infection of the brain by a form of the measles virus causes subacute sclerosing panencephalitis. This condition leads to brain inflammation and the death of nerve cells.
Tuberous sclerosis (TSC): TSC is a genetic disorder. In this disorder, tumors may grow in the brain and other vital organs like kidneys, heart, eyes, lungs, and skin. In this condition, noncancerous (benign) tumors, hamartomas, grow in the brain.
Leukodystrophy: In this condition, the myelin sheath does not develop in a normal way, causing white matter in the brain to eventually fail and disintegrate.
Treatment
Loss of language and skills related to social interaction and self-care are serious. The affected children face ongoing disabilities in certain areas and require long-term care. Treatment of CDD involves both behavior therapy, environmental therapy and medications.
Behavior therapy: Applied Behavior Analysis (ABA) is considered to be the most effective form of treatment for Autism spectrum disorders by the American Academy of Pediatrics. The primary goal of ABA is to improve quality of life, and independence by teaching adaptive behaviors to children with autism, and to diminish problematic behaviors like running away from home, or self-injury by using positive or negative reinforcement to encourage or discourage behaviors over time.
Environmental Therapy: Sensory Enrichment Therapy uses enrichment of the sensory experience to improve symptoms in autism, many of which are common to CDD.
Medications: There are no medications available to directly treat CDD. Antipsychotic medications are used to treat severe behavior problems like aggressive stance and repetitive behavior patterns. Anticonvulsant medications are used to control seizures.
References
Further reading
Maurice, Catherine (1993). Let me hear your voice: a familys triumph over autism. New York: Knopf. ISBN 978-0-679-40863-5. OCLC 26633221.
Westphal A, Schelinski S, Volkmar F, Pelphrey K (February 2013). "Revisiting regression in autism: Hellers dementia infantilis. Includes a translation of Über Dementia Infantilis". J Autism Dev Disord. 43 (2): 265–71. doi:10.1007/s10803-012-1559-z. PMID 22677931. S2CID 3924122.
Dobbs, David (2016). "The most terrifying childhood condition youve never heard of." Spectrum 6 July 2016, accessed 6 May 2017 at en:Childhood_disintegrative_disorder?action=edit, oldid 778841596&wteswitched=1
External links
NIH/Medline |
Bubonic plague | Bubonic plague is one of three types of plague caused by the plague bacterium (Yersinia pestis). One to seven days after exposure to the bacteria, flu-like symptoms develop. These symptoms include fever, headaches, and vomiting, as well as swollen and painful lymph nodes occurring in the area closest to where the bacteria entered the skin. Acral necrosis, the dark discoloration of skin, is another symptom. Occasionally, swollen lymph nodes, known as "buboes," may break open.The three types of plague are the result of the route of infection: bubonic plague, septicemic plague, and pneumonic plague. Bubonic plague is mainly spread by infected fleas from small animals. It may also result from exposure to the body fluids from a dead plague-infected animal. Mammals such as rabbits, hares, and some cat species are susceptible to bubonic plague, and typically die upon contraction. In the bubonic form of plague, the bacteria enter through the skin through a flea bite and travel via the lymphatic vessels to a lymph node, causing it to swell. Diagnosis is made by finding the bacteria in the blood, sputum, or fluid from lymph nodes.Prevention is through public health measures such as not handling dead animals in areas where plague is common. While vaccines against the plague have been developed, the World Health Organization recommends that only high-risk groups, such as certain laboratory personnel and health care workers, get inoculated. Several antibiotics are effective for treatment, including streptomycin, gentamicin, and doxycycline.Without treatment, plague results in the death of 30% to 90% of those infected. Death, if it occurs, is typically within 10 days. With treatment, the risk of death is around 10%. Globally between 2010 and 2015 there were 3,248 documented cases, which resulted in 584 deaths. The countries with the greatest number of cases are the Democratic Republic of the Congo, Madagascar, and Peru.The plague is considered the likely cause of the Black Death that swept through Asia, Europe, and Africa in the 14th century and killed an estimated 50 million people, including about 25% to 60% of the European population. Because the plague killed so many of the working population, wages rose due to the demand for labor. Some historians see this as a turning point in European economic development. The disease is also considered to have been responsible for the Plague of Justinian, originating in the Eastern Roman Empire in the 6th century CE, as well as the third epidemic, affecting China, Mongolia, and India, originating in the Yunnan Province in 1855. The term bubonic is derived from the Greek word βουβών, meaning "groin".
Cause
Bubonic plague is an infection of the lymphatic system, usually resulting from the bite of an infected flea, Xenopsylla cheopis (the Oriental rat flea). Several flea species carried the bubonic plague, such as Pulex irritans (the human flea), Xenopsylla cheopis, and Ceratophyllus fasciatus. Xenopsylla cheopis was the most effective flea species for transmittal. In very rare circumstances, as in septicemic plague, the disease can be transmitted by direct contact with infected tissue or exposure to the cough of another human. The flea is parasitic on house and field rats and seeks out other prey when its rodent hosts die. Rats were an amplifying factor to bubonic plague due to their common association with humans as well as the nature of their blood. The rats blood allowed the rat to withstand a major concentration of the plague. The bacteria form aggregates in the gut of infected fleas and this results in the flea regurgitating ingested blood, which is now infected, into the bite site of a rodent or human host. Once established, bacteria rapidly spread to the lymph nodes and multiply. The fleas that transmit the disease only directly infect humans when the rat population in the area is wiped out from a mass infection. Furthermore, in areas of a large population of rats, the animals can harbor low levels of the plague infection without causing human outbreaks. With no new rat inputs being added to the population from other areas, the infection would only spread to humans in very rare cases of overcrowding.
Signs and symptoms
After being transmitted via the bite of an infected flea, the Y. pestis bacteria become localized in an inflamed lymph node, where they begin to colonize and reproduce. Infected lymph nodes develop hemorrhages, which result in the death of tissue.Y. pestis bacilli can resist phagocytosis and even reproduce inside phagocytes and kill them. As the disease progresses, the lymph nodes can hemorrhage and become swollen and necrotic. Bubonic plague can progress to lethal septicemic plague in some cases. The plague is also known to spread to the lungs and become the disease known as the pneumonic plague. Symptoms appear 2–7 days after getting bitten and they include:
Chills
General ill feeling (malaise)
High fever >39 °C (102.2 °F)
Muscle cramps
Seizures
Smooth, painful lymph gland swelling called a bubo, commonly found in the groin, but may occur in the armpits or neck, most often near the site of the initial infection (bite or scratch)
Pain may occur in the area before the swelling appears
Gangrene of the extremities such as toes, fingers, lips, and tip of the nose.The best-known symptom of bubonic plague is one or more infected, enlarged, and painful lymph nodes, known as buboes. Buboes associated with the bubonic plague are commonly found in the armpits, upper femoral, groin, and neck region. Symptoms include heavy breathing, continuous vomiting of blood (hematemesis), aching limbs, coughing, and extreme pain caused by the decay or decomposition of the skin while the person is still alive. Additional symptoms include extreme fatigue, gastrointestinal problems, spleen inflammation, lenticulae (black dots scattered throughout the body), delirium, coma, organ failure, and death. Organ failure is a result of the bacteria infecting organs through the bloodstream. Other forms of the disease include septicemic plague and pneumonic plague in which the bacterium reproduces in the persons blood and lungs respectively.
Diagnosis
Laboratory testing is required in order to diagnose and confirm plague. Ideally, confirmation is through the identification of Y. pestis culture from a patient sample. Confirmation of infection can be done by examining serum taken during the early and late stages of infection. To quickly screen for the Y. pestis antigen in patients, rapid dipstick tests have been developed for field use. Samples taken for testing include:Buboes: Swollen lymph nodes (buboes) characteristic of bubonic plague, a fluid sample can be taken from them with a needle.
Blood
Lungs
Prevention
Bubonic plague outbreaks are controlled by pest control and modern sanitation techniques. This disease uses fleas commonly found on rats as a vector to jump from animals to humans. The mortality rate hits its peak during the hot and humid months of June, July, and August. Furthermore, the plague most affected those of poor upbringing due to greater exposure, poor sanitation techniques and lack of a healthy immune system due to a poor diet. The successful control of rat populations in dense urban areas is essential to outbreak prevention. One example is the use of a machine called the Sulfurozador, used to deliver sulphur dioxide to eradicate the pest that spread the bubonic plague, in Buenos Aires, Argentina during the early 18th century. Targeted chemoprophylaxis, sanitation, and vector control also played a role in controlling the 2003 Oran outbreak of the bubonic plague. Another means of prevention in large European cities was a city-wide quarantine to not only limit interaction with people who were infected, but also to limit the interaction with the infected rats.
Treatment
Several classes of antibiotics are effective in treating bubonic plague. These include aminoglycosides such as streptomycin and gentamicin, tetracyclines (especially doxycycline), and the fluoroquinolone ciprofloxacin. Mortality associated with treated cases of bubonic plague is about 1–15%, compared to a mortality of 40–60% in untreated cases.People potentially infected with the plague need immediate treatment and should be given antibiotics within 24 hours of the first symptoms to prevent death. Other treatments include oxygen, intravenous fluids, and respiratory support. People who have had contact with anyone infected by pneumonic plague are given prophylactic antibiotics. Using the broad-based antibiotic streptomycin has proven to be dramatically successful against the bubonic plague within 12 hours of infection.
Epidemiology
Globally between 2010 and 2015, there were 3,248 documented cases, which resulted in 584 deaths. The countries with the greatest number of cases are the Democratic Republic of the Congo, Madagascar, and Peru.For over a decade since 2001, Zambia, India, Malawi, Algeria, China, Peru, and the Democratic Republic of the Congo had the most plague cases with over 1,100 cases in the Democratic Republic of the Congo alone. From 1,000 to 2,000 cases are conservatively reported per year to the WHO. From 2012 to 2017, reflecting political unrest and poor hygienic conditions, Madagascar began to host regular epidemics.Between 1900 and 2015, the United States had 1,036 human plague cases with an average of 9 cases per year. In 2015, 16 people in the Western United States developed plague, including 2 cases in Yosemite National Park. These US cases usually occur in rural northern New Mexico, northern Arizona, southern Colorado, California, southern Oregon, and far western Nevada.In November 2017, the Madagascar Ministry of Health reported an outbreak to the WHO (World Health Organization) with more cases and deaths than any recent outbreak in the country. Unusually, most of the cases were pneumonic rather than bubonic.In June 2018, a child was confirmed to be the first person in Idaho to be infected by bubonic plague in nearly 30 years.A couple died in May 2019, in Mongolia, while hunting marmots. Another two people in the province of Inner Mongolia, China were treated in November 2019 for the disease.
In July 2020, in Bayannur, Inner Mongolia of China, a human case of bubonic plague was reported. Officials responded by activating a city-wide plague-prevention system for the remainder of the year. Also in July 2020, in Mongolia, a teenager died from bubonic plague after consuming infected marmot meat.
History
Yersinia pestis has been discovered in archaeological finds from the Late Bronze Age (~3800 BP). The bacteria is identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago.
First pandemic
The first recorded epidemic affected the Sasanian Empire and their arch-rivals, the Eastern Roman Empire (Byzantine Empire) and was named the Plague of Justinian after emperor Justinian I, who was infected but survived through extensive treatment. The pandemic resulted in the deaths of an estimated 25 million (6th century outbreak) to 50 million people (two centuries of recurrence). The historian Procopius wrote, in Volume II of History of the Wars, of his personal encounter with the plague and the effect it had on the rising empire. In the spring of 542, the plague arrived in Constantinople, working its way from port city to port city and spreading around the Mediterranean Sea, later migrating inland eastward into Asia Minor and west into Greece and Italy. The Plague of Justinian is said to have been "completed" in the middle of the 8th century. Because the infectious disease spread inland by the transferring of merchandise through Justinians efforts in acquiring luxurious goods of the time and exporting supplies, his capital became the leading exporter of the bubonic plague. Procopius, in his work Secret History, declared that Justinian was a demon of an emperor who either created the plague himself or was being punished for his sinfulness.
Second pandemic
In the Late Middle Ages Europe experienced the deadliest disease outbreak in history when the Black Death, the infamous pandemic of bubonic plague, hit in 1347, killing one-third of the European human population. Some historians believe that society subsequently became more violent as the mass mortality rate cheapened life and thus increased warfare, crime, popular revolt, waves of flagellants, and persecution. The Black Death originated in Central Asia and spread from Italy and then throughout other European countries. Arab historians Ibn Al-Wardni and Almaqrizi believed the Black Death originated in Mongolia. Chinese records also showed a huge outbreak in Mongolia in the early 1330s.In 2022, researchers presented evidence that the plague originated near Lake Issyk-Kul in Kyrgyzstan. The Mongols had cut the trade route (the Silk Road) between China and Europe, which halted the spread of the Black Death from eastern Russia to Western Europe. The European epidemic began with an attack that Mongols launched on the Italian merchants last trading station in the region, Caffa in the Crimea.In late 1346, plague broke out among the besiegers and from them penetrated the town. The Mongol forces catapulted plague-infested corpses into Caffa as a form of attack, one of the first known instances of biological warfare. When spring arrived, the Italian merchants fled on their ships, unknowingly carrying the Black Death. Carried by the fleas on rats, the plague initially spread to humans near the Black Sea and then outwards to the rest of Europe as a result of people fleeing from one area to another. Rats migrated with humans, traveling among grain bags, clothing, ships, wagons, and grain husks. Continued research indicates that black rats, those that primarily transmitted the disease, prefer grain as a primary meal. Due to this, the major bulk grain fleets that transported major citys food shipments from Africa and Alexandria to heavily populated areas, and were then unloaded by hand, played a role in increasing the transmission effectiveness of the plague.
Third pandemic
The plague resurfaced for a third time in the mid-19th century; this is also known as "the modern pandemic". Like the two previous outbreaks, this one also originated in Eastern Asia, most likely in Yunnan, a province of China, where there are several natural plague foci. The initial outbreaks occurred in the second half of the 18th century. The disease remained localized in Southwest China for several years before spreading. In the city of Canton, beginning in January 1894, the disease had killed 80,000 people by June. Daily water-traffic with the nearby city of Hong Kong rapidly spread the plague there, killing over 2,400 within two months during the 1894 Hong Kong plague.The third pandemic spread the disease to port cities throughout the world in the second half of the 19th century and the early 20th century via shipping routes. The plague infected people in Chinatown in San Francisco from 1900 to 1904, and in the nearby locales of Oakland and the East Bay again from 1907 to 1909. During the former outbreak, in 1902, authorities made permanent the Chinese Exclusion Act, a law originally signed into existence by President Chester A. Arthur in 1882. The Act was supposed to last for 10 years, but was renewed in 1892 with the Geary Act, then followed by the 1902 decision. The last major outbreak in the United States occurred in Los Angeles in 1924, though the disease is still present in wild rodents and can be passed to humans that come in contact with them. According to the World Health Organization, the pandemic was considered active until 1959, when worldwide casualties dropped to 200 per year. In 1994, a plague outbreak in five Indian states caused an estimated 700 infections (including 52 deaths) and triggered a large migration of Indians within India as they tried to avoid the disease.It was during the 1894 Hong Kong plague outbreak that Alexandre Yersin isolated the bacterium responsible (Yersinia pestis), a few days after Japanese bacteriologist Kitasato Shibasaburō had isolated it. However, the latters description was imprecise and also expressed doubts of its relation to the disease, and thus the bacterium is today only named after Yersin.
Society and culture
The scale of death and social upheaval associated with plague outbreaks has made the topic prominent in many historical and fictional accounts since the disease was first recognized. The Black Death in particular is described and referenced in numerous contemporary sources, some of which, including works by Chaucer, Boccaccio, and Petrarch, are considered part of the Western canon. The Decameron, by Boccaccio, is notable for its use of a frame story involving individuals who have fled Florence for a secluded villa to escape the Black Death. First-person, sometimes sensationalized or fictionalized, accounts of living through plague years have also been popular across centuries and cultures. For example, Samuel Pepyss diary makes several references to his first-hand experiences of the Great Plague of London in 1665–6.Later works, such as Albert Camuss novel The Plague or Ingmar Bergmans film The Seventh Seal have used bubonic plague in settings, such as quarantined cities in either medieval or modern times, as a backdrop to explore a variety of concepts. Common themes include the breakdown of society, institutions, and individuals during the plague, the cultural and psychological existential confrontation with mortality, and the allegorical use of the plague about contemporary moral or spiritual questions.
Biological warfare
Some of the earliest instances of biological warfare were said to have been products of the plague, as armies of the 14th century were recorded catapulting diseased corpses over the walls of towns and villages to spread the pestilence. This was done by Jani Beg when he attacked the city of Kaffa in 1343.Later, plague was used during the Second Sino-Japanese War as a bacteriological weapon by the Imperial Japanese Army. These weapons were provided by Shirō Ishiis units and used in experiments on humans before being used on the field. For example, in 1940, the Imperial Japanese Army Air Service bombed Ningbo with fleas carrying the bubonic plague. During the Khabarovsk War Crime Trials, the accused, such as Major General Kiyoshi Kawashima, testified that, in 1941, 40 members of Unit 731 air-dropped plague-contaminated fleas on Changde. These operations caused epidemic plague outbreaks.
Continued research
Substantial research has been done regarding the origin of the plague and how it traveled through the continent. Mitochondrial DNA of modern rats in Western Europe indicated that these rats came from two different areas, one being Africa and the other being unclear of a specific origin. The research regarding this pandemic has greatly increased with technology. Through archaeo-molecular investigation, researchers have discovered the DNA of plague bacillus in the dental core of those that fell ill to the plague. Analysis of teeth of the deceased allows researchers to further understand both the demographics and mortuary patterns of the disease. For example, in 2013 in England, archeologists uncovered a burial mound to reveal 17 bodies, mainly children, who had died of the Bubonic plague. They analyzed these burial remains using radiocarbon dating to determine they were from the 1530s, and dental core analysis revealed the presence of Yersinia pestis.Other evidence for rats that are currently still being researched consists of gnaw marks on bones, predator pellets and rat remains that were preserved in situ. This research allows individuals to trace early rat remains to track the path traveled and in turn connect the impact of the Bubonic Plague to specific breeds of rats. Burial sites, known as plague pits, offer archaeologists an opportunity to study the remains of people who died from the plague.Another research study indicates that these separate pandemics were all interconnected. A current computer model indicates that the disease did not go away in between these pandemics. It rather lurked within the rat population for years without causing human epidemics.
See also
List of cutaneous conditions
List of epidemics
Miasma theory
Plague (disease)
Plague doctor
References
Further reading
== External links == |
Diffuse unilateral subacute neuroretinitis | Diffuse unilateral subacute neuroretinitis (DUSN) is a rare condition that occurs in otherwise healthy, often young patients and is due to the presence of a subretinal nematode.
Signs and symptoms
The clinical findings in this disease can be divided into acute and end-stage manifestations:
In the acute phase, patients often present with decreased visual acuity, vitritis, papillitis, and crops of gray-white or yellow-white outer retinal lesions. The clustering of the retinal lesions is important because this often helps to localize the causative nematode.
If left untreated, patients ultimately develop late sequel, which may include optic atrophy, retinal arterial narrowing, diffuse retinal pigment epithelial changes, and an abnormal electroretinogram. The late findings of this condition are often misinterpreted as unilateral retinitis pigmentosa.
Cause
DUSN may be caused by a helminthic infection with Toxocara canis, Baylisascaris procyonis, or Ancylostoma caninum. The characteristic lesions are believed to result from a single nematode migrating within the subretinal space. Although previously thought to be endemic in some areas, that belief was likely due to under awareness. DUSN has been diagnosed in patients in many countries and climates including America, Brazil, China and India.
Diagnosis
Treatment
If the nematode can be seen by an ophthalmologist, which occurs in less than half of cases, it should be treated with photocoagulation for extramacular location and surgical removal in case the larva is lying in the macula. After the worm is killed, visual acuity loss usually does not progress. Alternatively, Antihelminthic treatment such as high dose oral Albendazole and prednisolone may be used.
References
== External links == |
Infection | An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable disease, is an illness resulting from an infection.
Infections can be caused by a wide range of pathogens, most prominently bacteria and viruses. Hosts can fight infections using their immune system. Mammalian hosts react to infections with an innate response, often involving inflammation, followed by an adaptive response.
Specific medications used to treat infections include antibiotics, antivirals, antifungals, antiprotozoals, and antihelminthics. Infectious diseases resulted in 9.2 million deaths in 2013 (about 17% of all deaths). The branch of medicine that focuses on infections is referred to as infectious disease.
Types
Infections are caused by infectious agents (pathogens) including:
Bacteria (e.g. Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli, Clostridium botulinum, and Salmonella spp.)
Viruses and related agents such as viroids. (E.g. HIV, Rhinovirus, Lyssaviruses such as Rabies virus, Ebolavirus and Severe acute respiratory syndrome coronavirus 2)
Fungi, further subclassified into:
Ascomycota, including yeasts such as Candida (the most common fungal infection); filamentous fungi such as Aspergillus; Pneumocystis species; and dermatophytes, a group of organisms causing infection of skin and other superficial structures in humans.
Basidiomycota, including the human-pathogenic genus Cryptococcus.
Parasites, which are usually divided into:Unicellular organisms (e.g. malaria, Toxoplasma, Babesia)
Macroparasites (worms or helminths) including nematodes such as parasitic roundworms and pinworms, tapeworms (cestodes), and flukes (trematodes, such as schistosomes). Diseases caused by helminths are sometimes termed infestations, but are sometimes called infections.
Arthropods such as ticks, mites, fleas, and lice, can also cause human disease, which conceptually are similar to infections, but invasion of a human or animal body by these macroparasites is usually termed infestation.
Prions (although they do not secrete toxins)
Signs and symptoms
The signs and symptoms of an infection depend on the type of disease. Some signs of infection affect the whole body generally, such as fatigue, loss of appetite, weight loss, fevers, night sweats, chills, aches and pains. Others are specific to individual body parts, such as skin rashes, coughing, or a runny nose.In certain cases, infectious diseases may be asymptomatic for much or even all of their course in a given host. In the latter case, the disease may only be defined as a "disease" (which by definition means an illness) in hosts who secondarily become ill after contact with an asymptomatic carrier. An infection is not synonymous with an infectious disease, as some infections do not cause illness in a host.
Bacterial or viral
As bacterial and viral infections can both cause the same kinds of symptoms, it can be difficult to distinguish which is the cause of a specific infection. Distinguishing the two is important, since viral infections cannot be cured by antibiotics whereas bacterial infections can.
Pathophysiology
There is a general chain of events that applies to infections, sometimes called the chain of infection. The chain of events involves several steps – which include the infectious agent, reservoir, entering a susceptible host, exit and transmission to new hosts. Each of the links must be present in a chronological order for an infection to develop. Understanding these steps helps health care workers target the infection and prevent it from occurring in the first place.
Colonization
Infection begins when an organism successfully enters the body, grows and multiplies. This is referred to as colonization. Most humans are not easily infected. Those with compromised or weakened immune systems have an increased susceptibility to chronic or persistent infections. Individuals who have a suppressed immune system are particularly susceptible to opportunistic infections. Entrance to the host at host-pathogen interface, generally occurs through the mucosa in orifices like the oral cavity, nose, eyes, genitalia, anus, or the microbe can enter through open wounds. While a few organisms can grow at the initial site of entry, many migrate and cause systemic infection in different organs. Some pathogens grow within the host cells (intracellular) whereas others grow freely in bodily fluids.Wound colonization refers to non-replicating microorganisms within the wound, while in infected wounds, replicating organisms exist and tissue is injured. All multicellular organisms are colonized to some degree by extrinsic organisms, and the vast majority of these exist in either a mutualistic or commensal relationship with the host. An example of the former is the anaerobic bacteria species, which colonizes the mammalian colon, and an example of the latter are the various species of staphylococcus that exist on human skin. Neither of these colonizations are considered infections. The difference between an infection and a colonization is often only a matter of circumstance. Non-pathogenic organisms can become pathogenic given specific conditions, and even the most virulent organism requires certain circumstances to cause a compromising infection. Some colonizing bacteria, such as Corynebacteria sp. and viridans streptococci, prevent the adhesion and colonization of pathogenic bacteria and thus have a symbiotic relationship with the host, preventing infection and speeding wound healing.
The variables involved in the outcome of a host becoming inoculated by a pathogen and the ultimate outcome include:
the route of entry of the pathogen and the access to host regions that it gains
the intrinsic virulence of the particular organism
the quantity or load of the initial inoculant
the immune status of the host being colonizedAs an example, several staphylococcal species remain harmless on the skin, but, when present in a normally sterile space, such as in the capsule of a joint or the peritoneum, multiply without resistance and cause harm.An interesting fact that gas chromatography–mass spectrometry, 16S ribosomal RNA analysis, omics, and other advanced technologies have made more apparent to humans in recent decades is that microbial colonization is very common even in environments that humans think of as being nearly sterile. Because it is normal to have bacterial colonization, it is difficult to know which chronic wounds can be classified as infected and how much risk of progression exists. Despite the huge number of wounds seen in clinical practice, there are limited quality data for evaluated symptoms and signs. A review of chronic wounds in the Journal of the American Medical Associations "Rational Clinical Examination Series" quantified the importance of increased pain as an indicator of infection. The review showed that the most useful finding is an increase in the level of pain [likelihood ratio (LR) range, 11–20] makes infection much more likely, but the absence of pain (negative likelihood ratio range, 0.64–0.88) does not rule out infection (summary LR 0.64–0.88).
Disease
Disease can arise if the hosts protective immune mechanisms are compromised and the organism inflicts damage on the host. Microorganisms can cause tissue damage by releasing a variety of toxins or destructive enzymes. For example, Clostridium tetani releases a toxin that paralyzes muscles, and staphylococcus releases toxins that produce shock and sepsis. Not all infectious agents cause disease in all hosts. For example, less than 5% of individuals infected with polio develop disease. On the other hand, some infectious agents are highly virulent. The prion causing mad cow disease and Creutzfeldt–Jakob disease invariably kills all animals and people that are infected.Persistent infections occur because the body is unable to clear the organism after the initial infection. Persistent infections are characterized by the continual presence of the infectious organism, often as latent infection with occasional recurrent relapses of active infection. There are some viruses that can maintain a persistent infection by infecting different cells of the body. Some viruses once acquired never leave the body. A typical example is the herpes virus, which tends to hide in nerves and become reactivated when specific circumstances arise.Persistent infections cause millions of deaths globally each year. Chronic infections by parasites account for a high morbidity and mortality in many underdeveloped countries.
Transmission
For infecting organisms to survive and repeat the infection cycle in other hosts, they (or their progeny) must leave an existing reservoir and cause infection elsewhere. Infection transmission can take place via many potential routes:Droplet contact, also known as the respiratory route, and the resultant infection can be termed airborne disease. If an infected person coughs or sneezes on another person the microorganisms, suspended in warm, moist droplets, may enter the body through the nose, mouth or eye surfaces.
Fecal-oral transmission, wherein foodstuffs or water become contaminated (by people not washing their hands before preparing food, or untreated sewage being released into a drinking water supply) and the people who eat and drink them become infected. Common fecal-oral transmitted pathogens include Vibrio cholerae, Giardia species, rotaviruses, Entameba histolytica, Escherichia coli, and tape worms. Most of these pathogens cause gastroenteritis.
Sexual transmission, with the resulting disease being called sexually transmitted disease
Oral transmission, diseases that are transmitted primarily by oral means may be caught through direct oral contact such as kissing, or by indirect contact such as by sharing a drinking glass or a cigarette.
Transmission by direct contact, Some diseases that are transmissible by direct contact include athletes foot, impetigo and warts.
Vehicle transmission, transmission by an inanimate reservoir (food, water, soil)
Vertical transmission, directly from the mother to an embryo, fetus or baby during pregnancy or childbirth. It can occur as a result of a pre-existing infection or one acquired during pregnancy.
Iatrogenic transmission, due to medical procedures such as injection or transplantation of infected material.
Vector-borne transmission, transmitted by a vector, which is an organism that does not cause disease itself but that transmits infection by conveying pathogens from one host to another.The relationship between virulence versus transmissibility is complex; with studies have shown that there were no clear relationship between the two. There is still a small number of evidence that partially suggests a link between virulence and transmissibility.
Diagnosis
Diagnosis of infectious disease sometimes involves identifying an infectious agent either directly or indirectly. In practice most minor infectious diseases such as warts, cutaneous abscesses, respiratory system infections and diarrheal diseases are diagnosed by their clinical presentation and treated without knowledge of the specific causative agent. Conclusions about the cause of the disease are based upon the likelihood that a patient came in contact with a particular agent, the presence of a microbe in a community, and other epidemiological considerations. Given sufficient effort, all known infectious agents can be specifically identified. The benefits of identification, however, are often greatly outweighed by the cost, as often there is no specific treatment, the cause is obvious, or the outcome of an infection is benign.
Diagnosis of infectious disease is nearly always initiated by medical history and physical examination. More detailed identification techniques involve the culture of infectious agents isolated from a patient. Culture allows identification of infectious organisms by examining their microscopic features, by detecting the presence of substances produced by pathogens, and by directly identifying an organism by its genotype. Other techniques (such as X-rays, CAT scans, PET scans or NMR) are used to produce images of internal abnormalities resulting from the growth of an infectious agent. The images are useful in detection of, for example, a bone abscess or a spongiform encephalopathy produced by a prion.
Symptomatic diagnostics
The diagnosis is aided by the presenting symptoms in any individual with an infectious disease, yet it usually needs additional diagnostic techniques to confirm the suspicion. Some signs are specifically characteristic and indicative of a disease and are called pathognomonic signs; but these are rare. Not all infections are symptomatic.In children the presence of cyanosis, rapid breathing, poor peripheral perfusion, or a petechial rash increases the risk of a serious infection by greater than 5 fold. Other important indicators include parental concern, clinical instinct, and temperature greater than 40 °C.
Microbial culture
Many diagnostic approaches depend on microbiological culture to isolate a pathogen from the appropriate clinical specimen. In a microbial culture, a growth medium is provided for a specific agent. A sample taken from potentially diseased tissue or fluid is then tested for the presence of an infectious agent able to grow within that medium. Many pathogenic bacteria are easily grown on nutrient agar, a form of solid medium that supplies carbohydrates and proteins necessary for growth, along with copious amounts of water. A single bacterium will grow into a visible mound on the surface of the plate called a colony, which may be separated from other colonies or melded together into a "lawn". The size, color, shape and form of a colony is characteristic of the bacterial species, its specific genetic makeup (its strain), and the environment that supports its growth. Other ingredients are often added to the plate to aid in identification. Plates may contain substances that permit the growth of some bacteria and not others, or that change color in response to certain bacteria and not others. Bacteriological plates such as these are commonly used in the clinical identification of infectious bacterium. Microbial culture may also be used in the identification of viruses: the medium, in this case, being cells grown in culture that the virus can infect, and then alter or kill. In the case of viral identification, a region of dead cells results from viral growth, and is called a "plaque". Eukaryotic parasites may also be grown in culture as a means of identifying a particular agent.In the absence of suitable plate culture techniques, some microbes require culture within live animals. Bacteria such as Mycobacterium leprae and Treponema pallidum can be grown in animals, although serological and microscopic techniques make the use of live animals unnecessary. Viruses are also usually identified using alternatives to growth in culture or animals. Some viruses may be grown in embryonated eggs. Another useful identification method is Xenodiagnosis, or the use of a vector to support the growth of an infectious agent. Chagas disease is the most significant example, because it is difficult to directly demonstrate the presence of the causative agent, Trypanosoma cruzi in a patient, which therefore makes it difficult to definitively make a diagnosis. In this case, xenodiagnosis involves the use of the vector of the Chagas agent T. cruzi, an uninfected triatomine bug, which takes a blood meal from a person suspected of having been infected. The bug is later inspected for growth of T. cruzi within its gut.
Microscopy
Another principal tool in the diagnosis of infectious disease is microscopy. Virtually all of the culture techniques discussed above rely, at some point, on microscopic examination for definitive identification of the infectious agent. Microscopy may be carried out with simple instruments, such as the compound light microscope, or with instruments as complex as an electron microscope. Samples obtained from patients may be viewed directly under the light microscope, and can often rapidly lead to identification. Microscopy is often also used in conjunction with biochemical staining techniques, and can be made exquisitely specific when used in combination with antibody based techniques. For example, the use of antibodies made artificially fluorescent (fluorescently labeled antibodies) can be directed to bind to and identify a specific antigens present on a pathogen. A fluorescence microscope is then used to detect fluorescently labeled antibodies bound to internalized antigens within clinical samples or cultured cells. This technique is especially useful in the diagnosis of viral diseases, where the light microscope is incapable of identifying a virus directly.Other microscopic procedures may also aid in identifying infectious agents. Almost all cells readily stain with a number of basic dyes due to the electrostatic attraction between negatively charged cellular molecules and the positive charge on the dye. A cell is normally transparent under a microscope, and using a stain increases the contrast of a cell with its background. Staining a cell with a dye such as Giemsa stain or crystal violet allows a microscopist to describe its size, shape, internal and external components and its associations with other cells. The response of bacteria to different staining procedures is used in the taxonomic classification of microbes as well. Two methods, the Gram stain and the acid-fast stain, are the standard approaches used to classify bacteria and to diagnosis of disease. The Gram stain identifies the bacterial groups Bacillota and Actinomycetota, both of which contain many significant human pathogens. The acid-fast staining procedure identifies the Actinomycetota genera Mycobacterium and Nocardia.
Biochemical tests
Biochemical tests used in the identification of infectious agents include the detection of metabolic or enzymatic products characteristic of a particular infectious agent. Since bacteria ferment carbohydrates in patterns characteristic of their genus and species, the detection of fermentation products is commonly used in bacterial identification. Acids, alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media.The isolation of enzymes from infected tissue can also provide the basis of a biochemical diagnosis of an infectious disease. For example, humans can make neither RNA replicases nor reverse transcriptase, and the presence of these enzymes are characteristic., of specific types of viral infections. The ability of the viral protein hemagglutinin to bind red blood cells together into a detectable matrix may also be characterized as a biochemical test for viral infection, although strictly speaking hemagglutinin is not an enzyme and has no metabolic function.Serological methods are highly sensitive, specific and often extremely rapid tests used to identify microorganisms. These tests are based upon the ability of an antibody to bind specifically to an antigen. The antigen, usually a protein or carbohydrate made by an infectious agent, is bound by the antibody. This binding then sets off a chain of events that can be visibly obvious in various ways, dependent upon the test. For example, "Strep throat" is often diagnosed within minutes, and is based on the appearance of antigens made by the causative agent, S. pyogenes, that is retrieved from a patients throat with a cotton swab. Serological tests, if available, are usually the preferred route of identification, however the tests are costly to develop and the reagents used in the test often require refrigeration. Some serological methods are extremely costly, although when commonly used, such as with the "strep test", they can be inexpensive.Complex serological techniques have been developed into what are known as immunoassays. Immunoassays can use the basic antibody – antigen binding as the basis to produce an electro-magnetic or particle radiation signal, which can be detected by some form of instrumentation. Signal of unknowns can be compared to that of standards allowing quantitation of the target antigen. To aid in the diagnosis of infectious diseases, immunoassays can detect or measure antigens from either infectious agents or proteins generated by an infected organism in response to a foreign agent. For example, immunoassay A may detect the presence of a surface protein from a virus particle. Immunoassay B on the other hand may detect or measure antibodies produced by an organisms immune system that are made to neutralize and allow the destruction of the virus.
Instrumentation can be used to read extremely small signals created by secondary reactions linked to the antibody – antigen binding. Instrumentation can control sampling, reagent use, reaction times, signal detection, calculation of results, and data management to yield a cost-effective automated process for diagnosis of infectious disease.
PCR-based diagnostics
Technologies based upon the polymerase chain reaction (PCR) method will become nearly ubiquitous gold standards of diagnostics of the near future, for several reasons. First, the catalog of infectious agents has grown to the point that virtually all of the significant infectious agents of the human population have been identified. Second, an infectious agent must grow within the human body to cause disease; essentially it must amplify its own nucleic acids in order to cause a disease. This amplification of nucleic acid in infected tissue offers an opportunity to detect the infectious agent by using PCR. Third, the essential tools for directing PCR, primers, are derived from the genomes of infectious agents, and with time those genomes will be known, if they are not already.Thus, the technological ability to detect any infectious agent rapidly and specifically are currently available. The only remaining blockades to the use of PCR as a standard tool of diagnosis are in its cost and application, neither of which is insurmountable. The diagnosis of a few diseases will not benefit from the development of PCR methods, such as some of the clostridial diseases (tetanus and botulism). These diseases are fundamentally biological poisonings by relatively small numbers of infectious bacteria that produce extremely potent neurotoxins. A significant proliferation of the infectious agent does not occur, this limits the ability of PCR to detect the presence of any bacteria.
Metagenomic sequencing
Given the wide range of bacterial, viral, fungal, protozoal, and helminthic pathogens that cause debilitating and life-threatening illnesses, the ability to quickly identify the cause of infection is important yet often challenging. For example, more than half of cases of encephalitis, a severe illness affecting the brain, remain undiagnosed, despite extensive testing using the standard of care (microbiological culture) and state-of-the-art clinical laboratory methods. Metagenomic sequencing-based diagnostic tests are currently being developed for clinical use and show promise as a sensitive, specific, and rapid way to diagnose infection using a single all-encompassing test. This test is similar to current PCR tests; however, an untargeted whole genome amplification is used rather than primers for a specific infectious agent. This amplification step is followed by next-generation sequencing or third-generation sequencing, alignment comparisons, and taxonomic classification using large databases of thousands of pathogen and commensal reference genomes. Simultaneously, antimicrobial resistance genes within pathogen and plasmid genomes are sequenced and aligned to the taxonomically classified pathogen genomes to generate an antimicrobial resistance profile – analogous to antibiotic sensitivity testing – to facilitate antimicrobial stewardship and allow for the optimization of treatment using the most effective drugs for a patients infection.
Metagenomic sequencing could prove especially useful for diagnosis when the patient is immunocompromised. An ever-wider array of infectious agents can cause serious harm to individuals with immunosuppression, so clinical screening must often be broader. Additionally, the expression of symptoms is often atypical, making a clinical diagnosis based on presentation more difficult. Thirdly, diagnostic methods that rely on the detection of antibodies are more likely to fail. A rapid, sensitive, specific, and untargeted test for all known human pathogens that detects the presence of the organisms DNA rather than antibodies is therefore highly desirable.
Indication of tests
There is usually an indication for a specific identification of an infectious agent only when such identification can aid in the treatment or prevention of the disease, or to advance knowledge of the course of an illness prior to the development of effective therapeutic or preventative measures. For example, in the early 1980s, prior to the appearance of AZT for the treatment of AIDS, the course of the disease was closely followed by monitoring the composition of patient blood samples, even though the outcome would not offer the patient any further treatment options. In part, these studies on the appearance of HIV in specific communities permitted the advancement of hypotheses as to the route of transmission of the virus. By understanding how the disease was transmitted, resources could be targeted to the communities at greatest risk in campaigns aimed at reducing the number of new infections. The specific serological diagnostic identification, and later genotypic or molecular identification, of HIV also enabled the development of hypotheses as to the temporal and geographical origins of the virus, as well as a myriad of other hypothesis. The development of molecular diagnostic tools have enabled physicians and researchers to monitor the efficacy of treatment with anti-retroviral drugs. Molecular diagnostics are now commonly used to identify HIV in healthy people long before the onset of illness and have been used to demonstrate the existence of people who are genetically resistant to HIV infection. Thus, while there still is no cure for AIDS, there is great therapeutic and predictive benefit to identifying the virus and monitoring the virus levels within the blood of infected individuals, both for the patient and for the community at large.
Classification
Subclinical versus clinical (latent versus apparent)
Symptomatic infections are apparent and clinical, whereas an infection that is active but does not produce noticeable symptoms may be called inapparent, silent, subclinical, or occult. An infection that is inactive or dormant is called a latent infection. An example of a latent bacterial infection is latent tuberculosis. Some viral infections can also be latent, examples of latent viral infections are any of those from the Herpesviridae family.The word infection can denote any presence of a particular pathogen at all (no matter how little) but also is often used in a sense implying a clinically apparent infection (in other words, a case of infectious disease). This fact occasionally creates some ambiguity or prompts some usage discussion; to get around this it is common for health professionals to speak of colonization (rather than infection) when they mean that some of the pathogens are present but that no clinically apparent infection (no disease) is present.
Course of infection
Different terms are used to describe how and where infections present over time. In an acute infection, symptoms develop rapidly; its course can either be rapid or protracted. In chronic infection, symptoms usually develop gradually over weeks or months and are slow to resolve. In subacute infections, symptoms take longer to develop than in acute infections but arise more quickly than those of chronic infections. A focal infection is an initial site of infection from which organisms travel via the bloodstream to another area of the body.
Primary versus opportunistic
Among the many varieties of microorganisms, relatively few cause disease in otherwise healthy individuals. Infectious disease results from the interplay between those few pathogens and the defenses of the hosts they infect. The appearance and severity of disease resulting from any pathogen depend upon the ability of that pathogen to damage the host as well as the ability of the host to resist the pathogen. However, a hosts immune system can also cause damage to the host itself in an attempt to control the infection. Clinicians, therefore, classify infectious microorganisms or microbes according to the status of host defenses – either as primary pathogens or as opportunistic pathogens.
Primary pathogens
Primary pathogens cause disease as a result of their presence or activity within the normal, healthy host, and their intrinsic virulence (the severity of the disease they cause) is, in part, a necessary consequence of their need to reproduce and spread. Many of the most common primary pathogens of humans only infect humans, however, many serious diseases are caused by organisms acquired from the environment or that infect non-human hosts.
Opportunistic pathogens
Opportunistic pathogens can cause an infectious disease in a host with depressed resistance (immunodeficiency) or if they have unusual access to the inside of the body (for example, via trauma). Opportunistic infection may be caused by microbes ordinarily in contact with the host, such as pathogenic bacteria or fungi in the gastrointestinal or the upper respiratory tract, and they may also result from (otherwise innocuous) microbes acquired from other hosts (as in Clostridium difficile colitis) or from the environment as a result of traumatic introduction (as in surgical wound infections or compound fractures). An opportunistic disease requires impairment of host defenses, which may occur as a result of genetic defects (such as chronic granulomatous disease), exposure to antimicrobial drugs or immunosuppressive chemicals (as might occur following poisoning or cancer chemotherapy), exposure to ionizing radiation, or as a result of an infectious disease with immunosuppressive activity (such as with measles, malaria or HIV disease). Primary pathogens may also cause more severe disease in a host with depressed resistance than would normally occur in an immunosufficient host.
Secondary infection
While a primary infection can practically be viewed as the root cause of an individuals current health problem, a secondary infection is a sequela or complication of that root cause. For example, an infection due to a burn or penetrating trauma (the root cause) is a secondary infection. Primary pathogens often cause primary infection and often cause secondary infection. Usually, opportunistic infections are viewed as secondary infections (because immunodeficiency or injury was the predisposing factor).
Other types of infection
Other types of infection consist of mixed, iatrogenic, nosocomial, and community-acquired infection. A mixed infection is an infection that is caused by two or more pathogens. An example of this is appendicitis, which is |
Infection | caused by Bacteroides fragilis and Escherichia coli. The second is an iatrogenic infection. This type of infection is one that is transmitted from a health care worker to a patient. A nosocomial infection is also one that occurs in a health care setting. Nosocomial infections are those that are acquired during a hospital stay. Lastly, a community-acquired infection is one in which the infection is acquired from a whole community.
Infectious or not
One manner of proving that a given disease is infectious, is to satisfy Kochs postulates (first proposed by Robert Koch), which require that first, the infectious agent be identifiable only in patients who have the disease, and not in healthy controls, and second, that patients who contract the infectious agent also develop the disease. These postulates were first used in the discovery that Mycobacteria species cause tuberculosis.However, Kochs postulates cannot usually be tested in modern practice for ethical reasons. Proving them would require experimental infection of a healthy individual with a pathogen produced as a pure culture. Conversely, even clearly infectious diseases do not always meet the infectious criteria; for example, Treponema pallidum, the causative spirochete of syphilis, cannot be cultured in vitro – however the organism can be cultured in rabbit testes. It is less clear that a pure culture comes from an animal source serving as host than it is when derived from microbes derived from plate culture.Epidemiology, or the study and analysis of who, why and where disease occurs, and what determines whether various populations have a disease, is another important tool used to understand infectious disease. Epidemiologists may determine differences among groups within a population, such as whether certain age groups have a greater or lesser rate of infection; whether groups living in different neighborhoods are more likely to be infected; and by other factors, such as gender and race. Researchers also may assess whether a disease outbreak is sporadic, or just an occasional occurrence; endemic, with a steady level of regular cases occurring in a region; epidemic, with a fast arising, and unusually high number of cases in a region; or pandemic, which is a global epidemic. If the cause of the infectious disease is unknown, epidemiology can be used to assist with tracking down the sources of infection.
Contagiousness
Infectious diseases are sometimes called contagious diseases when they are easily transmitted by contact with an ill person or their secretions (e.g., influenza). Thus, a contagious disease is a subset of infectious disease that is especially infective or easily transmitted. Other types of infectious, transmissible, or communicable diseases with more specialized routes of infection, such as vector transmission or sexual transmission, are usually not regarded as "contagious", and often do not require medical isolation (sometimes loosely called quarantine) of those affected. However, this specialized connotation of the word "contagious" and "contagious disease" (easy transmissibility) is not always respected in popular use.
Infectious diseases are commonly transmitted from person to person through direct contact. The types of contact are through person to person and droplet spread. Indirect contact such as airborne transmission, contaminated objects, food and drinking water, animal person contact, animal reservoirs, insect bites, and environmental reservoirs are another way infectious diseases are transmitted.
By anatomic location
Infections can be classified by the anatomic location or organ system infected, including:
Urinary tract infection
Skin infection
Respiratory tract infection
Odontogenic infection (an infection that originates within a tooth or in the closely surrounding tissues)
Vaginal infections
Intra-amniotic infectionIn addition, locations of inflammation where infection is the most common cause include pneumonia, meningitis and salpingitis.
Prevention
Techniques like hand washing, wearing gowns, and wearing face masks can help prevent infections from being passed from one person to another. Aseptic technique was introduced in medicine and surgery in the late 19th century and greatly reduced the incidence of infections caused by surgery. Frequent hand washing remains the most important defense against the spread of unwanted organisms. There are other forms of prevention such as avoiding the use of illicit drugs, using a condom, wearing gloves, and having a healthy lifestyle with a balanced diet and regular exercise. Cooking foods well and avoiding foods that have been left outside for a long time is also important.
Antimicrobial substances used to prevent transmission of infections include:
antiseptics, which are applied to living tissue/skin
disinfectants, which destroy microorganisms found on non-living objects.
antibiotics, called prophylactic when given as prevention rather as treatment of infection. However, long term use of antibiotics leads to resistance of bacteria. While humans do not become immune to antibiotics, the bacteria does. Thus, avoiding using antibiotics longer than necessary helps preventing bacteria from forming mutations that aide in antibiotic resistance.One of the ways to prevent or slow down the transmission of infectious diseases is to recognize the different characteristics of various diseases. Some critical disease characteristics that should be evaluated include virulence, distance traveled by those affected, and level of contagiousness. The human strains of Ebola virus, for example, incapacitate those infected extremely quickly and kill them soon after. As a result, those affected by this disease do not have the opportunity to travel very far from the initial infection zone. Also, this virus must spread through skin lesions or permeable membranes such as the eye. Thus, the initial stage of Ebola is not very contagious since its victims experience only internal hemorrhaging. As a result of the above features, the spread of Ebola is very rapid and usually stays within a relatively confined geographical area. In contrast, the human immunodeficiency virus (HIV) kills its victims very slowly by attacking their immune system. As a result, many of its victims transmit the virus to other individuals before even realizing that they are carrying the disease. Also, the relatively low virulence allows its victims to travel long distances, increasing the likelihood of an epidemic.
Another effective way to decrease the transmission rate of infectious diseases is to recognize the effects of small-world networks. In epidemics, there are often extensive interactions within hubs or groups of infected individuals and other interactions within discrete hubs of susceptible individuals. Despite the low interaction between discrete hubs, the disease can jump and spread in a susceptible hub via a single or few interactions with an infected hub. Thus, infection rates in small-world networks can be reduced somewhat if interactions between individuals within infected hubs are eliminated (Figure 1). However, infection rates can be drastically reduced if the main focus is on the prevention of transmission jumps between hubs. The use of needle exchange programs in areas with a high density of drug users with HIV is an example of the successful implementation of this treatment method. Another example is the use of ring culling or vaccination of potentially susceptible livestock in adjacent farms to prevent the spread of the foot-and-mouth virus in 2001.A general method to prevent transmission of vector-borne pathogens is pest control.
In cases where infection is merely suspected, individuals may be quarantined until the incubation period has passed and the disease manifests itself or the person remains healthy. Groups may undergo quarantine, or in the case of communities, a cordon sanitaire may be imposed to prevent infection from spreading beyond the community, or in the case of protective sequestration, into a community. Public health authorities may implement other forms of social distancing, such as school closings, to control an epidemic.
Immunity
Infection with most pathogens does not result in death of the host and the offending organism is ultimately cleared after the symptoms of the disease have waned. This process requires immune mechanisms to kill or inactivate the inoculum of the pathogen. Specific acquired immunity against infectious diseases may be mediated by antibodies and/or T lymphocytes. Immunity mediated by these two factors may be manifested by:
a direct effect upon a pathogen, such as antibody-initiated complement-dependent bacteriolysis, opsonoization, phagocytosis and killing, as occurs for some bacteria,
neutralization of viruses so that these organisms cannot enter cells,
or by T lymphocytes, which will kill a cell parasitized by a microorganism.The immune system response to a microorganism often causes symptoms such as a high fever and inflammation, and has the potential to be more devastating than direct damage caused by a microbe.Resistance to infection (immunity) may be acquired following a disease, by asymptomatic carriage of the pathogen, by harboring an organism with a similar structure (crossreacting), or by vaccination. Knowledge of the protective antigens and specific acquired host immune factors is more complete for primary pathogens than for opportunistic pathogens.
There is also the phenomenon of herd immunity which offers a measure of protection to those otherwise vulnerable people when a large enough proportion of the population has acquired immunity from certain infections.
Immune resistance to an infectious disease requires a critical level of either antigen-specific antibodies and/or T cells when the host encounters the pathogen. Some individuals develop natural serum antibodies to the surface polysaccharides of some agents although they have had little or no contact with the agent, these natural antibodies confer specific protection to adults and are passively transmitted to newborns.
Host genetic factors
The organism that is the target of an infecting action of a specific infectious agent is called the host. The host harbouring an agent that is in a mature or sexually active stage phase is called the definitive host. The intermediate host comes in contact during the larvae stage. A host can be anything living and can attain to asexual and sexual reproduction.
The clearance of the pathogens, either treatment-induced or spontaneous, it can be influenced by the genetic variants carried by the individual patients. For instance, for genotype 1 hepatitis C treated with Pegylated interferon-alpha-2a or Pegylated interferon-alpha-2b (brand names Pegasys or PEG-Intron) combined with ribavirin, it has been shown that genetic polymorphisms near the human IL28B gene, encoding interferon lambda 3, are associated with significant differences in the treatment-induced clearance of the virus. This finding, originally reported in Nature, showed that genotype 1 hepatitis C patients carrying certain genetic variant alleles near the IL28B gene are more possibly to achieve sustained virological response after the treatment than others. Later report from Nature demonstrated that the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus.
Treatments
When infection attacks the body, anti-infective drugs can suppress the infection. Several broad types of anti-infective drugs exist, depending on the type of organism targeted; they include antibacterial (antibiotic; including antitubercular), antiviral, antifungal and antiparasitic (including antiprotozoal and antihelminthic) agents. Depending on the severity and the type of infection, the antibiotic may be given by mouth or by injection, or may be applied topically. Severe infections of the brain are usually treated with intravenous antibiotics. Sometimes, multiple antibiotics are used in case there is resistance to one antibiotic. Antibiotics only work for bacteria and do not affect viruses. Antibiotics work by slowing down the multiplication of bacteria or killing the bacteria. The most common classes of antibiotics used in medicine include penicillin, cephalosporins, aminoglycosides, macrolides, quinolones and tetracyclines.Not all infections require treatment, and for many self-limiting infections the treatment may cause more side-effects than benefits. Antimicrobial stewardship is the concept that healthcare providers should treat an infection with an antimicrobial that specifically works well for the target pathogen for the shortest amount of time and to only treat when there is a known or highly suspected pathogen that will respond to the medication.
Epidemiology
In 2010, about 10 million people died of infectious diseases.The World Health Organization collects information on global deaths by International Classification of Disease (ICD) code categories. The following table lists the top infectious disease by number of deaths in 2002. 1993 data is included for comparison.
The top three single agent/disease killers are HIV/AIDS, TB and malaria. While the number of deaths due to nearly every disease have decreased, deaths due to HIV/AIDS have increased fourfold. Childhood diseases include pertussis, poliomyelitis, diphtheria, measles and tetanus. Children also make up a large percentage of lower respiratory and diarrheal deaths. In 2012, approximately 3.1 million people have died due to lower respiratory infections, making it the number 4 leading cause of death in the world.
Historic pandemics
With their potential for unpredictable and explosive impacts, infectious diseases have been major actors in human history. A pandemic (or global epidemic) is a disease that affects people over an extensive geographical area. For example:
Plague of Justinian, from 541 to 542, killed between 50% and 60% of Europes population.
The Black Death of 1347 to 1352 killed 25 million in Europe over 5 years. The plague reduced the old world population from an estimated 450 million to between 350 and 375 million in the 14th century.
The introduction of smallpox, measles, and typhus to the areas of Central and South America by European explorers during the 15th and 16th centuries caused pandemics among the native inhabitants. Between 1518 and 1568 disease pandemics are said to have caused the population of Mexico to fall from 20 million to 3 million.
The first European influenza epidemic occurred between 1556 and 1560, with an estimated mortality rate of 20%.
Smallpox killed an estimated 60 million Europeans during the 18th century (approximately 400,000 per year). Up to 30% of those infected, including 80% of the children under 5 years of age, died from the disease, and one-third of the survivors went blind.
In the 19th century, tuberculosis killed an estimated one-quarter of the adult population of Europe; by 1918 one in six deaths in France were still caused by TB.
The Influenza Pandemic of 1918 (or the Spanish flu) killed 25–50 million people (about 2% of world population of 1.7 billion). Today Influenza kills about 250,000 to 500,000 worldwide each year.
Emerging diseases
In most cases, microorganisms live in harmony with their hosts via mutual or commensal interactions. Diseases can emerge when existing parasites become pathogenic or when new pathogenic parasites enter a new host.
Coevolution between parasite and host can lead to hosts becoming resistant to the parasites or the parasites may evolve greater virulence, leading to immunopathological disease.
Human activity is involved with many emerging infectious diseases, such as environmental change enabling a parasite to occupy new niches. When that happens, a pathogen that had been confined to a remote habitat has a wider distribution and possibly a new host organism. Parasites jumping from nonhuman to human hosts are known as zoonoses. Under disease invasion, when a parasite invades a new host species, it may become pathogenic in the new host.Several human activities have led to the emergence of zoonotic human pathogens, including viruses, bacteria, protozoa, and rickettsia, and spread of vector-borne diseases, see also globalization and disease and wildlife disease:
Encroachment on wildlife habitats. The construction of new villages and housing developments in rural areas force animals to live in dense populations, creating opportunities for microbes to mutate and emerge.
Changes in agriculture. The introduction of new crops attracts new crop pests and the microbes they carry to farming communities, exposing people to unfamiliar diseases.
The destruction of rain forests. As countries make use of their rain forests, by building roads through forests and clearing areas for settlement or commercial ventures, people encounter insects and other animals harboring previously unknown microorganisms.
Uncontrolled urbanization. The rapid growth of cities in many developing countries tends to concentrate large numbers of people into crowded areas with poor sanitation. These conditions foster transmission of contagious diseases.
Modern transport. Ships and other cargo carriers often harbor unintended "passengers", that can spread diseases to faraway destinations. While with international jet-airplane travel, people infected with a disease can carry it to distant lands, or home to their families, before their first symptoms appear.
Germ theory of disease
In Antiquity, the Greek historian Thucydides (c. 460 – c. 400 BCE) was the first person to write, in his account of the plague of Athens, that diseases could spread from an infected person to others. In his On the Different Types of Fever (c. 175 AD), the Greco-Roman physician Galen speculated that plagues were spread by "certain seeds of plague", which were present in the air. In the Sushruta Samhita, the ancient Indian physician Sushruta theorized: "Leprosy, fever, consumption, diseases of the eye, and other infectious diseases spread from one person to another by sexual union, physical contact, eating together, sleeping together, sitting together, and the use of same clothes, garlands and pastes." This book has been dated to about the sixth century BC.A basic form of contagion theory was proposed by Persian physician Ibn Sina (known as Avicenna in Europe) in The Canon of Medicine (1025), which later became the most authoritative medical textbook in Europe up until the 16th century. In Book IV of the Canon, Ibn Sina discussed epidemics, outlining the classical miasma theory and attempting to blend it with his own early contagion theory. He mentioned that people can transmit disease to others by breath, noted contagion with tuberculosis, and discussed the transmission of disease through water and dirt. The concept of invisible contagion was later discussed by several Islamic scholars in the Ayyubid Sultanate who referred to them as najasat ("impure substances"). The fiqh scholar Ibn al-Haj al-Abdari (c. 1250–1336), while discussing Islamic diet and hygiene, gave warnings about how contagion can contaminate water, food, and garments, and could spread through the water supply, and may have implied contagion to be unseen particles.When the Black Death bubonic plague reached Al-Andalus in the 14th century, the Arab physicians Ibn Khatima (c. 1369) and Ibn al-Khatib (1313–1374) hypothesised that infectious diseases were caused by "minute bodies" and described how they can be transmitted through garments, vessels and earrings. Ideas of contagion became more popular in Europe during the Renaissance, particularly through the writing of the Italian physician Girolamo Fracastoro. Anton van Leeuwenhoek (1632–1723) advanced the science of microscopy by being the first to observe microorganisms, allowing for easy visualization of bacteria.
In the mid-19th century John Snow and William Budd did important work demonstrating the contagiousness of typhoid and cholera through contaminated water. Both are credited with decreasing epidemics of cholera in their towns by implementing measures to prevent contamination of water. Louis Pasteur proved beyond doubt that certain diseases are caused by infectious agents, and developed a vaccine for rabies. Robert Koch provided the study of infectious diseases with a scientific basis known as Kochs postulates. Edward Jenner, Jonas Salk and Albert Sabin developed effective vaccines for smallpox and polio, which would later result in the eradication and near-eradication of these diseases, respectively. Alexander Fleming discovered the worlds first antibiotic, penicillin, which Florey and Chain then developed. Gerhard Domagk developed sulphonamides, the first broad spectrum synthetic antibacterial drugs.
Medical specialists
The medical treatment of infectious diseases falls into the medical field of Infectious Disease and in some cases the study of propagation pertains to the field of Epidemiology. Generally, infections are initially diagnosed by primary care physicians or internal medicine specialists. For example, an "uncomplicated" pneumonia will generally be treated by the internist or the pulmonologist (lung physician). The work of the infectious diseases specialist therefore entails working with both patients and general practitioners, as well as laboratory scientists, immunologists, bacteriologists and other specialists.
An infectious disease team may be alerted when:
The disease has not been definitively diagnosed after an initial workup
The patient is immunocompromised (for example, in AIDS or after chemotherapy);
The infectious agent is of an uncommon nature (e.g. tropical diseases);
The disease has not responded to first line antibiotics;
The disease might be dangerous to other patients, and the patient might have to be isolated
Society and culture
Several studies have reported associations between pathogen load in an area and human behavior. Higher pathogen load is associated with decreased size of ethnic and religious groups in an area. This may be due high pathogen load favoring avoidance of other groups, which may reduce pathogen transmission, or a high pathogen load preventing the creation of large settlements and armies that enforce a common culture. Higher pathogen load is also associated with more restricted sexual behavior, which may reduce pathogen transmission. It also associated with higher preferences for health and attractiveness in mates. Higher fertility rates and shorter or less parental care per child is another association that may be a compensation for the higher mortality rate. There is also an association with polygyny which may be due to higher pathogen load, making selecting males with a high genetic resistance increasingly important. Higher pathogen load is also associated with more collectivism and less individualism, which may limit contacts with outside groups and infections. There are alternative explanations for at least some of the associations although some of these explanations may in turn ultimately be due to pathogen load. Thus, polygyny may also be due to a lower male: female ratio in these areas but this may ultimately be due to male infants having increased mortality from infectious diseases. Another example is that poor socioeconomic factors may ultimately in part be due to high pathogen load preventing economic development.
Fossil record
Evidence of infection in fossil remains is a subject of interest for paleopathologists, scientists who study occurrences of injuries and illness in extinct life forms. Signs of infection have been discovered in the bones of carnivorous dinosaurs. When present, however, these infections seem to tend to be confined to only small regions of the body. A skull attributed to the early carnivorous dinosaur Herrerasaurus ischigualastensis exhibits pit-like wounds surrounded by swollen and porous bone. The unusual texture of the bone around the wounds suggests they were affected by a short-lived, non-lethal infection. Scientists who studied the skull speculated that the bite marks were received in a fight with another Herrerasaurus. Other carnivorous dinosaurs with documented evidence of infection include Acrocanthosaurus, Allosaurus, Tyrannosaurus and a tyrannosaur from the Kirtland Formation. The infections from both tyrannosaurs were received by being bitten during a fight, like the Herrerasaurus specimen.
Outer space
A 2006 Space Shuttle experiment found that Salmonella typhimurium, a bacterium that can cause food poisoning, became more virulent when cultivated in space. On April 29, 2013, scientists in Rensselaer Polytechnic Institute, funded by NASA, reported that, during spaceflight on the International Space Station, microbes seem to adapt to the space environment in ways "not observed on Earth" and in ways that "can lead to increases in growth and virulence". More recently, in 2017, bacteria were found to be more resistant to antibiotics and to thrive in the near-weightlessness of space. Microorganisms have been observed to survive the vacuum of outer space.
See also
References
External links
European Center for Disease Prevention and Control
U.S. Centers for Disease Control and Prevention,
Infectious Disease Society of America (IDSA)
Infectious Disease Index of the Public Health Agency of Canada (PHAC)
Vaccine Research Center Information concerning vaccine research clinical trials for Emerging and re-Emerging Infectious Diseases.
Microbes & Infection (journal)
Table: Global deaths from communicable diseases, 2010 – Canadian Broadcasting Corp. |
Leukoencephalopathy with vanishing white matter | Leukoencephalopathy with vanishing white matter (VWM disease) is an autosomal recessive neurological disease. The cause of the disease are mutations in any of the 5 genes encoding subunits of the translation initiation factor eIF2B: EIF2B1, EIF2B2, EIF2B3, EIF2B4, or EIF2B5. The disease belongs to a family of conditions called the Leukodystrophies.
Symptoms and signs
Onset usually occurs in childhood, however some adult cases have been found. Generally, physicians look for the symptoms in children. Symptoms include cerebellar ataxia, spasticity, optic atrophy, epilepsy, loss of motor functions, irritability, vomiting, coma, and even fever has been tied to VWM. The neurological disorders and symptoms which occur with VWM are not specific to countries; they are the same all over the world. Neurological abnormalities may not always be present in those who experience onset as adults. Symptoms generally appear in young children or infants who were previously developing fairly normally.
Causes
VWM is a leukodystrophy which has unique biochemical abnormalities. A unique characteristic of VWM is that only oligodendrocytes and astrocytes are negatively affected while other glial cells and neurons seem to be unaffected. This is the central question behind VWM. The real reasons behind this behavior are unknown since the cells are in the brain and have been rarely studied. However, there is a theory which is generally accepted by most experts in the field. The main characteristic of these cells is the fact that they synthesize a lot of proteins. These cells produce a large amount of proteins from a small amount of precursors and so are constantly working and under a reasonable amount of stress. So with a mutation in eIF2B, slight increases in the amount of stress these cells encounter occur, making them more susceptible to failure due to stress. The large amount of oligodendrocytes which display apoptotic characteristics and express apoptotic proteins suggests cell number reduction in the early stages of the disease. Premature ovarian failure has also been associated with diminishing white matter. However through an intensive survey, it was determined that even if an individual has premature ovarian failure, she does not necessarily have VWM.
eIF2Bs role
eIF2B is the guanine nucleotide-exchange factor for eIF2, and is composed of 5 subunits. The largest subunit, eIF2B5 contains the most mutations for VWM. eIF2B is a complex which is very involved with the regulation of in the translation of mRNA into proteins. eIF2B is essential for the exchange of guanosine diphosphate(GDP) for guanosine-5-triphosphate(GTP) in the initiation of translation via eIF2, because eIF2 is regenerated through this exchange. A decrease in eIF2B activity has been correlated with the onset of VWM. A common factor among VWM patients is mutations in the five subunits of eIF2B (21 discovered thus far), expressed in over 60% of the patients. These mutations lead to the decreased activity of eIF2B. The most common mutation is R113H, which is the mutation of histidine to arginine. The homozygous form of the mutation is the least severe form. This mutation has also been documented in rodents, but they do not acquire VWM, while humans do. Another common mutation is G584A found in the eIF2B5 subunit. A correlation with stress has also been made, as eIF2B plays a central role in stress management – it is essential in down regulation protein synthesis in different stress conditions – and VWM patients are highly sensitive to stress. Protein eIF2B exists in all cells, and if this protein is reduced enough the cell will be negatively affected, and if it is reduced to zero, the cell will die. In affected cells, the protein is reduced to about 50%, which is acceptable for functionality in most cells, but not in glial cells since they synthesize a large amount of proteins constantly and need as many functioning proteins within them as possible. This would lower the baseline of the amount of stress a cell can handle, and thus in a stressed environment, it would have detrimental effects on these cells. Mutations in three of the subunits of eIF2B (2,4,&5) has been seen in both VWM and premature ovarian failure. The North American Cree population has also been found to have a distinctive mutation, R195H, which can lead to VWM. All patients who have been studied only have one mutation present in the gene, causing the eIF2B to still be active, which leads to VWM. If two mutations occurred, then eIF2B activity would be stopped by the body.
Neuropathology
Upon autopsy, the full effect of VWM has been documented. The gray matter remains normal in all characteristics while the white matter changes texture, becoming soft and gelatinous. Rarefaction of the white matter is seen through light microscopy and the small number of axons and U-fibers that were affected can also be seen. Numerous small cavities in the white matter are also apparent. The key characteristic that sets VWM apart from the other leukodystrophies is the presence of foamy oligodendrocytes. These foamy oligodendrocytes tend to have increased cytoplasmic structures, a greater number of irregular mitochondria and a higher rate of apoptosis. Abnormally shaped astrocytes with fibrile infections are very prevalent throughout the capillaries in the brain. Strangely, astrocytes are affected more than oligodendrocytes; there is even a reduction in the astrocyte progenitors, yet axons remain relatively unharmed.
Diagnosis
Most diagnosis occurs in the early years of life around 2 to 6 years old. There have been cases in which onset and diagnosis have occurred late into adulthood. Those with onset at this time have different signs, particularly the lack of cognitive deterioration. Overall, detection of adult forms of VWM is difficult as MRI was not a common tool when they were diagnosed. Common signs to look for include chronic progressive neurological deterioration with cerebellar ataxia, spasticity, mental decline, decline of vision, mild epilepsy, hand tremor, the ability to chew and swallow food becomes difficult, rapid deterioration and fibrile infections following head trauma or fright, loss of motor functions, irritability, behavioural changes, vomiting, and even coma. Those who go into coma, if they do come out usually die within a few years. The diagnosis can be difficult if the physician does not take an MRI.
Case report on diagnosis of adult-onset VWM
The individual was examined at age 32, but he stated that he started noting differences 5 years before. He noticed sexual impotency, social isolation, unexplained aggression and sadness, loss of motivation, inert laughs, auditory hallucinations, thought insertion, delusions, and imperative commenting. He showed very minimal physical impairments, commonly seen in child-onsets. However, his MRI showed characteristic signs of VWM disease.
MRI
The MRI of patients with VWM shows a well defined leukodystrophy. These MRIs display reversal of signal intensity of the white matter in the brain. Recovery sequences and holes in the white matter are also visible. Over time, the MRI is excellent at showing rarefaction and cystic degeneration of the white matter as it is replaced by fluid. To show this change, displaying white matter as a high signal (T2-weighted), proton density, and Fluid attenuated inversion recovery (FLAIR) images are the best approach. T2-weighted images also displaying cerebrospinal fluid and rarefied/cystic white matter. To view the remaining tissue, and get perspective on the damage done (also helpful in determining the rate of deterioration) (T1-weighted), proton density, and FLAIR images are ideal as they show radiating stripe patterns in the degenerating white matter. A failure of MRI images is their ineffectiveness and difficulty in interpretation in infants since the brain has not fully developed yet. Though some patterns and signs may be visible, it is still difficult to conclusively diagnose. This often leads to misdiagnosis in infants particularly if the MRI results in equivocal patterns or because of the high water content in infants brains. The easiest way to fix this problem is a follow-up MRI in the following weeks. A potentially similar appearance of MRI with white matter abnormalities and cystic changes may be seen in some patients with hypomelanosis of Ito, some forms of Lowes (oculocerebrorenal) disease, or some of the mucopolysaccharidoses.
Common misdiagnosis
Often with VWM, the lack of knowledge of the disease causes a misdiagnosis among physicians. As VWM is a member of the large group of leukodystrophy syndromes, it is often misdiagnosed as another type such as metachromatic leukodystrophy. More often than not, it is simply classified as a non-specific leukodystrophy. The characteristics of the brain upon autopsy are often very similar to atypical diffuse sclerosis, such as the presence of fibrillary astrocytes and scant sudanophilic lipids. Adult-onset VWM disease can present with psychosis and may be hard to differentiate from schizophrenia. Common misdiagnosis from misinterpreting the MRI include asphyxia, congenital infections, metabolic diseases.Multiple sclerosis is often a misdiagnosis, but only in children due to its neurological characteristics, onset in early years, and MRI abnormalities. However, there are many differences between the two diseases. The glial cells express a loss of myelin. This loss of myelin is different from that seen in other diseases where hypomyelination occurs. In VWM, the cells never produce the normal amounts, whereas with diseases like MS, the cells normal amounts are deteriorated. Also, with MS, the demyelination occurs due to inflammation, which is not the case in VWM. Cell differences include a lower penetration of the macrophages and microglia, as well as the lack of T cells and B cells in VWM. Finally, patients with MS have widespread demyelination, but those with VWM only express demyelination in a localized area.Some atypical forms of multiple sclerosis (multiple sclerosis with cavitary lesions) can be specially difficult to differentiate but there are some clues in MRI imaging that can help.
Treatment
There are no treatments, only precautions which can be taken, mainly to reduce trauma to the head and avoiding physiological stress. Melatonin has been shown to provide cytoprotective traits to glial cells exposed to stressors such as excitotoxicity and oxidative stress. These stressors would be detrimental to cells with a genetically reduced activity of protein eIF2B. However, research connecting these ideas have not been conducted yet.
Epidemiology
Extensive pathological and biochemical tests were performed, however the cause was found by studying a small population in which mutations in the eIF2B gene were found. No effective systemic studies have been conducted to determine the incidence around the world, but through the studies conducted thus far, it appears to be more prevalent in the white populations. VWM appears to have a lower number of cases in the Middle East, and Turkey has not yet had a reported case. Its prevalence is limited by the physicians ability to identify the disease. As of 2006, more than 200 people have been identified with VWM, many of whom were originally diagnosed with an unclassified leukodystrophy.
History
The first time this disease was documented was in 1962 when Eickle studied a 36-year-old woman. Her first symptoms, gait difficulties and secondary amenorrhoea, occurred when she was 31 years old. Throughout the duration of her life, she experienced chronic episodes with extensive deterioration of her brain following minor physical trauma. Upon death, autopsy was performed in which the cerebral white matter displayed dispersed cystic areas. These areas were surrounded by a dense net of oligodendrocytes in which only mild fibrillary astrocytes and scant sudanophilic lipids were found.As the years progressed, more accounts of similar patients with similar symptoms were documented; however no one classified all the accounts as the same disease. It was not until 1993-94 when Dr. Hanefeld and Dr. Schiffmann and their colleagues identified the disease as childhood-onset progressive leukoencephalopathy. They determined it was autosomal recessive. They too saw that head trauma was a trigger for the onset of VWM. The key factor which allowed them to connect these patients together was the results of the magnetic-resonance spectroscopy in which the normal white matter signals were gone and often replaced with resonances indicative of lactate and glucose. They determined the cause was hypomyelination. in 1997–98, Dr. Marjo S. van der Knaap and colleagues saw the same characteristics in another set of patients, but these patients also expressed febrile infections. Dr. van der Knaap used MRI as well as magnetic-resonance spectroscopy and determined that ongoing cystic degeneration of the cerebral white matter and matter rarefaction was more descriptive of the disease rather than hypomyelination and proposed the name vanishing white matter. The name proposed by Dr. Schiffmann in 1994, childhood ataxia with central hypomyelination (CACH) is another commonly accepted name.
See also
The Stennis Foundation
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
Progressive multifocal leukoencephalopathy
Metachromatic leukodystrophy
General leukoencephalopathies
References
External links
"Leukoencephalopathy with vanishing white matter". Neurographics. 2 (1). March 2012. |
Herpes simplex virus | Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names Human alphaherpesvirus 1 and Human alphaherpesvirus 2, are two members of the human Herpesviridae family, a set of viruses that produce viral infections in the majority of humans. Both HSV-1 and HSV-2 are very common and contagious. They can be spread when an infected person begins shedding the virus.
As of 2016, about 67% of the world population under the age of 50 had HSV-1. In the United States, about 47.8% and 11.9% are estimated to have HSV-1 and HSV-2, respectively, though actual prevalence may be much higher. Because it can be transmitted through any intimate contact, it is one of the most common sexually transmitted infections.
Symptoms
Many of those who are infected never develop symptoms. Symptoms, when they occur, may include watery blisters in the skin or mucous membranes of the mouth, lips, nose, genitals, or eyes (herpes simplex keratitis). Lesions heal with a scab characteristic of herpetic disease. Sometimes, the viruses cause mild or atypical symptoms during outbreaks. However, they can also cause more troublesome forms of herpes simplex. As neurotropic and neuroinvasive viruses, HSV-1 and -2 persist in the body by hiding from the immune system in the cell bodies of neurons, particularly in sensory ganglia. After the initial or primary infection, some infected people experience sporadic episodes of viral reactivation or outbreaks. In an outbreak, the virus in a nerve cell becomes active and is transported via the neurons axon to the skin, where virus replication and shedding occur and may cause new sores.
Transmission
HSV-1 and HSV-2 are transmitted by contact with an infected person who has reactivations of the virus. HSV-2 is periodically shed, most often asymptomatically. Most sexual transmissions occur during periods of asymptomatic shedding. Asymptomatic reactivation means that the virus causes atypical, subtle, or hard-to-notice symptoms that are not identified as an active herpes infection, so acquiring the virus is possible even if no active HSV blisters or sores are present. In one study, daily genital swab samples detected HSV-2 at a median of 12–28% of days among those who had an outbreak, and 10% of days among those with asymptomatic infection (no prior outbreaks), with many of these episodes occurring without visible outbreak ("subclinical shedding").In another study, 73 subjects were randomized to receive valaciclovir 1 g daily or placebo for 60 days each in a two-way crossover design. A daily swab of the genital area was self-collected for HSV-2 detection by polymerase chain reaction, to compare the effect of valaciclovir versus placebo on asymptomatic viral shedding in immunocompetent, HSV-2 seropositive subjects without a history of symptomatic genital herpes infection. The study found that valaciclovir significantly reduced shedding during subclinical days compared to placebo, showing a 71% reduction; 84% of subjects had no shedding while receiving valaciclovir versus 54% of subjects on placebo. About 88% of patients treated with valaciclovir had no recognized signs or symptoms versus 77% for placebo.For HSV-2, subclinical shedding may account for most of the transmission. Studies on discordant partners (one infected with HSV-2, one not) show that the transmission rate is approximately 5 per 10,000 sexual contacts. Atypical symptoms are often attributed to other causes, such as a yeast infection. HSV-1 is often acquired orally during childhood. It may also be sexually transmitted, including contact with saliva, such as kissing and oral sex. Historically HSV-2 was primarily a sexually transmitted infection, but rates of HSV-1 genital infections have been increasing for the last few decades.Both viruses may also be transmitted vertically during childbirth. However, the risk of transmission is minimal if the mother has no symptoms nor exposed blisters during delivery. The risk is considerable when the mother is infected with the virus for the first time during late pregnancy, reflecting high viral load. Contrary to popular myths, herpes cannot be transmitted from surfaces such as toilet seats because the herpes virus begins to die immediately after leaving the body.Herpes simplex viruses can affect areas of skin exposed to contact with an infected person (although shaking hands with an infected person does not transmit this disease). An example of this is herpetic whitlow, which is a herpes infection on the fingers. This condition was common for dental surgeons prior to the routine use of gloves when conducting treatment on patients. Genital infection of HSV-2 increases the risk of acquiring HIV.
Virology
HSV has been a model virus for many studies in molecular biology. For instance, one of the first functional promoters in eukaryotes was discovered in HSV (of the thymidine kinase gene) and the virion protein VP16 is one of the most-studied transcriptional activators.
Viral Structure
Animal herpes viruses all share some common properties. The structure of herpes viruses consists of a relatively large, double-stranded, linear DNA genome encased within an icosahedral protein cage called the capsid, which is wrapped in a lipid bilayer called the envelope. The envelope is joined to the capsid by means of a tegument. This complete particle is known as the virion. HSV-1 and HSV-2 each contain at least 74 genes (or open reading frames, ORFs) within their genomes, although speculation over gene crowding allows as many as 84 unique protein coding genes by 94 putative ORFs. These genes encode a variety of proteins involved in forming the capsid, tegument and envelope of the virus, as well as controlling the replication and infectivity of the virus. These genes and their functions are summarized in the table below.The genomes of HSV-1 and HSV-2 are complex and contain two unique regions called the long unique region (UL) and the short unique region (US). Of the 74 known ORFs, UL contains 56 viral genes, whereas US contains only 12. Transcription of HSV genes is catalyzed by RNA polymerase II of the infected host. Immediate early genes, which encode proteins for example ICP22 that regulate the expression of early and late viral genes, are the first to be expressed following infection. Early gene expression follows, to allow the synthesis of enzymes involved in DNA replication and the production of certain envelope glycoproteins. Expression of late genes occurs last; this group of genes predominantly encode proteins that form the virion particle.Five proteins from (UL) form the viral capsid - UL6, UL18, UL35, UL38, and the major capsid protein UL19.
Cellular Entry
Entry of HSV into a host cell involves several glycoproteins on the surface of the enveloped virus binding to their transmembrane receptors on the cell surface. Many of these receptors are then pulled inwards by the cell, which is thought to open a ring of three gHgL heterodimers stabilizing a compact conformation of the gB glycoprotein, so that it springs out and punctures the cell membrane. The envelope covering the virus particle then fuses with the cell membrane, creating a pore through which the contents of the viral envelope enters the host cell.The sequential stages of HSV entry are analogous to those of other viruses. At first, complementary receptors on the virus and the cell surface bring the viral and cell membranes into proximity. Interactions of these molecules then form a stable entry pore through which the viral envelope contents are introduced to the host cell. The virus can also be endocytosed after binding to the receptors, and the fusion could occur at the endosome. In electron micrographs, the outer leaflets of the viral and cellular lipid bilayers have been seen merged; this hemifusion may be on the usual path to entry or it may usually be an arrested state more likely to be captured than a transient entry mechanism.In the case of a herpes virus, initial interactions occur when two viral envelope glycoprotein called glycoprotein C (gC) and glycoprotein B (gB) bind to a cell surface polysaccharide called heparan sulfate. Next, the major receptor binding protein, glycoprotein D (gD), binds specifically to at least one of three known entry receptors. These cell receptors include herpesvirus entry mediator (HVEM), nectin-1 and 3-O sulfated heparan sulfate. The nectin receptors usually produce cell-cell adhesion, to provide a strong point of attachment for the virus to the host cell. These interactions bring the membrane surfaces into mutual proximity and allow for other glycoproteins embedded in the viral envelope to interact with other cell surface molecules. Once bound to the HVEM, gD changes its conformation and interacts with viral glycoproteins H (gH) and L (gL), which form a complex. The interaction of these membrane proteins may result in a hemifusion state. gB interaction with the gH/gL complex creates an entry pore for the viral capsid. gB interacts with glycosaminoglycans on the surface of the host cell.
Genetic Inoculation
After the viral capsid enters the cellular cytoplasm, it is transported to the cell nucleus. Once attached to the nucleus at a nuclear entry pore, the capsid ejects its DNA contents via the capsid portal. The capsid portal is formed by 12 copies of portal protein, UL6, arranged as a ring; the proteins contain a leucine zipper sequence of amino acids, which allow them to adhere to each other. Each icosahedral capsid contains a single portal, located in one vertex.
The DNA exits the capsid in a single linear segment.
Immune Evasion
HSV evades the immune system through interference with MHC class I antigen presentation on the cell surface, by blocking the transporter associated with antigen processing (TAP) induced by the secretion of ICP-47 by HSV. In the host cell, TAP transports digested viral antigen epitope peptides from the cytosol to the endoplasmic reticulum, allowing these epitopes to be combined with MHC class I molecules and presented on the surface of the cell. Viral epitope presentation with MHC class I is a requirement for activation of cytotoxic T-lymphocytes (CTLs), the major effectors of the cell-mediated immune response against virally-infected cells. ICP-47 prevents initiation of a CTL-response against HSV, allowing the virus to survive for a protracted period in the host. HSV usually produces cytopathic effect (CPE) within 24–72 hours post-infection in permissive cell lines which is observed by classical plaque formation. However, HSV-1 clinical isolates have also been reported that did not show any CPE in Vero and A549 cell cultures over several passages with low level of virus protein expression. Probably these HSV-1 isolates are evolving towards a more "cryptic" form to establish chronic infection thereby unravelling yet another strategy to evade the host immune system, besides neuronal latency.
Replication
Following infection of a cell, a cascade of herpes virus proteins, called immediate-early, early, and late, is produced. Research using flow cytometry on another member of the herpes virus family, Kaposis sarcoma-associated herpesvirus, indicates the possibility of an additional lytic stage, delayed-late. These stages of lytic infection, particularly late lytic, are distinct from the latency stage. In the case of HSV-1, no protein products are detected during latency, whereas they are detected during the lytic cycle.The early proteins transcribed are used in the regulation of genetic replication of the virus. On entering the cell, an α-TIF protein joins the viral particle and aids in immediate-early transcription. The virion host shutoff protein (VHS or UL41) is very important to viral replication. This enzyme shuts off protein synthesis in the host, degrades host mRNA, helps in viral replication, and regulates gene expression of viral proteins. The viral genome immediately travels to the nucleus, but the VHS protein remains in the cytoplasm.The late proteins form the capsid and the receptors on the surface of the virus. Packaging of the viral particles — including the genome, core and the capsid - occurs in the nucleus of the cell. Here, concatemers of the viral genome are separated by cleavage and are placed into formed capsids. HSV-1 undergoes a process of primary and secondary envelopment. The primary envelope is acquired by budding into the inner nuclear membrane of the cell. This then fuses with the outer nuclear membrane. The virus acquires its final envelope by budding into cytoplasmic vesicles.
Latent Infection
HSVs may persist in a quiescent but persistent form known as latent infection, notably in neural ganglia. HSV-1 tends to reside in the trigeminal ganglia, while HSV-2 tends to reside in the sacral ganglia, but these are historical tendencies only. During latent infection of a cell, HSVs express latency-associated transcript (LAT) RNA. LAT regulates the host cell genome and interferes with natural cell death mechanisms. By maintaining the host cells, LAT expression preserves a reservoir of the virus, which allows subsequent, usually symptomatic, periodic recurrences or "outbreaks" characteristic of nonlatency. Whether or not recurrences are symptomatic, viral shedding occurs to infect a new host.A protein found in neurons may bind to herpes virus DNA and regulate latency. Herpes virus DNA contains a gene for a protein called ICP4, which is an important transactivator of genes associated with lytic infection in HSV-1. Elements surrounding the gene for ICP4 bind a protein known as the human neuronal protein neuronal restrictive silencing factor (NRSF) or human repressor element silencing transcription factor (REST). When bound to the viral DNA elements, histone deacetylation occurs atop the ICP4 gene sequence to prevent initiation of transcription from this gene, thereby preventing transcription of other viral genes involved in the lytic cycle. Another HSV protein reverses the inhibition of ICP4 protein synthesis. ICP0 dissociates NRSF from the ICP4 gene and thus prevents silencing of the viral DNA.
Genome
The HSV genome spans about 150,000 bp and consists of two unique segments, named unique long (UL) and unique short (US), as well as terminal inverted repeats found to the two ends of them named repeat long (RL) and repeat short (RS). There are also minor "terminal redundancy" (α) elements found on the further ends of RS. The overall arrangement is RL-UL-RL-α-RS-US-RS-α with each pair of repeats inverting each other. The whole sequence is then encapsuled in a terminal direct repeat. The long and short parts each have their own origins of replication, with OriL located between UL28 and UL30 and OriS located in a pair near the RS. As the L and S segments can be assembled in any direction, they can be inverted relative to each other freely, forming various linear isomers.
Gene expression
HSV genes are expressed in 3 temporal classes: immediate early (IE or α), early (E or ß) and late (γ) genes. However, the progression of viral gene expression is rather gradual than in clearly distinct stages. Immediate early genes are transcribed right after infection and their gene products activate transcription of the early genes. Early gene products help to replicate the viral DNA. Viral DNA replication, in turn, stimulates the expression of the late genes, encoding the structural proteins.Transcription of the immediate early (IE) genes begins right after virus DNA enters the nucleus. All virus genes are transcribed by host RNA polymerase II. Although host proteins are sufficient for virus transcription, viral proteins are necessary for the transcription of certain genes. For instance, VP16 plays an important role in IE transcription and the virus particle apparently brings it into the host cell, so that it does not need to be produced first. Similarly, the IE proteins RS1 (ICP4), UL54 (ICP27), and ICP0 promote the transcription of the early (E) genes. Like IE genes, early gene promoters contain binding sites for cellular transcription factors. One early protein, ICP8, is necessary for both transcription of late genes and DNA replication.Later in the life cycle of HSV, expression of immediate early and early genes is shut down. This is mediated by specific virus proteins, e.g. ICP4, which represses itself by binding to elements in its own promoter. As a consequence, the down-regulation of ICP4 levels leads to a reduction of early and late gene expression, as ICP4 is important for both.Importantly, HSV shuts down host cell RNA, DNA and protein synthesis to direct cellular resources to virus production. First, the virus protein vhs induces the degradation of existing mRNAs early in infection. Other viral genes impede cellular transcription and translation. For instance, ICP27 inhibits RNA splicing, so that virus mRNAs (which are usually not spliced) gain an advantage over host mRNAs. Finally, virus proteins destabilize certain cellular proteins involved in the host cell cycle, so that both cell division and host cell DNA replication disturbed in favor of virus replication.
Evolution
The herpes simplex 1 genomes can be classified into six clades. Four of these occur in East Africa, one in East Asia and one in Europe and North America. This suggests that the virus may have originated in East Africa. The most recent common ancestor of the Eurasian strains appears to have evolved ~60,000 years ago. The East Asian HSV-1 isolates have an unusual pattern that is currently best explained by the two waves of migration responsible for the peopling of Japan.Herpes simplex 2 genomes can be divided into two groups: one is globally distributed and the other is mostly limited to sub Saharan Africa. The globally distributed genotype has undergone four ancient recombinations with herpes simplex 1. It has also been reported that HSV-1 and HSV-2 can have contemporary and stable recombination events in hosts simultaneously infected with both pathogens. All of the cases are HSV-2 acquiring parts of the HSV-1 genome, sometimes changing parts of its antigen epitope in the process.The mutation rate has been estimated to be ~1.38×10−7 substitutions/site/year. In clinical setting, the mutations in either the thymidine kinase gene or DNA polymerase gene has caused resistance to aciclovir. However, most of the mutations occur in the thymidine kinase gene rather than the DNA polymerase gene.Another analysis has estimated the mutation rate in the herpes simplex 1 genome to be 1.82×10−8 nucleotide substitution per site per year. This analysis placed the most recent common ancestor of this virus ~710,000 years ago.Herpes simplex 1 and 2 diverged about 6 million years ago.
Treatment
Similar to other herpesviridae, the herpes simplex viruses establish latent lifelong infection, and thus cannot be eradicated from the body with current treatments.Treatment usually involves general-purpose antiviral drugs that interfere with viral replication, reduce the physical severity of outbreak-associated lesions, and lower the chance of transmission to others. Studies of vulnerable patient populations have indicated that daily use of antivirals such as aciclovir and valaciclovir can reduce reactivation rates. The extensive use of antiherpetic drugs has led to the development of some drug resistance, which in turn may lead to treatment failure. Therefore, new sources of drugs are broadly investigated to address the problem. In January 2020, a comprehensive review article was published that demonstrated the effectiveness of natural products as promising anti-HSV drugs. Pyrithione, a zinc ionophore, has shown antiviral activity against herpes simplex.
Alzheimers disease
In 1979, it was reported that there is a possible link between HSV-1 and Alzheimers disease, in people with the epsilon4 allele of the gene APOE. HSV-1 appears to be particularly damaging to the nervous system and increases ones risk of developing Alzheimers disease. The virus interacts with the components and receptors of lipoproteins, which may lead to the development of Alzheimers disease. This research identifies HSVs as the pathogen most clearly linked to the establishment of Alzheimers. According to a study done in 1997, without the presence of the gene allele, HSV-1 does not appear to cause any neurological damage or increase the risk of Alzheimers. However, a more recent prospective study published in 2008 with a cohort of 591 people showed a statistically significant difference between patients with antibodies indicating recent reactivation of HSV and those without these antibodies in the incidence of Alzheimers disease, without direct correlation to the APOE-epsilon4 allele.The trial had a small sample of patients who did not have the antibody at baseline, so the results should be viewed as highly uncertain. In 2011, Manchester University scientists showed that treating HSV1-infected cells with antiviral agents decreased the accumulation of β-amyloid and tau protein and also decreased HSV-1 replication.A 2018 retrospective study from Taiwan on 33,000 patients found that being infected with herpes simplex virus increased the risk of dementia 2.56 times (95% CI: 2.3-2.8) in patients not receiving anti-herpetic medications (2.6 times for HSV-1 infections and 2.0 times for HSV-2 infections). However, HSV-infected patients who were receiving anti-herpetic medications (acyclovir, famciclovir, ganciclovir, idoxuridine, penciclovir, tromantadine, valaciclovir, or valganciclovir) showed no elevated risk of dementia compared to patients uninfected with HSV.
Multiplicity reactivation
Multiplicity reactivation (MR) is the process by which viral genomes containing inactivating damage interact within an infected cell to form a viable viral genome. MR was originally discovered with the bacterial virus bacteriophage T4, but was subsequently also found with pathogenic viruses including influenza virus, HIV-1, adenovirus simian virus 40, vaccinia virus, reovirus, poliovirus and herpes simplex virus.When HSV particles are exposed to doses of a DNA damaging agent that would be lethal in single infections, but are then allowed to undergo multiple infection (i.e. two or more viruses per host cell), MR is observed. Enhanced survival of HSV-1 due to MR occurs upon exposure to different DNA damaging agents, including methyl methanesulfonate, trimethylpsoralen (which causes inter-strand DNA cross-links), and UV light. After treatment of genetically marked HSV with trimethylpsoralen, recombination between the marked viruses increases, suggesting that trimethylpsoralen damage stimulates recombination. MR of HSV appears to partially depend on the host cell recombinational repair machinery since skin fibroblast cells defective in a component of this machinery (i.e. cells from Blooms syndrome patients) are deficient in MR.These observations suggest that MR in HSV infections involves genetic recombination between damaged viral genomes resulting in production of viable progeny viruses. HSV-1, upon infecting host cells, induces inflammation and oxidative stress. Thus it appears that the HSV genome may be subjected to oxidative DNA damage during infection, and that MR may enhance viral survival and virulence under these conditions.
Use as an anti-cancer agent
Modified Herpes simplex virus is considered as a potential therapy for cancer and has been extensively clinically tested to assess its oncolytic (cancer killing) ability. Interim overall survival data from Amgens phase 3 trial of a genetically attenuated herpes virus suggests efficacy against melanoma.
Use in neuronal connection tracing
Herpes simplex virus is also used as a transneuronal tracer defining connections among neurons by virtue of traversing synapses.
Other related outcomes
HSV-2 the most common cause of Mollarets meningitis. HSV-1 can lead to potentially fatal cases of herpes simplex encephalitis. Herpes simplex viruses have also been studied in the central nervous system disorders such as multiple sclerosis, but research has been conflicting and inconclusive.Following a diagnosis of genital herpes simplex infection, patients may develop an episode of profound depression. In addition to offering antiviral medication to alleviate symptoms and shorten their duration, physicians must also address the mental health impact of a new diagnosis. Providing information on the very high prevalence of these infections, their effective treatments, and future therapies in development may provide hope to patients who are otherwise demoralized.
Research
There exist commonly used vaccines to some herpesviruses, such as the veterinary vaccine HVT/LT (Turkey herpesvirus vector laryngotracheitis vaccine). However, it prevents atherosclerosis (which histologically mirrors atherosclerosis in humans) in target animals vaccinated.
The only human vaccines available for herpesviruses are for Varicella zoster virus, given to children around their first birthday to prevent chickenpox (varicella), or to adults to prevent an outbreak of shingles (herpes zoster) . There is, however, no human vaccine for herpes simplex viruses. As of 2022, there are active pre-clinical and clinical studies underway on herpes simplex in humans; vaccines are being developed for both treatment and prevention.
References
External links
"Genital Herpes". Public Health Agency of Canada. 2006-05-29.
Herpes simplex: Host viral protein interactions: A database of HSV-1 interacting host proteins Archived 2010-08-12 at the Wayback Machine
3D macromolecular structures of the Herpes simplex virus archived in the EM Data Bank(EMDB) |
Delusional parasitosis | Delusional parasitosis (DP) is a mental disorder in which individuals have a persistent belief that they are infested with living or nonliving pathogens such as parasites, insects, or bugs, when no such infestation is present. They usually report tactile hallucinations known as formication, a sensation resembling insects crawling on or under the skin. Morgellons is considered to be a subtype of this condition, in which individuals have sores that they believe contain harmful fibers.Delusional parasitosis is classified as a delusional disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM5). The cause is unknown, but is thought to be related to excess dopamine in the brain. Delusional parasitosis is diagnosed when the delusion is the only symptom of psychosis and the delusion—that cannot be better explained by another condition—has lasted a month or longer. Few individuals with the condition willingly accept treatment, because they do not recognize the illness as a delusion. Antipsychotic medications offer a potential cure, while cognitive behavioral therapy and antidepressants can be used to help alleviate symptoms.The condition is rare, and is observed twice as often in women as men. The average age of people with the disorder is 57. An alternative name, Ekboms syndrome, refers to the neurologist Karl-Axel Ekbom, who published seminal accounts of the disease in 1937 and 1938.
Classification
Delusional infestation is classified as a delusional disorder of the somatic subtype in the Diagnostic and Statistical Manual of Mental Disorders (DSM5). The name delusional parasitosis has been the most common name since 2015, but the condition has also been called delusional infestation, delusory parasitosis, delusional ectoparasitosis, psychogenic parasitosis, Ekbom syndrome, dermatophobia, parasitophobia, formication and "cocaine bugs".Morgellons is a form of delusional parasitosis in which people have painful skin sensations that they believe contain fibers of various kinds; its presentation is very similar to other delusional infestations, but people with this self-diagnosed condition also believe that strings or fibers are present in their skin lesions.Delusory cleptoparasitosis is a form of delusion of parasitosis where the person believes the infestation is in their dwelling, rather than on or in their body.
Signs and symptoms
People with delusional parasitosis believe that "parasites, worms, mites, bacteria, fungus" or some other living organism has infected them, and reasoning or logic will not dissuade them from this belief. Details vary among those who have the condition, though it typically manifests as a crawling and pin-pricking sensation that is most commonly described as involving perceived parasites crawling upon or burrowing into the skin, sometimes accompanied by an actual physical sensation (known as formication). Affected people may injure themselves in attempts to be rid of the "parasites"; resulting skin damage includes excoriation, bruising and cuts, as well as damage caused from using chemical substances and obsessive cleansing routines.A "preceding event such as a bug bite, travel, sharing clothes, or contact with an infected person" is often identified by individuals with DP; such events may lead the individual to misattribute symptoms because of more awareness of symptoms they were previously able to ignore. Nearly any marking upon the skin, or small object or particle found on the person or their clothing, can be interpreted as evidence for the parasitic infestation, and individuals with the condition commonly compulsively gather such "evidence" to present to medical professionals. This presentation is known as the "matchbox sign", "Ziploc bag sign" or "specimen sign", because the "evidence" is frequently presented in a small container, such as a matchbox. The matchbox sign is present in five to eight out of every ten people with DP. Related is a "digital specimen sign", in which individuals bring collections of photographs to document their condition.Similar delusions may be present in close relatives—a shared condition known as a folie à deux—that occurs in 5 to 15% of cases and is considered a shared psychotic disorder. Because the internet and the media contribute to furthering shared delusions, DP has also been called folie à Internet; when affected people are separated, their symptoms typically subside, but most still require treatment.Approximately eight out of ten individuals with DP have co-occurring conditions—mainly depression, followed by substance abuse and anxiety; their personal and professional lives are frequently disrupted as they are extremely distressed about their symptoms.A 2011 Mayo Clinic study of 108 patients failed to find evidence of skin infestation in skin biopsies and patient-provided specimens; the study concluded that the feeling of skin infestation was DP.
Cause
The cause of delusional parasitosis is unknown. It may be related to excess dopamine in the brains striatum, resulting from diminished dopamine transporter (DAT) function, which regulates dopamine reuptake in the brain. Evidence supporting the dopamine theory is that medications that inhibit dopamine reuptake (for example cocaine and amphetamines) are known to induce symptoms such as formication. Other conditions that also demonstrate reduced DAT functioning are known to cause secondary DP; these conditions include "schizophrenia, depression, traumatic brain injury, alcoholism, Parkinsons and Huntingtons diseases, human immunodeficiency virus infection, and iron deficiency". Further evidence is that antipsychotics improve DP symptoms, which may be because they affect dopamine transmission.
Diagnosis
Delusional parasitosis is diagnosed when the delusion is the only symptom of psychosis, the delusion has lasted a month or longer, behavior is otherwise not markedly odd or impaired, mood disorders—if present at any time—have been comparatively brief, and the delusion cannot be better explained by another medical condition, mental disorder, or the effects of a substance. For diagnosis, the individual must attribute abnormal skin sensations to the belief that they have an infestation, and be convinced that they have an infestation even when evidence shows they do not.The condition is recognized in two forms: primary and secondary. In primary delusional parasitosis, the delusions are the only manifestation of a psychiatric disorder. Secondary delusional parasitosis occurs when another psychiatric condition, medical illness or substance (medical or recreational) use causes the symptoms; in these cases, the delusion is a symptom of another condition rather than the disorder itself. Secondary forms of DP can be functional (due to mainly psychiatric disorders) or organic (due to other medical illness or organic disease. The secondary organic form may be related to vitamin B12 deficiency, hypothyroidism, anemia, hepatitis, diabetes, HIV/AIDS, syphilis, or abuse of cocaine.Examination to rule out other causes is key to diagnosis. Parasitic infestations are ruled out via skin examination and laboratory analyses. Bacterial infections may be present as a result of the individual constantly manipulating their skin. Other conditions that can cause itching skin are also ruled out; this includes a review of medications that may lead to similar symptoms. Testing to rule out other conditions helps build a trusting relationship with the physician; this can include laboratory analysis such as a complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, C-reactive protein, urinalysis for toxicology and thyroid-stimulating hormone, in addition to skin biopsies and dermatological tests to detect or rule out parasitic infestations. Depending on symptoms, tests may be done for "human immunodeficiency virus, syphilis, viral hepatitis, B12 or folate deficiency," and allergies.
Differential
Delusional parasitosis must be distinguished from scabies, mites, and other psychiatric conditions that may occur along with the delusion; these include schizophrenia, dementia, anxiety disorders, obsessive–compulsive disorder, and affective or substance-induced psychoses or other conditions such as anemia that may cause psychosis.Pruritus and other skin conditions are most commonly caused by mites, but may also be caused by "grocers itch" from agricultural products, pet-induced dermatitis, caterpillar/moth dermatitis, or exposure to fiberglass. Several drugs, legal or illegal, such as amphetamines, dopamine agonists, opioids, and cocaine may also cause the skin sensations reported. Diseases that must be ruled out in differential diagnosis include hypothyroidism, and kidney or liver disease. Many of these physiological factors, as well as environmental factors such as airborne irritants, are capable of inducing a "crawling" sensation in otherwise healthy individuals; some people become fixated on the sensation and its possible meaning, and this fixation may then develop into DP.
Treatment
As of 2019, there have not been any studies that compare available treatments to placebo. The only treatment that provides a cure, and the most effective treatment, is low doses of antipsychotic medication. Cognitive behavioral therapy (CBT) can also be useful. Risperidone is the treatment of choice. For many years, the treatment of choice was pimozide, but it has a higher side effect profile than the newer antipsychotics. Aripiprazole and ziprasidone are effective but have not been well studied for delusional parasitosis. Olanzapine is also effective. All are used at the lowest possible dosage, and increased gradually until symptoms remit.People with the condition often reject the professional medical diagnosis of delusional parasitosis, and few willingly undergo treatment, despite demonstrable efficacy, making the condition difficult to manage. Reassuring the individual with DP that there is no evidence of infestation is usually ineffective, as the patient may reject that. Because individuals with DP typically see many physicians with different specialties, and feel a sense of isolation and depression, gaining the patients trust, and collaborating with other physicians, are key parts of the treatment approach. Dermatologists may have more success introducing the use of medication as a way to alleviate the distress of itching. Directly confronting individuals about delusions is unhelpful because by definition, the delusions are not likely to change; confrontation of beliefs via CBT is accomplished in those who are open to psychotherapy. A five-phase approach to treatment is outlined by Heller et al. (2013) that seeks to establish rapport and trust between physician and patient.
Prognosis
The average duration of the condition is about three years. The condition leads to social isolation and affects employment. Cure may be achieved with antipsychotics or by treating underlying psychiatric conditions.
Epidemiology
While a rare disorder, delusional parasitosis is the most common of the hypochondriacal psychoses, and more common than other types of delusions such as those associated with body odor or halitosis. It may be undetected because those who have it do not see a psychiatrist because they dont recognize the condition as a delusion. A population-based study in Olmsted County, Minnesota found a prevalence of 27 per 100,000 person-years and an incidence of almost 2 cases per 100,000 person-years. The majority of dermatologists will see at least one person with DP during their career.It is observed twice as often in women than men. The highest incidence occurs in people in their 60s, but there is also a higher occurrence in people in their 30s, associated with substance use. It occurs most often in "socially isolated" women with an average age of 57.Since the early 2000s, a strong internet presence has led to increasing self-diagnosis of Morgellons.
History
Karl-Axel Ekbom, a Swedish neurologist, first described delusional parasitosis as "pre-senile delusion of infestation" in 1937. The common name has changed many times since then. Ekbom originally used the German word dermatozoenwahn, but other countries used the term Ekboms syndrome. That term fell out of favor because it also referred to restless legs syndrome. Other names that referenced "phobia" were rejected because anxiety disorder was not typical of the symptoms. The eponymous Ekboms disease was changed to "delusions of parasitosis" in 1946 in the English literature, when researchers J Wilson and H Miller described a series of cases, and to "delusional infestation" in 2009. The most common name since 2015 has been "delusional parasitosis".Ekboms original was translated to English in 2003; the authors hypothesized that James Harrington (1611–1677) may have been the "first recorded person to suffer from such delusions when he began to imagine that his sweat turned to flies, and sometimes to bees and other insects."
Morgellons
Mary Leitao, the founder of the Morgellons Research Foundation, coined the name Morgellons in 2002, reviving it from a letter written by a physician in the mid-1600s. Leitao and others involved in her foundation (who self-identified as having Morgellons) successfully lobbied members of the U.S. Congress and the U.S. Centers for Disease Control and Prevention (CDC) to investigate the condition in 2006. The CDC published the results of its multi-year study in January 2012. The study found no underlying infectious condition and few disease organisms were present in people with Morgellons; the fibers found were likely cotton, and the condition was "similar to more commonly recognized conditions such as delusional infestation".An active online community has supported the notion that Morgellons is an infectious disease, and propose an association with Lyme disease. Publications "largely from a single group of investigators" describe findings of spirochetes, keratin and collagen in skin samples of a small number of individuals; these findings are contradicted by the much larger studies conducted by the CDC.
Society and culture
Jay Traver (1894–1974), a University of Massachusetts entomologist, was known for "one of the most remarkable mistakes ever published in a scientific entomological journal", after publishing a 1951 account of what she called a mite infestation which was later shown to be incorrect, and that has been described by others as a classic case of delusional parasitosis as evidenced by her own detailed description. Matan Shelomi argues that the historical paper should be retracted because it has misled people about their delusion. He says the paper has done "permanent and lasting damage" to people with delusional parasitosis, "who widely circulate and cite articles such as Travers and other pseudoscientific or false reports" via the internet, making treatment and cure more difficult.Shelomi published another study in 2013 of what he called scientific misconduct when a 2004 article in the Journal of the New York Entomological Society included what he says is photo manipulation of a matchbox specimen to support the claim that individuals with DP are infested with collembola.
See also
Stimulant psychosis
Formication
References
Further reading
Halvorson CR (October 2012). "An approach to the evaluation of delusional infestation". Cutis (Review). 90 (4): E1–E4. PMID 24005827.
Simpson L, Baier M (August 2009). "Disorder or delusion? Living with Morgellons disease". Journal of Psychosocial Nursing and Mental Health Services (Case report and review). 47 (8): 36–41. doi:10.3928/02793695-20090706-03. PMID 19681520. |
Hematometra | Hematometra is a medical condition involving collection or retention of blood in the uterus. It is most commonly caused by an imperforate hymen or a transverse vaginal septum.
Signs and symptoms
Hematometra typically presents as cyclic, cramping pain in the midline of the pelvis or lower abdomen. Patients may also report urinary frequency and urinary retention. Premenopausal women with hematometra often experience abnormal vaginal bleeding, including dysmenorrhea (pain during menstruation) or amenorrhea (lack of menstruation), while postmenopausal women are more likely to be asymptomatic. Due to the accumulation of blood in the uterus, patients may develop low blood pressure or a vasovagal response. When palpated, the uterus will typically feel firm and enlarged.
Pathophysiology
Hematometra develops when the uterus becomes distended with blood secondary to obstruction or atresia of the lower reproductive tract—the uterus, cervix or vagina—which would otherwise provide an outflow for menstrual blood. It is most commonly caused by congenital abnormalities, including imperforate hymen, transverse vaginal septum or vaginal hypoplasia. Other causes are acquired, such as cervical stenosis, intrauterine adhesions, endometrial cancer, and cervical cancer.Additionally, hematometra may develop as a complication of uterine or cervical surgery such as endometrial ablation, where scar tissue in the endometrium can "wall off" sections of endometrial glands and stroma causing blood to accumulate in the uterine cavity. It can also develop after abortion, as well as after childbirth. It can also develop after female genital mutilation.
Diagnosis
Although hematometra can often be diagnosed based purely on the patients history of amenorrhea and cyclic abdominal pain, as well as a palpable pelvic mass on examination, the diagnosis can be confirmed by ultrasound, which will show blood pooled in the uterus and an enlargement of the uterine cavity. A pyelogram or laparoscopy may assist in diagnosing any congenital disorder that is suspected to be the underlying cause of the hematometra.
Management
Hematometra is usually treated by surgical cervical dilation to drain the blood from the uterus. Other treatments target the underlying cause of the hematometra; for example, a hysteroscopy may be required to resect adhesions that have developed following a previous surgery. If the cause of the hematometra is unclear, a biopsy of endometrial tissue can be taken to test for the presence of a neoplasm (cancer). Antibiotics may be given as prophylaxis against the possibility of infection.
See also
Hematocolpos, collection of menstrual blood in the vagina
References
== External links == |
Interstitial pregnancy | An interstitial pregnancy is a uterine but ectopic pregnancy; the pregnancy is located outside the uterine cavity in that part of the fallopian tube that penetrates the muscular layer of the uterus. The term cornual pregnancy is sometimes used as a synonym, but remains ambiguous as it is also applied to indicate the presence of a pregnancy located within the cavity in one of the two upper "horns" of a bicornuate uterus. Interstitial pregnancies have a higher mortality than ectopics in general.
Anatomy
The part of the Fallopian tube that is located in the uterine wall and connects the remainder of the tube to the endometrial cavity is called its "interstitial" part, hence the term "interstitial pregnancy"; it has a length of 1–2 cm and a width of 0.7 cm. Its borders are the opening (ostium) of the tube to the endometrial cavity within the uterus and, laterally, the visible narrow segment of the tube. The area is well supplied by the Sampson artery which is connected to both the uterine and the ovarian arteries. Surrounded by uterine muscle (myometrium) it can expand significantly when it hosts a pregnancy.
Interstitial pregnancies can be confused with angular pregnancies; the latter, however, are located within the endometrial cavity in the corner where the tube connects; typically those pregnancies are viable although a high rate of miscarriage has been reported. A pregnancy located next to the interstitial section laterally is an isthmic tubal pregnancy.
The definition of an ectopic pregnancy is a pregnancy outside the uterine cavity, not outside the uterus, as the interstitial pregnancy is still a uterine pregnancy.
Diagnosis
Early diagnosis is important and today facilitated by the use of sonography and the quantitative human chorionic gonadotropin (hCG) assay. As in other cases of ectopic pregnancy, risk factors are: previous tubal pregnancy, IVF therapy, tubal surgery, and a history of sexual infection.
Typical symptoms of an interstitial pregnancy are the classic signs of ectopic pregnancy, namely abdominal pain and vaginal bleeding. Hemorrhagic shock is found in almost a quarter of patients.; this explains the relatively high mortality rate.
In pregnant patients, sonography is the primary method to make the diagnosis, even when patients have no symptoms. The paucity of myometrium around the gestational sac is diagnostic, while, in contrast, the angular pregnancy has at least 5 mm of myometrium on all of its sides. Ultrasonic criteria for the diagnosis include an empty uterine cavity, a gestational sac separate from the uterine cavity, and a myometrial thinning of less than 5 mm around the gestational sac; typically the interstitial line sign—an echogenic line from the endometrial cavity to the corner next to the gestational mass—is seen. MRI can be used particularly when it is important to distinguish between an interstitial and angular pregnancy.
On average, the gestational age at presentation is about 7–8 weeks. In a 2007 series, 22% of patients presented with rupture and hemorrhagic shock, while a third of the patients were asymptomatic; the remainder had abdominal pain and/or vaginal bleeding. Cases that are not diagnosed until surgery show an asymmetrical bulge in the upper corner of the uterus.
Treatment
Choice of treatment is largely dictated by the clinical situation. A ruptured interstitial pregnancy is a medical emergency that requires an immediate surgical intervention either by laparoscopy or laparotomy to stop the bleeding and remove the pregnancy.Surgical methods to remove the pregnancy include cornual evacuation, incision of the cornua with removal of the pregnancy (cornuostomy), resection of the cornual area or a cornual wedge resection, typically combined with an ipsilateral salpingectomy, and hysterectomy. Because of the vascularity of the interstitial region particularly during pregnancy, blood loss during surgery may be substantial. Postoperatively, patients with conservative surgical therapy are at risk for development of a persistent ectopic pregnancy due to the presence of deeply embedded surviving trophoblastic tissue; thus, monitoring of hCG levels is indicated until they become undetectable.
In patients with an asymptomatic interstitial pregnancy methotrexate has been successfully used, however, this approach may fail and result in cornual rupture of the pregnancy. Selective uterine artery embolization has been successfully performed to treat interstitial pregnancies.
Subsequent pregnancies
Patients with an ectopic pregnancy are generally at higher risk for a recurrence, however, there are no specific data for patients with an interstitial pregnancy. When a new pregnancy is diagnosed it is important to monitor the pregnancy by transvaginal sonography to assure that is it properly located, and that the surgically repaired area remains intact. Cesarean delivery is recommended to avoid uterine rupture during labor.
Epidemiology
Interstitial pregnancies account for 2–4% of all tubal pregnancies, or for 1 in 2,500 to 5,000 live births. About one in fifty women with an interstitial pregnancy dies. Patients with an interstitial pregnancies have a seven-times higher mortality than those with ectopics in general. With the growing use of assisted reproductive technologies, the incidence of interstitial pregnancy is rising.
References
External links
The Ectopic Pregnancy Trust - Information and support for those who have had the condition by a medically overseen and moderated UK based charity, recognised by the National Health Service (UK) Department of Health (UK) and Royal College of Obstetricians and Gynaecologists |
Acroosteolysis | Acroosteolysis is resorption of the distal bony phalanges. Acroosteolysis has two patterns of resorption in adults: diffuse and bandlike.
The diffuse pattern of resorption has a widely diverse differential diagnosis which includes: pyknodysostosis, collagen vascular disease and vasculitis, Raynauds neuropathy, trauma, epidermolysis bullosa, psoriasis, frostbite, sarcoidosis, hypertrophic osteoarthropathy, acromegaly, and advanced leprosy.The bandlike pattern of resorption may be seen with polyvinyl chloride exposure and Hadju-Cheney syndrome.A mnemonic commonly used for acro-osteolysis is PINCHFO.Pyknodysostosis, Psoriasis,
Injury (thermal burn, frostbite),
Neuropathy (diabetes),
Collagen vascular disease (scleroderma, Raynauds),
Hyperparathyroidism,
Familial (Hadju-Cheney, progeria),
Occupational (polyvinyl exposure),
Acroosteolysis may be associated with minimal skin changes or with ischemic skin lesions that may result in digital necrosis.: 665
See also
Nail anatomy
== References == |
Primary lateral sclerosis | Primary lateral sclerosis (PLS) is a very rare neuromuscular disease characterized by progressive muscle weakness in the voluntary muscles. PLS belongs to a group of disorders known as motor neuron diseases. Motor neuron diseases develop when the nerve cells that control voluntary muscle movement degenerate and die, causing weakness in the muscles they control.
PLS only affects upper motor neurons. There is no evidence of the degeneration of spinal motor neurons or muscle wasting (amyotrophy) that occurs in amyotrophic lateral sclerosis (ALS).
Symptoms and signs
Onset of PLS usually occurs spontaneously after age 50 and progresses gradually over a number of years, or even decades. The disorder usually begins in the legs, but it may start in the tongue or the hands. Symptoms may include difficulty with balance, weakness and stiffness in the legs, and clumsiness. Other common symptoms are spasticity (involuntary muscle contraction due to the stretching of muscle, which depends on the velocity of the stretch) in the hands, feet, or legs, foot dragging, and speech and swallowing problems due to involvement of the facial muscles. Breathing may also become compromised in the later stages of the disease, causing those patients who develop ventilatory failure to require noninvasive ventilatory support. Hyperreflexia is another key feature of PLS as seen in patients presenting with the Babinskis sign. Some people present with emotional lability and bladder urgency, and occasionally people with PLS experience mild cognitive changes detectable on neuropsychological testing, particularly on measures of executive function.PLS is not considered hereditary when onset is in adulthood; however, juvenile primary lateral sclerosis (JPLS) has been linked to a mutation in the ALS2 gene which encodes the cell-signalling protein alsin.The issue of whether PLS exists as a different entity from ALS is not clear, as some patients initially diagnosed as having PLS ultimately develop lower motor neuron signs. When this happens it is classed as ALS.
Spasticity
Primary lateral sclerosis (PLS) usually presents with gradual-onset, progressive, lower-extremity stiffness and pain due to muscle spasticity. Onset is often asymmetrical. Although the muscles do not appear to atrophy as in ALS (at least initially), the disabling aspect of PLS is muscle spasticity and cramping, and intense pain when those muscles are stretched, resulting in joint immobility. A normal walking stride may become a tiny step shuffle with related instability and falling.
Cause
Researchers do not fully understand what causes PLS, although it is thought it could be due to a combination of environmental and genetic factors. Studies are being done to evaluate the possible causes, although linking causality can be difficult due to the relatively low number of people who are diagnosed with PLS.Juvenile PLS may be caused by the ALS2 gene, although this condition is very rare.
Diagnosis
There are no specific tests for the diagnosis of PLS. Therefore, the diagnosis occurs as the result of eliminating other possible causes of the symptoms and by an extended observation period.Like ALS, diagnosing PLS is a diagnosis of exclusion, as there is no one test that can confirm a diagnosis of PLS. The Pringle Criteria, proposed by Pringle et al., provides a guideline of nine points that, if confirmed, can suggest a diagnosis of PLS. Due to the fact that a person with ALS may initially present with only upper motor neuron symptoms, indicative of PLS, one key aspect of the Pringle Criteria is requiring a minimum of three years between symptom onset and symptom diagnosis. When these criteria are met, a diagnosis of PLS is highly likely. Other aspects of Pringle Criteria include normal EMG findings, thereby ruling out lower motor neuron involvement that is indicative of ALS, and absence of family history for Hereditary Spastic Paraplegia (HSP) and ALS. Imaging studies to rule out structural or demyelinating lesions may be done as well. Hoffmans sign and Babinski reflex may be present and indicative of upper motor neuron damage.
Treatment
Treatment for individuals with PLS is symptomatic. Baclofen and tizanidine may reduce spasticity. Quinine or phenytoin may decrease cramps. Some patients who do not receive adequate relief from oral treatment may consider intrathecal baclofen (i.e., infusion of medication directly into the cerebrospinal fluid via a surgically placed continuous infusion pump). However, patients are carefully selected for this type of procedure to ensure that they will likely benefit from this invasive procedure.Physical therapy often helps prevent joint immobility. Speech therapy may be useful for those with involvement of the facial muscles. Physiotherapy treatment focuses on reducing muscle tone, maintaining or improving range of motion, increasing strength and coordination, and improving functional mobility. In PLS, stretching is thought to improve flexibility and can also reduce muscle spasticity and cramps.Patients with PLS may find it beneficial to have an evaluation, as well as follow-up visits at multidisciplinary clinics, similar to those available for people with ALS. These multidisciplinary clinics may provide patients with the necessary treatment that they require by having an occupational therapist, physical therapist, speech language pathologist, dietician and nutritionist, all in one site.
Prognosis
Patients can often live with PLS for many years and very often outlive their neurological disease and succumb to some unrelated condition. There is currently no effective cure, and the progression of symptoms varies. Some people may retain the ability to walk without assistance, but others eventually require wheelchairs, canes, or other assistive devices.
References
External links
primary_lateral_sclerosis at NINDS |
Epithelial basement membrane dystrophy | Epithelial basement membrane dystrophy (EBMD) is a disorder of the eye that can cause pain and dryness.
It is sometimes included in the group of corneal dystrophies. It diverges from the formal definition of corneal dystrophy since it is non-familial in most cases. It also has a fluctuating course, while for a typical corneal dystrophy the course is progressive. When it is considered part of this group, it is the most common type of corneal dystrophy.
Signs and symptoms
Patients may complain of severe problems with dry eyes, or with visual obscurations. It can also be asymptomatic, and only discovered because of subtle lines and marks seen during an eye exam.EBMD is a bilateral anterior corneal dystrophy characterized by grayish epithelial fingerprint lines, geographic map-like lines, and dots (or microcysts) on slit-lamp examination. Findings are variable and can change with time. While the disorder is usually asymptomatic, up to 10% of patients may have recurrent corneal erosions, usually beginning after age 30; conversely, 50% of patients presenting with idiopathic recurrent erosions have evidence of this dystrophy.
Pathophysiology
In some families autosomal dominant inheritance and point mutations in the TGFBI gene encoding keratoepithelin have been identified, but according to the International Committee for Classification of Corneal Diseases (IC3D) the available data still does not merit a confident inclusion of EBMD in the group of corneal dystrophies. In view of this, the more accurate designation of the disease is possibly not dystrophy but corneal degeneration.The main pathological feature of the disease is thickened, multilaminar and disfigured basement membrane of corneal epithelium. The change in the structure affects the epithelium, some cells of which may become entrapped in the rugged membrane and fail to migrate to the surface where they should undergo desquamation.
Treatment
Phototherapeutic keratectomy (PTK) done by an ophthalmologist can restore and preserve useful visual function for a significant period of time in patients with anterior corneal dystrophies including EBMD.
See also
Corneal dystrophy
== References == |
Visceral leishmaniasis | Visceral leishmaniasis (VL), also known as kala-azar (Hindi: kālā āzār, "black sickness") or "black fever", is the most severe form of leishmaniasis and, without proper diagnosis and treatment, is associated with high fatality. Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania.
The parasite migrates to the internal organs such as the liver, spleen (hence "visceral"), and bone marrow, and, if left untreated, will almost always result in the death of the host. Signs and symptoms include fever, weight loss, fatigue, anemia, and substantial swelling of the liver and spleen. Of particular concern, according to the World Health Organization (WHO), is the emerging problem of HIV/VL co-infection.VL is the second-largest parasitic killer in the world (after malaria), responsible for an estimated 20,000 to 30,000 deaths each year worldwide.Upendranath Brahmachari synthesised urea stibamine (carbostibamide) in 1922 and determined that it was an effective substitute for the other antimony-containing compounds in the treatment of VL caused by Leishmania donovani.
Signs and symptoms
When people develop visceral leishmaniasis, the most typical symptoms are fever and the enlargement of the spleen, with enlargement of the liver sometimes being seen as well. The blackening of the skin that gave the disease its common name in India does not appear in most strains of the disease, and the other symptoms are very easy to mistake for those of malaria. Misdiagnosis is dangerous, as without proper treatment the mortality rate for kala-azar is close to 100%. L. donovani itself is not usually the direct cause of death in people with kala-azar, however. Pneumonia, tuberculosis, and dysentery are omnipresent in the immuno-depressed regions where leishmaniasis thrives, and, as with AIDS, it is these opportunistic infections that are more likely to kill, flaring up in a host whose immune system has been weakened by the L. donovani infection. Progress of the disease is extremely variable, taking anywhere from one to twenty weeks, but a typical duration for the Sudanese strain of the disease is narrower, between twelve and sixteen weeks.Even with recovery, kala-azar does not always leave its hosts unmarked. Some time after successful treatment—generally a few months with African kala-azar, or as much as several years with the Indian strain—a secondary form of the disease may set in, called post kala-azar dermal leishmaniasis, or PKDL. This condition manifests first as small, measle-like skin lesions on the face, which gradually increase in size and spread over the body. Eventually the lesions may coalesce to form disfiguring, swollen structures resembling leprosy, and occasionally causing blindness if they spread to the eyes. (This disease is not the same as cutaneous leishmaniasis, a milder disease caused by another protozoan of the Leishmania genus which also causes skin lesions.)
Cause
Two species of Leishmania are known to give rise to the visceral form of the disease. The species commonly found in East Africa and the Indian subcontinent is L. donovani and the species found in Europe, North Africa, and Latin America is L. infantum, also known as L. chagasi.The insect vectors are species of sandfly of the genus Phlebotomus in the Old World, and of Lutzomyia in the New World. Sandflies are tiny flies, measuring 3–6 mm long by 1.5–3 mm in diameter, and are found in tropical or temperate regions throughout the world. The sandfly species Lutzomyia longipalpis is the primary vector of this disease. The larvae grow in warm, moist organic matter (such as old trees, house walls, or waste) making them hard to eradicate.Visceral Leishmaniasis/kala-azar samples from India revealed the presence of not only the primary causative protozoan parasite, i.e. Leishmania donovani (LD) but also co-infection with another protozoan member called Leptomonas seymouri (LS). The latter parasite (LS) further contained a RNA virus known as Leptomonas seymouri narna-like virus 1 (Lepsey NLV1). So, it appears that a great majority of kala-azar patients in the Indian subcontinent are exposed to a RNA virus in LS, the co-infecting parasite with LD i.e. the "LD-LS-Lepsey NLV1 triple pathogen" phenomenon.
Life cycle
The life cycle of Leishmania is completed in two hosts, humans and sandflies. The adult female sandfly is a bloodsucker, usually feeding at night on sleeping prey. When the fly bites an individual infected with Leishmania, the pathogen is ingested along with the preys blood. The protozoan is in the smaller of its two forms, called an amastigote, which is round, non-motile, and only 3–7 micrometers in diameter. Inside the stomach of the sandfly, the amastigotes quickly transform into elongated and motile forms called the promastigotes. Promastigote is spindle-shaped, triple the size of the amastigote, and has a single flagellum that allows mobility. The promastigotes live extracellularly in the alimentary canal, reproducing asexually, then migrate to the proximal end of the gut where they become poised for a regurgitational transmission. As the fly bites, the promastigotes are released from the proboscis and introduced locally at the bite site.Once inside the human host, promastigotes invade macrophages. Inside the cells they transform back into the smaller amastigote form. The amastigotes replicate in the most hostile part of the macrophage cell, inside the phagolysosome, whose normal defensive response they are able to prevent. After repeated multiplication, they break down their host cell by sheer pressure of mass, but there is some recent speculation that they are able to leave the cell by triggering the exocytosis response of the macrophage. The daughter cells protozoans then migrate to fresh cells or through the bloodstream to find new hosts. In this way the infection is progressive, spreading to the hosts mononuclear phagocyte system, particularly the spleen and liver. The free amastigotes in peripheral tissues are then ingested by sandfly to enter another cycle.
Regulatory T and B cells
The cell-mediated immunity (CMI) that kills Leishmania also produces inflammation. If the inflammation is excessive, it can cause tissue damage. The role of regulatory T and regulatory B cells is to suppress CMI enough to prevent tissue damage. However, an excessive regulatory response can prevent clearance of Leishmania and could explain the anergy of VL, poor response to drug treatment, development of PKDL, and relapses. A role for regulatory cells in VL has long been suspected. A variety of regulatory T and B cells have been implicated in VL, including Type 1 T helper cells that secrete IL-10 in addition to IFN-γ, natural T reg, Tr1, CD8+ T reg, and B reg. All of these lymphocytes act, at least in part, by secreting IL-10 and other suppressive cytokines.CD4+ T regs are present at increased frequency in the bone marrow of VL patients, are one source of IL-10, and proliferate in response to Leishmania antigen. Levels of FoxP3 mRNA were also up-regulated in lesional tissue from PKDL patients. However, T regs are not elevated in spleen cells from VL patients nor does depletion of T regs increase Leishmania antigen specific IFN-γ secretion The highest levels of IL-10 mRNA in spleen cells is in CD8+ and other non-FoxP3+ T cells. White blood cell CD8+ T cells from VL patients have elevated IL-10 levels. There is a 9.6 fold increase in IL-10 expressing CD8+ T cells among PBMC lymphocytes from PKDL patients. In the one study of T cell clones from VL patients, the clones isolated from VL PBMC were 100% CD8+. When mixed with self PBMC one or three years after successful treatment the CD8+ T cells decreased Leishmania antigen specific proliferation and IFN-γ secretion and increased IL-10 secretion. Depletion of CD8+ T cells from VL PBMC stopped endogenous IL-10 secretion but increased Leishmania antigen specific IL-10 secretion, suggesting that CD8+ regulatory T cells are responsible for endogenous IL-10 secretion. CD4+ clones could only be isolated from VL PBMC after CD8+ T cell depletion. The CD4+ clones had little effect on IL-10 secretion but decreased IFN-γ secretion when mixed with self PBMC collected after successful treatment.Regulatory B cells are known to favor development of regulatory T cells and suppress development of Type 1 T helper cells by producing IL-10 and other down-regulatory cytokines. IL-10 levels are elevated in B cells from VL PBMC. A study of dogs with naturally acquired VL showed that the percentage of regulatory B cells increased three-fold during VL. Depletion of B cells increased CD4+ T cell proliferation and IFN-γ secretion but decreased IL-10 secretion. Blocking IL-10 or programmed cell death receptors on B cells increased Leishmania antigen specific T cell proliferation and IFN-γ secretion. Co-culture of T cells with B cells decreased the percentage of CD4+ T cell proliferation and IFN-γ secretion four-fold.
Diagnosis
The gold standard for diagnosis is visualization of the amastigotes in splenic aspirate or bone marrow aspirate. This is a technically challenging procedure that is frequently unavailable in areas of the world where visceral leishmaniasis is endemic.Serological testing is much more frequently used in areas where leishmaniasis is endemic. A 2014 Cochrane review evaluated different rapid diagnostic tests. One of them (the rK39 immunochromatographic test) gave correct, positive results in 92% of the people with visceral leishmaniasis and it gave correct, negative results in 92% of the people who did not have the disease. A second rapid test (called latex agglutination test) gave correct, positive results in 64% of the people with the disease and it gave correct, negative results in 93% of the people without the disease. Other types of tests have not been studied thoroughly enough to ascertain their efficacy.The K39 dipstick test is easy to perform, and village health workers can be easily trained to use it. The kit may be stored at ambient temperature and no additional equipment needs to be carried to remote areas. The DAT anti-leishmania antigen test, standard within MSF, is much more cumbersome to use and appears not to have any advantages over the K39 test.There are a number of problems with serological testing: in highly endemic areas, not everyone who becomes infected will actually develop clinical disease or require treatment. Indeed, up to 32% of the healthy population may test positive, but not require treatment. Conversely, because serological tests look for an immune response and not for the organism itself, the test does not become negative after the patient is cured, it cannot be used as a check for cure, or to check for re-infection or relapse. Likewise, patients with abnormal immune systems (e.g., HIV infection) will have false-negative tests.Other tests being developed include detects erythrosalicylic acid.
Prevention
As of 2018, there are no vaccines or preventive drugs for visceral leishmaniasis, but vaccines are in development. The most effective method to prevent infection is to protect from sand fly bites. To decrease the risk of being bitten, these precautionary measures are suggested:
Outdoors:1. Avoid outdoor activities, especially from dusk to dawn, when sand flies generally are the most active.
2. When outdoors (or in unprotected quarters), minimize the amount of exposed (uncovered) skin to the extent that is tolerable in the climate. Wear long-sleeved shirts, long pants, and socks; and tuck your shirt into your pants.
3. Apply insect repellent to exposed skin and under the ends of sleeves and pant legs. Follow the instructions on the label of the repellent. The most effective repellents generally are those that contain the chemical DEET (N,N-diethylmetatoluamide).
Indoors:1. Stay in well-screened or air-conditioned areas.
2. Keep in mind that sand flies are much smaller than mosquitoes and therefore can get through smaller holes.
3. Spray living/sleeping areas with an insecticide to kill insects.
4. If you are not sleeping in a well-screened or air-conditioned area, use a bed net and tuck it under your mattress. If possible, use a bed net that has been soaked in or sprayed with a pyrethroid-containing insecticide. The same treatment can be applied to screens, curtains, sheets, and clothing (clothing should be retreated after five washings)."
Treatments
As with many diseases in developing nations, (including trypanosomiasis and malaria) effective and affordable chemotherapy is sorely lacking and parasites or insect vectors are becoming increasingly resistant to existing anti-parasite drugs. Possibly due to the lack of financial return, new drugs are slow to emerge and much of the basic research into potential drug targets takes place in universities, funded by charitable organizations. Product Development Partnership, Drugs for Neglected Diseases initiative works on the development of new treatments (combination treatments and new chemical entities) for visceral leishmaniasis.The traditional treatment is with pentavalent antimonials such as sodium stibogluconate and meglumine antimoniate. Resistance is now common in India, and rates of resistance have been shown to be as high as 60% in parts of Bihar, India.The treatment of choice for visceral leishmaniasis acquired in India is now amphotericin B in its various liposomal preparations. In East Africa, the WHO recommended treatment is SSG&PM (sodium stibogluconate and paromomycin) developed by Drugs for Neglected Diseases initiative (DNDi) in 2010.Miltefosine is the first oral treatment for this disease. The cure rate of miltefosine in Phase III clinical trials is 95%; Studies in Ethiopia show that is also effective in Africa. In HIV immunosuppressed people which are coinfected with leishmaniasis it has shown that even in resistant cases 2/3 of the people responded to this new treatment.
Miltefosine has received approval by the Indian regulatory authorities in 2002, in Germany in 2004 and in U.S.A. in 2014. It is now registered in many countries.The drug is generally better tolerated than other drugs. Main side effects are gastrointestinal disturbance in the first or second day of treatment (a course of treatment is 28 days) which does not affect the efficacy. Because it is available as an oral formulation, the expense and inconvenience of hospitalization is avoided, and outpatient distribution of the drug becomes an option, making miltefosine a drug of choice. However, there are some important disadvantages: 1) there is evidence of reduced efficacy after a decade of use 2) it is teratogenic and cannot be used in women of child-bearing age without anticonception during and for 4 months after treatment.Incomplete treatment has been cited as a major reason of death from visceral leishmaniasis.The nonprofit Institute for OneWorld Health has adopted the broad spectrum antibiotic paromomycin for use in treating VL; its antileishmanial properties were first identified in the 1980s. A treatment with paromomycin costs about US$15. The drug had originally been identified in the 1960s. The Indian government approved paromomycin for sale and use in August 2006.
Prognosis
Protective immunity
Immunity to Leishmania is determined by the interplay of white blood cells, cytokines, immune complexes, and genetic and environmental factors.
Protective immunity develops either after successful treatment of VL (cured) or after asymptomatic infections that resolve without development of VL (asymptomatic). Both types of immunity are characterized by cell-mediated immunity (CMI), including skin test positivity, proliferation, and interleukin 2 (IL-2), interferon gamma (IFN-γ), and interleukin 12 (IL-12) secretion by peripheral blood mononuclear cells (PBMC) in response to Leishmania antigens. T cells isolated from both cured and asymptomatic PBMC activate autologous macrophages to kill intracellular amastigotes. IFN-γ activates macrophages to kill intracellular parasites so its role in VL has been studied extensively and IFN-γ production is often used as a marker of protective immunity. Cured PBMC generally secrete less IFN-γ and more interleukin 10 (IL-10) in response to Leishmania antigens than asymptomatic PBMC. IL-12 is important in the development and maintenance of Type 1 T helper cell responses and protective immunity so its role in VL has also been studied. Addition of IL-12 to some VL PBMC increases proliferation and IFN-γ secretion in response to Leishmania antigens and anti-IL-12 inhibits proliferation and IFN-γ secretion by some cured PBMC. Other cytokines also appear to be important in immunity to Leishmania but their roles are not as well characterized.Leishmania antigen stimulation of PBMC from cured patients show a mixed T helper cell and regulatory T cell response. Both CD4+ and CD8+ T cells contributed to IFN-γ production. Studies of Leishmania antigen specific T cell clones from cured patient PBMC confirm that cured patients have a mixed T cell response that involves both CD4+ helper T cells and CD4+ and CD8+ regulatory T cells. Two studies of asymptomatic T cell clones show that most have Type 1 profiles and secrete more IFN-γ than T cell clones from cured patients. Neither study revealed the presence of Type 2 or regulatory T cells. Some clones secreted soluble factors that caused the death of CD8+ regulatory T cells but not CD4+ T cells from VL patients, which might explain the strong protective immunity of asymptomatic patients.
Non-protective immunity
VL patients are unable to clear their infections because they lack CMI. This anergy may be limited to Leishmania antigens or extend to mitogens and other antigens as the disease progresses. In addition to skin test negativity, VL patient PBMC do not proliferate or secrete IL-2 or IFN-γ in response to Leishmania antigens. Memory T cells may be depleted in VL patient PBMC. Since IL-10 is known to suppress innate and acquired immunity and prevent IFN-γ from activating macrophages, its role in VL has been studied extensively and elevated IL-10 production is often used as a marker of non-protective immunity in VL. Elevated levels of IL-10 in the plasma, infected tissues, and PBMC of VL patients accompany the anergy of VL. PKDL patients also have elevated IL-10 levels. VL patients with the highest IL-10 levels are more likely to be unresponsive to treatment and progress to PKDL. PBMC secretion of IL-10 without the addition of Leishmania antigen (endogenous) is inversely correlated with antigen specific IFN-γ secretion but Leishmania antigen specific IL-10 and IFN-γ secretion are not correlated, suggesting that endogenous secretion is more important in pathology. Addition of anti-IL-10 increases proliferation and IFN-γ secretion by PBMC from some patients. Both CD4+ and CD8+ T cells have been shown to contribute to IL-10 secretion by VL PBMC. The high level of immune complexes characteristic of VL have also been shown to increase IL-10 levels.
Epidemiology
More than 90% of the global burden of visceral leishmaniasis (VL) was contributed by seven countries in 2015: Brazil, Ethiopia, India, Kenya, Somalia, South Sudan and Sudan. In India, more than 70% of VL cases are reported from the state of Bihar. North Bihar, India (including Araria, Purnea, and Kishanganj) is the endemic zone of this disease. The disease is endemic in more than 60 countries. In Iran this includes Ardabil, Fars, and North Khorasan.However, while the diseases geographical range is broad, it is not continuous. The disease clusters around areas of drought, famine, and high population density. In Africa, this has meant a knot of infection centers mostly in South Sudan, Sudan, Ethiopia, Kenya, and Somalia. Living conditions here have changed very little in the past century, and the people are not normally very mobile. Parts of South Sudan, in particular the Upper Nile region, are almost totally cut off from the rest of the country, and most people tend to remain at their place of birth although there have been huge population movements due to the civil war, leading to severe epidemics.
History
Kala-azar first came to the attention of Western doctors in 1824 in Jessore, India (now Bangladesh), where it was initially thought to be a form of malaria. Assam gave kala-azar one of its common names, Assam fever. Another common name, kala-azar (Hindustani: काला आज़ार (Devanagari) کالا آزار (Nastaleeq) kālā āzār), is derived from kala which means black in Sanskrit, as well as in the languages descended from it, including Assamese, Hindi and Urdu; the word azar means Fever in Persian and Hindustani; as such the disease is named for the darkening of the skin on the extremities and abdomen that is a symptom of the Indian form of the disease. The agent of the disease was also first isolated in India by Scottish doctor William Leishman (who observed the parasite in spleen smears of a soldier who died of the disease in Dumdum, Calcutta, India - hence the name dumdum fever) and Irish physician Charles Donovan, working independently of each other. As they published their discovery almost simultaneously, the species was named for both of them—Leishmania donovani.
Today, the name kala-azar is used interchangeably with the scientific name visceral leishmaniasis for the most acute form of the disease caused by L. donovani. The disease is endemic in West Bengal, where it was first discovered, but is seen at its most deadly in north and east Africa. It can also be found throughout the Arab world and southern Europe (where the causative organism is L. infantum), and a slightly different strain of the pathogen, L. chagasi, is responsible for leishmaniasis in the new world. Several species of canines serve as reservoir hosts of L. infantum (chagasi).Contemporary life has made itself felt even here, however—not as "progress" but in the form of the many small wars of Africas post-colonial era. In the Sudan, where civil war has been continuous since 1983, the violence has been concentrated in the more populated south, and kala-azar was concentrated there too. But the wars have driven a steady stream of refugees out of the region, and these traveled either across the southern border or into the remoter western part of the country called the Upper Nile, where both war and the disease that went with it had not yet penetrated.These refugees, moving at foot-speed, carried the disease with them, and when it arrived it hit the Upper Nile with a force comparable to smallpox hitting the American Indians. The isolated people of the Upper Nile had no access to medicine or education about the new disease among them. Worse, their immune systems were defenseless against this new pathogen, foreign to them though it came only from another part of their own country. One village at the center of the epidemic, Duar, was left with four survivors out of a population of a thousand, and from the late eighties to the mid-nineties a total of 100,000 died from the sickness in that region alone. In the words of Jill Seaman, the doctor who led relief efforts in the Upper Nile for the French organization Médecins Sans Frontières, "Where else in the world could 50% of a population die without anyone knowing?" Due to the South Sudanese Civil War, kala-azar has spread rapidly among the population.
The Indian medical practitioner Upendra Nath Brahmachari was nominated for the Nobel Prize in Physiology or Medicine in 1929 for his discovery of ureastibamine (an antimonial compound for the treatment of kala-azar) and a new disease, post kala-azar dermal leishmaniasis. Brahmacharis cure for visceral leishmaniasis was the urea salt of para-amino-phenyl stibnic acid which he called Urea Stibamine.During the nineteenth century, kala-azar was discovered near moving bodies of water in southeast Asia. Dr. Jean Dow and Dr. William McClure, are credited with finding the cure for the disease in China. Largely uncredited for her contribution, Dr. Jean Dow was one of the first to isolate the microorganism in China and conduct clinical studies on its origin. This work continued under Ernest Struthers and Lionel Napier at the School of Tropical Medicine at Calcutta to discover that kala-azar was transmitted by sandflies.
Research
Combination drug therapies are currently under investigation, particularly by the Drugs for Neglected Diseases initiative (DNDi). Combination therapies allow for the use of existing drugs in combination, each in lower doses, which helps to decrease the incidence of severe side effects and drug toxicity, as well as the risk for development of resistance against the drugs; they have been shown to be cost-effective strategies.
Comparative homology modelling of the enzyme Hypoxanthine-guanine phosphoribosyl transferase (HGPRT; EC 2.4.2.8) in L. donovani suggest that among all of the computationally screened compounds, pentamidine, 1,3-dinitroadamantane, acyclovir and analogs of acyclovir had higher binding affinities than the real substrate (guanosine monophosphate).DNDi has a number of compounds in preclinical and phase 1 development, but no novel drugs are expected in the next 5 years. In the meantime, new combination therapies, and well as improvements to existing drugs targets, are under development. Single-dosage administrations of liposomal amphotericin B have been shown to be effective, and oral formulations are currently under development to increase access and facilitate distribution of the efficacious drug in the field.A 2018 study published details of a new potential preclinical drug candidate for the treatment for visceral leishmaniasis with an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold.There is no good vaccine candidate which prevents kala azar. A 2019 paper described designing an immunologic adjuvant which would make a VL vaccine more effective.
References
== External links == |
Hematidrosis | Hematidrosis, also called blood sweat, is a very rare condition in which a human sweats blood. The term is from Ancient Greek haîma/haímatos (αἷμα/αἵματος), meaning blood, and hīdrṓs (ἱδρώς), meaning sweat.
Signs and symptoms
Blood usually oozes from the forehead, nails, umbilicus, and other skin surfaces. In addition, oozing from mucocutaneous surfaces causing nosebleeds, bloodstained tears, and vicarious menstruation are common. The episodes may be preceded by intense headache and abdominal pain and are usually self-limiting. In some conditions, the secreted fluid is more dilute and appears to be blood-tinged, while others may have darker bright red secretions resembling blood.While the extent of blood loss generally is minimal, hematidrosis also results in the skin becoming extremely tender and fragile.
Causes
Hematidrosis is a condition in which capillary blood vessels that feed the sweat glands rupture, causing them to exude blood, occurring under conditions of extreme physical or emotional stress. Severe mental anxiety activates the sympathetic nervous system to invoke the stress- Fight-or-flight response to such a degree as to cause hemorrhage of the vessels supplying the sweat glands. It has been suggested that acute fear and extreme stress can cause hematidrosis.
Diagnosis
Investigation such as platelets count, platelet aggregation test, coagulation profile and skin biopsy reveal no abnormalities and direct light microscopy of fluid demonstrates presence of normal red blood cells. Investigations also failed to show any vasculitis or skin appendages (i.e. sweat glands, sebaceous glands and hair follicles) abnormalities.A 2015 case study investigated hematidrosis with a patient who has epilepsy.
Treatment
Effect on the body is weakness and mild to moderate dehydration from the severe anxiety and both blood and sweat loss.The condition is very rare but there are reports in medical literature of successful treatment with beta blockers (propranolol 10 mg) with significant reduction in the frequency of spontaneous blood oozing. The successful use of beta blockers supports the theory that the condition is induced by stress and anxiety yet this etiology is not established yet as the high prevalence of stress and anxiety in the modern era did not change the incidence of this extremely rare disease, suggesting that other co-abnormality also play a key role in this disease. Atropine sulfate transdermal patches have also been used successfully.Favorable results with psychiatric counselling to reduce stress highlight the relationship between psychogenic causes and hematohidrosis.
Instances
Dermatological research notes the presence of hematidrosis in people awaiting execution. It has also been proposed as a possible explanation for Jesus agony in the garden of Gethsemane (Luke 22:44) and for claims associated with stigmata.Leonardo da Vinci described a soldier who sweated blood before battle. The phenomenon has also been observed in individuals in fear for their lives; a case occurred during the London blitz, and a case of fear of a storm while sailing, etc.
See also
Haemolacria – blood in tears
Hyperhidrosis
== References == |
Congenital generalized lipodystrophy | Congenital generalized lipodystrophy (also known as Berardinelli–Seip lipodystrophy) is an extremely rare autosomal recessive condition, characterized by an extreme scarcity of fat in the subcutaneous tissues. It is a type of lipodystophy disorder where the magnitude of fat loss determines the severity of metabolic complications. Only 250 cases of the condition have been reported, and it is estimated that it occurs in 1 in 10 million people worldwide.
Presentation
Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder which manifests with insulin resistance, absence of subcutaneous fat and muscular hypertrophy. Homozygous or compound heterozygous mutations in four genes are associated with the four subtypes of CGL. The condition appears in early childhood with accelerated linear growth, quick aging of bones, and a large appetite. As the child grows up, acanthosis nigricans (hyperpigmentation and thickening of skin) will begin to present itself throughout the body – mainly in the neck, trunk, and groin. The disorder also has characteristic features like hepatomegaly or an enlarged liver which arises from fatty liver and may lead to cirrhosis, muscle hypertrophy, lack of adipose tissue, splenomegaly, hirsutism (excessive hairiness) and hypertriglyceridemia. Fatty liver and muscle hypertrophy arise from the fact that lipids are instead stored in these areas; whereas in a healthy individual, lipids are distributed more uniformly throughout the body subcutaneously. The absence of adipose tissue where they normally occur causes the body to store fat in the remaining areas. Common cardiovascular problems related to this syndrome are cardiac hypertrophy and arterial hypertension (high blood pressure). This disorder can also cause metabolic syndrome. Most with the disorder also have a prominent umbilicus or umbilical hernia. Commonly, patients will also have acromegaly with enlargement of the hands, feet, and jaw. After puberty, additional symptoms can develop. In women, clitoromegaly and polycystic ovary syndrome can develop. This impairs fertility for women, and only a few documented cases of successful pregnancies in women with CGL exist. However, the fertility of men with the disorder is unaffected.
Type 1 vs Type 2 Differences
There are differences in how Type 1 vs Type 2 patients are affected by the disease. In type 1 patients, they still have mechanical adipose tissue, but type 2 patients do not have any adipose tissue, including mechanical. In type 2 patients, there is a greater likelihood of psychomotor retardation and intellectual impairment.
Genetics
Mechanism
Type 1
In individuals with Type 1 CGL, the disorder is caused by a mutation at the AGPAT2 gene encoding 1-acylglycerol-3-phosphate O-acyltransferase 2 and located at 9q34.3. This enzyme catalyzes the acylation of lysophosphatidic acid to form phosphatidic acid, which is important in the biosynthesis of fats. This enzyme is highly expressed in adipose tissue, so it can be concluded that when the enzyme is defective in CGL, lipids cannot be stored in the adipose tissue.
Type 2
In those who have Type 2 CGL, a mutation in the BSCL2 gene encoding the Seipin protein and located at 11q13. This gene encodes a protein, Seipin, whose function is unknown. Expression of mRNA for the seipin protein is high in the brain, yet low in adipose tissues. Additionally, patients which have mutations in this protein have a higher incidence of mental retardation and lack mechanically active adipose tissue, which is present in those with AGPAT2 mutations.
Type 3
Type 3 CGL involves a mutation in the CAV1 gene. This gene codes for the Caveolin protein, which is a scaffolding membrane protein. This protein plays a role in lipid regulation. High levels of Cav1 are normally expressed in adipocytes. Thus, when the CAV1 gene mutates the adipocytes do not have Cav1 and are unable to properly regulate lipid levels.
Type 4
A mutation in the PTRF gene causes Type 4 CGL. This gene codes for a protein called polymerase I and transcript release factor. One of the roles the PTRF product has it to stabilize and aid in formation of caveolae. Thus, the mechanism is similar to Type 3, in that the caveolae are unable to properly form and carry out their role in lipid regulation in both. Types 3 and 4 are two different mutations but they share a common defective pathway.
Diagnosis
Medical diagnosis of CGL can be made after observing the physical symptoms of the disease: lipoatrophy (loss of fat tissues) affecting the trunk, limbs, and face; hepatomegaly; acromegaly; insulin resistance; and high serum levels of triglycerides. Genetic testing can also confirm the disease, as mutations in the AGPAT2 gene is indicative of CGL1, a mutation in the BSCL2 gene is indicative of CGL2, and mutations in the CAV1 and PTRF genes are indicative of CGL3 and CGL4 respectively. Physical diagnosis of CGL is easier, as CGL patients are recognizable from birth, due to their extreme muscular appearance, which is caused by the absence of subcutaneous fat.CGL3 patients have serum creatine kinase concentrations much higher than normal (2.5 to 10 times the normal limit). This can be used to diagnose type 3 patients and differentiate them from CGL 1 and 2 without mapping their genes. Additionally, CGL3 patients have low muscle tone when compared with other CGL patients.
Treatment
Metformin is the main drug used for treatment, as it is normally used for patients with hyperglycemia. Metformin reduces appetite and improves symptoms of hepatic steatosis and polycystic ovary syndrome. Leptin can also be used to reverse insulin resistance and hepatic steatosis, to cause reduced food intake, and decrease blood glucose levels.
Diet
CGL patients have to maintain a strict diet for life, as their excess appetite will cause them to overeat. Carbohydrate intake should be restricted in these patients. To avoid chylomicronemia, CGL patients with hypertriglyceridemia need to have a diet very low in fat. CGL patients also need to avoid total proteins, trans fats, and eat high amounts of soluble fiber to avoid getting high levels of cholesterol in the blood.
History
Congenital Generalized Lipodystrophy, also known as Berardinelli–Seip lipodystrophy was first described in 1954 by Berardinelli and later by Seip in 1959. The gene for type 1 CGL was identified as AGPAT2 at chromosome 9q34, and later the gene for type 2 CGL was identified as BSCL2 at chromosome 11q13. More recently, type 3 CGL was identified as a separate type of CGL, which was identified as a mutation in the CAV1 gene. Then, a separate type 4 CGL was identified as a mutation in the PTRF gene.
See also
Lipodystrophy
Familial partial lipodystrophy
List of cutaneous conditions
Skin lesion
Seipin
References
Further reading
GeneReviews/NCBI/NIH/UW entry on Berardinelli-Seip Congenital Lipodystrophy
== External links == |
Camptodactyly | Camptodactyly is a medical condition that causes one or more fingers or toes to be permanently bent. It involves fixed flexion deformity of the proximal interphalangeal joints.
Camptodactyly can be caused by a genetic disorder. In that case, it is an autosomal dominant trait that is known for its incomplete genetic expressivity. This means that when a person has the genes for it, the condition may appear in both hands, one, or neither. A linkage scan proposed that the chromosomal locus of camptodactyly was 3q11.2-q13.12.
Causes
The specific cause of camptodactyly remains unknown, but there are a few deficiencies that lead to the condition. A deficient lumbrical muscle controlling the flexion of the fingers, and abnormalities of the flexor and extensor tendons.A number of congenital syndromes may also cause camptodactyly:
Jacobsen syndrome
Beals syndrome
Blau syndrome
Freeman–Sheldon syndrome
Cerebrohepatorenal syndrome
Weaver syndrome
Christian syndrome 1
Gordon syndrome
Jacobs arthropathy-camptodactyly syndrome
Lenz microphthalmia syndrome
Marshall–Smith–Weaver syndrome
Oculo-dento-digital syndrome
Tel Hashomer camptodactyly syndrome
Toriello–Carey syndrome
Trisomy 13
Stuve–Wiedemann syndrome
Loeys–Dietz syndrome
Fetal alcohol syndrome
Fryns syndrome
Marfan syndrome
Carnio-carpo-tarsal dysthropy
Genetics
The pattern of inheritance is determined by the phenotypic expression of a gene—which is called expressivity. Camptodactyly can be passed on through generations in various levels of phenotypic expression, which include both or only one hand. This means that the genetic expressivity is incomplete. It can be inherited from either parent.
In most of its cases, camptodactyly occurs sporadically, but it has been found in several studies that it is inherited as an autosomal dominant condition.
Treatment
If a contracture is less than 30 degrees, it may not interfere with normal functioning. The common treatment is splinting and occupational therapy. Surgery is the last option for most cases as the result may not be satisfactory.
Etymology
The name is derived from the ancient Greek words kamptos (bent) and daktylos (finger).
See also
Clinodactyly
References
External links
Media related to camptodactyly at Wikimedia Commons
The dictionary definition of camptodactyly at Wiktionary |
Acquired idiopathic generalized anhidrosis | Acquired idiopathic generalized anhidrosis (AIGA) is characterized by generalized absence of sweating without other autonomic and neurologic dysfunction.AIGA is classified into 3 subgroups: idiopathic pure sudomotor failure (IPSF), sweat gland failure (SGF), and sudomotor neuropathy, with each subgroup presenting a different pathogenesis.
Diagnosis
Quantitative sudomotor axon reflex test and microneurography are used in the diagnosis of AIGA. However, these refined methods are mostly used for research purposes and not generally available.Skin biopsy analysis may play a crucial role in the identification of AIGA subgroups.
See also
Hypohidrosis
References
== External links == |
Meacham syndrome | Meacham syndrome is a rare genetic disorder which is characterized by lung, diaphragmatic and genitourinary anomalies.
Signs and symptoms
Often people with this condition are born with both underdeveloped lungs and a herniated diaphragm.
Urinary symptoms include a horseshoe kidney
Genital symptoms are different according to the biological sex of the baby, genetic males (46,XX) usually have pseudohermaphroditism, ambiguous genitalia, and perineal hypospadias. Genetic females (46,XX) often have septate uterus and duplication of the vagina. In some cases, karyotype is needed to know the biological sex of the baby.Additional symptoms include neoplasm, cryptorchidism, ventricular septal defect, atrial septal defect, hernia, patent ductus arteriosus, Tetralogy of Fallot, and penile hypoplasia.
Causes
This condition is caused by an autosomal dominant missense mutation in the WT1 gene, in chromosome 11. This was found through two half-siblings reported by Suri et al.
Epidemiology
According to OMIM, only 12 cases have been described in medical literature.
== References == |
Dacryocystitis | Dacryocystitis is an infection of the lacrimal sac, secondary to obstruction of the nasolacrimal duct at the junction of lacrimal sac. The term derives from the Greek dákryon (tear), cysta (sac), and -itis (inflammation). It causes pain, redness, and swelling over the inner aspect of the lower eyelid and epiphora. When nasolacrimal duct obstruction is secondary to a congenital barrier it is referred to as dacryocystocele. It is most commonly caused by Staphylococcus aureus and Streptococcus pneumoniae. The most common complication is corneal ulceration, frequently in association with S. pneumoniae. The mainstays of treatment are oral antibiotics, warm compresses, and relief of nasolacrimal duct obstruction by dacryocystorhinostomy.
Signs and symptoms
Pain, swelling, redness over the lacrimal sac at medial canthus
Tearing, crusting, fever
Digital pressure over the lacrimal sac may extrude pus through the punctum
In chronic cases, tearing may be the only symptom
Pathophysiology
A variety of causes may lead to dacryocystitis. Most notably, obstruction of the nasolacrimal duct leads to stasis of the nasolacrimal fluid, which predisposes to infection. Staphylococcus aureus is a common bacterial pathogen causing infectious dacryocystitis. Sometimes, especially in women, stones may develop in the lacrimal gland, causing recurrent bouts of dacryocystitis; this condition is called "acute dacryocystic retention syndrome."
Also due to pneumococcus, infection due to surrounding structure such as paranasal sinuses.
Prognosis
About 60 percent of initial attacks of dacryocystitis will recur. Individuals with a poorly functioning immune system (immunocompromised) may develop orbital cellulitis, which may lead to optic neuritis, proptosis, motility abnormalities, or blindness.
See also
Dacryocystocele
Canaliculitis
References
== External links == |
Finger | A finger is a limb of the body and a type of digit, an organ of manipulation and sensation found in the hands of most of the Tetrapods, so also with humans and other primates. Most land vertebrates have five fingers (Pentadactyly).
Land vertebrate fingers
The five-rayed anterior limbs of terrestrial vertebrates can be derived phylogenetically from the pectoral fins of fish. Within the taxa of the terrestrial vertebrates, the basic pentadactyl plan, and thus also the fingers and phalanges, undergo many variations.Morphologically the different fingers of terrestrial vertebrates are homolog. The wings of birds and those of bats are not homologous, they are analogue flight organs. However, the phalanges within them are homologous.Chimpanzees have lower limbs that are specialized for manipulation, and (arguably) have fingers on their lower limbs as well. In the case of Primates in general, the digits of the hand are overwhelmingly referred to as "fingers". Primate fingers have both fingernails and fingerprints.Research has been carried out on the embryonic development of domestic chickens showing that an interdigital webbing forms between the tissues that become the toes, which subsequently regresses by apoptosis. If apoptosis fails to occur, the interdigital skin remains intact. Many animals have developed webbed feet or skin between the fingers from this like the Wallaces flying frog.
Human fingers
Usually humans have five digits, the bones of which are termed phalanges, on each hand, although some people have more or fewer than five due to congenital disorders such as polydactyly or oligodactyly, or accidental or intentional amputations. The first digit is the thumb, followed by index finger, middle finger, ring finger, and little finger or pinkie. According to different definitions, the thumb can be called a finger, or not.
English dictionaries describe finger as meaning either one of the five digits including the thumb, or one of the four excluding the thumb (in which case they are numbered from 1 to 4 starting with the index finger closest to the thumb).
Anatomy
Skeleton
The thumb (connected to the trapezium) is located on one of the sides, parallel to the arm.
The palm has five bones known as metacarpal bones, one to each of the five digits. Human hands contain fourteen digital bones, also called phalanges, or phalanx bones: two in the thumb (the thumb has no middle phalanx) and three in each of the four fingers. These are the distal phalanx, carrying the nail, the middle phalanx, and the proximal phalanx.
Joints are formed wherever two or more of these bones meet. Each of the fingers has three joints:
metacarpophalangeal joint (MCP) – the joint at the base of the finger
proximal interphalangeal joint (PIP) – the joint in the middle of the finger
distal interphalangeal joint (DIP) – the joint closest to the fingertip.Sesamoid bones are small ossified nodes embedded in the tendons to provide extra leverage and reduce pressure on the underlying tissue. Many exist around the palm at the bases of the digits; the exact number varies between different people.
The articulations are: interphalangeal articulations between phalangeal bones, and metacarpophalangeal joints connecting the phalanges to the metacarpal bones.
Muscles
Each finger may flex and extend, abduct and adduct, and so also circumduct. Flexion is by far the strongest movement. In humans, there are two large muscles that produce flexion of each finger, and additional muscles that augment the movement. The muscle bulks that move each finger may be partly blended, and the tendons may be attached to each other by a net of fibrous tissue, preventing completely free movement. Although each finger seems to move independently, moving one finger also moves the other fingers slightly which is called finger interdependence or finger enslaving.Fingers do not contain muscles (other than arrector pili). The muscles that move the finger joints are in the palm and forearm. The long tendons that deliver motion from the forearm muscles may be observed to move under the skin at the wrist and on the back of the hand.
Muscles of the fingers can be subdivided into extrinsic and intrinsic muscles.
The extrinsic muscles are the long flexors and extensors. They are called extrinsic because the muscle belly is located on the forearm.
The fingers have two long flexors, located on the underside of the forearm. They insert by tendons to the phalanges of the fingers. The deep flexor attaches to the distal phalanx, and the superficial flexor attaches to the middle phalanx. The flexors allow for the actual bending of the fingers. The thumb has one long flexor and a short flexor in the thenar muscle group. The human thumb also has other muscles in the thenar group (opponens and abductor brevis muscle), moving the thumb in opposition, making grasping possible.
The extensors are located on the back of the forearm and are connected in a more complex way than the flexors to the dorsum of the fingers. The tendons unite with the interosseous and lumbrical muscles to form the extensorhood mechanism. The primary function of the extensors is to straighten out the digits. The thumb has two extensors in the forearm; the tendons of these form the anatomical snuff box. Also, the index finger and the little finger have an extra extensor, used for instance for pointing. The extensors are situated within six separate compartments. The first compartment contains abductor pollicis longus and extensor pollicis brevis. The second compartment contains extensors carpi radialis longus and brevis. The third compartment contains extensor pollicis longus. The extensor digitorum indicis and extensor digitorum communis are within the fourth compartment. Extensor digiti minimi is in the fifth, and extensor carpi ulnaris is in the sixth.
The intrinsic muscle groups are the thenar and hypothenar muscles (thenar referring to the thumb, hypothenar to the small finger), the dorsal and palmar interossei muscles (between the metacarpal bones) and the lumbrical muscles. The lumbricals arise from the deep flexor (and are special because they have no bony origin) and insert on the dorsal extensor hood mechanism.
Skin
Aside from the genitals, the fingertips possess the highest concentration of touch receptors and thermoreceptors among all areas of the human skin, making them extremely sensitive to temperature, pressure, vibration, texture and moisture. Recent studies suggest fingers can feel nano-scale wrinkles on a seemingly smooth surface, a level of sensitivity not previously recorded. This makes the fingers commonly used sensory probes to ascertain properties of objects encountered in the world, making them prone to injury.
The pulp of a finger is the fleshy mass on the palmar aspect of the extremity of the finger.
Fingertip wrinkling in water
Although a common phenomenon, the underlying functions and mechanism of fingertip wrinkling following immersion in water are relatively unexplored. Originally it was assumed that the wrinkles were simply the result of the skin swelling in water, but it is now understood that the furrows are caused by the blood vessels constricting due to signalling by the sympathetic nervous system in response to water exposure. One hypothesis for why this occurs, the “rain tread” hypothesis, posits that the wrinkles may help the fingers grip things when wet, possibly being an adaption from a time when humans dealt with rain and dew in forested primate habitats. A 2013 study supporting this hypothesis found that the wrinkled fingertips provided better handling of wet objects but gave no advantage for handling dry objects. However, a 2014 study attempting to reproduce these results was unable to demonstrate any improvement of handling wet objects with wrinkled fingertips.
Regrowth of the fingertips
Fingertips, after having been torn off children, have been observed to regrow in less than 8 weeks. However, these fingertips do not look the same, although they do look more appealing than a skin graft or a sewn fingertip. No healing occurs if the tear happens below the nail. This works because the distal phalanges are regenerative in youth, and stem cells in the nails create new tissue that ends up as the fingertip.
Brain representation
Each finger has an orderly somatotopic representation on the cerebral cortex in the somatosensory cortex area 3b, part of area 1 and a distributed, overlapping representations in the supplementary motor area and primary motor area.The somatosensory cortex representation of the hand is a dynamic reflection of the fingers on the external hand: in syndactyly people have a clubhand of webbed, shortened fingers. However, not only are the fingers of their hands fused, but the cortical maps of their individual fingers also form a club hand. The fingers can be surgically divided to make a more useful hand. Surgeons did this at the Institute of Reconstructive Plastic Surgery in New York to a 32-year-old man with the initials O. G.. They touched O. G.’s fingers before and after surgery while using MRI brain scans. Before the surgery, the fingers mapped onto his brain were fused close together; afterward, the maps of his individual fingers did indeed separate and take the layout corresponding to a normal hand.
Clinical significance
Anomalies, injuries and diseases
A rare anatomical variation affects 1 in 500 humans, in which the individual has more than the usual number of digits; this is known as polydactyly. A human may also be born without one or more fingers or underdevelopment of some fingers such as symbrachydactyly. Extra fingers can be functional. One individual with seven fingers not only used them but claimed that they "gave him some advantages in playing the piano".Phalanges are commonly fractured. A damaged tendon can cause significant loss of function in fine motor control, such as with a mallet finger. They can be damaged by cold, including frostbite and non-freezing cold injury (NFCI); and heat, including burns.
The fingers are commonly affected by diseases such as rheumatoid arthritis and gout. Diabetics often use the fingers to obtain blood samples for regular blood sugar testing. Raynauds phenomenon and Paroxysmal hand hematoma are neurovascular disorders that affects the fingers.
Research has linked the ratio of lengths between the index and ring fingers to higher levels of testosterone, and to various physical and behavioral traits such as penis length and risk for development of alcohol dependence or video game addiction.
Etymology
The English word finger stems from Old English finger, ultimately from Proto-Germanic *fingraz (finger). It is cognate with Gothic figgrs, Old Norse fingr, or Old High German fingar. Linguists generally assume that *fingraz is a ro-stem deriving from a previous form *fimfe, ultimately from Proto-Indo-European *pénkʷe (five).The name pinkie derives from Dutch pinkje, of uncertain origin. In English only the digits on the hand are known as fingers. However, in some languages the translated version of fingers can mean either the digits on the hand or feet. In English a digit on a foot has the distinct name of toe.
See also
Finger snapping
Fingerprint
Nail (anatomy)
Paroxysmal hand hematoma
Notes
References
== External links == |
Stimmler syndrome | Stimmler syndrome is a rare autosomal recessive congenital disorder first described by Stimmler et al. in 1970. It is characterized by dwarfism, diabetes, a small head, and high levels of alanine in the urine.
Symptoms
Symptoms for the disease include microcephaly, a low birth weight, dwarfism, small teeth, and diabetes. The symptoms of Stimmler syndrome are closely related to a disease studied by Haworth et al. in 1967 as well as Leigh subacute necrotizing encephalopathy with lactic acidosis
Pathophysiology
Stimmler syndrome is an autosomal recessive genetic disorder whose symptoms appear before birth or during infancy. In a study of two sisters born within a year of each other, both with Stimmler syndrome, it was found that high levels of alanine, pyruvate, and lactate were present in both the blood and urine. It was believed that the alanine was derived from the pyruvate.
Diagnosis
Treatment
References
== External links == |
Ovarian pregnancy | Ovarian pregnancy refers to an ectopic pregnancy that is located in the ovary. Typically the egg cell is not released or picked up at ovulation, but fertilized within the ovary where the pregnancy implants. Such a pregnancy usually does not proceed past the first four weeks of pregnancy. An untreated ovarian pregnancy causes potentially fatal intra-abdominal bleeding and thus may become a medical emergency.
Cause and pathology
The cause of ovarian pregnancy is unknown, specifically as the usual causative factors – pelvic inflammatory disease and pelvic surgery – implicated in tubal ectopic pregnancy seem to be uninvolved. There appears to be a link to the intrauterine device (IUD), however, it cannot be concluded that this is causative as it could be that IUDs prevent other but not ovarian pregnancies. Some have suggested that patients who undergo IVF therapy are at higher risk for ovarian pregnancy.An ovarian pregnancy is usually understood to begin when a mature egg cell is not expelled or picked up from its follicle and a sperm enters the follicle and fertilizes the egg, giving rise to an intrafollicular pregnancy. It has also been debated that an egg cell fertilized outside of the ovary could implant on the ovarian surface, perhaps aided by a decidual reaction or endometriosis. Ovarian pregnancies rarely go longer than 4 weeks; nevertheless, there is the possibility that the trophoblast finds further support outside the ovary and thus may affect the tube and other organs. In very rare occasions the pregnancy may find a sufficient foothold outside the ovary to continue as an abdominal pregnancy, and an occasional delivery has been reported.y
Diagnosis
The diagnosis is made in asymptomatic pregnant women by obstetric ultrasonography. On pelvic examination a unilateral adnexal mass may be found. Typical symptoms are abdominal pain and, to a lesser degree, vaginal bleeding during pregnancy. Patients may present with hypovolemia or be in circulatory shock because of internal bleeding.Ideally, ultrasound will show the location of the gestational sac in the ovary, while the uterine cavity is "empty", and if there is internal bleeding, it can be identified. Because of the proximity of the tube, the sonographic distinction between a tubal and an ovarian pregnancy may be difficult. Serial hCG levels generally show not the normal progressive rise.
In a series of 12 patients the mean gestation age was 45 days.Histologically, the diagnosis has been made by Spiegelberg criteria on the surgical specimen of the removed ovary and tube. However, the tube and ovary are not usually removed as sonography allows for earlier diagnosis and surgeons strive to preserve the ovary. Prior to the introduction of Spiegelbergs criteria in 1878, the existence of ovarian pregnancy was in doubt; his criteria helped to identify the ovarian pregnancy from other ectopics:
The gestational sac is located in the region of the ovary.
The gestational sac is attached to the uterus by the ovarian ligament.
Ovarian tissue is histologically proven in the wall of the gestational sac.
The oviduct on the affected side is intact (this criterion, however, holds not true for a longer ongoing ovarian pregnancy).An ovarian pregnancy can be mistaken for a tubal pregnancy or a hemorrhagic ovarian cyst or corpus luteum prior to surgery. Sometimes, only the presence of trophoblastic tissue during the histologic examination of material of a bleeding ovarian cyst shows that an ovarian pregnancy was the cause of the bleeding.
Management
Ovarian pregnancies are dangerous and prone to internal bleeding. Thus, when suspected, intervention is called for.
Traditionally, an explorative laparotomy was performed, and once the ovarian pregnancy was identified, an oophorectomy or salpingo-oophorectomy was performed, including the removal of the pregnancy. Today, the surgery can often be performed via laparoscopy. The extent of surgery varies according to the amount of tissue destruction that has
occurred. Patients with an ovarian pregnancy have a good prognosis for future fertility and therefore conservative surgical management is advocated. Further, in attempts to preserve ovarian tissue, surgery may involve just the removal of the pregnancy with only a part of the ovary. This can be accomplished by an ovarian wedge resection.Ovarian pregnancies have been successfully treated with methotrexate since it was introduced in the management of ectopic pregnancy in 1988.An ovarian pregnancy can develop together with a normal intrauterine pregnancy; such a heterotopic pregnancy will call for expert management as not to endanger the intrauterine pregnancy.
Epidemiology
Ovarian pregnancies are rare: the vast majority of ectopic pregnancies occur in the fallopian tube; only about 0.15-3% of ectopics occur in the ovary. The incidence has been reported to be about 1:3,000 to 1:7,000 deliveries.
History
In 1614 Mercier (also shown as Mercerus) described ovarian pregnancy for the first time, as a condition separate from a tubal pregnancy. Once the study of physiology emerged, Boehmer classified extra-uterine pregnancy into three classes: abdominal, ovarian, and tubal. There were many doubters that such a condition existed, particularly Mayer, who wrote an essay not only denying the existence of ovarian pregnancy, but demonstrating that recorded cases to that time were other conditions. Then Cohnstein proposed four criteria that would need to be present for ovarian pregnancy exist. His requirements were: 1) absence of the ovary on the side in which the alleged pregnancy was located; 2) connection of the uterus and sac via an ovarian ligament; 3) cylindrical tissue must line the layers of the sac with direct connection between the tunica albuginea and sac wall; and 4) evidence of the amniotic cavity connection to the ovarian follicle or corpus luteum. These were replaced by Otto Spiegelbergs criteria in 1878, which have been used into the 20th century with additions and modifications.Up to 1845, about 80 cases of ovarian pregnancy were proposed. With Mayers 1845 denial that ovarian pregnancy could exist, physicians began taking more care in their descriptions and analysis of cases. Though numerous cases were evaluated, some failed to provide microscopic evidence and others failed to show the necessary histological changes of pregnancy, or failed on one or more of the criteria. In 1899, Catharine van Tussenbroek finally settled the question of the existence of ovarian pregnancy, by providing the first accurate clinical and histological description of a case. Though doubted, her results were confirmed three years later in a case by Thompson.
References
Citations
Sources
Jacobson, Sidney D. (1908). "True Primary Ovarian Pregnancy: Operation; Recovery". In Brooks, Henry T. (ed.). Contributions to the Science of Medicine and Surgery: In celebration of the twenty-fifth anniversary, 1882-1907, of the founding of the New York Post-Graduate Medical School and Hospital. New York: Jacobson New York Post-graduate Medical School and Hospital Faculty / Royal College of Physicians of Edinburgh.
McDonald, Ellice (1914). Studies in gynecology and obstetrics. New York: American Medical Publishing Co. OCLC 11339026.
Ray, Henry M. (June 1921). "Primary Ovarian and Primary Abdominal Pregnancy: Their Morphological Possibility". Surgery, Gynecology & Obstetrics. Chicago: Journal of the American College of Surgeons / Franklin H. Martin Memorial Foundation. 32. Retrieved 21 March 2016.
Rizk, Botros R. M. B. (2010). Ultrasonography in Reproductive Medicine and Infertility. Cambridge, England: Cambridge University Press. ISBN 978-1-139-48457-2.
Thorek, Max (February 1926). "Case of Ovarian Pregnancy with Histological Findings". The Illinois Medical Journal. Chicago: Illinois State Medical Society. 49: 106–111. Retrieved 6 April 2016.
"Obstetrical Society of London". The British Medical Journal. London: Royal Medical and Chirurgical Society. 2 (2081): 1442. 17 November 1900. PMC 2463948.
External links
The Ectopic Pregnancy Trust - Information and support for those who have suffered the condition by a medically overseen and moderated UK based charity, recognised by the National Health Service (UK) Department of Health (UK) and the Royal College of Obstetricians and Gynaecologists |
Sarcoma botryoides | Sarcoma botryoides or botryoid sarcoma is a subtype of embryonal rhabdomyosarcoma, that can be observed in the walls of hollow, mucosa lined structures such as the nasopharynx, common bile duct, urinary bladder of infants and young children or the vagina in females, typically younger than age 8. The name comes from the gross appearance of "grape bunches" (botryoid in Greek).
Presentation
For botryoid rhabdomyosarcoma of the vagina, the most common clinical finding is vaginal bleeding but vaginal bleeding is not specific for sarcoma botryoides: other vaginal cancers are possible. They may appear as a polypoid mass, somewhat yellow in color and are friable: thus, they (possibly) may break off, leading to vaginal bleeding or infections.
Histology
Under the microscope one can see rhabdomyoblasts that may contain cross-striations. Tumor cells are crowded in a distinct layer beneath the vaginal epithelium (cambium layer). Spindle-shaped tumor cells that are desmin positive.
Treatment
The disease used to be uniformly fatal, with a 5-year survival rate between 10 and 35%. As a result, treatment was radical surgery. New multidrug chemotherapy regimens with or without radiation therapy are now used in combination with less radical surgery with good results, although outcome data are not yet available.
Epidemiology
Sarcoma botryoides normally is found in children under 8 years of age. Onset of symptoms occurs at age 3 years (38.3 months) on average. Cases of older women with this condition have also been reported.
References
External links
humpath.com #12369 |
Lower urinary tract symptoms | Lower urinary tract symptoms (LUTS) refer to a group of clinical symptoms involving the bladder, urinary sphincter, urethra and, in men, the prostate. The term is more commonly applied to men—over 40% of older men are afected—but lower urinary tract symptoms also affect women. The condition is also termed prostatism in men, but LUTS is preferred.
Symptoms and signs
Symptoms can be categorised into:
Filling (storage) or irritative symptoms
Increased frequency of urination
Increased urgency of urination
Urge incontinence
Excessive passage of urine at night
Voiding or obstructive symptoms
Poor stream (unimproved by straining)
Hesitancy (worsened if bladder is very full)
Terminal dribbling
Incomplete voiding
Urinary retention
Overflow incontinence (occurs in chronic retention)
Episodes of near retentionAs the symptoms are common and non-specific, LUTS is not necessarily a reason to suspect prostate cancer. Large studies of patients have also failed to show any correlation between lower urinary tract symptoms and a specific diagnosis. Also, recently a report of lower urinary tract symptoms even with malignant features in the prostate failed to be associated with prostate cancer after further laboratory investigation of the biopsy.
Causes
Benign prostatic hyperplasia (BPH)
Bladder stone
Cancer of the bladder and prostate
Detrusor muscle weakness and/or instability
Diabetes
Use of ketamine
Neurological conditions; for example multiple sclerosis, spinal cord injury, cauda equina syndrome
Prostatitis, including IgG4-related prostatitis
Urethral stricture
Urinary tract infections (UTIs)
Diagnosis
The International Prostate Symptom Score (IPSS) can be used to gauge the symptoms, along with physician examination. Other primary and secondary tests are often carried out, such as a PSA (Prostate-specific antigen) test, urinalysis, ultrasound, urinary flow studies, imaging, temporary prostatic stent placement, prostate biopsy and/or cystoscopy.
Placement of a temporary prostatic stent as a differential diagnosis test can help identify whether LUTS symptoms are directly related to obstruction of the prostate or to other factors worth investigation.
Treatment
Treatment will depend on the cause, if one is found. For example; with a UTI, a course of antibiotics would be given; appropriate medication would be administered to treat benign prostatic hyperplasia.
Lifestyle changes
Other treatments include lifestyle advice; for example, avoiding dehydration in recurrent cystitis.Men with prostatic hypertrophy are advised to sit down whilst urinating. A 2014 meta-analysis found that, for elderly males with LUTS, sitting to urinate meant there was a decrease in post-void residual volume (PVR, ml), increased maximum urinary flow (Qmax, ml/s), which is comparable with pharmacological intervention, and decreased the voiding time (VT, s). The improved urodynamic profile is related to a lower risk of urologic complications, such as cystitis and bladder stones.Physical activity
Physical activity has been recommended as a treatment for urinary tract symptoms. A 2019 Cochrane review of six studies involving 652 men assessing the effects of physical activity alone, physical activity as a part of a self-management program, among others. The evidence from this review states that there are important uncertainties whether physical activity is helpful in men experiencing urinary symptoms caused by benign prostatic hyperplasia.
Medications
With benign prostatic enlargement causes of LUTS, people may be offered a variety of medications (as a single drug or combining them) when there are persistent moderate symptoms:
Alpha blockers
5-alpha reductase inhibitors
Phosphodiesterase inhibitors
Muscarinic receptor antagonists
Plants extracts (phytotherapy)
Beta-3 agonistIf medical treatment fails, or is not an option; a number of surgical techniques to destroy part or all of the prostate have been developed.
Surgical treatment
Surgical treatment of LUTS can include:
Ablation procedures - used in treating both bladder tumours and bladder outlet obstruction, such as prostate conditions.
Bladder-neck incision (BNI)
Removal of the prostate - open, robotic, and endoscopic techniques are used.
Stenting of the prostate and urethra.
Transurethral resection of the prostate (TURP)
Transurethral microwave thermotherapy
Urethral dilatation, a common treatment for strictures.
Epidemiology
Prevalence increases with age. The prevalence of nocturia in older men is about 78%. Older men have a higher incidence of LUTS than older women.
Around one third of men will develop urinary tract (outflow) symptoms, of which the principal underlying cause is benign prostatic hyperplasia.
Once symptoms arise, their progress is variable and unpredictable with about one third of patients improving, one third remaining stable and one third deteriorating.
References
Further reading
External links
LUTS in men - Patient.info
LUTS in women - Patient.info |
Childhood absence epilepsy | Childhood absence epilepsy (CAE), is one of the most frequent pediatric epilepsy syndromes. CAE is an idiopathic generalized epilepsy that occurs in otherwise normal children. The only seizure type at the time of diagnosis is the typical absence seizure. CAE is a well-known pediatric epilepsy syndrome affecting 10–17% of all children with epilepsy. It was previously known as pyknolepsy. The word pyknolepsy originates from the Greek piknoz (picnós), which means recurrent or grouped. The usual age of onset of CAE is between 4 and 10 years, with peak between 5 and 7 years.The typical absence seizure has a sudden onset of altered awareness and ends also abruptly. Electroencephalogram demonstrate characteristic "typical 3Hz spike-wave" generalized rhythmic discharges that begin and end abruptly. Prognosis is generally good with fair rates of response to treatment and with most patients growing out of their absencese. However, learning difficulties and seizure occurrence rates remain higher than the general population even after several years. When typical absence seizures start the age of 8– 9 years old when the absence seizures are infrequent or when the absence seizures are observed in a patient that had experienced a generalized tonic-clonic seizure, a diagnosis of juvenile absence epilepsy should be considered.
Signs and symptoms
CAE is characterized by the presence of absence seizures. The absence seizures are usually brief (about 4 to 30 seconds) but occur frequently, usually around a dozen per day but sometimes even hundreds of times per day. They involve abrupt impairment of consciousness with loss of awareness and responsiveness, behavioral arrest, and arrest of the activity that may vary from complete arrest to continuing the activity with an altered status. Other seizure features include starring, eyelid movement or eye-opening and pallor. Mild automatisms and mild movements at the beginning of the seizures are frequent, but major motor involvement, as atonic falls, early in the course of the disease excludes this diagnosis.The International League Against Epilepsy commission defined absence seizure as “of sudden onset, interruption of ongoing activities, staring, possible upwards version of eyes with few seconds duration, associated with symmetrical 2–4 Hz, mainly 3 Hz spike-wave complexes, normal background activity. Absence seizure was divided into two subgroups (Penry et al. 1975), first with consciousness impairment, and others were associated with the other clinical component, namely clonic, atonic, tonic, autonomic, and with automatisms. Though CAE usually occurs in children with normal neurodevelopment and are sensitive to antiepileptic treatments children with CAE have a risk of academic failure and high rates of attention deficits.
Neuropsychological impairment
Neuropsychological impairment in children with CAE is frequent and includes executive dysfunction, attention problems, learning disabilities, and language problems. These problems even persist after seizures are treated. Monitoring with validated cognition scales should be performed. Many existing data illustrate that children with CAE have an average IQ but present subtle cognitive difficulties. In cases with lower IQ, significant social difficulties can be often seen. Behavioral issues may also be present and their occurrence might be associated with significantly worse cognitive development. Some evidence suggest that are impairment is more prominent in verbal rather than non-verbal capacities of children with CAE or are even limited to few areas of verbal expression as phonological and category fluency. Attention deficit disorder and specific learning disorders are also frequently found in the CAE and can interfere with academic performance as well as with day to day activities of the children.
Causes
CAE is considered as a complex polygenic disorder. This fact is supported by the high occurrence (up to 20%) of generalized epilepsies or febrile seizures in family members of children with CAE. In cases with early onset or accompanying features, Glut-1 deficiency (a metabolic disorder responding well to ketogenic diet) could be the cause of the absence seizures. Genetic mutations have been identified in recent years involving mainly GABA receptors and calcium channel modulator genes.
Pathophysiology
Pathophysiology of absence seizures has been widely studied in animal models but is not fully decoded to date. There is however solid evidence for the involvement of bilateral cortical and subcortical networks which are part of the default state system. Pathophysiology when genetic mutations are present is further discussed below. Particularly in the Han Chinese population, there is an association between mutations in the calcium channel, voltage-dependent, T type, alpha 1H subunit (CACNA1H), and childhood absence epilepsy. These mutations cause increased channel activity and associated increased neuronal excitability. Seizures are believed to originate in the thalamus, where there is an abundance of T-type calcium channels such as those encoded by the CACNA1H gene (12). In a European study CACNA1H associated with CAE, 20 mutations have been identified. These mutations are likely not wholly causative and should instead be thought of as giving susceptibility. This is particularly true since some groups have found no connection between CAE and CACNA1H mutations. Many of the CACNA1H mutations have a measurable effect on channel kinetics on activation time constant and voltage dependence, on deactivation time constant, and on inactivation time constant and voltage dependence. should leading either to neuronal excitability or hypo excitability. However, these predictions result from mathematical modeling and may differ from what occurs in neurons (in vivo) where other proteins, some of which may interact with CACNA1H, are present. Along with mutations in the CACNA1H gene, two mutations in gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), the gene encoding a GABAA receptor gamma subunit, are also associated with a CAE-like phenotype that also overlaps with generalized epilepsy with febrile seizures plus type-3. The first of these, R43Q, abolishes benzodiazepine potentiation of gamma-aminobutyric acid induced currents. The second associated mutation, C588T, has not been further characterized.
Diagnosis
CAE can be diagnosed during an outpatient clinic visit with a careful history, physical exam including hyperventilation, and a routine electroencephalogram. The diagnosis is made upon the history of absence seizures during early childhood without other seizure types and the observation of 3 Hz generalized spike waves paroxysmal discharges on the EEG. In children with CAE without atypical features electroclinical features, no neuroimaging is needed.
Management
There are three antiepileptic drugs that have been used for the first-line treatment for CAE; these are ethosuximide (ETX), valproic acid (VPA), and lamotrigine (LTG). ETX is an effective first-line treatment for seizures only by blocking the low-threshold calcium currents produced by T-type calcium channels in the thalamus. The peak level occurs after 3–5 hours of intake; steady levels of the drug in the blood are achieved after 7–10 days of the same daily dose. The usual dosage is 20–30 mg/kg/day divided into two doses. Common side effects include gastrointestinal disturbances such as hiccups, vomiting, abdominal discomfort, and diarrheic and exceptionally. The other symptoms, like fatigue, insomnia, dizziness and ataxia. Valproate (VPA) has also been proven effective monotherapy in CAE although ETX is usually preferred as it has a lower impact on attention according to the Childhood Epilepsy study. There are several mechanisms related to VPA’s antiepileptic action, including raising the level of gamma-aminobutyric acid (GABA), calcium-dependent potassium activating, and blocking of voltage-sensitive sodium channels, but there is no specific evidence for the mechanism by which VPA controls absence seizures. VPA also has a wide range of side effects, like high-frequency tremor, altered mental status, increased appetite and weight gain, pancreatitis, and hepatic failure, thrombocytopenia, teratogenesis during pregnancy, although serious side effects are rare and usually dose-dependent. Usual maintenance dose in children is 20–30 mg/kg/day. Lamotrigine (LTG) could be can be used as alternative add-on treatment for CAE along with VPA and ETX. Other possible treatments in the rare cases of pharmacoresistant include levetiracetam, clobazam, topiramate, zonisamide.
Epidemiology
The occurrence of absence seizures varies from 0.7 to 4.6/100,000 in the overall population and from 6 to 8/100,000 in children up to 15 years old. There is some evidence showing that girls are more frequently affected by CAE than boys.
See also
Generalized epilepsy with febrile seizures plus
Calcium channel
Spike and Wave
References
Perez-Reyes E (2006). "Molecular characterization of T-type calcium channels". Cell Calcium. 40 (2): 89–96. doi:10.1016/j.ceca.2006.04.012. PMID 16759699.
Footnotes
== External links == |
Orgasm | Orgasm (from Greek ὀργασμός, orgasmos; "excitement, swelling") or sexual climax is the sudden discharge of accumulated sexual excitement during the sexual response cycle, resulting in rhythmic, involuntary muscular contractions in the pelvic region characterized by sexual pleasure. Experienced by males and females, orgasms are controlled by the involuntary or autonomic nervous system. They are usually associated with involuntary actions, including muscular spasms in multiple areas of the body, a general euphoric sensation and, frequently, body movements and vocalizations. The period after orgasm (known as the refractory period) is typically a relaxing experience, attributed to the release of the neurohormones oxytocin and prolactin as well as endorphins (or "endogenous morphine").Human orgasms usually result from physical sexual stimulation of the penis in males (typically accompanying ejaculation) and of the clitoris in females. Sexual stimulation can be by self-practice (masturbation) or with a sex partner (penetrative sex, non-penetrative sex, or other sexual activity).
The health effects surrounding the human orgasm are diverse. There are many physiological responses during sexual activity, including a relaxed state created by prolactin, as well as changes in the central nervous system such as a temporary decrease in the metabolic activity of large parts of the cerebral cortex while there is no change or increased metabolic activity in the limbic (i.e., "bordering") areas of the brain. There is also a wide range of sexual dysfunctions, such as anorgasmia. These effects affect cultural views of orgasm, such as the beliefs that orgasm and the frequency or consistency of it are either important or irrelevant for satisfaction in a sexual relationship, and theories about the biological and evolutionary functions of orgasm.
Definitions
In a clinical context, orgasm is usually defined strictly by the muscular contractions involved during sexual activity, along with the characteristic patterns of change in heart rate, blood pressure, and often respiration rate and depth. This is categorized as the sudden discharge of accumulated sexual tension during the sexual response cycle, resulting in rhythmic muscular contractions in the pelvic region. However, definitions of orgasm vary and there is sentiment that consensus on how to consistently classify it is absent. At least twenty-six definitions of orgasm were listed in the journal Clinical Psychology Review.There is some debate whether certain types of sexual sensations should be accurately classified as orgasms, including female orgasms caused by G-spot stimulation alone, and the demonstration of extended or continuous orgasms lasting several minutes or even an hour. The question centers around the clinical definition of orgasm, but this way of viewing orgasm is merely physiological, while there are also psychological, endocrinological, and neurological definitions of orgasm. In these and similar cases, the sensations experienced are subjective and do not necessarily involve the involuntary contractions characteristic of orgasm. However, the sensations in both sexes are extremely pleasurable and are often felt throughout the body, causing a mental state that is often described as transcendental, and with vasocongestion and associated pleasure comparable to that of a full-contractionary orgasm. For example, modern findings support distinction between ejaculation and male orgasm. For this reason, there are views on both sides as to whether these can be accurately defined as orgasms.
Achieving orgasm
Orgasms can be achieved during a variety of activities, including vaginal, anal or oral sex, non-penetrative sex or masturbation. They may also be achieved by the use of a sex toy, such as a sensual vibrator or an erotic electrostimulation. Achieving orgasm by stimulation of the nipples or other erogenous zones is rarer. Multiple orgasms are also possible, especially in women, but they are also uncommon. Multiple orgasms are orgasms that occur within a short period of one another.In addition to physical stimulation, orgasm can be achieved from psychological arousal alone, such as during dreaming (nocturnal emission for males or females) or by forced orgasm. Orgasm by psychological stimulation alone was first reported among people who had spinal cord injury. Although sexual function and sexuality after spinal cord injury is very often impacted, this injury does not deprive one of sexual feelings such as sexual arousal and erotic desires.Scientific literature focuses on the psychology of female orgasm significantly more than it does on the psychology of male orgasm, which "appears to reflect the assumption that female orgasm is psychologically more complex than male orgasm," but "the limited empirical evidence available suggests that male and female orgasm may bear more similarities than differences. In one controlled study by Vance and Wagner (1976), independent raters could not differentiate written descriptions of male versus female orgasm experiences".
Males
Variabilities
In men, the most common way of achieving orgasm is by physical sexual stimulation of the penis. This is usually accompanied by ejaculation, but it is possible, though also rare, for men to orgasm without ejaculation (known as a "dry orgasm"). Prepubescent boys have dry orgasms. Dry orgasms can also occur as a result of retrograde ejaculation, or hypogonadism. Men may also ejaculate without reaching orgasm, which is known as anorgasmic ejaculation. They may also achieve orgasm by stimulation of the prostate (see below).
Two-stage model
The traditional view of male orgasm is that there are two stages: emission accompanying orgasm, almost instantly followed by a refractory period. The refractory period is the recovery phase after orgasm during which it is physiologically impossible for a man to have additional orgasms. In 1966, Masters and Johnson published pivotal research about the phases of sexual stimulation. Their work included women and men, and, unlike Alfred Kinsey in 1948 and 1953, tried to determine the physiological stages before and after orgasm.
Masters and Johnson argued that, in the first stage, "accessory organs contract and the male can feel the ejaculation coming; two to three seconds later the ejaculation occurs, which the man cannot constrain, delay, or in any way control" and that, in the second stage, "the male feels pleasurable contractions during ejaculation, reporting greater pleasure tied to a greater volume of ejaculate". They reported that, unlike females, "for the man the resolution phase includes a superimposed refractory period" and added that "many males below the age of 30, but relatively few thereafter, have the ability to ejaculate frequently and are subject to only very short refractory periods during the resolution phase". Masters and Johnson equated male orgasm and ejaculation and maintained the necessity for a refractory period between orgasms.
Subsequent and multiple orgasms
There has been little scientific study of multiple orgasm in men. Dunn and Trost defined male multiple orgasm as "two or more orgasms with or without ejaculation and without, or with only very limited, de-tumescence (loss of erection) during one and the same sexual encounter". Although, due to the refractory period, it is rare for men to achieve multiple orgasms, some men have reported having multiple, consecutive orgasms, particularly without ejaculation. There may not be an obvious refractory period, and the final orgasm may cause a refractory period. Multiple orgasms are more commonly reported in very young men than in older men. In younger men, the refractory period may only last a few minutes, but last more than an hour in older men.An increased infusion of the hormone oxytocin during ejaculation is believed to be chiefly responsible for the refractory period, and the amount by which oxytocin is increased may affect the length of each refractory period. A scientific study to successfully document natural, fully ejaculatory, multiple orgasms in an adult man was conducted at Rutgers University in 1995. During the study, six fully ejaculatory orgasms were experienced in 36 minutes, with no apparent refractory period.
Females
Orgasmic factors and variabilities
In women, the most common way to achieve orgasm is by direct sexual stimulation of the clitoris (meaning consistent manual, oral, or other concentrated friction against the external parts of the clitoris). General statistics indicate that 70–80% of women require direct clitoral stimulation to achieve orgasm, although indirect clitoral stimulation (for example, via vaginal penetration) may also be sufficient. The Mayo Clinic stated, "Orgasms vary in intensity, and women vary in the frequency of their orgasms and the amount of stimulation necessary to trigger an orgasm." Clitoral orgasms are easier to achieve because the glans of the clitoris, or clitoris as a whole, has more than 8,000 sensory nerve endings, which is as many (or more in some cases) nerve endings as are present in the human penis or glans penis. As the clitoris is homologous to the penis, it is the equivalent in its capacity to receive sexual stimulation.
One misconception, particularly in older research publications, is that the vagina is completely insensitive. However, there are areas in the anterior vaginal wall and between the top junction of the labia minora and the urethra that are especially sensitive. With regard to specific density of nerve endings, while the area commonly described as the G-spot may produce an orgasm, and the urethral sponge, an area in which the G-spot may be found, runs along the "roof" of the vagina and can create pleasurable sensations when stimulated, intense sexual pleasure (including orgasm) from vaginal stimulation is occasional or otherwise absent because the vagina has significantly fewer nerve endings than the clitoris. The greatest concentration of vaginal nerve endings are at the lower third (near the entrance) of the vagina.Sex educator Rebecca Chalker states that only one part of the clitoris, the urethral sponge, is in contact with the penis, fingers, or a dildo in the vagina. Hite and Chalker state that the tip of the clitoris and the inner lips, which are also very sensitive, are not receiving direct stimulation during penetrative intercourse. Because of this, some couples may engage in the woman on top position or the coital alignment technique to maximize clitoral stimulation. For some women, the clitoris is very sensitive after climax, making additional stimulation initially painful.Masters and Johnson argued that all women are potentially multiply orgasmic, but that multiply orgasmic men are rare, and stated that "the female is capable of rapid return to orgasm immediately following an orgasmic experience, if re-stimulated before tensions have dropped below plateau phase response levels". Though generally reported that women do not experience a refractory period and thus can experience an additional orgasm, or multiple orgasms, soon after the first one, some sources state that both men and women experience a refractory period because women may also experience a period after orgasm in which further sexual stimulation does not produce excitement. After the initial orgasm, subsequent orgasms for women may be stronger or more pleasurable as the stimulation accumulates.
Clitoral and vaginal categories
Discussions of female orgasm are complicated by orgasms in women typically being divided into two categories: clitoral orgasm and vaginal (or G-spot) orgasm. In 1973, Irving Singer theorized that there are three types of female orgasms; he categorized these as vulval, uterine, and blended, but because he was a philosopher, "these categories were generated from descriptions of orgasm in literature rather than laboratory studies". In 1982, Ladas, Whipple and Perry also proposed three categories: the tenting type (derived from clitoral stimulation), the A-frame type (derived from G-spot stimulation), and the blended type (derived from clitoral and G-spot stimulation). In 1999, Whipple and Komisaruk proposed cervix stimulation as being able to cause a fourth type of female orgasm.Female orgasms by means other than clitoral or vaginal/G-spot stimulation are less prevalent in scientific literature and most scientists contend that no distinction should be made between "types" of female orgasm. This distinction began with Sigmund Freud, who postulated the concept of "vaginal orgasm" as separate from clitoral orgasm. In 1905, Freud stated that clitoral orgasms are purely an adolescent phenomenon and that upon reaching puberty, the proper response of mature women is a change-over to vaginal orgasms, meaning orgasms without any clitoral stimulation. While Freud provided no evidence for this basic assumption, the consequences of this theory were considerable. Many women felt inadequate when they could not achieve orgasm via vaginal intercourse alone, involving little or no clitoral stimulation, as Freuds theory made penile-vaginal intercourse the central component to womens sexual satisfaction.The first major national surveys of sexual behavior were the Kinsey Reports. Alfred Kinsey was the first researcher to harshly criticize Freuds ideas about female sexuality and orgasm when, through his interviews with thousands of women, Kinsey found that most of the women he surveyed could not have vaginal orgasms. He "criticized Freud and other theorists for projecting male constructs of sexuality onto women" and "viewed the clitoris as the main center of sexual response" and the vagina as "relatively unimportant" for sexual satisfaction, relaying that "few women inserted fingers or objects into their vaginas when they masturbated". He "concluded that satisfaction from penile penetration [is] mainly psychological or perhaps the result of referred sensation".Masters and Johnsons research into the female sexual response cycle, as well as Shere Hites, generally supported Kinseys findings about female orgasm. Masters and Johnsons research on the topic came at the time of the second-wave feminist movement, and inspired feminists such as Anne Koedt, author of The Myth of the Vaginal Orgasm, to speak about the "false distinction" made between clitoral and vaginal orgasms and womens biology not being properly analyzed.
Clitoral and vaginal relationships
Accounts that the vagina is capable of producing orgasms continue to be subject to debate because, in addition to the vaginas low concentration of nerve endings, reports of the G-spots location are inconsistent—it appears to be nonexistent in some women and may be an extension of another structure, such as the Skenes gland or the clitoris, which is a part of the Skenes gland. In a January 2012 The Journal of Sexual Medicine review examining years of research into the existence of the G-spot, scholars stated that "[r]eports in the public media would lead one to believe the G-spot is a well-characterized entity capable of providing extreme sexual stimulation, yet this is far from the truth".Possible explanations for the G-spot were examined by Masters and Johnson, who were the first researchers to determine that the clitoral structures surround and extend along and within the labia. In addition to observing that the majority of their female subjects could only have clitoral orgasms, they found that both clitoral and vaginal orgasms had the same stages of physical response. On this basis, they argued that clitoral stimulation is the source of both kinds of orgasms, reasoning that the clitoris is stimulated during penetration by friction against its hood; their notion that this provides the clitoris with sufficient sexual stimulation has been criticized by researchers such as Elisabeth Lloyd.Australian urologist Helen OConnells 2005 research additionally indicates a connection between orgasms experienced vaginally and the clitoris, suggesting that clitoral tissue extends into the anterior wall of the vagina and that therefore clitoral and vaginal orgasms are of the same origin. Some studies, using ultrasound, have found physiological evidence of the G-spot in women who report having orgasms during vaginal intercourse, but OConnell suggests that the clitoriss interconnected relationship with the vagina is the physiological explanation for the conjectured G-spot. Having used MRI technology which enabled her to note a direct relationship between the legs or roots of the clitoris and the erectile tissue of the "clitoral bulbs" and corpora, and the distal urethra and vagina, she stated that the vaginal wall is the clitoris; that lifting the skin off the vagina on the side walls reveals the bulbs of the clitoris—triangular, crescental masses of erectile tissue. OConnell et al., who performed dissections on the female genitals of cadavers and used photography to map the structure of nerves in the clitoris, were already aware that the clitoris is more than just its glans and asserted in 1998 that there is more erectile tissue associated with the clitoris than is generally described in anatomical textbooks. They concluded that some females have more extensive clitoral tissues and nerves than others, especially having observed this in young cadavers as compared to elderly ones, and therefore whereas the majority of females can only achieve orgasm by direct stimulation of the external parts of the clitoris, the stimulation of the more generalized tissues of the clitoris via intercourse may be sufficient for others.French researchers Odile Buisson and Pierre Foldès reported similar findings to that of OConnells. In 2008, they published the first complete 3D sonography of the stimulated clitoris, and republished it in 2009 with new research, demonstrating the ways in which erectile tissue of the clitoris engorges and surrounds the vagina, arguing that women may be able to achieve vaginal orgasm via stimulation of the G-spot because the highly innervated clitoris is pulled closely to the anterior wall of the vagina when the woman is sexually aroused and during vaginal penetration. They assert that since the front wall of the vagina is inextricably linked with the internal parts of the clitoris, stimulating the vagina without activating the clitoris may be next to impossible. In their 2009 published study, the "coronal planes during perineal contraction and finger penetration demonstrated a close relationship between the root of the clitoris and the anterior vaginal wall". Buisson and Foldès suggested "that the special sensitivity of the lower anterior vaginal wall could be explained by pressure and movement of clitoriss root during a vaginal penetration and subsequent perineal contraction".Supporting a distinct G-spot is a study by Rutgers University, published 2011, which was the first to map the female genitals onto the sensory portion of the brain; brain scans showed that the brain registered distinct feelings between stimulating the clitoris, the cervix and the vaginal wall – where the G-spot is reported to be – when several women stimulated themselves in a functional magnetic resonance (fMRI) machine. "I think that the bulk of the evidence shows that the G-spot is not a particular thing," stated Barry Komisaruk, head of the research findings. "Its not like saying, What is the thyroid gland? The G-spot is more of a thing like New York City is a thing. Its a region, its a convergence of many different structures." Commenting on Komisaruks research and other findings, Emmanuele Jannini, a professor of endocrinology at the University of Aquila in Italy, acknowledged a series of essays published in March 2012 in The Journal of Sexual Medicine, which document evidence that vaginal and clitoral orgasms are separate phenomena that activate different areas of the brain and possibly suggest key psychological differences between women.
Other factors and research
Regular difficulty reaching orgasm after ample sexual stimulation, known as anorgasmia, is significantly more common in women than in men (see below). In addition to sexual dysfunction being a cause for womens inability to reach orgasm, or the amount of time for sexual arousal needed to reach orgasm being variable and longer in women than in men, other factors include a lack of communication between sexual partners about what is needed for the woman to reach orgasm, feelings of sexual inadequacy in either partner, a focus on only penetration (vaginal or otherwise), and men generalizing womens trigger for orgasm based on their own sexual experiences with other women.Scholars state "many couples are locked into the idea that orgasms should be achieved only through intercourse [vaginal sex]" and that "[e]ven the word foreplay suggests that any other form of sexual stimulation is merely preparation for the main event.......Because women reach orgasm through intercourse less consistently than men, they are more likely than men to have faked an orgasm". Sex counselor Ian Kerner stated, "Its a myth that using the penis is the main way to pleasure a woman." He cites research concluding that women reach orgasm about 25% of the time with intercourse, compared with 81% of the time during oral sex (cunnilingus).In the first large-scale empirical study worldwide to link specific practices with orgasm, reported in the Journal of Sex Research in 2006, demographic and sexual history variables were comparatively weakly associated with orgasm. Data was analyzed from the Australian Study of Health and Relationships, a national telephone survey of sexual behavior and attitudes and sexual health knowledge carried out in 2001–2002, with a representative sample of 19,307 Australians aged 16 to 59. Practices included "vaginal intercourse alone (12%), vaginal + manual stimulation of the mans and/or womans genitals (49%), and vaginal intercourse + manual + oral (32%)" and the "[e]ncounters may also have included other practices. Men had an orgasm in 95% of encounters and women in 69%. Generally, the more practices engaged in, the higher a womans chance of having an orgasm. Women were more likely to reach orgasm in encounters including cunnilingus".Other studies suggest that women exposed to lower levels of prenatal androgens are more likely to experience orgasm during vaginal intercourse than other women.
Exercise-induced
Kinsey, in his 1953 book Sexual Behavior in the Human Female, stated that exercise could bring about sexual pleasure, including orgasm. A review in 1990 on the sexual response itself as exercise, reviewed the literature and stated that the field was poorly researched; it also said that studies had found that aerobic or isotonic exercise that resembles sexual activity or sexual positions can induce sexual pleasure, including orgasm. A 2007 review of the relationship between pelvic floor dysfunction and sexual problems in men and women found that they are commonly linked and suggested that physical therapy strengthening the pelvic floor could help address the sexual problems but that it was not well studied enough to recommend. Starting in at least 2007, the term, "coregasm" was used in popular media to refer to exercise-induced orgasm or in academic parlance termed exercise-induced sexual pleasure or EISP, and an extensive discussion of the "yogasm" occurred in a 2011 Daily Beast posting. A paper published in 2012 presented results of an online survey of women who had experienced an orgasm or other sexual pleasure during exercise. The paper was widely discussed in popular media when it was published. The authors of the paper said that research on the relationship between exercise and sexual response was still lacking.
Anal and prostate stimulation
In both sexes, pleasure can be derived from the nerve endings around the anus and the anus itself, such as during anal sex. It is possible for men to achieve orgasms through prostate stimulation alone. The prostate is the male homologue (variation) to the Skenes glands (which are believed to be connected to the female G-spot), and can be sexually stimulated through anal sex, perineum massage or via a vibrator. Much of the available information about prostate-induced orgasms comes from anecdotal reports by individuals, and the exact mechanisms by which such orgasms are produced are unclear; some sources suggest this occurs via stimulation of nerves in the prostatic plexus surrounding the organ, others suggest it is via nerves within the prostate itself, and others say changes in the brain (neuroplasticity) are required to derive pleasure from prostate stimulation. Regardless, prostate-induced orgasms are often reported to be intensely pleasurable. Prostate stimulation can produce a deeper orgasm, described by some men as more widespread and intense, longer-lasting, and allowing for greater feelings of ecstasy than orgasm elicited by penile stimulation only. The practice of pegging (consisting of a woman penetrating a mans anus with a strap-on dildo) stimulates the prostate. It is typical for a man to not reach orgasm as a receptive partner solely from anal sex.For women, penile-anal penetration may also indirectly stimulate the clitoris by the shared sensory nerves, especially the pudendal nerve, which gives off the inferior anal nerves and divides into the perineal nerve and the dorsal nerve of the clitoris. The G-spot area, which is considered to be interconnected with the clitoris, may also be indirectly stimulated during anal sex. Although the anus has many nerve endings, their purpose is not specifically for inducing orgasm, and so a woman achieving orgasm solely by anal stimulation is rare. Direct stimulation of the clitoris, a G-spot area, or both, while engaging in anal sex can help some women enjoy the activity and reach orgasm during it.The aforementioned orgasms are sometimes referred to as anal orgasms, but sexologists and sex educators generally believe that orgasms derived from anal penetration are the result of the relationship between the nerves of the anus, rectum, clitoris or G-spot area in women, and the anuss proximity to the prostate and relationship between the anal and rectal nerves in men, rather than orgasms originating from the anus itself.
Nipple stimulation
For women, stimulation of the breast area during sexual intercourse or foreplay, or solely having the breasts fondled, can create mild to intense orgasms, sometimes referred to as a breast orgasm or nipple orgasm. Few women report experiencing orgasm from nipple stimulation. Before Komisaruk et al.s functional magnetic resonance (fMRI) research on nipple stimulation in 2011, reports of women achieving orgasm from nipple stimulation relied solely on anecdotal evidence. Komisaruks study was the first to map the female genitals onto the sensory portion of the brain; it indicates that sensation from the nipples travels to the same part of the brain as sensations from the vagina, clitoris and cervix, and that these reported orgasms are genital orgasms caused by nipple stimulation, and may be directly linked to the genital sensory cortex ("the genital area of the brain").An orgasm is believed to occur in part because of the hormone oxytocin, which is produced in the body during sexual excitement and arousal and labor. It has also been shown that oxytocin is produced when a man or womans nipples are stimulated and become erect. Komisaruk also relayed, however, that preliminary data suggests that nipple nerves may directly link up with the relevant parts of the brain without uterine mediation, acknowledging the men in his study who showed the same pattern of nipple stimulation activating genital brain regions.
Medical aspects
Physiological responses
Masters and Johnson were some of the first researchers to study the sexual response cycle in the early 1960s, based on the observation of 382 women and 312 men. They described a cycle that begins with excitement as blood rushes into the genitals, then reaches a plateau during which they are fully aroused, which leads to orgasm, and finally resolution, in which the blood leaves the genitals.In the 1970s, Helen Singer Kaplan added the category of desire to the cycle, which she argued precedes sexual excitation. She stated that emotions of anxiety, defensiveness and the failure of communication can interfere with desire and orgasm. In the late 1980s and after, Rosemary Basson proposed a more cyclical alternative to what had largely been viewed as linear progression. In her model, desire feeds arousal and orgasm, and is in turn fueled by the rest of the orgasmic cycle. Rather than orgasm being the peak of the sexual experience, she suggested that it is just one point in the circle and that people could feel sexually satisfied at any stage, reducing the focus on climax as an end-goal of all sexual activity.
Males
As a man nears orgasm during stimulation of the penis, he feels an intense and highly pleasurable pulsating sensation of neuromuscular euphoria. These pulsating sensations originates from the contractions of pelvic floor muscles that begin in the anal sphincter and travels to the tip of the penis, commonly described as a "throbbing" or "tingling" sensation. They eventually increase in speed and intensity as the orgasm approaches, until a final "plateau" (the orgasmic) pleasure sustained for several seconds.During orgasm, a human male experiences rapid, rhythmic contractions of the anal sphincter, the prostate, and the bulbospongiosus muscles of the penis. The sperm are transmitted up the vas deferens from the testicles, into the prostate gland as well as through the seminal vesicles to produce what is known as semen. The prostate produces a secretion that forms one of the components of ejaculate. Except for in cases of a dry orgasm, contraction of the sphincter and prostate force stored semen to be expelled through the peniss urethral opening. The process takes from three to ten seconds, and produces a pleasurable feeling. Ejaculation may continue for a few seconds after the euphoric sensation gradually tapers off. It is believed that the exact feeling of "orgasm" varies from one man to another. After ejaculation, a refractory period usually occurs, during which a man cannot achieve another orgasm. This can last anywhere from less than a minute to several hours or days, depending on age and other |
Orgasm | individual factors.
Females
A womans orgasm may, in some cases, last a little longer than a mans. Womens orgasms have been estimated to last, on average, approximately 20 seconds, and to consist of a series of muscular contractions in the pelvic area that includes the vagina, the uterus, and the anus. For some women, on some occasions, these contractions begin soon after the woman reports that the orgasm has started and continue at intervals of about one second with initially increasing, and then reducing, intensity. In some instances, the series of regular contractions is followed by a few additional contractions or shudders at irregular intervals. In other cases, the woman reports having an orgasm, but no pelvic contractions are measured at all.Womens orgasms are preceded by erection of the clitoris and moistening of the opening of the vagina. Some women exhibit a sex flush, a reddening of the skin over much of the body due to increased blood flow to the skin. As a woman nears orgasm, the clitoral glans retracts under the clitoral hood, and the labia minora (inner lips) become darker. As orgasm becomes imminent, the outer third of the vagina tightens and narrows, while overall the vagina lengthens and dilates and also becomes congested from engorged soft tissue.Elsewhere in the body, myofibroblasts of the nipple-areolar complex contract, causing erection of the nipples and contraction of the areolar diameter, reaching their maximum at the start of orgasm. A woman experiences full orgasm when her uterus, vagina, anus, and pelvic muscles undergo a series of rhythmic contractions. Most women find these contractions very pleasurable.
Researchers from the University Medical Center of Groningen in the Netherlands correlated the sensation of orgasm with muscular contractions occurring at a frequency of 8–13 Hz centered in the pelvis and measured in the anus. They argue that the presence of this particular frequency of contractions can distinguish between voluntary contraction of these muscles and spontaneous involuntary contractions, and appears to more accurately correlate with orgasm as opposed to other metrics like heart rate that only measure excitation. They assert that they have identified "[t]he first objective and quantitative measure that has a strong correspondence with the subjective experience that orgasm ultimately is" and state that the measure of contractions that occur at a frequency of 8–13 Hz is specific to orgasm. They found that using this metric they could distinguish from rest, voluntary muscular contractions, and even unsuccessful orgasm attempts.Since ancient times in Western Europe, women could be medically diagnosed with a disorder called female hysteria, the symptoms of which included faintness, nervousness, insomnia, fluid retention, heaviness in abdomen, muscle spasm, shortness of breath, irritability, loss of appetite for food or sex, and "a tendency to cause trouble". Women considered suffering from the condition would sometimes undergo "pelvic massage" — stimulation of the genitals by the doctor until the woman experienced "hysterical paroxysm" (i.e., orgasm). Paroxysm was regarded as a medical treatment, and not a sexual release. The disorder has ceased to be recognized as a medical condition since the 1920s.
Brain
There have been very few studies correlating orgasm and brain activity in real time. One study examined 12 healthy women using a positron emission tomography (PET) scanner while they were being stimulated by their partners. Brain changes were observed and compared between states of rest, sexual stimulation, faked orgasm, and actual orgasm. Differences were reported in the brains of men and women during stimulation. However, changes in brain activity were observed in both sexes in which the brain regions associated with behavioral control, fear and anxiety shut down. Regarding these changes, Gert Holstege said in an interview with The Times, "What this means is that deactivation, letting go of all fear and anxiety, might be the most important thing, even necessary, to have an orgasm."While stroking the clitoris, the parts of the female brain responsible for processing fear, anxiety and behavioral control start to diminish in activity. This reaches a peak at orgasm when the female brains emotion centers are effectively closed down to produce an almost trance-like state. Holstege is quoted as saying, at the 2005 meeting of the European Society for Human Reproduction and Development: "At the moment of orgasm, women do not have any emotional feelings."However, a subsequent report by Rudie Kortekaas, et al. stated, "Gender commonalities were most evident during orgasm... From these results, we conclude that during the sexual act, differential brain responses across genders are principally related to the stimulatory (plateau) phase and not to the orgasmic phase itself."Research has shown that as in women, the emotional centers of a mans brain also become deactivated during orgasm but to a lesser extent than in women. Brain scans of both sexes have shown that the pleasure centers of a mans brain show more intense activity than in women during orgasm.Male and female brains demonstrate similar changes during orgasm, with brain activity scans showing a temporary decrease in the metabolic activity of large parts of the cerebral cortex with normal or increased metabolic activity in the limbic areas of the brain.EEG tracings from volunteers during orgasm were first obtained by Mosovich and Tallaferro in 1954. These research workers recorded EEG changes resembling petit mal or the clonic phase of a grand mal seizure. Further studies in this direction were carried out by Sem-Jacobsen (1968), Heath (1972), Cohen et al. (1976), and others. Sarrel et al. reported a similar observation in 1977. These reports continue to be cited. Unlike them, Craber et al. (1985) failed to find any distinctive EEG changes in four men during masturbation and ejaculation; the authors concluded that the case for the existence of EEG changes specifically related to sexual arousal and orgasm remained unproven. So disagreement arises as to whether the experiment conducted by Mosovich & Tallaferro casts a new light on the nature of orgasm. In some recent studies, authors tend to adopt the opposite point of view that there are no remarkable EEG changes during ejaculation in humans.
Health
General
Orgasm, and sexual activity as a whole, are physical activities that can require exertion of many major bodily systems. A 1997 study in the BMJ based upon 918 men age 45–59 found that after a ten-year follow-up, men who had fewer orgasms were twice as likely to die of any cause as those having two or more orgasms a week. A follow-up in 2001 which focused more specifically on cardiovascular health found that having sex three or more times a week was associated with a 50% reduction in the risk of heart attack or stroke.
There is some research suggesting that greater resting heart rate variability is associated with orgasms through penile-vaginal intercourse without additional simultaneous clitoral stimulation.A small percentage of men have a disease called postorgasmic illness syndrome (POIS), which causes severe muscle pain throughout the body and other symptoms immediately following ejaculation. The symptoms last for up to a week. Some doctors speculate that the frequency of POIS "in the population may be greater than has been reported in the academic literature", and that many POIS sufferers are undiagnosed.
Dysfunction and satisfaction
The inability to have orgasm, or regular difficulty reaching orgasm after ample sexual stimulation, is called anorgasmia or inorgasmia. If a male experiences erection and ejaculation but no orgasm, he is said to have sexual anhedonia (a condition in which an individual cannot feel pleasure from an orgasm) or ejaculatory anhedonia. Anorgasmia is significantly more common in women than in men, which has been attributed to the lack of sex education with regard to womens bodies, especially in sex-negative cultures, such as clitoral stimulation usually being key for women to orgasm.Approximately 25% of women report difficulties with orgasm, 10% of women have never had an orgasm, and 40% or 40–50% have either complained about sexual dissatisfaction or experienced difficulty becoming sexually aroused at some point in their lives. A 1994 study by Laumann et al. found that 75.0% of men and 28.6% of women always had orgasms with their spouse, while 40.2% of men and 79.7% of women thought their spouse always orgasmed during sex. These rates were different in non-marital straight relationships (cohabitational, long-term and short-term heterosexual relationships), with rates increasing to 80.5% for men and 43.0% for women orgasming during sex with their short-term partners, and 69.3% for men and 82.6% for women thinking their short-term partners always orgasmed. Women are much more likely to be nearly always or always orgasmic when alone than with a partner. However, in a 1996 study by Davis et al., 62% of women in a partnered relationship said they were satisfied with the frequency/consistency of their orgasms. Additionally, some women express that their most satisfying sexual experiences entail being connected to someone, rather than solely basing satisfaction on orgasm.Kinseys 1953 Sexual Behavior in the Human Female showed that, over the previous five years of sexual activity, 78% of women had orgasms in 60% to 100% of sexual encounters with other women, compared with 55% for heterosexual sex. Kinsey attributed this difference to female partners knowing more about womens sexuality and how to optimize womens sexual satisfaction than male partners do. Like Kinsey, scholars such as Peplau, Fingerhut and Beals (2004) and Diamond (2006) found that lesbians have orgasms more often and more easily in sexual interactions than heterosexual women do, and that female partners are more likely to emphasize the emotional aspects of lovemaking. In contrast, research by Diane Holmberg and Karen L. Blair (2009), published in the Journal of Sex Research, found that women in same-sex relationships enjoyed identical sexual desire, sexual communication, sexual satisfaction, and satisfaction with orgasm as their heterosexual counterparts.Specifically in relation to simultaneous orgasm and similar practices, many sexologists claim that the problem of premature ejaculation is closely related to the idea encouraged by a scientific approach in the early 20th century when mutual orgasm was overly emphasized as an objective and a sign of true sexual satisfaction in intimate relationships.
If orgasm is desired, anorgasmia may be attributed to an inability to relax. It may be associated with performance pressure and an unwillingness to pursue pleasure, as separate from the other persons satisfaction; often, women worry so much about the pleasure of their partner that they become anxious, which manifests as impatience with the delay of orgasm for them. This delay can lead to frustration of not reaching orgasmic sexual satisfaction. Psychoanalyst Wilhelm Reich, in his 1927 book Die Funktion des Orgasmus (published in English in 1980 as Genitality in the Theory and Therapy of Neurosis) was the first to make orgasm central to the concept of mental health, and defined neurosis in terms of blocks to having orgastic potency. Although orgasm dysfunction can have psychological components, physiological factors often play a role. For instance, delayed orgasm or the inability to achieve orgasm is a common side effect of many medications.
Menopause may involve loss of hormones supporting sexuality and genital functionality. Vaginal and clitoral atrophy and dryness affects up to 50%–60% of postmenopausal women. Testosterone levels in men fall as they age. Sexual dysfunction overall becomes more likely with poor physical and emotional health. "Negative experiences in sexual relationships and overall well-being" are associated with sexual dysfunction.
Theoretical biological and evolutionary functions of female orgasm
Shifts in research
The function or functions of the human female orgasm have been debated among researchers. Researchers have several hypotheses about the role, if any, of the female orgasm in the reproductive and therefore evolutionary process. The literature started with the argument that female orgasm is a byproduct of shared early male ontogeny, where male orgasm is an adaptation. Research has shifted to investigate and also support the sire-choice hypothesis, which proposes that female orgasm has been shaped by natural selection to function in the selection of high quality sires (male parents) for offspring. Therefore, orgasm increases the chances of conceiving with males of a high genetic quality. Research by Randy Thornhill et al. (1995) suggested that female orgasm is more frequent during intercourse with a male partner with low fluctuating asymmetry.
Selective pressure and mating
Wallen K and Lloyd EA stated, "In men, orgasms are under strong selective pressure as orgasms are coupled with ejaculation and thus contribute to male reproductive success. By contrast, womens orgasms in intercourse are highly variable and are under little selective pressure as they are not a reproductive necessity."Desmond Morris suggested in his 1967 popular-science book The Naked Ape that the female orgasm evolved to encourage physical intimacy with a male partner and help reinforce the pair bond. Morris suggested that the relative difficulty in achieving female orgasm, in comparison to the males, might be favorable in Darwinian evolution by leading the female to select mates who bear qualities like patience, care, imagination, and intelligence, as opposed to qualities like size and aggression, which pertain to mate selection in other primates. Such advantageous qualities thereby become accentuated within the species, driven by the differences between male and female orgasm. If males were motivated by, and taken to the point of, orgasm in the same way as females, those advantageous qualities would not be needed, since self-interest would be enough.
Fertility
There are theories that the female orgasm might increase fertility. For example, it has been suggested that the 30% reduction in size of the vagina could help clench onto the penis (much like, or perhaps caused by, the pubococcygeus muscles), which would make it more stimulating for the male (thus ensuring faster or more voluminous ejaculation). The British biologists Baker and Bellis have suggested that the female orgasm may have a peristalsis or "upsuck" action (similar to the esophagus ability to swallow when upside down), resulting in the retaining of favorable sperm and making conception more likely. They posited a role of female orgasm in sperm competition.
The observation that women tend to reach orgasm more easily when they are ovulating also has led to the suggestion that it is tied to increasing fertility. Evolutionary biologist Robin Baker argues in Sperm Wars that occurrence and timing of orgasms are all a part of the female bodys unconscious strategy to collect and retain sperm from more evolutionary fit men. This theory suggests that an orgasm during intercourse functions as a bypass button to a womans natural cervical filter against sperm and pathogens, and that an orgasm before functions to strengthen the filter.
Desmond Morris proposed that orgasm might facilitate conception by exhausting the female and keeping her horizontal, thus preventing the sperm from leaking out. This possibility, sometimes called the "Poleaxe Hypothesis" or the "Knockout Hypothesis", is now considered unlikely. A 1994 Learning Channel documentary on sex had fiber optic cameras inside the vagina of a woman while she had sexual intercourse. During her orgasm, her pelvic muscles contracted and her cervix repeatedly dipped into a pool of semen in the vaginal fornix, which might ensure that sperm would proceed by the external orifice of the uterus, making conception more likely.Evolutionary psychologists Christopher Ryan and Cacilda Jethá, in their discussion of the female orgasm, address how long it takes for females to achieve orgasm compared to males, and females ability to have multiple orgasms, hypothesizing how especially well suited to multiple partners and insemination this is. They quote primate sexuality specialist Alan Dixson in saying that the monogamy-maintenance explanation for female orgasm "seems far-fetched" because "females of other primate species, and particularly those with multimale-multifemale [promiscuous] mating systems such as macaques and chimpanzees, exhibit orgasmic responses in the absence of such bonding or the formation of stable family units." On the other hand, Dixson states that "Gibbons, which are primarily monogamous, do not exhibit obvious signs of female orgasm."The female promiscuity explanation of female sexuality was echoed at least 12 years earlier by other evolutionary biologists, and there is increasing scientific awareness of the female proceptive phase. Though Dixson classifies humans as mildly polygynous in his survey of primate sexuality, he appears to have doubts, when he writes, "One might argue that... the females orgasm is rewarding, increases her willingness to copulate with a variety of males rather than one partner, and thus promotes sperm competition." Ryan and Jethá use this as evidence for their theory that partible paternity and promiscuity were common for early modern humans.
Adaptive or vestigial
The clitoris is homologous to the penis; that is, they both develop from the same embryonic structure. While researchers such as Geoffrey Miller, Helen Fisher, Meredith Small and Sarah Blaffer Hrdy "have viewed the clitoral orgasm as a legitimate adaptation in its own right, with major implications for female sexual behavior and sexual evolution," others, such as Donald Symons and Stephen Jay Gould, have asserted that the clitoris is vestigial or nonadaptive, and that the female orgasm serves no particular evolutionary function. However, Gould acknowledged that "most female orgasms emanate from a clitoral, rather than vaginal (or some other), site" and stated that his nonadaptive belief "has been widely misunderstood as a denial of either the adaptive value of female orgasm in general, or even as a claim that female orgasms lack significance in some broader sense". He explained that although he accepts that "clitoral orgasm plays a pleasurable and central role in female sexuality and its joys," "[a]ll these favorable attributes, however, emerge just as clearly and just as easily, whether the clitoral site of orgasm arose as a spandrel or an adaptation". He said that the "male biologists who fretted over [the adaptionist questions] simply assumed that a deeply vaginal site, nearer the region of fertilization, would offer greater selective benefit" due to their Darwinian, summum bonum beliefs about enhanced reproductive success.Proponents of the nonadaptive hypothesis, such as Elisabeth Lloyd, refer to the relative difficulty of achieving female orgasm through vaginal sex, the limited evidence for increased fertility after orgasm and the lack of statistical correlation between the capacity of a woman to orgasm and the likelihood that she will engage in intercourse. "Lloyd is by no means against evolutionary psychology. Quite the opposite; in her methods and in her writing, she advocates and demonstrates a commitment to the careful application of evolutionary theory to the study of human behavior," stated Meredith L. Chivers. She added that Lloyd "meticulously considers the theoretical and empirical bases for each account and ultimately concludes that there is little evidence to support an adaptionist account of female orgasm" and that Lloyd instead "views female orgasm as an ontogenetic leftover; women have orgasms because the urogenital neurophysiology for orgasm is so strongly selected for in males that this developmental blueprint gets expressed in females without affecting fitness, just as males have nipples that serve no fitness-related function".A 2005 twin study found that one in three women reported never or seldom achieving orgasm during sexual intercourse, and only one in ten always orgasmed. This variation in ability to orgasm, generally thought to be psychosocial, was found to be 34% to 45% genetic. The study, examining 4000 women, was published in Biology Letters, a Royal Society journal. Elisabeth Lloyd has cited this as evidence for the notion that female orgasm is not adaptive.Miller, Hrdy, Helen OConnell and Natalie Angier have criticized the "female orgasm is vestigial" hypothesis as understating and devaluing the psychosocial value of the female orgasm. Hrdy stated that the hypothesis smacks of sexism. OConnell said, "It boils down to rivalry between the sexes: the idea that one sex is sexual and the other reproductive. The truth is that both are sexual and both are reproductive." OConnell used MRI technology to define the true size and shape of the clitoris, suggesting that it extends into the anterior wall of the vagina (see above).
OConnell describes typical textbook descriptions of the clitoris as lacking detail and including inaccuracies, saying that the work of Georg Ludwig Kobelt in the early 19th century provides a most comprehensive and accurate description of clitoral anatomy. She argues that the bulbs appear to be part of the clitoris and that the distal urethra and vagina are intimately related structures, although they are not erectile in character, forming a tissue cluster with the clitoris that appears to be the center of female sexual function and orgasm. By contrast, Nancy Tuana, at the 2002 conference for Canadian Society of Women in Philosophy, argues that the clitoris is unnecessary in reproduction, but that this is why it has been "historically ignored", mainly because of "a fear of pleasure. It is pleasure separated from reproduction. Thats the fear". She reasoned that this fear is the cause of the ignorance that veils female sexuality.
Fringe theories
Brody Costa et al. suggest that womens vaginal orgasm consistency is associated with being told in childhood or adolescence that the vagina is the important zone for inducing female orgasm. Other proposed factors include how well women focus mentally on vaginal sensations during penile-vaginal intercourse, the greater duration of intercourse, and preference for above-average penis length. Costa theorizes that vaginal orgasm is more prevalent among women with a prominent tubercle of the upper lip. His research indicates that "[a] prominent and sharply raised lip tubercle has been associated with greater odds (odds ratio = 12.3) of ever having a vaginal orgasm, and also with greater past month vaginal orgasm consistency (an effect driven by the women who never had a vaginal orgasm), than less prominent lip tubercle categories." However, lip tubercle was not associated with social desirability responding, or with orgasm triggered by masturbation during penile-vaginal sex, solitary or partner clitoral or vaginal masturbation, vibrator, or cunnilingus.An empirical study carried out in 2008 provides evidence for Freuds implied link between inability to have a vaginal orgasm and psychosexual immaturity. In the study, women reported their past month frequency of different sexual behaviors and corresponding orgasm rates and completed the Defense Style Questionnaire (DSQ-40), which is associated with various psychopathologies. The study concluded that a "vaginal orgasm was associated with less somatization, dissociation, displacement, autistic fantasy, devaluation, and isolation of affect." Moreover, "vaginally anorgasmic women had immature defenses scores comparable to those of established (depression, social anxiety disorder, panic disorder, and obsessive–compulsive disorder) outpatient psychiatric groups." In the study, a vaginal orgasm (as opposed to a clitoral orgasm) was defined as being triggered solely by penile–vaginal intercourse. According to Wilhelm Reich, the lack of womens capacity to have a vaginal orgasm is due to a lack of orgastic potency, which he believed to be the result of cultures suppression of genital sexuality.
Involuntary orgasm
Medical research shows that the genital reflex is also regulated by the spinal cord, and not necessarily under conscious control.An involuntary orgasm may occur as the result of sexual assault or rape, which may result in feelings of shame caused by internalization of victim-blaming attitudes. The incidence of those who experience unsolicited sexual contact and experience orgasm is very low, though possibly under-reported due to shame or embarrassment of the victim. Such orgasms may happen to either gender.An unwanted orgasm may arise from a persistent genital arousal disorder.
In consensual BDSM play, forced orgasm may be practised to exercise orgasm control.
Tantric sex
Tantric sex, which is not the same as Buddhist tantra (Vajrayana), is the ancient Indian spiritual tradition of sexual practices. It attributes a different value to orgasm than traditional cultural approaches to sexuality. Some practitioners of tantric sex aim to eliminate orgasm from sexual intercourse by remaining for a long time in the pre-orgasmic and non-emission state. Advocates of this, such as Rajneesh, claim that it eventually causes orgasmic feelings to spread out to all of ones conscious experience.Advocates of tantric and neotantric sex who claim that Western culture focuses too much on the goal of climactic orgasm, which reduces the ability to have intense pleasure during other moments of the sexual experience, suggest that eliminating this enables a richer, fuller and more intense connection.
Literature
Orgasm has been widely described in literature over the centuries. In antiquity, Latin literature addressed the subject as much as Greek literature: Book III of Ovids Metamorphoses retells a discussion between Jove and Juno, in which the former states: "The sense of pleasure in the male is far / More dull and dead, than what you females share." Juno rejects this thought; they agree to ask the opinion of Tiresias ("who had known Venus/Love in both ways," having lived seven years as a female). Tiresias offends Juno by agreeing with Jove, and she strikes him blind on the spot (Jove lessens the blow by giving Tiresias the gift of foresight, and a long life). Earlier, in the Ars Amatoria, Ovid states that he abhors sexual intercourse that fails to complete both partners.The theme of orgasm survived during Romanticism and is incorporated in many homoerotic works. In FRAGMENT: Supposed to be an Epithalamium of Francis Ravaillac and Charlotte Cordé, Percy Bysshe Shelley (1792–1822), "a translator of extraordinary range and versatility", wrote the phrase "No life can equal such a death." That phrase has been seen as a metaphor for orgasm, and it was preceded by the rhythmic urgency of the previous lines "Suck on, suck on, I glow, I glow!", which has been seen as alluding to fellatio. For Shelley, orgasm was "the almost involuntary consequences of a state of abandonment in the society of a person of surpassing attractions". Edward Ellerker Williams, the last love of Shelleys life, was remembered by the poet in "The Boat on the Serchio", which has been considered as possibly "the grandest portrayal of orgasm in literature":Shelley, in this poem, associates orgasm with death when he writes "the death which lovers love". In French literature, the term la petite mort (the little death) is a famous euphemism for orgasm; it is the representation of man who forgets himself and the world during orgasm. Jorge Luis Borges, in the same vision, wrote in one of the several footnotes of "Tlön, Uqbar, Orbis Tertius" that one of the churches of Tlön claims Platonically that "All men, in the vertiginous moment of coitus, are the same man. All men who repeat a line from Shakespeare are William Shakespeare." Shakespeare himself was knowledgeable of this idea: lines "I will live in thy heart, die in thy lap, and be buried in thy eyes" and "I will die bravely, like a smug bridegroom", said respectively by Benedick in Much Ado About Nothing and by King Lear in the play of that ilk, are interpreted as "to die in a womans lap" = "to experience a sexual orgasm". Sigmund Freud with his psychoanalytic projects, in The Ego and the Id (1923), speculates that sexual satisfaction by orgasm make Eros ("life instinct") exhausted and leaves the field open to Thanatos ("death instinct"), in other words, with orgasm Eros fulfills its mission and gives way to Thanatos. Other modern authors have chosen to represent the orgasm without metaphors. In the novel Lady Chatterleys Lover (1928), by D. H. Lawrence, we can find an explicit narrative of a sexual act between a couple: "As he began to move, in the sudden helpless orgasm there awoke in her strange thrills rippling inside her..."
Other animals
The mechanics of male orgasm are similar in most male mammals. Females of some mammal and some non-mammal species, such as alligators, have clitorises. There has been ongoing research about the sexuality of dolphins, one of many species which engage in sexual intercourse for reasons other than reproduction. The duration of orgasm varies considerably among different mammal species.
See also
References
Further reading
Banker-Riskin, Anita; Grandinetti, Deborah (1997). Simultaneous Orgasm: And Other Joys of Sexual Intimacy. Hunter House. ISBN 0-89793- |
Orgasm | 221-8, ISBN 978-0-89793-221-9.
Gabriele Froböse, Rolf Froböse, Michael Gross (Translator): Lust and Love: Is it More than Chemistry? Publisher: Royal Society of Chemistry, ISBN 0-85404-867-7, (2006).
Komisaruk, Barry R.; Beyer-Flores, Carlos; Whipple, Beverly (2006). The Science of Orgasm. Baltimore, MD: The Johns Hopkins University Press. ISBN 9780801888953. OCLC 614506284.
PARTRIDGE, Eric (2001). Shakespeares bawdy: Classics Series Routledge classics. 2nd ed., Routledge. ISBN 0-415-25400-0, ISBN 978-0-415-25400-7.
Plato (2001). The Banquet. (P.B. Shelley, Trans., J. Lauritsen, Ed., Foreword). Provincetown, MA: Pagan Press.
WEBB, Timothy (1976). The violet in the crucible: Shelley and translation, 1976. Oxford: Clarendon Press.
External links
Mens Health: Male Orgasm
Net Doctor: Female Orgasm
TED Talk by Mary Roach on 10 things you didnt know about orgasm |
Marjolins ulcer | Marjolins ulcer refers to an aggressive ulcerating squamous cell carcinoma presenting in an area of previously traumatized, chronically inflamed, or scarred skin.: 737 They are commonly present in the context of chronic wounds including burn injuries, varicose veins, venous ulcers, ulcers from osteomyelitis, and post radiotherapy scars.
The term was named after French surgeon, Jean-Nicolas Marjolin, who first described the condition in 1828. The term was later coined by J C De Costa.
Presentation
Slow growth, painlessness (as the ulcer is usually not associated with nerve tissue), and absence of lymphatic spread due to local destruction of lymphatic channels.
Histology
Histologically, the tumour is a well-differentiated squamous cell carcinoma. This carcinoma is aggressive in nature, spreads locally and is associated with a poor prognosis. The cancer has a 18-38% rate of metastasis.
40% occur on the lower limb and the malignant change is usually painless. This malignant change of the wound happens a long time after initial trauma, usually 10–25 years later. Its edge is everted and not always raised. More recent transcriptional analysis suggests that chronically impeded extracellular matrix turnover and epithelium-to-mesenchyme transitions in neglected scar tissue might give rise to this malignancy.
Diagnosis
Wedge biopsy is the favored method of diagnosis. Tissue specimens obtained should be taken from both the centre and margin of lesion, as the central ulcerated deposits may be necrotic.
Treatment
Treatment is usually surgical, with a wide excision of the lesion; typically a 1 cm margin all around is required.
See also
Saree cancer
References
== External links == |
Spastic diplegia | Spastic diplegia is a form of cerebral palsy (CP) that is a chronic neuromuscular condition of hypertonia and spasticity—manifested as an especially high and constant "tightness" or "stiffness"—in the muscles of the lower extremities of the human body, usually those of the legs, hips and pelvis. Doctor William John Littles first recorded encounter with cerebral palsy is reported to have been among children who displayed signs of spastic diplegia.
Spastic diplegia accounts for about 22% of all diagnoses of cerebral palsy, and together with spastic quadriplegia and spastic triplegia make up the broad classification spastic cerebral palsy, which accounts for 70% of all cerebral palsy diagnoses.
Presentation
Individuals with spastic diplegia are very tight and stiff and must work very hard to successfully resist and "push through" the extra tightness they perpetually experience. Other than this, however, these individuals are almost always normal in every significant clinical sense. When they are younger, spastic diplegic individuals typically undergo gait analysis so that their clinicians can determine the best assistive devices for them, if any are necessary, such as a walker or crutches. The main difference between spastic diplegia and a normal gait pattern is its signature "scissor gait"—a style that some non-disabled people might tend to confuse with the effects of drunkenness, multiple sclerosis, or another nerve disease. The degree of spasticity in spastic diplegia (and, for that matter, other types of spastic CP) varies widely from person to person. No two people with spastic diplegia are exactly alike. Balance problems and/or stiffness in gait can range from barely noticeable all the way to misalignments so pronounced that the person needs crutches (typically forearm crutches/lofstrand crutches) or a cane / walking stick to assist in ambulation. Less often, spasticity is severe enough to compel the person to use a wheelchair. In general, however, lower-extremity spasticity in spastic diplegia is rarely so great as to totally prevent ambulation—most people with the condition can walk, and can do so with at least a basic amount of overall stability. Regardless, from case to case, steeply varying degrees of imbalance, potential tripping over uneven terrain while walking, or needing to hold on to various surfaces or walls in certain circumstances to keep upright, are typically ever-present potential issues and are much more common occurrences amongst those with spastic diplegia than among those with a normal or near-normal gait pattern. Among some of the people with spastic diplegia who choose to be ambulatory on either an exclusive or predominant basis, one of the seemingly common lifestyle choices is for the person to ambulate within his or her home without an assistive device, and then to use the assistive device, if any, once outdoors. Others may use no assistive device in any indoor situation at all, while always using one when outdoors. Above the hips, persons with spastic diplegia typically retain normal or near-normal muscle tone and range of motion, though some lesser spasticity may also affect the upper body, such as the trunk and arms, depending on the severity of the condition in the individual (the spasticity condition affecting the whole body equally, rather than just the legs, is spastic quadriplegia, a slightly different classification). In addition, because leg tightness often leads to instability in ambulation, extra muscle tension usually develops in the shoulders, chest, and arms due to compensatory stabilisation movements, regardless of the fact that the upper body itself is not directly affected by the condition.
Social implications
Although the term "spastic" technically describes the attribute of spasticity in spastic cerebral palsy and was originally an acceptable and common term to use in both self-description and in description by others, it has since gained more notoriety as a pejorative, in particular when used in pop culture to insult non-disabled people when they seem overly anxious or unskilled in sports (see also the article Spastic (word)).
In 1952, a UK charitable organization with a membership mainly of those with spastic CP was formed; this organization called itself The Spastics Society. However, the charity changed its name to Scope in 1994 due to the term spastics having become enough of a pejorative to warrant the name change.Spastic diplegias social implications tend to vary with the intensity of the condition in the individual. If its effects are severely disabling, resulting in very little physical activity for the person, social elements can also suffer. Workplace environments can also be limited, since most labor-intensive work requires basic physical agility that spastic diplegics may not possess. However, the degree of variability among individuals with spastic diplegia means that no greater or lesser degree of stigma or real-world limitation is standard. Lesser effects usually mean fewer physical limitations, better-quality exercise, and more real-world flexibility, but the person is still in general seen as different from the norm. How such a person chooses to react to outside opinion is of paramount importance when social factors are considered.
Mechanism
Spastic diplegias particular type of brain damage inhibits the proper development of upper motor neuron function, impacting the motor cortex, the basal ganglia and the corticospinal tract. Nerve receptors in the spine leading to affected muscles become unable to properly absorb gamma amino butyric acid (GABA), the amino acid that regulates muscle tone in humans. Without GABA absorption to those particular nerve rootlets (usually centred, in this case, around the sectors L1-S1 and L2-S2), affected nerves (here, the ones controlling the legs) perpetually fire the message for their corresponding muscles to permanently, rigidly contract, and the muscles become permanently hypertonic (spastic).The abnormally high muscle tone that results creates lifelong difficulty with all voluntary and passive movement in the legs, and in general creates stress over time—depending on the severity of the condition in the individual, the constant spasticity ultimately produces pain, muscle/joint breakdown including tendinitis and arthritis, premature physical exhaustion (i.e., becoming physically exhausted even when you internally know that you have more energy than you are able to use), contractures, spasms, and progressively worse deformities/mis-alignments of bone structure around areas of the tightened musculature as the persons years progress. Severe arthritis, tendinitis, and similar breakdown can start as early as the spastic diplegic persons mid-20s (as a comparison, typical people with normal muscle tone are not at risk of arthritis, tendinitis, and similar breakdown until well into their 50s or 60s, if even then).No type of CP is officially a progressive condition, and indeed spastic diplegia does not clinically "get worse" given the nerves, damaged permanently at birth, neither recover nor degrade. This aspect is clinically significant because other neuromuscular conditions with similar surface characteristics in their presentations, like most forms of multiple sclerosis, indeed do degrade the body over time and do involve actual progressive worsening of the condition, including the spasticity often seen in MS. However, spastic diplegia is indeed a chronic condition; the symptoms themselves cause compounded effects on the body that are typically just as stressful on the human body as a progressive condition is. Despite this reality and the fact that muscle tightness is the symptom of spastic diplegia and not the cause, symptoms rather than cause are typically seen as the primary area of focus for treatment, especially surgical treatment, except when a selective dorsal rhizotomy is brought into consideration, or when an oral baclofen regimen is attempted.Unlike any other condition that may present with similar effects, spastic diplegia is entirely congenital in origin—that is, it is almost always acquired shortly before or during a babys birth process. Things like exposure to toxins, traumatic brain injury, encephalitis, meningitis, drowning, or suffocation do not tend to lead to spastic diplegia in particular or even cerebral palsy generally. Overall, the most common cause of spastic diplegia is Periventricular leukomalacia, more commonly known as neonatal asphyxia or infant hypoxia—a sudden in-womb shortage of oxygen-delivery through the umbilical cord. This sudden lack of oxygen is also almost always combined with premature birth, a phenomenon that, even by itself, would inherently risk the infant developing some type of CP. On the other hand, the presence of certain maternal infections during pregnancy such as congenital rubella syndrome can also lead to spastic diplegia, since such infections can have similar end results to infant hypoxia.
Treatment
As a matter of everyday maintenance, muscle stretching, range of motion exercises, yoga, contact improvisation, modern dance, resistance training, and other physical activity regimens are often utilized by those with spastic CP to help prevent contractures and reduce the severity of symptoms.
Major clinical treatments for spastic diplegia are:
Baclofen (and its derivatives), a gamma amino butyric acid (GABA) substitute in oral (pill-based) or intrathecal form. Baclofen is essentially chemically identical to the GABA that the damaged, over-firing nerves cannot absorb, except that it has an extra chemical marker on it that makes the damaged nerves think it is a different compound, and thus those nerves will absorb it. Baclofen is noted for being the sole medication available for GABA-deficiency-based spasticity which acts on the actual cause of the spasticity rather than simply reducing symptomatology as muscle relaxants and painkillers do. The intrathecal solution is a liquid injected into the spinal fluid for trial, and if successful in reducing spasticity, thereafter administered via an intrathecal pump, which has variously been proven potentially very dangerous on one or another level with long-term use (see article), including sudden and potentially lethal baclofen overdose, whereas the oral route, which comes in 10- or 20-milligram tablets and the dosage of which can be gently titrated either upward or downward, as well as safely ceased entirely, has not.
Antispasmodic muscle relaxant chemicals such as tizanidine and botulinum toxin (Botox), injected directly into the spastic muscles; Botox wears off every three months.
Phenol and similar chemical nerve deadeners, injected selectively into the over-firing nerves in the legs on the muscle end to reduce spasticity in their corresponding muscles by preventing the spasticity signals from reaching the legs; Phenol wears off every six months.
Orthopedic surgery to release the spastic muscles from their hypertonic state, a usually temporary result because the spasticity source is the nerves, not the muscles; spasticity can fully reassert itself as little as one year post-surgery.
Selective dorsal rhizotomy, a neurosurgery directly targeting and eliminating ("cutting" or "lesioning") the over-firing nerve rootlets and leaving the properly firing ones intact, thereby permanently eliminating the spasticity but compelling the person to spend months re-strengthening muscles that will have been severely weakened by the loss of the spasticity, due to the fact of those muscles not really having had actual strength to begin with.
Prognosis
Unusually, cerebral palsy, including spastic cerebral palsy, is notable for a glaring overall research deficiency—the fact that it is one of the very few major groups of conditions on the planet in human beings for which medical science has not yet (as of 2011) collected wide-ranging empirical data on the development and experiences of young adults, the middle aged and older adults. An especially puzzling aspect of this lies in the fact that cerebral palsy as defined by modern science was first discovered and specifically addressed well over 100 years ago and that it would therefore be reasonable to expect by now that at least some empirical data on the adult populations with these conditions would have long since been collected, especially over the second half of the 20th century when existing treatment technologies rapidly improved and new ones came into being. The vast majority of empirical data on the various forms of cerebral palsy is concerned near-exclusively with children (birth to about 10 years of age) and sometimes pre-teens and early teens (11-13). Some doctors attempt to provide their own personal justifications for keeping their CP specialities purely paediatric, but there is no objectively apparent set of reasons backed by any scientific consensus as to why medical science has made a point of researching adult cases of multiple sclerosis, muscular dystrophy and the various forms of cancer in young and older adults, but has failed to do so with CP. There are a few orthopaedic surgeons and neurosurgeons who claim to be gathering pace with various studies as of the past few years, but these claims do not yet seem to have been matched by real-world actualisation in terms of easily accessible and objectively verifiable resources available to the general public on the internet and in-person, where many, including medical-science researchers and doctors themselves, would more than likely agree such resources would ideally belong.
Prevalence
In the industrialized world, the incidence of overall cerebral palsy, which includes but is not limited to spastic diplegia, is about 2 per 1000 live births. Thus far, there is no known study recording the incidence of CP in the overall nonindustrialized world. Therefore, it is safe to assume that not all spastic CP individuals are known to science and medicine, especially in areas of the world where healthcare systems are less advanced. Many such individuals may simply live out their lives in their local communities without any medical or orthopedic oversight at all, or with extremely minimal such treatment, so that they are never able to be incorporated into any empirical data that orthopedic surgeons or neurosurgeons might seek to collect. It is shocking to note that—as with people with physical disability overall—some may even find themselves in situations of institutionalization, and thus barely see the outside world at all.
From what is known, the incidence of spastic diplegia is higher in males than in females; the Surveillance of Cerebral Palsy in Europe (SCPE), for example, reports a M:F ratio of 1.33:1. Variances in reported rates of incidence across different geographical areas in industrialized countries are thought to be caused primarily by discrepancies in the criteria used for inclusion and exclusion.
When such discrepancies are taken into account in comparing two or more registers of patients with cerebral palsy and also the extent to which children with mild cerebral palsy are included, the incidence rates still converge toward the average rate of 2:1000.
In the United States, approximately 10,000 infants and babies are born with CP each year, and 1200–1500 are diagnosed at preschool age when symptoms become more obvious. Those with extremely mild spastic CP may not even be aware of their condition until much later in life: Internet chat forums have recorded men and women as old as 30 who were diagnosed only recently with their spastic CP.
Overall, advances in care of pregnant mothers and their babies have not resulted in a noticeable decrease in CP; in fact, because medical advances in areas related to the care of premature babies have resulted in a greater survival rate in recent years, it is actually more likely for infants with cerebral palsy to be born into the world now than it would have been in the past. Only the introduction of quality medical care to locations with less-than-adequate medical care has shown any decreases in the incidences of CP; the rest either have shown no change or have actually shown an increase. The incidence of CP increases with premature or very low-weight babies regardless of the quality of care.
See also
Inclusion (disability rights)
Cerebral palsy
Spasticity
Gamma amino butyric acid
Rhizotomy
Tizanidine
References
Further reading
Miller, F.; Bachrach, S.J. (2006). Cerebral Palsy A Complete Guide for Caregiving (2nd ed.). Johns Hopkins University Press. ISBN 978-0801883552.
Miller, Freeman; Bachrach, Steven J. (1998). Cerebral Palsy: A Complete Guide for Caregiving. Johns Hopkins University Press. ISBN 978-0-8018-5949-6.
Kasper, D.L. et al. (2005), Harrisons Principles of Internal Medicine, McGraw-Hill
Collison, L (2020). Spastic Diplegia - Bilateral Cerebral Palsy. Gillette Childrens Healthcare Press. ISBN 978-1952181009.
== External links == |
Phosphene | A phosphene is the phenomenon of seeing light without light entering the eye. The word phosphene comes from the Greek words phos (light) and phainein (to show). Phosphenes that are induced by movement or sound may be associated with optic neuritis.Phosphenes can be induced by mechanical, electrical, or magnetic stimulation of the retina or visual cortex, or by random firing of cells in the visual system. Phosphenes have also been reported by meditators (called nimitta), people who endure long periods without visual stimulation (the prisoners cinema), or those who ingest psychedelic drugs.
Causes
Mechanical stimulation
The most common phosphenes are pressure phosphenes, caused by rubbing or applying pressure on or near the closed eyes. They have been known since antiquity, and described by the Greeks. The pressure mechanically stimulates the cells of the retina. Experiences include a darkening of the visual field that moves against the rubbing, a diffuse colored patch that also moves against the rubbing, well defined shapes such as bright circles that exist near or opposite to where pressure is being applied, a scintillating and ever-changing and deforming light grid with occasional dark spots (like a crumpling fly-spotted flyscreen), and a sparse field of intense blue points of light. Pressure phosphenes can persist briefly after the rubbing stops and the eyes are opened, allowing the phosphenes to be seen on the visual scene. Hermann von Helmholtz and others have published drawings of their pressure phosphenes. One example of a pressure phosphene is demonstrated by gently pressing the side of ones eye and observing a colored ring of light on the opposite side, as detailed by Isaac Newton.Another common phosphene is "seeing stars" from a sneeze, laughter, a heavy and deep cough, blowing of the nose, a blow on the head or low blood pressure (such as on standing up too quickly or prior to fainting). It is possible these involve some mechanical stimulation of the retina, but they may also involve mechanical and metabolic (such as from low oxygenation or lack of glucose) stimulation of neurons of the visual cortex or of other parts of the visual system.Less commonly, phosphenes can also be caused by some diseases of the retina and nerves, such as multiple sclerosis. The British National Formulary lists phosphenes as an occasional side effect of at least one anti-anginal medication.
The name "phosphene" was coined by J. B. H. Savigny, better known as the ships surgeon of the wrecked French frigate Méduse. It was first employed by Serre dUzes to test retinal function prior to cataract surgery.
Electrical stimulation
Phosphenes have been created by electrical stimulation of the brain, reported by neurologist Otfrid Foerster as early as 1929. Brindley and Lewin (1968) inserted a matrix of stimulating electrodes directly into the visual cortex of a 52-year-old blind female, using small pulses of electricity to create phosphenes. These phosphenes were points, spots, and bars of colorless or colored light. Brindley and Rushton (1974) used the phosphenes to create a visual prosthesis, in this case by using the phosphenes to depict Braille spots.
In recent years, researchers have successfully developed experimental brain–computer interfaces or neuroprostheses that stimulate phosphenes to restore vision to people blinded through accidents. Notable successes include the human experiments by William H. Dobelle and Mark Humayun and animal research by Dick Normann.
A noninvasive technique that uses electrodes on the scalp, transcranial magnetic stimulation, has also been shown to produce phosphenes.Experiments with humans have shown that when the visual cortex is stimulated above the calcarine fissure, phosphenes are produced in the lower part of the visual field, and vice versa.
Others
Phosphenes have been produced by intense, changing magnetic fields, such as with transcranial magnetic stimulation (TMS). These fields can be positioned on different parts of the head to stimulate cells in different parts of the visual system. They also can be induced by alternating currents that entrain neural oscillation as with transcranial alternating current stimulation. In this case they appear in the peripheral visual field. This claim has been disputed. The alternative hypothesis is that current spread from the occipital electrode evokes phosphenes in the retina. Phosphenes created by magnetic fields are known as magnetophosphenes.
Astronauts exposed to radiation in space have reported seeing phosphenes. Patients undergoing radiotherapy have reported seeing blue flashes of light during treatment; the underlying phenomenon has been shown to resemble Cherenkov radiation.Phosphenes can be caused by some medications, such as Ivabradine.
Mechanism
Most vision researchers believe that phosphenes result from the normal activity of the visual system after stimulation of one of its parts from some stimulus other than light. For example, Grüsser et al. showed that pressure on the eye results in activation of retinal ganglion cells in a similar way to activation by light. An ancient, discredited theory is that light is generated in the eye. A version of this theory has been revived, except, according to its author, that "phosphene lights are [supposed to be] due to the intrinsic perception of induced or spontaneous increased biophoton emission of cells in various parts of the visual system (from retina to cortex)"
Anthropological research
In 1988, David Lewis-Williams and T. A. Dowson published an article about phosphenes and other entoptic phenomena. They argued that non-figurative art of the Upper Paleolithic depicts visions of phosphenes and neurological "form constants", probably enhanced by hallucinogenic drugs.
Research
Research has looked into visual prosthesis for the blind, which involves use of arrays of electrodes implanted in the skull over the occipital lobe to produce phosphenes. There have been long term implants of this type. Risks such as infections and seizures, have been an impediment to their development.
A possible use of phosphenes as part of a brain to brain communication system has been reported. The system called BrainNet, produces phosphenes using transcranial magnetic stimulation (TMS). The goal of the research is to connect thoughts brain to brain using a system where signals are detected using electroencephalography (EEG) and delivered using transcranial magnetic stimulation (TMS). An experiment was conducted with 5 different groups, each contained three people. The subjects were split into two groups. Two subjects functioned as the senders, and were connected to EEG electrodes, and a third person functioned as the receiver, who wore the TMS helmet. Each person was stationed in front of a television screen with a Tetris-style game. The senders had to determine if there was a need to rotate the falling blocks, but without the ability to rotate them – only the receiver was able to perform this operation. At the edges of each screen, were two icons with two flashing lights in two different frequencies, (one at 15 Hz and the other at 17 Hz). The sender focused on one icon, or the other to signal that the block should be rotated to the right or the left. The EEG produced a unique signal, which was transmitted to the TMS helmet of the receiver, who perceived phosphenes which differed for the 15 Hz and 17 Hz signal, and rotated the block in the relevant direction. The experiment achieved 81% success.
See also
References
External links
https://www.oubliette.org.uk/ Entoptic Phenomena: Review of J. D. Lewis-Williams and T. A. Dowsons researchhttps://www.wynja.com/arch/entoptic.com Altered States: Review of J. D. Lewis-Williams and T. A. Dowsons researchBiophysical pictures within the brain |
Craniofrontonasal dysplasia | Craniofrontonasal dysplasia (craniofrontonasal syndrome, craniofrontonasal dysostosis, CFND) is a very rare X-linked malformation syndrome caused by mutations in the ephrin-B1 gene (EFNB1). Phenotypic expression varies greatly amongst affected individuals, where females are more commonly and generally more severely affected than males. Common physical malformations are: craniosynostosis of the coronal suture(s), orbital hypertelorism, bifid nasal tip, dry frizzy curled hair, longitudinal ridging and/or splitting of the nails, and facial asymmetry.The diagnosis CFND is determined by the presence of a mutation in the EFNB1 gene. Physical characteristics may play a supportive role in establishing the diagnosis.
The treatment is always surgical and is based on each patients specific phenotypic presentation.
Presentation
Phenotypic expression varies greatly between individuals with CFND. Some of the more prominent characteristics are:
Craniosynostosis of the coronal suture(s) (fusion of the coronal sutures),
Orbital hypertelorism (increased interocular distance),
Bifid nasal tip,
Dry frizzy curled hair,
Longitudinal ridging and / or splitting of the nails,
Facial Asymmetry.Other characteristics that are less frequently seen are: broad nasal base, low anterior hair line, low set ears, crowding of the teeth, maxillary hypoplasia, rounded and sloping shoulders, pectus excavatum, scoliosis, high arched palate, orbital dystopia, low implant of the breasts with asymmetric nipples and volume, webbed neck, hand or foot abnormalities such as clinodactyly (most common is a curved 5th finger) and cutaneous syndactyly (webbed fingers / toes).Females are more commonly and usually more severely affected than males. Males can however have (some of) the same symptoms as females, but this is not frequently seen. Most males have mild symptoms such as hypertelorism and a broad nasal base with bifid nose, but can also be a carrier of the mutation yet stay clinically unaffected.
Genetics
CFND is a very rare X-linked malformation syndrome caused by mutations in the ephrin-B1 gene (EFNB1). The EFNB1 gene codes for a membrane-anchored ligand which can bind to an ephrin tyrosine-kinase receptor. This ephrin receptor is, amongst other things, responsible for the regulation of embryonic tissue-border formation, and is important for skeletal and craniofacial development. As the ephrin receptor and its EFNB1 ligand are both bound to the (trans)membrane of the cell its cascade is activated through cell-cell interactions. These cell-cell interactions are disturbed due to the presence of cells with the mutant EFNB1 gene, as a result causing incomplete tissue-border formation.Paradoxical to other X-linked conditions, with CFND the females are more severely affected than males. This is due to the process of X-inactivation in females, where at random either the maternal or paternal X-chromosome is inactivated in a cell. Due to this process, the body’s tissues contain either cells with normal EFNB1 or the mutated EFNB1. This is called a mosaic pattern. This mosaic pattern of cells interferes with the functionality of the cell-cell interactions, as a result causing the severe physical malformations in females.As with all X-linked conditions CFND has a preset chance of being passed down from parents to their offspring. Females have two X-chromosomes and males have one X-chromosome. When a mother is a carrier of CFND, there is a 50% chance of her passing down the X-chromosome containing the mutated EFNB1 gene to her offspring, regardless if the child is a boy or girl. If the father is a carrier there is a 100% chance of him passing down his X-chromosome with the EFNB1 mutation to a daughter, and 0% chance of him passing it down to a son.
Diagnosis
The diagnosis CFND is established only after the presence of a mutation in the EFNB1 gene has been determined. Physical manifestations are not necessarily part of the diagnostic criteria, but can help guide in the right direction. This is due to the large heterogeneity between patients regarding phenotypic expression.20% of the patients that present with CFND-like characteristics do not display a mutation in the EFNB1 gene. The group of patients diagnosed with CFND is thus often overestimated. However, it is important to distinguish this population from CFND for research purposes. On the other hand, especially in males, it is possible that someone is a carrier of the EFNB1 gene mutation yet does not present with any physical manifestations. Screening for the presence of an EFNB1 mutation is thus the most reliable method to establish the diagnosis CFND.Genetic counseling or prenatal screening may be advised if there is a reason to suspect the presence of an EFNB1 gene mutation. Prenatal screening may be done by performing an ultrasound, where can be searched specifically for hypertelorism or a bifid nasal tip. However, this is quite difficult as facial involvement may not be obvious at such an early age, especially in cases with mild phenotypic presentation. The most definitive way to prove the presence of CFND is done by genetic testing, through amniocentesis and chorionic villus sampling. This however carries a greater risk of premature termination of the pregnancy.
Treatment
There is no ‘standard treatment’ for people with CFND due to the large variations in phenotypic expression. Each patient needs to be assessed and treated based on their specific presentation in order to restore the aesthetic and functional balance.Surgical corrections for the main symptoms;
Craniosynostosis correction: The preferred age for this procedure is between 6–9 months of age. Performing this surgery at such an early age can limit the further development of facial asymmetry, if the asymmetry is caused by the craniosynostosis, and prevents prolonged elevated intracranial pressure (ICP). However, the data for the exact risk of an elevated intracranial pressure for patients with CFND is lacking in the published literature. The surgery involves a frontal bone advancement in combination with remodelling of the supraorbital rim.
Orbital hypertelorism: It is preferred to wait with this treatment until the age of 5–8 years old, after permanent dentition. The procedures that can be performed are the facial bipartition and the box osteotomy. Facial bipartition is the preferable choice as there are less additional corrections needed, as well as providing a more stable long-term result after treatment. After the correction of the orbitas, the medial corners of the eyes are put more into a horizontal line.
Nasal deformity correction: The correction of the broad nasal base is simultaneously done with the orbital hypertelorism repair. This is for good alignment of the eyes with the nose for the best aesthetic result. A bifid nose tip will only be treated at the age of 18, when the patients skeleton has fully matured.
Epidemiology
Craniofrontonasal dysplasia is a very rare genetic condition. As such there is little information and no consensus in the published literature regarding the epidemiological statistics.The incidence values that were reported ranged from 1:100,000 to 1:120,000.
References
External links
Craniofrontonasal dysplasia at NIHs Office of Rare Diseases
Craniofrontonasal dysplasiaTeebi type at NIHs Office of Rare Diseases |
Amnion nodosum | Amnion nodosum are nodules found on the amnion, and is frequently present in oligohydramnios. The nodules are composed of squamous cell aggregates derived from the vernix caseosa on the fetal skin.
Amnion nodosum is caused by the unexpected abrasion of amnion with depositions of the fetal surface cells and acellular debris on the eroded areas(due to moderate or severe oligohydramnios, the amnion can get "touch" with the fetal skin). Amnion nodosum and oligohydramnios are associated with pulmonary hypoplasia and renal agenesis. Amnion nodosum is granules on amnion whereas whitish nodules on the cord suggest a candidal infection.
== References == |
Glossoptosis | Glossoptosis is a medical condition and abnormality which involves the downward displacement or retraction of the tongue. It may cause non-fusion of the hard palate, causing cleft palate.
It is one of the features of Pierre Robin sequence and Down syndrome.
== References == |
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy | Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is disease of the arteries in the brain, which causes tissue loss in the subcortical region of the brain and the destruction of myelin in the CNS. CARASIL is characterized by symptoms such as gait disturbances, hair loss, low back pain, dementia, and stroke. CARASIL is a rare disease, having only been diagnosed in about 50 patients, of which ten have been genetically confirmed. Most cases have been reported in Japan, but Chinese and caucasian individuals have also been diagnosed with the disease. CARASIL is inherited in an autosomal recessive pattern. There is currently no cure for CARASIL. Other names for CARASIL include familial young-adult-onset arteriosclerotic leukoencephalopathy with alopecia and lumbago without arterial hypertension, Nemoto disease and Maeda syndrome.
Signs and symptoms
Symptoms of CARASIL may include spondylosis deformans, lumbago (lower back pain) due to herniated disks, alopecia, spasticity in the limbs leading to gait disturbances, dysarthria, urinary incontinence, pseudobulbular signs, arteriosclerosis of cerebral arteries, mood changes, stroke, and dementia.Individuals with CARASIL may experience spondylosis and alopecia beginning in their teens, although alopecia is not seen in all patients. Other signs of the disease, particularly neurological abnormalities, may present from ages 20-40 with symptoms worsening over time. About 50% of affected patients present with stroke, and most strokes experienced by patients are lacunar infarcts. Many patients experience some form of mood changes, personality disorders, and/or dementia over time.
Cause
CARASIL is caused by mutation of the HTRA1 gene which encodes the HtrA serine peptidase 1 protein (HTRA1). HTRA1 is located on chromosome 10 and encodes an enzyme that regulates signaling by the TGF-β family of proteins. TGF-β protein family plays an important role in cellular functions, especially in angiogenesis. Individuals with CARASIL have mutations in HTRA1 which leads to a reduced amount of HTRA1 protein or no HTRA1 protein at all. The mutant proteins are unable to suppress TGF-β activity. Increase in TGF-β1 activity has been seen in the tunica media of affected small arteries.CARASIL is an autosomal recessive disease, meaning that both parents must be a carrier for the allele in order for the disease to be passed on to the child. As with other autosomal recessive diseases, the likelihood of receiving a recessive allele from both parents increases if the parents are closely related to each other (consanguineous). This trend has been observed for CARASIL.
Pathophysiology
A few different types of mutations to the HTRA1 gene have been observed in CARASIL patients. Nonsense mutations have been shown to cause no HTRA1 protein to be produced, while missense mutations have been shown to produce some HTRA1 protein, but with reduced activity. Regardless of whether or not HTRA1 protein is produced, or its activity is greatly reduced, the normal regulatory activity of the HTRA1 protein is lost. This means that TGF-β (transforming growth factor beta) signaling cannot be repressed as normal. When TGF-β activity goes unchecked, it alters the structure of the small blood vessels in the brain, increasing an individuals risk of stroke and other neurological abnormalities. Abnormally increased TGF-β activity is also suspected to be involved in the alopecia and lumbago seen in CARASIL patients, but that has not been confirmed and the mechanism is not yet known.CARASIL is a disease characterized by damage to the small blood vessels of the brain. When blood vessels in the brain are damaged, blood flow can be reduced or stopped leading to stroke. It can also lead to a variety of different symptoms depending on what area of the brain has lost its blood supply. This is what causes the spasticity in the limbs, slurred speech, urinary incontinence, and dysarthria seen in some patients.Progressive damage to and loss of the white matter, or myelinated areas, in the brain leads to some of the other neurological symptoms, such as forgetfulness progressing to dementia, mood changes, confusion, and apathy.
Diagnosis
CARASIL can be tentatively diagnosed by a thorough medical history, examination of symptoms, differential diagnoses, and MRI scans of the brain. Diffuse white matter changes (leukoencephalopathy) and multiple lacunar infarcts in the basal ganglia of the thalamus are usually determining factors seen on MRI scans of affected individuals. Further genetic testing must be used to confirm the diagnosis.It is suspected that there are many cases of CARASIL that have not been diagnosed because of the similarities with other neurological disorders. Several disease that are frequently used for differential diagnoses include Binswangers disease, CADASIL, Nasu-Hakula disease, and chronic progressive multiple sclerosis.
Treatment
There is currently no treatment or cure for CARASIL. Most frequently, a combination of supportive care and medications to prevent the occurrence of stroke are recommended. Counseling or other forms of emotional support may be beneficial to both patients and family members. Medications or therapies may be used to treat specific symptoms of the disease. Tizanidine and baclofen may be used to treat the spasticity of the limbs. A walker or cane may be used to assist individuals with gait disturbances. Anxiolytics may be prescribed for mood changes.
Prognosis
The prognosis for individuals with CARASIL is progressive neurological decline over the course of 10–20 years after the onset of symptoms, ultimately ending in death. CARASIL is a degenerative disease, and most patients live only 10 years past symptom onset, although some may live for 20–30 more years.
Epidemiology
Of the approximately 50 cases worldwide, the majority were found in Japan, with a few cases in China, Spain, Portugal, and Romania. CARASIL appears to affect males more often than females. A ratio of 7.5 males to 1 female was observed in Japan.
Research
Research consists primarily of case studies reporting observed cases of CARASIL, one study suggests that a possible future treatment option may be inhibition of TGF-β signaling by an angiotensin I receptor agonist, due to the fact that an excess of TGF-β signaling is involved in causing CARASIL. This approach has been used in Marfan syndrome, which also involves excessive TGF-β signaling This suggestion has not yet been testedA study examining the MRI scans of seven CARASIL patients in Japan found a characteristic "arc sign" in advanced cases. This may be used in the future to determine which patients should undergo genetic testing for CARASIL.
See also
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
References
== External links == |
Ectopic testis | A ectopic testis is a testicle that, although not an undescended testicle, has taken a non-standard path through the body and ended up in an unusual location.The positions of the ectopic testis may be: in the lower part of the abdomen, front of thigh, femoral canal, skin of penis or behind the scrotum. The testis is usually developed, and accompanied by an indirect inguinal hernia. It may be divorced from the epididymis which may lie in the scrotum.
See also
Cryptorchidism
Orchiopexy
References
== External links == |
Pigeon toe | Pigeon toe, also known as in-toeing, is a condition which causes the toes to point inward when walking. It is most common in infants and children under two years of age and, when not the result of simple muscle weakness, normally arises from underlying conditions, such as a twisted shin bone or an excessive anteversion (femoral head is more than 15° from the angle of torsion) resulting in the twisting of the thigh bone when the front part of a persons foot is turned in.
Causes
The cause of in-toeing can be differentiated based on the location of the misalignment. The variants are:
Curved foot (metatarsus adductus)
Twisted shin (tibial torsion)
Twisted thighbone (femoral anteversion)
Metatarsus adductus
The most common form of being pigeon toed, when the feet bend inward from the middle part of the foot to the toes. This is the most common congenital foot abnormality, occurring every 1 in 5,000 births. The rate of metatarsus adductus is higher in twin pregnancies and preterm deliveries. Most often self-resolves by one year of age and 90% of cases will resolve spontaneously (without treatment) by age 4.Signs and Symptoms
C-shaped lateral border of foot
Intoeing gait
Pressure sites during shoe wear
Tibial torsion
The tibia or lower leg slightly or severely twists inward when walking or standing. Usually seen in 1-3 year olds, internal tibial torsion is the most common cause of intoeing in toddlers. It is usually bilateral (both legs) condition that typically self-resolves by 4 to 5 years of age.Signs and Symptoms
Frequent tripping and clumsiness
Intoeing gait
Femoral anteversion
The neck of the femur is angled forward compared to the rest of the bone, causing a compensatory internal rotation of the leg. As a result, all structures downstream of the hip including the thigh, knee, and foot will turn in toward mid-line. Femoral anteversion is the most common cause of in toeing in children older than 3 years of age. It is most commonly bilateral, affects females twice as much as males, and in some families can show a hereditary pattern. This condition may progressively worsen from years 4 to 7, yet the majority of case still spontaneously resolve by 8 years of age.Signs and Symptoms
W-Sitting and inability to sit cross-legged
Intoeing gait
Circumduction Gait (legs swing around one another)
Frequent tripping and clumsiness
Diagnosis
Pigeon toe can be diagnosed by physical examination alone. This can classify the deformity into "flexible", when the foot can be straightened by hand, or otherwise "nonflexible". Still, X-rays are often done in the case of nonflexible pigeon toe. On X-ray, the severity of the condition can be measured with a "metatarsus adductus angle", which is the angle between the directions of the metatarsal bones, as compared to the lesser tarsus (the cuneiforms, the cuboid and the navicular bone). Many variants of this measurement exist, but Sgarlatos angle has been found to at least have favorable correlation with other measurements. Sgarlatos angle is defined as the angle between:
A line through the longitudinal axis of the second metatarsal bone.
The longitudinal axis of the lesser tarsal bones. For this purpose, one line is drawn between the lateral limits of the fourth tarsometatarsal joint and the calcaneocuboid joint, and another line is drawn between the medial limits of the talonavicular joint and the 1st tarsometatarsal joint. The transverse axis is defined as going through the middle of those lines, and hence the longitudinal axis is perpendicular to this axis.This angle is normally up to 15°, and an increased angle indicates pigeon toe. Yet, it becomes more difficult to infer the locations of the joints in younger children due to incomplete ossification of the bones, especially when younger than 3–4 years.
Internal Tibial Torsion
Internal tibial torsion is diagnosed by physical exam. The principle clinical exam is an assessment of the thigh-foot angle. The affected individual is placed in prone position with the knees flexed to 90 degrees. An imaginary line is drawn along the longitudinal axis of the thigh, and of the sole of the foot from a birds-eye view and the angle at the intersection of these two lines is measured. A value greater than 10 degrees of internal rotation is considered internal tibial torsion. A thigh-foot angle less than 10 degrees internal, and up to 30 degrees of external rotation is considered normal.Femoral Anteversion
Femoral anteversion is diagnosed by physical exam. The principle physical exam maneuver is an assessment of hip mobility. The child is evaluated in the prone position with knees flexed to 90 degrees. Using the tibia as a lever arm the femur is rotated both internally and externally. A positive exam demonstrates internal rotation of greater than 70 degrees and external rotation reduced to less than 20 degrees. Normal values for internal rotation are between 20 and 60 degrees and normal values for external rotation are between 30 and 60 degrees.
Treatment
In those less than eight years old with simple in-toeing and minor symptoms, no specific treatment is needed.Metatarsus Adductus
Nonoperative management: Non operative treatment of metatarsus adductus is dictated by the flexibility of the forefoot. If the child can actively correct the forefoot to midline no treatment is indicated. If the adduction cannot be corrected actively but is flexible in passive correction by an examiner, at-home stretching that mimics this maneuver can be performed by parents. In the case of a rigid deformity serial casting can straighten the foot.Surgical Management: Most cases of metatarsus adductus that does not resolve is asymptomatic in adulthood and does not require surgery. Occasionally, persistent rigid metatarsus adductus can produce difficulty and significant pain associated with inability to find accommodating footwear. Surgical options include tasometatarsal capsulotomy with tendontransfers or tarsal osteotomies. Due to the high failure rate of capsulotomy and tendon transfer it is generally avoided. Osteotomy (cutting of bone) and realignment of the medial cuneiform, cuboid, or second through fourth metatarsal the safer and most effective surgery in patients over the age of 3 years old with residual rigid metatarsus adductus.Internal Tibial Torsion
Nonoperative management: There are no bracing, casting, or orthotic techniques that have been shown to impact resolution of tibial torsion. This rotational limb variant does not increase risk for functional disability or higher rates of arthritis if unresolved. Management involves parental education and observational visits to monitor for failure to resolve.Surgical management: Indications for surgical correction are a thigh foot angle greater than 15 degrees in a child greater than 8 years of age that is experiencing functional limitations because of their condition. Surgical correction is achieved most commonly through a tibial derotational osteotomy. This procedure involves the cutting (osteotomy) and straightening (derotation) of the tibia, followed by internal fixation to allow the bone to heal in place.Femoral Anteversion
Nonoperative management: Nonoperative treatment includes observation and parental education. Treatment modalities such as bracing, physical therapy, and sitting restrictions have not demonstrated any significant impact on the natural history of femoral anteversion.Surgical management: Operative treatment is reserved for children with significant functional or cosmetic difficulties due to residual femoral anteversion greater than 50 degrees or internal hip rotation greater than 80 degrees after age 8. Surgical correction is achieved though a femoral derotation osteotomy. This procedure involves the cutting (osteotomy) and straightening (derotation) of the femur, followed by internal fixation and to allow the bone to heal in place.
See also
Bow-leggedness
References
External links
UK information from Oxford Hospitals NHS Trust
Metatarsus Adductus on POSNA—The Pediatric Orthopaedic Society of North America |
Chronic neutrophilic leukemia | Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm that features a persistent neutrophilia in peripheral blood, myeloid hyperplasia in bone marrow, hepatosplenomegaly, and the absence of the Philadelphia chromosome or a BCR/ABL fusion gene.
Signs and symptoms
The most common clinical finding is hepatosplenomegaly. Pruritus, gout, and mucocutaneous bleeding are occasionally seen.
Cause
The cause of CNL is currently unknown. An association between CNL and multiple myeloma has been suggested based on the observation of myeloma in 20% of CNL cases.
However, a clonal genetic abnormality has not been detected in these myeloma-associated cases of CNL, raising the possibility that the neutrophilia is a reaction due to the neoplastic myeloma cells. The postulated cell of origin is a limited-potential, marrow-derived stem cell.
Genetics
The majority (90%) of cases have not had detectable cytogenetic abnormalities. Most importantly, the Philadelphia chromosome and other BCR/ABL fusion genes are not detected.
Diagnosis
Laboratory findings
Peripheral blood neutrophilia (> 25 x 109/L) with myeloid precursors (promyelocytes, myelocytes, metamyelocytes) comprising less than 5% of leukocytes.
Sites of involvement
Peripheral blood, bone marrow, spleen, and liver are most common, but any organ or tissue can be infiltrated by neutrophils.
Bone marrow biopsy
On both the bone marrow aspirate and the core biopsy, a hypercellular marrow with an increased myeloid:erythroid ratio of 20:1 or greater. Myelocytes and neutrophils are increased, and blasts and promyelocytes are not increased. Due to the myeloproliferative nature of the disease, an increase in megakaryocytes and erythroid precursors may be observed, but dyspoiesis in not seen in any cell lineage. Also, reticulin fibrosis is rare. There is a reported association between CNL and multiple myeloma, so the bone marrow biopsy may show evidence of a plasma cell dyscrasia with increased numbers of atypical plasma cells.
Spleen
Splenic infiltrates are typically found only in the red pulp.
Liver
Hepatic infiltrates can be found in either the sinusoids, portal triad regions, or both.
Immunophenotype
No distinct immunophenotype abnormality for CNL has been described.
See OHSU 2013 findings of gene CSF3R, mutation p. T6181
Epidemiology
This is a rare disease, with less than 100 cases reported. Of these cases, an equal male:female ratio was observed,
with cases typically seen in older adults.
References
== External links == |
Foster Kennedy syndrome | Foster Kennedy syndrome is a constellation of findings associated with tumors of the frontal lobe.Although Foster Kennedy syndrome is sometimes called "Kennedy syndrome", it should not be confused with Kennedy disease, or spinal and bulbar muscular atrophy, which is named after William R. Kennedy.
Pseudo-Foster Kennedy syndrome is defined as one-sided optic atrophy with papilledema in the other eye but with the absence of a mass.
Presentation
The syndrome is defined as the following changes:
optic atrophy in the ipsilateral eye
disc edema in the contralateral eye
central scotoma (loss of vision in the middle of the visual fields) in the ipsilateral eye
anosmia (loss of smell) ipsilaterallyThis syndrome is due to optic nerve compression, olfactory nerve compression, and increased intracranial pressure (ICP) secondary to a mass (such as meningioma or plasmacytoma, usually an olfactory groove meningioma). There are other symptoms present in some cases such as nausea and vomiting, memory loss and emotional lability (i.e., frontal lobe signs).
Diagnosis
Brain tumor can be visualized very well on CT scan, but MRI gives better detail and is the
preferred study.
Clinical localization of brain tumors may be possible by virtue of specific neurologic deficits or
symptom patterns.
Tumor at the base of the frontal lobe produces inappropriate behavior, optic nerve
atrophy on the side of the tumor, papilledema on the other side, and anosmia.
Treatment
The treatment, and therefore prognosis, varies depending upon the underlying tumour. While awaiting surgical removal, treat any increased intracranial pressure
with high-dose steroids (i.e., dexamethasone).
History
The syndrome was first extensively noted by Robert Foster Kennedy in 1911, an Irish neurologist, who spent most of his career working in the United States of America. However, the first mention of the syndrome came from a William Gowers in 1893. Schultz–Zehden described the symptoms again in 1905. A later description was written by Wilhelm Uhthoff in 1915.
References
== External links == |
Serrated polyposis syndrome | Serrated polyposis syndrome (SPS), previously known as hyperplastic polyposis syndrome, is a disorder characterized by the appearance of serrated polyps in the colon. While serrated polyposis syndrome does not cause symptoms, the condition is associated with a higher risk of colorectal cancer (CRC). The lifelong risk of CRC is between 25 and 40%. SPS is the most common polyposis syndrome affecting the colon, but is under recognized due to a lack of systemic long term monitoring. Diagnosis requires colonoscopy, and is defined by the presence of either of two criteria: ≥5 serrated lesions/polyps proximal to the rectum (all ≥ 5 mm in size, with two lesions ≥10 mm), or >20 serrated lesions/polyps of any size distributed throughout the colon with 5 proximal to the rectum.A family history of SPS and smoking tobacco are associated with a higher risk of serrated polyposis syndrome, whereas the use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a lower risk. While the only validated genetic cause of SPS is RNF43, additional important genetic abnormalities include BRAF mutations, abnormal CpG island methylator phenotype, and microsatellite instability. However, most individuals with the syndrome do not have an associated germline mutation. The types of polyps found in SPS include sessile serrated adenomas/polyps, traditional serrated adenomas, and hyperplastic polyps. SPS occurs in 2 phenotypes: proximal and distal. Proximal SPS has a greater risk of CRC than distal SPS.
The vast majority of cases may be managed with colonoscopy with removal polyps (polypectomy). Polyp removal is recommended to decrease the risk of colorectal cancer. Repeat colonoscopy should be performed every 1–2 years. If polyps are very large, numerous, or increase in number rapidly, then surgery may be necessary. Surgery may also be warranted if CRC is suspected or confirmed. First-degree relatives of people with SPS have an increased risk of CRC, and should undergo early screening with colonoscopy.
Types
SPS may occur with one of two phenotypes: distal or proximal. The distal phenotype may demonstrate numerous small polyps in the distal colon (sigmoid) and rectum, whereas the proximal phenotype may be characterized by relatively fewer, but larger polyps in the proximal colon (cecum, ascending colon, etc.). Individuals meeting only criterion 3 from 2010 criteria, or only criterion 2 from the 2019 classification, have a distal phenotype have a lower risk of CRC compared with the proximal phenotype.
Signs and symptoms
Serrated polyposis syndrome often does not cause symptoms. The risk of colon cancer is between 25 and 40%.Sessile serrated polyps, as seen during endoscopy or colonoscopy, are flat (rather than raised) and are easily overlooked. Serrated lesions range in size from small (<5 mm) to large, and often have a "mucous cap" overlying the polyp. Serrated lesions are frequently located on the folds of the colon (haustral folds).
Pathophysiology
SPS is not caused by a single gene mutation. Several genetic abnormalities are associated with the condition, and a familial or inherited pattern may occur. Key genetic abnormalities include mutations in BRAF, abnormal CpG island methylator phenotype, and microsatellite instability. Additional implicated genes include: SMAD4, BMPR1A, PTEN, GREM1, and MUTYH. The only validated genetic cause of SPS is RNF43. However, most individuals with SPS do not have a germline mutation in any of the associated genes, including RNF43. As the underlying genetic risks for SPS are not fully understood, genetic testing is not recommended. Both autosomal dominant and autosomal recessive patterns of inheritance have been reported, as well as sporadic. Individuals with SPS have serrated polyps, which include hyperplastic polyps, traditional serrated adenomas, and sessile serrated polyps. In addition to serrated polyps, adenomas are often identified.
Diagnosis
The diagnosis of serrated polyposis syndrome is achieved when either one of two criteria are met: ≥5 serrated lesions/polyps proximal to the rectum (all ≥ 5 mm in size, with two lesions ≥10 mm), or >20 serrated lesions/polyps of any size distributed throughout the large bowel with 5 proximal to the rectum. Any serrated polyp is counted towards the diagnosis, including sessile serrated lesions, hyperplastic polyps, and traditional serrated adenomas. In addition, the cumulative number of serrated lesions is cumulative over time and includes multiple colonoscopies. The diagnosis of SPS is often overlooked, and requires lifelong tracking of cumulative serrated polyps.
Treatment
Colonoscopy is the mainstay of treatment for SPS, which allows for the identification of polyps and removal. Polyp removal is recommended to prevent the development of colorectal cancer. If polyps are relatively few, then removal may be achieved with colonoscopy. After polyps are removed, repeat colonoscopy is recommended in 1 to 3 year intervals. On average, about 2.8 colonscopies are necessary to achieve control of disease. The majority of cases may be managed with colonoscopy alone. Narrow-band imaging, an imaging technique used to enhance features of mucosa seen during colonoscopy, may improve detection of serrated lesions; however, one multicenter trial did not show improved detection.If polyps are very numerous, very large, or their growth cannot be controlled with colonoscopy, then surgery may be necessary. When surgery is necessary, a total abdominal colectomy with ileorectal anastomosis should be considered to minimize the risk of colon cancer. If surgery is necessary and involvement of polyps is focal or largely confined to a particular section of bowel, then segmental resection may be considered. Segmental resection is also recommended for cancer. In most cases, the rectum is left in place. Any remaining segments of colon or rectum require annual surveillance with colonoscopy.First degree relatives of people with SPS are at a higher risk of colorectal cancer and SPS. As such, these individuals should undergo screening with colonoscopy beginning at the earliest of the following: 40 years of age, the age of the youngest diagnosis of SPS in the family, or 10 years younger than the earliest CRC related to SPS. Repeat colonoscopy should be performed at 5 year intervals.
Prognosis
The overall risk of colorectal cancer is about 19.9%. However, the risk of cancer varies widely and depends on age, polyp burden, phenotype and the presence of dysplasia on histology. Endoscopic surveillance can decrease the risk of progression to cancer.
History
The condition was originally known as hyperplastic polyposis syndrome. When the syndrome was first recognized, only hyperplastic polyps were included in its definition, and the syndrome was believed to not be associated with a higher risk of colorectal cancer. In 1996, a case series revealed an association of the syndrome with cancer and serrated adenomas. Subsequently, other types of serrated polyps were found to occur in this condition, so the name was adjusted to the present "serrated polyposis syndrome."The World Health Organization released diagnostic criteria in 2010, which were updated in 2010 and again in 2019. The 2010 classification defined SPS as meeting any of the following criteria: 1) five or more serrated polyps proximal to the sigmoid colon with 2 larger than 10 mm in size, 2) any serrated polyps found proximal to the sigmoid colon in a person with a first-degree relative with serrated polyposis, or 3) more than 20 serrated colon polyps. The updated 2019 classification revised the first criterion to include lesions in the sigmoid colon, and excluded very small polyps (<5 mm). The updated 2019 classification also removed the criterion that included any serrated lesions proximal to the sigmoid colon in a person with a first degree relative with SPS.
Epidemiology
Data regarding overall prevalence of SPS is lacking, but it is estimated to occur in roughly 1 in 100,000. SPS is equally common among men and women. Most individuals with SPS are diagnosed between 40 and 60 years of age, with an average age of 55 years. Nearly half of individuals with SPS have a family member with colorectal cancer. Most individuals (37–70%) with SPS fulfill criterion 3 of the 2010 criteria (now criteria 2 from the 2019 classification). Of the remaining individuals with SPS, roughly half meet only criterion 1 and half meet both criteria 1 and 3 (2010 classification).
Among individuals undergoing colonoscopy for the evaluation of an abnormal fecal occult blood test, the prevalence of SPS ranges from 0.34 to 0.66%. The overall prevalence of SPS is 0.03–0.5%. The prevalence of SPS is between 1 in 127 and 1 in 242 among individuals undergoing colonoscopy. SPS is associated with tobacco use. Aside from colorectal cancer, the risk of others cancers is not increased in people with SPS. Aspirin and nonsteroidal anti-inflammatory drug (NSAIDs) may be associated with a lower risk of SPS. SPS is the most common polyposis syndrome affecting the colon.There is no clear association of SPS with any cancers other than colorectal cancer. However, there is mixed evidence regarding a possible association with SPS and pancreatic cancer. Individuals with a history of lymphoma have a higher risk of developing sessile serrated polyposis syndrome.
== References == |
Legius syndrome | Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was first described in 2007 and is often mistaken for neurofibromatosis type I (NF-1). It is caused by mutations in the SPRED1 gene. It is also known as neurofibromatosis type 1-like syndrome (NFLS).
Symptoms and signs
Nearly all individuals with Legius syndrome show multiple café au lait spots on their skin.
Symptoms may include:
Freckles in the axillary and inguinal skin fold
Lipomas, developing in adulthood
Macrocephaly
Learning disabilities
ADHD
Developmental delayFeatures common in neurofibromatosis – like Lisch nodules (iris hamartomas diagnosed on slit lamp exam), bone abnormalities, neurofibromas, optic pathway gliomas and malignant peripheral nerve sheath tumors – are absent in Legius syndrome.
Cause
Legius syndrome is a phakomatosis and a RASopathy, a developmental syndrome due to germline mutations in genes. The condition is autosomal dominant in regards to inheritance and caused by mutations to the SPRED1 gene at chromosome 15, specifically 15q14 (or (GRCh38): 15:38,252,086-38,357,248). The gene in question demonstrates almost 100 mutations.
Mechanism
A mutated SPRED1 protein adversely regulates Ras-MAPK signaling, which is a chain of proteins in a cell that sends signals from the surface of a cell to the nucleus which in turn causes the symptoms of this condition.
Diagnosis
Genetic testing is necessary to identify the syndrome. The DNA test is necessary sometimes, because symptoms may not be sufficient to definitely diagnose this condition.
Differential diagnosis
The symptoms of Legius syndrome and NF-1 are very similar; An important difference between Legius syndrome and NF-1 is the absence of tumor growths Lisch nodules and neurofibromas which are common in NF-1.A genetic test is often the only way to make sure a person has LS and not NF-1; the similarity of symptoms stem from the fact that the different genes affected in the two syndromes code for proteins that carry out a similar task in the same reaction pathway.
Treatment
Management of Legius syndrome is done via the following:
Physical therapy
Speech therapy
Pharmacologic therapy (e.g. methylphenidate for ADHD)The prognosis of this condition is generally considered good with appropriate treatment.
See also
List of cutaneous conditions
List of genes mutated in cutaneous conditions
References
Further reading
MD, Robert P. Erickson; PhD, Anthony J. Wynshaw-Boris MD (2016). Epsteins Inborn Errors of Development: The Molecular Basis of Clinical Disorders of Morphogenesis. Oxford University Press. ISBN 9780190275426. Retrieved 1 June 2017.
Zhang, Jia (2016). "Molecular screening strategies for NF1-like syndromes with café-au-lait macules". Molecular Medicine Reports. 14 (5): 4023–4029. doi:10.3892/mmr.2016.5760. PMC 5112360. PMID 27666661. Review
External links
PubMed |
Marshall syndrome | Marshall syndrome is a genetic disorder of the connective tissue which can cause hearing loss. The three most common areas to be affected are the eyes which are uncommonly large, joints and the mouth and facial structures. Marshall syndrome and Stickler syndrome closely resemble each other; in fact they are so similar, some say they are the same.
Presentation
Eyes
Myopia is the most common eye problem in Marshall syndrome. Cataracts also occur more frequently and detached retina less frequently than in Stickler syndrome. Myopia also is the most common problem with the eyes in Stickler syndrome. In the latter syndrome, extreme myopia may lead to severe eye problems such as detached retina more frequently than in Marshall syndrome.
Joints
The joint changes include hyperextensibility (double-jointedness) and arthritis. Babies and young children with Stickler syndrome usually have very hyperextensible joints. As an affected child gets older, they may experience pain and stiffness from overuse of a joint. Osteoarthritis of the large joints often develops during the third or fourth decade. The joint changes in Marshall syndrome are of the same type but to a lesser degree. There also may be changes in the bones that show up on X-ray but generally are not a problem.
Orofacial Structure
The most severe problem associated with Stickler syndrome is Pierre Robin syndrome. This refers to a cleft palate resulting from a very small lower jaw. During early fetal life, the roof of the mouth is normally open and the sides of the palate have to come together to close. If the jaw is too small, there is not enough room for the tongue which is then pushed up and gets in the way of the closing palate. Sometimes the chin is so small the baby has problems with eating and breathing if the tongue blocks the back of the throat. Cleft palate is found less frequently in Marshall Syndrome than in Stickler syndrome but still more frequently than in the general population.The facial features of Marshall Syndrome include a flat midface, the appearance of large eyes, short upturned nose, and a round face. The facial features of Stickler syndrome are less prominent but include a rather long flat face, and depressed nasal bridge.
Hearing loss
The hearing loss associated with Stickler syndrome can be progressive and usually involves the high frequencies. Sensorineural hearing loss has been reported in as many as 100% and as low as 20% of affected individuals. A conductive loss due to otitis can magnify an existing sensorineural loss and is a frequent problem for children with Stickler or Marshall Syndrome.
Genetics
Stickler syndrome and Marshall syndrome have an autosomal dominant pattern of inheritance. However, there is a great deal of variation within and among families with regard to gene expression. Some may be more severely affected and others may be very mildly affected. Often these syndromes are not recognized in a family until a baby is born with Pierre Robin syndrome or some members have detached retinas or cataracts at a young age.Both syndromes where correlated with mutations in the COL11A1 gene.
Diagnosis
Diagnosis is made based on features as well as by the very early onset of serious eye and ear disease. Because Marshall syndrome is an autosomal dominant hereditary disease, physicians can also note the characteristic appearance of the biological parent of the child. A genetic test can be performed in Stickler syndrome diagnosis is made by doing a genetic test for the several collagen genes as well as other genes that are associated with Stickler as well as considering the presence and severity of Spondyloepiphyseal Dysplasia with association of reduced height and growth rate as well as other connective tissue features like skin hyperextensibility and poor wound healing. It is an area of active research, also the genetic testing being expensive supports that the diagnosis is made depending on the features.
Treatment
There is no medical treatment for either syndrome but there are some recommendations that can help with prevention or early identification of some of the problems. Children with either syndrome should have their hearing tested, and adults should be aware that the hearing loss may not develop until the adult years. Yearly visits to an ophthalmologist or other eye care professional who has been informed of the diagnosis of Stickler or Marshall syndrome is important for all affected individuals. Children should have the opportunity to have myopia corrected as early as possible, and treatment for cataracts or detached retinas may be more effective with early identification. Support for the joints is especially important during sports, and some recommend that contact sports should be avoided by those who have very loose joints.
References
== External links == |
Hailey–Hailey disease | Hailey–Hailey disease, or familial benign chronic pemphigus: 559 or familial benign pemphigus,: 622 was originally described by the Hailey brothers (Hugh Edward and William Howard) in 1939. It is a genetic disorder that causes blisters to form on the skin.
Signs and symptoms
HHD is characterized by outbreaks of rashes and blisters on the skin. Affected areas of skin undergo repeated blistering and inflammation, and may be painful to the touch. Areas where the skin folds, as well as the armpits, groin, neck, buttocks and under the breasts are most commonly affected. In addition to blistering, other symptoms which accompany HHD include acantholysis, erythema and hyperkeratosis.
Causes
The cause of the disease is a haploinsufficiency of the enzyme ATP2C1; the ATP2C1 gene is located on chromosome 3, which encodes the protein hSPCA1. A mutation on one copy of the gene causes only half of this necessary protein to be made and the cells of the skin do not adhere together properly due to malformation of intercellular desmosomes, causing acantholysis, blisters and rashes. There is no known cure.
Diagnosis
Classification
While the term pemphigus typically refers to "a rare group of blistering autoimmune diseases" affecting "the skin and mucous membranes", Hailey–Hailey disease is not an autoimmune disorder and there are no autoantibodies. According to Pemphigus Pemphigoid Foundation (IPPF), "familial benign chronic pemphigus, or Hailey-Hailey disease, is a different condition from Pemphigus".
Differential diagnosis
The differential diagnosis includes intertrigo, candidiasis, frictional or contact dermatitis, and inverse psoriasis. A biopsy and/or family history can confirm. The lack of oral lesions and intercellular antibodies distinguishes familial benign pemphigus from other forms of pemphigus.
Treatment
Topical steroid preparations often help outbreaks; use of the weakest corticosteroid that is effective is recommended to help prevent thinning of the skin. Drugs such as antibiotics, antifungals, corticosteroids, dapsone, methotrexate, thalidomide, etretinate, cyclosporine and, most recently, intramuscular alefacept may control the disease but are ineffective for severe chronic or relapsing forms of the disease. Intracutaneous injections of botulinum toxin to inhibit perspiration may be of benefit. Maintaining a healthy weight, avoiding heat and friction of affected areas, and keeping the area clean and dry may help prevent flares.Some have found relief in laser resurfacing that burns off the top layer of the epidermis, allowing healthy non-affected skin to regrow in its place.Secondary bacterial, fungal and/or viral infections are common and may exacerbate an outbreak. Some have found that outbreaks are triggered by certain foods, hormone cycles and stress.
In many cases naltrexone, taken daily in low doses, appears to help.
See also
List of cutaneous conditions
References
== External links == |
Placental infarction | A placental infarction results from the interruption of blood supply to a part of the placenta, causing its cells to die.
Small placental infarcts, especially at the edge of the placental disc, are considered to be normal at term. Large placental infarcts are associated with vascular abnormalities, e.g. hypertrophic decidual vasculopathy, as seen in hypertension. Very large infarcts lead to placental insufficiency and may result in fetal death.
Relation to maternal floor infarct
Maternal floor infarcts are not considered to be true placental infarcts, as they result from deposition of fibrin around the chorionic villi, i.e. perivillous fibrin deposition.
See also
Placental disease
References
External links
Gross pathology of a placental infarct (utah.edu) |
Periodontal abscess | A periodontal abscess (also termed lateral abscess, or parietal abscess), is a localized collection of pus (i.e. an abscess) within the tissues of the periodontium. It is a type of dental abscess. A periodontal abscess occurs alongside a tooth, and is different from the more common periapical abscess, which represents the spread of infection from a dead tooth (i.e. which has undergone pulpal necrosis). To reflect this, sometimes the term "lateral (periodontal) abscess" is used. In contrast to a periapical abscess, periodontal abscesses are usually associated with a vital (living) tooth. Abscesses of the periodontium are acute bacterial infections classified primarily by location.
Signs and symptoms
The main symptom is pain, which often suddenly appears, and is made worse by biting on the involved tooth, which may feel raised and prominent in the bite. The tooth may be mobile, and the lesion may contribute to destruction of the periodontal ligament and alveolar bone. The pain is deep and throbbing. The oral mucosa covering an early periodontal abscess appears erythematous (red), swollen and painful to touch. The surface may be shiny due to stretching of the mucosa over the abscess. Before pus has formed, the lesion will not be fluctuant, and there will be no purulent discharge. There may be regional lymphadenitis.
When pus forms, the pressure increases, with increasing pain, until it spontaneously drains and relieves the pain. When pus drains into the mouth, a bad taste and smell are perceived. Usually drainage occurs via the periodontal pocket, or else the infection may spread as a cellulitis or a purulent odontogenic infection. Local anatomic factors determine the direction of spread (see fascial spaces of the head and neck). There may be systemic upset, with an onset of pain and fever.
Causes
A periodontal abscess most commonly occurs as a complication of advanced periodontal disease (which is normally painless). A periodontal pocket contains dental plaque, bacteria and subgingival calculus. Periodontal pathogens continually find their way into the soft tissues, but normally they are held in check by the immune system. A periodontal abscess represents a change in this balance, related to decreased local or systemic resistance of the host. An inflammatory response occurs when bacteria invade and multiply within the soft tissue of the gingival crevice/periodontal pocket. A pus-filled abscess forms when the immune system responds and attempts to isolate the infection from spreading.
Communication with the oral environment is maintained via the opening of the periodontal pocket. However, if the opening of a periodontal pocket becomes obstructed, as may occur if the pocket has become very deep (e.g. with furcation involvement), then plaque and calculus are trapped inside. Food packing may also obstruct a periodontal pocket. Food packing is usually caused by failure to accurately reproduce the contact points when dental restorations are placed on the interproximal surfaces of teeth. Another potential cause occurs when a periodontal pocket is scaled incompletely. Following this procedure, the gingival cuff tightens around the tooth, which may be enough to trap the bacteria left in the pocket. A gingival retraction cord which is accidentally left in situ is an occasional cause of a periodontal abscess.
Penetrating injury to the gingiva--for example, with a toothbrush bristle, fishbone, toothpick or periodontal instrument--may inoculate bacteria into the tissues. Trauma to the tissues, such as serious impact on a tooth or excessive pressure exerted on teeth during orthodontic treatment, can be a possible cause as well. Occlusal overload may also be involved in the development of a periodontal abscess, but this is rare and usually occurs in combination with other factors. Bruxism is a common cause of excessive occlusal forces.
Systemic immune factors such as diabetes can predispose a person to the formation of periodontal abscesses.
Perforation of a root canal during endodontic therapy can also lead to a periodontal abscess which if left untreated could become "prolonged" ultimately rupture then enter the blood stream and could lead to serious situations such as endocarditis.
Diagnosis
Periodontal abscesses may be difficult to distinguish from periapical abscesses. Since the management of a periodontal abscess is different from a periapical abscess, this differentiation is important to make (see Dental abscess#Diagnostic approach) For example, root canal therapy is unnecessary and has no impact on pain in a periodontal abscess.
Classification
There are four types of abscesses that can involve the periodontal tissues:
Gingival abscess—a localized, purulent infection involves only the soft gum tissue near the marginal gingiva or the interdental papilla.
Periodontal abscess—a localized, purulent infection involving a greater dimension of the gum tissue, extending apically and adjacent to a periodontal pocket.
Pericoronal abscess—a localized, purulent infection within the gum tissue surrounding the crown of a partially or fully erupted tooth. Usually associated with an acute episode of pericoronitis around a partially erupted and impacted mandibular third molar (lower wisdom tooth).
combined periodontal/endodontic abscess
Treatment
An important factor is whether the involved tooth is to be extracted or retained. Although the pulp is usually still vital, a history of recurrent periodontal abscesses and significantly compromised periodontal support indicate that the prognosis for the tooth is poor and it should be removed.
The initial management of a periodontal abscess involves pain relief and control of the infection. The pus needs to be drained, which helps both of these aims. If the tooth is to be removed, drainage will occur via the socket. Otherwise, if pus is already discharging from the periodontal pocket, this can be encouraged by gentle irrigation and scaling of the pocket whilst massaging the soft tissues. If this does not work, incision and drainage is required, as described in Dental abscess#Treatment.
Antibiotics are of secondary importance to drainage, which if satisfactory renders antibiotics unnecessary. Antibiotics are generally reserved for severe infections, in which there is facial swelling, systemic upset and elevated temperature. Since periodontal abscesses frequently involve anaerobic bacteria, oral antibiotics such as amoxicillin, clindamycin (in penicillin allergy or pregnancy) and/or metronidazole are given (although metronidazole should be used in conjunction with a penicillin given its lack of aerobic gram positive coverage).. Ideally, the choice of antibiotic is dictated by the results of microbiological culture and sensitivity testing of a sample of the pus aspirated at the start of any treatment, but this rarely occurs outside the hospital setting.
Other measures that are taken during management of the acute phase might include reducing the height of the tooth with a dental drill, so it no longer contacts the opposing tooth when biting down; and regular use of hot salt water mouth washes (antiseptic) that encourages further drainage of the infection.
The management following the acute phase involves removing any residual infection, and correcting the factors that lead to the formation of the periodontal abscess. Usually, this will be therapy for periodontal disease, such as oral hygiene instruction and periodontal scaling.
References
== External links == |
Ketoacidosis | Ketoacidosis is a metabolic state caused by uncontrolled production of ketone bodies that cause a metabolic acidosis. While ketosis refers to any elevation of blood ketones, ketoacidosis is a specific pathologic condition that results in changes in blood pH and requires medical attention. The most common cause of ketoacidosis is diabetic ketoacidosis but can also be caused by alcohol, medications, toxins, and rarely starvation.
Signs and symptoms
The symptoms of ketoacidosis are variable depending on the underlying cause. The most common symptoms include nausea, vomiting, abdominal pain, and weakness. Breath may also develop the smell of acetone as it is a volatile ketone that can be exhaled. Rapid deep breathing, or Kussmaul breathing, may be present to compensate for the metabolic acidosis. Altered mental status is more common in diabetic than alcoholic ketoacidosis.
Causes
Ketoacidosis is caused by the uncontrolled production of ketone bodies. Usually the production of ketones is carefully controlled by several hormones, most importantly insulin. If the mechanisms that control ketone production fail, ketone levels may become dramatically elevated and cause dangerous changes in physiology such as a metabolic acidosis.
Diabetes
The most common cause of ketoacidosis is a deficiency of insulin in type 1 diabetes or late-stage type 2 diabetes. This is called diabetic ketoacidosis and is characterized by hyperglycemia, dehydration and metabolic acidosis. Other electrolyte disturbances such as hyperkalemia and hyponatremia may also be present. A lack of insulin in the bloodstream allows unregulated fatty acid release from adipose tissue which increases fatty acid oxidation to acetyl CoA, some of which is diverted to ketogenesis. This raises ketone levels significantly above what is seen in normal physiology.
Alcohol
Alcoholic ketoacidosis is caused by complex physiology that is usually the result of prolonged and heavy alcohol intake in the setting of poor nutrition. Chronic alcohol use can cause depleted hepatic glycogen stores and ethanol metabolism further impairs gluconeogenesis. This can reduce glucose availability and lead to hypoglycemia and increased reliance on fatty acid and ketone metabolism. An additional stressor such as vomiting or dehydration can cause an increase in counterregulatory hormones such as glucagon, cortisol and growth hormone which may further increase free fatty acid release and ketone production. Ethanol metabolism can also increase blood lactic acid levels which may also contribute to a metabolic acidosis.
Starvation
Starvation is a rare cause of ketoacidosis, usually instead causing physiologic ketosis without ketoacidosis. Ketoacidosis from starvation most commonly occurs in the setting of an additional metabolic stressor such as pregnancy, lactation, or acute illness.
Medications
Certain medications can also cause elevated ketones, such as SGLT2 inhibitors causing euglycemic ketoacidosis. Overdose of salicylates or isoniazid can also cause ketoacidosis.
Toxins
Ketoacidosis can be the result of ingestion of methanol, ethylene glycol, isopropyl alcohol, and acetone.
Pathophysiology
Ketones are primarily produced from free fatty acids in the mitochondria of liver cells. The production of ketones is strongly regulated by insulin and an absolute or relative lack of insulin underlies the pathophysiology of ketoacidosis. Insulin is a potent inhibitor of fatty acid release, so insulin deficiency can cause an uncontrolled release of fatty acids from adipose tissue. Insulin deficiency can also enhance ketone production and inhibit peripheral use of ketones. This can occur during states of complete insulin deficiency (such as untreated diabetes) or relative insulin deficiency in states of elevated glucagon and counter-regulatory hormones (such as starvation, heavy chronic alcohol use or illness).Acetoacetic acid and β-hydroxybutyrate are the most abundant circulating ketone bodies. Ketone bodies are acidic; however, at physiologic concentrations, the bodys acid/base buffering system prevents them from changing blood pH.
Management
Treatment depends on the underlying cause of the ketoacidosis. Diabetic ketoacidosis is resolved with insulin infusion, intravenous fluids, electrolyte replacement and supportive care. Alcoholic ketoacidosis is treated with intravenous dextrose and supportive care and usually does not require insulin. Starvation ketoacidosis can be resolved with intravenous dextrose with attention to electrolyte changes that can occur with refeeding syndrome.
Epidemiology
Certain populations are predisposed to develop ketoacidosis including people with diabetes, people with a history of prolonged and heavy alcohol use, pregnant women, breastfeeding women, children, and infants.
People with diabetes that produce very little or no insulin are predisposed to develop ketoacidosis, especially during periods of illness or missed insulin doses. This includes people with type 1 diabetes or ketosis prone diabetes.Prolonged heavy alcohol use is a risk of ketoacidosis, especially in people with poor nutrition or a concurrent illness.Pregnant women have high levels of hormones including glucagon and human placental lactogen that increase circulating free fatty acids which increases ketone production. Lactating women also are predisposed to increased ketone production. These populations are at risk of developing ketoacidosis in the setting of metabolic stressors such as fasting, low-carbohydrate diets, or acute illness.Children and infants have lower glycogen stores and may develop high levels of glucagon and counter-regulatory hormones during acute illness, especially gastrointestinal illness. This allows children and infants to easily produce ketones and although rare, can progress to ketoacidosis in acute illness.
See also
Alcoholic ketoacidosis
Diabetic ketoacidosis
Ketosis
Kussmaul breathing
Metabolic acidosis
Type I diabetes
== References == |
Cirsoid aneurysm | A cirsoid aneurysm, also referred to as an arteriovenous hemangioma is the dilation of a group of blood vessels due to congenital malformations with arterio venous (AV) shunting. "Cirsoid" means resembling a varix. They are most common on the head or neck.Cirsoid aneurysms appear as nodules or papules. Histologically, they are composed of both thick- and thin-walled blood vessels.
== References == |
Achondroplasia | Achondroplasia is a genetic disorder with an autosomal dominant pattern of inheritance whose primary feature is dwarfism. In those with the condition, the arms and legs are short, while the torso is typically of normal length. Those affected have an average adult height of 131 centimetres (4 ft 4 in) for males and 123 centimetres (4 ft) for females. Other features can include an enlarged head and prominent forehead. Complications can include sleep apnea or recurrent ear infections. Achondroplasia includes short-limb skeletal dysplasia with severe combined immunodeficiency.
Achondroplasia is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene that results in its protein being overactive. Achondroplasia results in impaired endochondral bone growth (bone growth within cartilage). The disorder has an autosomal dominant mode of inheritance, meaning only one mutated copy of the gene is required for the condition to occur. About 80% of cases occur in children of parents of average stature and result from a new mutation, which most commonly originates as a spontaneous change during spermatogenesis. The rest are inherited from a parent with the condition. The risk of a new mutation increases with the age of the father. In families with two affected parents, children who inherit both affected genes typically die before birth or in early infancy from breathing difficulties. The condition is generally diagnosed based on the clinical features but may be confirmed by genetic testing.Treatments may include support groups and growth hormone therapy. Efforts to treat or prevent complications such as obesity, hydrocephalus, obstructive sleep apnea, middle ear infections or spinal stenosis may be required. Achondroplasia is the most common cause of dwarfism and affects about 1 in 27,500 people.
Signs and symptoms
Disproportionate dwarfism
Shortening of the proximal limbs (called rhizomelic shortening)
Short fingers and toes, with "trident hands" (short hands with stubby fingers, and a separation between the middle and ring fingers – reminiscent of a trident on fetal ultrasound )
Large head with prominent forehead frontal bossing
Small midface with a flattened nasal bridge
Spinal kyphosis (convex curvature) or lordosis (concave curvature)
Varus (bowleg) or valgus (knock knee) deformities
Frequent ear infections (due to Eustachian tube blockages), sleep apnea (which can be central or obstructive), and hydrocephalus
Complications
Children
Children with achondroplasia often have less muscle tone; because of this it is common for them to have delayed walking and motor skills. It is also common for children to have bowed legs, scoliosis, lordosis, arthritis, issues with joint flexibility, breathing problems, ear infections, and crowded teeth. These issues can be treated with surgery, braces, or physical therapy.
Hydrocephalus is a severe effect associated with achondroplasia in children. This condition occurs when cerebrospinal fluid is not able to flow in and out of the skull because of how the spine narrows. This fluid build up is associated with an enlarged head, vomiting, lethargy, headaches, and irritability. A shunt surgery is commonly performed to treat this condition, but an endoscopic third ventriculostomy can also be done.
Adults
Adults with achondroplasia often face issues with obesity and sleep apnea. It is also typical for adults to experience numbness or tingling in their legs because of nerve compression.
Some research has found that adults with achondroplasia may also experience psychosocial complications, usually associated with short stature.Pregnancy in women with achondroplasia is considered higher risk. Women with achondroplasia generally have their babies delivered through C-sections to prevent complications that could occur with a natural birth. The life expectancy of people with achondroplasia is approximately 10 years less than average.
Causes
Achondroplasia is caused by a mutation in fibroblast growth factor receptor 3 (FGFR3) gene. This gene encodes a protein called fibroblast growth factor receptor 3, which contributes to the production of collagen and other structural components in tissues and bones. When the FGFR3 gene is mutated it interferes with how this protein interacts with growth factors leading to complications with bone production. Cartilage is not able to fully develop into bone, causing the individual to be disproportionately shorter in height.In normal development FGFR3 has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones. The effect is genetically dominant, with one mutant copy of the FGFR3 gene being sufficient to cause achondroplasia, while two copies of the mutant gene are invariably fatal (recessive lethal) before or shortly after birth (known as a lethal allele). This occurs due to respiratory failure from an underdeveloped ribcage. A person with achondroplasia thus has a 50% chance of passing dwarfism to each of their offspring. People with achondroplasia are often born to parents that do not have the condition due to spontaneous mutation.Achondroplasia can be inherited through autosomal dominance. In couples where one partner has achondroplasia there is a 50% chance of passing the disorder on to their child every pregnancy. In situations where both parents have achondroplasia there is a 50% chance the child will have achondroplasia, 25% chance the child will not, and a 25% chance that the child will inherit the gene from both parents resulting in double dominance and leading to severe or lethal bone dysplasia.Studies have demonstrated that new gene mutations for achondroplasia are exclusively inherited from the father and occur during spermatogenesis; it has been theorized that sperm carrying the mutation in FGFR3 have a selective advantage over sperm with normal FGFR3. The frequency of mutations in sperm leading to achondroplasia increases in proportion to paternal age, as well as in proportion to exposure to ionizing radiation. The occurrence rate of achondroplasia in the children of fathers over 50 years of age is 1 in 1,875, compared to 1 in 15,000 in the general population. Research by urologist Harry Fisch of the Male Reproductive Center at Columbia Presbyterian Hospital in 2013 indicated that in humans this defect may be exclusively inherited from the father and becomes increasingly probable with paternal age, specifically males reproducing after 35.There are two other syndromes with a genetic basis similar to achondroplasia: hypochondroplasia and thanatophoric dysplasia.
Diagnosis
Achondroplasia can be detected before birth by prenatal ultrasound, although signs are often subtle and not apparent before the 24th week of pregnancy. A DNA test can be performed before birth to detect homozygosity, wherein two copies of the mutant gene are inherited, a lethal condition leading to stillbirths. Postnatal diagnosis of achondroplasia is typically uncomplicated, involving an assessment of physical and radiographic features. Clinical features include megalocephaly, short limbs, prominent forehead, thoracolumbar kyphosis and mid-face hypoplasia. Complications like dental malocclusion, hydrocephalus and repeated otitis media can be observed. The risk of death in infancy is increased due to the likelihood of compression of the spinal cord with or without upper airway obstruction.
Radiologic findings
A skeletal survey is useful to confirm the diagnosis of achondroplasia. The skull is large, with a narrow foramen magnum, and relatively small skull base. The vertebral bodies are short and flattened with relatively large intervertebral disk height, and there is congenitally narrowed spinal canal. The iliac wings are small and squared, with a narrow sciatic notch and horizontal acetabular roof. The tubular bones are short and thick with metaphyseal cupping and flaring and irregular growth plates. Fibular overgrowth is present. The hand is broad with short metacarpals and phalanges, and a trident configuration. The ribs are short with cupped anterior ends. If the radiographic features are not classic, a search for a different diagnosis should be entertained. Because of the extremely deformed bone structure, people with achondroplasia are often "double jointed". The diagnosis can be made by fetal ultrasound by progressive discordance between the short femur length and biparietal diameter by age. The trident hand configuration can be seen if the fingers are fully extended.Another common characteristic of the syndrome is thoracolumbar gibbus in infancy.
Treatment
There is no known cure for achondroplasia even though the cause of the mutation in the growth factor receptor has been found. Although used by those without achondroplasia to aid in growth, human growth hormone does not help people with achondroplasia, which involve a different hormonal pathway. Usually, the best results appear within the first and second year of therapy. After the second year of growth hormone therapy, beneficial bone growth decreases, so the therapy is not a satisfactory long-term treatment. As of December 2020, the treatment of achondroplasia with human growth hormone was approved only in Japan.An experimental drug called vosoritide has shown promise in stage 3 human trials, although its long-term effects are unknown.Limb-lengthening will increase the length of the legs and arms of someone with achondroplasia, but little medical consensus exists regarding this practice. The age of surgery can vary from early childhood to adulthood.Research has also shown that introducing parents of children with achondroplasia to support and advocacy groups at the time of diagnosis can improve outcomes. Several patient advocacy groups exist to support people with achondroplasia and their families.
Epidemiology
Achondroplasia is one of several congenital conditions with similar presentations, such as osteogenesis imperfecta, multiple epiphyseal dysplasia tarda, achondrogenesis, osteopetrosis, and thanatophoric dysplasia. This makes estimates of prevalence difficult, with changing and subjective diagnostic criteria over time. One detailed and long-running study in the Netherlands found that the prevalence determined at birth was only 1.3 per 100,000 live births. Another study at the same time found a rate of 1 per 10,000. A 2020 review and meta-analysis estimated a worldwide prevalence of 4.6 per 100,000.
Research
As of 2019, tentative evidence has found that the experimental peptide drug vosoritide increases growth velocity in those with achondroplasia. The drug inhibits the activity of FGFR3.
Animals
Based on their disproportionate dwarfism, some dog breeds traditionally have been classified as "achondroplastic". This is the case for the dachshund, basset hound, corgi and bulldog breeds. Data from whole genome association studies in short-limbed dogs reveal a strong association of this trait with a retro-gene coding for fibroblast growth factor 4 (FGF4). Therefore, it seems unlikely that dogs and humans are achondroplastic for the same reasons. However, histological studies in some achondroplastic dog breeds have shown altered cell patterns in cartilage that are very similar to those observed in humans exhibiting achondroplasia.A similar form of achondroplasia was found in a litter of piglets from a phenotypically normal Danish sow. The dwarfism was inherited dominant in the offspring from this litter. The piglets were born phenotypically normal, but became more and more symptomatic as they reached maturity. This involved a mutation of the protein collagen, type X, alpha 1, encoded by the COL10A1 gene. In humans a similar mutation (G595E) has been associated with Schmid metaphyseal chondrodysplasia (SMCD), a relatively mild skeletal disorder that is also associated with dwarfism.The now-extinct Ancon sheep was created by humans through the selective breeding of common domestic sheep with achondroplasia. The average-sized torso combined with the relatively smaller legs produced by achondroplasia was valued for making affected sheep less likely to escape without affecting the amount of wool or meat each sheep produced.
See also
Achondroplasia in children
List of radiographic findings associated with cutaneous conditions
References
External links
Achondroplasia at Curlie
Pauli RM (1998). "Achondroplasia". In Pagon RA, Bird TD, Dolan CR, et al. (eds.). GeneReviews. Seattle WA: University of Washington, Seattle. PMID 20301331. NBK1152. |
Partialism | Partialism is sexual fetish with an exclusive focus on a specific part of the body other than genitals. Partialism is categorized as a fetishistic disorder in the DSM-5 of the American Psychiatric Association only if it causes significant psychosocial distress for the person or has detrimental effects on important areas of their life. In the DSM-IV, it was considered a separate paraphilia (not otherwise specified), but was merged into fetishistic disorder by the DSM-5. Individuals who exhibit partialism sometimes describe the anatomy of interest to them as having equal or greater erotic attraction for them as do the genitals.Partialism occurs in heterosexual, bisexual, and homosexual individuals. Foot fetishism is considered one of the most common partialisms.
Types
The following are some of the partialisms commonly found among people:
See also
Erogenous zone
Body worship
== References == |
Mortons neuroma | Mortons neuroma is a benign neuroma of an intermetatarsal plantar nerve, most commonly of the second and third intermetatarsal spaces (between the second/third and third/fourth metatarsal heads; the first is of the big toe), which results in the entrapment of the affected nerve. The main symptoms are pain and/or numbness, sometimes relieved by ceasing to wear footwear with tight toe boxes and high heels (which have been linked to the condition). The condition is named after Thomas George Morton, though it was first correctly described by a chiropodist named Durlacher.Some sources claim that entrapment of the plantar nerve resulting from compression between the metatarsal heads, as originally proposed by Morton, is highly unlikely, because the plantar nerve is on the plantar side of the transverse metatarsal ligament and thus does not come into contact with the metatarsal heads. It is more likely that the transverse metatarsal ligament is the cause of the entrapment.Though the condition is labeled as a neuroma, many sources do not consider it a true tumor, but rather a perineural fibroma (fibrous tissue formation around nerve tissue).
Signs and symptoms
Symptoms include pain on weight bearing, frequently after only a short time. The nature of the pain varies widely among individuals. Some people experience shooting pain affecting the contiguous halves of two toes. Others describe a feeling akin to having a pebble in the shoe or walking on razor blades. Burning, numbness, and paresthesia may also be experienced. The symptoms progress over time, often beginning as a tingling sensation in the ball of the foot.Mortons neuroma lesions have been found using MRI in patients without symptoms.
Diagnosis
Negative signs include a lack of obvious deformities, erythema, signs of inflammation, or limitation of movement. Direct pressure between the metatarsal heads will replicate the symptoms, as will compression of the forefoot between the finger and thumb so as to compress the transverse arch of the foot. This is referred to as Mulders sign.There are other causes of pain in the forefoot that often lead to miscategorization as neuroma, such as capsulitis, which is an inflammation of ligaments that surround two bones at the level of the joint. If the ligaments that attach the phalanx (bone of the toe) to the metatarsal bone are impacted, the resulting inflammation may put pressure on an otherwise healthy nerve and produce neuroma-type symptoms. Additionally, an intermetatarsal bursitis between the third and fourth metatarsal bones will also give neuroma-type symptoms because it too puts pressure on the nerve. Freiberg disease, which is an osteochondritis of the metatarsal head, causes pain on weight-bearing or compression. Other conditions that could be clinically confused with a neuroma include stress fractures/reactions and plantar plate disruption.
Histopathology
Microscopically, the affected nerve is markedly distorted, with extensive concentric perineural fibrosis. The arterioles are thickened and occlusion by thrombi are occasionally present.
Imaging
Though a neuroma is a soft-tissue abnormality and will not be visualized by standard radiographs, the first step in the assessment of forefoot pain is an X-ray to detect the presence of arthritis and exclude stress fractures/reactions and focal bone lesions, which may mimic the symptoms of a neuroma. Ultrasound (sonography) accurately demonstrates thickening of the interdigital nerve within the web space of greater than 3mm, diagnostic of a Morton’s neuroma. This typically occurs at the level of the intermetatarsal ligament. Frequently, intermetatarsal bursitis coexists with the diagnosis. MRI can distinguish conditions that mimic the symptoms of Mortons neuroma, but when more than one abnormality exists, ultrasound has the added advantage of determining the precise source of the patient’s pain by applying direct pressure with the probe. Ultrasound may also be used to guide treatment such as cortisone injections into the webspace, as well as alcohol ablation of the nerve.
Treatment
Conservative
Orthotics and improved footwear are the first-line treatments for Morton’s neuroma. In addition to traditional orthotic arch supports, a small foam or fabric pad may be positioned under the space between the two affected metatarsals, immediately behind the bone ends. This pad helps to splay the metatarsal bones and create more space for the nerve so as to relieve pressure and irritation. However, it may also elicit mild uncomfortable sensations of its own, such as the feeling of having an awkward object under ones foot. Toe spreaders are another form of conservative orthotic treatment that may yield relief for Mortons neuroma symptoms. Footwear and orthotics are most effective in neuromas that have existed less than four and a half months and are smaller than 4–5 millimetres (0.16–0.20 in). To prevent or treat Mortons neuroma, comfortable shoes that are sufficiently long and have a wide toe box, flat heel, and thick sole are recommended.Corticosteroid injections can relieve inflammation in some patients and help end the symptoms. For some patients, however, the inflammation and pain recur after some weeks or months, and corticosteroids may only be used a limited number of times because they cause progressive degeneration of ligamentous and tendinous tissues. About 30% of people who receive steroid injections go on to have surgery. According to a 2021 review, it is most effective in neuromas smaller than 6.3 millimetres (0.25 in).Sclerosing alcohol injections are an increasingly available treatment alternative if other management approaches fail. Dilute alcohol (4%) is injected directly into the area of the neuroma, causing toxicity to the fibrous nerve tissue. Frequently, treatment must be performed two to four times, with one to three weeks between interventions. A 60–80% success rate has been achieved in clinical studies, equal to or exceeding the success rate for surgical neurectomy, with fewer risks and less significant recovery. If done with more concentrated alcohol under ultrasound guidance, the success rate is considerably higher and fewer repeat procedures are needed.Radiofrequency ablation is also used in the treatment of Mortons neuroma. The outcomes appear to be similar to, or even more reliable than, alcohol injections, especially if the procedure is performed under ultrasound guidance.A 2019 systematic review of randomised controlled trials found that corticosteroid injections or manipulation/mobilisation reduced pain more than control, extracorporeal shockwave therapy or varus/valgus foot wedges (which did not reduce pain more than control or comparison treatment, and pain reduction was not reported in any wider foot/metatarsal padding studies). The review also found no randomised controlled trials for sclerosing alcohol injections, radiofrequency ablations, cryoneurolysis or botulinum toxin injections. These treatments have only been assessed with pre-test/post-test case series, which do not measure the benefit of treatment beyond any placebo effect, sham treatment or any natural improvement over time.
Surgery
If non-surgical interventions fail, patients are commonly offered neurectomy, a surgery that involves removing the affected piece of nerve tissue. Postoperative scar tissue formation (known as stump neuroma) can occur in approximately 20–30% of cases, causing a return of neuroma symptoms. Neurectomy may be performed using one of two general methods. Making the incision from the dorsal side (the top of the foot) is the more common method but requires cutting the deep transverse metatarsal ligament that connects the third and fourth metatarsals in order to access the nerve beneath it. This results in exaggerated postoperative splaying of the third and fourth digits (toes) resulting from the loss of the supporting ligamentous structure. This has aesthetic concerns for some patients and possible, though unquantified, long-term implications for foot structure and health. Alternatively, making the incision from the ventral side (the sole of the foot) allows more direct access to the affected nerve without cutting other structures. However, this approach requires a greater post-operative recovery time in which the patient must avoid weight-bearing on the affected foot, because the ventral aspect of the foot is more highly enervated and impacted by pressure when standing. It also carries an increased risk of scar-tissue formation in a location that causes ongoing pain.When a patient has multiple neuromas in the same foot, the most common surgical approach is to remove them all using a single incision.Cryogenic neuroablation (also known as cryoinjection therapy, cryoneurolysis, cryosurgery or cryoablation) is a lesser-known alternative to neurectomy surgery. It involves the destruction of axons to prevent them from carrying painful impulses. This is accomplished by making a small incision (~3 mm) and inserting a cryoneedle that applies extremely low temperatures of between −50 °C to −70 °C to the nerve/neuroma, resulting in degeneration of the intracellular elements, axons and myelin sheath (which houses the neuroma) with wallerian degeneration. The epineurium and perineurium remain intact, thus preventing the formation of stump neuroma. The preservation of these structures differentiates cryogenic neuroablation from surgical excision and neurolytic agents such as alcohol. An initial study showed that cryoneuroablation is initially equal in effectiveness to surgery but does not have the risk of stump neuroma formation.An increasing range of procedures are being performed at specialist centers to treat Mortons neuroma under ultrasound guidance. Studies have examined the treatment of the condition with ultrasound-guided sclerosing alcohol injections, radiofrequency ablation and cryoablation.
References
== External links == |
Idioventricular rhythm | An idioventricular rhythm is a cardiac rhythm characterized by a rate of <50 beats per minute (bpm), absence of P waves and widening of the QRS complex. In cases where the heart rate is between 50 and 110 bpm, it is known as accelerated idioventricular rhythm and ventricular tachycardia if the rate exceeds 120 bpm. Causes of idioventricular rhythms are varied and can include drugs or a heart defect at birth. It is typically benign and not life-threatening.
Etiology
Various etiologies may contribute to the formation of an idioventricular rhythm, and include:
Heart block
Reperfusion after myocardial infarction
Electrolyte abnormalities
Heart diseases present at birth
Certain drugs (eg. digoxin, β-agonists, anaesthetics)
Pathophysiology
The physiological pacemaker of the heart is the sinoatrial node. If the sinoatrial node is rendered dysfunctional, the AV node may act as the pacemaker. If both of these fail, the ventricles begin to act as the dominant pacemaker in the heart. The ventricles acting as their own pacemaker gives rise to an idioventricular rhythm.
Diagnosis
An ECG trace is required for diagnosis.
Treatment
As this rhythm is not life-threatening, treatment has limited value for the patient. If underlying pathologies are identified, they should be treated appropriately. Antidysrhythmics may be utilised if the patient suffers from dysrhythmias.
== References == |
Platybasia | Platybasia is a spinal disease of a malformed relationship between the occipital bone and cervical spine.
It may be caused by Pagets disease. Platybasia is also a feature of Gorlin-Goltz syndrome, commonly known as basal cell nevus syndrome.
It may be developmental in origin or due to softening of the skull base bone, allowing it to be pushed upward. The developmental variant is the result of a wider angle between the skull base of the frontal or anterior fossa and the clivus, which defines the anterior wall of the posterior fossa. It is sometimes associated with other congenital abnormalities of the bone structure, such as fusion of the first cervical vertebrae to the skull atlas assimilation.
Further reading
Pearce JM (2007). "Platybasia and basilar invagination". Eur. Neurol. 58 (1): 62–4. doi:10.1159/000102172. PMID 17483591.
== External links == |
Carotid-cavernous fistula | A carotid-cavernous fistula results from an abnormal communication between the arterial and venous systems within the cavernous sinus in the skull. It is a type of arteriovenous fistula. As arterial blood under high pressure enters the cavernous sinus, the normal venous return to the cavernous sinus is impeded and this causes engorgement of the draining veins, manifesting most dramatically as a sudden engorgement and redness of the eye of the same side.
Presentation
CCF symptoms include bruit (a humming sound within the skull due to high blood flow through the arteriovenous fistula), progressive visual loss, and pulsatile proptosis or progressive bulging of the eye due to dilatation of the veins draining the eye. Pain is the symptom that patients often find the most difficult to tolerate.Patients usually present with sudden or insidious onset of redness in one eye, associated with progressive proptosis or bulging.They may have a history of similar episodes in the past.
Causes
Carotid cavernous fistulae may form following closed or penetrating head trauma, surgical damage, rupture of an intracavernous aneurysm, or in association with connective tissue disorders, vascular diseases and dural fistulas.
Diagnosis
This is based on MRI scan, magnetic resonance angiography and CT scan. A cerebral digital subtraction angiography (DSA) enhances visualization of the fistula.
CT scans classically show an enlarged superior ophthalmic vein, cavernous sinus enlargement ipsilateral (same side) as the abnormality and possibly diffuse enlargement of all the extraocular muscles resulting from venous engorgement.
Selective arteriography is used to evaluate arteriovenous fistulas.
High resolution digital subtraction angiography may help in classifying CCF into dural and direct type and thus formulate a strategy to treat it either by a balloon or coil or both with or without preservation of parent ipsilateral carotid artery.
Classification
Various classifications have been proposed for CCF. They may be divided into low-flow or high-flow, traumatic or spontaneous and direct or indirect. The traumatic CCF typically occurs after a basal skull fracture. The spontaneous dural cavernous fistula which is more common usually results from a degenerative process in older patients with systemic hypertension
and atherosclerosis. Direct fistulas occur when the Internal Carotid artery (ICA) itself fistulizes into the Cavernous sinus whereas indirect is when a branch of the ICA or External Carotid artery (ECA) communicates with the cavernous sinus.A popular classification divides CCF into four varieties depending on the type of arterial supply.
Treatment
The mainstay of treatment for CCF is endovascular therapy. This may be transarterial (mostly in the case of direct CCF) or transvenous (most commonly in indirect CCF). Occasionally, more direct approaches, such as direct transorbital puncture of the cavernous sinus or cannulation of the draining superior orbital vein are used when conventional approaches are not possible. Spontaneous resolution of indirect fistulae has been reported but is uncommon. Staged manual compression of the ipsilateral carotid has been reported to assist with spontaneous closure in selected cases.Direct CCF may be treated by occlusion of the affected cavernous sinus (coils, balloon, liquid agents), or by reconstruction of the damaged internal carotid artery (stent, coils or liquid agents).Indirect CCF may be treated by occlusion of the affected cavernous sinus with coils, liquid agents or a combination of both.
References
== External links == |
Pantothenic acid | Pantothenic acid, also called vitamin B5 is a water-soluble B vitamin and therefore an essential nutrient. All animals require pantothenic acid in order to synthesize coenzyme A (CoA) – essential for fatty acid metabolism – as well as to, in general, synthesize and metabolize proteins, carbohydrates, and fats.Pantothenic acid is the combination of pantoic acid and β-alanine. Its name derives from the Greek pantos, meaning "from everywhere", as minimally, at least small quantities of pantothenic acid are found in nearly every food. Human deficiency is very rare. As a dietary supplement or animal feed ingredient, the form commonly used is calcium pantothenate because of chemical stability, and hence long product shelf life, compared to sodium pantothenate or free pantothenic acid.
Definition
Pantothenic acid is a water-soluble vitamin, one of the B vitamins. It is synthesized from the amino acid β-alanine and pantoic acid (see biosynthesis and structure of coenzyme A figures). Unlike vitamin E or vitamin K, which occurs in several chemically related forms known as vitamers, pantothenic acid is only one chemical compound. It is a starting compound in the synthesis of coenzyme A (CoA), a cofactor for many enzyme processes.
Use in biosynthesis of coenzyme A
Pantothenic acid is a precursor to CoA via a five-step process. The biosynthesis requires pantothenic acid, cysteine, four equivalents of ATP (see figure).
Pantothenic acid is phosphorylated to 4′-phosphopantothenate by the enzyme pantothenate kinase. This is the committed step in CoA biosynthesis and requires ATP.
A cysteine is added to 4′-phosphopantothenate by the enzyme phosphopantothenoylcysteine synthetase to form 4-phospho-N-pantothenoylcysteine (PPC). This step is coupled with ATP hydrolysis.
PPC is decarboxylated to 4′-phosphopantetheine by phosphopantothenoylcysteine decarboxylase
4′-Phosphopantetheine is adenylated (or more properly, AMPylated) to form dephospho-CoA by the enzyme phosphopantetheine adenylyl transferase
Finally, dephospho-CoA is phosphorylated to coenzyme A by the enzyme dephosphocoenzyme A kinase. This final step also requires ATP.This pathway is suppressed by end-product inhibition, meaning that CoA is a competitive inhibitor of pantothenate kinase, the enzyme responsible for the first step.Coenzyme A is necessary in the reaction mechanism of the citric acid cycle. This process is the bodys primary catabolic pathway and is essential in breaking down the building blocks of the cell such as carbohydrates, amino acids and lipids, for fuel. CoA is important in energy metabolism for pyruvate to enter the tricarboxylic acid cycle (TCA cycle) as acetyl-CoA, and for α-ketoglutarate to be transformed to succinyl-CoA in the cycle. CoA is also required for acylation and acetylation, which, for example, are involved in signal transduction, and various enzyme functions. In addition to functioning as CoA, this compound can act as an acyl group carrier to form acetyl-CoA and other related compounds; this is a way to transport carbon atoms within the cell. CoA is also required in the formation of acyl carrier protein (ACP), which is required for fatty acid synthesis. Its synthesis also connects with other vitamins such as thiamin and folic acid.
Dietary recommendations
The US Institute of Medicine (IOM) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for B vitamins in 1998. At that time there was not sufficient information to establish EARs and RDAs for pantothenic acid. In instances such as this, the Board sets Adequate Intakes (AIs), with the understanding that at some later date, AIs may be replaced by more exact information.The current AI for teens and adults ages 14 and up is 5 mg/day. This was based in part on the observation that for a typical diet, urinary excretion was approximately 2.6 mg/day, and that bioavailability of food-bound pantothenic acid was roughly 50%. AI for pregnancy is 6 mg/day. AI for lactation is 7 mg/day. For infants up to 12 months the AI is 1.8 mg/day. For children ages 1–13 years the AI increases with age from 2 to 4 mg/day. Collectively the EARs, RDAs, AIs and ULs are referred to as Dietary Reference Intakes (DRIs).
While for many nutrients, the US Department of Agriculture uses food composition data combined with food consumption survey results to estimate average consumption, the surveys and reports do not include pantothenic acid in the analyses. Less formal estimates of adult daily intakes report about 4 to 7 mg/day.The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL are defined the same as in the US. For women and men over age 11 the Adequate Intake (AI) is set at 5 mg/day. AI for pregnancy is 5 mg/day, for lactation 7 mg/day. For children ages 1–10 years the AI is 4 mg/day. These AIs are similar to the US AIs.
Safety
As for safety, the IOM sets Tolerable upper intake levels (ULs) for vitamins and minerals when evidence is sufficient. In the case of pantothenic acid there is no UL, as there is no human data for adverse effects from high doses. The EFSA also reviewed the safety question and reached the same conclusion as in United States – that there was not sufficient evidence to set a UL for pantothenic acid.
Labeling requirements
For US food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For pantothenic acid labeling purposes 100% of the Daily Value was 10 mg, but as of 27 May 2016 it was revised to 5 mg to bring it into agreement with the AI.
Compliance with the updated labeling regulations was required by 1 January 2020 for manufacturers with US$10 million or more in annual food sales, and by 1 January 2021 for manufacturers with lower volume food sales. A table of the old and new adult daily values is provided at Reference Daily Intake.
Sources
Dietary
Food sources of pantothenic acid include animal-sourced foods, including dairy foods and eggs. Potatoes, tomato products, oat-cereals, sunflower seeds, avocado and mushrooms are good plant sources. Whole grains are another source of the vitamin, but milling to make white rice or white flour removes much of the pantothenic acid, as it is found in the outer layers of whole grains. In animal feeds, the most important sources are alfalfa, cereal, fish meal, peanut meal, molasses, rice bran, wheat bran, and yeasts.
Supplements
Dietary supplements of pantothenic acid commonly use pantothenol (or panthenol), a shelf-stable analog, which is converted to pantothenic acid once consumed. Calcium pantothenate – a salt – may be used in manufacturing because it is more resistant than pantothenic acid to factors that deteriorate stability, such as acid, alkali or heat. The amount of pantothenic acid in dietary supplement products may contain up to 1,000 mg (200 times the Adequate Intake level for adults), without evidence that such large amounts provide any benefit. According to WebMD, pantothenic acid supplements have a long list of claimed uses, but there is insufficient scientific evidence to support any of them.As a dietary supplement, pantothenic acid is not the same as pantethine, which is composed of two pantothenic acid molecules linked by a disulfide bridge. Sold as a high-dose supplement (600 mg), pantethine may be effective for lowering blood levels of LDL cholesterol – a risk factor for cardiovascular diseases – but its long-term effects are unknown, requiring that its use be supervised by a physician. Dietary supplementation with pantothenic acid does not have the same effect on LDL.
Fortification
According to the Global Fortification Data Exchange, pantothenic acid deficiency is so rare that no countries require that foods be fortified.
Absorption, metabolism and excretion
When found in foods, most pantothenic acid is in the form of CoA or bound to acyl carrier protein (ACP). For the intestinal cells to absorb this vitamin, it must be converted into free pantothenic acid. Within the lumen of the intestine, CoA and ACP are hydrolyzed into 4-phosphopantetheine. The 4-phosphopantetheine is then dephosphorylated into pantetheine. Pantetheinase, an intestinal enzyme, then hydrolyzes pantetheine into free pantothenic acid. Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium-dependent active transport system. At high levels of intake, when this mechanism is saturated, some pantothenic acid may also be additionally absorbed via passive diffusion. As a whole, when intake increases 10-fold, absorption rate decreases to 10%.Pantothenic acid is excreted in urine. This occurs after its release from CoA. Urinary amounts are on the order of 2.6 mg/day, but decreased to negligible amounts when subjects in multi-week experimental situations were fed diets devoid of the vitamin.
Deficiency
Pantothenic acid deficiency in humans is very rare and has not been thoroughly studied. In the few cases where deficiency has been seen (prisoners of war during World War II, victims of starvation, or limited volunteer trials), nearly all symptoms were reversed with orally administered pantothenic acid. Symptoms of deficiency are similar to other vitamin B deficiencies. There is impaired energy production, due to low CoA levels, which could cause symptoms of irritability, fatigue, and apathy. Acetylcholine synthesis is also impaired; therefore, neurological symptoms can also appear in deficiency; they include sensation of numbness in hands and feet, paresthesia and muscle cramps. Additional symptoms could include restlessness, malaise, sleep disturbances, nausea, vomiting and abdominal cramps.In animals, symptoms include disorders of the nervous, gastrointestinal, and immune systems, reduced growth rate, decreased food intake, skin lesions and changes in hair coat, and alterations in lipid and carbohydrate metabolism. In rodents, there can be loss of hair color, which led to marketing of pantothenic acid as a dietary supplement which could prevent or treat graying of hair in humans (despite the lack of any human trial evidence).Pantothenic acid status can be assessed by measuring either whole blood concentration or 24-hour urinary excretion. In humans, whole blood values less than 1 μmol/L are considered low, as is urinary excretion of less than 4.56 mmol/day.
Animal nutrition
Calcium pantothenate and dexpanthenol (D-panthenol) are European Food Safety Authority (EFSA) approved additives to animal feed. Supplementation is on the order of 8–20 mg/kg for pigs, 10–15 mg/kg for poultry, 30–50 mg/kg for fish and 8–14 mg/kg feed for pets. These are recommended concentrations, designed to be higher than what are thought to be requirements. There is some evidence that feed supplementation increases pantothenic acid concentration in tissues, i.e., meat, consumed by humans, and also for eggs, but this raises no concerns for consumer safety.No dietary requirement for pantothenic acid has been established in ruminant species. Synthesis of pantothenic acid by ruminal microorganisms appears to be 20 to 30 times more than dietary amounts. Net microbial synthesis of pantothenic acid in the rumen of steer calves has been estimated to be 2.2 mg/kg of digestible organic matter consumed per day. Supplementation of pantothenic acid at 5 to 10 times theoretical requirements did not improve growth performance of feedlot cattle.
Synthesis
Biosynthesis
Bacteria synthesize pantothenic acid from the amino acids aspartate and a precursor to the amino acid valine. Aspartate is converted to β-alanine. The amino group of valine is replaced by a keto-moiety to yield α-ketoisovalerate, which, in turn, forms α-ketopantoate following transfer of a methyl group, then D-pantoate (also known as pantoic acid) following reduction. β-alanine and pantoic acid are then condensed to form pantothenic acid (see figure).
Industrial synthesis
The industrial synthesis of pantothenic acid starts with the aldol condensation of isobutyraldehyde and formaldehyde. The resulting hydroxypivaldehyde is converted to its cyanohydrin derivative. which is cyclised to give racemic pantolactone. This sequence of reactions was first published in 1904.
Synthesis of the vitamin is completed by resolution of the lactone using quinine, for example, followed by treatment with the calcium or sodium salt of β-alanine.
History
The term vitamin is derived from the word vitamine, which was coined in 1912 by Polish biochemist Casimir Funk, who isolated a complex of water-soluble micronutrients essential to life, all of which he presumed to be amines. When this presumption was later determined not to be true, the "e" was dropped from the name, hence "vitamin". Vitamin nomenclature was alphabetical, with Elmer McCollum calling these fat-soluble A and water-soluble B. Over time, eight chemically distinct, water-soluble B vitamins were isolated and numbered, with pantothenic acid as vitamin B5.The essential nature of pantothenic acid was discovered by Roger J. Williams in 1933 by showing it was required for the growth of yeast. Three years later Elvehjem and Jukes demonstrated that it was a growth and anti-dermatitis factor in chickens. Williams dubbed the compound "pantothenic acid", deriving the name from the Greek word pantothen, which translates as "from everywhere". His reason was that he found it to be present in almost every food he tested. Williams went on to determine the chemical structure in 1940. In 1953, Fritz Lipmann shared the Nobel Prize in Physiology or Medicine "for his discovery of co-enzyme A and its importance for intermediary metabolism", work he had published in 1946.
== References == |
Hyperpituitarism | Hyperpituitarism is a condition due to the primary hypersecretion of pituitary hormones; it typically results from a pituitary adenoma. In children with hyperpituitarism, disruption of growth regulation is rare, either because of hormone hypersecretion or because of manifestations caused by local compression of the adenoma.
Symptoms and signs
Symptoms caused by hormone excess and associated mass effects include:
Cause
The cause of hyperpituitarism in most cases is due to pituitary adenomas. They usually come from the anterior lobe, are functional and secrete the hormone, GH and prolactin.
Mechanism
Evidence indicates that the mechanism of hyperpituitarism can originate from genetic disruption causing pituitary tumorigenesis, most pituitary adenomas are monoclonal, which in turn indicates their origin from an event in a single cell. There are three hormones that are oversecreted resulting in the pituitary adenoma: prolactin, adrenocorticotropic hormone (ACTH), and growth hormone (GH).Excess prolactin may result in a prolactinoma Excess GH results in gigantism, the severity of gigantism depends on whether the epiphyseal plate is open. The four most common types of hyperpituitarism are caused by 4 types of pituitary adenoma, as follows: prolactinoma, corticotropinoma (Cushings disease), somatotropinoma (gigantism), and thyrotropinoma .
Diagnosis
For the diagnosis of hyperpituitarism it depends on the cell type(s) affected, clinical manifestations of hormone excess may include, gigantism or acromegaly, which can be identified by clinical and radiographic results. Cushings disease diagnosis is done with a physical examination, laboratory tests and X rays of the pituitary glands (to locate tumors) For prolactinoma, diagnosis comes in the form of the measurement of serum prolactin levels and x-ray of pituitary gland.
Treatment
Treatment (for hyperpituitarism) in the case of prolactinoma consists of long-term medical management. Dopamine agonists are strong suppressors of PRL secretion and establish normal gonadal function. It also inhibits tumor cell replication (in some cases causes tumor shrinkage) Treatment for gigantism begins with establishing target goals for IGF-1, transsphenoidal surgery (somatostatin receptor ligands- preoperatively) and postoperative imaging assessment. For Cushings disease there is surgery to extract the tumor; after surgery, the gland may slowly start to work again, though not always.
See also
Hypopituitarism
References
Further reading
Handbook of Medical-surgical Nursing. Lippincott Williams & Wilkins. 2006-01-01. ISBN 9781582554457.
Atreja, Gaurav; Jain, Nitul; Atreja, ShikhaHanda; Sukhija, Urvashi (2012). "Oral manifestations in growth hormone disorders". Indian Journal of Endocrinology and Metabolism. 16 (3): 381–3. doi:10.4103/2230-8210.95678. PMC 3354844. PMID 22629503.
Illustrated Manual of Nursing Practice. Lippincott Williams & Wilkins. 2002-01-01. ISBN 9781582550824.
== External links == |
Small fiber peripheral neuropathy | Small fiber peripheral neuropathy is a type of peripheral neuropathy that occurs from damage to the small unmyelinated and myelinated peripheral nerve fibers. These fibers, categorized as C fibers and small Aδ fibers, are present in skin, peripheral nerves, and organs. The role of these nerves is to innervate the skin (somatic fibers) and help control autonomic function (autonomic fibers). It is estimated that 15–20 million people in the United States have some form of peripheral neuropathy.
Signs and symptoms
Small fiber neuropathy is a condition characterized by severe pain. Symptoms typically begin in the feet or hands but can start in other parts of the body. Some people initially experience a more generalized, whole-body pain. The pain is often described as stabbing or burning, or abnormal skin sensations such as tingling or itchiness. In some individuals, the pain is more severe during times of rest or at night. The signs and symptoms of small fiber neuropathy can occur at any point in life depending on the underlying cause.
Individuals with small fiber neuropathy often cannot feel pain that is concentrated in a very small area, such as the prick of a pin. However, they have an increased sensitivity to pain in general (hyperalgesia) and experience pain from stimulation that typically does not cause pain (allodynia). People affected with this condition may also have a reduced ability to differentiate between hot and cold.
Sudomotor dysfunction is one of the most common and earliest neurophysiological manifestations of small fiber neuropathies.In some instances, the small fibers of the autonomic nervous system can be affected, leading to urinary or bowel problems, episodes of rapid heartbeat (palpitations), dry eyes or mouth, or abnormal sweating. They can also experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting.
Small fiber neuropathy is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain. Insensitivity to pain can be particularly problematic. One may be bleeding or have a skin injury without even knowing it.
Topographic pattern
Like many polyneuropathies, the symptoms are typically length-dependent, starting in the longer nerves and progressively attacking shorter nerves. This means that symptoms often start in the hands and feet before progressing upwards, and that symptoms are usually more severe in the extremities. Some patients have a widespread, non-length dependent, or "patchy", presentation which is sporadic and can affect many nerves.
Patients with Fabry disease have isolated small fiber engagement, and can have a more widespread small fiber disruption.
Causes
Mutations in the SCN9A or SCN10A gene can cause small fiber neuropathy. These genes provide instructions for making pieces (the alpha subunits) of sodium channels. The SCN9A gene instructs the production of the alpha subunit for the NaV1.7 sodium channel and the SCN10A gene instructs the production of the alpha subunit for the NaV1.8 sodium channel. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cells ability to generate and transmit electrical signals. The NaV1.7 and NaV1.8 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain.
The SCN9A gene mutations that cause small fiber neuropathy result in NaV1.7 sodium channels that do not close completely when the channel is turned off. Many SCN10A gene mutations result in NaV1.8 sodium channels that open more easily than usual. The altered channels allow sodium ions to flow abnormally into nociceptors. This increase in sodium ions enhances transmission of pain signals, causing individuals to be more sensitive to stimulation that might otherwise not cause pain. In this condition, the small fibers that extend from the nociceptors through which pain signals are transmitted (axons) degenerate over time. The cause of this degeneration is unknown, but it likely accounts for signs and symptoms such as the loss of temperature differentiation and pinprick sensation. The combination of increased pain signaling and degeneration of pain-transmitting fibers leads to a variable condition with signs and symptoms that can change over time.
SCN9A gene mutations have been found in approximately 30 percent of individuals with small fiber neuropathy; SCN10A gene mutations are responsible for about 5 percent of cases. In some instances, other health conditions cause this disorder. Diabetes mellitus and impaired glucose tolerance are the most common diseases that lead to this disorder, with 6 to 50 percent of diabetics or pre-diabetics developing small fiber neuropathy. Other causes of this condition include a metabolic disorder called Fabry disease, immune disorders such as celiac disease or Sjogren syndrome, an inflammatory condition called sarcoidosis, and human immunodeficiency virus (HIV) infection.Recently several studies have suggested an association between autonomic small fiber neuropathy and postural orthostatic tachycardia syndrome. Other notable studies have shown a link between erythromelalgia, fibromyalgia, and Ehlers–Danlos Syndrome.
Diagnosis
The diagnosis of small fiber neuropathy often requires ancillary testing. Nerve conduction studies and electromyography are commonly used to evaluate large myelinated sensory and motor nerve fibers, but are ineffective in diagnosing small fiber neuropathies.Quantitative sensory testing (QST) assesses small fiber function by measuring temperature and vibratory sensation. Abnormal QST results can be attributed to dysfunction in the central nervous system. Furthermore, QST is limited by a patients subjective experience of pain sensation. Electrochemical skin conductance and quantitative sudomotor axon reflex testing (QSART) measures sweating response at local body sites to evaluate the small nerve fibers that innervate sweat glands.Electrochemical skin conductance has been evaluated for both early diagnosis of small fiber neuropathy and follow-up of treatment efficacy.
Skin biopsy
A skin biopsy for the measurement of epidermal nerve fiber density is an increasingly common technique for the diagnosis of small fiber peripheral neuropathy. Physicians can biopsy the skin with a 3-mm circular punch tool and immediately fix the specimen in 2% paraformaldehyde lysine-periodate or Zambonis fixative. Specimens are sent to a specialized laboratory for processing and analysis where the small nerve fibers are quantified by a neuropathologist to obtain a diagnostic result.This skin punch biopsy measurement technique is called intraepidermal nerve fiber density (IENFD). The following table describes the IENFD values in males and females of a 3 mm biopsy 10 cm above the lateral malleolus (above ankle outer side of leg). Any value measured below the 0.05 Quantile IENFD values per age span, is considered a reliable positive diagnosis for small fiber peripheral neuropathy.
Treatment
Treatment is based on the underlying cause, if any. Where the likely underlying condition is known, treatment of this condition is indicated to reduce progression of the disease and symptoms. For cases without those conditions, there is only symptomatic treatment.
See also
Neuropathy
Polyneuropathy
Wartenbergs migratory sensory neuropathy
Burning feet syndrome
Electrochemical skin conductance
References
External links
Peripheral Neuropathy Fact Sheet – NINDS
[1] |
Abruzzo–Erickson syndrome | Abruzzo–Erickson syndrome is an extremely rare disorder characterized by deafness, protruding ears, coloboma, a cleft palate or palatal rugosity, radial synostosis, and short stature. It was first characterized by Abruzzo and Erickson in 1977 as a CHARGE like syndrome as variably expressed among a family of two brothers, their mother, and their maternal uncle. Members of this family exhibited many of the CHARGE symptoms, but notably did not have choanal atresia and the brothers experienced typical genital development. Due to the recent discovery of this disorder, its etiology is not fully known but it is understood that it arises from mutations on the TBX22 gene on the X-chromosome. The disorder is inherited in an X-linked recessive manner. There is currently no known cure but its symptoms can be treated.
Signs and Symptoms
Abruzzo-Erikson syndrome is characterized by cleft palate, coloboma, hypospadias, deafness, short stature, and radial synostosis. There are also additional symptoms that are very similar to CHARGE syndrome such as large and protruding ears, wide spacing between the second and third fingers, ulnar deviation, facial asymmetry, dental abnormalities, and congenital heart malformation. However, in contrast to CHARGE syndrome, patients with Abruzzo-Erikson syndrome do not display intellectual disability, choanal atresia, or genital hypoplasia. As with most diseases, the symptoms will vary from person to person.
Genetics
While the complete etiology is not fully known, Abruzzo-Erickson Syndrome arises in part due to mutations on the TBX22 gene, a gene that is located on the X-chromosome (around 80,014,753 to 80,031,774 bp), and is inherited in an X-linked recessive manner. The T-box transcription factor TBX22 plays an essential role in normal craniofacial development. Nonsense, frameshift, splice-site and missense mutations in this region can result in patients with X-linked cleft palate (CPX) and ankyloglossia phenotypes. The CPX phenotype observed in individuals with Abruzzo-Erickson Syndrome most likely results from a loss of protein function as severely truncated proteins can result from the introduction of a premature stop codon can result from nonsense, splice-site, or frame shift sequence changes, while missense mutations in this region have less of a structural effect on the protein, but instead interferes with DNA binding and transcriptional activity.
Diagnosis
Abruzzo–Erickson syndrome can be diagnosed on the basis of a complete physical examination (as patients with the syndrome often possess noticeable physical characteristics such as a cleft palate, large protruding ears, and facial asymmetry). As the syndrome is inherited, a complete medical history is also taken, and additional assessments may be made based on the results of laboratory tests, biopsies, and imaging studies. Genetic and molecular tests such as DNA sequencing can also be used for a complete diagnosis of Abruzzo–Erickson syndrome.
Treatment
There is no cure for this condition. However, children with Abruzzo-Erikson syndrome can survive into adulthood and live productive lives as long as they are treated from an early age. Many life-threatening problems may arise in these children which need to be addressed. Treatment is generally focused on addressing the specific symptoms and not the syndrome itself. Since hearing problems are common with this syndrome, it is usually the first issue addressed. Correction of some abnormalities can be corrected with the use of extensive multidisciplinary craniofacial surgery. Physical therapy and occupational therapy are important to ensure they can live a normal and productive life. Monitoring the heart for defects is also common and there are medications to educe this risk or surgery is available to correct some of conditions.
Epidemiology
Abruzzo-Erickson Syndrome is an extremely rare condition, prevalent among less than one in a million of individuals. As of 2021, only four cases have been characterized in literature.
See also
CHARGE syndrome
References
External links
Abruzzo–Erickson syndrome at NIHs Office of Rare Diseases |
Micronychia | The term Micronychia may refer to
Micronychia (plant), a genus of plants in the family Anacardiaceae
Micronychia (fly), a genus of flies in the family Tachinidae
abnormally small finger- and toenails |
Anemia of prematurity | Anemia of prematurity (AOP) refers to a form of anemia affecting preterm infants with decreased hematocrit. AOP is a normochromic, normocytic hypoproliferative anemia. The primary mechanism of AOP is a decrease in erythropoietin (EPO), a red blood cell growth factor.
Pathophysiology
Preterm infants are often anemic and typically experience heavy blood losses from frequent laboratory testing in the first few weeks of life. Although their anemia is multifactorial, repeated blood sampling and reduced erythropoiesis with extremely low serum levels of erythropoietin (EPO) are major causative factors. Blood sampling done for laboratory testing can easily remove enough blood to produce anemia. Obladen, Sachsenweger and Stahnke (1987) studied 60 very low birth weight infants during the first 28 days of life. Infants were divided into 3 groups, group 1 (no ventilator support, 24 ml/kg blood loss), group 2(minor ventilated support, 60 ml/kg blood loss), and group 3(ventilated support for respiratory distress syndrome, 67 ml/kg blood loss). Infants were checked for clinical symptoms and laboratory signs of anemia 24 hours before and after the blood transfusion. The study found that groups 2 and 3 who had significant amount of blood loss, showed poor weight gain, pallor and distended abdomen. These reactions are the most frequent symptoms of anemia in very low birth weight infants.During the first weeks of life, all infants experience a decline in circulating red blood cell (RBC) volume generally expressed as blood hemoglobin concentration (Hb). As anemia develops, there is even more of a significant reduction in the concentration of hemoglobin. Normally this stimulates a significant increased production of erythropoietin (EPO), but this response is diminished in premature infants. Dear, Gill, Newell, Richards and Schwarz (2005) conducted a study to show that there is a weak negative correlation between EPO and Hb. The researchers recruited 39 preterm infants from 10 days of age or as soon as they could manage without respiratory support. They estimated total EPO and Hb weekly and 2 days after a blood transfusion. The study found that when Hb>10, EPO mean was 20.6 and when Hb≤10, EPO mean was 26.8. As Hb goes down, EPO goes up. While the reason for this decreased response is not fully understood, Strauss (n.d.) states that it results from both physiological factors (e.g., the rapid rate of growth and need for a commensurate increase in RBC mass to accompany the increase in blood volume) and, in sick premature infants, from phlebotomy blood losses. In premature infants this decline occurs earlier and more pronounced that it does in healthy term infants. Healthy term infants Hb rarely falls below 9 g/dL at an age of approximately 10–12 weeks, while in premature infants, even in those without complicating illnesses, the mean Hb falls to approximately 8g/dL in infants of 1.0-1.5 kg birth weight and to 7g/dL in infants <1.0 kg. Because this postnatal drop in hemoglobin level is universal and is well tolerated in term infants, it is commonly referred to as the “physiologic” anemia of infancy. However, in premature infants the decline in Hb may be associated with abnormal clinical signs severe enough to prompt transfusions.
Treatment
Transfusion
AOP is usually treated by blood transfusion but the indications for this are still unclear. Blood transfusions have both infectious and non-infectious risks associated with them. Also, blood transfusions are costly and may add to parental anxiety. The best treatment for AOP is prevention of worsening of anemia by minimizing the amount of blood drawn from the infant (ie, anemia from phlebotomy). It is found that since blood loss attributable to laboratory testing is the primary cause of anemia among preterm infants during the first weeks of life, it would be useful to quantify blood loss attributable to phlebotomy overdraw (ie, blood collected in excess than what is strictly required for the requested lab tests). Lin and colleagues performed a study to see when and if phlebotomy overdraw was actually a significant problem. They recorded all of the data that could be of influence such as the test performed, the blood collection container used, the infants location (neonatal intensive care unit (NICU) and intermediate intensive care unit), the infant’s weight sampling and the phlebotomist’s level of experience, work shift, and clinical role. Infants were classified by weight into 3 groups: <1 kg, 1 to 2 kg, and >2 kg. The volume of blood removed was calculated by subtracting the weight of the empty collection container from that of the container filled with blood. They found that the mean volume of blood drawn for the 578 tests exceeded that requested by the hospital laboratory by 19.0% ± 1.8% per test. The main factors of overdraw was: collection in blood containers without fill-lines, lighter weight infants and critically ill infants being cared for in the NICU.
EPO
Recombinant EPO (r-EPO) may be given to premature infants to stimulate red blood cell production. Brown and Keith studied two groups of 40 very low birth weight (VLBW) infants to compare the erythropoietic response between two and five times a week dosages of recombinant human erythropoietin (r-EPO) using the same dose. They established that more frequent dosing of the same weekly amount of r-EPO generated a significant and continuous increase in Hb in VLBW infants. The infants that received five dosages had higher absolute reticulocyte counts (219,857 mm³) than those infants that received only two dosages (173,361 mm³). However, it was noted that the response to r-EPO typically takes up to two weeks. This study also showed responses between two dosage schedules (two times a week and five times a week). Infants were recruited for gestational age—age since conception—≤27 weeks and 28 to 30 weeks and then randomized into the two groups, each totaling 500 U/kg a week. Brown and Keith found that after two weeks of r-EPO administration, Hb counts had increased and leveled off; the infants who received r-EPO five times a week had significantly higher Hb counts. This was present at four weeks for all infants ≤30 weeks gestation and at 8 weeks for infants ≤27 weeks gestation.To date, studies of r-EPO use in premature infants have had mixed results. Ohls et al. examined the use of early r-EPO plus iron and found no short-term benefits in two groups of infants (172 infants less than 1000 g and 118 infants 1000–1250 g). All r-EPO treated infants received 400 U/g three times a week until they reached 35 weeks gestational age. The use of r-EPO did not decrease the average number of transfusions in the infants born at less than 1000 g, or the percentage of infants in the 1000 to 1250 group. A multi-center European trial studied early versus late r-EPO in 219 infants with birth weights between 500 and 999 g. An r-EPO close of 750 U/kg/week was given to infants in both the early (1–9 weeks) and late (4–10 weeks) groups. The two r-EPO groups were compared to a control group who did not receive r-EPO. Infants in all three groups received 3 to 9 mg/kg of enteral iron. These investigators reported a slight decrease in transfusion and donor exposures in the early r-EPO group (1–9 weeks): 13% early, 11% late and 4% control group. It is likely that only a carefully selected subpopulation of infants may benefit from its use. Contrary to what just said, Bain and Blackburn (2004) also state in another study the use of r-EPO does not appear to have a significant effect on reducing the numbers of early transfusions in most infants, but may be useful to reduce numbers of late transfusion in extremely low-birth-weight infants. A British task force to establish transfusion guidelines for neonates and young children and to help try to explain this confusion recently concluded that “the optimal dose, timing, and nutritional support required during EPO treatment has yet to be defined and currently the routine use of EPO in this patient population is not recommended as similar reduction in blood use can probably be achieved with appropriate transfusion protocols.”
Transfusion management
Other strategies involve the reduction of blood loss during phlebotomy.For extremely low birth weight infants, laboratory blood testing using bedside devices offers a unique opportunity to reduce blood transfusions. This practice has been referred to as point-of-care testing or POC. Use of POC tests to measure the most commonly ordered blood tests could significantly decrease phlebotomy loss and lead to a reduction in the need for blood transfusions among critically ill premature neonates as these tests frequently require much less volume of blood to be collected from the patient. A study was done by Madan and colleagues to test this theory by conducting a retrospective chart review on all inborn infants <1000g admitted to the NICU that survived for 2 weeks of age during two separate 1 year time periods. Conventional bench top laboratory analysis during the first year was done using Radiometer Blood Gas and Electrolyte Analyzer. Bedside blood gas analysis during the second year was performed using a point-of-care analyzer (iSTAT). An estimated blood loss in the two groups was determined based on the number of specific blood tests on individual infants. The study found that there was an estimated 30% reduction in the total volume of blood removed for the blood tests. This study concluded that there is modern technology that can be used to limit the amount of blood removed from these infants thereby reducing the need for blood product transfusions (or the number of transfusions) and r-EPO.
See also
List of circulatory system conditions
List of hematologic conditions
References
== External links == |
Phacolytic glaucoma | Phacolytic glaucoma (PG) is a form of glaucoma which is caused due to a leaking mature or immature cataract. Inflammatory glaucoma which occurs in phacolysis is a condition which is a result of the leakage of protein within the lens into the capsule of a mature or hyper mature cataract and involves a simple procedure to be cured that is referred to as cataract extraction.The main symptoms of glaucoma include pain in the eye, redness and loss of sight, all of which reduce an individuals independence, in turn, reducing quality of life and an individuals ability fulfill other societal roles (such as driving and reading) as it reduces visual clarity. Phacolysis tends to be more frequently reported in underdeveloped countries because of the lack of resources necessary to treat such as condition.
Signs and symptoms
There are a variety of characteristics which indicate that an individual may have phacolytic glaucoma. Within older people, the lens of the eye may appear to be yellow and lose its transparency (becomes cloudy). Once the protein begins to seep into the lens, permanent damage to the lens may be caused as the precipitate in lens impairs vision.
Another symptom includes the fading of visual clarity. This symptom makes the eye create an image commonly described to appear as though looking through a waterfall. If the lens becomes completely opaque the individual will become blind, even though the photoreceptor cells are completely functional. Other common symptoms include;
clouding of the eyes natural lens
increase in intraocular pressure, which lies behind the iris and the pupil
red eyes
acute onset pain
tearing
corneal edema
photophobia (experience of discomfort to the eyes because of the exposure of high levels of light or by presence of physical sensitivity within the eyes)
significantly decreased vision.The major influencers of this illness include high exposure to the sun and age as this is a rare condition for individuals under the age of 35.
Causes
Cataracts, if left untreated, can develop into a mature state or hyper mature state, and may progressively become leaky thereby excreting proteins. Cataracts are caused by a breakdown of proteins which allows the lens to become cloudy and gradually turn opaque, causing a decrease in vision. Through the leakage of proteins that have a high molecular weight an obstruction of the drainage mechanism of the eye is caused.
Diagnosis
A variety of procedures can be used to physically diagnose phacolytic glaucoma as there are a variety of other types of glaucoma which may be confused with phacolysis such as acute angle-closure glaucoma (AACG), lens-particle glaucoma, neovascular glaucoma, phacomorphic glaucoma and uveitic glaucoma which can cause confusion in which procedures need to be conducted to revamp vision.The first type of diagnostic procedure referred to as a ‘slit lamp examination’ of phacolytic glaucoma allows for specific identification of microcystic corneal edema and the presence of macrophages, white material (dotted with patches within the inside capsule of the lens) and intense flare and iridescent or hyper-refringent particles specific to phacolytic glaucoma. The time period which symptoms have been affecting the patient should be obtained as experiencing symptoms for a period longer than 5 days may result in further issues such as glaucomatous disc damage or poorer prognosis. Additionally, previous cataract or trauma surgery which have been conducted must be accounted for so that an accurate diagnosis of current symptoms which could be caused because of these previous experiences.An ophthalmologic examination is another procedure which must be conducted to effectively diagnose phacolytic glaucoma. This test will indicate high levels of inflammation due to high intraocular pressures within the eyes. Additionally, the presence of calcium oxalate and cholesterol crystals from the degenerating cataract lens is an indication of phacolytic glaucoma but can only be identified by puncturing the cataract. This is specifically used to differentiate between uveitic glaucoma where keratic precipitates are present rather than calcium oxalate.
Target Population
Phacolysis is evident, more commonly, within elderly people as a result of cataracts that have developed over time. There are other factors which contribute to the development of phacolysis in seniors. This is clearly indicated through the increase of intraocular pressure, which usually occurs when anterior flow faces obstruction of the anterior flow to the aqueous humor. Essentially, the eye requires a photosynthetic pigment which allows for light to become chemical energy. Within seniors, this pigment over time splits with the oxygen to thereby generate phacolysis.
Treatment
The procedure involved in the curing of phacolysis includes the reduction of intraocular pressure (IOP) in the eye followed by cataract extraction surgery. Medical management is commonly used simply to control the inflammation temporarily. The reduction of intraocular pressure can be conducted through the use of a combination of topical and systemic IOP-lowering agents, cycloplegics, aqueous suppressants, hyper-osmotic agents, and anti-inflammatory drugs. Topical steroids also may assist in lowering intraocular pressure and decreasing pain.Previous to cataract surgery a variety of optometrical tests have to be conducted to comprehensively analyse an individuals eye-sight prior to the surgery. A refraction is also conducted to determine how much nearsightedness, farsightedness and/or astigmatism an individual may have. Additional specific measurements of the eye will be necessary in order to determine the curvature and length of the cornea in order to choose the most effective IOL which will need to be inserted during the surgery.Cataract surgery has become a very simple process which, with modern-day technology, can be conducted in a local anaesthetic procedure in an average time period of 15 minutes. The aim of cataract surgery is to replace the lens within the eye with an artificial lens to clear vision while removing any residue which could cloud vision. The cataract extraction surgery involves four major steps which includes; local anaesthetic, clearing of eye, intraocular lens is inserted and finally the contact lens to protect the eye which dissolves releasing antibiotics.Before major advancements in medical technology, cuts had to be manually made to the lens to conduct cataract extraction surgery, however, with the improvements in technology the LASIK procedure is the main procedure used to conduct cataract surgeries. This procedure involves the use of femtosecond lasers which allow for precision cuts to create the corneal flap necessary to clear the cataract which were substituted for use instead of a surgical tool which is generally hand-held by the surgeon to conduct the same incision manually. The corneal incision, the anterior capsulotomy and lens and cataract fragmentation are steps in which can be an alternative. Within this process, lasers strike a titanium-like target that are attached to an irrigation-aspiration probe. It is said that the utilisation of this laser will enable for better precision, accuracy and reproducibility for the corneal incision, the anterior capsulotomy and lens and cataract, therefore ensuring the reduction of risks and enabling for refined visual development of phacolysis and the extraction of cataract.When completing the surgery the utilisation of laser cataract surgery will allow for a precise incision resulting in a self-sealing process, enabling for the reduction of infection after the surgery. Therefore, as a result of the advancements in which the laser cataract surgery has provided, regarding the removal of the lens, surgeons have been able to complete the procedure in a more efficient manner and thereby ensure an improvement in the outcomes for individuals suffering from phacolysis. Additionally, the laser cataract procedures which are used to cure phacolysis have a success rate of 98% further proving this procedures effectiveness.The main issue with this technology is that the process costs about $300,000 to $500,000 and like all surgical procedures there is a degree of risk. Within the cataract removal procedures which take place a variety of complications may occur including;
chronic inflammation inside the eye
retinal detachment
infection
Rehabilitation
There are several medications which need to be consumed in order to treat phacolytic glaucoma. The medicines induced ensure the management of glaucoma and reduce inflammation. These medications consist of: Aqueous suppressants, anti-inflammatory drugs, hyper-osmotic agents, cycloplegics, anti-glaucoma medications. Medical therapy, however, is only a temporary treatment until cataract surgery can take place.The use of an eyepatch for a certain amount of time, as well as a contact lens to protect the eye which dissolves releasing antibiotics, must be incorporated in the rehabilitation process to reduce the risk of infection of the eye and to allow for an effective healing process. Additionally, the patient must consistently visit the specialist in order to ensure a successful removal of phacolytic glaucoma. There may be a need for medical therapies which treat arising issues for the eye such as inflammation. These medical therapy procedures for phacolysis consist of controlling the intraocular pressure which may include the use of topical steroids in order to decrease inflammation in the eye, and mydriatics in order to prevent the formation of synechiae.
Medication
It is found that with most cases, of phacolytic glaucoma post surgery patients are not exposed to many further obstacles in the healing process which therefore avoids the need for medication. Although, it is mostly encouraged that patients take antiglaucoma medication in order to deter the possibility of glaucoma and inflammation implicating the eye. One of these medications include eye drops which contain prostaglandin analogs. Prostaglandin analogs aim to lower intraocular pressure which thereby avoids inflammation to ensure an efficient healing process after cataract removal. Carbonic anhydrase inhibitors (CAI) in the form of pills, disables the production of the sodium pump in the aqueous humor and thereby decreases inflammation to, in turn, lower intraocular pressure.
The only major obstacle which could affect the healing process after the surgery necessary to treat phacolytic glaucoma would be an infection to the eye. The ophthalmologists conducting the surgery must aim to reduce the amount of microbes which are present on the ocular surface and avoid intracocular contamination during the procedure. These tasks can be conducted through the use of intracameral and topical antibiotics. Intracameral antibiotics are usually injections which are put into the eye or ocular surface to rid of microbes. Topical antibiotics come in the form of tablets which can be consumed through the mouth to treat bacterial infection. The use of either or both are left to the surgeon and their personal opinion on the possibility of bacterial infection.
Astigmatism correction
Astigmatism involves a deficiency in the optical capacity of the eye whereby the angle of light passing through the eye deviates and becomes distorted visuals due to the light rays, avoiding a common focus. Astigmatisms are the result of the cornea forming more in the shape of a curve in comparison to other meridians. Therefore, in order to reduce this, minor incisions must be taken in place of the cornea which, as previously mentioned, is forming in the shape of a curve, which will flatten the turn to a little extent, thereby allowing the cornea to be rounder and uniform. By performing astigmatism in order to correct the removal of cataract the requirement of prescription glasses and reading glasses post cataract extraction is avoided and ensures better vision for patients. Astigmatism rates increase dramatically from 14.3% in the under 15-year-old age group to 67.2% in the age group of over 65-years old. Since astigmatism affects the population of people over 65-years old which are more likely to suffer from phacolytic glaucoma it is an effective procedure which can take place during the cataract surgery used to correct phacolytic glaucoma and improve the quality of life of sufferers.
Epidemiology
The youngest patient found to be diagnosed with Phacolytic Glaucoma was 35 years of age, which thereby highlights its significant prevalence in senior patients. Moreover, Phacolytic Glaucoma is more likely seen in underdeveloped countries as a result of the lack of access to ophthalmologic care. When being faced with Phacolytic Glaucoma most cases ameliorate when the cataract is extracted thereby enhancing vision. On the other hand, this disease is less prevalent in developed countries such as Australia and the United States, due to a greater access to health care and earlier cataract surgery.
== References == |
Myxoma | A myxoma (New Latin from Greek muxa for mucus) is a myxoid tumor of primitive connective tissue. It is most commonly found in the heart (and is the most common primary tumor of the heart in adults) but can also occur in other locations.
Types
Table below:
1.^ SMA, smooth muscle actin. 2.^ MSA, muscle-specific actin. 3.^ EMA, epithelial membrane antigen.
Symptoms and signs
Symptoms associated with cardiac myxomas are typically due to the effect of the mass of the tumor obstructing the normal flow of blood within the chambers of the heart. Because pedunculated myxomas are somewhat mobile, symptoms may only occur when the patient is in a particular position.
Some symptoms of myxoma may be associated with the release of interleukin 6 (IL-6) by the myxoma. High levels of IL-6 may be associated with a higher risk of embolism of the myxoma.Symptoms of a cardiac myxoma include:
Dyspnea on exertion
Paroxysmal nocturnal dyspnea
Fever
Weight loss (see cachexia)
Lightheadedness or syncope (Loss of consciousness)
Hemoptysis
Sudden death
Tachycardia or milder heartrate, i.e. 75 - 100 cycl/min
Location
Ocular myxoma
Myxoma is a rare, benign stromal tumor of mesenchymal origin often confused with other conjunctival stromal tumors. Conjunctival myxomas are thought to originate in Tenons capsule and can masquerade as conjunctival lymphoma, lymphangioma, ocular surface squamous neoplasia (OSSN), or amelanotic melanoma.
Atrial myxoma
Cutaneous myxoma
Odontogenic myxoma
Atrial myxoma
Myxomas are usually located in either the left or right atrium of the heart; about 86 percent occur in the left atrium.Myxomas are typically pedunculated, with a stalk that is attached to the interatrial septum. The most common location for attachment of the stalk is the fossa ovalis region of the interatrial septum.An atrial myxoma may create an extra heart sound, audible to auscultation just after S2. It is most seen on echocardiography, as a pedunculated mass that is heterogeneous in appearance. A left atrial myxoma will cause an increase in pulmonary capillary wedge pressure.The differential diagnosis include other cardiac tumors such as lipomas and rhabdomyomas (and rarely teratomas). These other tumors of the heart are typically not pedunculated, however, and are more likely to infiltrate the muscle of the heart. Cardiac magnetic resonance imaging (MRI) can help non-invasively diagnose cardiac tumors. However, diagnosis usually requires examination of a tissue sample by a pathologist.
Treatment
Myxomas are usually removed surgically. The surgeon removes the myxoma, along with at least 5 surrounding millimeters of atrial septum. The septum is then repaired, using material from the pericardium.
Epidemiology
Cardiac myxomas predominantly appear in females in their 30s to 40s. Myxomas are the most common primary cardiac tumor affecting adults, accounting for one quarter to half of primary cardiac tumors seen in clinical practice.
See also
Myxoid tumor
Cutaneous myxoma
Carney complex
Myxomatosis
Primary tumors of the heart
Myxomatous degeneration
References
External links
03-031b. at Merck Manual of Diagnosis and Therapy Home Edition
Myxomatous degeneration at Wikidoc |
Renal agenesis | Renal agenesis is a medical condition in which one (unilateral) or both (bilateral) fetal kidneys fail to develop.
Unilateral and bilateral renal agenesis in humans, mice and zebra fish has been linked to mutations in the gene GREB1L. It has also been associated with mutations in the genes RET or UPK3A. in humans and mice respectively.
Type
Bilateral
Bilateral renal agenesis is a condition in which both kidneys of a fetus fail to develop during gestation. It is incompatible with life. It is one causative agent of Potter sequence. This absence of kidneys causes oligohydramnios, a deficiency of amniotic fluid in a pregnant woman, which can place extra pressure on the developing baby and cause further malformations. The condition is frequently, but not always the result of a genetic disorder, and is more common in infants born to one or more parents with a malformed or absent kidney.
Unilateral
This is much more common, but is not usually of any major health consequence, as long as the single kidney is healthy. However, this kidney tends to be hypertrophied, ectopic and prone to infection and damage.It may be associated with an increased incidence of Müllerian duct abnormalities, which are abnormalities of the development of the female reproductive tract and can be a cause of infertility, blocked menstrual flow (hematocolpos), increased need for Caesarean sections, or other problems. Herlyn-Werner-Wunderlich syndrome is one such syndrome in which unilateral renal agenesis is combined with a blind hemivagina and uterus didelphys. Up to 40% of women with a urogenital tract anomaly also have an associated renal tract anomaly.Adults with unilateral renal agenesis have considerably higher chances of hypertension (high blood pressure). People with this condition are advised to approach contact sports with caution.
A possible complication later in life of unilateral renal agenesis is Focal Segmental Glomerular Sclerosis (FSGS) which will cause nephrotic syndrome, potentially resulting from glomerular overload.
Genetics
In 2008 researchers found autosomal dominant mutations in the RET and GDNF genes to be linked to renal agenesis in unrelated stillborn fetuses through PCR and direct sequence analysis. In the study, DNA from 33 stillborn fetuses were sequenced for mutations in RET, GDNF and GFRA1. Nineteen of the fetuses had BRA, ten had URA and 4 had congenital renal dysplasia. Seven of the 19 BRA fetuses were found to have a mutation in the RET gene (37%), while two of the ten URA fetuses did (20%). One of the URA fetuses had two RET mutations and one GDNF mutation. There were no GFRA1 mutations found.However, the results of Skinner et al. study were questioned by a more recent study with a larger number of cases. In this study 105 fetuses were analyzed. Sixty-five fetuses had BRA while 24 had URA with an abnormal contralateral kidney. Mutations in the RET gene were only found in seven of the fetuses (6.6%).In 2014 researchers found autosomal recessive mutations in ITGA8 in three members of two unrelated families utilizing Exome Sequencing. One of the families was consanguineous.In 2017 researchers identified heritable autosomal dominant mutations in the gene GREB1L in two unrelated families as being the cause of both BRA and URA utilizing Exome Sequencing and direct sequencing analysis. This is the first reported genetic lesion implicated in the activation of Retinoic Acid Receptor (RAR) Targets that has been associated with renal agenesis in humans. The researchers found two different GREB1L mutations, each being unique to their respective pedigrees. In total, there were 23 individuals analyzed between the two families, four of which had BRA and five of which had URA. GREB1L mutations were identified in all of the affected individuals as well as in three unaffected family members, demonstrating incomplete penetrance and variable expressivity.There are several hundred to perhaps several thousand genes that, if they had the right kind of mutation, could lead to renal agenesis in humans. It is possible that each individual or family experiencing renal agenesis has a unique gene or genetic mutation causing the condition due to the fact that there are so many genes that are critical to proper renal development.Chromosomal anomalies have been associated with BRA in certain cases (chromosomes 1, 2, 5 and 21), but these anomalies were not inherited and have not been observed in subsequent cases. Additionally, neither extreme substance abuse or environmental factors (high power line, mercury, ground water issues, etc.) have been reported to be linked to an increased incidence of BRA or other cause of Potter sequence. However, renal agenesis and other causes of oligohydramnios sequence have been linked to a number of other conditions and syndromes to include Down syndrome, Kallmann syndrome, branchio-oto-renal syndrome and others.
Prevalence
The prevalence of unilateral renal agenesis in the population is approximately 1 in about 1000 people. Bilateral agenesis occurs in 1 in about 2500 foetuses.
References
== External links == |
Infantile apnea | Infantile apnea is a rare disease that is characterized by cessation of breathing in an infant for at least 20 seconds or a shorter respiratory pause that is associated with a slow heart rate, bluish discolouration of the skin, extreme paleness, gagging, choking and/or decreased muscle tone. Infantile apnea occurs in children under the age of one and it is more common in premature infants. Symptoms of infantile apnea occur most frequently during the rapid eye movement (REM) stage of sleep. The nature and severity of breathing problems in patients can be detected in a sleep study called a polysomnography which measures the brain waves, heartbeat, body movements and breathing of a patient overnight. Infantile apnea can be caused by developmental problems that result in an immature brainstem or it can be caused other medical conditions. As children grow and develop, infantile apnea usually does not persist. Infantile apnea may be related to some cases of sudden infant death syndrome (SIDS) however, the relationship between infantile apnea and SIDS is not known.
Cause
√ having a family history of sleep apnea.
√ being overweight or obese.
✓ having certain medical conditions (cerebral palsy, Down syndrome, sickle cell disease, abnormalities in the skull or face)
✓ being born with a low birth weight.
✓ having a large tongue.
Diagnosis
Classification
There are three major categories of apnea known as central, obstructive, and mixed apnea.
Central Apnea
Central apnea is characterized by insufficient responsiveness from respiratory centers such as the medulla, which results in poor coordination of the body systems that are necessary for breathing. Respiratory muscles and nerves to lose the ability to effectively receive and process signals from the brain causing respiratory efforts to cease. Central apnea is quite common and can be found in healthy, full-term infants for short periods of time before breathing patterns in the infant stabilize. In premature infants, central apnea is attributed to an underdeveloped respiratory system which results in decreased response to higher carbon dioxide levels and difficulty breathing. Head trauma may also cause central apnea as it interferes with normal signalling of the central respiratory system, this might be present in infants who suffer from abuse so investigating patient background is an important consideration.
Obstructive Apnea
Obstructive apnea occurs when the airway passages are obstructed and little to no air exchange occurs, resulting in impaired breathing. In some cases, it occurs when patients are born with a small airway opening. Patients with obstructive apnea often have vigorous inspiratory effort but the efforts are still ineffective. Normally, the muscles at the level of the throat relax and dilate while asleep in order to open up airway however, patients with obstructive apnea may have decreased neuromuscular tone of the muscles responsible for dilating the pharynx during sleep. The inability of the vocal cords to move and the presence of a foreign body may also cause obstructive apnea. Cases of obstructive apnea are rarely found in infants that are healthy.
Mixed Apnea
Mixed apnea is a combination of both central and obstructive factors. The majority of premature infants with sleep apnea have mixed apnea.
Epidemiology
When infants have a lower birth weight or younger gestational age, there is a greater risk of infantile apnea. With the advancement of neonatal intensive care units and the greater technology available, there are more successful premature births compared to the past. With the greater number of premature infants being born, there is also a greater number of children with infantile apnea. Approximately 85 percent of infants born with a weight less than 2.2 pounds (1 kg) experience infantile apnea within the first month after birth. This risk decreases to 25 percent for infants weighing less than 5.5 pounds (2.5 kg). Studies have found that almost 2% of the pediatric population experience obstructive sleep apnea.
== References == |
Hypogonadism | Hypogonadism means diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estrogen (e.g., estradiol) as hypoestrogenism. These are responsible for the observed signs and symptoms in both males and females.
Hypogonadism, commonly referred to by the symptom "low testosterone" or "Low T", can also decrease other hormones secreted by the gonads including progesterone, DHEA, anti-Müllerian hormone, activin, and inhibin. Sperm development (spermatogenesis) and release of the egg from the ovaries (ovulation) may be impaired by hypogonadism, which, depending on the degree of severity, may result in partial or complete infertility.
In January 2020, the American College of Physicians issued clinical guidelines for testosterone treatment in adult men with age-related low levels of testosterone. The guidelines are supported by the American Academy of Family Physicians. The guidelines include patient discussions regarding testosterone treatment for sexual dysfunction; annual patient evaluation regarding possible notable improvement and, if none, to discontinue testosterone treatment; physicians should consider intramuscular treatments, rather than transdermal treatments, due to costs and since the effectiveness and harm of either method is similar; and, testosterone treatment for reasons other than possible improvement of sexual dysfunction may not be recommended.
Classification
Deficiency of sex hormones can result in defective primary or secondary sexual development, or withdrawal effects (e.g., premature menopause) in adults. Defective egg or sperm development results in infertility. The term hypogonadism usually means permanent rather than transient or reversible defects, and usually implies deficiency of reproductive hormones, with or without fertility defects. The term is less commonly used for infertility without hormone deficiency. There are many possible types of hypogonadism and several ways to categorize them. Hypogonadism is also categorized by endocrinologists by the level of the reproductive system that is defective. Physicians measure gonadotropins (LH and FSH) to distinguish primary from secondary hypogonadism. In primary hypogonadism the LH and/or FSH are usually elevated, meaning the problem is in the testicles (hyper-gonatropic hypogonadism); whereas in secondary hypogonadism, both are normal or low, suggesting the problem is in the brain (hypo-gonatropic hypogonadism).
Affected system
Hypogonadism resulting from defects of the gonads is referred to as hypergonadotropic hypogonadism or primary hypogonadism. Examples include Klinefelter syndrome and Turner syndrome. Mumps is known to cause testicular failure, and in recent years has been immunized against in the US. A varicocele can reduce hormonal production as well.
Hypogonadism resulting from hypothalamic or pituitary defects is termed hypogonadotropic hypogonadism (HH), secondary hypogonadism, or central hypogonadism (referring to the central nervous system).Examples of hypothalamic defects include Kallmann syndrome.
Examples of pituitary defects include hypopituitarism and pituitary hypoplasia.
An example of a hypogonadism resulting from the lack of hormone response is androgen insensitivity syndrome, where there are inadequate receptors to bind the testosterone, resulting in varying clinical phenotypes of sexual characteristics despite XY chromosomes.
Isolated hypogonadotropic hypogonadism (IHH), also called idiopathic or congenital hypogonadotropic hypogonadism (CHH) as well as isolated or congenital gonadotropin-releasing hormone deficiency (IGD) accounts for a small subset of cases of hypogonadotropic hypogonadism (HH) due to deficiency in or insensitivity to gonadotropin-releasing hormone (GnRH) where the function and anatomy of the anterior pituitary are otherwise normal and secondary causes of HH are not present.
Primary or secondary
Primary - defect is inherent within the gonad: e.g. Noonan syndrome, Turner syndrome (45X,0), Klinefelter syndrome (47XXY), XY with SRY gene-immunity
Secondary - defect lies outside of the gonad: e.g. Polycystic ovary syndrome, and Kallmann syndrome, also called hypogonadotropic hypogonadism. Hemochromatosis and diabetes mellitus can be causes of this as well.
Congenital vs. acquired
Examples of congenital causes of hypogonadism, that is, causes that are present at birth:Turner syndrome and Klinefelter syndrome. It is also one of the signs of CHARGE syndrome.
Examples of acquired causes of hypogonadism:Opioid Induced Androgen Deficiency (resulting from the prolonged use of opioid class drugs, e.g. codeine, Dihydrocodeine, morphine, oxycodone, methadone, fentanyl, hydromorphone, etc.)
Anabolic steroid-induced hypogonadism (ASIH)
Childhood mumps
Children born to mothers who had ingested the endocrine disruptor diethylstilbestrol for potential miscarriage
Traumatic brain injury, even in childhood
In males, normal aging causes a decrease in androgens, which is sometimes called "male menopause" (also known by the coinage "manopause"), late-onset hypogonadism (LOH), and "andropause" or androgen decline in the aging male (ADAM), among other names.
It is a symptom of hereditary hemochromatosis
Hormones vs. fertility
Hypogonadism can involve just hormone production or just fertility, but most commonly involves both.
Examples of hypogonadism that affect hormone production more than fertility are hypopituitarism and Kallmann syndrome; in both cases, fertility is reduced until hormones are replaced but can be achieved solely with hormone replacement.
Examples of hypogonadism that affect fertility more than hormone production are Klinefelter syndrome and Kartagener syndrome.
Other
Hypogonadism can occur in other conditions, like Prader–Willi syndrome.
Signs and symptoms
Women with hypogonadism do not begin menstruating and it may affect their height and breast development. Onset in women after puberty causes cessation of menstruation, lowered libido, loss of body hair, and hot flashes. In men, it causes impaired muscle and body hair development, gynecomastia, decreased height, erectile dysfunction, and sexual difficulties. If hypogonadism is caused by a disorder of the central nervous system (e.g., a brain tumor), then this is known as central hypogonadism. Signs and symptoms of central hypogonadism may involve headaches, impaired vision, double vision, milky discharge from the breast, and symptoms caused by other hormone problems.
Hypogonadotrophic hypogonadism
The symptoms of hypogonadotrophic hypogonadism, a subtype of hypogonadism, include late, incomplete or lack of development at puberty, and sometimes short stature or the inability to smell; in females, a lack of breasts and menstrual periods, and in males a lack of sexual development, e.g., facial hair, penis and testes enlargement, deepening voice.
Diagnosis
Women
Testing serum LH and FSH levels are often used to assess hypogonadism in women, particularly when menopause is believed to be happening. These levels change during a womans normal menstrual cycle, so the history of having ceased menstruation coupled with high levels aids the diagnosis of being menopausal. Commonly, the post-menopausal woman is not called hypogonadal if she is of typical menopausal age. Contrast with a young woman or teen, who would have hypogonadism rather than menopause. This is because hypogonadism is an abnormality, whereas menopause is a normal change in hormone levels. In any case, the LH and FSH levels will rise in cases of primary hypogonadism or menopause, while they will be low in women with secondary or tertiary hypogonadism.Hypogonadism is often discovered during evaluation of delayed puberty, but ordinary delay, which eventually results in normal pubertal development, wherein reproductive function is termed constitutional delay. It may be discovered during an infertility evaluation in either men or women.
Men
Low testosterone can be identified through a simple blood test performed by a laboratory, ordered by a health care provider. Blood for the test must be taken in the morning hours, when levels are highest, as levels can drop by as much as 13% during the day and all normal reference ranges are based on morning levels. However, low testosterone in the absence of any symptoms does not clearly need to be treated.Normal total testosterone levels depend on the mans age but generally range from 240 to 950 ng/dL (nanograms per deciliter) or 8.3-32.9 nmol/L (nanomoles per liter). According to American Urological Association, the diagnosis of low testosterone can be supported when the total testosterone level is below 300 ng/dl. Some men with normal total testosterone have low free or bioavailable testosterone levels which could still account for their symptoms. Men with low serum testosterone levels should have other hormones checked, particularly luteinizing hormone to help determine why their testosterone levels are low and help choose the most appropriate treatment (most notably, testosterone is usually not appropriate for secondary or tertiary forms of male hypogonadism, in which the LH levels are usually reduced).Treatment is often prescribed for total testosterone levels below 230 ng/dL with symptoms. If the serum total testosterone level is between 230 and 350 ng/dL, free or bioavailable testosterone should be checked as they are frequently low when the total is marginal.The standard range given is based on widely varying ages and, given that testosterone levels naturally decrease as humans age, age-group specific averages should be taken into consideration when discussing treatment between doctor and patient. In men, testosterone falls approximately 1 to 3 percent each year.
Blood testingA position statement by the Endocrine Society expressed dissatisfaction with most assays for total, free, and bioavailable testosterone. In particular, research has questioned the validity of commonly administered assays of free testosterone by radioimmunoassay. The free androgen index, essentially a calculation based on total testosterone and sex hormone-binding globulin levels, has been found to be the worst predictor of free testosterone levels and should not be used. Measurement by equilibrium dialysis or mass spectroscopy is generally required for accurate results, particularly for free testosterone which is normally present in very small concentrations.
Screening
Screening males who do not have symptoms for hypogonadism is not recommended as of 2018.
Treatment
Male primary or hypergonadotropic hypogonadism is often treated with testosterone replacement therapy if they are not trying to conceive. Adverse effects of testosterone replacement therapy include increased cardiovascular events (including strokes and heart attacks) and death. The Food and Drug Administration (FDA) stated in 2015 that neither the benefits nor the safety of testosterone have been established for low testosterone levels due to aging. The FDA has required that testosterone pharmaceutical labels include warning information about the possibility of an increased risk of heart attacks and stroke.While historically, men with prostate cancer risk were warned against testosterone therapy, that has shown to be a myth.Other side effects can include an elevation of hematocrit to levels that require blood withdrawal (phlebotomy) to prevent complications from excessively thick blood. Gynecomastia (growth of breasts in men) sometimes occurs. Finally, some physicians worry that obstructive sleep apnea may worsen with testosterone therapy, and should be monitored.Another treatment for hypogonadism is human chorionic gonadotropin (hCG). This stimulates the LH receptor, thereby promoting testosterone synthesis. This will not be effective in men whose testes simply cannot synthesize testosterone anymore (primary hypogonadism), and the failure of hCG therapy is further support for the existence of true testicular failure in a patient. It is particularly indicated in men with hypogonadism who wish to retain their fertility, as it does not suppress spermatogenesis (sperm production) as testosterone replacement therapy does.For both men and women, an alternative to testosterone replacement is low-dose clomifene treatment, which can stimulate the body to naturally increase hormone levels while avoiding infertility and other side effects that can result from direct hormone replacement therapy. Clomifene blocks estrogen from binding to some estrogen receptors in the hypothalamus, thereby causing an increased release of gonadotropin-releasing hormone and subsequently LH from the pituitary. Clomifene is a selective estrogen receptor modulator (SERM). Generally, clomifene does not have adverse effects at the doses used for this purpose. Clomifene at much higher doses is used to induce ovulation and has significant adverse effects in such a setting.
See also
References
External links
Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency Overview at National Center for Biotechnology Information.
MedlinePlus Encyclopedia: Hypogonadism
Hypogonadism at eMedicine |
Thymoma | A thymoma is a tumor originating from the epithelial cells of the thymus that is considered a rare malignancy. Thymomas are frequently associated with neuromuscular disorders such as myasthenia gravis; thymoma is found in 20% of patients with myasthenia gravis. Once diagnosed, thymomas may be removed surgically. In the rare case of a malignant tumor, chemotherapy may be used.
Signs and symptoms
A third of all people with a thymoma have symptoms caused by compression of the surrounding organs by an expansive mass. These problems may take the form of superior vena cava syndrome, dysphagia (difficulty swallowing), cough, or chest pain.One-third of patients have their tumors discovered because they have an associated autoimmune disorder. As mentioned earlier, the most common of those conditions is myasthenia gravis (MG); 10–15% of patients with MG have a thymoma and, conversely, 30–45% of patients with thymomas have MG. Additional associated autoimmune conditions include thymoma-associated multiorgan autoimmunity, pure red cell aplasia and Good syndrome (thymoma with combined immunodeficiency and hypogammaglobulinemia). Other reported disease associations are with acute pericarditis, agranulocytosis, alopecia areata, ulcerative colitis, Cushings disease, hemolytic anemia, limbic encephalopathy, myocarditis, nephrotic syndrome, panhypopituitarism, pernicious anemia, polymyositis, rheumatoid arthritis, sarcoidosis, scleroderma, sensorimotor radiculopathy, stiff person syndrome, systemic lupus erythematosus and thyroiditis.One-third to one-half of all persons with thymoma have no symptoms at all, and the mass is identified on a chest X-ray or CT/CAT scan performed for an unrelated problem.
Pathology
Thymoma originates from the epithelial cell population in the thymus, and several microscopic subtypes are now recognized. There are three principal histological types of thymoma, depending on the appearance of the cells by microscopy:
Type A if the epithelial cells have an oval or fusiform shape (less lymphocyte count);
Type B if they have an epithelioid shape (Type B has three subtypes: B1 (lymphocyte-rich), B2 (cortical) and B3 (epithelial).);
Type AB if the tumor contains a combination of both cell types.Thymic cortical epithelial cells have abundant cytoplasm, vesicular nucleus with finely divided chromatin and small nucleoli and cytoplasmic filaments contact adjacent cells.
Thymic medullary epithelial cells in contrast are spindle shaped with oval dense nucleus and scant cytoplasm
thymoma if recapitulates cortical cell features more, is thought to be less benign.
Diagnosis
When a thymoma is suspected, a CT/CAT scan is generally performed to estimate the size and extent of the tumor, and the lesion is sampled with a CT-guided needle biopsy. Increased vascular enhancement on CT scans can be indicative of malignancy, as can be pleural deposits. Limited biopsies are associated with a very small risk of pneumomediastinum or mediastinitis and an even-lower risk of damaging the heart or large blood vessels. Sometimes thymoma metastasize for instance to the abdomen.The diagnosis is made via histologic examination by a pathologist, after obtaining a tissue sample of the mass. Final tumor classification and staging is accomplished pathologically after formal surgical removal of the thymic tumor.
Selected laboratory tests can be used to look for associated problems or possible tumor spread. These include: full blood count, protein electrophoresis, antibodies to the acetylcholine receptor (indicative of myasthenia), electrolytes, liver enzymes and renal function.
Staging
The Masaoka Staging System is used widely and is based on the anatomic extent of disease at the time of surgery:
I: Completely encapsulated
IIA: Microscopic invasion through the capsule into surrounding fatty tissue
IIB: Macroscopic invasion into capsule
III: Macroscopic invasion into adjacent organs
IVA: Pleural or pericardial implants
IVB: Lymphogenous or hematogenous metastasis to distant (extrathoracic) sites
Treatment
Surgery is the mainstay of treatment for thymoma. If the tumor is apparently invasive and large, preoperative (neoadjuvant) chemotherapy and/or radiotherapy may be used to decrease the size and improve resectability, before surgery is attempted. When the tumor is an early stage (Masaoka I through IIB), no further therapy is necessary. Removal of the thymus in adults does not appear to induce immune deficiency. In children, however, postoperative immunity may be abnormal and vaccinations for several infectious agents are recommended. Invasive thymomas may require additional treatment with radiotherapy and chemotherapy (cyclophosphamide, doxorubicin and cisplatin).. Recurrences of thymoma are described in 10-30% of cases up to 10 years after surgical resection, and in the majority of cases also pleural recurrences can be removed. Recently, surgical removal of pleural recurrences can be followed by hyperthermic intrathoracic perfusion chemotherapy or intrathoracic hyperthermic perfused chemotherapy (ITH).
Prognosis
Prognosis is much worse for stage III or IV thymomas as compared with stage I and II tumors. Invasive thymomas uncommonly can also metastasize, generally to pleura, bones, liver or brain in approximately 7% of cases. A study found that slightly over 40% of observed patients with stage III and IV tumors survived for at least 10 years after diagnosis. The median age of these patients at the time of thymoma diagnosis was 57 years. Patients who have undergone thymectomy for thymoma should be warned of possible severe side effects after yellow fever vaccination. This is probably caused by inadequate T-cell response to live attenuated yellow fever vaccine. Deaths have been reported.
Epidemiology
Men and women are equally affected by thymomas. The typical age at diagnosis is 30–40, although cases have been described in every age group, including children.
Gallery
See also
Mediastinal tumor
References
== External links == |
Nonbacterial thrombotic endocarditis | Nonbacterial thrombotic endocarditis (NBTE) is a form of endocarditis in which small sterile vegetations are deposited on the valve leaflets. Formerly known as marantic endocarditis, which comes from the Greek marantikos, meaning "wasting away". The term "marantic endocarditis" is still sometimes used to emphasize the association with a wasting state such as cancer.
Risk factors
Marantic vegetations are often associated with previous rheumatic fever. Other risk factors include:
hypercoagulable states
malignant cancers, especially mucin-producing adenocarcinomas (most commonly associated with pancreatic adenocarcinomas)
systemic lupus erythematosus: Referred to as Libman-Sacks endocarditis
trauma (e.g., catheters)
Valve predilection
The disease affects the valves with following predilection: mitral valve > aortic valve > tricuspid valve > pulmonary valve
Histopathology
Grossly, vegetations form along lines of valve closure and are generally symmetric with a smooth or verrucoid (warty) texture. Histologically, lesions are composed of fibrin (eosinophilic) and platelets but, unlike bacterial etiologies, contain little evidence of PMNs, microorganisms or inflammation.
Diagnosis
Due to the non-invasive nature of NBTE, clinical examination may or may not reveal a new murmur. An embolic stroke may be the first feature to suggest diagnosis of NBTE. An echocardiograph may be used to further assess for valvular lesions.
References
== External links == |
Esophageal dysphagia | Esophageal dysphagia is a form of dysphagia where the underlying cause arises from the body of the esophagus, lower esophageal sphincter, or cardia of the stomach, usually due to mechanical causes or motility problems.
Signs and symptoms
Patients usually complain of dysphagia (the feeling of food getting stuck several seconds after swallowing), and will point to the suprasternal notch or behind the sternum as the site of obstruction.
Causes
If there is dysphagia to both solids and liquids, then it is most likely a motility problem. If there is dysphagia initially to solids but progresses to also involve liquids, then it is most likely a mechanical obstruction. Once a distinction has been made between a motility problem and a mechanical obstruction, it is important to note whether the dysphagia is intermittent or progressive. An intermittent motility dysphagia likely can be diffuse esophageal spasm (DES) or nonspecific esophageal motility disorder (NEMD). Progressive motility dysphagia disorders include scleroderma or achalasia with chronic heartburn, regurgitation, respiratory problems, or weight loss. Intermittent mechanical dysphagia is likely to be an esophageal ring. Progressive mechanical dysphagia is most likely due to peptic stricture or esophageal cancer.Schematically the above can be presented as a tree diagram:
Differential diagnosis
Esophageal stricture, or narrowing of the esophagus, is usually a complication of acid reflux, most commonly due to gastroesophageal reflux disease (GERD). These patients are usually older and have had GERD for a long time. Esophageal stricture can also be due to other causes, such as acid reflux from Zollinger–Ellison syndrome, trauma from a nasogastric tube placement, and chronic acid exposure in patients with poor esophageal motility from scleroderma. Other non-acid related causes of peptic strictures include infectious esophagitis, ingestion of chemical irritant, pill irritation, and radiation. Peptic stricture is a progressive mechanical dysphagia, meaning patients will complain of initial intolerance to solids followed by inability to tolerate liquids. When the diameter of the stricture is less than 12 mm the patient will always have dysphagia, while dysphagia is not seen when the diameter of the stricture is above 30 mm. Symptoms relating to the underlying cause of the stricture usually will also be present.
Esophageal cancer also presents with progressive mechanical dysphagia. Patients usually come with
rapidly progressive dysphagia first with solids then with liquids, weight loss (> 10 kg), and anorexia (loss of appetite). Esophageal cancer usually affects the elderly. Esophageal cancers can be either squamous cell carcinoma or adenocarcinoma. Adenocarcinoma is the most prevalent in the US and is associated with patients with chronic GERD who have developed Barretts esophagus (intestinal metaplasia of esophageal mucosa). Squamous cell carcinoma is more prevalent in Asia and is associated with tobacco smoking and alcohol use.
Esophageal rings and webs, are actual rings and webs of tissue that may occlude the esophageal lumen.
Rings --- Also known as Schatzki rings from the discoverer, these rings are usually mucosal rings rather than muscular rings, and are located near the gastroesophageal junction at the squamo-columnar junction. Presence of multiple rings may suggest eosinophilic esophagitis. Rings cause intermittent mechanical dysphagia, meaning patients will usually present with transient discomfort and regurgitation while swallowing solids and then liquids, depending on the constriction of the ring.
Webs --- Usually squamous mucosal protrusion into the esophageal lumen, especially anterior cervical esophagus behind the cricoid area. Patients are usually asymptomatic or have intermittent dysphagia. An important association of esophageal webs is to the Plummer–Vinson syndrome in iron deficiency, in which case patients will also have anemia, koilonychia, fatigue, and other symptoms of anemia.
Achalasia is an idiopathic motility disorder characterized by failure of lower esophageal sphincter (LES) relaxation as well as loss of peristalsis in the distal esophagus, which is mostly smooth muscle. Both of these features impair the ability of the esophagus to empty contents into the stomach. Patients usually complain of dysphagia to both solids and liquids. Dysphagia to liquids, in particular, is a characteristic of achalasia. Other symptoms of achalasia include regurgitation, night coughing, chest pain, weight loss, and heartburn. The combination of achalasia, adrenal insufficiency, and alacrima (lack of tear production) in children is known as the triple-A (Allgrove) syndrome. In most cases the cause is unknown (idiopathic), but in some regions of the world, achalasia can also be caused by Chagas disease due to infection by Trypanosoma cruzi.
Scleroderma is a disease characterized by atrophy and sclerosis of the gut wall, most commonly of the distal esophagus (~90%). Consequently, the lower esophageal sphincter cannot close and this can lead to severe gastroesophageal reflux disease (GERD). Patients typically present with progressive dysphagia to both solids and liquids secondary to motility problems or peptic stricture from acid reflux.
Spastic motility disorders include diffuse esophageal spasm (DES), nutcracker esophagus, hypertensive lower esophageal sphincter, and nonspecific spastic esophageal motility disorders (NEMD).
DES can be caused by many factors that affect muscular or neural functions, including acid reflux, stress, hot or cold food, or carbonated drinks. Patients present with intermittent dysphagia, chest pain, or heartburn.Rare causes of esophageal dysphagia not mentioned above
Diverticulum
Aberrant subclavian artery, or (dysphagia lusoria)
Cervical osteophytes
Enlarged aorta
Enlarged left atrium
Mediastinal tumor
Diagnostic tools
Once a patient complains of dysphagia they should have an upper endoscopy (EGD). Commonly patients are found to have esophagitis and may have an esophageal stricture. Biopsies are usually done to look for evidence of esophagitis even if the EGD is normal. Usually no further testing is required if the diagnosis is established on EGD. Repeat endoscopy may be needed for follow up.
If there is a suspicion of a proximal lesion such as:
history of surgery for laryngeal or esophageal cancer
history of radiation or irritating injury
achalasia
Zenkers diverticuluma barium swallow may be performed before endoscopy to help identify abnormalities that might increase the risk of perforation at the time of endoscopy.
If achalasia suspected an upper endoscopy is required to exclude a malignancy as a cause of the findings on barium swallow. Manometry is performed next to confirm. A normal endoscopy should be followed by manometry, and if manometry is also normal, the diagnosis is functional dysphagia.
Treatment
The patient is generally sent for a GI, pulmonary, or ENT, depending on the suspected underlying cause. Consultations with a speech therapist and registered dietitian nutritionist (RDN) are also needed, as many patients may need dietary modifications such as thickened fluids.
References
== External links == |
Trichodiscoma | A trichodiscoma is a cutaneous condition, a benign, usually skin-colored tumor most often affecting the face and upper trunk.: 674
See also
Birt–Hogg–Dubé syndrome
Fibrofolliculoma
List of cutaneous conditions
List of cutaneous neoplasms associated with systemic syndromes
References
== External links == |
Atypical facial pain | Atypical facial pain (AFP) is a type of chronic facial pain which does not fulfill any other diagnosis. There is no consensus as to a globally accepted definition, and there is even controversy as to whether the term should be continued to be used. Both the International Headache Society (IHS) and the International Association for the Study of Pain (IASP) have adopted the term persistent idiopathic facial pain (PIFP) to replace AFP. In the 2nd Edition of the International Classification of Headache Disorders (ICHD-2), PIFP is defined as "persistent facial pain that does not have the characteristics of the cranial neuralgias ... and is not attributed to another disorder." However, the term AFP continues to be used by the World Health Organizations 10th revision of the International Statistical Classification of Diseases and Related Health Problems and remains in general use by clinicians to refer to chronic facial pain that does not meet any diagnostic criteria and does not respond to most treatments.The main features of AFP are: no objective signs, negative results with all investigations/ tests, no obvious explanation for the cause of the pain, and a poor response to attempted treatments. AFP has been described variably as a medically unexplained symptom, a diagnosis of exclusion, a psychogenic cause of pain (e.g. a manifestation of somatoform disorder), and as a neuropathy. AFP is usually burning and continuous in nature, and may last for many years. Depression and anxiety are often associated with AFP, which are either described as a contributing cause of the pain, or the emotional consequences of suffering with unrelieved, chronic pain. For unknown reasons, AFP is significantly more common in middle aged or elderly people, and in females.
Atypical odontalgia (AO) is very similar in many respects to AFP, with some sources treating them as the same entity, and others describing the former as a sub-type of AFP. Generally, the term AO may be used where the pain is confined to the teeth or gums, and AFP when the pain involves other parts of the face. As with AFP, there is a similar lack of standardization of terms and no consensus regarding a globally accepted definition surrounding AO. Generally definitions of AO state that it is pain with no demonstrable cause which is perceived to be coming from a tooth or multiple teeth, and is not relieved by standard treatments to alleviate dental pain.
Depending upon the exact presentation of atypical facial pain and atypical odontalgia, it could be considered as craniofacial pain or orofacial pain. It has been suggested that, in truth, AFP and AO are umbrella terms for a heterogenous group of misdiagnosed or not yet fully understood conditions, and they are unlikely to each represent a single, discrete condition.
Signs and symptoms
Some sources list some non-specific signs that may be associated with AFP/AO. These include increased temperature and tenderness of the mucosa in the affected area, which is otherwise normal in every regard.Patient often reports symptoms of paresthesia, pain, and throbbing. Physical examination may be normal, but hypoesthesia, hyperesthesia, and allodynia may be found.
The features of atypical facial pain can be considered according to the Socrates pain assessment method (see table).
Causes
Health care associated
Sometimes dental treatment or surgical procedures in the mouth appear to precede the onset of AFP, or sometimes persons with AFP will blame clinicians for their pain.
Organic disease
Many persons with AFP blame organic disease for their pain.Research in individuals with AFP showed that there is increased cerebral activity (demonstrated during positron emission tomography), possibly suggesting that there is an overactive alerting mechanism to peripheral stimuli. It has been theorized that this can trigger neuropeptides to be released, and the formation of free radicals (capable of damaging cells), the release of eicosanoids (e.g. prostaglandins). There is some suggestion that AFP is an early form of trigeminal neuralgia.Pain may be referred from other parts of the head or other parts of the body to cause facial pain. Nowhere in the body is referred pain more well illustrated than in the face, and this is due to the richly and complexly innervated nature of the head and neck.
"Neuralgia-inducing cavitational osteonecrosis"
Neuralgia-inducing cavitational osteonecrosis (NICO) is a controversial term, and it is questioned to exist by many. Osteonecrosis of the jaws refers to the death of bone marrow in the maxilla or the mandible due to inadequate blood supply. It is not necessarily a painful condition, typically there will be no pain at all unless bone necrotic bone becomes exposed to the mouth or through the facial skin, and even then this continues to be painless in some cases. When pain does occur, it is variable in severity, and may be neuralgiform or neuropathic in nature. The term NICO is used to describe pain caused by ischemic osteonecrosis of the jaws, where degenerative extracellular cystic spaces (cavitations inside the bone) are said to develop as a result of ischemia and infarctions in the bone marrow, possibly in relation to other factors such as a hereditary predisposition for thrombus formation within blood vessels, chronic low-grade dental infections and the use of vasoconstrictors in local anesthetics during dental procedures. This proposed phenomenon has been postulated to be the cause of pain in some patients with AFP or trigeminal neuralgia, but this is controversial. NICO is said to be significantly more common in females, and the lesions may or may not be visible on radiographs. When they are visible, the appearance is very variable. About 60% of the lesions appear as a "hot spot" on an technetium 99 bone scan. Proponents of NICO recommend decortication (surgical removal of a section of the cortical plate, originally described as a treatment for osteomyelitis of the jaws) and curettage of the necrotic bone from the cavitation, and in some reported cases, this has relieved the chronic pain. However, NICO appears to show a tendency to recur and develop elsewhere in the jaws. The American Association of Endodontists Research and Scientific Affairs Committee published a position statement on NICO in 1996, stating:
"Most affected sites with a postoperative NICO diagnosis have been in edentulous areas [where the teeth have been lost]. However, some patients with long, frustrating histories of pain associated with endodontically treated teeth have been presented the treatment option of tooth extraction followed by periapical curettage in an attempt to alleviate pain. The American Association of Endodontists cannot condone this practice when NICO is suspected. Because of the lack of clear etiological data, a NICO diagnosis should be considered only as a last resort when all possible local odontogenic causes for facial pain have been eliminated. If a NICO lesion is suspected in relation to an endodontically treated tooth, if possible, periradicular surgery and curettage should be attempted, not extraction. In addition, the practice of recommending the extraction of endodontically treated teeth for the prevention of NICO, or any other disease, is unethical and should be reported immediately to the appropriate state board of dentistry."
Atypical trigeminal neuralgia
Some suggest that AFP is an early form of trigeminal neuralgia.
Psychologic
Sometimes stressful life events appear to precede the onset of AFP, such as bereavement or illness in a family member. Hypochondriasis, especially cancerophobia, is also often cited as being involved. Most people with AFP are "normal" people who have been under extreme stress, however other persons with AFP have neuroses or personality disorders, and a small minority have psychoses. Some have been separated from their parents as children.Depression, anxiety and altered behavior are strongly correlated with AFP. It is argued whether this is a sole or contributing cause of AFP, or the emotional consequences of suffering with chronic, unrelieved pain. It has been suggested that over 50% of people with AFP have concomitant depression or hypochondria. Furthermore, about 80% of persons with psychogenic facial pain report other chronic pain conditions such as listed in the table.
Diagnosis
Migraine
Dental diseases
Neoplasia
InfectionAFP and AO can be difficult to diagnose, and are often misdiagnosed with resultant inappropriate attempts of treatment, e.g. root canal therapy which may at best have only a temporary benefit, or at worst lead to an increase in the pain. Excluding an organic cause for the pain is the most important part of the diagnosis. Odontogenic pain should especially be ruled out, since this accounts for over 95% of cases of orofacial pain.There is considerable symptom overlap between atypical facial pain and temporomandibular joint dysfunction.The diagnosis of facial pain generally is often multidisciplinary.
Classification
AFP has also been described as a medically unexplained symptom, which are thought by some to be largely psychogenic in nature. However, true psychogenic pain is considered to be rare. Some sources have assigned or categorized AFP as a psychosomatic manifestation of somatoform disorder, as defined in the Diagnostic and Statistical Manual of the American Psychiatric Association. Distinction should be made between somatoform disorder, where affected individuals are not inventing the symptom for some benefit, and other conditions like factitious disorder or malingering.Recent evidence in chronic facial pain research appear to suggest that a proportion of individuals who have been diagnosed with AFP have neuropathic pain,AFP is described as one of the 4 recognizable symptom complexes of chronic facial pain, along with burning mouth syndrome, temporomandibular joint dysfunction (TMD) and atypical odontalgia. However, there is a degree of overlap between the features of these diagnoses, e.g. between AFP and TMD and burning mouth syndrome.
Atypical odontalgia is similar in nature to AFP, but the latter term generally is used where the pain is confined to the teeth or gums, and AFP when the pain involves other parts of the face. Other sources use atypical odontalgia and AFP as synonyms, or describe atypical odontalgia as a sub-type, variant, or intra-oral equivalent of AFP. Sometimes "phantom tooth pain" is listed as a synonym for AO, and sometimes it is defined as toothache which persists after a tooth has been extracted. It has been suggested that it is likely that these terms do not represent a single, discrete condition, but rather a collection of misdiagnosed and as yet unidentified causes. This pain is often similar to pain from organic dental disease such as periapical periodontitis, or pulpitis (toothache), but unlike normal dental pain, it is not relieved in the long term by dental treatments such as endodontic therapy (root canal treatment) or tooth extraction, and it may even be worsened, return soon after, or simply migrate to other areas in the mouth following dental treatment.
Definitions
Atypical facial pain
There is no universally accepted definition of AFP, and it is defined less by what it is as what it is not. Various definitions of AFP include:
"a nonmuscular or joint pain that has no detectable neurologic cause."
"a condition characterized by the absence of other diagnoses and causing continuous, variable-intensity, migrating, nagging, deep, and diffuse pain."
"a continuous unilateral deep aching pain sometimes with a burning component."
"facial pain not fulfilling other criteria" (previous IHS definition, which now uses the term "Persistent idiopathic facial pain", see below).
"persistent pain in the maxillofacial region that does not fit the diagnostic criteria of any other orofacial pain and has no identifiable cause." (Neville et al.)
Atypical odontalgia
There are no globally accepted definitions of AO, but some suggested definitions are listed below:
"continuous pain in the teeth or in a tooth socket after extraction in the absence of any identifiable dental cause," (International headache society, description included as a side note of "persistent idiopathic facial pain" in the ICHD-2, i.e. with is no separate diagnosis for atypical odontalgia).
"Severe throbbing pain in the tooth without major pathology" (IASP definition in the "Classification of Chronic Pain", listing AO as "tooth pain not associated with lesions").
"pain and hypersensitive teeth in the absence of detectable pathology".
"pain of an unidentifiable cause that is perceived to be originating in a tooth or teeth".
Naming controversy and proposed replacement terms
The term "atypical facial pain" has been criticized. Originally, AFP was intended to describe a group of individuals whose response to neurosurgical procedures was not typical. Some experts in facial pain have suggested that the term AFP be discarded, as it may serve as a catchall phrase to describe either individuals who have not had an adequate diagnostic assessment or individuals whose pain is purely psychogenic. AFP has also been described as an inappropriate term since many cases in this category conform to a recognizable pattern. Another cited reason for discontinuing use of the term AFP is that some cases appear to follow surgeries or injuries involving the face, teeth and gums, possibly suggesting infectious or traumatic etiologies. Some classifications of facial pain avoid the term in favor of other similar terms.
The IHS now use the term "Persistent idiopathic facial pain" in the ICHD-2, defining it as "persistent facial pain that does not have the characteristics of the cranial neuralgias ... and is not attributed to another disorder." The IASPs Classification of Chronic Pain does not have a diagnosis that corresponds to AFP, although it is listed in the differential diagnosis of "Glossodynia and sore mouth" (Burning mouth syndrome). However, in another IASP publication from 2011, the term PIFP is used and defined almost identically to the above. Despite the controversy surrounding the use of the term, it has a long history, and it is still in common use by clinicians to refer to chronic facial pain that does not meet any diagnostic criteria and does not respond to most treatments.
Re-classification of trigeminal neuralgia
Trigeminal neuralgia is another example of a cause of facial pain. Neuralgia refers to pain in the distribution of a nerve (or nerves), and commonly implies paroxysmal (sudden) pain, although the accepted IASP definition specifies that the term should not be restricted to mean paroxysmal pain. Classic trigeminal neuralgia refers to sudden, shooting pain in the face, which is usually short lived and brought on by accidental stimulation of trigger points on the face, as may occur when washing. Trigeminal neuralgia has been described as one of the most painful conditions possible. Trigeminal neuralgia and AFP are traditionally considered separate, since AFP typically involves constant, often burning pain and trigeminal neuralgia classically shows paroxysmal, shooting pain, but in reality there is some overlap in their features. In 2005 researchers proposed a new classification of trigeminal neuralgia which described a type of trigeminal neuralgia where the pain was constant and burning. They theorized that this type was a progression of untreated classic trigeminal neuralgia, and represented worsening neural injury. There were seven proposed sub-types of trigeminal neuralgia (TN) in this classification (see table), and the final category was reserved for facial pain caused by somatoform disorder. This last category (TN7) was termed atypical facial pain, although many cases that would otherwise be traditionally labelled as AFP would fall into other groups in this classification, especially into the second group. In a publication of the Trigeminal Neuralgia Association (TNA), the following was said about this new classification and AFP:
"The term atypical facial neuralgia or pain was a wastebasket term applied by a serious contributor of a former era to a group of patients he did not understand. Many of these patients were our trigeminal neuralgia type 2 patients. It is unfortunate that many of these people were told they had psychological problems. Many developed psychological problems after the fact when told by everyone that such was their problem. Over the years, our areas of ignorance have progressively narrowed. ... A non-pejorative and, hopefully, reasonable term for the ever-narrowing group of undiagnosed face pain problems: Facepain of Obscure Etiology (FOE or POE) to replace atypical facial pain in the Burchiel classification."
As a result, some sources list terms such as "atypical trigeminal neuralgia", "trigeminal neuropathic pain" and "atypical facial neuralgia" as synonyms of AFP.
ICHD-2 Diagnostic criteria
The ICHD-2 lists diagnostic criteria for "persistent idiopathic facial pain" (the term that replaces AFP in this classification):
A. Pain in the face, present daily and persisting for all or most of the day, fulfilling criteria B and C,B. Pain is confined at onset to a limited area on one side of the face, and is deep and poorly localized,C. Pain is not associated with sensory loss or other physical signs,D. Investigations including x-ray of face and jaws do not demonstrate any relevant abnormality.There are presently no accepted medical tests which consistently discriminate between facial pain syndromes or differentiate Atypical Facial Pain from other syndromes. However, a normal Radiograph, CT, and MRI may help to exclude other pathology such as arterio-veinous malformation, tumor, temporomandibular joint disorder, or MS.
Management
Psychosocial interventions
Psychosocial interventions for AFP include cognitive behavioral therapy and biofeedback. A systematic review reported that there was weak evidence to support the use of these treatments to improve long-term outcomes in chronic orofacial pain, however these results were based primarily upon temporomandibular joint dysfunction and burning mouth syndrome rather than ATP and AO.
Psychosocial interventions assume 2 models of chronic facial pain, namely "inactivity" and "over activity". The former is where people with pain become conditioned to avoid physical activity as a result of exacerbating their pain. These negative thoughts and behaviors in fact prolong and intensify their symptoms. Some psychosocial interventions work on this fear-avoidance behaviour to improve functioning and thereby alleviate symptoms. The over activity model involves factors such as anxiety, depression or anger acting to increase pain by triggering autonomic, visceral and skeletal activity.
Medication
Analgesics
Antidepressants
Centrally acting muscle relaxants
Anticonvulsants
Surgical
Some have suggested that surgery is not an appropriate for treatment for AFP, however the frequent failure medical treatment to relieve pain has occasionally lead surgeons to attempt surgical treatments. Surgery may give a temporary remission from pain, but rarely is there a long term cure achieved via these measures. Sometimes the pain may be increased or simply migrate to an adjacent area following a surgical procedure. Descriptions of procedures such as removal of a portion of the affected branch of the trigeminal nerve, or direct injections of a caustic substance (e.g. phenol, glycerol, alcohol) into the nerve have been reported. Proponents of the so-called "Neuralgia inducing cavitational necrosis" suggest surgical exploration of the bone marrow surrounding the intra-bony course of the affected nerve to discover diseased marrow.
Prognosis
Research suggests that people with AFP are not helped greatly by health care professionals. One study reported that on average, individuals had consulted 7.5 different doctors. 91% had seen dentists, 80% physicians, 66% neurologists, 63% ear, nose and throat surgeons, 31% orthopedic and maxillofacial surgeons, 23% psychiatrists, 14% neurosurgeons and 6% ophthalmologists and dermatologists. In this study, the individuals had been subjected to a wide variety of different treatments, from surgery, antidepressants, analgesics and physical therapies. None of the persons reported that surgery was beneficial, and in many cases the pain was worsened by surgery. The article cited as the source of this information was withdrawn from publication, saying the information was out of date and not meeting Cochrane methodological standards.It has been suggested that the onset of chronic facial pain will likely be a life changing development for those affected.
Epidemiology
AFP is sometimes described as being fairly common, and one estimated prevalence is about 1–2% of the general population. However, the IASP described PIFP as being rare, less common than trigeminal neuralgia (which has a prevalence of about 0.01–0.3% in the general population), and possessing no available epidemiologic data for estimated prevalence in the general population. The predominant age group is 30–50, and females are more often affected than males, with most reports stating that about 80% of people with AFP are female.
References
== External links == |
Stockholm syndrome | Stockholm syndrome is a theorized condition in which hostages develop a psychological bond with their captors during captivity. It is supposed to result from a rather specific set of circumstances, namely the power imbalances contained in hostage-taking, kidnapping, and abusive relationships. Therefore, it is difficult to find a large number of people who experience Stockholm syndrome to conduct studies with any sort of power. This makes it hard to determine trends in the development and effects of the condition— and, in fact, it is a "contested illness" due to doubt about the legitimacy of the condition.Emotional bonds may be formed between captors and captives, during intimate time together, but these are generally considered irrational in light of the danger or risk endured by the victims. Stockholm syndrome has never been included in the Diagnostic and Statistical Manual of Mental Disorders or DSM, the standard tool for diagnosis of psychiatric illnesses and disorders in the US, mainly due to the lack of a consistent body of academic research. The syndrome is rare: according to data from the FBI, about 8% of hostage victims show evidence of Stockholm syndrome.This term was first used by the media in 1973 when four hostages were taken during a bank robbery in Stockholm, Sweden. The hostages defended their captors after being released and would not agree to testify in court against them. It was noted that in this case, however, the police were perceived to have acted with little care for the hostages safety, providing an alternative reason for their unwillingness to testify. Stockholm syndrome is paradoxical because the sympathetic sentiments that captives feel towards their captors are the opposite of the fear and disdain which an onlooker might feel towards the captors.
There are four key components that characterize Stockholm syndrome:
A hostages development of positive feelings towards the captor
No previous relationship between hostage and captor
A refusal by hostages to cooperate with police and other government authorities
A hostages belief in the humanity of the captor, ceasing to perceive them as a threat, when the victim holds the same values as the aggressor.The term "Stockholm syndrome" has also been used to describe the reactions of some abuse victims beyond the context of kidnappings or hostage-taking. Actions and attitudes similar to those with Stockholm syndrome have also been found in victims of sexual abuse, human trafficking, extremism, terrorism, economic oppression, financial repression, political repression and religious persecution.
This is because Stockholm syndrome can be argued as "another method of coping with the stress and danger...similar to some forms of coping in that the participants do not directly address the problem but find a way to cope with the situation by identifying with the aggressor. Coping mechanisms such as these can have a large impact on PTSD."Helsinki syndrome is a term sometimes used incorrectly instead of Stockholm syndrome. The confusion is often deliberate and used for ironic effect.
It originates in the substitution of one Nordic capital (Stockholm, Sweden) for another (Helsinki, Finland). It entered popular culture when used in the Bruce Willis film Die Hard, by a doctor appearing on a television show and describing the phenomenon. The bumbling host says this refers to "Helsinki, Sweden", and the doctor corrects him, saying "Finland".
History
Stockholm bank robbery
In 1973, Jan-Erik Olsson, a convict on parole, took four employees (three women and one man) of Kreditbanken, one of the largest banks in Stockholm, Sweden, hostage during a failed bank robbery. He negotiated the release from prison of his friend Clark Olofsson to assist him. They held the hostages captive for six days (23–28 August) in one of the banks vaults. When the hostages were released, none of them would testify against either captor in court; instead, they began raising money for their defense.Nils Bejerot, a Swedish criminologist and psychiatrist coined the term after the Stockholm police asked him for assistance with analyzing the victims reactions to the 1973 bank robbery and their status as hostages. As the idea of brainwashing was not a new concept, Bejerot, speaking on "a news cast after the captives release" described the hostages reactions as a result of being brainwashed by their captors. He called it Norrmalmstorgssyndromet (after Norrmalmstorg Square where the attempted robbery took place), meaning "the Norrmalmstorg syndrome"; it later became known outside Sweden as Stockholm syndrome. It was originally defined by psychiatrist Frank Ochberg to aid the management of hostage situations.This analysis was provided by Nils Bejerot after he was criticized on Swedish radio by Kristin Enmark, one of the hostages. Enmark claims she had strategically established a rapport with the captors. She had criticized Bejerot for endangering their lives by behaving aggressively and agitating the captors. She had criticized the police for pointing guns at the convicts while the hostages were in the line of fire and she had told news outlets that one of the captors tried to protect the hostages from being caught in the crossfire. She was also critical of prime minister Olof Palme, as she had negotiated with the captors for freedom, but the prime minister told her that she would have to content herself to die at her post rather than give in to the captors demands.
Olsson later said in an interview:It was the hostages fault. They did everything I told them to. If they hadnt, I might not be here now. Why didnt any of them attack me? They made it hard to kill. They made us go on living together day after day, like goats, in that filth. There was nothing to do but get to know each other.
Mary McElroy
Mary McElroy was abducted from her home in 1933 at age 25 by four men who held a gun to her, demanded her compliance, took her to an abandoned farmhouse and chained her to a wall. She defended her kidnappers when she was released, explaining that they were only businessmen. She then continued to visit her captors while they were in jail. She eventually committed suicide and left the following note: “My four kidnappers are probably the only people on Earth who dont consider me an utter fool. You have your death penalty now – so, please, give them a chance."
Patty Hearst
Patty Hearst, the granddaughter of publisher William Randolph Hearst, was taken and held hostage by the Symbionese Liberation Army, "an urban guerilla group", in 1974. She was recorded denouncing her family as well as the police under her new name, "Tania", and was later seen working with the SLA to rob banks in San Francisco. She publicly asserted her "sympathetic feelings" toward the SLA and their pursuits as well. After her 1975 arrest, pleading Stockholm syndrome (although the term was not used then, due to the recency of the event) did not work as a proper defense in court, much to the chagrin of her defense lawyer F. Lee Bailey. Her seven-year prison sentence was later commuted, and she was eventually pardoned by President Bill Clinton, who was informed that she was not acting under her own free will.
Sexual abuse victims
There is evidence that some victims of childhood sexual abuse come to feel a connection with their abuser. They often feel flattered by adult attention or are afraid that disclosure will create family disruption. In adulthood, they resist disclosure for emotional and personal reasons.
Lima syndrome
An inversion of Stockholm syndrome, called Lima syndrome, has been proposed, in which abductors develop sympathy for their hostages. An abductor may also have second thoughts or experience empathy towards their victims.Lima syndrome was named after an abduction at the Japanese embassy in Lima, Peru, in 1996, when members of a militant movement took hostage hundreds of people attending a party at the official residence of Japans ambassador.
Symptoms and behaviors
Victims of the formal definition of Stockholm syndrome develop "positive feelings toward their captors and sympathy for their causes and goals, and negative feelings toward the police or authorities". These symptoms often follow escaped victims back into their previously ordinary lives.
Physical and psychological effects
Cognitive: confusion, blurred memory, delusion, and recurring flashbacks.
Emotional: lack of feeling, fear, helplessness, hopelessness, aggression, depression, guilt, dependence on captor, and development of post-traumatic stress disorder (PTSD).
Social: anxiety, irritability, cautiousness, and estrangement.
Physical: increase in effects of pre-existing conditions; development of health conditions due to possible restriction from food, sleep, and exposure to outdoors.
Ronald Fairbairns object relations theory of attachment to the abuser
Ronald Fairbairn wrote a complete psychoanalytic model in a series of papers (1940, 1941, 1943, 1944) which are collected in his 1952 text Psychoanalytic Studies of the Personality. His model explains the surprising psychological reality that abused children become deeply attached to their abusers. He saw that lack of love, chronic indifference and abuse led to a counter-intuitive emotional attachment to the very parent who was abusing them. The childs unmet dependency needs from chronic emotional deprivation, as well as the complete lack of other human alternatives in their environment, leaves the child stuck at an earlier emotional age, as they have not been able to continue their developmental progress in the absence of parental help and support. Thus the child may be 12, but emotionally and developmentally they may experience the world like a six-year-old, as their increasingly developmental needs force them to focus on the abuser, waiting for any hint of developmental support. The child becomes concerned for the abusers welfare because their developmental progress hinges upon on the whims, moods and emotional state of the abusive parent. In addition to the pressure from unmet developmental needs, the child is also aware of the potential danger that can emerge from the volatile and aggressive parent, and anything that they can do to placate, please or draw praise from the abuser increases their chance of survival.
The neglected or abused childs utter helplessness and absolute dependency upon the goodwill of their parents prevents them from "seeing" or remembering those interpersonal events in which they have faced indifference or physical abuse, as this awareness would overwhelm them and submerge them in a torrent of dread. This feeling of dread is most often experienced as a massive abandonment panic during those moments when the child realizes that they are living in constant danger with no one to help them to survive. The solution to this enormous problem is for the child to encase themself within a thick psychological cocoon of denial and fantasy that creates a false reality in which they believe that they are living in a loving and caring family.
The first way that the child protects themself is by using the greatest reality-altering defense that humans have at their disposal, which is the defense of dissociation. The dissociative defense mechanism is seen in adults who have suffered a life-threatening trauma, and dissociation prevents them from fully realizing what has happened. In children, the same defense protects the child by forcing intolerable memories of neglect, abuse, or total indifference that they suffered at the hands of their parents into their unconscious, where these memories will not disturb the childs illusion that they live in a safe and loving family. The dissociative defense is the basis of what is commonly called denial. The more frequent the abuse, the more frequently dissociation is required and the larger and larger the number of intolerable memories are forced into the unconscious. Once lodged in their unconscious, the child cannot remember the horrifying incidents that they previously experienced.
Splitting defense
The child not only dissociates memories of the abusive parent, but also memories of themselves in those anxiety-filled encounters with the rejecting parent. Their memory of themselves in these situations is one of being a frightened, impotent, and vulnerable child who is overwhelmed and deeply ashamed because they are unable to protect themselves when confronted by the aggressive parent. If they had access to these memories of themselves, they would inform their conscious ego that they were in a dire, life-threatening situation, information that is too catastrophic to accept. Over time, these memories of themselves in relationship to their rejecting parent coalesce and form internal representations. The process of dissociation of memories of the self and of the parent is called "splitting of the ego" or simply "splitting", because part of the childs original conscious ego (or self) is "split off" from the rest of their normal view of themselves and hidden in their unconscious. Similarly, the memories of that part of the angry, enraged and irritated parent are split off from the "normal" aspects of the parent and held in the unconscious as well. The memories of the angry parent are appropriately called the "Rejecting Object" in Fairbairns model. "Object" is an awkward term used in psychoanalytic theory to designate a person outside the self. So both the terrified memory of themselves and the abusive aspect of the parent (the object) are split off from the conscious self and they become "part selves" and "part objects", The terrified part of the self (called the "Antilibidinal Ego" in Fairbairns model) and the terrorizing part of the object are cut off from consciousness and are no longer associated with the conscious representation of either the self or the object. This affords the child a (false) sense of security that prevents them from feeling anxious about their fate from moment to moment.
Now that the abused child has split off memories of abuse, they have a second equally significant problem, which is to create an illusion for themselves that they are living in a safe environment. Splitting is the perfect defense for the abused child because not only is it able to isolate the unacceptable aspects of the parents in the unconscious, but, equally importantly, it is able to create a fantasy-based view of the parent out of their neglectful, indifferent or abusive parent(s). This psychological mechanism begins when the child selectively takes those few moments of attention or tenderness that has been shown to them by their parent and magnifying them and creating a “better parent”. The process is the same, in that the few positive incidents from the real parent are split off from the actual parent, and are forced into their unconscious as well. This view of the parent (which is unrealistic) is "enhanced by the child’s unmet needs and [their] use of fantasy." The child holds a view that somewhere in their parents heart there is a hidden storehouse of love, if they only knew how to reach it. This fantasy-based view of the parent is called "the Exciting Object" in Fairbairns model, as the child feels excitement when they fantasize that they have a loving parent. The childs part-ego (or self) that relates to the Exciting Object is called "the Libidinal Ego". In Fairbairns model, Libidinal means loving. Fairbairn had seen children with libidinal fantasies in the orphanage where he worked from 1927 to 1935. For a full discussion of the splitting defense, and Fairbairns structural theory see Celani, 2010. The two pairs of unconscious structures do not know about each other, which allows the child "to relate to the parent as if [they] were two different people." The splitting defense prevents the integration of good and bad object images into a single ambivalent object, which is a key developmental milestone.
Literature is filled with real examples of children creating fantasy parents out of their failed actual parents, as the following one-page essay by the writer Junot Diaz, who was born in Santo Domingo, describes. Unlike many neglected children, Diazs fantasy was more conscious than unconscious and based on the "promise" that his father was going to take the whole family to the United States to join him. He added the hope that his father would save him and the family in the process. But my earliest exposure to television was a Spider-Man cartoon - one of the flipped out Ralph Bakshi episodes from the late sixties...A little context: I had a father in New York City whom I did not remember, and who (it was promised) would one day deliver my family to the States. And here was my first television and my first cartoon and my first superhero — a hero who like my father, was in America—and somehow it all came together for me in a lightning bolt of longing and imagination. My fathers’ absence made perfect sense. He couldnt come back right away because he was busy fighting crime in NYC...as Spider–Man. The diasporic imagination really is its own superpower...I believed I had seen my father on that TV, and if I paid close enough attention it would show him to me again...For the record: my father did eventually return and take us to the States...My father was the worst shock of all. He had no problem laying hands on us kids for the slightest infraction. Beatings like he was making up for lost time. Like he was mad that he had a family...Are you surprised, then, that I was drawn back to the television? Because I was lost, because I wanted help with my English, because my father was a nightmare. And because I was convinced, foolish little fantasist that I was, that somehow my family and I had ended up in the wrong America and that the country and the father I’d first glimpsed on TV in Santo Domingo, the country and father I’d been promised, was still out there somewhere. I just had to find them. Never did. (Diaz, 2017, p.42 )
This essay demonstrates just how strong the need for a “good object” parent is, and how it motivates children to hold on to illusions, despite the overwhelming crush of reality. A "Good Object" is a parent or parent-like figure who fulfills the parenting role, including being interested in, and respectful of, the childs developmental needs. When the writers first elaborate fantasy was disproved, he did not give up fantasizing, because his need for a parent continued to be great, so he assumed that there was a second America where his good father resided. For a full description of the libidinal ego and the exciting object see Celani, 2010, pp. 58–115.
Intense relationships between the ego structures
The relationship between the two split off part-selves and their respective part-objects is intense because they were created out of enormous need, pain and desire. The intense need of the child for a good, loving object cannot be described in a more powerful way that the preceding quote by Diaz. He notes that his desperation was fueled because he was lost, he needed help learning English and needed an escape from his violent father. He was seeking a new father that would right all the wrongs that he had suffered.
On the other side of the split is the childs antilibidinal ego, which is intensely motivated to force the rejecting object parent to become a good object, and own up to the mistakes they have made by rejecting their child. Conversely, the rejecting internalized parent (who is an internalization of the original parent) holds its ground and endlessly argues that the child was deserving of their condemnation. This dialogue continues in the unconscious, as described in the following quote by Odgen (2010)Neither the rejecting object nor the internal saboteur (the antilibidinal ego) is willing or able to think about, much less relinquish, that tie. In fact, there is no desire on the part of either to change. The power of that bond is impossible to overestimate. The rejecting object and the internal saboteur are determined to nurse their feelings of having been deeply wronged, cheated, humiliated, betrayed, exploited, treated unfairly, discriminated against, and so on. The mistreatment at the hands of the other is felt to be unforgivable. An apology is forever expected by each, but never offered by either (Odgen, 2010, p. 109).The “tie” that Odgen mentions is the emotional investment that each part-ego, or part-object structure, has in fighting with the other. The combination of the libidinal egos tie to finding love in the elusive and ever-shifting exciting object, and the equally motivated antilibidinal egos desire to force the rejecting object to apologize and see his/her value as a human being constitute what Fairbairn called "The Attachment to the Bad Object". The "Bad Object" is a parent or other significant caretaker who has failed the child, but is still cherished by the libidinal ego and fought against by the antilibidinal ego. This model, of separate ego states, that see different “parts” of the other (the object) explains the extraordinary attachment between the battered woman and her abuser (see Celani, 1995).
Model of attachment to the bad object
Fairbairn saw his model of human behavior as universal, that is, he assumed that all children, no matter how benevolent their family environment was, had to dissociate a few intensely frustrating events and, at other times, had to fantasize that their parents had hidden love that they were not displaying; that is, they used the same psychological mechanisms as did children from abusive families, but to a lesser extent. The following analysis is not based on interviews of the four victims, but rather is the result of applying Fairbairns model to the reported behavior of the four individuals.
Antilibidinal ego-rejecting object side of the split
When the bank robber and his accomplice, who was released from prison and allowed to join him, began their six-day hostage taking, the four adult prisoners faced the same environment as do abused children; that is, their lives were absolutely dependent upon the good will of their captors, who had unlimited power over their lives. Their captors were far more important to them than were the police, who were a threat to all of them, captives and criminals alike. Fairbairns model assumes that the captives used the splitting defense to abolish the most terrorizing aspects of their captivity, in order to keep from breaking down into an absolute state of anxiety. This initial dissociation of the most terrifying events they experienced with their captors prevented the four victims from facing the disintegration of their ego structures. Once freed, the most frightening and toxic actual events they experienced are assumed to be still held out of awareness, as revisiting those events are likely to bring up overwhelming emotions. Fairbairn noted that one of the primary reasons for keeping horrifying memories in the unconscious was because of the emotional disruption caused when they are re-experienced.There is little doubt in my mind, in conjunction with another factor to be mentioned later, that the deepest source of resistance is fear of the release of bad objects from the unconscious: for when such bad objects are released, "the world around the patient becomes peopled with devils which are too terrifying to face" (Fairbairn, 1952, p.69-70).
This quote graphically describes the results of suddenly remembering those memories of interpersonal events between the captives and captors that were saturated with fear, dread and hopelessness. There is no reason now, given the fact that the captivity is long over, for the four victims to remember the horrifying details.
Libidinal ego-exciting object side of the split
The other side of the split is abundantly obvious. All four victims refused to testify against their captors, and in fact raised money for their defense. Thus, given Fairbairns theory, they continue to see their captors through their libidinal egos as if the captors have a hidden storehouse of goodness somewhere in them. This view of reality could not continue, in Fairbairns theory, if the four captives were able to access the fear, terror and, indeed, rage assumed to be held in their Antilibidinal Ego-Rejecting Object structures. The depth of their fear and rage at being abused, would clash with their split-off, opposite view of the hidden “goodness” in the captors. As mentioned, the splitting defense allows the user to see others as if they are two different people.
This offers a second possible reason that the terrifying memories of events remain dissociated (in the Antilibidinal Ego-Rejecting Object structures in the unconscious). If one or more of the captives were able to experience these feelings directly (including the impotent rage), during the six days when they were held captive in the presence of the captors, they might have been killed for being disruptive and threatening. This ultimate terror, of being killed for experiencing the fear/rage and humiliation that is assumed to have been dissociated into the unconscious, may be the motivation that promotes the libidinal egos view of the two captors to continue, and simultaneously avoiding the enormously toxic memories of their six days in captivity. Thus, Fairbairns model offers a sound psychological explanation for attachment to abusers (Celani, 1995).
Possible evolutionary explanations
Evolutionarily speaking, research evidence exists to support the genuine scientific nature of Stockholm syndrome. Responses similar to those in human captives have been detected in some reptiles and mammals, primates in particular. Abuse and subsequent submission and appeasement by the victim have been observed among chimpanzees, leading to the theory that the Stockholm syndrome may have its roots in evolutionary needs.Life in the "environment of evolutionary adaptedness" (EEA) is thought by researchers such as Israeli military historian Azar Gat to be similar to that of the few remaining hunter-gatherer societies. Gat asserts that war and abductions were typical of human pre-history. Being captured by neighbouring tribes was a relatively common event for women. In some of those tribes (the Yanomamo, for instance), practically everyone in the tribe is descended from a captive within the last three generations. As high as one in ten of females were abducted and incorporated into the tribe that captured them. Being captured and having their children killed may have been common; women who resisted capture risked being killed. When selection is intense and persistent, adaptive traits (such as capture-bonding) become universal to the population or species.
Loving to survive
First published in 1994, author Dee Graham uses the Stockholm syndrome label to describe group or collective responses to trauma, rather than individual reactions. Graham focuses specifically on the impact of Stockholm syndrome on battered and abused women as a community. She claimed that in both the psychological and societal senses, these women are defined by their sense of fear surrounding the threat of male violence. This constant fear is what drives these women to perform actions that they know will be pleasing to men in order to avoid emotional, physical, or sexual assault as a result of male anger. Graham draws parallels between women and kidnapping victims in the sense that these women bond to men to survive, as captives bond to their captors to survive. In 1995, Graham developed a 49 item scale for use is determining Stockholm syndrome.
Recovery
Recovering from Stockholm syndrome ordinarily involves "psychiatric or psychological counseling", in which the patient is helped to realize that their actions and feelings stemmed from inherent human survival techniques. The process of recovery includes reinstating normalcy into the lives of victims, including helping the victim learn how to decrease their survival-driven behaviors.
Criticism
Diagnostic and Statistical Manual (DSM 5, 2013)
The DSM-5 is widely used as the "classification system for psychological disorders" by the American Psychiatric Association. Stockholm syndrome has not historically appeared in the manual, as many believe it falls under trauma bonding or post-traumatic stress disorder (PTSD) and there is no consensus about the correct clarification. In addition, there is no extensive body of research or consensus to help solve the argument, although before the fifth edition (DSM 5) was released, Stockholm syndrome was under consideration to be included under Disorders of Extreme Stress, Not Otherwise Specified. The work was updated in 2013, but Stockholm syndrome was not present.
Namnyak et al. (2008)
A research group led by Namnyak has found that although there is a lot of media coverage of Stockholm syndrome, there has not been a lot of research into the phenomenon. What little research has been done is often contradictory and does not always agree on what Stockholm syndrome is. The term has grown beyond kidnappings to all definitions of abuse. It stated that there is no clear definition of symptoms to diagnose the syndrome.
FBI law enforcement bulletin (1999)
A 1998 report by the FBI containing over 1,200 hostage incidents found that only 8% of kidnapping victims showed signs of Stockholm syndrome. When victims who showed negative and positive feelings toward the law enforcement personnel are excluded, the percentage decreases to 5%. A survey of 600 police agencies in 1989, performed by the FBI and the University of Vermont, found not a single case when emotional involvement between the victim and the kidnapper interfered with or jeopardized an assault. In short, this |
Stockholm syndrome | database provides empirical support that the Stockholm syndrome remains a rare occurrence. The sensational nature of dramatic cases causes the public to perceive this phenomenon as the rule rather than the exception. The bulletin concludes that, although depicted in fiction and film and often referred to by the news media, the phenomenon actually occurs rarely. Therefore, crisis negotiators should place the Stockholm syndrome in proper perspective.
Robbins and Anthony (1982)
Robbins and Anthony, who had historically studied a condition similar to Stockholm syndrome, known as destructive cult disorder, observed in their 1982 study that the 1970s were rich with apprehension surrounding the potential risks of brainwashing. They assert that media attention to brainwashing during this time resulted in the fluid reception of Stockholm syndrome as a psychological condition.
Jess Hill (2019)
In her 2019 treatise on domestic violence See What You Made Me Do, Australian journalist Jess Hill described the syndrome as a "dubious pathology with no diagnostic criteria", and stated that it is "riddled with misogyny and founded on a lie"; she also noted that a 2008 literature review revealed "most diagnoses [of Stockholm syndrome] are made by the media, not by psychologists or psychiatrists." In particular, Hills analysis revealed that Stockholm authorities — under direct guidance from Bejerot — responded to the robbery in a way that put the hostages at greater risk from the police than from their captors (hostage Kristin Enmark, who during the siege was granted a phone call with Swedish Prime Minister Olof Palme, reported that Palme told her that the government would not negotiate with criminals, and that "you will have to content yourself that you will have died at your post"); as well, she observed that not only was Bejerots diagnosis of Enmark made without ever having spoken to her, it was in direct response to her public criticism of his actions during the siege.
See also
References
External links
deFabrique, N.; Romano, S.; Vecchi, G.; Hasselt, Vincent Van (1 January 2007). "Understanding Stockholm Syndrome". FBI Law Enforcement Bulletin. 76: 10–15. |
Embolism | An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (gas embolism), amniotic fluid (amniotic fluid embolism), or foreign material. An embolism can cause partial or total blockage of blood flow in the affected vessel. Such a blockage (a vascular occlusion) may affect a part of the body distant from the origin of the embolus. An embolism in which the embolus is a piece of thrombus is called a thromboembolism.
An embolism is usually a pathological event, i.e., accompanying illness or injury. Sometimes it is created intentionally for a therapeutic reason, such as to stop bleeding or to kill a cancerous tumor by stopping its blood supply. Such therapy is called embolization.
Classification
There are different types of embolism, some of which are listed below.
Embolism can be classified based on where it enters the circulation, either in arteries or in veins. Arterial embolism are those that follow and, if not dissolved on the way, lodge in a more distal part of the systemic circulation. Sometimes, multiple classifications apply; for instance a pulmonary embolism is classified as an arterial embolism as well, in the sense that the clot follows the pulmonary artery carrying deoxygenated blood away from the heart. However, pulmonary embolism is generally classified as a form of venous embolism, because the embolus forms in veins, e.g. deep vein thrombosis.
Arterial
Arterial embolism can cause occlusion in any part of the body. It is a major cause of infarction (tissue death from blockage of the blood supply).An embolus lodging in the brain from either the heart or a carotid artery will most likely be the cause of a stroke due to ischemia.An arterial embolus might originate in the heart (from a thrombus in the left atrium, following atrial fibrillation or be a septic embolus resulting from endocarditis). Emboli of cardiac origin are frequently encountered in clinical practice. Thrombus formation within the atrium occurs mainly in patients with mitral valve disease, and especially in those with mitral valve stenosis (narrowing), with atrial fibrillation (AF). In the absence of AF, pure mitral regurgitation has a low incidence of thromboembolism.The risk of emboli forming in AF depends on other risk factors such as age, hypertension, diabetes, recent heart failure, or previous stroke.
Thrombus formation can also take place within the ventricles, and it occurs in approximately 30% of anterior-wall myocardial infarctions, compared with only 5% of inferior ones. Some other risk factors are poor ejection fraction (<35%), size of infarct, and the presence of AF. In the first three months after infarction, left-ventricle aneurysms have a 10% risk of emboli forming.Patients with prosthetic valves also carry a significant increase in risk of thromboembolism. Risk varies, based on the valve type (bioprosthetic or mechanical); the position (mitral or aortic); and the presence of other factors such as AF, left-ventricular dysfunction, and previous emboli.
Emboli often have more serious consequences when they occur in the so-called "end circulation": areas of the body that have no redundant blood supply, such as the brain and heart.
Venous
Assuming a normal circulation, an embolus formed in a systemic vein will always impact in the lungs, after passing through the right side of the heart. This will form a pulmonary embolism that will result in a blockage of the main artery of the lung and can be a complication of deep-vein thrombosis. The most common sites of origin of pulmonary emboli are the femoral veins. The deep veins of the calf are the most common sites of actual thrombi.
Paradoxical (venous to arterial)
In paradoxical embolism, also known as crossed embolism, an embolus from the veins crosses to the arterial blood system. This is generally found only with heart problems such as septal defects (holes in the cardiac septum) between the atria or ventricles. The most common such abnormality is patent foramen ovale, occurring in about 25% of the adult population, but here the defect functions as a valve which is normally closed, because pressure is slightly higher in the left side of the heart. Sometimes, for example if a patient coughs just when an embolus is passing, it might cross to the arterial system.
Direction
The direction of the embolus can be one of two types:
Anterograde
RetrogradeIn anterograde embolism, the movement of emboli is in the direction of blood flow. In retrograde embolism, the emboli move in opposition to the blood flow direction; this is usually significant only in blood vessels with low pressure (veins) or with emboli of high weight.
Etymology
The word embolism comes from the Greek ἐμβολισμός, meaning "interpressure".
See also
Embolectomy
References
External links
MR of Fat Embolism Brain Injury from Fat Embolism |
Familial benign copper deficiency | Familial benign copper deficiency, also known as Familial benign hypocupremia is a rare genetic disorder which is characterized by hypocupremia that causes symptoms such as epilepsy, hypotonia, seborrheic skin, thriving failure and mild anemia. Radiological findings include tibia and femur spurring. Transmission is thought to be either autosomal dominant or X-linked dominant.Symptoms are caused by a familial tendency of having low levels of copper within the body and can be improved (treated and managed) with oral supplements of copper.It has been described in members of a 3-generation Hungarian family.
== References == |
Granuloma gluteale infantum | Granuloma gluteale infantum is a cutaneous condition that appears in the anogenital region of infants as a complication of diaper dermatitis.According to some, no granulomas are found.
See also
Superficial granulomatous pyoderma
List of cutaneous conditions
References
== External links == |
Lipoatrophic diabetes | Lipoatrophic diabetes is a type of diabetes mellitus presenting with severe lipodystrophy in addition to the traditional signs of diabetes.
See also
Familial partial lipodystrophy
Congenital generalized lipodystrophy
External links
Iglesias P, Alvarez Fidalgo P, Codoceo R, Díez J (2004). "Lipoatrophic diabetes in an elderly woman: clinical course and serum adipocytokine concentrations". Endocr J. 51 (3): 279–86. doi:10.1507/endocrj.51.279. PMID 15256772.
Morse A, Whitaker M (2000). "Successful pregnancy in a woman with lipoatrophic diabetes mellitus. A case report". J Reprod Med. 45 (10): 850–2. PMID 11077638.
Meyer L, Hadjadj S, Guerci B, Delbachian I, Ziegler O, Drouin P (1998). "Lipoatrophic diabetes mellitus treated by continuous subcutaneous insulin infusion". Diabetes Metab. 24 (6): 544–6. PMID 9932222. |
Esophageal disease | Esophageal diseases can derive from congenital conditions, or they can be acquired later in life.
Many people experience a burning sensation in their chest occasionally, caused by stomach acids refluxing into the esophagus, normally called heartburn. Extended exposure to heartburn may erode the lining of the esophagus, leading potentially to Barretts esophagus which is associated with an increased risk of adenocarcinoma most commonly found in the distal one-third of the esophagus.
Some people also experience a sensation known as globus esophagus, where it feels as if a ball is lodged in the lower part of the esophagus.
The following are additional diseases and conditions that affect the esophagus:
Achalasia
Acute esophageal necrosis
Barretts esophagus
Boerhaave syndrome
Caustic injury to the esophagus
Chagas disease
Diffuse esophageal spasm
Esophageal atresia and tracheoesophageal fistula
Esophageal cancer
Esophageal dysphagia
Esophageal varices
Esophageal web
Esophagitis
GERD
Hiatus hernia
Jackhammer esophagus (hypercontractile peristalsis)
Killian–Jamieson diverticulum
Mallory–Weiss syndrome
Neurogenic dysphagia
Nutcracker esophagus
Schatzkis ring
Zenkers diverticulum
References
External links
Esophageal and Swallowing Disorders, Merck & Company Inc. |
Narcissistic personality disorder | Narcissistic personality disorder (NPD) is a mental disorder characterized by a life-long pattern of exaggerated feelings of self-importance, an excessive need for admiration, a diminished ability to empathize with others feelings, and interpersonally exploitative behavior. Narcissistic personality disorder is one of the sub-types of the broader category known as personality disorders. It is often comorbid with other mental disorders and associated with significant functional impairment and psychosocial disability.Personality disorders are a class of mental disorders characterized by enduring and inflexible maladaptive patterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by any culture. These patterns develop by early adulthood, and are associated with significant distress or impairment. Criteria for diagnosing personality disorders are listed in the fifth chapter of the International Classification of Diseases (ICD) and in the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM).
There is no standard treatment for NPD. Its high comorbidity with other mental disorders influences treatment choice and outcomes. Psychotherapeutic treatments generally fall into two categories: psychoanalytic/psychodynamic and cognitive behavioral therapy, with growing support for integration of both in therapy. However, there is an almost complete lack of studies determining the effectiveness of treatments.
Signs and symptoms
DSM-5
The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) describes NPD as possessing at least five of the following nine criteria.
A grandiose sense of self-importance
Preoccupation with fantasies of unlimited success, power, brilliance, beauty, or ideal love
Believing that they are "special" and unique and can only be understood by, or should associate with, other special or high-status people (or institutions)
Requiring excessive admiration
A sense of entitlement (unreasonable expectations of especially favorable treatment or automatic compliance with their expectations)
Being interpersonally exploitative (taking advantage of others to achieve their own ends)
Lacking empathy (unwilling to recognize or identify with the feelings and needs of others)
Often being envious of others or believing that others are envious of them
Showing arrogant, haughty behaviors or attitudesWithin the DSM-5, NPD is a cluster B personality disorder. Individuals with cluster B personality disorders often appear dramatic, emotional, or erratic. Narcissistic personality disorder is a mental disorder characterized by a life-long pattern of exaggerated feelings of self-importance, an excessive craving for admiration, and a diminished ability to empathize with others feelings.A diagnosis of NPD, like other personality disorders, is made by a qualified healthcare professional in a clinical interview. The process of diagnosis often involves asking the client to describe people emotionally close to them, which can reveal extreme arrogance or a lack of empathy.Narcissistic personality disorder usually develops either in youth or in early adulthood. True symptoms of NPD are pervasive, apparent in varied social situations, and are rigidly consistent over time. Severe symptoms of NPD can significantly impair the persons mental capabilities to develop meaningful human relationships, such as friendship, kinship, and marriage. Generally, the symptoms of NPD also impair the persons psychological abilities to function socially, either at work or at school, or within important societal settings. The DSM-5 indicates that, in order to qualify as symptomatic of NPD, the persons manifested personality traits must substantially differ from social norms.
ICD-11 and ICD-10
In the International Statistical Classification of Diseases and Related Health Problems, 11th Edition ICD-11 of the World Health Organization (WHO), all personality disorders are diagnosed under a single title called "personality disorder". The criteria for diagnosis are mainly concerned with assessing dysfunction, distress and maladaptive behavior as opposed to attributing specific personality traits.
In the previous edition, the ICD-10, narcissistic personality disorder (NPD) is listed under the category of "other specific personality disorders". This means similarly to the ICD-11, the ICD-10 required that cases otherwise described as NPD in the DSM-5 would only need to meet a general set of diagnostic criteria.
Associated features
People with NPD exaggerate their skills, accomplishments, and their degree of intimacy with people they consider high-status. A sense of personal superiority may lead them to monopolize conversations, look down on others or to become impatient and disdainful when other persons talk about themselves. This behavior correlates to an overall worse functioning in areas of life like work and intimate romantic relationships.People with NPD have been observed to use psychosocial strategies, such as the tendency to devalue and derogate and to insult and blame other people, usually with anger and hostility towards peoples responses to their anti-social behavior. Narcissistic personalities are more likely to respond with anger or aggressiveness when presented with rejection. Because they are sensitive to perceived criticism or defeat, people with NPD are prone to feelings of shame, humiliation, and worthlessness over minor incidents of daily life and imagined, personal slights, and usually mask such feelings from people, by feigning humility, responding with outbursts of rage and defiance, or seeking revenge.The DSM-5 indicates that: "Many highly successful individuals display personality traits that might be considered narcissistic. Only when these traits are inflexible, maladaptive, and persisting, and cause significant functional impairment or subjective distress, do they constitute narcissistic personality disorder." Given the high-function sociability associated with narcissism, some people with NPD might not view such a diagnosis as a functional impairment to their lives. Although overconfidence tends to make people with NPD very ambitious, such a mindset does not necessarily lead to professional high achievement and success, because they refuse to take risks, in order to avoid failure or the appearance of failure. Moreover, the psychological inability to tolerate disagreement, contradiction, and criticism, makes it difficult for persons with NPD to work cooperatively or to maintain long-term, professional relationships with superiors and colleagues.
Differential diagnosis
The occurrence of narcissistic personality disorder presents a high rate of comorbidity with other mental disorders. People with NPD are prone to bouts of psychological depression, often to the degree that meets the clinical criteria for a co-occurring depressive disorder. NPD is associated with the occurrence of bipolar disorder and substance use disorders, especially cocaine use disorder. NPD may also be comorbid or differentiated with the occurrence of other mental disorders, including histrionic personality disorder, borderline personality disorder, antisocial personality disorder, or paranoid personality disorder. NPD should also be differentiated from mania and hypomania as these cases can also present with grandiosity, but present with different levels of functional impairment. Narcissistic personality disorder differs from self-confidence which is associated with a strong sense of self. It is common for children and adolescents to display personality traits that resemble NPD, but such occurrences are usually transient, and register below the clinical criteria for a formal diagnosis of NPD.
Subtypes
Although the DSM-5 diagnostic criteria for NPD has been viewed as homogeneous, there are a variety of subtypes used for classification of NPD. There is poor consensus on how many subtypes exist, but there is broad acceptance that there are at least two: grandiose or overt narcissism, and vulnerable or covert narcissism. However, none of the subtypes of NPD are recognized in the DSM-5 or in the ICD-11.
Grandiose/overt and vulnerable/covert
Similar to the definition of NPD in the DSM-IV, Grandiose narcissism is defined by an inflated sense of self-worth and high self-esteem, interpersonal exploitativeness, social dominance and assertiveness, shamelessness and a sense of entitlement derived from feelings of superiority or prestige.The counterpart to grandiose narcissism is vulnerable narcissism, characterized by the personality traits of defensiveness, fragility, social withdrawal, and sensitivity to criticism.
Oblivious and hypervigilant
The psychiatrist and psychoanalyst Glen Gabbard described two subtypes of NPD in 1989, later referred to as equivalent to, the grandiose and vulnerable subtypes. The first was the "oblivious" subtype of narcissist, equivalent to the grandiose subtype. It was described as being grandiose, arrogant and thick-skinned, while also exhibiting personality traits of helplessness and emotional emptiness, low self-esteem and shame. These were observed in people with NPD to be expressed as socially avoidant behavior in situations where self-presentation is difficult or impossible, leading to withdrawal from situations where social approval is not given.
The second subtype Gabbard described was termed "hypervigilant", equivalent to the vulnerable subtype. People with this subtype of NPD were described as having easily hurt feelings, an oversensitive temperament, and persistent feelings of shame.
High functioning or exhibitionist
A third subtype for classifying people with NPD, also initially theorised by Gabbard, is termed high functioning or exhibitionistic. It has been described as "high functioning narcissists [who] were grandiose, competitive, attention-seeking, and sexually provocative; they tended to show adaptive functioning and utilize their narcissistic traits to succeed."
Millons subtypes
In the study Disorders of Personality: DSM-IV-TM and Beyond (1996), Theodore Millon suggested five subtypes of NPD, although they did not identify specific treatments per subtype.
Mastersons subtypes (exhibitionist and closet)
In 1993, James F. Masterson proposed two subtypes for pathological narcissism, exhibitionist and closet. Both fail to adequately develop an age- and phase- appropriate self because of defects in the quality of psychological nurturing provided, usually by the mother. A person with exhibitionist narcissism is similar to NPD described in the DSM-IV and differs from closet narcissism in several ways. A person with closet narcissism is more likely to be described as having a deflated, inadequate self-perception and greater awareness of emptiness within. A person with exhibitionist narcissism would be described as having an inflated, grandiose self-perception with little or no conscious awareness of feelings of emptiness. Such a person would assume that their condition was normal and that others were just like them. A person with closet narcissism is described to seek constant approval from others and appears similar to those with borderline personality disorder in the need to please others. A person with exhibitionist narcissism seeks perfect admiration all the time from others.
Malignant narcissism
Malignant narcissism, a term first coined in Erich Fromms 1964 book The Heart of Man: Its Genius for Good and Evil, is a syndrome consisting of a combination of NPD, antisocial personality disorder, and paranoid traits. A person with malignant narcissism was described as deriving higher levels of psychological gratification from accomplishments over time, suspected to worsen the disorder. Because a person with malignant narcissism becomes more involved in psychological gratification, it was suspected to be a risk factor for developing antisocial, paranoid, and schizoid personality disorders. The term malignant is added to the term narcissist to indicate that individuals with this disorder have a severe form of narcissistic disorder that is characterized also by features of paranoia, psychopathy (anti-social behaviors), aggression, and sadism.
Assessment and screening
Narcissistic Personality Inventory
Risk factors for NPD and grandiose/overt and vulnerable/covert subtypes are measured using the narcissistic personality inventory, an assessment tool originally developed in 1979, has undergone multiple iterations with new versions in 1984, 2006 and 2014. The subtype is also assessed with the pathological narcissism inventory (PNI). The PNI is a screening tool for antisocial, borderline, narcissistic personality disorders. The PNI scales exhibited significant associations with parasuicidal behavior, suicide attempts, homicidal ideation, and several aspects of psychotherapy utilization. Pathological narcissism a term for concurrent grandiose and vulnerable narcissism, which is linked to poor self-esteem, lack of empathy, feelings of shame, interpersonal distress, aggression, and significant impairments in personality functioning across both clinical and non-clinical samples. Despite the phenomenological and empirical distinction between vulnerable and grandiose narcissism, some theories suggest that grandiose narcissists also have fragile personality traits. There are a number of other assessment tools for narcissism and NPD subtypes.
Millon Clinical Multiaxial Inventory
The Millon Clinical Multiaxial Inventory (MCMI) is another diagnostic test developed by Theodore Millon. The MCMI includes a scale for narcissism. The NPI and MCMI have been found to be well correlated. Whereas the MCMI measures narcissistic personality disorder (NPD), the NPI measures narcissism as it occurs in the general population; the MCMI is a screening tool. In other words, the NPI measures "normal" narcissism; i.e., most people who score very high on the NPI do not have NPD. Indeed, the NPI does not capture any sort of narcissism taxon as would be expected if it measured NPD.A 2020 study found that females scored significantly higher on vulnerable narcissism than males, but no gender differences were found for grandiose narcissism.
Causes
Although there are no specific causes for NPD, it is described using the biopsychosocial model which describes a combination of risk factors from biological, psychological and socio-environmental factors. This includes but is not limited to genetics, neurobiology, trauma, abuse and parenting.
Genetic
Evidence suggests there is a high heritability of NPD, with a number of genetic influences indicating varying rates of heritability based on subtype. A number of twin studies historically suggested for the heritability of NPD, including personality disorders in general.
Environment
Environmental and social factors also influence development of NPD. In some people, pathological narcissism may develop from an impaired emotional attachment to primary caregivers (usually parents). That lack of psychological and emotional attachment to a parental figure can result in the childs perception of themselves as unimportant and unconnected to other people, usually, family, community and society. Typically, the child comes to believe that they have a personality defect that makes them unvalued and unwanted; overindulgent, permissive parenting or insensitive and over-controlling parenting are risk factors towards the development of NPD in a child.In Gabbards Treatments of Psychiatric Disorders (2014), the following factors are identified as promoting the development of narcissistic personality disorder:
An oversensitive temperament (individual differences of behavior) at birth
Excessive admiration that is never balanced with realistic criticism
Excessive praise for good behaviors, or excessive criticism for bad behaviors in childhood
Overindulgence and overvaluation by family or peers
Being praised by adults for perceived exceptional physical appearance or abilities
Trauma caused by psychological abuse, physical abuse or sexual abuse in childhood
Unpredictable or unreliable parental caregiving
Learning the behaviors of psychological manipulation from parents or peersMoreover, the research reported in "Modernity and Narcissistic Personality Disorders" (2014) indicates that cultural elements also influence the prevalence of NPD, because narcissistic personality traits more commonly occur in modern societies than in traditionalist conservative societies.
Pathophysiology
Studies of the occurrence of narcissistic personality disorder identified structural abnormalities in the brains of people with NPD, specifically, a lesser volume of gray matter in the left, anterior insular cortex. The results of a 2015 study associated the condition of NPD with a reduced volume of gray matter in the prefrontal cortex. The regions of the brain identified and studied – the insular cortex and the prefrontal cortex – are associated with the human emotions of empathy and compassion, and with the mental functions of cognition and emotional regulation. The neurologic findings of the studies suggest that NPD may be related to a compromised (damaged) capacity for emotional empathy and emotional regulation.
Management
Treatment for NPD is primarily psychotherapeutic; there is no clear evidence that psychopharmacological treatment is effective for NPD, although it can prove useful for treating comorbid disorders. Psychotherapeutic treatment falls into two general categories: psychoanalytic/psychodynamic and cognitive behavioral. Psychoanalytic therapies include schema therapy, transference focused psychotherapy, mentalization-based treatment and metacognitive psychotherapy. Cognitive behavioral therapies include cognitive behavioral therapy and dialectical behavior therapy. Formats also include group therapy and couples therapy. The specific choice of treatment varies based on individual presentations.Management of narcissistic personality disorder has not been well studied, however many treatments tailored to NPD exist. Therapy is complicated by the lack of treatment-seeking behavior in people with NPD, despite mental distress. Additionally, people with narcissistic personality disorders have decreased life satisfaction and lower qualities of life, irrespective of diagnosis. People with NPD often present with comorbid mental disorders, complicating diagnosis and treatment. NPD is rarely the primary reason for which people seek mental health treatment. When people with NPD enter treatment (psychologic or psychiatric), they often express seeking relief from a comorbid mental disorder, including major depressive disorder, a substance use disorder (drug addiction), or bipolar disorder.
Prognosis
As of 2020, no treatment guidelines exist for NPD and no empirical studies have been conducted on specific NPD groups to determine efficacy for psychotherapies and pharmacology.The presence of NPD in patients undergoing psychotherapy for the treatment of other mental disorders is associated with slower treatment progress and higher dropout rates.
Epidemiology
As of 2018, overall prevalence is estimated to range from 0.8% to 6.2%. In 2008 under the DSM-IV, lifetime prevalence of NPD was estimated to be 6.2%, with 7.7% for men and 4.8% for women, with a 2015 study confirming the gender difference. In clinical settings, prevalence estimates range from 1% to 15%. The occurrence of narcissistic personality disorder presents a high rate of comorbidity with other mental disorders.
History
The term "narcissism" comes from a first century (written in the year 8 AD) book by the Roman poet Ovid. Metamorphoses Book III is a myth about two main characters, Narcissus and Echo. Narcissus is a handsome young man who spurns the advances of many potential lovers. When Narcissus rejects the nymph Echo, named this way because she was cursed to only echo the sounds that others made, the gods punish him by making him fall in love with his own reflection in a pool of water. When Narcissus discovers that the object of his love cannot love him back, he slowly pines away and dies.The concept of excessive selfishness has been recognized throughout history. In ancient Greece, the concept was understood as hubris. It is only since the late 1800s that narcissism has been defined in psychological terms:
Havelock Ellis (1898) was the first psychologist to use the term when he linked the myth to the condition in one of his patients.
Sigmund Freud (1905-1953) used the terms "narcissistic libido" in his Three Essays on the Theory of Sexuality.
Ernest Jones (1913/1951) was the first to construe extreme narcissism as a character flaw.
Robert Waelder (1925) published the first case study of narcissism. His patient was a successful scientist with an attitude of superiority, an obsession with fostering self-respect, and a lack of normal feelings of guilt. The patient was aloof and independent from others and had an inability to empathize with others situations, and was selfish sexuality. Waelders patient was also overly logical and analytical and valued abstract intellectual thought (thinking for thinkings sake) over the practical application of scientific knowledge.Narcissistic personality was first described by the psychoanalyst Robert Waelder in 1925. The term narcissistic personality disorder (NPD) was coined by Heinz Kohut in 1968. Waelders initial study has been influential in the way narcissism and the clinical disorder Narcissistic personality disorder are defined today
Freudianism and psychoanalysis
Much early history of narcissism and NPD originates from psychoanalysis. Regarding the adult neurotics sense of omnipotence, Sigmund Freud said that "this belief is a frank acknowledgement of a relic of the old megalomania of infancy"; and concluded that: "we can detect an element of megalomania in most other forms of paranoic disorder. We are justified in assuming that this megalomania is essentially of an infantile nature, and that, as development proceeds, it is sacrificed to social considerations."Narcissistic injury and narcissistic scar are terms used by Freud in the 1920s. Narcissistic wound and narcissistic blow are other, almost interchangeable, terms. When wounded in the ego, either by a real or a perceived criticism, a narcissistic persons displays of anger can be disproportionate to the nature of the criticism suffered; but typically, the actions and responses of the NPD person are deliberate and calculated. Despite occasional flare-ups of personal insecurity, the inflated self-concept of the NPD person is primarily stable.In The Psychology of Gambling (1957), Edmund Bergler considered megalomania to be a normal occurrence in the psychology of a child, a condition later reactivated in adult life, if the individual takes up gambling. In The Psychoanalytic Theory of Neurosis (1946), Otto Fenichel said that people who, in their later lives, respond with denial to their own narcissistic injury usually undergo a similar regression to the megalomania of childhood.
Narcissistic supply
Narcissistic supply was a concept introduced by Otto Fenichel in 1938, to describe a type of admiration, interpersonal support, or sustenance drawn by an individual from his or her environment and essential to their self-esteem. The term is typically used in a negative sense, describing a pathological or excessive need for attention or admiration in codependents and the orally fixated, that does not take into account the feelings, opinions, or preferences of other people.
Narcissistic rage
The term narcissistic rage was a concept introduced by Heinz Kohut in 1972. Narcissistic rage was theorised as a reaction to a perceived threat to a narcissists self-esteem or self-worth. Narcissistic rage occurs on a continuum from aloofness, to expressions of mild irritation or annoyance, to serious outbursts, including violent attacks.Narcissistic rage reactions are not necessarily limited to NPD. They may also be seen in catatonic, paranoid delusion, and depressive episodes. It was later suggested that narcissistic people have two layers of rage; the first layer of rage being directed constant anger towards someone else, with the second layer being self-deprecating.
Object relations
In the second half of the 20th century, in contrast to Freuds perspective of megalomania as an obstacle to psychoanalysis, in the US and UK Kleinian psychologists used the object relations theory to re-evaluate megalomania as a defence mechanism. This Kleinian therapeutic approach built upon Heinz Kohuts view of narcissistic megalomania as an aspect of normal mental development, by contrast with Otto Kernbergs consideration of such grandiosity as a pathological distortion of normal psychological development.To the extent that people are pathologically narcissistic, the person with NPD can be a self-absorbed individual who passes blame by psychological projection and is intolerant of contradictory views and opinions; is apathetic towards the emotional, mental, and psychological needs of other people; and is indifferent to the negative effects of their behaviors, whilst insisting that people should see them as an ideal person. The merging of the terms "inflated self-concept" and "actual self" is evident in later research on the grandiosity component of narcissistic personality disorder, along with incorporating the defence mechanisms of idealization and devaluation and of denial.
Comparison to other personality disorders
NPD shares properties with borderline personality disorder, including social stigma, unclear causes and prevalence rates. In a 2020 study, it was argued that NPD is following a similar historical trend to borderline personality disorder: "In the past three decades, enormous progress has been made to elucidate the psychopathology, longitudinal course, and effective treatment for BPD. NPD, which remains as similarly stigmatized and poorly understood as BPD once was, now carries the potential for a new wave of investigation and treatment development."However, NPD also shares some commonality with the now discredited "multiple personality disorder" (MPD) personality constellation in popular culture and clinical lore. MPD received a high level of mainstream media attention the 1980s, followed by a nearly complete removal from public discourse within the following two decades; this was in part due to thorough debunking many of its propositions and the evident societal harm created by its entry into the legal defence realm. Similar to MPD, NPD has been the subject of high levels of preoccupation in social and popular media forums, without a firm empirical basis despite over a century of description in clinical lore. The NPD label may be misused colloquially and clinically to disparage a target for the purpose of buttressing ones own self-esteem, or other motives that are detrimental for the person receiving the label. Finally, the rise in popular interest in NPD is not accompanied by hypothesized increases in narcissism among recent generations despite widespread assumptions to the contrary.
Controversy
The extent of controversy about narcissism was on display when the committee on personality disorders for the 5th Edition (2013) of the Diagnostic and Statistical Manual of Mental Disorders recommended the removal of Narcissistic Personality from the manual. A contentious three-year debate unfolded in the clinical community with one of the sharpest critics being John Gunderson, who led the DSM personality disorders committee for the 4th edition of the manual.The American Psychiatric Associations (APA) formulation, description, and definition of narcissistic personality disorder, as published in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Ed., Text Revision (DSM-IV-TR, 2000), was criticised by clinicians as inadequately describing the range and complexity of the personality disorder that is NPD. That it is excessively focused upon "the narcissistic individuals external, symptomatic, or social interpersonal patterns – at the expense of... internal complexity and individual suffering", which reduced the clinical utility of the NPD definition in the DSM-IV-TR.In revising the diagnostic criteria for personality disorders, the work group for the list of "Personality and Personality Disorders" proposed the elimination of narcissistic personality disorder (NPD) as a distinct entry in the DSM-5, and thus replaced a categorical approach to NPD with a dimensional approach, which is based upon the severity of the dysfunctional-personality-trait domains. Clinicians critical of the DSM-5 revision characterized the new diagnostic system as an "unwieldy conglomeration of disparate models that cannot happily coexist", which is of limited usefulness in clinical practice. Despite the reintroduction of the NPD entry, the APAs re-formulation, re-description, and re-definition of NPD, towards a dimensional view based upon personality traits, remains in the list of personality disorders of the DSM-5.
A 2011 study concluded that narcissism should be conceived as personality dimensions pertinent to the full range of personality disorders, rather than as a distinct diagnostic category. In a 2012 literature review about NPD, the researchers concluded that narcissistic personality disorder "shows nosological inconsistency, and that its consideration as a trait domain needed further research would be strongly beneficial to the field." In a 2018 latent structure analysis, results suggested that the DSM-5 NPD criteria fail to distinguish some aspects of narcissism relevant to diagnosis of NPD and subclinical narcissism.
In popular culture
Game of Thrones series and television adaptation of George R. R. Martins A Song of Ice and Fire:
The Lannisters have been deemed a "family of narcissists". Licensed Mental Health Counselor (LMHC) Colleen Jordan has said the incestuous twins Cersei and Jaime have a combination of borderline personality disorder and narcissistic personality disorder, and their younger brother Tyrion is an alcoholic narcissist. Additionally, a clinical psychologist posted as Redditor Rain12913: "People seem to be falling into the trap of thinking that Cersei really does genuinely love her brother and her (late) children. While she certainly says that she does quite a bit, and while her behaviour may seem to suggest that she does, it is highly unlikely that such a narcissistic character is capable of true love." About the familys patriarch, Jordan observes that "Tywin Lannister is actually the worst of them".
Of Lord Petyr Baelish (nicknamed "Littlefinger") Jordan observes: "If you look at Littlefinger, we know hes not remotely personally interested in Lysa, but he likes the attention |
Narcissistic personality disorder | . And he needs her. Narcissists use people for functions, which he does."
Suzanne Stone-Maretto, Nicole Kidmans character in the film To Die For (1995), wants to appear on television at all costs, even if this involves murdering her husband. A psychiatric assessment of her character noted that she "was seen as a prototypical narcissistic person by the raters: on average, she satisfied 8 of 9 criteria for narcissistic personality disorder... had she been evaluated for personality disorders, she would receive a diagnosis of narcissistic personality disorder".
Jay Gatsby, the eponymous character of F. Scott Fitzgeralds novel The Great Gatsby (1925), "an archetype of self-made American men seeking to join high society", has been described as a "pathological narcissist" for whom the "ego-ideal" has become "inflated and destructive" and whose "grandiose lies, poor sense of reality, sense of entitlement, and exploitive treatment of others" conspire toward his own demise.
See also
Dark triad, a concept in applied psychology associating personality traits of narcissism with Machiavellianism and psychopathy.
References
== Further reading == |
Hypoglycemia | Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipples triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly.The most common cause of hypoglycemia is medications used to treat diabetes such as insulin, sulfonylureas, and biguanides. Risk is greater in diabetics who have eaten less than usual, recently exercised, or consumed alcohol. Other causes of hypoglycemia include severe illness, sepsis, kidney failure, liver disease, hormone deficiency, tumors such as insulinomas or non-B cell tumors, inborn errors of metabolism, several medications, and alcohol. Low blood sugar may occur in otherwise healthy newborns who have not eaten for a few hours.Hypoglycemia is treated by eating a sugary food or drink, for example glucose tabs or gel, apple juice, soda, or candy. The person must be conscious and able to swallow. The goal is to consume 10-20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L). If a person is not able to take food by mouth, glucagon by injection or in the nose may help. The treatment of hypoglycemia unrelated to diabetes includes treating the underlying problem.Among people with diabetes, prevention starts with learning the signs and symptoms of hypoglycemia. Diabetes medications, like insulin, sulfonylureas, and biguanides can also be adjusted or stopped to prevent hypoglycemia. Frequent and routine blood glucose testing is recommended. Some may find continuous glucose monitors with insulin pumps to be helpful in the management of diabetes and prevention of hypoglycemia.
Definition
Blood sugar levels naturally fluctuate throughout the day, however hypoglycemia, also called low blood sugar or low blood glucose, is when blood sugar levels drop below 70 mg/dL (3.9 mmol/L).Blood sugar levels are generally maintained between 70 and 110 mg/dL (3.9-6.1 mmol/L). Although 70 mg/dL (3.9 mmol/L) is the lower limit of normal glucose, symptoms of hypoglycemia usually do not occur until 55 mg/dL (3.0 mmol/L) or lower. The blood glucose level at which symptoms of hypoglycemia develop in someone with several prior episodes of hypoglycemia may be even lower.
Whipples triad
The symptoms of low blood sugar alone are not specific enough to characterize a hypoglycemic episode. A single blood sugar reading below 70 mg/dL is also not specific enough characterize a hypoglycemic episode. Whipples triad is a set of three conditions that need to be met in order to accurately characterize a hypoglycemic episode.The three conditions are the following:
The signs and symptoms of hypoglycemia are present (see section below on Signs and Symptoms)
A low blood glucose measurement is present, typically less than 70 mg/dL (3.9 mmol/L)
The signs and symptoms of hypoglycemia resolve after blood glucose levels have returned to normal
Age
The biggest difference in blood glucose levels between the adult and pediatric population occurs in newborns during the first 48 hours of life. After the first 48 hours of life, the Pediatric Endocrine Society cites that there is little difference in blood glucose level and the use of glucose between adults and children. During the 48 hour neonatal period, the neonate adjusts glucagon and epinephrine levels following birth, which may cause temporary hypoglycemia. As a result, there has been difficulty in developing guidelines on interpretation and treatment of low blood glucose in neonates aged less than 48 hours. Following a data review, the Pediatric Endocrine Society concluded that neonates aged less than 48 hours begin to respond to hypoglycemia at serum glucose levels of 55–65 mg/dL (3.0-3.6 mmol/L). This is contrasted by the value in adults, children, and older infants, which is approximately 80–85 mg/dL (4.4-4.7 mmol/L).In children who are aged greater than 48 hours, serum glucose on average ranges from 70 to 100 mg/dL (3.9-5.5 mmol/L), similar to adults. Whipples triad is used to identify hypoglycemia in children who can communicate their symptoms.
Differential diagnosis
Other conditions that may present similarly to hypoglycemia include the following:
Alcohol or drug intoxication
Cardiac arrhythmia
Valvular heart disease
Postprandial syndrome
Hyperthyroidism
Pheochromocytoma
Post-gastric bypass hypoglycemia
Generalized anxiety disorder
Surreptitious insulin use
Lab or blood draw error (lack of antiglycolytic agent in collection tube or during processing)
Signs and symptoms
Hypoglycemic symptoms are divided into two main categories. The first category is symptoms caused by low glucose in the brain, called neuroglycopenic symptoms. The second category of symptoms is caused by the bodys reaction to low glucose in the brain, called adrenergic symptoms.
Everyone experiences different symptoms of hypoglycemia, so someone with hypoglycemia may not have all of the symptoms listed above. Symptoms also tend to have quick onset. It is important to quickly obtain a blood glucose measurement in someone presenting with symptoms of hypoglycemia to properly identify the hypoglycemic episode.
Pathophysiology
Glucose is the main source of energy for the brain, and a number of mechanisms are in place to prevent hypoglycemia and protect energy supply to the brain. The body can adjust insulin production and release, adjust glucose production by the liver, and adjust glucose use by the body. The body naturally produces the hormone insulin, in an organ called the pancreas. Insulin helps to regulate the amount of glucose in the body, especially after meals. Glucagon is another hormone involved in regulating blood glucose levels, and can be thought of as the opposite of insulin. Glucagon helps to increase blood glucose levels, especially in states of hunger.When blood sugar levels fall to the low-normal range, the first line of defense against hypoglycemia is decreasing insulin release by the pancreas. This drop in insulin allows the liver to increase glycogenolysis. Glycogenolysis is the process of glycogen breakdown that results in the production of glucose. Glycogen can be thought of as the inactive, storage form of glucose. Decreased insulin also allows for increased gluconeogenesis in the liver and kidneys. Gluconeogenesis is the process of glucose production from non-carbohydrate sources, supplied from muscles and fat.Once blood glucose levels fall out of the normal range, additional protective mechanisms work to prevent hypoglycemia. The pancreas is signaled to release glucagon, a hormone that increases glucose production by the liver and kidneys, and increases muscle and fat breakdown to supply gluconeogenesis. If increased glucagon does not raise blood sugar levels to normal, the adrenal glands release epinephrine. Epinephrine works to also increase gluconeogenesis and glycogenolysis, while also decreasing the use of glucose by organs, protecting the brains glucose supply.After hypoglycemia has been prolonged, cortisol and growth hormone are released to continue gluconeogenesis and glycogenolysis, while also preventing the use of glucose by other organs. The effects of cortisol and growth hormone are far less effective than epinephrine. In a state of hypoglycemia, the brain also signals a sense of hunger and drives the person to eat, in an attempt to increase glucose.
Causes
Hypoglycemia is most common in those with diabetes treated by insulin, glinides, and sulfonylureas. Hypoglycemia is rare in those without diabetes, because there are many regulatory mechanisms in place to appropriately balance glucose, insulin, and glucagon. Please refer to Pathophysiology section (above) for more information on glucose, insulin, and glucagon.
Diabetics
Medications
The most common cause of hypoglycemia in diabetics is medications used to treat diabetes such as insulin, sulfonylureas, and biguanides. This is often due to excessive doses or poorly timed doses. Sometimes diabetics may take insulin in anticipation of a meal or snack, and missing or forgetting that meal will lead to hypoglycemia. This is due to increased insulin without the presence of glucose from the planned meal.
Hypoglycemic unawareness
Recurrent episodes of hypoglycemia can lead to hypoglycemic unawareness, or the decreased ability to recognize hypoglycemia. As diabetics experience more episodes of hypoglycemia, the blood glucose level which triggers symptoms of hypoglycemia decreases. In other words, people without hypoglycemic unawareness experience symptoms of hypoglycemia at a blood glucose of about 55 mg/dL (3.0 mmol/L). Those with hypoglycemic unawareness experience the symptoms of hypoglycemia at far lower levels of blood glucose. This is dangerous for a number of reasons. The hypoglycemic person not only gains awareness of hypoglycemia at very low blood glucose levels, but they also require high levels of carbohydrates or glucagon to recover their blood glucose to normal levels. These individuals are also at far greater risk of severe hypoglycemia.While the exact cause of hypoglycemic unawarenss is still under research, it is thought that these individuals progressively begin to develop fewer adrenergic-type symptoms, resulting in the loss of neuroglycopenic-type symptoms. Neuroglycopenic symptoms are caused by low glucose in the brain, and can result in tiredness, confusion, difficulty with speech, seizures, and loss of consciousness. Adrenergic symptoms are caused by the bodys reaction to low glucose in the brain, and can result in fast heart rate, sweating, nervousness, and hunger. See section above on Signs and Symptoms for further explanation of neuroglycopenic symptoms and adrenergic symptoms.
In terms of epidemiology, hypoglycemic unawarenss occurs in 20-40% of type 1 diabetics.
Other causes
Other causes of hypoglycemia in diabetics include the following:
Fasting, whether it be a planned fast or overnight fast, as there is a long period of time without glucose intake
Exercising more than usual as it leads to more use of glucose, especially by the muscles
Drinking alcohol, especially when combined with diabetic medications, as alcohol inhibits glucose production
Kidney disease, as insulin cannot be cleared out of circulation well
Non-diabetics
Serious illness
Serious illness may result in low blood sugar. Severe disease of many organ systems can cause hypoglycemia as a secondary problem. Hypoglycemia is especially common in those in the intensive care unit or those in whom food and drink is withheld as a part of their treatment plan.Sepsis, a common cause of hypoglycemia in serious illness, can lead to hypoglycemia through many ways. In a state of sepsis, the body uses large amounts of glucose for energy. Glucose use is further increased by cytokine production. Cytokines are a protein produced by the body in a state of stress, particularly when fighting an infection. Cytokines may inhibit glucose production, further decreasing the bodys energy stores. Finally, the liver and kidneys are sites of glucose production, and in a state of sepsis those organs may not receive enough oxygen, leading to decreased glucose production due to organ damage.Other causes of serious illness that may cause hypoglycemia include liver failure and kidney failure. The liver is the main site of glucose production in the body, and any liver failure or damage will lead to decreased glucose production. While the kidneys are also sites of glucose production, their failure of glucose production is not significant enough to cause hypoglycemia. Instead, the kidneys are responsible for removing insulin from the body, and when this function is impaired in kidney failure, the insulin stays in circulation longer, leading to hypoglycemia.
Drugs
A number of medications have been identified which may cause hypoglycemia, through a variety of ways. Moderate quality evidence implicates the non-steroidal anti-inflammatory drug indomethacin and the anti-malarial quinine. Low quality evidence implicates lithium, used for bipolar disorder. Finally, very low quality evidence implicates a number of hypertension medications including angiotensin converting enzyme inhibitors (also called ACE-inhibitors), angiotensin receptor blockers (also called ARBs), and β-adrenergic blockers (also called beta blockers). Other medications with very low quality evidence include the antibiotics levofloxacin and trimethoprim-sulfamethoxazole, progesterone blocker mifepristone, anti-arrhythmic disopyramide, anti-coagulant heparin, and chemotherapeutic mercaptopurine.If a person without diabetes accidentally takes medications that are traditionally used to treat diabetes, this may also cause hypoglycemia. These medications include insulin, glinides, and sulfonylureas. This may occur through medical errors in a healthcare setting or through pharmacy errors, also called iatrogenic hypoglycemia.
Surreptitious insulin use
When individuals take insulin without needing it, to purposefully induce hypoglycemia, this is referred to as surreptitious insulin use or factitious hypoglycemia. Some people may use insulin to induce weight loss, whereas for others this may be due to malingering or factitious disorder, which is a psychiatric disorder. Demographics affected by factitious hypoglycemia include women aged 30–40, particularly those with diabetes, relatives with diabetes, healthcare workers, or those with history of a psychiatric disorder. The classic way to identify surreptitious insulin use is through blood work revealing high insulin levels with low C-peptide and proinsulin.
Alcohol misuse
The production of glucose is blocked by alcohol. In those who misuse alcohol, hypoglycemia may be brought on by a several-day alcohol binge associated with little to no food intake. The cause of hypoglycemia is multifactorial, where glycogen becomes depleted in a state of starvation. Glycogen stores are then unable to be repleted due to the lack of food intake, all compounded the inhibition of glucose production by alcohol.
Hormone deficiency
Children with primary adrenal failure, also called Addisons disease, may experience hypoglycemia after long periods of fasting. Addisons disease is associated with chronically low levels of the stress hormone cortisol, which leads to decreased glucose production.Hypopituitarism, leading to decreased growth hormone, is another cause of hypoglycemia in children, particularly with long periods of fasting or increased exercise.
Inborn errors of metabolism
Briefly, inborn errors of metabolism are a group rare of genetic disorders that are associated with the improper breakdown or storage of proteins, carbohydrates, or fatty acids. Inborn errors of metabolism may cause infant hypoglycemia, and much less commonly adult hypoglycemia. Disorders that are related to the breakdown of glycogen, called glycogen storage diseases, may cause hypoglycemia. Normally, breakdown of glycogen leads to increased glucose levels, particularly in a fasting state. In glycogen storage diseases however, glycogen cannot be properly broken-down, leading to inappropriately decreased glucose levels in a fasting state, and thus hypoglycemia. The glycogen storage diseases associated with hypoglycemia include type 0, type I, type III, and type IV, as well as Fanconi syndrome.
Insulinomas
A primary B-cell tumor, such as an insulinoma, is associated with hypoglycemia. This is a tumor located in the pancreas. An insulinoma produces insulin, which in turn decreases glucose levels, causing hypoglycemia. Normal regulatory mechanisms are not in place, which prevent insulin levels from falling during states of low blood glucose. During an episode of hypoglycemia, plasma insulin, C-peptide, and proinsulin will be inappropriately high.
Non-B cell tumors
Hypoglycemia may occur in people with non-B cell tumors such as hepatomas, adrenocorticoid carcinomas, and carcinoid tumors. These tumors lead to a state of increased insulin, specifically increased insulin-like growth factor II, which decreases glucose levels.
Post-gastric bypass postprandial hypoglycemia
The Roux-en-Y gastric bypass, is a weight-loss surgery performed on the stomach, and has been associated with hypoglycemia, called post-gastric bypass postprandial hypoglycemia. Although the entire mechanism of hypoglycemia following this surgery is not fully understood, it is thought that meals cause very high levels of glucagon-like peptide-1 (also called GLP-1), a hormone that increases insulin, causing glucose levels to drop.
Autoimmune hypoglycemia
Antibodies can be formed against insulin, leading to autoimmune hypoglycemia. Antibodies are immune cells produced by the body, that normally attack bacteria and viruses, but sometimes can attack normal human cells, leading to an autoimmune disorder. In autoimmune hypoglycemia, there are two possible mechanisms. In one instance, antibodies bind to insulin following its release associated with a meal, resulting in insulin being non-functional. At a later time, the antibodies fall off insulin, causing insulin to be functional again leading late hypoglycemia after a meal, called late postprandial hypoglycemia. Another mechanism causing hypoglycemia is due to antibodies formed against insulin receptors, called insulin receptor antibodies. The antibodies attach to insulin receptors and prevent insulin breakdown, or degradation, leading to inappropriately high insulin levels and low glucose levels.
Neonatal hypoglycemia
Low blood sugar may occur in healthy neonates aged less than 48 hours who have not eaten for a few hours. During the 48 hour neonatal period, the neonate adjusts glucagon and epinephrine levels following birth, which may trigger transient hypoglycemia. In children who are aged greater than 48 hours, serum glucose on average ranges from 70 to 100 mg/dL (3.9-5.5 mmol/L), similar to adults, with hypoglycemia being far less common.
Diagnostic approach
The most reliable method of identifying hypoglycemia is through identifying Whipples triad. The components of Whipples triad are a blood sugar level below 70 mg/dL (3.9 mmol/L), symptoms related to low blood sugar, and improvement of symptoms when blood sugar is restored to normal. Identifying Whipples triad in a patient helps to avoid unnecessary diagnostic testing and decreases healthcare costs.In those with a history of diabetes treated with insulin, glinides, or sulfonylurea, who demonstrate Whipples triad, it is reasonable to assume the cause of hypoglycemia is due to insulin, glinides, or sulfonylurea use. In those without a history of diabetes with hypoglycemia, further diagnostic testing is necessary to identify the cause. Testing, during an episode of hypoglycemia, should include the following:
Plasma glucose level, not point-of-care measurement
Insulin level
C-peptide level
Proinsulin level
Beta-hydroxybutyrate level
Oral hypoglycemic agent screen
Response of blood glucose level to glucagon
Insulin antibodiesIf necessary, a diagnostic hypoglycemic episode can be produced in an inpatient or outpatient setting. This is called a diagnostic fast, in which a patient undergoes an observed fast to cause a hypoglyemic episode, allowing for appropriate blood work to be drawn. In some, the hypoglycemic episode may be reproduced simply after a mixed meal, whereas in others a fast may last up to 72 hours.In those with a suspected insulinoma, imaging is the most reliable diagnostic technique, including ultrasound, computed tomography imaging (also called CT imaging), and magnetic resonsance imaging (also called MRI).
Treatment
After hypoglycemia in a person is identified, rapid treatment is necessary and can be life-saving. The main goal of treatment is to raise blood glucose back to normal levels, which is done through various ways of administering glucose, depending on the severity of the hypoglycemia, what is on-hand to treat, and who is administering the treatment. A general rule used by the American Diabetes Association is the "15-15 Rule," which suggests consuming or administering 15 grams of a carbohydrate, followed by a 15-minute wait and re-measurement of blood glucose level to assess if blood glucose has returned to normal levels.
Self-treatment
If an individual recognizes the symptoms of hypoglycemia coming on, blood sugar should promptly be measured, and a sugary food or drink should be consumed. The person must be conscious and able to swallow. The goal is to consume 10-20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L).Examples of products to consume are:
Glucose tabs or gel (refer to instructions on packet)
Juice containing sugar like apple, grape, or cranberry juice, 4 ounces or 1/2 cup
Soda or a soft-drink, 4 ounces or 1/2 cup (not diet soda)
Candy
Table sugar or honey, 1 tablespoonImprovement in blood sugar levels and symptoms are expected to occur in 15–20 minutes, at which point blood sugar should be measured again. If the repeat blood sugar level is not above 70 mg/dL (3.9 mmol/L), consume another 10-20 grams of a carbohydrate and remeasure blood sugar levels after 15–20 minutes. Repeat until blood glucose levels have returned to normal levels. The greatest improvements in blood glucose will be seen if the carbohydrate chewed or drunk, and then swallowed. This results in the greatest bioavaliablity of glucose, meaning the greatest amount of glucose enters the body producing the best possible improvements in blood glucose levels. The second best way to consume a carbohydrate it to allow it to dissolve under the tongue, also referred to as sublingual administration. For example, a hard candy can be dissolved under the tongue, however the best improvements in blood glucose will occur if the hard candy is chewed and crushed, then swallowed.After correcting blood glucose levels, people may consume a full meal within one hour in order to replenish glycogen stores.
Education
Family, friends, and co-workers of a person with diabetes may provide life-saving treatment in the case of a hypoglycemic episode It is important for these people to receive training on how to recognize hypoglycemia, what foods to help the hypoglycemic eat, how to administer injectable or intra-nasal glucagon, and how use a glucose meter.
Treatment by family, friends, or co-workers
Family, friends, and co-workers of those with hypoglycemia are often first to identify hypoglycemic episodes, and may offer help. Upon recognizing the signs and symptoms of hypoglycemia in a diabetic, a blood sugar level should first be measured using a glucose meter. If blood glucose is below 70 mg/dL (3.9 mmol/L), treatment will depend on whether the person is conscious and can swallow safely. If the person is conscious and able to swallow, the family, friend, or co-worker can help the hypoglycemic consume 10-20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L). Improvement in blood sugar level and symptoms is expected to occur in 15–20 minutes, at which point blood sugar is measured again. If the repeat blood sugar level is not above 70 mg/dL (3.9 mmol/L), the hypoglycemic should consume another 10-20 grams of a carbohydrate and with remeasurement of blood sugar levels after 15–20 minutes. Repeat until blood glucose levels have returned to normal levels, or call emergency services for further assistance.If the person is unconscious, a glucagon kit may be used to treat severe hypoglycemia, which delivers glucagon either by injection into a muscle or through nasal inhalation. In the United States, glucacon kits are available by prescription for diabetic patients to carry in case of an episode of severe hypoglycemia. Emergency services should be called for further assistance.
Treatment by medical professionals
In a healthcare setting, treatment depends on the severity of symptoms and intravenous access. If a patient is conscious and able to swallow safely, food or drink may be administered, as well as glucose tabs or gel. In those with intravenous access, 25 grams of 50% dextrose is commonly administered. When there is no intravenous access, intramuscular or intra-nasal glucagon may be administered.
Other treatments
While the treatment of hypoglycemia is typically managed with carbohydrate consumption, glucagon injection, or dextrose administration, there are some other treatments available. Medications like diazoxide and octreotide decrease insulin levels, increasing blood glucose levels. Dasiglucagon was approved for medical use in the United States in March 2021, to treat severe hypoglycemia. Dasiglucagon (brand name Zegalogue) is unique because it is glucagon in a prefilled syringe or auto-injector pen, as opposed to traditional glucagon kits that require mixing powdered glucagon with a liquid.The soft drink Lucozade has been used for hypoglycemia in the United Kingdom, but it has recently replaced much of its glucose with artificial sweeteners, which do not treat hypoglycemia.
Prevention
Diabetics
The prevention of hypoglycemia depends on the cause. In those with diabetes treated by insulin, glinides, or sulfonylurea, the prevention of hypoglycemia has a large focus on patient education and medication adjustments. The foundation of diabetes education is learning how to recognize the signs and symptoms of hypoglycemia, as well as learning how to act quickly to prevent worsening of an episode. Another cornerstone of prevention is strong self-monitoring of blood glucose, with consistent and frequent measurements. Research has shown that patients with type 1 diabetes who use continuous glucose monitoring systems with insulin pumps significantly improve blood glucose control. Insulin pumps help to prevent high glucose spikes, and help prevent inappropriate insulin dosing. Continuous glucose monitors can sound alarms when blood glucose is too low or too high, especially helping those with nocturnal hypoglycemia or hypoglycemic unawareness. In terms of medication adjustments, medication doses and timing can be adjusted in order to prevent hypoglycemia, or a medication can be stopped altogether.
Non-diabetics
In those with hypoglycemia who do not have diabetes, there are a number of preventative measures dependent on the cause. Hypoglycemia caused by hormonal dysfunction like lack of cortisol in Addisons disease or lack of growth hormone in hypopituitarism can be prevented with appropriate hormone replacement. The hypoglycemic episodes associated with non-B cell tumors can be decreased following surgical removal of the tumor, as well as following radiotherapy or chemotherapy to reduce the size of the tumor. In some cases, those with non-B cell tumors may have hormone therapy with growth hormone, glucocorticoid, or octreotide to also lessen hypoglycemic episodes. Post-gastric bypass hypoglycemia can be prevented by eating smaller, more frequent meals, avoiding |
Hypoglycemia | sugar-filled foods, as well as medical treatment with an alpha-glucosidase inhibitor, diazoxide, or octreotide.Some causes of hypoglycemia require treatment of the underlying cause to best prevent hypoglycemia. This is the case for insulinomas which often require surgical removal of the tumor in order for hypoglycemia to remit. In patients who cannot undergo surgery for removal of the insulinoma, diazoxide or octreotide may be used.
Epidemiology
Hypoglycemia is common in people with type 1 diabetes, and in people with type 2 diabetes taking insulin, glinides, or sulfonylurea. It is estimated that type 1 diabetics experience two mild, symptomatic episodes of hypoglycemia per week. Additionally, people with type 1 diabetes have at least one severe hypoglyemic episode per year, requiring treatment assistance. In terms of mortality, hypoglycemia causes death in 6-10% of type 1 diabetics.In those with type 2 diabetes, hypoglycemia is less common compared to type 1 diabetics, because medications that treat type 2 diabetes like metformin, glitazones, alpha-glucosidase inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase IV inhibitors, do not cause hypoglycemia. Hypoglycemia is common in type 2 diabetics who take insulin, glinides, or sulfonylurea. Insulin use remains a key risk factor in developing hypoglycemia, regardless of diabetes type.
History
Hypoglycemia was first discovered by James Collip when he was working with Frederick Banting on purifying insulin in 1922. Collip was asked to develop an assay to measure the activity of insulin. He first injected insulin into a rabbit, and then measured the reduction in blood-glucose levels. Measuring blood glucose was a time-consuming step. Collip observed that if he injected rabbits with a too large a dose of insulin, the rabbits began convulsing, went into a coma, and then died. This observation simplified his assay. He defined one unit of insulin as the amount necessary to induce this convulsing hypoglycemic reaction in a rabbit. Collip later found he could save money, and rabbits, by injecting them with glucose once they were convulsing.
Etymology
The word hypoglycemia is also spelled hypoglycaemia or hypoglycæmia. The term means low blood sugar from Greek ὑπογλυκαιμία, from ὑπο- hypo- under + γλυκύς glykys sweet + αἷμᾰ haima blood.
References
External links
Hypoglycemia at the Mayo Clinic
American Diabetes Association
"Hypoglycemia". MedlinePlus. U.S. National Library of Medicine. |
Alexander disease | Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions caused by anomalies in the myelin which protects nerve fibers in the brain. The most common type is the infantile form that usually begins during the first 2 years of life. Symptoms include mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size and seizures. The juvenile form of Alexander disease has an onset between the ages of 2 and 13 years. These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control. Adult-onset forms of Alexander disease are less common. The symptoms sometimes mimic those of Parkinson’s disease or multiple sclerosis, or may present primarily as a psychiatric disorder.
According to the National Institute of Neurological Disorders and Stroke, the destruction of white matter is accompanied by the formation of Rosenthal fibers—abnormal clumps of protein that accumulate in astrocytes in the brain.
The disease occurs in both males and females, and no ethnic, racial, geographic or cultural/economic differences are seen in its distribution. Alexander disease is a progressive and often fatal disease.
Presentation
Delays in development of some physical, psychological and behavioral skills; progressive enlargement of the head (macrocephaly), seizures, spasticity, and in some cases also hydrocephalus, idiopathic intracranial hypertension, and dementia.
Cause
Alexander disease is a genetic disorder affecting the midbrain and cerebellum of the central nervous system. It is caused by mutations in the gene for glial fibrillary acidic protein (GFAP) that maps to chromosome 17q21. It is inherited in an autosomal dominant manner, such that the child of a parent with the disease has a 50% chance of inheriting the condition, if the parent is heterozygotic. However, most cases arise de novo as the result of sporadic mutations.Alexander disease belongs to leukodystrophies, a group of diseases that affect the growth or development of the myelin sheath. The destruction of white matter in the brain is accompanied by the formation of fibrous, eosinophilic deposits known as Rosenthal fibers. Rosenthal fibers appear not to be present in healthy people, but occur in specific diseases, like some forms of cancer, Alzheimer’s, Parkinson’s, Huntington’s, and ALS. The Rosenthal fibers found in Alexander disease do not share the distribution or concentration of other diseases and disorders.
Pathology
Alexander disease causes the gradual loss of bodily functions and the ability to talk. It also causes an overload of long-chain fatty acids in the brain, which destroy the myelin sheath. The cause of Alexander disease is a mutation in the gene encoding GFAP.A CT scan shows:
Decreased density of white matter
Frontal lobe predominance
Dilated lateral ventricles may present
Diagnosis
Detecting the signs of Alexander disease is possible with magnetic resonance imaging (MRI), which looks for specific changes in the brain that may be tell-tale signs for the disease. It is even possible to detect adult-onset Alexander disease with MRI. Alexander disease may also be revealed by genetic testing for its known cause. A rough diagnosis may also be made through revealing of clinical symptoms, including enlarged head size, along with radiological studies, and negative tests for other leukodystrophies.
Treatment
No cure or standard procedure for treatment is known, although a University of Wisconsin study shows promise with gene editing of the astrocytes. A phase III clinical trial of an antisense therapy, sponsored by Ionis Pharmaceuticals, began in 2021. A bone marrow transplant has been attempted on a child, but it made no improvement. Hydrocephalus may be seen in younger patients and can be relieved with surgery or by implanting a shunt to relieve pressure.
Prognosis
The prognosis is generally poor. With early onset, death usually occurs within 10 years from the onset of symptoms. Individuals with the infantile form usually die before the age of seven. Usually, the later the disease occurs, the slower its course.
Prevalence
Its occurrence is very rare. The infantile form occurs from birth to 2 years of age. The average duration of the infantile form is usually about 3 years. Onset of the juvenile form presents between 2 and 12 years of age. Duration of this form is in most cases about 6 years. The adult form occurs after 12 years. In younger patients, seizures, megalencephaly, developmental delay, and spasticity are usually present. Neonatal onset is also reported. Onset in adults is least frequent. In older patients, bulbar or pseudobulbar symptoms and spasticity predominate. Symptoms of the adult form may also resemble multiple sclerosis. No more than 500 cases have been reported.
See also
The Myelin Project
The Stennis Foundation
References
External links
OMIM entries on Alexander disease
Infantile-onset Alexander disease in a child with long-term follow-up by serial magnetic resonance imaging: a case report
Alexander Disease: New Insights From Genetics |
Podoconiosis | Podoconiosis, also known as nonfilarial elephantiasis, is a disease of the lymphatic vessels of the lower extremities that is caused by chronic exposure to irritant soils. It is the second most common cause of tropical lymphedema after lymphatic filariasis, and it is characterized by prominent swelling of the lower extremities, which leads to disfigurement and disability. Methods of prevention include wearing shoes and using floor coverings. Mainstays of treatment include daily foot hygiene, compression bandaging, and when warranted, surgery of overlying nodules.
Signs and symptoms
Podoconiosis causes bilateral yet asymmetrical leg swelling with overlying firm nodules. Early on, symptoms may include itching, tingling, widening of the forefoot, and swelling which then progress to soft edema, skin fibrosis, papillomatosis, and nodule formation resembling moss, giving rise to the diseases alternate name of "mossy foot" in some regions of the world. As with other forms of tropical lymphedema, chronic disease can lead to rigid toes, ulceration, and bacterial superinfection. During acute episodes of adenolymphangitis, patients may develops fevers, extremity warmth, redness, and pain. These episodes are extremely debilitating and account for many days of activity and productivity loss each year.
Psychological consequences
As a result of its appearance, podoconiosis can cause social stigmatization and discrimination. People with podoconiosis also report a lower quality of life than people in similar neighborhood circumstances except without podoconiosis and also higher levels of mental distress and depression.
Pathophysiology
According to the World Health Organization "Evidence suggests that podoconiosis is the result of a genetically determined abnormal inflammatory reaction to mineral particles in irritant red clay soils derived from volcanic deposits".The pathophysiology of podoconiosis is a combination of genetic susceptibility, possibly through associations with HLA-DQA1, HLA-DQB1, and HLA-DRB1 variants, and a cumulative exposure to irritant soil. In susceptible individuals, irritant soil particles penetrate the feet and collect in lymphatic vessels. Over time, chronic inflammation within the lymphatic vessels leads to fibrosis and occlusion.
Diagnosis
Differential diagnosis
The differential diagnosis for podoconiosis includes other causes of tropical lymphedema, such as filariasis or leprosy, and mycetoma pedis.While filariasis is generally unilateral, podoconiosis affects the legs bilaterally albeit asymmetrically and in an ascending manner. Podoconiosis very rarely affects the groin while filariasis frequently involves the groin: a high ratio of lymphoedema/hydrocele cases in an area suggests podoconiosis as the dominant cause of lymphedema. In some cases, the history and clinical presentation alone are unable to differentiate between the two causes of tropical lymphedema. Local epidemiology can also be a clue to diagnosis, as podoconiosis is typically found in higher altitude areas with volcanic soils while filariasis is common in low-lying areas where mosquitos are prevalent. Blood smears for identification of microfilariae and antigen detection techniques can be helpful in the diagnosis of lymphatic filariasis.Lepromatous lymphedema can also mimic podoconiosis clinically, but the former will have loss of sensation in the toes and feet, thickened nerves, and trophic ulcers. Other causes of lymphedema include Kaposi sarcoma, mycetoma, and elephantiasis nostras verrucosa.
Prevention
Elimination of podoconiosis relies on prevention with widespread shoe implementation, stringent foot hygiene, and floor coverings. Community-based initiatives are crucial to achieving elimination of this disease. In Ethiopia, The Mossy Foot Treatment and Prevention Association (now Mossy Foot International) works to transform patients into community podoconiosis agents who in turn visit patients, teach basic treatment techniques such as foot hygiene, and educate families about the disease. This model has been adapted by several other non-government groups as they have started programs in other regions of Ethiopia.
Treatment
The cornerstone of prevention and treatment of podoconiosis is avoidance of exposure to irritant soils. Wearing shoes in the presence of irritant soils is the primary method of exposure reduction. In Rwanda, a country of high disease prevalence, the government has banned walking barefoot in public, in order to prevent podoconiosis and other soil-borne diseases. Increasing the availability of footwear must be coupled with education on the benefits of wearing shoes as cultural influences, such as barefoot traditions, can hinder widespread use of footwear.Once the disease has developed, rigorous foot hygiene including daily washing with soap and water, application of an emollient, and nightly elevation of the affected extremity has been shown to reduce frequency of acute attacks. Nodules will not resolve with these conservative measures, although surgical removal of the nodules can be performed.
Epidemiology
Podoconiosis is most frequently seen in the highland areas of Africa, India, and Central America. The highest prevalence is seen in Uganda, Tanzania, Kenya, Rwanda, Burundi, Sudan, and Ethiopia. A recent review has summarized the global distribution of podoconiosis. In some areas of Ethiopia, the prevalence is as high as 4%. The incidence of podoconiosis increases with age, likely due to cumulative exposure to irritant soil. It is very rare to see podoconiosis in the 0–5 year old age group, and the incidence rapidly rises from 6 to 20 years of age, with the highest prevalence after 45 years of age. Podoconiosis is most commonly seen in higher altitude areas with volcanic soil, and it is estimated to affect 4 million people worldwide. Productivity losses associated with the disease are significant. In Ethiopia (where 1.6 million people are estimated to be affected), the condition is thought to have caused US $200 million in lost productivity per year in 2004.
History
After parasitic filariae were discovered to be an important cause of tropical lymphedema in the 19th century, early investigators assumed that filariae were the sole cause of lymphedema in the tropics. It was later discovered that the distribution of tropical lymphedema and filariasis did not perfectly overlap, and researchers began to recognize that some forms of tropical lymphedema were not associated with filariasis. Ernest W Price, a British surgeon living in Ethiopia, discovered the true etiology of podoconiosis in the 1970s and 1980s by studying the lymph nodes and vessels of those afflicted with the disease. Using light microscopy, he observed macrophage cells laden with micro-particles in lymph nodes of the affected extremity. After examining the same tissue using electron microscopy, he was able to identify the presence of silicon, aluminum, and other soil metals both in the phagosomes of macrophages and adhered to the surface of lymphocytes. Price demonstrated that the lymphatic vessels of these patients experienced subendothelial edema and eventual collagenization of the lumen leading to complete blockage. He wrote a monograph on podoconiosis which was published after his death in 1990.
Current situation
Podoconiosis is now recognised as one of the WHO Neglected Tropical Diseases, its importance as a public health problem is well recognised in Ethiopia. Footwork is a charity which bring together public and private partners to support prevention and treatment of podoconiosis. There is an active research group led by Gail Davey at the Wellcome Trust Brighton and Sussex Centre for Global Health Research which co-ordinates research worldwide. A recent article in The Lancet includes some excellent illustrations.
References
External links
World Health Organization section on podoconiosis |
Allergic transfusion reaction | An allergic transfusion reaction is when a blood transfusion results in allergic reaction. It is among the most common transfusion reactions to occur. Reported rates depend on the degree of active surveillance versus passing reporting to the blood bank. Overall, they are estimated to complicate up to 3% of all transfusions. The incidence of allergic transfusion reactions is associated with the amount of plasma in the product. More than 90% of these reactions occur during transfusion.
Signs and symptoms
Cause
Allergic reactions from blood transfusion may occur from the presence of allergy-causing antigens within the donors blood, or transfusion of antibodies from a donor who has allergies, followed by antigen exposure.An allergic transfusion reaction is a type of transfusion reaction that is defined according to the Center for Disease Control (CDC) as:
Diagnosis
An allergic transfusion reaction is diagnosed if two or more of the following occur within 4 hours of cessation of transfusion:
A probable diagnosis results if any one of the following occurring within 4 hours of cessation of transfusion:
The UK hemovigilance reporting system (SHOT), has classified allergic reactions in to mild, moderate and severe. Reactions can occur that have features of both allergic and febrile reactions.
Mild
A rash, urticaria, or flushing
Moderate
Wheeze (bronchospasm) or angioedema but blood pressure normal and no respiratory compromise. There may or may not be an associated rash or urticaria.
Severe
This can be due to:
Severe breathing problems (Bronchospasm, stridor), angioedema, or circulatory problems (e.g. hypotension) which require immediate medical treatment OR admission to hospital OR lengthens the duration of hospital admission.
Anaphylaxis
Prevention
To prevent allergic transfusion reaction it is possible to use patients own blood for transfusion, this is referred to as autologous blood transfusion. Patients own blood is collected and washed to produce concentrated red blood cells (this blood product is also called packed red blood cells). There are multiple ways to wash red blood cells. The two main methods that are used to wash the cells are centrifugation, or filtration methods like the Hemoclear microfilter. The last option is reinfusion without washing. This is the least preferred method because of the chance of complications.There is no evidence that antihistamine premedication prevents allergic transfusion reactions, although these drugs can mitigate symptoms once they occur.
Treatment
Treatment of an allergic transfusion reaction is to immediately stop the transfusion. If the only symptoms are mild (i.e., hives and itching), the patient may be treated with an antihistamine and if the symptoms completely disappear and the patient feels well, the transfusion may be restarted. A mild transfusion reaction during infusion usually does not progress to a more severe anaphylactic reaction after infusion of additional product from the same unit. If the symptoms are more than mild, the transfusion should not be restarted.
== References == |
Vitreous touch syndrome | Vitreous touch syndrome is a late complication of intra capsular cataract extraction wherein the vitreous bulges through the pupillary aperture, and touches and attaches to the corneal endothelium.
References
Further reading
Dr. Kushal Banerjee (2006). "A review and clinical evaluation of per-operative and post-operative complications in case of manual small incision cataract surgery and extracapsular cataract extraction with posterior chamber intra-ocular lens implantation" (PDF). Archived from the original (PDF) on 5 June 2014. Retrieved 1 June 2014. Dissertation submitted Rajib Gandhi University of Health Sciences
== External links == |
Cold urticaria | Cold urticaria (essentially meaning cold hives) is a disorder in large red welts called hives (urticaria) form on the skin after exposure to a cold stimulus. The hives are usually itchy and often the hands and feet will become itchy and swollen as well. Hives vary in size from about 7 mm in diameter to as big as about 27 mm or larger.
This disorder, or perhaps two disorders with the same clinical manifestations, can be inherited (familial cold urticaria) or acquired (primary acquired cold urticaria). The acquired form is most likely to begin between ages 18 and 25, although it can occur as early as 5 years old in some cases. Life-threatening risks include suffocation resulting from swollen tissue (pharyngeal angioedema) induced by cold foods or beverages, drowning after shock from swimming in cold water, and anaphylactic shock.
Types
Cold urticaria may be divided into the following types:
Primary cold contact urticaria
Primary cold contact urticaria is a cutaneous condition characterized by wheals, and occurs in rainy, windy weather, and after swimming in cold water and after contact with cold objects, including ice cubes.
Secondary cold contact urticaria
Secondary cold contact urticaria is a cutaneous condition characterized by wheals, due to serum abnormalities such as cryoglobulinemia or cryofibrinogenemia are extremely rare, and are then associated with other manifestations such as Raynauds phenomenon or purpura.
Reflex cold urticaria
Reflex cold urticaria is a cutaneous condition in which generalized cooling of the body induces widespread welting.
Familial cold urticaria
Familial cold urticaria (also properly known as familial cold autoinflammatory syndrome, FCAS) is an autosomal dominant condition characterized by rash, conjunctivitis, fever/chills and arthralgias elicited by exposure to cold - sometimes temperatures below 22 °C (72 °F).It has been mapped to CIAS1 and is a slightly milder member of the disease family including Muckle–Wells syndrome and NOMID. It is rare and is estimated as having a prevalence of 1 per million people and mainly affects Americans and Europeans.FCAS is one of the cryopyrin-associated periodic syndromes (CAPS) caused by mutations in the CIAS1/NALP3 (aka NLRP3) gene at location 1q44.The effect of FCAS on the quality of life of patients is far reaching. A survey of patients in the United States in 2008 found that "[t]o cope with their underlying disease and to try to avoid symptomatic, painful, flares patients reported limiting their work, school, family, and social activities. Seventy-eight percent of survey participants described an impact of the disease on their work, including absenteeism and impaired job advancement; frequently, they quit their job as a consequence of their disease".Treatment using anakinra (Kineret) has been shown effective for FCAS, although this does mean daily injections of the immunosuppressant into an area such as the lower abdomen. The monoclonal antibody canakinumab (Ilaris) is also used.
Signs and symptoms
When the body is exposed to the cold in individuals affected by the condition, hives appear and the skin in the affected area typically becomes itchy. Hives result from dilation of capillaries which allow fluid to flow out into the surrounding tissue which is the epidermis. They resolve when the body absorbs this fluid. The border of a hive is described as polycyclic, or made up of many circles, and changes as fluid leaks out and then is absorbed. Pressing on a hive causes the skin to blanch (turn pale as blood flow is interrupted), distinguishing it from a bruise or papule.
Hives may appear immediately or after a delay. Hives can last for a few minutes or a few days, and vary from person to person. Also, a burning sensation occurs. A serious reaction is most likely to occur for patients where the hives occur with less than 3 minutes of exposure (during a cold test).
Cause
The hives are a histamine reaction in response to cold stimuli, including a drastic drop in temperature, cold air, and cold water. There are many causes for cold hives, most are idiopathic (meaning they have no known cause). Some rare conditions can cause cold hives, and it can be useful to test for these conditions if the cold hives are in any way unusual.
Scientists from the USA National Institutes of Health have identified a genetic mutation in three unrelated families that causes a rare immune disorder characterized by excessive and impaired immune function: immune deficiency, autoimmunity, inflammatory skin disorders and cold-induced hives (cold urticaria).
"The mutation discovered occurs in a gene for phospholipase C-gamma2 (PLCG2), an enzyme involved in the activation of immune cells. The investigators have named the condition PLCG2-associated antibody deficiency and immune dysregulation, or PLAID."
Diagnosis
Diagnosis is typically obtained by an allergist or other licensed practitioner performing a cold test. During the cold test, a piece of ice is placed inside a thin plastic bag and held against the forearm, typically for 3–4 minutes. A positive result is a specific looking mark of raised red hives. The hives may be the shape of the ice, or it may radiate from the contact area of the ice. However, while these techniques assist in diagnosis, they do not provide information about temperature and stimulation time thresholds at which patients will start to develop symptoms, which is essential because it can establish disease severity and monitor the effectiveness of treatment.
Management
Management largely consists of avoiding exposures that could trigger a reaction and taking medicine to manage the reaction. The best treatment for this allergy is avoiding exposure to cold temperatures.
Avoiding triggers
Anything that lowers the skin temperature (not bodys core temperature) can trigger a reaction in affected people. Avoiding exposures limits the risk of a reaction. The reaction usually affects the body parts that are exposed, so cold air could trigger a reaction to exposed skin or in the breathing passages if cold air is inhaled. Risky exposures include:
Situations:
Cold weather, including snow: Exposure to cold or cool air can quickly trigger a reaction; for example walking by the open freezer cases in a supermarket.
Air conditioning: Entering a cool building during a summer day can result in a reaction.
Cool/cold surfaces: Sitting on sidewalks which are cool, leaning on or grabbing a cold pole can result in hives forming on the area which had contact with the cool surfaces.
Cold IV lines: Sometimes IV lines are cold, which can result in a reaction. A line of hives may appear within 6 to 8 inches from the IV site in the pattern of a line going up the limb.
Activities:
Cold foods and drinks: Eating or drinking cold or cool substances such as ice cream or iced tea may result in a reaction inside the mouth and throat.
Swimming: Swimming can be especially dangerous, as the rapid heart rate combined with the onset of hives can lead to hypotension, shock, and drowning.
Sweat: A reaction may even occur on a warm day when there is sweat on the skin, since the reaction is triggered by skin temperature, not core temperature. If there is a breeze, it will rapidly cool the skin and create hives.
Restriction of blood flow: Activities which cause tense muscles and reduce blood flow can cool the body parts enough to trigger itching and hives.
Drugs
The first-line therapy is symptomatic relief with second-generation H1-antihistamines. If standard dosing is ineffective, increasing dosages up to fourfold is recommended to control symptoms.The second-generation H1-antihistamine rupatadine was found to significantly reduce the development of chronic cold urticaria symptom without an increase in adverse effects at doses of 200 mg and 40 mg.Allergy medications containing antihistamines such as diphenhydramine (Benadryl), cetirizine (Zyrtec), loratadine (Claritin), cyproheptadine (Periactin), and fexofenadine (Allegra) may be taken orally to prevent and relieve some of the hives. For those who have severe anaphylactic reactions, a prescribed medicine such as doxepin, taken daily, should help to prevent and/or lessen the likelihood of a reaction and thus, anaphylaxis. The effectiveness of topical antihistamine creams against hives induced by cold temperature has not been evaluated.Cold hives can result in a potentially serious or even fatal systemic reaction (anaphylactic shock). People with cold hives may have to carry an injectable form of epinephrine (like Epi-pen or Twinject) for use in the event of a serious reaction.Studies have found that omalizumab (Xolair) may be an effective and safe treatment for cold urticaria in patients who do not sufficiently respond to standard treatments.Ebastine has been proposed as an approach to prevent acquired cold urticaria.
See also
Amyloidosis
Cholinergic urticaria, a similar hives reaction in response to heat
Aquagenic urticaria
Diascopy
Erythema
Goose bumps, an unrelated, normal response to cold temperatures
List of cutaneous conditions
Skin lesion
Plaid syndrome
References
== External links == |
Toxic oil syndrome | Toxic oil syndrome
(TOS) or simply toxic syndrome (Spanish: síndrome del aceite tóxico or síndrome tóxico) is a musculoskeletal disease. A 1981 outbreak in Spain which affected about 20,000 people, with over 300 dying within a few months and a few thousand remaining disabled, is thought to have been caused by contaminated colza (rapeseed) oil. It was unique because of its size, the novelty of the clinical condition, and the complexity of its aetiology. Its first appearance was as a lung disease, with unusual features, though the symptoms initially resembled a lung infection. The disease appeared to be restricted to certain geographical localities, and several members of a family could be affected, even while their neighbours had no symptoms. Following the acute phase, a range of other chronic symptoms was apparent.
Alternative mechanisms
The conclusion of the Joint WHO/CISAT Scientific Committee for the Toxic Oil Syndrome from 2002, that oil was the cause for TOS, is based only on epidemiological evidence, since up to now, experimental studies performed in a variety of laboratory animals have failed to reproduce the symptoms of human TOS. None of the in vivo or in vitro studies performed with toxic-oil-specific components, such as fatty acid anilides, and esters of 3-(N-phenylamino)-1,2-propanediol (abbreviated as PAP), have provided evidence that these markers are causally involved in the pathogenesis of TOS.Specifically, three possible causative agents of TOS are PAP (3-(N-phenylamino)-1,2-propanediol), the 1,2-dioleoyl ester of PAP (abbreviated OOPAP), and the 3-oleoyl ester of PAP (abbreviated OPAP). These three compounds are formed by means of similar chemical processes, and oil that contains one of the three substances is likely to contain the other two. Oil samples that are suspected to have been ingested by people who later developed TOS often contain all three of these contaminants (among other substances), but are most likely to contain OOPAP. However, when these three substances were given to laboratory animals, OOPAP was not acutely toxic, PAP was toxic only after injection, but not after oral administration, and OPAP was toxic only after injection of high doses. Therefore, none of these three substances is thought to cause TOS. Similar results were obtained after administration of fatty acid anilides.Data discrepancies combined with both a high level of secrecy surrounding the huge investigation and the fact that the first cases of the syndrome were located in Madrid (near the U.S. military base in Torrejón de Ardoz) spread the idea of a conspiracy. Several of those affected by TOS claim they never consumed any of the tainted oil products. Furthermore, the tainted oil was primarily sold in low-cost street markets; yet, a considerable percentage of the patients were wealthy. Another theory suggests the toxic reaction was triggered by organophosphate poisoning (e. g., from pesticide residues in tomatoes) and covered up by the Spanish government and the WHO.
See also
Eosinophilia-myalgia syndrome
Ginger Jake
Health crisis
The Jungle
List of food contamination incidents
References
External links
WHO Report: Toxic Oil Syndrome - Ten years of progress |
Tumoral calcinosis | Tumoral calcinosis is a rare condition in which there is calcium deposition in the soft tissue in periarticular location, around joints, outside the joint capsule. They are frequently (0.5–3%) seen in patients undergoing renal dialysis. Clinically also known as hyperphosphatemic familial tumoral calcinosis (HFTC), is often caused by genetic mutations in genes that regulate phosphate physiology in the body (leading to too much phosphate (hyperphosphatemia)). Best described genes that harbour mutations in humans are FGF-23, Klotho (KL), or GALNT3. A zebrafish animal model with reduced GALNT3 expression also showed HFTC-like phenotype, indicating an evolutionary conserved mechanism that is involved in developing tumoral calcinosis.
Clinical features
The name indicates calcinosis (calcium deposition) which resembles tumor (like a new growth). They are not true neoplasms – they dont have dividing cells. They are just deposition of inorganic calcium with serum exudate. Children and adolescents (6 to 25 years) are the most commonly affected. The symptom that the accumulations cause is not pain but swelling around joints. They have propensity to enlarge progressively and ulcerate the overlying skin and extrude. They are most common around shoulders, hips and elbows. Laboratory evaluation reveal normal serum calcium levels and hyperphosphatemia. Rarely ALP (alkaline phosphatase – an enzyme active at sites of bone formation) may be elevated. Treatment is normalization of serum phosphate levels and resection of lesions. Surgical removal should be complete and if part of it is left, recurrence is likely to occur. Cutting through the excised calcium deposition reveals semifluid calcium suspension in albumin encapsulated by fibrous tissue.
Additional images
References
External links
Genetests/NCBI/NIH/UW entries on Hyperphosphatemic Familial Tumoral Calcinosis |
Duplicated ureter | Duplicated ureter or Duplex Collecting System is a congenital condition in which the ureteric bud, the embryological origin of the ureter, splits (or arises twice), resulting in two ureters draining a single kidney. It is the most common renal abnormality, occurring in approximately 1% of the population.
Pathophysiology
Ureteral development begins in the human fetus around the 4th week of embryonic development. A ureteric bud, arising from the mesonephric (or Wolffian) duct, gives rise to the ureter, as well as other parts of the collective system. In the case of a duplicated ureter, the ureteric bud either splits or arises twice. In most cases, the kidney is divided into two parts, an upper and lower lobe, with some overlap due to intermingling of collecting tubules. However, in some cases the division is so complete as to give rise to two separate parts, each with its own renal pelvis and ureter.
Diagnosis
Prenatally diagnosed hydronephrosis (fluid-filled kidneys) suggest post-natal follow-up examination.
The strongest neo-natal presentation is urinary tract infection. A hydronephrotic kidney may present as a palpable abdominal mass in the newborn, and may suggest an ectopic ureter or ureterocele.
In older children, ureteral duplication may present as:
Urinary tract infection - most commonly due to vesicoureteral reflux (flow of urine from the bladder into the ureter, rather than vice versa).
Urinary incontinence in females occurs in cases of ectopic ureter entering the vagina, urethra or vestibule.
Classification
Ureteral duplication is either of:
Partial
I.e., the two ureters drain into the bladder via a single common ureter. Partial, or incomplete, ureteral duplication is rarely clinically significant.
Complete
In which the two ureters drain separately. Complete ureteral duplication may result in one ureter opening normally into the bladder, and the other being ectopic, ending in the vagina, the urethra or the vulval vestibule. These cases occur when the ureteric bud arises twice (rather than splitting).
Prevalence
Duplicated ureter is the most common renal abnormality, occurring in approximately 1% of the population. It occurs in about 0.7% of healthy adults and in 2% to 4% of people with urinary tract issues.
Race
Duplicated ureter is more common in White Americans than in African-Americans.
Sex
Duplicated ureter is more common in females. However, this may be due to the higher frequency of urinary tract infections in females, leading to a higher rate of diagnosis of duplicated ureter.
Complications
A duplicated ureter increased the risk of:
Hydronephrosis
Urinary tract infection (UTI)
Vesicoureteral reflux
Incontinence
See also
Ureterocele
Ectopic ureter
Kidney development
== References == |
Post-thrombotic syndrome | Post-thrombotic syndrome (PTS), also called postphlebitic syndrome and venous stress disorder is a medical condition that may occur as a long-term complication of deep vein thrombosis (DVT).
Signs and symptoms
Signs and symptoms of PTS in the leg may include:
pain (aching or cramping)
heaviness
itching or tingling
swelling (edema)
varicose veins
brownish or reddish skin discoloration
ulcerThese signs and symptoms may vary among patients and over time. With PTS, these symptoms typically are worse after walking or standing for long periods of time and improve with resting or elevating the leg.PTS lowers a persons quality of life after DVT, specifically with regards to physical and psychological symptoms and limitations in daily activities.
Cause
Despite outgoing research, the cause of PTS is not entirely clear. Inflammation is thought to play a role as well as damage to the venous valves from the thrombus itself. This valvular incompetence combined with persistent venous obstruction from thrombus increases the pressure in veins and capillaries. Venous hypertension induces a rupture of small superficial veins, subcutaneous hemorrhage and an increase of tissue permeability. That is manifested by pain, swelling, discoloration, and even ulceration.
Risk factors
The following factors increase the risk of developing PTS:
age > 65
proximal DVT
a second DVT in same leg as first DVT (recurrent ipsilateral DVT)
persistent DVT symptoms 1 month after DVT diagnosis
obesity
poor quality of anticoagulation control (i.e. dose too low) during the first 3 months of treatment
Diagnosis
When physicians find a DVT in the clinical history of their patients, a postthrombotic syndrome is possible if the patients have suggestive symptoms. Ultrasonography for deep venous thrombosis must be performed to evaluate the situation: the degree of obstruction by clots, the location of these clots, and the detection of deep and/or superficial venous insufficiency. Since signs and symptoms of DVT and PTS may be quite similar, a diagnosis of PTS should be delayed for 3–6 months after DVT diagnosis so an appropriate diagnosis can be made.
Prevention
Prevention of PTS begins with prevention of initial and recurrent DVT. For people hospitalized at high-risk of DVT, prevention methods may include early ambulation, use of compression stockings or electrostimulation devices, and/or anticoagulant medications. Elastic compression stockings may reduce the occurrence of PTS after clinically confirmed DVT.Increasingly, catheter-directed thrombolysis has been employed. This is a procedure in which a vascular interventionist will break up a clot using a variety of methods.For people who have already had a single DVT event, the best way to prevent a second DVT is appropriate anticoagulation therapy.A second prevention approach may be weight loss for those who are overweight or obese. Increased weight can put more stress and pressure on leg veins, and can predispose patients to developing PTS.
Treatment
Treatment options for PTS include proper leg elevation, compression therapy with elastic stockings, or electrostimulation devices, pharmacotherapy (pentoxifylline), herbal remedies (such as horse chestnut, rutosides), and wound care for leg ulcers.The benefits of compression bandages is unclear. They may be useful to treat edemas.
Upper extremities
Patients with upper-extremity DVT may develop upper-extremity PTS, but the incidence is lower than that for lower-extremity PTS (15–25%). No treatment or prevention methods are established, but patients with upper-extremity PTS may wear a compression sleeve for persistent symptoms.
Epidemiology
PTS can affect 23 to 60% of patients in the two years following DVT of the leg. Of those, 10% may go on to develop severe PTS, involving venous ulcers.
Society and culture
Treatment of PTS adds significantly to the cost of treating DVT. The annual health care cost of PTS in the United States has been estimated at $200 million, with costs over $3800 per patient in the first year alone, and increasing with disease severity. PTS also causes lost work productivity: people with severe PTS and venous ulcers lose up to 2 work days per year.
Research directions
The field of PTS still holds many unanswered questions that are important targets for more research. Those include
Fully defining the pathophysiology of PTS, including the role of inflammation and residual thrombus after completion of an appropriate duration of anticoagulant therapy
Developing a PTS risk prediction model
Role of thrombolytic ("clot-busting") drugs in PTS prevention
Defining the true efficacy of elastic compression stockings for PTS prevention (and if effective, elucidating the minimum compression strength necessary and the optimal timing and duration of compression therapy)
Whether PTS prevention methods are necessary for patients with asymptomatic or distal DVT
Additional treatment options for PTS with demonstrated safety and efficacy (compression and pharmacologic therapies)
References
== External links == |
Phlegmasia cerulea dolens | Phlegmasia cerulea dolens (PCD) (literally: painful blue inflammation), not to be confused with preceding phlegmasia alba dolens, is an uncommon severe form of lower extremity deep venous thrombosis (DVT) that obstructs blood outflow from a vein. Upper extremity PCD is less common, occurring in under 10% of all cases. PCD results from extensive thrombotic occlusion (blockage by a thrombus) of extremity veins, most commonly an "iliofemoral" DVT of the iliac vein and/or common femoral vein. It is a medical emergency requiring immediate evaluation and treatment.
Symptoms and signs
Primary symptoms
It is characterized by progressive lower extremity edema distal to the thigh, tight shiny skin, cyanosis (inadequate blood oxygenation), petechiae or purpura, and sudden severe pain of the affected limb in proportion to the level of venous blockage. Patients often have difficulty walking. Blisters, bullae, paresthesias, and motor weakness may develop in severe cases, along with gangrene in ~50% of cases. Distal pulses are palpable early on but may diminish over time, and doppler signal can be usually heard throughout disease progression. The left limb is more commonly affected due to its vascular anatomy (the right internal iliac artery directly overlies the left iliac vein).
Associated diseases
PCD is associated with an underlying malignancy in 20-40% of cases. There is a high risk of massive pulmonary embolism, even under anticoagulation.
Etiology
Risk factors, present in around 50% of documented cases, include malignancy, hyper-coagulable states, cardiac disease, venous stasis, venous insufficiency, May-Thurner syndrome (right iliac artery compressing the left iliac vein that runs beneath it), surgery, trauma, pregnancy, inferior vena cava (IVC) filter, hormone therapy, oral contraceptives, prolonged immobilization, inflammatory bowel disease, heart failure, and central venous catheters. Etiology is unknown in ~10% of PCD cases.
Pathophysiology
When a thrombus occludes an extremity vein, pressure backs up in the venous system leading plasma fluid to leak out into the interstitium of the affected limb. This increases the pressure of that limb compartment, which can collapse the arteries and lead to acute ischemia, gangrene, hypovolemia, and hemodynamic instability.
Diagnosis
PCD is best diagnosed with contrast venography, but venous duplex ultrasonography is used more commonly in clinical practice. Magnetic resonance and computed tomography venography can also be used.
Differential Diagnosis
DDx is as follows:
Cellulitis
Venous insufficiency
Superficial thrombophlebitis
DVT
Arterial embolism
Lymphedema
Ruptured Bakers cyst
Treatment
Treatment for PCD includes immediate anticoagulation, fluid resuscitation, bed rest, limb elevation above 60º, limb wrap to reduce pain and edema, and either catheter-based thrombolysis, percutaneous transluminal angioplasty, or surgical venous thrombectomy +/- fasciotomy to remove the blood clot. Some people also suggest an IVC filter before thrombolysis.
Prognosis
PCD is fully reversible if the causal venous thrombus is promptly removed. In the 40-60% of people who go on to develop venous gangrene, there is a 20-50% risk of amputation and 20-40% mortality rate. Following PCD resolution patients are more likely to develop venous insufficiency and post-thrombotic syndromeA grading system has been established:
Grade I = non-complicated (no blistering, strong sensory-motor function and strong distal pulses)
Grade II = impending venous gangrene (blistering, weak sensory-motor function and weak distal pulses)
Grade III = venous gangrene
Epidemiology
PCD is most likely to occur in people in their 50s and 60s, but can occur as early as 6 months old. There is slight male predominance of around 1.5:1.
History
This phenomenon was first discovered by Fabricus Hildanius in the 16th century, and was officially termed "phlegmasia cerulea dolens" by Gregoire in 1938. Phlegmasia originates from the Greek root phlegma (inflammation), cerulea originates from Latin root caeruleus (dark blue), and dolens originates from Latin word dolens (suffering).
References
== External links == |
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