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Dysbarism | Dysbarism refers to medical conditions resulting from changes in ambient pressure. Various activities are associated with pressure changes. Underwater diving is the most frequently cited example, but pressure changes also affect people who work in other pressurized environments (for example, caisson workers), and people who move between different altitudes.
Ambient pressure
Ambient pressure is the pressure in the water around the diver (or the air, with caisson workers etc.). As a diver descends, the ambient pressure increases. At 10 meters (33 feet) in salt water, it is twice the normal pressure than that at the surface. At 40 meters (a common recommended limit for recreational diving) it is 5 times the pressure than at sea level.
Pressure decreases as we rise above sea level, but less dramatically. At 3000 feet altitude (almost 1000 meters), the ambient pressure is almost 90% of sea level pressure. Ambient pressure does not drop to 50% of sea level pressure until 20,000 feet or 6,000 meters altitude.
Effects of pressure on the body
Direct effects on tissues
This is not of practical importance, because the body is mostly composed of barely compressible materials such as water. People often wonder whether scuba divers feel their body being crushed by the pressure, but divers would have to reach depths of thousands of feet before their flesh began to suffer significant compression.
Gas filled spaces
Gas is very compressible. Humans have many air spaces: sinuses, middle ears, gas in our bowels, cavities in our teeth, and largest of all, our lungs. On land in our daily lives, the pressure in our air spaces is usually exactly the same as the pressure outside, because our air spaces are connected to the outside world. If there was a pressure difference between the outside world and one of our air spaces, then we experience painful pressure on the walls of that air space, as air pushes from the higher-pressure side to the lower-pressure side. This is why we sometimes get painful ears on air trips.
Dissolved gas
A percentage of the gas we breathe (air) is always dissolved in our blood, like the gas dissolved in a carbonated drink bottle with the lid on. If a person moves to a higher ambient pressure, then the gas inhaled is at a higher pressure, so more of it dissolves in the blood and diffuses into body tissues (Henrys and Ficks gas laws). If they slowly move back to a lower pressure, then the extra gas comes out slowly until they are back to their normal amount of dissolved gas. But if they move quickly to a lower ambient pressure, then the gas comes out of our blood and tissues violently, in large bubbles, in the same way that quickly removing the cap from a bottle of soft drink produces far more bubbles than slowly opening the bottle.
Types of dysbarism
Different types of illness result from increases in pressure (for example, descent during an underwater dive, descent during a plane flight), versus decreases in pressure (for example, coming up from a caisson, or ascending a mountain). Dysbarism comprises several types of illness:
Decompression sickness (DCS)
Decompression sickness, also called caisson workers disease and the bends, is the most well-known complication of scuba diving. It occurs as divers ascend, and often from ascending too fast or without doing decompression stops. Bubbles are large enough and numerous enough to cause physical injury. It is quite possible that all divers have microbubbles in their blood to some extent, but that most of the time these bubbles are so few and so small that they cause no harm. When DCS occurs, bubbles disrupt tissues in the joints, brain, spinal cord, lungs, and other organs. Symptoms vary enormously. DCS may be as subtle as unusual tiredness after a dive, or an aching elbow, or a mottled skin rash. Or, it may present dramatically, with unconsciousness, seizures, paralysis, shortness of breath, or death. Paraplegia is not uncommon.
Nitrogen narcosis
Nitrogen narcosis is also called “L’ivresse des grandes profondeurs” or "rapture of the deep". Nitrogen comprises 79% of the air, but at surface pressures it has no sedating effect. At greater depths, however, nitrogen affects the brain in the same way as nitrous oxide (also known as laughing gas) and other anaesthetic gases. The effect is similar to the effects of alcohol, and to some extent there is cross-tolerance. Unlike alcohol, the onset and disappearance are near instantaneous. A diver may be quite clear-headed at 20 meters, and yet giddy and silly at 30 meters. Ascending to 20 meters will almost instantly clear the head.
High pressure nervous syndrome (HPNS)
Barotrauma
Barotrauma is injury caused by pressure effects on gas spaces. This may occur during ascent or descent. The ears are the most commonly affected body part. The most serious injury is lung barotrauma, which can result in pneumothorax, pneumomediastinum, pneumopericardium, subcutaneous emphysema, and arterial gas embolism. All divers, commercial air travelers, people traveling overland between different altitudes, and people who work in pressurized environments have had to deal with some degree of barotrauma effect upon their ears, sinuses, and other air spaces. At the most extreme, barotrauma can cause ruptured eardrums, bleeding sinuses, exploding tooth cavities, and the lung injuries described above. This is the reason why divers follow a procedure of not holding their breath during ascent. By breathing continuously, they keep the airways open and avoid pressure differences between their lungs and ambient pressure.
Arterial gas embolism (AGE)
Arterial gas embolism (AGE) is a complication of lung barotrauma of ascent. It occurs when breathing gas is introduced to the circulation on the arterial side via lung over-pressure trauma. AGE can present in similar ways to arterial blockages seen in other medical situations. Affected people may suffer strokes, with paralysis or numbness down one side; they may suffer heart attacks; they may suffer pulmonary embolism with shortness of breath and chest pain. It is often impossible to distinguish AGE from DCS, but luckily it is rarely necessary for physicians to be able to distinguish between the two, as treatment is the same. Sometimes AGE and DCS are lumped into a single entity, Decompression Illness (DCI).
Classification
In addition to the foregoing, dysbarism is sometimes classified according to the source of the excess gas, with "trapped gas" dysbarism referring to the expansion of pockets that were already in a gaseous state in the body, and "evolved gas" dysbarism referring to gasses (primarily nitrogen or helium) dissolved in the body coming out of solution to form gas bubbles.
See also
List of diving hazards and precautions – Hazards associated with underwater diving
Dysbaric osteonecrosis – Ischemic bone disease caused by decompression bubbles
References
== External links == |
Tricuspid valve stenosis | Tricuspid valve stenosis is a valvular heart disease that narrows the opening of the hearts tricuspid valve. It is a relatively rare condition that causes stenosis (increased restriction of blood flow through the valve).
Cause
Causes of tricuspid valve stenosis are:
Rheumatic disease
Carcinoid syndrome
Pacemaker leads (complication)
Diagnosis
A mild diastolic murmur can be heard during auscultation caused by the blood flow through the stenotic valve. It is best heard over the left sternal border with rumbling character and tricuspid opening snap with wide-splitting S2. The diagnosis will typically be confirmed by an echocardiograph, which will also allow the physician to assess its severity.
Treatment
Tricuspid valve stenosis itself usually does not require treatment. If stenosis is mild, monitoring the condition closely suffices. However, severe stenosis, or damage to other valves in the heart, may require surgical repair or replacement.
The treatment is usually by surgery (tricuspid valve replacement) or percutaneous balloon valvuloplasty. The resultant tricuspid regurgitation from percutaneous treatment is better tolerated than the insufficiency occurring during mitral valvuloplasty.
See also
Echocardiography
Tricuspid valve
References
== External links == |
Brain abscess | Brain abscess (or cerebral abscess) is an abscess caused by inflammation and collection of infected material, coming from local (ear infection, dental abscess, infection of paranasal sinuses, infection of the mastoid air cells of the temporal bone, epidural abscess) or remote (lung, heart, kidney etc.) infectious sources, within the brain tissue. The infection may also be introduced through a skull fracture following a head trauma or surgical procedures. Brain abscess is usually associated with congenital heart disease in young children. It may occur at any age but is most frequent in the third decade of life.
Signs and symptoms
Fever, headache, and neurological problems, while classic, only occur in 20% of people with brain abscess.The famous triad of fever, headache and focal neurologic findings are highly suggestive of brain abscess. These symptoms are caused by a combination of increased intracranial pressure due to a space-occupying lesion (headache, vomiting, confusion, coma), infection (fever, fatigue etc.) and focal neurologic brain tissue damage (hemiparesis, aphasia etc.).The most frequent presenting symptoms are headache, drowsiness, confusion, seizures, hemiparesis or speech difficulties together with fever with a rapidly progressive course. Headache is characteristically worse at night and in the morning, as the intracranial pressure naturally increases when in the supine position. This elevation similarly stimulates the medullary vomiting center and area postrema, leading to morning vomiting.Other symptoms and findings depend largely on the specific location of the abscess in the brain. An abscess in the cerebellum, for instance, may cause additional complaints as a result of brain stem compression and hydrocephalus. Neurological examination may reveal a stiff neck in occasional cases (erroneously suggesting meningitis).
Pathophysiology
Bacterial
Anaerobic and microaerophilic cocci and gram-negative and gram-positive anaerobic bacilli are the predominant bacterial isolates. Many brain abscesses are polymicrobial. The predominant organisms include: Staphylococcus aureus, aerobic and anaerobic streptococci (especially Streptococcus intermedius), Bacteroides, Prevotella, and Fusobacterium species, Enterobacteriaceae, Pseudomonas species, and other anaerobes. Less common organisms include: Haemophillus influenzae, Streptococcus pneumoniae and Neisseria meningitidis.Bacterial abscesses rarely (if ever) arise de novo within the brain, although establishing a cause can be difficult in many cases. There is almost always a primary lesion elsewhere in the body that must be sought assiduously, because failure to treat the primary lesion will result in relapse. In cases of trauma, for example in compound skull fractures where fragments of bone are pushed into the substance of the brain, the cause of the abscess is obvious. Similarly, bullets and other foreign bodies may become sources of infection if left in place. The location of the primary lesion may be suggested by the location of the abscess: infections of the middle ear result in lesions in the middle and posterior cranial fossae; congenital heart disease with right-to-left shunts often result in abscesses in the distribution of the middle cerebral artery; and infection of the frontal and ethmoid sinuses usually results in collection in the subdural sinuses.
Other organisms
Fungi and parasites may also cause the disease. Fungi and parasites are especially associated with immunocompromised patients. Other causes include: Nocardia asteroides, Mycobacterium, Fungi (e.g. Aspergillus, Candida, Cryptococcus, Mucorales, Coccidioides, Histoplasma capsulatum, Blastomyces dermatitidis, Bipolaris, Exophiala dermatitidis, Curvularia pallescens, Ochroconis gallopava, Ramichloridium mackenziei, Pseudallescheria boydii), Protozoa (e.g. Toxoplasma gondii, Entamoeba histolytica, Trypanosoma cruzi, Schistosoma, Paragonimus), and Helminths (e.g. Taenia solium). Organisms that are most frequently associated with brain abscess in patients with AIDS are poliovirus, Toxoplasma gondii, and Cryptococcus neoformans, though in infection with the latter organism, symptoms of meningitis generally predominate.These organisms are associated with certain predisposing conditions:
Sinus and dental infections—Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli (e.g. Prevotella, Porphyromonas, Bacteroides), Fusobacterium, S. aureus, and Enterobacteriaceae
Penetrating trauma—S. aureus, aerobic streptococci, Enterobacteriaceae, and Clostridium spp.
Pulmonary infections—Aerobic and anaerobic streptococci, anaerobic gram-negative bacilli (e.g. Prevotella, Porphyromonas, Bacteroides), Fusobacterium, Actinomyces, and Nocardia
Congenital heart disease—Aerobic and microaerophilic streptococci, and S. aureus
HIV infection—T. gondii, Mycobacterium, Nocardia, Cryptococcus, and Listeria monocytogenes
Transplantation—Aspergillus, Candida, Cryptococcus, Mucorales, Nocardia, and T. gondii
Neutropenia—Aerobic gram-negative bacilli, Aspergillus, Candida, and Mucorales
Diagnosis
The diagnosis is established by a computed tomography (CT) (with contrast) examination. At the initial phase of the inflammation (which is referred to as cerebritis), the immature lesion does not have a capsule and it may be difficult to distinguish it from other space-occupying lesions or infarcts of the brain. Within 4–5 days the inflammation and the concomitant dead brain tissue are surrounded with a capsule, which gives the lesion the famous ring-enhancing lesion appearance on CT examination with contrast (since intravenously applied contrast material can not pass through the capsule, it is collected around the lesion and looks as a ring surrounding the relatively dark lesion). Lumbar puncture procedure, which is performed in many infectious disorders of the central nervous system is contraindicated in this condition (as it is in all space-occupying lesions of the brain) because removing a certain portion of the cerebrospinal fluid may alter the concrete intracranial pressure balances and causes the brain tissue to move across structures within the skull (brain herniation).Ring enhancement may also be observed in cerebral hemorrhages (bleeding) and some brain tumors. However, in the presence of the rapidly progressive course with fever, focal neurologic findings (hemiparesis, aphasia etc.) and signs of increased intracranial pressure, the most likely diagnosis should be the brain abscess.
Treatment
The treatment includes lowering the increased intracranial pressure and starting intravenous antibiotics (and meanwhile identifying the causative organism mainly by blood culture studies).Hyperbaric oxygen therapy (HBO2 or HBOT) is indicated as a primary and adjunct treatment which provides four primary functions.
Firstly, HBOT reduces intracranial pressure. Secondly, high partial pressures of oxygen act as a bactericide and thus inhibits the anaerobic and functionally anaerobic flora common in brain abscess. Third, HBOT optimizes the immune function thus enhancing the host defense mechanisms and fourth, HBOT has been found to be of benefit when brain abscess is concomitant with cranial osteomyelitis.
Secondary functions of HBOT include increased stem cell production and up-regulation of VEGF which aid in the healing and recovery process.Surgical drainage of the abscess remains part of the standard management of bacterial brain abscesses. The location and treatment of the primary lesion also crucial, as is the removal of any foreign material (bone, dirt, bullets, and so forth).
There are few exceptions to this rule: Haemophilus influenzae meningitis is often associated with subdural effusions that are mistaken for subdural empyemas. These effusions resolve with antibiotics and require no surgical treatment. Tuberculosis can produce brain abscesses that look identical to conventional bacterial abscesses on CT imaging. Surgical drainage or aspiration is often necessary to identify Mycobacterium tuberculosis, but once the diagnosis is made no further surgical intervention is necessary.
CT guided stereotactic aspiration is also indicated in the treatment of brain abscess. The use of pre-operative imaging, intervention with post-operative clinical and biochemical monitoring used to manage brain abscesses today dates back to the Pennybacker system pioneered by Somerset, Kentucky-born neurosurgeon Joseph Buford Pennybacker, director of the neurosurgery department of the Radcliffe Infirmary, Oxford from 1952 to 1971.
Prognosis
While death occurs in about 10% of cases, people do well about 70% of the time. This is a large improvement from the 1960s due to improved ability to image the head, more effective neurosurgery and more effective antibiotics.
References
External links
Brain abscess at eMedicine
MR Diagnosis MedPix Imaging Brain Abscess |
Chronic venous insufficiency | Chronic venous insufficiency (CVI) is a medical condition in which blood pools in the veins, straining the walls of the vein. The most common cause of CVI is superficial venous reflux which is a treatable condition. As functional venous valves are required to provide for efficient blood return from the lower extremities, this condition typically affects the legs. If the impaired vein function causes significant symptoms, such as swelling and ulcer formation, it is referred to as chronic venous disease. It is sometimes called chronic peripheral venous insufficiency and should not be confused with post-thrombotic syndrome in which the deep veins have been damaged by previous deep vein thrombosis.
Most cases of CVI can be improved with treatments to the superficial venous system or stenting the deep system. Varicose veins for example can now be treated by local anesthetic endovenous surgery.
Rates of CVI are higher in women than in men. Other risk factors include genetics, smoking, obesity, pregnancy, and prolonged standing.
Signs and symptoms
Signs and symptoms of CVI in the leg include the following:
Varicose veins
Itching (pruritus)
Hyperpigmentation
Phlebetic lymphedema
Chronic swelling of the legs and ankles
Venous ulcerationCVI in the leg may cause the following:
Venous stasis
Ulcers
Stasis dermatitis, also known as varicose eczema
Contact dermatitis, a disrupted epidermal barrier due to venous insufficiency, making patients more susceptible than the general population to contact sensitization and subsequent dermatitis.
Atrophie blanche, an end point of a variety of conditions that appears as atrophic plaques of ivory white skin with telangiectasias. It represents late sequelae of lipodermatosclerosis where the skin has lost its nutrient blood flow.
Lipodermatosclerosis, an indurated plaque in the medial malleolus.
Malignancy, malignant degeneration being a rare but important complication of venous disease since tumors that develop in the setting of an ulcer tend to be more aggressive.
Pain, a feature of venous disease often overlooked and commonly undertreated.
Anxiety
Depression
Inflammation
Cellulitis
Causes
The most common cause of chronic venous insufficiency is reflux of the venous valves of superficial veins. This may in turn be caused by several conditions:
Deep vein thrombosis (DVT), that is, blood clots in the deep veins. Chronic venous insufficiency caused by DVT may be described as postthrombotic syndrome. DVT triggers an inflammatory response subsequently injuring the vein wall.
Superficial vein thrombosis.
Phlebitis
May–Thurner syndrome. This is a rare condition in which blood clots occur in the iliofemoral vein due to compression of the blood vessels in the leg. The specific problem is compression of the left common iliac vein by the overlying right common iliac artery. Many May-Thurner compressions are overlooked when there is no blood clot. More and more of them get nowadays diagnosed and treated (by stenting) due to advanced imaging techniques.Deep and superficial vein thrombosis may in turn be caused by thrombophilia, which is an increased propensity of forming blood clots.Arteriovenous fistula (an abnormal connection or passageway between an artery and a vein) may cause chronic venous insufficiency even with working vein valves.
Diagnosis
History and examination by a clinician for characteristic signs and symptoms are sufficient in many cases in ruling out systemic causes of venous hypertension such as hypervolemia and heart failure. A duplex ultrasound (doppler ultrasonography and b-mode) can detect venous obstruction or valvular incompetence as the cause, and is used for planning venous ablation procedures, but it is not necessary in suspected venous insufficiency where surgical intervention is not indicated.Insufficiency within a venous segment is defined as reflux of more than 0.5 seconds with distal compression. Invasive venography can be used in patients who may require surgery or have suspicion of venous stenosis. Other modalities that may be employed are: ankle-brachial index to exclude arterial pathology, air or photoplethysmography, intravascular ultrasound, and ambulatory venous pressures, which provides a global assessment of venous competence. Venous plethysmography can assess for reflux and muscle pump dysfunction but the test is laborious and rarely done.The venous filling time after the patient is asked to stand up from a seated position also is used to assess for CVI. Rapid filling of the legs less than 20 seconds is abnormal.
Classification
CEAP classification is based on Clinical, Etiological (causal), Anatomical, and Pathophysiological factors. According to Widmer Classification for assessment of chronic venous insufficiency (CVI), diagnosis of chronic venous insufficiency is clearly differentiated from varicose veins. It has been developed to guide decision-making in chronic venous insufficiency evaluation and treatment.The CEAP classification for CVI is as follows:
Clinical
C0: no obvious feature of venous disease
C1: the presence of reticular or spider veins
C2: Obvious varicose veins
C3: Presence of edema but no skin changes
C4: skin discoloration, pigmentation
C5: Ulcer that has healed
C6: Acute ulcer
Etiology
Primary
Secondary (trauma, birth control pill)
Congenital (Klipper trenaunay)
No cause is known
Anatomic
Superficial
Deep
Perforator
No obvious anatomic location
Pathophysiology
Obstruction, thrombosis
Reflux
Obstruction and reflux
No venous pathology
Management
Conservative
Conservative treatment of CVI in the leg involves symptomatic treatment and efforts to prevent the condition from getting worse instead of effecting a cure. This may include
Manual compression lymphatic massage therapy
Red vine leaf extract may have a therapeutic benefit.
Sequential compression pump
Ankle pump
Compression stockings
Blood pressure medicine
Hydroxyethylrutoside medication
Frequent periods of rest elevating the legs above the heart level
Tilting the bed so that the feet are above the heart. This may be achieved by using a 20 cm (7-inch) bed wedge or sleeping in a 6 degree Trendelenburg position.
Surgical
Surgical treatment of CVI attempts a cure by physically changing the veins with incompetent valves. Surgical treatments for CVI include the following:
Ligation. Tying off a vein to prevent blood flow
Vein stripping. Removal of the vein.
Surgical repair.
Endovenous Laser Ablation
Vein transplant.
Subfascial endoscopic perforator surgery. Tying off the vein with an endoscope.
Valve repair (experimental)
Valve transposition (experimental)
Hemodynamic surgeries.Venous insufficiency conservative, hemodynamic and ambulatory treatment (CHIVA method) is an ultrasound guided, minimally invasive surgery strategic for the treatment of varicose veins, performed under local anaesthetic.
Prognosis
CVI is not a benign disorder and, with its progression, can lead to morbidity. Venous ulcers are common and very difficult to treat. Chronic venous ulcers are painful and debilitating. Even with treatment, recurrences are common if venous hypertension persists. Nearly 60% develop phlebitis which often progresses to deep vein thrombosis in more than 50% of patients. The venous insufficiency can also lead to severe hemorrhage. Surgery for CVI remains unsatisfactory despite the availability of numerous procedures.
See also
References
== External links == |
Testicular cancer | Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility.Risk factors include an undescended testis, family history of the disease, and previous history of testicular cancer. The most common type is germ cell tumors which are divided into seminomas and nonseminomas. Other types include sex-cord stromal tumors and lymphomas. Diagnosis is typically based on a physical exam, ultrasound, and blood tests. Surgical removal of the testicle with examination under a microscope is then done to determine the type.Testicular cancer is highly treatable and usually curable. Treatment options may include surgery, radiation therapy, chemotherapy, or stem cell transplantation. Even in cases in which cancer has spread widely, chemotherapy offers a cure rate greater than 80%.Globally testicular cancer affected about 686,000 people in 2015. That year it resulted in 9,400 deaths up from 7,000 deaths in 1990. Rates are lower in the developing than the developed world. Onset most commonly occurs in males 20 to 34 years old, rarely before 15 years old. The five-year survival rate in the United States is about 95%. Outcomes are better when the disease remains localized.
Signs and symptoms
One of the first signs of testicular cancer is often a lump or swelling in the testes. The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening for testicular cancer in asymptomatic adolescent and adults including routine testicular self-exams. However, the American Cancer Society suggests that some men should examine their testicles monthly, especially if they have a family history of cancer, and the American Urological Association recommends monthly testicular self-examinations for all young men.Symptoms may also include one or more of the following:
a lump in one testis which may or may not be painful
sharp pain or a dull ache in the lower abdomen or scrotum
a feeling often described as "heaviness" in the scrotum
firmness of the testicle
breast enlargement (gynecomastia) from hormonal effects of β-hCG
low back pain (lumbago) due to the cancer spreading to the lymph nodes along the backIt is not very common for testicular cancer to spread to other organs, apart from the lungs. If it has, however, the following symptoms may be present:
shortness of breath (dyspnea), cough or coughing up blood (hemoptysis) from metastatic spread to the lungs
a lump in the neck due to metastases to the lymph nodesTesticular cancer, cryptorchidism, hypospadias, and poor semen quality make up the syndrome known as testicular dysgenesis syndrome.
Causes
A major risk factor for the development of testis cancer is cryptorchidism (undescended testicles). It is generally believed that the presence of a tumor contributes to cryptorchidism; when cryptorchidism occurs in conjunction with a tumor then the tumor tends to be large. Other risk factors include inguinal hernias, Klinefelter syndrome, and mumps orchitis. Physical activity is associated with decreased risk and sedentary lifestyle is associated with increased risk. Early onset of male characteristics is associated with increased risk. These may reflect endogenous or environmental hormones.Higher rates of testicular cancer in Western nations have been linked to the use of cannabis.
Mechanisms
Most testicular germ cell tumors have too many chromosomes, and most often they are triploid to tetraploid. An isochromosome 12p (the short arm of chromosome 12 on both sides of the same centromere) is present in about 80% of the testicular cancers, and also the other cancers usually have extra material from this chromosome arm through other mechanisms of genomic amplification.
Diagnosis
The main way testicular cancer is diagnosed is via a lump or mass inside a testis. More generally, if a young adult or adolescent has a single enlarged testicle, which may or may not be painful, this should give doctors reason to suspect testicular cancer.
Other conditions may also have symptoms similar to testicular cancer:
Epididymitis or epididymoorchitis
Hematocele
Varicocele
Orchitis
Prostate infections or inflammations (prostatitis), bladder infections or inflammations (cystitis), or kidney (renal) infections (nephritis) or inflammations which have spread to and caused swelling in the vessels of the testicles or scrotum
Testicular torsion or a hernia
Infection, inflammation, retro-peritonitis, or other conditions of the lymph nodes or vessels near the scrotum, testicles, pubis, anorectal area, and groin
Benign tumors or lesions of the testicles
Metastasis to the testicles from another, primary tumor site(s)The nature of any palpated lump in the scrotum is often evaluated by scrotal ultrasound, which can determine exact location, size, and some characteristics of the lump, such as cystic vs solid, uniform vs heterogeneous, sharply circumscribed or poorly defined. The extent of the disease is evaluated by CT scans, which are used to locate metastases.
The differential diagnosis of testicular cancer requires examining the histology of tissue obtained from an inguinal orchiectomy - that is, surgical excision of the entire testis along with attached structures (epididymis and spermatic cord). A biopsy should not be performed, as it raises the risk of spreading cancer cells into the scrotum.Inguinal orchiectomy is the preferred method because it lowers the risk of cancer cells escaping. This is because the lymphatic system of the scrotum, through which white blood cells (and, potentially, cancer cells) flow in and out, links to the lower extremities, while that of the testicle links to the back of the abdominal cavity (the retroperitoneum). A transscrotal biopsy or orchiectomy will potentially leave cancer cells in the scrotum and create two routes for cancer cells to spread, while in an inguinal orchiectomy only the retroperitoneal route exists.Blood tests are also used to identify and measure tumor markers (usually proteins present in the bloodstream) that are specific to testicular cancer. Alpha-fetoprotein, human chorionic gonadotropin (the "pregnancy hormone"), and LDH-1 are the typical tumor markers used to spot testicular germ cell tumors.A pregnancy test may be used to detect high levels of chorionic gonadotropin; however, the first sign of testicular cancer is usually a painless lump. Note that only about 25% of seminomas have elevated chorionic gonadotropin, so a pregnancy test is not very sensitive for making out testicular cancer.
Screening
The American Academy of Family Physicians recommends against screening males without symptoms for testicular cancer.
Staging
After removal, the testicle is fixed with Bouins solution because it better conserves some morphological details such as nuclear conformation. Then the testicular tumor is staged by a pathologist according to the TNM Classification of Malignant Tumors as published in the AJCC Cancer Staging Manual. Testicular cancer is categorized as being in one of three stages (which have subclassifications). The size of the tumor in the testis is irrelevant to staging. In broad terms, testicular cancer is staged as follows:
Stage I: the cancer remains localized to the testis.
Stage II: the cancer involves the testis and metastasis to retroperitoneal and/or paraaortic lymph nodes (lymph nodes below the diaphragm).
Stage III: the cancer involves the testis and metastasis beyond the retroperitoneal and paraaortic lymph nodes. Stage 3 is further subdivided into non-bulky stage 3 and bulky stage 3.Further information on the detailed staging system is available on the website of the American Cancer Society.
Classification
Although testicular cancer can be derived from any cell type found in the testicles, more than 95% of testicular cancers are germ cell tumors (GCTs). Most of the remaining 5% are sex cord–gonadal stromal tumours derived from Leydig cells or Sertoli cells. Correct diagnosis is necessary to ensure the most effective and appropriate treatment. To some extent, this can be done via blood tests for tumor markers, but definitive diagnosis requires examination of the histology of a specimen by a pathologist.
Most pathologists use the World Health Organization classification system for testicular tumors:
Germ cell tumors
Precursor lesions
Intratubular germ cell neoplasia
Unclassified type (carcinoma in situ)
Specified types
Tumors of one histologic type (pure forms)
Seminoma
Variant - Seminoma with syncytiotrophoblastic cells
Spermatocytic tumor
Variant - spermatocytic tumor with sarcoma
Embryonal carcinoma
Yolk sac tumor
Trophoblastic tumors
Choriocarcinoma
Variant - monophasic choriocarcinoma
Placental site trophoblastic tumour
Cystic trophoblastic tumor
Teratoma
Variant - Dermoid cyst
Variant - Epidermoid cyst
Variant - Monodermal teratoma (Carcinoid), Primitive neuroectodermal tumor (PNET), Nephroblastoma-like tumor, others.
Variant - Teratomic with somatic-type malignancy
Tumours of more than one histologic type (mixed forms)
Embryonal carcinoma and teratoma
Teratoma and seminoma
Choriocarcinoma and teratoma.embryonal carcinoma
Others
Sex cord/Gonadal stromal tumors
Leydig cell tumor
Sertoli cell tumor
Lipid rich variant
Scleriosing variant
Large cell calcifying variant
Intratubular sertoli cell neoplasia in Peutz–Jeghers syndrome
Granulosa cell tumor
Adult type
Juvenile type
Thecoma fibroma group
Thecoma
Fibroma
Sex cord/gonadal stromal tumor - incompletely differentiated
Sex cord/gonadal stromal tumor - mixed types
Mixed germ cell and sex cord/gonadal stromal tumors
Gonadoblastoma
Germ cell-sex cord/gonadal stromal tumor, unclassified
Miscellaneous tumours of the testis
Lymphomas
Primary testicular diffuse large B-cell lymphoma
Mantle cell lymphoma of the testes
extranodal marginal zone B cell lymphoma of the testes
Extranodal NK/T-cell lymphoma, nasal type of the testes
Peripheral T-cell lymphoma of the testes
activin receptor-like kinase-1–negative anaplastic large cell lymphoma of the testes
pediatric-type follicular lymphoma of the testes
Carcinoid
Tumors of ovarian epithelial types
Serous tumor of borderline malignancy
Serous carcinoma
Well differentiated endometrioid tumor
Mucinous cystadenoma
Mucinous cystadenocarcinoma
Brenner tumor
Nephroblastoma
Paraganglioma
Haematopoietic tumors
Tumours of collecting ducts and rete
Adenoma
Carcinoma
Tumors of the paratesticular structures
Adenomatoid tumor
Malignant and benign mesothelioma
Adenocarcinoma of the epididymis
Papillary cystadenoma of the epididymis
Melanotic neuroectodermal tumor
Desmoplastic small round cell tumor
Mesenchymal tumors of the spermatic cord and testicular adnexae
Lipoma
Liposarcoma
Rhabdomyosarcoma
Aggressive angiomyxoma
Angiomyofibroblastoma-like tumor (see Myxoma)
Fibromatosis
Fibroma
Solitary fibrous tumor
Others
Secondary tumors of the testis
Treatment
The three basic types of treatment are surgery, radiation therapy, and chemotherapy.Surgery is performed by urologists; radiation therapy is administered by radiation oncologists; and chemotherapy is the work of medical oncologists. In most patients with testicular cancer, the disease is cured readily with minimal long-term morbidity. While treatment success depends on the stage, the average survival rate after five years is around 95%, and stage 1 cancer cases, if monitored properly, have essentially a 100% survival rate.
Testicle removal
The initial treatment for testicular cancer is surgery to remove the affected testicle (orchiectomy). While it may be possible, in some cases, to remove testicular cancer tumors from a testis while leaving the testis functional, this is almost never done, as the affected testicle usually contains pre-cancerous cells spread throughout the entire testicle. Thus removing the tumor alone without additional treatment greatly increases the risk that another cancer will form in that testicle.Since only one testis is typically required to maintain fertility, hormone production, and other male functions, the affected testis is almost always removed completely in a procedure called inguinal orchiectomy. (The testicle is almost never removed through the scrotum; an incision is made beneath the belt line in the inguinal area.) In the UK, the procedure is known as a radical orchidectomy.
Retroperitoneal lymph node dissection
In the case of nonseminomas that appear to be stage I, surgery may be done on the retroperitoneal/paraaortic lymph nodes (in a separate operation) to accurately determine whether the cancer is in stage I or stage II and to reduce the risk that malignant testicular cancer cells that may have metastasized to lymph nodes in the lower abdomen. This surgery is called retroperitoneal lymph node dissection (RPLND). However, this approach, while standard in many places, especially the United States, is out of favor due to costs and the high level of expertise required to perform successful surgery. Sperm banking is frequently carried out prior to the procedure (as with chemotherapy), as there is a risk that RPLND may damage the nerves involved in ejaculation, causing ejaculation to occur internally into the bladder rather than externally.Many patients are instead choosing surveillance, where no further surgery is performed unless tests indicate that the cancer has returned. This approach maintains a high cure rate because of the growing accuracy of surveillance techniques.
Adjuvant treatment
Since testicular cancers can spread, patients are usually offered adjuvant treatment - in the form of chemotherapy or radiotherapy - to kill any cancerous cells that may exist outside of the affected testicle. The type of adjuvant therapy depends largely on the histology of the tumor (i.e. the size and shape of its cells under the microscope) and the stage of progression at the time of surgery (i.e. how far cells have escaped from the testicle, invaded the surrounding tissue, or spread to the rest of the body). If the cancer is not particularly advanced, patients may be offered careful surveillance by periodic CT scans and blood tests, in place of adjuvant treatment.Before 1970, survival rates from testicular cancer were low. Since the introduction of adjuvant chemotherapy, chiefly platinum-based drugs like cisplatin and carboplatin, the outlook has improved substantially. Although 7000 to 8000 new cases of testicular cancer occur in the United States yearly, only 400 men are expected to die of the disease.
In the UK, a similar trend has emerged: since improvements in treatment, survival rates have risen rapidly to cure rates of over 95%.
Radiation therapy
Radiation may be used to treat stage II seminoma cancers, or as adjuvant (preventative) therapy in the case of stage I seminomas, to minimize the likelihood that tiny, non-detectable tumors exist and will spread (in the inguinal and para-aortic lymph nodes). Radiation is ineffective against and is therefore never used as a primary therapy for nonseminoma.
Chemotherapy
Non-seminoma
Chemotherapy is the standard treatment for non-seminoma when the cancer has spread to other parts of the body (that is, stage 2B or 3). The standard chemotherapy protocol is three, or sometimes four, rounds of Bleomycin-Etoposide-Cisplatin (BEP). BEP as a first-line treatment was first reported by Professor Michael Peckham in 1983. The landmark trial published in 1987 which established BEP as the optimum treatment was conducted by Dr. Lawrence Einhorn at Indiana University. An alternative, equally effective treatment involves the use of four cycles of Etoposide-Cisplatin (EP).Lymph node surgery may also be performed after chemotherapy to remove masses left behind (stage 2B or more advanced), particularly in the cases of large nonseminomas.
Seminoma
As an adjuvant treatment, use of chemotherapy as an alternative to radiation therapy in the treatment of seminoma is increasing, because radiation therapy appears to have more significant long-term side effects (for example, internal scarring, increased risks of secondary malignancies, etc.). Two doses, or occasionally a single dose of carboplatin, typically delivered three weeks apart, is proving to be a successful adjuvant treatment, with recurrence rates in the same ranges as those of radiotherapy. The concept of carboplatin as a single-dose therapy was developed by Tim Oliver, Professor of Medical Oncology at Barts and The London School of Medicine and Dentistry. However, very long-term data on the efficacy of adjuvant carboplatin in this setting do not exist.Since seminoma can recur decades after the primary tumor is removed, patients receiving adjuvant chemotherapy should remain vigilant and not assume they are cured 5 years after treatment.
Prognosis
Treatment of testicular cancer is one of the success stories of modern medicine, with sustained response to treatment in more than 90% of cases, regardless of stage. In 2011 overall cure rates of more than 95% were reported, and 80% for metastatic disease—the best response by any solid tumor, with improved survival being attributed primarily to effective chemotherapy. By 2013 more than 96 per cent of the 2,300 men diagnosed each year in the U.K. were deemed cured, a rise by almost a third since the 1970s, the improvement attributed substantially to the chemotherapy drug cisplatin. In the United States, when the disease is treated while it is still localized, more than 99% of people survive 5 years.
Surveillance
For many patients with stage I cancer, adjuvant (preventative) therapy following surgery may not be appropriate and patients will undergo surveillance instead. The form this surveillance takes, e.g. the type and frequency of investigations and the length time it should continue, will depend on the type of cancer (non-seminoma or seminoma), but the aim is to avoid unnecessary treatments in the many patients who are cured by their surgery, and ensure that any relapses with metastases (secondary cancers) are detected early and cured. This approach ensures that chemotherapy and or radiotherapy is only given to the patients that need it. The number of patients ultimately cured is the same using surveillance as post-operative "adjuvant" treatments, but the patients have to be prepared to follow a prolonged series of visits and tests.For both non-seminomas and seminomas, surveillance tests generally include physical examination, blood tests for tumor markers, chest x-rays and CT scanning. However, the requirements of a surveillance program differ according to the type of disease since, for seminoma patients, relapses can occur later and blood tests are not as good at indicating relapse.CT scans are performed on the abdomen (and sometimes the pelvis) and also the chest in some hospitals. Chest x-rays are increasingly preferred for the lungs as they give sufficient detail combined with a lower false-positive rate and significantly smaller radiation dose than CT.The frequency of CT scans during surveillance should ensure that relapses are detected at an early stage while minimizing the radiation exposure.For patients treated for stage I non-seminoma, a randomised trial (Medical Research Council TE08) showed that, when combined with the standard surveillance tests described above, 2 CT scans at 3 and 12 months were as good as 5 over 2 years in detecting relapse at an early stage.
For patients treated for stage I seminoma who choose surveillance rather than undergoing adjuvant therapy, there have been no randomized trials to determine the optimum frequency of scans and visits, and the schedules vary very widely across the world, and within individual countries. In the UK there is an ongoing clinical trial called TRISST. This is assessing how often scans should take place and whether magnetic resonance imaging (MRI) can be used instead of CT scans. MRI is being investigated because it does not expose the patient to radiation and so, if it is shown to be as good at detecting relapses, it may be preferable to CT.For more advanced stages of testicular cancer, and for those cases in which radiation therapy or chemotherapy was administered, the extent of monitoring (tests) after treatment will vary on the basis of the circumstances, but normally should be done for five years in uncomplicated cases and for longer in those with higher risks of relapse.
Fertility
A man with one remaining testis may maintain fertile. However, sperm banking may be appropriate for men who still plan to have children, since fertility may be adversely affected by chemotherapy and/or radiotherapy. A man who loses both testicles will be infertile after the procedure, though he may elect to bank viable, cancer-free sperm prior to the procedure.
Epidemiology
Globally testicular cancer resulted in 8,300 deaths in 2013 up from 7,000 deaths in 1990. Testicular cancer has the highest prevalence in the U.S. and Europe, and is uncommon in Asia and Africa. Worldwide incidence has doubled since the 1960s, with the highest rates of prevalence in Scandinavia, Germany, and New Zealand.Although testicular cancer is most common among men aged 15–40 years, it has three peaks: infancy through the age of four as teratomas and yolk sac tumors, ages 25–40 years as post-pubertal seminomas and nonseminomas, and from age 60 as spermatocytic tumors.Germ cell tumors of the testis are the most common cancer in young men between the ages of 15 and 35 years.
United States
In the United States, about 8,900 cases are diagnosed a year. The risk of testicular cancer in white men is approximately 4-5 times the risk in black men, and more than three times that of Asian American men. The risk of testicular cancer in Latinos and American Indians is between that of white and Asian men. The cause of these differences is unknown.
United Kingdom
In the UK, approximately 2,000 people are diagnosed a year. Over a lifetime, the risk is roughly 1 in 200 (0.5%). It is the 16th most common cancer in men. It accounts for less than 1% of cancer deaths in men (around 60 men died in 2012).
Other animals
Testicular tumors occur also in other animals. In horses, these include interstitial cell tumors and teratomas. Typically, the former are found in older stallions (affected stallions may become extremely vicious, suggesting excessive production of androgen), and the latter are found in young horses and are large.
References
External links
Ball Checker, self-exam app from the Testicular Cancer Society
Testicular Cancer – detailed guide from the American Cancer Society
Testicular Cancer – National Health Service information and resource page (UK)
Testicular cancer statistics from Cancer Research UK |
Psittacosis | Psittacosis—also known as parrot fever, and ornithosis—is a zoonotic infectious disease in humans caused by a bacterium called Chlamydia psittaci and contracted from infected parrots, such as macaws, cockatiels, and budgerigars, and from pigeons, sparrows, ducks, hens, gulls and many other species of birds. The incidence of infection in canaries and finches is believed to be lower than in psittacine birds.
In certain contexts, the word is used when the disease is carried by any species of birds belonging to the family Psittacidae, whereas ornithosis is used when other birds carry the disease.
In humans
Signs and symptoms
In humans, after an incubation period of 5–19 days, the symptoms of the disease range from inapparent illness to systemic illness with severe pneumonia. It presents chiefly as an atypical pneumonia. In the first week of psittacosis, the symptoms mimic typhoid fever, prostrating high fevers, joint pains, diarrhea, conjunctivitis, nose bleeds, and low level of white blood cells. Rose spots called Horders spots can appear. Spleen enlargement is common towards the end of the first week. It may become a serious lung infection. Diagnosis can be suspected in case of respiratory infection associated with splenomegaly and/or epistaxis. Headache can be so severe that it suggests meningitis and some nuchal rigidity is not unusual. Towards the end of the first week, stupor or even coma can result in severe cases.The second week is more akin to acute bacteremic pneumococcal pneumonia with continuous high fevers, headaches, cough, and dyspnea. X-rays show patchy infiltrates or a diffuse whiteout of lung fields.Complications in the form of endocarditis, liver inflammation, inflammation of the hearts muscle, joint inflammation, keratoconjunctivitis (occasionally extranodal marginal zone lymphoma of the lacrimal gland/orbit), and neurologic complications (brain inflammation) may occasionally occur. Severe pneumonia requiring intensive-care support may also occur. Fatal cases have been reported (less than 1% of cases).
Transmission route
The Chlamydia psittaci bacterium that causes psittacosis can be transmitted by mouth-to-beak contact, or through the airborne inhalation of feather dust, dried faeces, or the respiratory secretions of infected birds. Person-to-person transmission is possible, but rare.
Diagnosis
Blood analysis usually shows a normal white cell count, but marked leukocytosis is occasionally apparent. Liver enzymes are abnormal in half of the patients, with mild elevation of aspartate transaminase. The erythrocyte sedimentation rate and C-reactive protein can be markedly elevated. Differential diagnosis must be made with typhus, typhoid, and atypical pneumonia by Mycoplasma, Legionella, or Q fever. Exposure history is paramount to diagnosis.
Diagnosis involves microbiological cultures from respiratory secretions of patients or serologically with a fourfold or greater increase in antibody titers against C. psittaci in blood samples combined with the probable course of the disease. Typical inclusions called "Leventhal-Cole-Lillie bodies" can be seen within macrophages in BAL (bronchoalveolar lavage) fluid. Culture of C. psittaci is hazardous and should only be carried out in biosafety laboratories.
Treatment
The infection is treated with antibiotics; tetracyclines and chloramphenicol are the choice for treating patients. Most people respond to oral therapy doxycycline, tetracycline hydrochloride, or chloramphenicol palmitate. For initial treatment of severely ill patients, doxycycline hyclate may be administered intravenously. Remission of symptoms is usually evident within 48–72 hours. However, relapse can occur, and treatment must continue for at least 10–14 days after fever subsides.
Epidemiology
Psittacosis was first reported in Europe in 1879.In 1929, a highly publicized outbreak of psittacosis hit the United States. Although not the first report of psittacosis in the United States, it was the largest up to that time. It led to greater controls on the import of pet parrots. The aftermath of the outbreak and how it was handled led to the establishment of the National Institutes of Health.From 2002 through 2009, 66 human cases of psittacosis were reported to the Centers for Disease Control and Prevention, and most resulted from exposure to infected pet birds, usually cockatiels, parakeets, and macaws. Many more cases may occur that are not correctly diagnosed or reported.
Bird owners, pet shop employees, zookeepers, and veterinarians are at risk of the infection. Some outbreaks of psittacosis in poultry-processing plants have been reported.
In birds
In birds, Chlamydia psittaci infection is referred to as avian chlamydiosis. Infected birds shed the bacteria through feces and nasal discharges, which can remain infectious for several months. Many strains remain quiescent in birds until activated under stress. Birds are excellent, highly mobile vectors for the distribution of chlamydial infection because they feed on, and have access to, the detritus of infected animals of all sorts.
Signs
C. psittaci in birds is often systemic and infections can be inapparent, severe, acute, or chronic with intermittent shedding. Signs in birds include "inflamed eyes, difficulty in breathing, watery droppings, and green urates."
Diagnosis
Initial diagnosis may be by symptoms, but is usually confirmed by an antigen and antibody test. A polymerase chain reaction-based test is also available. Although any of these tests can confirm psittacosis, false negatives are possible, so a combination of clinical and laboratory tests is recommended before giving the bird a clean bill of health. It may die within three weeks.
Epidemiology
Infection is usually by the droppings of another infected bird, though it can also be transmitted by feathers and eggs, and is typically either inhaled or ingested.C. psittaci strains in birds infect mucosal epithelial cells and macrophages of the respiratory tract. Septicaemia eventually develops and the bacteria become localized in epithelial cells and macrophages of most organs, conjunctiva, and gastrointestinal tract. It can also be passed in the eggs. Stress commonly triggers onset of severe symptoms, resulting in rapid deterioration and death. C. psittaci strains are similar in virulence, grow readily in cell culture, have 16S-rRNA genes that differ by <0.8%, and belong to eight known serovars. All should be considered to be readily transmissible to humans.C. psittaci serovar A is endemic among psittacine birds and has caused sporadic zoonotic disease in humans, other mammals, and tortoises. Serovar B is endemic among pigeons, has been isolated from turkeys, and has also been identified as the cause of abortion in a dairy herd. Serovars C and D are occupational hazards for slaughterhouse workers and for people in contact with birds. Serovar E isolates (known as Cal-10, MP, or MN) have been obtained from a variety of avian hosts worldwide, and although they were associated with the 1920s–1930s outbreak in humans, a specific reservoir for serovar E has not been identified. The M56 and WC serovars were isolated during outbreaks in mammals.
Treatment
Treatment is usually with antibiotics, such as doxycycline or tetracycline, and can be administered through drops in the water or injections. Many strains of C. psittaci are susceptible to bacteriophages.
Use as a biological weapon
Psittacosis was one of more than a dozen agents that the United States researched as potential biological weapons before the nation suspended its biological weapons program.
Notable casualties
In 1930, during the 1929–1930 psittacosis pandemic, Lena Rose Pepperdine died of parrot fever.
She was the first wife of George Pepperdine, the founder of Pepperdine University.
References
The initial content for this article was adapted from sources available at https://www.cdc.gov.
External links
Psittacosis on Birds n Ways
Ornithosis in Pigeons - Pigeonpedia |
SIDS | Sudden infant death syndrome (SIDS) is the sudden unexplained death of a child of less than one year of age. Diagnosis requires that the death remain unexplained even after a thorough autopsy and detailed death scene investigation. SIDS usually occurs during sleep. Typically death occurs between the hours of midnight and 9:00 a.m. There is usually no noise or evidence of struggle. SIDS remains the leading cause of infant mortality in Western countries, contributing to half of all post-neonatal deaths.The exact cause of SIDS is unknown. The requirement of a combination of factors including a specific underlying susceptibility, a specific time in development, and an environmental stressor has been proposed. These environmental stressors may include sleeping on the stomach or side, overheating, and exposure to tobacco smoke. Accidental suffocation from bed sharing (also known as co-sleeping) or soft objects may also play a role. Another risk factor is being born before 39 weeks of gestation. SIDS makes up about 80% of sudden and unexpected infant deaths (SUIDs). The other 20% of cases are often caused by infections, genetic disorders, and heart problems. While child abuse in the form of intentional suffocation may be misdiagnosed as SIDS, this is believed to make up less than 5% of sudden death cases.The most effective method of reducing the risk of SIDS is putting a child less than one year old on their back to sleep. Other measures include a firm mattress separate from but close to caregivers, no loose bedding, a relatively cool sleeping environment, using a pacifier, and avoiding exposure to tobacco smoke. Breastfeeding and immunization may also be preventive. Measures not shown to be useful include positioning devices and baby monitors. Evidence is not sufficient for the use of fans. Grief support for families affected by SIDS is important, as the death of the infant is sudden, without witnesses, and often associated with an investigation.Rates of SIDS vary nearly tenfold in developed countries from one in a thousand to one in ten thousand. Globally, it resulted in about 19,200 deaths in 2015, down from 22,000 deaths in 1990. SIDS was the third leading cause of death in children less than one year old in the United States in 2011. It is the most common cause of death between one month and one year of age. About 90% of cases happen before six months of age, with it being most frequent between two months and four months of age. It is more common in boys than girls. Rates of SIDS have decreased in areas with "safe sleep" campaigns by up to 80%.
Definition
The syndrome only applies to infants under one. SIDS is a diagnosis of exclusion and should be applied to only those cases in which an infants death is sudden and unexpected, and remains unexplained after the performance of an adequate postmortem investigation, including:
an autopsy (by an experienced pediatric pathologist, if possible);
investigation of the death scene and circumstances of the death; and
exploration of the medical history of the infant and family.After investigation, some of these infant deaths are found to be caused by suffocation, hyperthermia or hypothermia, neglect or some other defined cause.Australia and New Zealand shifted to sudden unexpected death in infancy (SUDI) for professional, scientific, and coronial clarity.
The term SUDI is now often used instead of sudden infant death syndrome (SIDS) because some coroners prefer to use the term undetermined for a death previously considered to be SIDS. This change is causing diagnostic shift in the mortality data. In addition, the US Centers for Disease Control and Prevention have proposed that such deaths be called sudden unexpected infant deaths (SUID) and that SIDS is a subset of SUID.
Age
SIDS has a four-parameter lognormal age distribution that spares infants shortly after birth — the time of maximal risk for almost all other causes of non-trauma infant death.
By definition, SIDS deaths occur under the age of one year, with the peak incidence occurring when the infant is two to four months old. This is considered a critical period because the infants ability to rouse from sleep is not yet mature.
Risk factors
The exact cause of SIDS is unknown. Although studies have identified risk factors for SIDS, such as putting infants to bed on their bellies, there has been little understanding of the syndromes biological process or its potential causes. Deaths from SIDS are unlikely to be due to a single cause, but rather to multiple risk factors. The frequency of SIDS does appear to be influenced by social, economic, or cultural factors, such as maternal education, race or ethnicity, or poverty. SIDS is believed to occur when an infant with an underlying biological vulnerability, who is at a critical development age, is exposed to an external trigger. The following risk factors generally contribute either to the underlying biological vulnerability or represent an external trigger:
Tobacco smoke
SIDS rates are higher in babies of mothers who smoke during pregnancy. Between no smoking and smoking one cigarette a day, on average, the risk doubles. About 22% of SIDS in the United States is related to maternal smoking. SIDS correlates with levels of nicotine and its derivatives in the baby. Nicotine and derivatives cause alterations in neurodevelopment.
Sleeping
Placing an infant to sleep while lying on the belly or side rather than on the back increases the risk for SIDS. This increased risk is greatest at two to three months of age. Elevated or reduced room temperature also increases the risk, as does excessive bedding, clothing, soft sleep surfaces, and stuffed animals in the bed. Bumper pads may increase the risk of SIDS due to the risk of suffocation. They are not recommended for children under one year of age, as this risk of suffocation greatly outweighs the risk of head bumping or limbs getting stuck in the bars of the crib.Sharing a bed with parents or siblings increases the risk for SIDS. This risk is greatest in the first three months of life, when the mattress is soft, when one or more persons share the infants bed, especially when the bed partners are using drugs or alcohol or are smoking. The risk remains, however, even in parents who do not smoke or use drugs. The American Academy of Pediatrics thus recommends "room-sharing without bed-sharing", stating that such an arrangement can decrease the risk of SIDS by up to 50%. Furthermore, the academy has recommended against devices marketed to make bed-sharing "safe", such as "in-bed co-sleepers".Room sharing as opposed to solitary sleeping is known to decrease the risk of SIDS.
Breastfeeding
Breastfeeding is associated with a lower risk of SIDS. It is not clear if co-sleeping among mothers who breastfeed without any other risk factors increases SIDS risk.
Pregnancy and infant factors
SIDS rates decrease with increasing maternal age, with teenage mothers at greatest risk. Delayed or inadequate prenatal care also increases risk. Low birth weight is a significant risk factor. In the United States from 1995 to 1998, the SIDS death rate for infants weighing 1000–1499 g was 2.89/1000, while for a birth weight of 3500–3999 g, it was only 0.51/1000. Premature birth increases the risk of SIDS death roughly fourfold. From 1995 to 1998, the U.S. SIDS rate for births at 37–39 weeks of gestation was 0.73/1000, while the SIDS rate for births at 28–31 weeks of gestation was 2.39/1000.Anemia has also been linked to SIDS (however, per item 6 in the list of epidemiologic characteristics below, extent of anemia cannot be evaluated at autopsy because an infants total hemoglobin can only be measured during life). SIDS incidence rises from zero at birth, is highest from two to four months of age, and declines toward zero after the infants first year.
Genetics
Genetics plays a role, as SIDS is more prevalent in males. There is a consistent 50% male excess in SIDS per 1000 live births of each sex. Given a 5% male excess birth rate, there appears to be 3.15 male SIDS cases per 2 female cases, for a male fraction of 0.61. This value of 61% in the US is an average of 57% black male SIDS, 62.2% white male SIDS and 59.4% for all other races combined. Note that when multiracial parentage is involved, infant race is arbitrarily assigned to one category or the other; most often it is chosen by the mother. The X-linkage hypothesis for SIDS and the male excess in infant mortality have shown that the 50% male excess might be related to a dominant X-linked allele, occurring with a frequency of 1⁄3 that is protective against transient cerebral anoxia. An unprotected male would occur with a frequency of 2⁄3 and an unprotected female would occur with a frequency of 4⁄9.
About 10 to 20% of SIDS cases are believed to be due to channelopathies, which are inherited defects in the ion channels which play an important role in the contraction of the heart.Genetic evidence published in November 2020 concerning the case of Kathleen Folbigg, who is in prison over the death of four of her children, showed that at least two of the children had genetic mutations in the CALM2 gene that predisposed them to heart complications.
Alcohol
Drinking of alcohol by parents is linked to SIDS. One study found a positive correlation between the two during New Years celebrations and weekends. Another found that alcohol use disorder was linked to a more than doubling of risk.
Other
A 2022 study found that infants who died of SIDS exhibited significantly lower specific activity of butyrylcholinesterase, an enzyme involved in the brains arousal pathway, shortly after birth. This can serve as a biomarker to identify infants with a potential autonomic cholinergic dysfunction and elevated risk for SIDS.SIDS has been linked to cold weather, with this association believed to be due to over-bundling and thus, overheating. Premature babies are at four times the risk of SIDS, possibly related to an underdeveloped ability to automatically control the cardiovascular system.A 1998 report found that antimony- and phosphorus-containing compounds used as fire retardants in PVC and other cot mattress materials are not a cause of SIDS. The report also states that toxic gas cannot be generated from antimony in mattresses and that babies had SIDS on mattresses that did not contain the compound.
It has been suggested that some cases of SIDS may be related to Staphylococcus aureus and Escherichia coli infections.
Diagnosis
Differential diagnosis
Some conditions that are often undiagnosed and could be confused with or comorbid with SIDS include:
medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD deficiency);
infant botulism;
long QT syndrome (accounting for less than 2% of cases);
Helicobacter pylori bacterial infections;
shaken baby syndrome and other forms of child abuse;
overlaying, child smothering during carers sleepFor example, an infant with MCAD deficiency might die by "classical SIDS" if found swaddled and prone, with its head covered, in an overheated room where parents were smoking. Genes indicating susceptibility to MCAD and Long QT syndrome do not protect an infant from dying of classical SIDS. Therefore, the presence of a susceptibility gene, such as for MCAD, means the infant might have died either from SIDS or from MCAD deficiency. It is currently impossible for a pathologist to distinguish between them.
A 2010 study looked at 554 autopsies of infants in North Carolina that listed SIDS as the cause of death, and suggested that many of these deaths may have been due to accidental suffocation. The study found that 69% of autopsies listed other possible risk factors that could have led to death, such as unsafe bedding or sleeping with adults.Several instances of infanticide have been uncovered in which the diagnosis was originally SIDS. The estimate of the percentage of SIDS deaths that are actually infanticide varies from less than 1% to up to 5% of cases.Some have underestimated the risk of two SIDS deaths occurring in the same family; the Royal Statistical Society issued a media release refuting expert testimony in one UK case, in which the conviction was subsequently overturned.
Prevention
A number of measures have been found to be effective in preventing SIDS, including changing the sleeping position to supine, breastfeeding, limiting soft bedding, immunizing the infant and using pacifiers. The use of electronic monitors has not been found to be useful as a preventative strategy. The effect that fans might have on the risk of SIDS has not been studied well enough to make any recommendation about them. Evidence regarding swaddling is unclear regarding SIDS. A 2016 review found tentative evidence that swaddling increases the risk of SIDS, especially among babies placed on their bellies or sides while sleeping.Measures not shown to be useful include positioning devices and baby monitors. In the United States, companies that sell the monitors do not have FDA approval for them as medical devices.
Sleep positioning
Sleeping on the back has been found to reduce the risk of SIDS. It is thus recommended by the American Academy of Pediatrics and promoted as a best practice by the US National Institute of Child Health and Human Development (NICHD) "Safe to Sleep" campaign. The incidence of SIDS has fallen in a number of countries in which this recommendation has been widely adopted. Sleeping on the back does not appear to increase the risk of choking, even in those with gastroesophageal reflux disease. While infants in this position may sleep more lightly, this is not harmful. Sharing the same room as the parents but in a different bed may decrease the SIDS risk by half.
Pacifiers
The use of pacifiers appears to decrease the risk of SIDS, although the reason is unclear. The American Academy of Pediatrics considers pacifier use to prevent SIDS to be reasonable. Pacifiers do not appear to affect breastfeeding in the first four months, even though this is a common misconception.
Bedding
Product safety experts advise against using pillows, overly soft mattresses, sleep positioners, bumper pads (crib bumpers), stuffed animals, or fluffy bedding in the crib, and recommend instead dressing the child warmly and keeping the crib "naked."Blankets or other clothing should not be placed over a babys head.The use of a "baby sleep bag" or "sleep sack", a soft bag with holes for the babys arms and head can be used as a type of bedding that warms the baby without covering its head.
Vaccination
Infants typically receive several vaccinations between the ages of 2 and 4 months, which is also the peak age for SIDS. Due to this coincidence, a number of studies have investigated the possible role of vaccinations as a cause of SIDS. These have found either no relation between vaccinations and SIDS, or a reduction of the risk of SIDS following vaccination. A 2007 meta-analysis found that vaccinations were associated with a halving of the risk of SIDS, and argued that immunisation should be a part of SIDS prevention campaigns.
Epidemiology
Globally, SIDS resulted in about 22,000 deaths as of 2010, down from 30,000 deaths in 1990. Rates vary significantly by population from 0.05 per 1000 in Hong Kong to 6.7 per 1000 in Native Americans.SIDS was responsible for 0.54 deaths per 1,000 live births in the US in 2005. It is responsible for far fewer deaths than congenital disorders and disorders related to short gestation, though it is the leading cause of death in healthy infants after one month of age.
SIDS deaths in the US decreased from 4,895 in 1992 to 2,247 in 2004, a 54% decrease. During a similar time period, 1989 to 2004, SIDS as the cause of death for sudden infant death (SID) decreased from 80% to 55%, a 31% decrease. According to John Kattwinkel, chairman of the Centers for Disease Control and Prevention (CDC) Special Task Force on SIDS "A lot of us are concerned that the rate (of SIDS) isnt decreasing significantly, but that a lot of it is just code shifting".
Race
In 2013, there were persistent disparities in SIDS deaths among racial and ethnic groups in the U.S. In 2009, the rates of death range from 20.3 per 100,000 live births for Asian/Pacific Islander to 119.2 per 100,000 live births for Native Americans/Alaska Native. African American infants have a 24% greater risk of having a SIDS-related death, compared to the U.S. population as a whole, and experience a 2.5 greater incidence of SIDS than in Caucasian infants. Rates are calculated per 100,000 live births to enable more accurate comparison across groups of different total population size.
Research suggests that factors which contribute more directly to SIDS risk—maternal age, exposure to smoking, safe sleep practices, etc.—vary by racial and ethnic group and therefore risk exposure also varies by these groups. Risk factors associated with prone sleeping patterns of African American families include mothers age, household poverty index, rural/urban status of residence, and infants age. More than 50% of African American infants were placed in non-recommended sleeping positions, according to a 2012 study completed in South Carolina, indicating that cultural factors can be protective as well as problematic.The rate of SIDS per 1000 births varies among ethnic groups in the United States:
Central Americans and South Americans: 0.20
Asian/Pacific Islanders: 0.28
Mexicans: 0.24
Puerto Ricans: 0.53
Whites: 0.51
African Americans: 1.08
Native American: 1.24
Society and culture
The rate of SIDS varies vastly among different cultures and countries around the world, with SIDS rates lowest among Asian and Pacific Islander infants. Some evidence supports the hypothesis that SIDS is not an ancient phenomenon and that it appears more commonly in western societies.
Much of the popular media portrayals of infants shows them in non-recommended sleeping positions.
See also
Fading puppy syndrome
Failure to thrive
Neonatal isoerythrolysis
Newborn care and safety
Sudden unexpected death syndrome
Sudden unexplained death in childhood
References
Further reading
Ottaviani, G. (2014). Crib death – Sudden infant Death Syndrome (SIDS). Sudden infant and perinatal unexplained death: the pathologists viewpoint. Berlin Heidelberg, Germany: Springer. ISBN 978-3-319-08346-9.
Joan Hodgman; Toke Hoppenbrouwers (2004). SIDS. Calabasas, Calif: Monte Nido Press. ISBN 978-0-9742663-0-5.
Lewak N (2004). "Book Review: SIDS". Arch Pediatr Adolesc Med. 158 (4): 405. doi:10.1001/archpedi.158.4.405. Archived from the original on 17 October 2008.
External links
SIDS at Curlie
"Sudden Unexpected Infant Death and Sudden Infant Death Syndrome". Data and Statistics. Center for Disease Control and Prevention. Retrieved 26 March 2017. |
Electrical injury | Electrical injury is a physiological reaction caused by electric current passing through the body. The injury depends on the density of the current, tissue resistance and duration of contact. Very small currents may be imperceptible or produce a light tingling sensation. A shock caused by low and otherwise harmless current could startle an individual and cause injury due to jerking away or falling. Stronger currents may cause some degree of discomfort or pain, while more intense currents may induce involuntary muscle contractions, preventing the person from breaking free of the source of electricity. Still larger currents result in tissue damage and may trigger ventricular fibrillation or cardiac arrest. Consequences of injury from electricity may include amputations, bone fractures and orthopedic and musculoskeletal injuries. If death results from an electric shock the cause of death is generally referred to as electrocution.
Electric injury occurs upon contact of a body part with electricity that causes a sufficient current to pass through the persons tissue. Contact with energized wiring or devices is the most common cause. In cases of exposure to high voltages, such as on a power transmission tower, direct contact may not be necessary as the voltage may "jump" the air gap to the electrical device.
Following an electrical injury from household current, if a person has no symptoms, no underlying heart problems, and is not pregnant further testing is not required. Otherwise an electrocardiogram, blood work to check the heart, and urine testing for signs of muscle breakdown may be performed.Management may involve resuscitation, pain medications, wound management, and heart monitoring. Electrical injuries affect more than 30,000 people a year in the United States and result in about 1,000 deaths.
Signs and symptoms
Burns
Heating due to resistance can cause extensive and deep burns. When applied to the hand, electricity can cause involuntary muscle contraction, producing the "no-let-go" phenomenon, and increasing the risk for serious burns. Voltage levels of 500 to 1000 volts tend to cause internal burns due to the large energy (which is proportional to the duration multiplied by the square of the voltage divided by resistance) available from the source. Damage due to current is through tissue heating and/or electroporation injury. For most cases of high-energy electrical trauma, the Joule heating in the deeper tissues along the extremity will reach damaging temperatures in a few seconds.
Ventricular fibrillation
A domestic power supply voltage (110 or 230 V), 50 or 60 Hz alternating current (AC) through the chest for a fraction of a second may induce ventricular fibrillation at currents as low as 30 milliamperes (mA). With direct current (DC), 300 to 500 mA is required. If the current has a direct pathway to the heart (e.g., via a cardiac catheter or other kind of electrode), a much lower current of less than 1 mA (AC or DC) can cause fibrillation. If not immediately treated by defibrillation, fibrillation is usually lethal because all of the heart muscle fibres move independently instead of in the coordinated pulses needed to pump blood and maintain circulation. Above 200 mA, muscle contractions are so strong that the heart muscles cannot move at all, but these conditions prevent fibrillation.
Neurological effects
Electrical current can cause interference with nervous control, especially over the heart and lungs. Electric shock which does not lead to death has been shown to cause neuropathy at the site where the current entered the body. The neurologic symptoms of electrical injury may occur immediately, which traditionally have a higher likelihood for healing, though they may also be delayed by days to years. The delayed neurologic consequences of electrical injury have a worse prognosis.When the patch of electrical current proceeds through the head, it appears that, with sufficient current applied, loss of consciousness almost always occurs swiftly. This is borne out by some limited self-experimentation by early designers of the electric chair and by research from the field of animal husbandry, where electric stunning has been extensively studied.If ventricular fibrillation occurs (as above), the blood supply to the brain is diminished, which may cause cerebral hypoxia (and its associated neurologic consequences).
Mental health
There are a variety of psychiatric effects that may occur as a result of electrical injuries. Behavioral changes can occur as well, even if the path of electrical current did not proceed through the head. Symptoms may include:
Depression, including feelings of low self-esteem and guilt
Anxiety spectrum disorders, including posttraumatic stress disorder and fear of electricity
Moodiness, including a lower threshold for frustration and "losing ones temper"
Memory loss, decreased attention span, and difficulty learning
Arc-flash hazards
OSHA found that up to 80 percent of its electrical injuries involve thermal burns due to arcing faults. The arc flash in an electrical fault produces the same type of light radiation from which electric welders protect themselves using face shields with dark glass, heavy leather gloves, and full-coverage clothing. The heat produced may cause severe burns, especially on unprotected flesh. The arc blast produced by vaporizing metallic components can break bones and damage internal organs. The degree of hazard present at a particular location can be determined by a detailed analysis of the electrical system, and appropriate protection worn if the electrical work must be performed with the electricity on.
Pathophysiology
The minimum current a human can feel depends on the current type (AC or DC) as well as frequency for AC. A person can sense electrical current as low as 1 mA (rms) for 60 Hz AC and as low as 5 mA for DC. At around 10 mA, DC current passing through the arm of a 68-kilogram (150 lb) human can cause powerful muscle contractions; the victim is unable to voluntarily control muscles and cannot release an electrified object. This is known as the "let go threshold" and is a criterion for shock hazard in electrical regulations.
The current may, if it is high enough and is delivered at sufficient voltage, cause tissue damage or fibrillation which can cause cardiac arrest; more than 30 mA of AC (rms, 60 Hz) or 300–500 mA of DC at high voltage can cause fibrillation. A sustained electric shock from AC at 120 V, 60 Hz is an especially dangerous source of ventricular fibrillation because it usually exceeds the let-go threshold, while not delivering enough initial energy to propel the person away from the source. However, the potential seriousness of the shock depends on paths through the body that the currents take. If the voltage is less than 200 V, then the human skin, more precisely the stratum corneum, is the main contributor to the impedance of the body in the case of a macroshock—the passing of current between two contact points on the skin. The characteristics of the skin are non-linear however. If the voltage is above 450–600 V, then dielectric breakdown of the skin occurs. The protection offered by the skin is lowered by perspiration, and this is accelerated if electricity causes muscles to contract above the let-go threshold for a sustained period of time.If an electrical circuit is established by electrodes introduced in the body, bypassing the skin, then the potential for lethality is much higher if a circuit through the heart is established. This is known as a microshock. Currents of only 10 µA can be sufficient to cause fibrillation in this case with a probability of 0.2%.
Body resistance
The voltage necessary for electrocution depends on the current through the body and the duration of the current. Ohms law states that the current drawn depends on the resistance of the body. The resistance of human skin varies from person to person and fluctuates between different times of day. The NIOSH states "Under dry conditions, the resistance offered by the human body may be as high as 100,000 ohms. Wet or broken skin may drop the bodys resistance to 1,000 ohms," adding that "high-voltage electrical energy quickly breaks down human skin, reducing the human bodys resistance to 500 ohms".The International Electrotechnical Commission gives the following values for the total body impedance of a hand to hand circuit for dry skin, large contact areas, 50 Hz AC currents (the columns contain the distribution of the impedance in the population percentile; for example at 100 V 50% of the population had an impedance of 1875Ω or less):
Skin
The voltage-current characteristic of human skin is non-linear and depends on many factors such as intensity, duration, history, and frequency of the electrical stimulus. Sweat gland activity, temperature, and individual variation also influence the voltage-current characteristic of skin. In addition to non-linearity, skin impedance exhibits asymmetric and time varying properties. These properties can be modeled with reasonable accuracy. Resistance measurements made at low voltage using a standard ohmmeter do not accurately represent the impedance of human skin over a significant range of conditions.
For sinusoidal electrical stimulation less than 10 volts, the skin voltage-current characteristic is quasilinear. Over time, electrical characteristics can become non-linear. The time required varies from seconds to minutes, depending on stimulus, electrode placement, and individual characteristics.
Between 10 volts and about 30 volts, skin exhibits non-linear but symmetric electrical characteristics. Above 20 volts, electrical characteristics are both non-linear and symmetric. Skin conductance can increase by several orders of magnitude in milliseconds. This should not be confused with dielectric breakdown, which occurs at hundreds of volts. For these reasons, current flow cannot be accurately calculated by simply applying Ohms law using a fixed resistance model.
Point of entry
Macroshock: Current across intact skin and through the body. Current from arm to arm, or between an arm and a foot, is likely to traverse the heart, therefore it is much more dangerous than current between a leg and the ground. This type of shock by definition must pass into the body through the skin.
Microshock: Very small current source with a pathway directly connected to the heart tissue. The shock is required to be administered from inside the skin, directly to the heart i.e. a pacemaker lead, or a guide wire, conductive catheter etc. connected to a source of current. This is a largely theoretical hazard as modern devices used in these situations include protections against such currents.
Lethality
Electrocution
The earliest usage of the term "electrocution" cited by the Oxford English Dictionary was an 1889 newspaper reference to the method of execution then being considered. Shortly thereafter, in 1892, the term was used in Science to refer generically to death or injury caused by electricity.
Factors in lethality of electric shock
The lethality of an electric shock is dependent on several variables:
Current. The higher the current, the more likely it is lethal. Since current is proportional to voltage when resistance is fixed (ohms law), high voltage is an indirect risk for producing higher currents.
Duration. The longer the duration, the more likely it is lethal—safety switches may limit time of current flow
Pathway. If current flows through the heart muscle, it is more likely to be lethal.
High voltage (over about 600 volts). In addition to greater current flow, high voltage may cause dielectric breakdown at the skin, thus lowering skin resistance and allowing further increased current flow.
Medical implants. Artificial cardiac pacemakers or implantable cardioverter-defibrillators (ICD) are sensitive to very small currents.
Pre-existing medical condition.
Age and sex.Other issues affecting lethality are frequency, which is an issue in causing cardiac arrest or muscular spasms. Very high frequency electric current causes tissue burning, but does not penetrate the body far enough to cause cardiac arrest (see electrosurgery). Also important is the pathway: if the current passes through the chest or head, there is an increased chance of death. From a main circuit or power distribution panel the damage is more likely to be internal, leading to cardiac arrest. Another factor is that cardiac tissue has a chronaxie (response time) of about 3 milliseconds, so electricity at frequencies of higher than about 333 Hz requires more current to cause fibrillation than is required at lower frequencies.
The comparison between the dangers of alternating current at typical power transmission frequences (i.e., 50 or 60 Hz), and direct current has been a subject of debate ever since the war of the currents in the 1880s. Animal experiments conducted during this time suggested that alternating current was about twice as dangerous as direct current per unit of current flow (or per unit of applied voltage).
It is sometimes suggested that human lethality is most common with alternating current at 100–250 volts; however, death has occurred below this range, with supplies as low as 42 volts. Assuming a steady current flow (as opposed to a shock from a capacitor or from static electricity), shocks above 2,700 volts are often fatal, with those above 11,000 volts being usually fatal, though exceptional cases have been noted. According to a Guinness Book of World Records comic, seventeen-year-old Brian Latasa survived a 230,000 volt shock on the tower of an ultra-high voltage line in Griffith Park, Los Angeles on November 9, 1967. A news report of the event stated that he was "jolted through the air, and landed across the line", and though rescued by firemen, he sustained burns over 40% of his body and was completely paralyzed except for his eyelids. The shock with the highest voltage reported survived was that of Harry F. McGrew, who came in contact with a 340,000 volt transmission line in Huntington Canyon, Utah.
Prevention
Grounding the electrical enclosure of high-voltage machinery.
Use of insulated gloves, insulated boots, mats and tools.
Protecting electrical circuit with a residual-current device (RCD).
Epidemiology
There were 550 reported electrocutions in the US in 1993, 2.1 deaths per million inhabitants. At that time, the incidence of electrocutions was decreasing. Electrocutions in the workplace make up the majority of these fatalities. From 1980–1992, an average of 411 workers were killed each year by electrocution. Workplace deaths caused by exposure to electricity in the U.S. increased by nearly 24% between 2015 and 2019, from 134 to 166. However, workplace electrical injuries dropped 23% between 2015 and 2019 from 2,480 to 1,900. In 2019, the top 5 states with the most workplace electrical fatalities were: (1) Texas (608); (2) California (451); (3) Florida (306); (4) New York (273); and (5) Georgia (207).A recent study conducted by the National Coroners Information System (NCIS) in Australia has revealed 321 closed case fatalities (and at least 39 case fatalities still under coronial investigation) that had been reported to Australian coroners where a person died from electrocution between July 2000 and October 2011.In Sweden, Denmark, Finland and Norway the number of electric deaths per million inhabitants was 0.6, 0.3, 0.3 and 0.2, respectively, in the years 2007–2011.People who survive electrical trauma may develop a host of injuries including loss of consciousness, seizures, aphasia, visual disturbances, headaches, tinnitus, paresis, and memory disturbances. Even without visible burns, electric shock survivors may be faced with long-term muscular pain and discomfort, exhaustion, headache, problems with peripheral nerve conduction and sensation, inadequate balance and coordination, among other symptoms. Electrical injury can lead to problems with neurocognitive function, affecting speed of mental processing, attention, concentration, and memory. The high frequency of psychological problems is well established and may be multifactorial. As with any traumatic and life-threatening experience, electrical injury may result in post traumatic psychiatric disorders. There exist several non-profit research institutes that coordinate rehabilitation strategies for electrical injury survivors by connecting them with clinicians that specialize in diagnosis and treatment of various traumas that arise as a result of electrical injury.
Deliberate uses
Medical uses
Electric shock is also used as a medical therapy, under carefully controlled conditions:
Electroconvulsive therapy or ECT, a psychiatric therapy for mental disorders
As a surgical tool for cutting or coagulation. An electrosurgical unit (ESU) uses high currents (e.g. 10 amperes) at high frequency (e.g. 500 kHz) with various schemes of amplitude modulation to cut or coagulate
As a treatment for fibrillation or irregular heart rhythms: see Defibrillation and Cardioversion
As a method of pain relief: see Transcutaneous electrical nerve stimulation (TENS)
As a treatment for excessive sweating with a process called iontophoresis
Electrodiagnosis, for example nerve conduction studies and electromyography
Electroporation for gene delivery
Entertainment
Mild electric shocks are also used for entertainment, especially as a practical joke for example in such devices as a shocking pen or a shocking gum. However devices such as a joy buzzer and most other machines in amusement parks today only use vibration that feels somewhat like an electric shock to someone not expecting it.
It is also used entertainingly for sex stimulation. This is usually done via the use of an erotic electrostimulator which induces erotic electrostimulation. These devices may include a violet wand, transcutaneous electrical nerve stimulation, electrical muscle stimulation, and made-for-play units.
Policing and personal defense
Electroshock weapons are incapacitant weapons used for subduing a person by administering electric shock to disrupt superficial muscle functions. One type is a conductive energy device (CED), an electroshock gun popularly known by the brand name "Taser", which fires projectiles that administer the shock through a thin, flexible wire. Although they are illegal for personal use in many jurisdictions, Tasers have been marketed to the general public. Other electroshock weapons such as stun guns, stun batons ("cattle prods"), and electroshock belts administer an electric shock by direct contact.
Electric fences are barriers that use electric shocks to deter animals or people from crossing a boundary. The voltage of the shock may have effects ranging from uncomfortable, to painful or even lethal. Most electric fencing is used today for agricultural fencing and other forms of animal control purposes, though it is frequently used to enhance security of restricted areas, and there exist places where lethal voltages are used.
Torture
Electric shocks are used as a method of torture, since the received voltage and current can be controlled with precision and used to cause pain and fear without always visibly harming the victims body.
Electrical torture has been used in war and by repressive regimes since the 1930s. The United States Army is known to have used electrical torture during World War II. During the Algerian War electrical torture was used by French military forces. Amnesty International published a statement that Russian military forces in Chechnya tortured local women with electric shocks by attaching wires onto their breasts.The parrilla (Spanish for grill) is a method of torture whereby the victim is strapped to a metal frame and subjected to electric shock. It has been used in a number of contexts in South America. The parrilla was commonly used at Villa Grimaldi, a prison complex maintained by Dirección de Inteligencia Nacional, a part of the Pinochet regime. In the 1970s, during the Dirty War, the parrilla was used in Argentina. Francisco Tenório Júnior (known as Tenorinho), a Brazilian piano player, was subjected to the parrilla during the military dictatorship in Brazil.Advocates for the mentally ill and some psychiatrists such as Thomas Szasz have asserted that electroconvulsive therapy (ECT) is torture when used without a bona fide medical benefit against recalcitrant or non-responsive patients.The Judge Rotenberg Center in Canton, Massachusetts has been condemned for torture by the United Nations special rapporteur on torture for its use of electric shocks as punishment as part of its behavior modification program.Japanese serial killer Futoshi Matsunaga used electric shocks to control his victims.
Capital punishment
Electric shock delivered by an electric chair is sometimes used as an official means of capital punishment in the United States, although its use has become rare from the 1990s onward due to the adoption of lethal injection. Although some original proponents of the electric chair considered it to be a more humane execution method than hanging, shooting, poison gassing, etc., it has now generally been replaced by lethal injections in states that practice capital punishment. Modern reporting has claimed that it sometimes takes several shocks to be lethal, and that the condemned person may actually catch fire before death.
Other than in parts of the United States, only the Philippines reportedly has used this method, from 1926 to 1976. It was intermittently replaced by the firing squad, until the death penalty was abolished in that country. Electrocution remains legal in at least 4 states (Florida, Alabama, North Carolina and Kentucky) of the United States.
See also
References
Cited sources
Reilly, J. Patrick (1998). Applied Bioelectricity: From Electrical Stimulation to Electropathology (2nd ed.). Springer. ISBN 978-0-387-98407-0. LCCN 97048860. OCLC 38067651.
External links
National Institute for Occupation Safety & Health: Worker Deaths by Electrocution, a CDC study
Effect of Electric Shock Currents on Humans
ELECTRICAL INJURY AND ITS EFFECTS[1] |
Foreign body aspiration | Foreign body aspiration occurs when a foreign body enters the airway which can cause difficulty breathing or choking. Objects may reach the respiratory tract and the digestive tract from the mouth and nose, but when an object enters the respiratory tract it is termed aspiration. The foreign body can then become lodged in the trachea or further down the respiratory tract such as in a bronchus. Regardless of the type of object, any aspiration can be a life-threatening situation and requires timely recognition and action to minimize risk of complications. While advances have been made in management of this condition leading to significantly improved clinical outcomes, there were still 2,700 deaths resulting from foreign body aspiration in 2018. Approximately one child dies every five days due to choking on food in the United States, highlighting the need for improvements in education and prevention.
Signs and symptoms
Signs and symptoms of foreign body aspiration vary based on the site of obstruction, the size of the foreign body, and the severity of obstruction. 20% of foreign bodies become lodged in the upper airway, while 80% become lodged in a bronchus. Signs of foreign body aspiration are usually abrupt in onset and can involve coughing, choking, and/or wheezing; however, symptoms can be slower in onset if the foreign body does not cause a large degree of obstruction of the airway. With this said, aspiration can also be asymptomatic on rare occasions.Classically, patients present with acute onset of choking. In these cases, the obstruction is classified as a partial or complete obstruction. Signs of partial obstruction include choking with drooling, stridor, and the patient maintains the ability to speak. Signs of complete obstruction include choking with inability to speak or absence of bilateral breath sounds among other signs of respiratory distress such as cyanosis. A fever may be present. When this is the case, it is possible the object may be chemically irritating or contaminated.Foreign bodies above the larynx often present with stridor, while objects below the larynx present with wheezing. Foreign bodies above the vocal cords often present with difficulty and pain with swallowing and excessive drooling. Foreign bodies below the vocal cords often present with pain and difficulty with speaking and breathing. Increased respiratory rate may be the only sign of foreign body aspiration in a child who cannot verbalize or report if they have swallowed a foreign body.If the foreign body does not cause a large degree of obstruction, patients may present with chronic cough, asymmetrical breath sounds on exam, or recurrent pneumonia of a specific lung lobe. If the aspiration occurred weeks or even months ago, the object may lead to an obstructive pneumonia or even a lung abscess. Therefore, it is important to consider chronic foreign body aspiration in patients whose histories include unexplained recurrent pneumonia or lung abscess with or without fever.In adults, the right lower lobe of the lung is the most common site of recurrent pneumonia in foreign body aspiration. This is due to the fact that the anatomy of the right main bronchus is wider and steeper than that of the left main bronchus, allowing objects to enter more easily than the left side. Unlike adults, there is only a slight propensity towards objects lodging in the right bronchus in children. This is likely due to the bilateral bronchial angles being symmetric until about 15 years of age when the aortic knob fully develops and displaces the left main bronchus.Signs and symptoms of foreign body aspiration in adults may also mimic other lung disorders such as asthma, COPD, and lung cancer.
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Causes
Most cases of foreign body aspiration are in children ages 6 months to 3 years due to the tendency for children to place small objects in the mouth and nose. Children of this age usually lack molars and cannot grind up food into small pieces for proper swallowing. Small, round objects including nuts, hard candy, popcorn kernels, beans, and berries are common causes of foreign body aspiration. Latex balloons are also a serious choking hazard in children that can result in death. A latex balloon will conform to the shape of the trachea, blocking the airway and making it difficult to expel with the Heimlich maneuver. In addition, if the foreign body is able to absorb water, such as a bean, seed, or corn, among other things, it may swell over time leading to a more severe obstruction.
In adults, foreign body aspiration is most prevalent in populations with impaired swallowing mechanisms such as the following: neurological disorders, alcohol use, advanced age leading to senility (most common in the 6th decade of life), and loss of consciousness. This inadequate airway protection may also be attributed to poor dentition, seizure, general anesthesia, or sedative drug use.
Diagnosis
The most important aspect of the assessment for a clinician is an accurate history provided by an event witness. Unfortunately, this is not always available.
Physical examination
A physical examination by a clinician should include, at a minimum, a general assessment in addition to cardiac and pulmonary exams. Auscultation of breath sounds may give additional information regarding object location and the degree of airway obstruction. The presence of drooling and dysphagia (drooling) should always be noted alongside the classic signs of airway obstruction as these can indicate involvement of the esophagus and impact management.
Diagnostic Imaging
Radiography is the most common form of imaging used in the initial assessment of a foreign body presentation. Most patients receive a chest x-ray to determine the location of the foreign body. Lateral neck, chest, and bilateral decubitus end-expiratory chest x-rays should be obtained in patients suspected of having aspirated a foreign body. However, the presence of normal findings on chest radiography should not rule out foreign body aspiration as not all objects can be visualized. In fact, up to 50% of cases can have normal findings on radiography. This is because visibility of an object depends on many factors, such as the objects material, size, anatomic location and surrounding structures, as well as the patients body habitus. X-ray beams only show an object if that objects composition blocks the rays from traveling through, making it radiopaque and appearing lighter or white on the image. This also requires it to not be stuck behind something that blocks the beams first. Objects that are radiopaque include items made of most metals except aluminum, bones except most fish bones, and glass. If the material does not block the x-ray beams it is considered radiolucent and will appear dark which prevents visualization. This includes material such as most plastics, most fish bones, wood, and most aluminum objects.Other diagnostic imaging modalities, such as magnetic resonance imaging, computed tomography, and ventilation perfusion scans play a limited role in the diagnosis of foreign body aspiration.Signs on x-ray that are more commonly seen than the object itself and can be indicative of foreign body aspiration include visualization of the foreign body or hyperinflation of the affected lung. Other x-ray findings that can be seen with foreign body aspiration include obstructive emphysema, atelectasis, and consolidation.While, x-ray can be used to visualize the location and identity of a foreign body, rigid bronchoscopy under general anesthesia is the gold-standard for diagnosis since the foreign body can be visualized and removed with this intervention. Rigid bronchoscopy is indicated when two of the three following criteria are met: report of foreign body aspiration by the patient or a witness, abnormal lung exam findings, or abnormal chest x-ray findings.
Management
See also: Choking § Treatment, Basic Life Support, Advanced Cardiovascular Life Support
Treatment of foreign body aspiration is determined by the age of the patient and the severity of obstruction of the airway involved.
Basic management
An airway obstruction can be partial or complete. In partial obstruction, the patient can usually clear the foreign body with coughing. In complete obstruction, acute intervention is required to remove the foreign body.If foreign body aspiration is suspected, finger sweeping in the mouth is not recommended due to the increased risk of displacing the foreign object further into the airway.For choking children less than 1 year of age, the child should be placed face down over the rescuers arm. Back blows should be delivered with the heel of the hand, then the patient should be turned face-up and chest thrusts should be administered. The rescuer should alternate five back blows followed by five chest thrusts until the object is cleared. The Heimlich maneuver should be used in choking patients older than 1 year of age to dislodge a foreign body. If the patient becomes unresponsive during physical intervention, cardiopulmonary resuscitation (CPR) should be started.
Advanced management
In the event that the basic measures do not remove the foreign body, and adequate ventilation cannot be restored, need for treatment by trained personnel becomes necessary. Laryngoscopy should be performed in unresponsive patients if non-invasive airway clearance techniques are unsuccessful. Laryngoscopy involves placing a device in the mouth to visualize the back of the airway. If the foreign body can be seen, it can be removed with forceps. An endotracheal tube should then be placed in order to prevent airway compromise from resulting inflammation after the procedure. If the foreign body cannot be visualized, intubation, tracheotomy, or needle cricothyrotomy can be done to restore an airway for patients who have become unresponsive due to airway compromise.If non-invasive measures do not dislodge the foreign body, and the patient can maintain adequate ventilation, rigid bronchoscopy under general anesthesia should be performed. Supplemental oxygen, cardiac monitoring, and a pulse oximeter should be applied to the patient. Efforts should be made to keep the patient calm and avoid agitating the patient to prevent further airway compromise. Flexible rather than rigid bronchoscopy might be used when the diagnosis or object location are unclear. When flexible bronchoscope is used, rigid bronchoscope is typically on standby and readily available as this is the preferred approach for removal. Rigid bronchoscopy allows good airway control, ready bleeding management, better visualization, and ability to manipulate the aspirated object with a variety of forceps. Flexible bronchoscopy may be used for extraction when distal access is needed and the operator is experienced in this technique. Potential advantages include avoidance of general anesthesia as well as the ability to reach subsegmental bronchi which are smaller in diameter and further down the respiratory tract than the main bronchi. The main disadvantage of using a flexible scope is the risk of further dislodging the object and causing airway compromise. Bronchoscopy is successful in removing the foreign body in approximately 95% of cases with a complication rate of only 1%.After the foreign body is removed, patients should receive nebulized beta-adrenergic medication and chest physiotherapy to further protect the airway. Steroidal anti-inflammatories and antibiotics are not routinely administered except in certain scenarios. These include situations such as when the foreign body is difficult or impossible to extract, when there is a documented respiratory tract infection, and when swelling within the airway occurs after removal of the object. Glucocorticoids may be administered when the foreign body is surrounded by inflamed tissue and extraction is difficult or impossible. In such cases, extraction may be delayed for a short course of glucocorticoids so that the inflammation may be reduced before subsequent attempts. These patients should remain under observation in the hospital until successful extraction as this practice can result in dislodgement of the foreign body. Antibiotics are appropriate when an infection has developed but should not delay extraction. In fact, removal of the object may improve infection control by removing the infectious source as well as using cultures taken during the bronchoscopy to guide antibiotic choice. When airway edema or swelling occur, the patient may have stridor. In these cases, glucocorticoids, aerosolized epinephrine, or helium oxygen therapy may be considered as part of the management plan.Patients who are clinically stable with no need for supplemental oxygen after extraction may be discharged from the hospital the same day as the procedure. Routine imaging such as a follow-up chest x-ray are not needed unless symptoms persist or worsen, or if the patient had imaging abnormalities previously to verify return to normal. Most children are discharged within 24 hours of the procedure.
Complications
Many complications can develop if a foreign body remains in the airway. There are also complications that may occur after removal of the object depending on the timeline of events. Cardiac arrest and death are possible complications if a sudden complete obstruction occurs and immediate medical care is not performed. The most common complication from a foreign body aspiration is a pulmonary infection, such as pneumonia or a lung abscess. This can be more difficult to overcome in the elderly population and lead to even further complications. Patients may develop inflammation of the airway walls from a foreign body remaining in the airway. Airway secretions can be retained behind the obstruction which creates an ideal environment for subsequent bacterial overgrowth. Hyperinflation of the airway distal to the obstruction can also occur if the foreign body is not removed. Episodes of recurrent pneumonia in the same lung field should prompt evaluation for a possible foreign body in the airway.Whether or not the foreign body is removed, complications such as chemical bronchitis, mucosal reactions, and the development of granulation tissue are possible.Complications can also arise from interventions used to remove a foreign body from the airway. Rigid bronchoscopy is the gold standard for removal of a foreign body, however this intervention does have potential risks. The most common complication from rigid bronchoscopy is damage to the patients teeth. Other less common complications include cuts to the mouth or esophagus, perforation of the bronchial tree, damage to the vocal cords, pneumothorax, atelectasis, stricture, and perforation.
Prevention
There are many factors to consider when determining how to decrease the likelihood of aspiration, especially in the extremely young and elderly populations.The major considerations in children are their developmental level in terms of swallowing and protecting their airway via mechanisms such as coughing and the gag reflex. Also, certain object characteristics such as size, shape, and material can increase their potential to cause choking among children. When there are multiple children in a shared environment, toys and foods that are acceptable for older children often pose a choking risk to the younger children. Education for parents and caretakers should continue to be prioritized when possible. This can be through positions such as pediatricians, dentists, and school teachers as well as media advertisements and printed materials. This education should include educating caretakers on how to recognize choking and perform first aid and cardiopulmonary resuscitation, check for warning labels and toy recalls, and avoid high risk objects and foods.Thanks to numerous public advancements, such as the Child Safety Protection Act and the Federal Hazardous Substance Act (FHSA), warning labels for choking hazards are required on packaging for small balls, marbles, balloons, and toys with small parts when these are intended for use by children in at-risk age groups. Also, the Consumer Product Safety Improvement Act of 2008 amended the FHSA to also require advertisements on websites, catalogues, and other printed materials to include the choking hazard warnings.
== References == |
End-of-life care | End-of-life care (EoLC) refers to health care provided in the time leading up to a persons death. End-of-life care can be provided in the hours, days, or months before a person dies and encompasses care and support for a persons mental and emotional needs, physical comfort, spiritual needs, and practical tasks.EoLC is most commonly provided at home, in the hospital, or in a long-term care facility with care being provided by family members, nurses, social workers, physicians, and other support staff. Facilities may also have palliative or hospice care teams that will provide end-of-life care services. Decisions about end-of-life care are often informed by medical, financial and ethical considerations.In most advanced countries, medical spending on people in the last twelve months of life makes up roughly 10% of total aggregate medical spending, while those in the last three years of life can cost up to 25%.
Medical
Advanced care planning
Advances in medicine in the last few decades have provided us with an increasing number of options to extend a personss life and highlighted the importance of ensuring that an individuals preferences and values for end-of-life care are honored. Advanced care planning is the process by which a person of any age is able to provide their preferences and ensure that their future medical treatment aligns with their personal values and life goals. It is typically a continual process, with ongoing discussions about a patients current prognosis and conditions as well as conversations about medical dilemmas and options. A person will typically have these conversations with their doctor and ultimately record their preferences in an advance healthcare directive. An advance healthcare directive is a legal document that either documents a persons decisions about desired treatment or indicates who a person has entrusted to make their care decisions for them. The two main types of advanced directives are a living will and durable power of attorney for healthcare. A living will includes a persons decisions regarding their future care, a majority of which address resuscitation and life support but may also delve into a patients’ preferences regarding hospitalization, pain control, and specific treatments that they may undergo in the future. The living will will typically take effect when a patient is terminally ill with low chances of recovery. A durable power of attorney for healthcare allows a person to appoint another individual to make healthcare decisions for them under a specified set of circumstances. Combined directives, such as the "Five Wishes", that include components of both the living will and durable power of attorney for healthcare, are being increasingly utilized. Advanced care planning often includes preferences for CPR initiation, nutrition (tube feeding), as well as decisions about the use of machines to keep a person breathing, or support their heart or kidneys. Many studies have reported benefits to patients who complete advanced care planning, specifically noting the improved patient and surrogate satisfaction with communication and decreased clinician distress. However, there is a notable lack of empirical data about what outcome improvements patients experience, as there are considerable discrepancies in what constitutes as advanced care planning and heterogeneity in the outcomes measured. Advanced care planning remains an underutilized tool for patients. Researchers have published data to support the use of new relationship-based and supported decision making models that can increase the use and maximize the benefit of advanced care planning.
End-of-life care conversations
End-of-life care conversations are part of the treatment planning process for terminally ill patients requiring palliative care involving a discussion of a patients prognosis, specification of goals of care, and individualized treatment planning. Current studies suggest that many patients prioritize proper symptom management, avoidance of suffering, and care that aligns with ethical and cultural standards. Specific conversations can include discussions about cardiopulmonary resuscitation (ideally occurring before the active dying phase as to not force the conversation during a medical crisis/emergency), place of death, organ donation, and cultural/religious traditions. As there are many factors involved in the end-of-life care decision-making process, the attitudes and perspectives of patients and families may vary. For example, family members may differ over whether life extension or life quality is the main goal of treatment. As it can be challenging for families in the grieving process to make timely decisions that respect the patients wishes and values, having an established advanced care directive in place can prevent over-treatment, under-treatment, or further complications in treatment management.Patients and families may also struggle to grasp the inevitability of death, and the differing risks and effects of medical and non-medical interventions available for end-of-life care. A systematic literature review reviewing the frequency of end-of-life care conversations between COPD patients and clinicians found that conversations regarding end-of-life care often occur when a patient has advanced stage disease and occur at a low frequency. To prevent interventions that are not in accordance with the patients wishes, end-of-life care conversations and advanced care directives can allow for the care they desire, as well as help prevent confusion and strain for family members.
Signs of dying
The National Cancer Institute in the United States (US) advises that the presence of some of the following signs may indicate that death is approaching:
Drowsiness, increased sleep, and/or unresponsiveness (caused by changes in the patients metabolism).
Confusion about time, place, and/or identity of loved ones; restlessness; visions of people and places that are not present; pulling at bed linen or clothing (caused in part by changes in the patients metabolism).
Decreased socialization and withdrawal (caused by decreased oxygen to the brain, decreased blood flow, and mental preparation for dying).
Changes in breathing (indicate neurologic compromise and impending death) and accumulation of upper airway secretions (resulting in crackling and gurgling breath sounds)
Decreased need for food and fluids, and loss of appetite (caused by the bodys need to conserve energy and its decreasing ability to use food and fluids properly).
Decreased oral intake and impaired swallowing (caused by general physical weakness and metabolic disturbances, including but not limited to hypercalcemia)
Loss of bladder or bowel control (caused by the relaxing of muscles in the pelvic area).
Darkened urine or decreased amount of urine (caused by slowing of kidney function and/or decreased fluid intake).
Skin becoming cool to the touch, particularly the hands and feet; skin may become bluish in color, especially on the underside of the body (caused by decreased circulation to the extremities).
Rattling or gurgling sounds while breathing, which may be loud (death rattle); breathing that is irregular and shallow; decreased number of breaths per minute; breathing that alternates between rapid and slow (caused by congestion from decreased fluid consumption, a buildup of waste products in the body, and/or a decrease in circulation to the organs).
Turning of the head toward a light source (caused by decreasing vision).
Increased difficulty controlling pain (caused by progression of the disease).
Involuntary movements (called myoclonus), increased heart rate, hypertension followed by hypotension, and loss of reflexes in the legs and arms are additional signs that the end of life is near.
Symptoms management
The following are some of the most common potential problems that can arise in the last days and hours of a patients life:
Pain
Typically controlled with opioids, like morphine, fentanyl, hydromorphone or, in the United Kingdom, diamorphine. High doses of opioids can cause respiratory depression, and this risk increases with concomitant use of alcohol and other sedatives. Careful use of opioids is important to improve the patients quality of life while avoiding overdoses.
Agitation
Delirium, terminal anguish, restlessness (e.g. thrashing, plucking, or twitching). Typically controlled using clonazepam or midazolam,antipsychotics such as haloperidol or levomepromazine may also be used instead of, or concomitantly with benzodiazepines. Symptoms may also sometimes be alleviated by rehydration, which may reduce the effects of some toxic drug metabolites.
Respiratory tract secretions
Saliva and other fluids can accumulate in the oropharynx and upper airways when patients become too weak to clear their throats, leading to a characteristic gurgling or rattle-like sound ("death rattle"). While apparently not painful for the patient, the association of this symptom with impending death can create fear and uncertainty for those at the bedside. The secretions may be controlled using drugs such as hyoscine butylbromide, glycopyrronium, or atropine. Rattle may not be controllable if caused by deeper fluid accumulation in the bronchi or the lungs, such as occurs with pneumonia or some tumours.
Nausea and vomiting
Typically controlled using haloperidol, metoclopramide, ondansetron, cyclizine; or other anti-emetics.
Dyspnea (breathlessness)
Typically controlled with opioids, like morphine, fentanyl or, in the United Kingdom, diamorphineConstipation
Low food intake and opioid use can lead to constipation which can then result in agitation, pain, and delirium. Laxatives and stool softeners are used to prevent constipation. In patients with constipation, the dose of laxatives will be increased to relieve symptoms. Methylnaltrexone is approved to treat constipation due to opioid use.Other symptoms that may occur, and may be mitigated to some extent, include cough, fatigue, fever, and in some cases bleeding.
Medication Administration
Subcutaneous injections are one preferred means of delivery when it has become difficult for patients to swallow or to take pills orally, and if repeated medication is needed, a syringe driver (or infusion pump in the US) is often likely to be used, to deliver a steady low dose of medication. In some settings, such as the home or hospice, sublingual routes of administration may be used for most prescriptions and medications.Another means of medication delivery, available for use when the oral route is compromised, is a specialized catheter designed to provide comfortable and discreet administration of ongoing medications via the rectal route. The catheter was developed to make rectal access more practical and provide a way to deliver and retain liquid formulations in the distal rectum so that health practitioners can leverage the established benefits of rectal administration. Its small flexible silicone shaft allows the device to be placed safely and remain comfortably in the rectum for repeated administration of medications or liquids. The catheter has a small lumen, allowing for small flush volumes to get medication to the rectum. Small volumes of medications (under 15mL) improve comfort by not stimulating the defecation response of the rectum and can increase the overall absorption of a given dose by decreasing pooling of medication and migration of medication into more proximal areas of the rectum where absorption can be less effective.
Integrated pathways
Integrated care pathways are an organizational tool used by healthcare professionals to clearly define the roles of each team-member and coordinate how and when care will be provided. These pathways are utilized to ensure best practices are being utilized for end-of-life care, such as evidence-based and accepted health care protocols, and to list the required features of care for a specific diagnosis or clinical prolem. Many institutions have a predetermined pathway for end of life care, and clinicians should be aware of and make use of these plans when possible. In the United Kingdom, end-of-life care pathways are based on the Liverpool Care Pathway. Originally developed to provide evidence based care to dying cancer patients, this pathway has been adapted and used for a variety of chronic conditions at clinics in the UK and internationally. Despite its increasing popularity, the 2016 Cochrane Review, which only analyzed one trial, showed limited evidence in the form of high-quality randomized clinical trials to measure the effectiveness of end-of-life care pathways on clinical outcomes, physical outcomes, and emotional/psychological outcomes. The BEACON Project group developed an integrated care pathway entitled the Comfort Care Order Set, which delinates care for the last days of life in either a hospice or acute care inpatient setting. This order set was implemented and evaluated in a multisite system throughout six United States Veterans Affairs Medical Centers, and the study found increased orders for opioid medication post-pathway implementation, as well as more orders for antipsychotic medications, more patients undergoing palliative care consultations, more advance directives, and increased sublingual drug administration. The intervention did not, however, decrease the proportion of deaths that occurred in an ICU setting or the utilization of restraints around death.
Home-based end-of-life care
While not possible for every person needing care, surveys of the general public suggest most people would prefer to die at home. In the period from 2003 to 2017, the number of deaths at home in the United States increased from 23.8% to 30.7%, while the number of deaths in the hospital decreased from 39.7% to 29.8%. Home-based end-of-life care may be delivered in a number of ways, including by an extension of a primary care practice, by a palliative care practice, and by home care agencies such as Hospice. High-certainty evidence indicates that implementation of home-based end-of-life care programs increases the number of adults who will die at home and slightly improves their satisfaction at a one-month follow-up. There is low-certainty evidence that there may be very little or no difference in satisfaction of the person needing care for longer term (6 months). The number of people who are admitted to hospital during an end-of-life care program is not known. In addition, the impact of home-based end-of-life care on caregivers, healthcare staff, and health service costs is not clear, however, there is weak evidence to suggest that this intervention may reduce health care costs by a small amount.
Disparities in end-of-life care
Not all groups in society have good access to end-of-life care. A systematic review conducted in 2021 investigated the end of life care experiences of people with severe mental illness, including those with schizophrenia, bipolar disorder, and major depressive disorder. The research found that individuals with a severe mental illness were unlikely to receive the most appropriate end of life care. The review recommended that there needs to be close partnerships and communication between mental health and end of life care systems, and these teams need to find ways to support people to die where they choose. More training, support and supervision needs to be available for professionals working in end of life care; this could also decrease prejudice and stigma against individuals with severe mental illness at the end of life, notably in those who are homeless. In addition, studies have shown that minority patients face several additional barriers to receiving quality end-of-life care. Minority patients are prevented from accessing care at an equitable rate for a variety of reasons including: individual discrimination from caregivers, cultural insensitivity, racial economic disparities, as well as medical mistrust.
Non-medical
Family and friends
Family members are often uncertain as to what they should be doing when a person is dying. Many gentle, familiar daily tasks, such as combing hair, putting lotion on delicate skin, and holding hands, are comforting and provide a meaningful method of communicating love to a dying person.Family members may be suffering emotionally due to the impending death. Their own fear of death may affect their behavior. They may feel guilty about past events in their relationship with the dying person or feel that they have been neglectful. These common emotions can result in tension, fights between family members over decisions, worsened care, and sometimes (in what medical professionals call the "Daughter from California syndrome") a long-absent family member arrives while a patient is dying to demand inappropriately aggressive care.
Family members may also be coping with unrelated problems, such as physical or mental illness, emotional and relationship issues, or legal difficulties. These problems can limit their ability to be involved, civil, helpful, or present.
Spirituality and Religion
Spirituality is thought to be of increased importance to an individuals wellbeing during a terminal illness or toward the end-of-life. Pastoral/spiritual care has a particular significance in end of life care, and is considered an essential part of palliative care by the WHO. In palliative care, responsibility for spiritual care is shared by the whole team, with leadership given by specialist practitioners such as pastoral care workers. The palliative care approach to spiritual care may, however, be transferred to other contexts and to individual practice.Spiritual, cultural, and religious beliefs may influence or guide patient preferences regarding end-of-life care. Healthcare providers caring for patients at the end of life can engage family members and encourage conversations about spiritual practices to better address the different needs of diverse patient populations. Studies have shown that people who identify as religious also report higher levels of well-being. Religion has also been shown to be inversely correlated with depression and suicide. While religion provides some benefits to patients, there is some evidence of increased anxiety and other negative outcomes in some studies. While spirituality has been associated with less aggressive end-of-life care, religion has been associated with an increased desire for aggressive care in some patients. Despite these varied outcomes, spiritual and religious care remains an important aspect of care for patients. Studies have shown that barriers to providing adequate spiritual and religious care include a lack of cultural understanding, limited time, and a lack of formal training or experience.Many hospitals, nursing homes, and hospice centers have chaplains who provide spiritual support and grief counseling to patients and families of all religious and cultural backgrounds.
Attitudes of healthcare professionals
End-of-life care is an interdisciplinary endeavor involving physicians, nurses, physical therapists, occupational therapists, pharmacists and social workers. Depending on the facility and level of care needed, the composition of the interprofessional team can vary. Health professional attitudes about end-of-life care depend in part on the providers role in the care team.
Physicians generally have favorable attitudes towards Advance Directives, which are a key facet of end-of-life care. Medical doctors who have more experience and training in end-of-life care are more likely to cite comfort in having end-of-life-care discussions with patients. Those physicians who have more exposure to end-of-life care also have a higher likelihood of involving nurses in their decision-making process.A systematic review assessing end-of-life conversations between heart failure patients and healthcare professionals evaluated physician attitudes and preferences towards end-of-life care conversations. The study found that physicians found difficulty initiating end-of-life conversations with their heart failure patients, due to physician apprehension over inducing anxiety in patients, the uncertainty in a patients prognosis, and physicians awaiting patient cues to initiate end-of-life care conversations.Although physicians make official decisions about end-of-life care, nurses spend more time with patients and often know more about patient desires and concerns. In a Dutch national survey study of attitudes of nursing staff about involvement in medical end-of-life decisions, 64% of respondents thought patients preferred talking with nurses than physicians and 75% desired to be involved in end-of-life decision making.
End-of-life care around the globe
Canada
In 2012, Statistics Canadas General Social Survey on Caregiving and care receiving found that 13% of Canadians (3.7 million) aged 15 and older reported that at some point in their lives they had provided end-of-life or palliative care to a family member or friend. For those in their 50s and 60s, the percentage was higher, with about 20% reporting having provided palliative care to a family member or friend. Women were also more likely to have provided palliative care over their lifetimes, with 16% of women reporting having done so, compared with 10% of men. These caregivers helped terminally ill family members or friends with personal or medical care, food preparation, managing finances or providing transportation to and from medical appointments.
United Kingdom
End of life care has been identified by the UK Department of Health as an area where quality of care has previously been "very variable," and which has not had a high profile in the NHS and social care. To address this, a national end of life care programme was established in 2004 to identify and propagate best practice, and a national strategy document published in 2008. The Scottish Government has also published a national strategy.In 2006 just over half a million people died in England, about 99% of them adults over the age of 18, and almost two-thirds adults over the age of 75. About three-quarters of deaths could be considered "predictable" and followed a period of chronic illness – for example heart disease, cancer, stroke, or dementia. In all, 58% of deaths occurred in an NHS hospital, 18% at home, 17% in residential care homes (most commonly people over the age of 85), and about 4% in hospices. However, a majority of people would prefer to die at home or in a hospice, and according to one survey less than 5% would rather die in hospital. A key aim of the strategy therefore is to reduce the needs for dying patients to have to go to hospital and/or to have to stay there; and to improve provision for support and palliative care in the community to make this possible. One study estimated that 40% of the patients who had died in hospital had not had medical needs that required them to be there.In 2015 and 2010, the UK ranked highest globally in a study of end-of-life care. The 2015 study said "Its ranking is due to comprehensive national policies, the extensive integration of palliative care into the National Health Service, a strong hospice movement, and deep community engagement on the issue." The studies were carried out by the Economist Intelligence Unit and commissioned by the Lien Foundation, a Singaporean philanthropic organisation.The 2015 National Institute for Health and Care Excellence guidelines introduced religion and spirituality among the factors which physicians shall take into account for assessing palliative care needs. In 2016, the UK Minister of Health signed a document which declared people "should have access to personalised care which focuses on the preferences, beliefs and spiritual needs of the individual." As of 2017, more than 47% of the 500,000 deaths in the UK occurred in hospitals.In 2021 the National Palliative and End of Life Care Partnership published their six ambitions for 2021–26. These include fair access to end of life care for everyone regardless of who they are, where they live or their circumstances, and the need to maximise comfort and wellbeing. Informed and timely conversations are also highlighted. Research funded by the National Institute for Health and Care Research (NIHR) has addressed these areas of need. Examples highlight inequalities faced by several groups and offers recommendations. These include the need for close partnership between services caring for people with severe mental illness, improved understanding of barriers faced by Gypsy, Traveller and Roma communities, the provision of flexible palliative care services for children from ethnic minorities or deprived areas.Other research suggests that giving nurses and pharmacists easier access to electronic patient records about prescribing could help people manage their symptoms at home. A named professional to support and guide patients and carers through the healthcare system could also improve the experience of care at home at the end of life. A synthesised review looking at palliative care in the UK created a resource showing which services were available and grouped them according to their intended purpose and benefit to the patient. They also stated that currently in the UK palliative services are only available to patients with a timeline to death, usually 12 months or less. They found these timelines to often be inaccurate and created barriers to patients accessing appropriate services. They call for a more holistic approach to end of life care which is not restricted by arbitrary timelines.
United States
As of 2019, physician-assisted dying is legal in eight states (California, Colorado, Hawaii, Maine, New Jersey, Oregon, Vermont, Washington) and Washington D.C.Spending on those in the last twelve months accounts for 8.5% of total aggregate medical spending in the United States.When considering only those aged 65 and older, estimates show that about 27% of Medicares annual $327 billion budget ($88 billion) in 2006 goes to care for patients in their final year of life. For the over-65s, between 1992 and 1996, spending on those in their last year of life represented 22% of all medical spending, 18% of all non-Medicare spending, and 25 percent of all Medicaid spending for the poor. These percentages appears to be falling over time, as in 2008, 16.8% of all medical spending on the over 65s went on those in their last year of life.Predicting death is difficult, which has affected estimates of spending in the last year of life; when controlling for spending on patients who were predicted as likely to die, Medicare spending was estimated at 5% of the total.
See also
Advance health care directive
Death midwife
Hospice
Liverpool Care Pathway
Palliative care
Childrens palliative care
Physician assisted suicide
Robert Martensen
References
Further reading
External links
"End of Life Issues". MedlinePlus.
"EndLink - Resource for End of Life Care Education". Robert H. Lurie Comprehensive Cancer Center. Northwestern University. Archived from the original on 2010-11-18.
"End of life care". NHS Choices. 29 May 2018.
"End of Life Care Strategy - promoting high quality care for all adults at the end of life". Publications policy and guidance. UK Department of Health.
"Survivorship A to Z: End-Of-Life". Survivorship.
"Before I Die: Medical Care and Personal Choices". Thirteen/WNET. Public Broadcasting Service. 22 April 1997. The program explores the medical, ethical, and social issues surrounding end-of-life care in America today. |
Androgen insensitivity syndrome | Androgen insensitivity syndrome (AIS) is a difference in sex development involving hormonal resistance due to androgen receptor dysfunction.It affects 1 in 20,000 to 64,000 XY (karyotypically male) births. The condition results in the partial or complete inability of cells to respond to androgens. This unresponsiveness can impair or prevent the development of male genitals, as well as impairing or preventing the development of male secondary sexual characteristics at puberty. It does not significantly impair female genital or sexual development. The insensitivity to androgens is therefore clinically significant only when it occurs in genetic males, (i.e. individuals with a Y-chromosome, or more specifically, an SRY gene). Clinical phenotypes in these individuals range from a typical male habitus with mild spermatogenic defect or reduced secondary terminal hair, to a full female habitus, despite the presence of a Y-chromosome.AIS is divided into three categories that are differentiated by the degree of genital masculinization: complete androgen insensitivity syndrome (CAIS) is indicated when the external genitalia are those of a typical female; mild androgen insensitivity syndrome (MAIS) is indicated when the external genitalia are those of a typical male, and partial androgen insensitivity syndrome (PAIS) is indicated when the external genitalia are partially, but not fully, masculinized. Androgen insensitivity syndrome is the largest single entity that leads to 46,XY undermasculinized genitalia.Management of AIS is currently limited to symptomatic management; no method is currently available to correct the malfunctioning androgen receptor proteins produced by AR gene mutations. Areas of management include sex assignment, genitoplasty, gonadectomy to reduce tumor risk, hormone replacement therapy, genetic counseling, and psychological counseling.
Genetics
The human androgen receptor (AR) is a protein encoded by a gene located on the proximal long arm of the X chromosome (locus Xq11-Xq12). The protein coding region consists of approximately 2,757 nucleotides (919 codons) spanning eight exons, designated 1-8 or A-H. Introns vary in size between 0.7 and 26 kb. Like other nuclear receptors, the AR protein consists of several functional domains: the transactivation domain (also called the transcription-regulation domain or the amino / NH2-terminal domain), the DNA-binding domain, the hinge region, and the steroid-binding domain (also called the carboxyl-terminal ligand-binding domain). The transactivation domain is encoded by exon 1, and makes up more than half of the AR protein. Exons 2 and 3 encode the DNA-binding domain, while the 5 portion of exon 4 encodes the hinge region. The remainder of exons 4 through 8 encodes the ligand binding domain.
Trinucleotide satellite lengths and AR transcriptional activity
The AR gene contains two polymorphic trinucleotide microsatellites in exon 1. The first microsatellite (nearest the 5 end) contains 8 to 60 repetitions of the glutamine codon "CAG" and is thus known as the polyglutamine tract. The second microsatellite contains 4 to 31 repetitions of the glycine codon "GGC" and is known as the polyglycine tract. The average number of repetitions varies by ethnicity, with Caucasians exhibiting an average of 21 CAG repeats, and Blacks 18. In men, disease states are associated with extremes in polyglutamine tract length; prostate cancer, hepatocellular carcinoma, and intellectual disability are associated with too few repetitions, while spinal and bulbar muscular atrophy (SBMA) is associated with a CAG repetition length of 40 or more. Some studies indicate that the length of the polyglutamine tract is inversely correlated with transcriptional activity in the AR protein, and that longer polyglutamine tracts may be associated with male infertility and undermasculinized genitalia in men. However, other studies have indicated no such correlation exists. A comprehensive meta-analysis of the subject published in 2007 supports the existence of the correlation, and concluded these discrepancies could be resolved when sample size and study design are taken into account. Some studies suggest longer polyglycine tract lengths are also associated with genital masculinization defects in men. Other studies find no such association.
AR mutations
As of 2010, over 400 AR mutations have been reported in the AR mutation database, and the number continues to grow. Inheritance is typically maternal and follows an X-linked recessive pattern; individuals with a 46,XY karyotype always express the mutant gene since they have only one X chromosome, whereas 46,XX carriers are minimally affected. About 30% of the time, the AR mutation is a spontaneous result, and is not inherited. Such de novo mutations are the result of a germ cell mutation or germ cell mosaicism in the gonads of one of the parents, or a mutation in the fertilized egg itself. In one study, three of eight de novo mutations occurred in the postzygotic stage, leading to the estimate that up to one-third of de novo mutations result in somatic mosaicism. Not every mutation of the AR gene results in androgen insensitivity; one particular mutation occurs in 8 to 14% of genetic males, and is thought to adversely affect only a small number of individuals when other genetic factors are present.
Other causes
Some individuals with CAIS or PAIS do not have any AR mutations despite clinical, hormonal, and histological features sufficient to warrant an AIS diagnosis; up to 5% of women with CAIS do not have an AR mutation, as well as between 27 and 72% of individuals with PAIS.
In one patient, the underlying cause for presumptive PAIS was a mutant steroidogenic factor-1 (SF-1) protein. In another patient, CAIS was the result of a deficit in the transmission of a transactivating signal from the N-terminal region of the androgen receptor to the basal transcription machinery of the cell. A coactivator protein interacting with the activation function 1 (AF-1) transactivation domain of the androgen receptor may have been deficient in this patient. The signal disruption could not be corrected by supplementation with any coactivators known at the time, nor was the absent coactivator protein characterized, which left some in the field unconvinced that a mutant coactivator would explain the mechanism of androgen resistance in CAIS or PAIS patients with a typical AR gene.
XY karyotype
Depending on the mutation, a person with a 46,XY karyotype and AIS can have either a male (MAIS) or female (CAIS) phenotype, or may have genitalia that are only partially masculinized (PAIS). The gonads are testes regardless of phenotype due to the influence of the Y chromosome. A 46,XY female, thus, does not have ovaries, and can not contribute an egg towards conception. In some cases, 46, XY females do form a vestigial uterus and have been able to gestate a children. Such examples are rare and have required the use of an egg donor, hormone therapy, and IVF.Several case studies of fertile 46,XY males with AIS have been published, although this group is thought to be a minority. In some cases, infertile males with MAIS have been able to conceive children after increasing their sperm count through the use of supplementary testosterone.A genetic male conceived by a man with AIS would not receive his fathers X chromosome, thus would neither inherit nor carry the gene for the syndrome. A genetic female conceived in such a way would receive her fathers X chromosome, thus would become a carrier.
XX karyotype
Genetic females (46,XX karyotype) have two X chromosomes, thus have two AR genes. A mutation in one (but not both) results in a minimally affected, fertile, female carrier. Some carriers have been noted to have slightly reduced body hair, delayed puberty, and/or tall stature, presumably due to skewed X-inactivation. A female carrier will pass the affected AR gene to her children 50% of the time. If the affected child is a genetic female, she, too, will be a carrier. An affected 46,XY child will have AIS.A genetic female with mutations in both AR genes could theoretically result from the union of a fertile man with AIS and a female carrier of the gene, or from de novo mutation. However, given the scarcity of fertile AIS men and low incidence of AR mutation, the chances of this occurrence are small. The phenotype of such an individual is a matter of speculation; as of 2010, no such documented case has been published.
Correlation of genotype and phenotype
Individuals with partial AIS, unlike those with the complete or mild forms, present at birth with ambiguous genitalia, and the decision to raise the child as male or female is often not obvious. Unfortunately, little information regarding phenotype can be gleaned from precise knowledge of the AR mutation itself; the same AR mutation may cause significant variation in the degree of masculinization in different individuals, even among members of the same family. Exactly what causes this variation is not entirely understood, although factors contributing to it could include the lengths of the polyglutamine and polyglycine tracts, sensitivity to and variations in the intrauterine endocrine milieu, the effect of coregulatory proteins active in Sertoli cells, somatic mosaicism, expression of the 5RD2 gene in genital skin fibroblasts, reduced AR transcription and translation from factors other than mutations in the AR coding region, an unidentified coactivator protein, enzyme deficiencies such as 21-hydroxylase deficiency, or other genetic variations such as a mutant steroidogenic factor-1 protein. The degree of variation, however, does not appear to be constant across all AR mutations, and is much more extreme in some. Missense mutations that result in a single amino acid substitution are known to produce the most phenotypic diversity.
Pathophysiology
Androgens and the androgen receptor
The effects that androgens have on the human body (virilization, masculinization, anabolism, etc.) are not brought about by androgens themselves, but rather are the result of androgens bound to androgen receptors; the androgen receptor mediates the effects of androgens in the human body. Likewise, the androgen receptor itself is generally inactive in the cell until androgen binding occurs.The following series of steps illustrates how androgens and the androgen receptor work together to produce androgenic effects:
In this way, androgens bound to androgen receptors regulate the expression of target genes, thus produce androgenic effects.Theoretically, certain mutant androgen receptors can function without androgens; in vitro studies have demonstrated that a mutant androgen receptor protein can induce transcription in the absence of androgen if its steroid binding domain is deleted. Conversely, the steroid-binding domain may act to repress the AR transactivation domain, perhaps due to the ARs unliganded conformation.
Androgens in fetal development
Human embryos develop similarly for the first six weeks, regardless of genetic sex (46,XX or 46,XY karyotype); the only way to tell the difference between 46,XX or 46,XY embryos during this time period is to look for Barr bodies or a Y chromosome. The gonads begin as bulges of tissue called the genital ridges at the back of the abdominal cavity, near the midline. By the fifth week, the genital ridges differentiate into an outer cortex and an inner medulla, and are called indifferent gonads. By the sixth week, the indifferent gonads begin to differentiate according to genetic sex. If the karyotype is 46,XY, testes develop due to the influence of the Y chromosome’s SRY gene. This process does not require the presence of androgen, nor a functional androgen receptor.Until around the seventh week of development, the embryo has indifferent sex accessory ducts, which consist of two pairs of ducts: the Müllerian ducts and the Wolffian ducts. Sertoli cells within the testes secrete anti-Müllerian hormone around this time to suppress the development of the Müllerian ducts, and cause their degeneration. Without this anti-Müllerian hormone, the Müllerian ducts develop into the female internal genitalia (uterus, cervix, fallopian tubes, and upper vaginal barrel). Unlike the Müllerian ducts, the Wolffian ducts will not continue to develop by default. In the presence of testosterone and functional androgen receptors, the Wolffian ducts develop into the epididymides, vasa deferentia, and seminal vesicles. If the testes fail to secrete testosterone, or the androgen receptors do not function properly, the Wolffian ducts degenerate.
Masculinization of the male external genitalia (the penis, penile urethra, and scrotum), as well as the prostate, are dependent on the androgen dihydrotestosterone. Testosterone is converted into dihydrotestosterone by the 5-alpha reductase enzyme. If this enzyme is absent or deficient, then dihydrotestosterone is not created, and the external male genitalia do not develop properly. As is the case with the internal male genitalia, a functional androgen receptor is needed for dihydrotestosterone to regulate the transcription of target genes involved in development.
Pathogenesis of AIS
Mutations in the androgen receptor gene can cause problems with any of the steps involved in androgenization, from the synthesis of the androgen receptor protein itself, through the transcriptional ability of the dimerized, androgen-AR complex. AIS can result if even one of these steps is significantly disrupted, as each step is required for androgens to activate the AR successfully and regulate gene expression. Exactly which steps a particular mutation will impair can be predicted, to some extent, by identifying the area of the AR in which the mutation resides. This predictive ability is primarily retrospective in origin; the different functional domains of the AR gene have been elucidated by analyzing the effects of specific mutations in different regions of the AR. For example, mutations in the steroid binding domain have been known to affect androgen binding affinity or retention, mutations in the hinge region have been known to affect nuclear translocation, mutations in the DNA-binding domain have been known to affect dimerization and binding to target DNA, and mutations in the transactivation domain have been known to affect target gene transcription regulation. Unfortunately, even when the affected functional domain is known, predicting the phenotypical consequences of a particular mutation (see Correlation of genotype and phenotype) is difficult.Some mutations can adversely impact more than one functional domain. For example, a mutation in one functional domain can have deleterious effects on another by altering the way in which the domains interact. A single mutation can affect all downstream functional domains if a premature stop codon or framing error results; such a mutation can result in a completely unusable (or unsynthesizable) androgen receptor protein. The steroid binding domain is particularly vulnerable to the effects of a premature stop codon or framing error, since it occurs at the end of the gene, and its information is thus more likely to be truncated or misinterpreted than other functional domains.Other, more complex relationships have been observed as a consequence of mutated AR; some mutations associated with male phenotypes have been linked to male breast cancer, prostate cancer, or in the case of spinal and bulbar muscular atrophy, disease of the central nervous system. The form of breast cancer seen in some men with PAIS is caused by a mutation in the ARs DNA-binding domain. This mutation is thought to cause a disturbance of the ARs target gene interaction that allows it to act at certain additional targets, possibly in conjunction with the estrogen receptor protein, to cause cancerous growth. The pathogenesis of spinal and bulbar muscular atrophy (SBMA) demonstrates that even the mutant AR protein itself can result in pathology. The trinucleotide repeat expansion of the polyglutamine tract of the AR gene that is associated with SBMA results in the synthesis of a misfolded AR protein that the cell fails to proteolyze and disperse properly. These misfolded AR proteins form aggregates in the cell cytoplasm and nucleus. Over the course of 30 to 50 years, these aggregates accumulate and have a cytotoxic effect, eventually resulting in the neurodegenerative symptoms associated with SBMA.
Diagnosis
The phenotypes that result from the insensitivity to androgens are not unique to AIS, thus the diagnosis of AIS requires thorough exclusion of other causes. Clinical findings indicative of AIS include the presence of a short vagina or undermasculinized genitalia, partial or complete regression of Müllerian structures, bilateral nondysplastic testes, and impaired spermatogenesis and/or virilization. Laboratory findings include a 46,XY karyotype and typical or elevated postpubertal testosterone, luteinizing hormone, and estradiol levels. The androgen binding activity of genital skin fibroblasts is typically diminished, although exceptions have been reported. Conversion of testosterone to dihydrotestosterone may be impaired. The diagnosis of AIS is confirmed if androgen receptor gene sequencing reveals a mutation, although not all individuals with AIS (particularly PAIS) will have an AR mutation (see Other Causes).Each of the three types of AIS (complete, partial, and mild) has a different list of differential diagnoses to consider. Depending on the form of AIS suspected, the list of differentials can include:
Classification
AIS is broken down into three classes based on phenotype: complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS), and mild androgen insensitivity syndrome (MAIS). A supplemental system of phenotypic grading that uses seven classes instead of the traditional three was proposed by pediatric endocrinologist Charmian A. Quigley et al. in 1995. The first six grades of the scale, grades 1 through 6, are differentiated by the degree of genital masculinization; grade 1 is indicated when the external genitalia is fully masculinized, grade 6 is indicated when the external genitalia is fully feminized, and grades 2 through 5 quantify four degrees of decreasingly masculinized genitalia that lie in the interim. Grade 7 is indistinguishable from grade 6 until puberty, and is thereafter differentiated by the presence of secondary terminal hair; grade 6 is indicated when secondary terminal hair is present, whereas grade 7 is indicated when it is absent. The Quigley scale can be used in conjunction with the traditional three classes of AIS to provide additional information regarding the degree of genital masculinization, and is particularly useful when the diagnosis is PAIS.
Complete AIS
Partial AIS
Mild AIS
Management
Management of AIS is currently limited to symptomatic management; no method is currently available to correct the malfunctioning androgen receptor proteins produced by AR gene mutations. Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, genetic counseling, and psychological counseling.
CAIS
PAIS
MAIS
Epidemiology
AIS represents about 15% to 20% of DSDs and affects 1 in 20,000 to 1 in 64,000 males.Estimates for the incidence of androgen insensitivity syndrome are based on a relatively small population size, thus are known to be imprecise. CAIS is estimated to occur in one of every 20,400 46,XY births. A nationwide survey in the Netherlands based on patients with genetic confirmation of the diagnosis estimates that the minimal incidence of CAIS is one in 99,000. The incidence of PAIS is estimated to be one in 130,000. Due to its subtle presentation, MAIS is not typically investigated except in the case of male infertility, thus its true prevalence is unknown.
Controversy
Preimplantation genetic diagnosis
Preimplantation genetic diagnosis (PGD or PIGD) refers to genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. When used to screen for a specific genetic sequence, its main advantage is that it avoids selective pregnancy termination, as the method makes it highly likely that a selected embryo will be free of the condition under consideration.In the UK, AIS appears on a list of serious genetic diseases that may be screened for via PGD. Some ethicists, clinicians, and intersex advocates have argued that screening embryos to specifically exclude intersex traits is based on social and cultural norms as opposed to medical necessity.
History
Recorded descriptions of the effects of AIS date back hundreds of years, although significant understanding of its underlying histopathology did not occur until the 1950s. The taxonomy and nomenclature associated with androgen insensitivity went through a significant evolution that paralleled this understanding.
Timeline of major milestones
1950: Lawson Wilkins administers daily methyltestosterone to a karyotype|46,XY female patient, who shows no signs of virilization. His experiment is the first documented demonstration of the pathophysiology of AIS.
1970: Mary F. Lyon and Susan Hawkes reported that a gene on the X chromosome caused complete insensitivity to androgens in mice.
1981: Barbara Migeon et al. narrowed down the locus of the human androgen receptor gene (or a factor controlling the androgen receptor gene) to somewhere between Xq11 and Xq13.
1988: The human androgen receptor gene is first cloned and partially analyzed by multiple parties. Terry Brown et al. reported the first mutations proven to cause AIS.
1989: Terry Brown et al. reported the exact locus of the AR gene (Xq11-Xq12), and Dennis Lubahn et al. published its intron-exon boundaries.
1994: The androgen receptor gene mutations database was created to provide a comprehensive listing of mutations published in medical journals and conference proceedings.
Early terminology
The first descriptions of the effects of AIS appeared in the medical literature as individual case reports or as part of a comprehensive description of intersex physicalities. In 1839, Scottish obstetrician Sir James Young Simpson published one such description in an exhaustive study of intersexuality that has been credited with advancing the medical communitys understanding of the subject. Simpsons system of taxonomy, however, was far from the first; taxonomies or descriptions for the classification of intersexuality were developed by Italian physician and physicist Fortuné Affaitati in 1549, French surgeon Ambroise Paré in 1573, French physician and sexology pioneer Nicolas Venette in 1687 (under the pseudonym Vénitien Salocini), and French zoologist Isidore Geoffroy Saint-Hilaire in 1832. All five of these authors used the colloquial term "hermaphrodite" as the foundation of their taxonomies, although Simpson himself questioned the propriety of the word in his publication. Use of the word "hermaphrodite" in the medical literature has persisted to this day, although its propriety is still in question. An alternative system of nomenclature has been recently suggested, but the subject of exactly which word or words should be used in its place still one of much debate.
Pseudohermaphroditism
"Pseudohermaphroditism" has, until very recently, been the term used in the medical literature to describe the condition of an individual whose gonads and karyotype do not match the external genitalia in the gender binary sense. For example, 46,XY individuals who have a female phenotype, but also have testes instead of ovaries—a group that includes all individuals with CAIS, as well as some individuals with PAIS—are classified as having "male pseudohermaphroditism", while individuals with both an ovary and a testis (or at least one ovotestis) are classified as having "true hermaphroditism". Use of the word in the medical literature antedates the discovery of the chromosome, thus its definition has not always taken karyotype into account when determining an individuals sex. Previous definitions of "pseudohermaphroditism" relied on perceived inconsistencies between the internal and external organs; the "true" sex of an individual was determined by the internal organs, and the external organs determined the "perceived" sex of an individual.German-Swiss pathologist Edwin Klebs is sometimes noted for using the word "pseudohermaphroditism" in his taxonomy of intersexuality in 1876, although the word is clearly not his invention as is sometimes reported; the history of the word "pseudohermaphrodite" and the corresponding desire to separate "true" hermaphrodites from "false", "spurious", or "pseudo" hermaphrodites, dates back to at least 1709, when Dutch anatomist Frederik Ruysch used it in a publication describing a subject with testes and a mostly female phenotype. "Pseudohermaphrodite" also appeared in the Acta Eruditorum later that same year, in a review of Ruyschs work. Also some evidence indicates the word was already being used by the German and French medical community long before Klebs used it; German physiologist Johannes Peter Müller equated "pseudohermaphroditism" with a subclass of hermaphroditism from Saint-Hilaires taxonomy in a publication dated 1834, and by the 1840s "pseudohermaphroditism" was appearing in several French and German publications, including dictionaries.
Testicular feminization
In 1953, American gynecologist John Morris provided the first full description of what he called "testicular feminization syndrome" based on 82 cases compiled from the medical literature, including two of his own patients. The term "testicular feminization" was coined to reflect Morris observation that the testicles in these patients produced a hormone that had a feminizing effect on the body, a phenomenon now understood to be due to the inaction of androgens, and subsequent aromatization of testosterone into estrogen. A few years before Morris published his landmark paper, Lawson Wilkins had shown through experiment that unresponsiveness of the target cell to the action of androgenic hormones was a cause of "male pseudohermaphroditism". Wilkins work, which clearly demonstrated the lack of a therapeutic effect when 46,XY patients were treated with androgens, caused a gradual shift in nomenclature from "testicular feminization" to "androgen resistance".
Other names
A distinct name has been given to many of the various presentations of AIS, such as Reifenstein syndrome (1947), Goldberg-Maxwell syndrome (1948), Morris syndrome (1953), Gilbert-Dreyfus syndrome (1957), Lubs syndrome (1959), "incomplete testicular feminization" (1963), Rosewater syndrome (1965), and Aimans syndrome (1979). Since it was not understood that these different presentations were all caused by the same set of mutations in the androgen receptor gene, a unique name was given to each new combination of symptoms, resulting in a complicated stratification of seemingly disparate disorders.Over the last 60 years, as reports of strikingly different phenotypes were reported to occur even among members of the same family, and as steady progress was made towards the understanding of the underlying molecular pathogenesis of AIS, these disorders were found to be different phenotypic expressions of one syndrome caused by molecular defects in the androgen receptor gene.AIS is now the accepted terminology for the syndromes resulting from unresponsiveness of the target cell to the action of androgenic hormones. CAIS encompasses the phenotypes previously described by "testicular feminization", Morris syndrome, and Goldberg-Maxwell syndrome; PAIS includes Reifenstein syndrome, Gilbert-Dreyfus syndrome, Lubs syndrome, "incomplete testicular feminization", and Rosewater syndrome; and MAIS includes Aimans syndrome.The more virilized phenotypes of AIS have sometimes been described as |
Androgen insensitivity syndrome | "undervirilized male syndrome", "infertile male syndrome", "undervirilized fertile male syndrome", etc., before evidence was reported that these conditions were caused by mutations in the AR gene. These diagnoses were used to describe a variety of mild defects in virilization; as a result, the phenotypes of some men who have been diagnosed as such are better described by PAIS (e.g. micropenis, hypospadias, and undescended testes), while others are better described by MAIS (e.g. isolated male infertility or gynecomastia).
Society and culture
In the film Orchids, My Intersex Adventure, Phoebe Hart and her sister Bonnie Hart, both women with CAIS, documented their exploration of AIS and other intersex issues.Recording artist Dalea is a Hispanic-American Activist who is public about her CAIS. She has given interviews about her condition and founded Girl Comet, a non-profit diversity awareness and inspiration initiative.In 2017, fashion model Hanne Gaby Odiele disclosed that they were born with the intersex trait androgen insensitivity syndrome. As a child, they underwent medical procedures relating to the condition, which they said took place without their or their parents informed consent. They were told about their intersex condition weeks before beginning their modelling career.In the 1991 Japanese horror novel Ring and its sequels, by Koji Suzuki (later adapted into Japanese, Korean, and American films), the central antagonist Sadako has this syndrome, as revealed by Dr Nagao when confronted by Ryuji and Asakawa. Sadakos condition is referred to by the earlier name "testicular feminisation syndrome".
In season 2, episode 13 ("Skin Deep") of the TV series House, the main patients cancerous testicle is mistaken for an ovary due to the patients undiscovered CAIS.In season 2 of the MTV series Faking It, a character has CAIS. The character, Lauren Cooper, played by Bailey De Young, was the first intersex series regular on American television.In season 8, episode 11 ("Delko for the Defense") of the TV series CSI: Miami, the primary suspect has AIS which gets him off a rape charge.In series 8, episode 5 of Call the Midwife, a woman discovers that she has AIS. She attends a cervical smear and brings up that she has never had a period, and is concerned about having children as she is about to be married. She is then diagnosed with "testicular feminisation syndrome", the old term for AIS.
People with AIS
Kitty Anderson (activist)
Eden Atwood
Bonnie Hart
Phoebe Hart
Maria José Martínez-Patiño
Hanne Gaby Odiele
Santhi Soundarajan
Miriam van der Have
Kimberly Zieselman
People with Complete androgen insensitivity syndrome
Georgiann Davis
Seven Graham
People with Partial androgen insensitivity syndrome
Tony Briffa
Favorinus of Arelate has been described as having partial androgen insensitivity syndrome.
Small Luk
Eliana Rubashkyn
Sean Saifa Wall
Sogto Ochirov
See also
Estrogen insensitivity syndrome
Spinal and bulbar muscular atrophy
Congenital adrenal hyperplasia
5α-Reductase 2 deficiency
References
External links
Information
Androgen Insensitivity Syndrome at NIH/UW GeneTests
Online Mendelian Inheritance in Man (OMIM): Androgen Insensitivity Syndrome - 300068, 313700 |
Conus medullaris | The conus medullaris (Latin for "medullary cone") or conus terminalis is the tapered, lower end of the spinal cord. It occurs near lumbar vertebral levels 1 (L1) and 2 (L2), occasionally lower. The upper end of the conus medullaris is usually not well defined, however, its corresponding spinal cord segments are usually S1-S5.
After the spinal cord tapers out, the spinal nerves continue to branch out diagonally, forming the cauda equina.The pia mater that surrounds the spinal cord, however, projects directly downward, forming a slender filament called the filum terminale, which connects the conus medullaris to the back of the coccyx. The filum terminale provides a connection between the conus medullaris and the coccyx which stabilizes the entire spinal cord.
Blood supply
The blood supply consists of three spinal arterial vessels—the anterior median longitudinal arterial trunk and the right and left posterior spinal arteries. Other less prominent sources of blood supply include radicular arterial branches from the aorta, lateral sacral arteries, and the fifth lumbar, iliolumbar, and middle sacral arteries. The latter contribute more to the vascular supply of the cauda equina.
Pathology
Conus medullaris syndrome is a collection of signs and symptoms associated with injury to the conus medullaris. It typically causes back pain and bowel and bladder dysfunction, spastic or flaccid weakness depending on the level of the lesion, and bilateral sensory loss. Comparatively, cauda equina syndrome may cause radicular pain, bowel/bladder dysfunction, patchy sensory loss or saddle anesthesia and lower extremity weakness at the level of the lumbar and sacral roots.
Pediatric patients may have a syrinx associated with their Chiari malformation and the conus medullaris will be located at or below the L2-L3 lumbar vertebrae disk space.Isolated infarcts of the conus medullaris are rare, but should be considered in patients with acute cauda equina syndrome, especially in females. According to a 2021 paper by You-Jiang Tan, et al., those with demonstrated causes or with vascular risk factors are less likely to walk without assistance.
References
External links
Atlas image: n3a2p5 at the University of Michigan Health System – "Lower Third of Spinal Cord, MRI" |
Neutral lipid storage disease | Neutral lipid storage disease (also known as Chanarin–Dorfman syndrome) is a congenital autosomal recessive disorder characterized by accumulation of triglycerides in the cytoplasm of leukocytes[1], (Jordan’s Anomaly) muscle, liver, fibroblasts, and other tissues. It commonly occurs as one of two subtypes, cardiomyopathic neutral lipid storage disease (NLSD-M), or ichthyotic neutral lipid storage disease (NLSD-I) which is also known as Chanarin–Dorfman syndrome), which are characterized primarily by myopathy and ichthyosis, respectively. Normally, the ichthyosis that is present is typically non-bullous congenital ichthyosiform erythroderma which appears as white scaling.
It has been associated genetically with mutations in the CGI58 gene, (for NLSD-I), or the ATGL gene (for NLSD-M.)
Cause
Neutral lipid storage disease is caused by the abnormal and excessive accumulation of lipids in certain bodily tissues, including the liver, the heart, and muscle. Normally, these lipids are stored as lipid droplets and are normally used for metabolism, cell signaling and trafficking of vesicles. Neutral lipid storage disease is a disease that is diagnosed with the simultaneous occurrence of myopathy and/or ichthyosis. Myopathy is defined as a disease of the muscle tissue. Ichthyosis is a skin related disease in which the skin becomes very scaly, thick, and dry.
Genetics
Neutral lipid storage disease (NLSD) occurs in one of two genetic and clinical subtypes. Both subtypes are autosomal recessive disorders, meaning that a mutant allele must be inherited from both parents in order to cause disease.Subtype I: Neutral Lipid Storage Disease with Myopathy (NLSD-M), is caused by a mutation in the PNPLA2 gene, which reduces the normal expression orfunction of the ATGL protein. PNPLA2 is located on chromosome 11. ATGL is an enzyme involved in catabolism of triglycerides (long-term fat storage) into fatty acids (short-term fat storage) within the body In the absence of fully functional ATGL, triglycerides accumulate in the bloodstream and bodily tissues. Interestingly, individuals with NLSD are not typically obese. It has been proposed that the assimilation, rather than degradation of triglycerides is the main factor in fat accumulation in adipose cells. In the absence of functional ATGL, triglycerides accumulate in the bloodstream and bodily tissues. Interestingly, individuals with NLSD are not typically obese. It has been proposed that the assimilation, rather than degradation of triglycerides is the main factor in fat accumulation in adipose cells. Patients with NLSD-M display progressive skeletal myopathy and severe cardiomyopathy in ~40% of cases. The pathophysiology and mechanistic basis of myopathy arising from deficits is lipid metabolism is not yet known.Subtype II: Neutral Lipid Storage Disease with Ichthyosis (NLSD-I), or Chanarin-Dorfman syndrome, is caused by a mutation in the CGI-58 protein. CGI-58 is a coactivator of ATGL, and together these proteins sustain blood lipid levels between meals. Disruption of CGI-58 gives rise to the symptoms of ichthyosis, a dermatological condition in which skin becomes very scaly, thick and dry.Ichthyosis is an inherited disorder, like NLSD, and has been found to be genetically linked in some situations with the PNPLA2 gene. Therefore, sometimes when there is a mutation in the PNPLA2 gene, the linked allele of CG-58 is mutated as well. This specific gene, however, does not produce ichthyosis on its own. Ichthyosis can be diagnosed individually in a patient and the genetic cause for unlinked ichthyosis is different from the gene linked with PNPLA2. Keep in mind these disorders may occur individually within a patient as well.
Pathophysiology
The functional changes that occur with this disease are mostly metabolic. Accumulation of triglycerides in the body without an efficient mode for catabolism is thought to lead to the eventual symptoms of this disease. Upon digestion and absorption of fat by the small intestine, triglycerides are combined with vitamins and cholesterol to form chylomicrons. Chylomicrons travel from the intestine into the lymph system before entering the bloodstream. Enzymatic catalysis of chylomicrons by lipases in the bloodstream enables the uptake of lipids and fatty acids by cells. In individuals with NLSD, their triglycerides are not catabolized in the blood, and cells accumulate partially processed lipid droplets over time, which may lead to dysfunction in absorbing tissues. In affected individuals, muscle cells, fibroblasts, and leukocytes appear to be prone to the excessive accumulation of triglycerides as lipid droplets. Excessive accumulation of lipids in tissues not designed for long term storage may underlie the clinical manifestations of weakened skeletal and cardiac muscle, fatty liver, pancreatitis, hypothyroidism, and type 2 diabetes.
Diagnosis
Main physical signs include a fatty liver, a weakened and enlarged heart (cardiomyopathy), inflammation of the pancreas (pancreatitis), reduced thyroid activity (hypothyroidism), type 2 diabetes, abnormal levels of creatine kinase in blood, and increased weakness of proximal muscles due to fatty replacement of skeletal muscle fibers. Accurate diagnosis is complicated by symptomatic overlap with other disorders. One of the earliest symptoms to manifest clinically is peripheral limb weakness, which becomes progressively more severe over time. Specifically, asymmetric right shoulder weakness is an idiosyncratic hallmark of NLSD enabling it to be distinguished from myopathies arising from alternative muscular disorders.
NLSD is often diagnosed by the presence of lipid inclusions within leukocytes (Jordan’ Anomaly), which can be detected using histochemical and electron microscopy. Image B shows the characteristic lipid accumulation in red blood cells, in a NLSD patient, as compared to a normal individual (Image A).
Classically, NLSD is associated with myopathy and can, in some cases, be linked with icthyosis. Therefore, with these symptoms or diagnosis, it is likely that the patient could and would be diagnosed with NLSD.
Although lipid accumulation is most prominent in myocytes, hepatocytes, and granulocytes, other tissues displayed elevated deposits as well. For the purpose of diagnosis, MRIs have been used to identify large fat deposits within muscle tissue.
People can live with NLSD, but there can be complications due to the affects this disease has on other major parts of the body like the liver, the heart, and skeletal muscle. Whereas myopathy won’t necessarily show up until a patient is in the third decade of their life, a child born with ichthyosis, is immediately evaluated for NLSD, in which it is detected very early on. Also, the earlier that NLSD can be detected and symptoms treated, the better quality of life the patient can have.
Treatment
Although there is no current treatment to correct the abnormal metabolic processes underlying this disease, there are approaches to ameliorate symptoms and decrease the effects of this disease. Because there is an increase of fat storage and a decrease in fat catabolism, low fat diets are recommended for slowing the progression of the disease, including the onset of type 2 diabetes and hypothyroidism. In addition, diets containing triglycerides composed of short chain fatty acids are more beneficial than TGAs containing long chain fatty acids. Ketone bodies can be rapidly transported, catabolized, and used by many tissues including the brain. Medium-chain fatty acids in an individual’s diet are rapidly used by the body, limiting storage and therefore alleviating lipid droplet accumulation. Foods with medium-chain fatty acids include dairy, fat and coconut oil. Supplements can also be taken to increase uptake of these fatty acids. Triaheptanoin, a triglyceride containing three seven-carbon chain fatty acids, has also been proposed as a possible dietary supplement. Treatment for the ichthyosis is limited; moisturizers are commonly used to help manage dry, flaky, itchy skin.
Epidemiology
The rarity and likely under-diagnosis of neutral lipid storage disease prevents an accurate epidemiological estimate of its frequency in human populations. Fewer than 100 cases of NLSD have been reported since the first case of two women with nonbullous ichthyosiform erythroderma was reported in 1974 by Maurice Dorfman. Many (but not all) of the cases reported since 1974 were in individuals of Middle Eastern.descent. A possible reason for the elevated rates of occurrence may be the higher frequency of consanguineous marriages in these populations, as opposed to an elevated frequency of carriers. Males and females are equally likely to be diagnosed with the disease. Genetic testing in families with a history of this disorder may be recommended.
History
Lipid inclusions in the leukocytes of blood smears were first articulated by G.H. Jordans in 1953.This is a feature of the disease, but he wasn’t necessarily finding the first case of the NLSD disease Now, having lipid deposits in the white blood cells of the individual is known and recognized as Jordan’s anomaly, due to the medical professional who discovered it. The first case of Neutral Lipid Storage Disease was reported by Maurice Dorfman when he treated two sisters with non bullous ichthyosiform erythroderma in 1974. His observations were then able to be confirmed with the emergence of other cases. Since then, less than 100 cases as of have been reported.
See also
List of cutaneous conditions
References
External links
NIH
GARD |
Keratitis | Keratitis is a condition in which the eyes cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired eyesight, photophobia (light sensitivity), red eye and a gritty sensation.
Classification (by chronicity)
Acute
Acute epithelial keratitis
Nummular keratitis
Interstitial keratitis
Disciform keratitis
Chronic
Neurotrophic keratitis
Mucous plaque keratitis
Classification (infective)
Viral
Herpes simplex keratitis (dendritic keratitis). Viral infection of the cornea is often caused by the herpes simplex virus (HSV) which frequently leaves what is called a dendritic ulcer.
Herpes zoster keratitis, associated with herpes zoster ophthalmicus, which is a form of shingles.
Bacterial
Bacterial keratitis. Bacterial infection of the cornea can follow from an injury or from wearing contact lenses. The bacteria involved are Staphylococcus aureus and for contact lens wearers, Pseudomonas aeruginosa. Pseudomonas aeruginosa contains enzymes that can digest the cornea.
Fungal
Fungal keratitis, caused by Aspergillus fumigatus and Candida albicans (cf. Fusarium, causing an outbreak of keratitis in 2005–2006 through the possible vector of Bausch & Lomb ReNu with MoistureLoc contact lens solution)
Amoebic
Acanthamoebic keratitis
Amoebic infection of the cornea is a serious corneal infection, often affecting contact lens wearers. It is usually caused by Acanthamoeba. On May 25, 2007, the U.S. Center for Disease Control issued a health advisory due to increased risk of Acanthamoeba keratitis associated with use of Advanced Medical Optics Complete Moisture Plus Multi-Purpose eye solution.
Parasitic
Onchocercal keratitis, which follows Onchocerca volvulus infection by infected blackfly bite. These blackfly, Simulium, usually dwell near fast-flowing African streams, so the disease is also called "river blindness".
Classification (by stage of disease)
Superficial punctate keratitis
Ulcerative keratitis
Classification (by environmental aetiology)
Exposure keratitis (also known as exposure keratopathy) — due to dryness of the cornea caused by incomplete or inadequate eyelid closure (lagophthalmos).
Photokeratitis — keratitis due to intense ultraviolet radiation exposure (e.g. snow blindness or welders arc eye.)
Contact lens acute red eye (CLARE) — a non-ulcerative sterile keratitis associated with colonization of Gram-negative bacteria on contact lenses.
Treatment
Treatment depends on the cause of the keratitis. Infectious keratitis can progress rapidly, and generally requires urgent antibacterial, antifungal, or antiviral therapy to eliminate the pathogen. Antibacterial solutions include levofloxacin, gatifloxacin, moxifloxacin, ofloxacin. It is unclear if steroid eye drops are useful or not.In addition, contact lens wearers are typically advised to discontinue contact lens wear and replace contaminated contact lenses and contact lens cases. (Contaminated lenses and cases should not be discarded as cultures from these can be used to identify the pathogen).
Aciclovir is the mainstay of treatment for HSV keratitis and steroids should be avoided at all costs in this condition. Application of steroids to a dendritic ulcer caused by HSV will result in rapid and significant worsening of the ulcer to form an amoeboid or geographic ulcer, so named because of the ulcers map like shape.
Prognosis
Some infections may scar the cornea to limit vision. Others may result in perforation of the cornea, endophthalmitis (an infection inside the eye), or even loss of the eye. With proper medical attention, infections can usually be successfully treated without long-term visual loss.
In non-humans
Feline eosinophilic keratitis — affecting cats and horses; possibly initiated by feline herpesvirus 1 or other viral infection.
See also
Chronic superficial keratitis, or pannus, for the disease in dogs
Thygesons superficial punctate keratopathy
Keratoendotheliitis fugax hereditaria
References
External links
Facts About the Cornea and Corneal Disease The National Eye Institute (NEI)
Filimentary keratitis |
Warfarin necrosis | Warfarin-induced skin necrosis is a condition in which skin and subcutaneous tissue necrosis (tissue death) occurs due to acquired protein C deficiency following treatment with anti-vitamin K anticoagulants (4-hydroxycoumarins, such as warfarin).Warfarin necrosis is a rare but severe complication of treatment with warfarin or related anticoagulants. The typical patient appears to be an obese, middle aged woman (median age 54 years, male to female ratio 1:3).: 122–3 This drug eruption usually occurs between the third and tenth days of therapy with warfarin derivatives. The first symptoms are pain and redness in the affected area. As they progress, lesions develop a sharp border and become petechial, then hard and purpuric. They may then resolve or progress to form large, irregular, bloody bullae with eventual necrosis and slow-healing eschar formation. Favored sites are breasts, thighs, buttocks and penis, all areas with subcutaneous fat.: 122 In rare cases, the fascia and muscle are involved.Development of the syndrome is associated with the use of large loading doses at the start of treatment.
Mechanism
Warfarin necrosis usually occurs three to five days after drug therapy is begun, and a high initial dose increases the risk of its development.: 122 Warfarin-induced necrosis can develop both at sites of local injection and - when infused intravenously - in a widespread pattern.: 123 In warfarins initial stages of action, inhibition of protein C and Factor VII is stronger than inhibition of the other vitamin K-dependent coagulation factors II, IX, and X. This results from the fact that these proteins have different half-lives: 1.5 to six hours for factor VII and eight hours for protein C, versus one day for factor IX, two days for factor X and two to five days for factor II. The larger the initial dose of vitamin K-antagonist, the more pronounced these differences are. This coagulation factor imbalance leads to paradoxical activation of coagulation, resulting in a hypercoagulable state and thrombosis. The blood clots interrupt the blood supply to the skin, causing necrosis. Protein C is an innate anticoagulant, and as warfarin further decreases protein C levels, it can lead to massive thrombosis with necrosis and gangrene of limbs.
Notably, the prothrombin time (or international normalized ratio, INR) used to test the effect of warfarin is highly dependent on factor VII, which explains why patients can have a therapeutic INR (indicating good anticoagulant effect) but still be in a hypercoagulable state.In one third of cases, warfarin necrosis occurs in patients with an underlying, innate and previously unknown deficiency of protein C. The condition is related to purpura fulminans, a complication in infants with sepsis which also involves skin necrosis. These infants often have protein C deficiency as well. There have also been cases in patients with other deficiency, including protein S deficiency, activated protein C resistance (Factor V Leiden) and antithrombin III deficiency.Although the above hypothesis is the most commonly accepted, others believe that it is a hypersensitivity reaction or a direct toxic effect.
Diagnosis
Differential diagnosis
Many conditions mimic or may be mistaken for warfarin necrosis, including pyoderma gangrenosum or necrotizing fasciitis. Warfarin necrosis is also different from another drug eruption associated with warfarin, purple toe syndrome, which usually occurs three to eight weeks after the start of anticoagulation therapy. No report has described this disorder in the immediate postpartum period in patients with protein S deficiency.
Prevention
Vitamin K1 can be used to reverse the effects of warfarin, and heparin or its low molecular weight heparin (LMWH) can be used in an attempt to prevent further clotting. None of these suggested therapies have been studied in clinical trials.
Heparin and LMWH act by a different mechanism than warfarin, so these drugs can also be used to prevent clotting during the first few days of warfarin therapy and thus prevent warfarin necrosis (this is called bridging).
Treatment
The first element of treatment is usually to discontinue the offending drug, although there have been reports describing how the eruption evolved little after it had established in spite of continuing the medication.Based on the assumption that low levels of protein C are involved in the underlying mechanism, common treatments in this setting include fresh frozen plasma or pure activated protein C.Since the clot-promoting effects of starting administration of 4-hydroxycoumarins are transitory, patients with protein C deficiency or previous warfarin necrosis can still be restarted on these drugs if appropriate measures are taken. These include gradual increase starting from low doses and supplemental administration of protein C (pure or from fresh frozen plasma).The necrotic skin areas are treated as in other conditions, sometimes healing spontaneously with or without scarring, sometimes going on to require surgical debridement or skin grafting.
History
While skin necrosis in patients had been previously described, Verhagen was the first to publish a paper on this relationship in the medical literature, in 1954.
See also
List of cutaneous conditions
== References == |
SERKAL syndrome | SERKAL syndrome (SEx Reversion, Kidneys, Adrenal and Lung dysgenesis) is an autosomal recessive disorder in XX humans. It is caused by loss of function in WNT4, a protein involved in sex development. The main outcome is female to male sex reversal. Other names include sex reversion-kidneys and adrenal and lung dysgenesis syndrome. The conditions prevalence is lower than 1 in 1,000,000.
Presentation
The effect of the disorder is female to male sex reversal. Patients also exhibit renal, adrenal, and lung dysgenesis. One indicator is low levels of unconjugated estriol in maternal serum, because this denotes adrenal hypoplasia.
Genetics
The disorder is linked to a mutation in the Wnt4 gene. There is an intraexonic homozygous C to T transition at cDNA position 341. This leads to an alanine to valine residue substitution at amino acid position 114, a location highly conserved in all organisms, including zebrafish and Drosophila. A subsequent influence on mRNA stability leads to protein loss of function. WNT4 usually represses male sex development.
Diagnosis
References
External links
SERKAL syndrome (The Monarch Initiative) |
CRLF1 | Cytokine receptor-like factor 1 is a protein that in humans is encoded by the CRLF1 gene.
Function
This gene encodes a member of the cytokine type I receptor family. The protein forms a secreted complex with cardiotrophin-like cytokine factor 1 and acts on cells expressing ciliary neurotrophic factor receptors. The complex can promote survival of neuronal cells.
Clinical significance
Mutations in this gene are associated with two conditions, both rare:
Cold-induced sweating syndrome, characterized by profuse hyperhidrosis in cold environmental temperature and characteristic craniofacial and skeletal features)
Crisponi syndrome (CS), characterized by neonatal-onset paroxysmal muscular contractions, abnormal function of the autonomic nervous system and craniofacial and skeletal manifestations such as thick and arched eyebrows, a short nose with anteverted nostrils, full cheeks, an inverted upper lip and a small mouth.It is unknown whether the two conditions are distinct clinical entities or a single clinical entity with variable expressions.
Other characteristic features in CRLF1 mutation include marfanoid habitus with progressive kyphoscoliosis and craniofacial characteristics including dolichocephaly, a slender face with poor expression, a nose with hypoplastic nares, malar hypoplasia and prognathism.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Cold-Induced Sweating Syndrome including Crisponi Syndrome
OMIM enries on Cold-Induced Sweating Syndrome including Crisponi Syndrome
Human CRLF1 genome location and CRLF1 gene details page in the UCSC Genome Browser.This article incorporates text from the United States National Library of Medicine, which is in the public domain. |
Overriding aorta | An overriding aorta is a congenital heart defect where the aorta is positioned directly over a ventricular septal defect (VSD), instead of over the left ventricle. The result is that the aorta receives some blood from the right ventricle, causing mixing of oxygenated and deoxygenated blood, and thereby reducing the amount of oxygen delivered to the tissues.
It is one of the four findings in the classic tetralogy of Fallot. The other three findings are right ventricular outflow tract (RVOT) obstruction (most often subpulmonary stenosis), right ventricular hypertrophy (RVH), and ventricular septal defect (VSD).
References
== External links == |
Hereditary sensory and autonomic neuropathy | Hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy (HSN) is a condition used to describe any of the types of this disease which inhibit sensation.
They are less common than Charcot-Marie-Tooth disease.
Classification
Eight different clinical entities have been described under hereditary sensory and autonomic neuropathies – all characterized by progressive loss of function that predominantly affects the peripheral sensory nerves. Their incidence has been estimated to be about 1 in 250,000.
Type 1
Hereditary sensory neuropathy type 1 is a condition characterized by nerve abnormalities in the legs and feet (peripheral neuropathy). Many people with this condition have tingling, weakness, and a reduced ability to feel pain and sense hot and cold. Some affected individuals do not lose sensation, but instead feel shooting pains in their legs and feet. As the disorder progresses, the sensory abnormalities can affect the hands, arms, shoulders, and abdomen. Affected individuals may also experience muscle wasting and weakness as they get older, but this varies widely within families.
Affected individuals typically get open sores (ulcers) on their feet or hands or infections of the soft tissue of the fingertips (whitlows) that are slow to heal. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may require amputation of the surrounding area.
Albeit rarely, people with hereditary sensory neuropathy type 1 may develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss).
The signs and symptoms of hereditary sensory neuropathy type 1 typically appear during a persons teens or twenties. While the features of this disorder tend to worsen over time, affected individuals have a normal life expectancy if signs and symptoms are properly treated.
Type 1 is the most common form among the 5 types of HSAN. Its historical names include mal perforant du pied, ulcero-mutilating neuropathy, hereditary perforating ulcers, familial trophoneurosis, familial syringomyelia, hereditary sensory radicular neuropathy, among others. This type includes a popular disease Charcot-Marie-Tooth type 2B syndrome (HMSN 2B). that is also named as HSAN sub-type 1C.
Type 1 is inherited as an autosomal dominant trait. The disease usually starts during early adolescence or adulthood. The disease is characterized by the loss of pain sensation mainly in the distal parts of the lower limbs; that is, in the parts of the legs farther away from the center of the body. Since the affected individuals cannot feel pain, minor injuries in this area may not be immediately recognized and may develop into extensive ulcerations. Once infection occurs, further complications such as progressive destruction of underlying bones may follow and may necessitate amputation. In rare cases, the disease is accompanied with nerve deafness and muscle wasting. Autonomic disturbance, if present, appears as anhidrosis, a sweating abnormality. Examinations of the nerve structure and function showed signs of neuronal degeneration such as a marked reduction in the number of myelinated fibers and axonal loss. Sensory neurons lose the ability to transmit signals, while motor neurons has reduced ability to transmit signals.Genes related to Hereditary sensory and autonomic neuropathy Type 1:
Mutations in the SPTLC1 gene cause hereditary sensory neuropathy type 1. The SPTLC1 gene provides instructions for making one part (subunit) of an enzyme called serine palmitoyltransferase (SPT). The SPT enzyme is involved in making certain fats called sphingolipids. Sphingolipids are important components of cell membranes and play a role in many cell functions.
SPTLC1 gene mutations reduce the amount of SPTLC1 subunit that is produced and result in an SPT enzyme with decreased function. A lack of functional SPT enzyme leads to a decrease in sphingolipid production and a harmful buildup of certain byproducts. Sphingolipids are found in myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. A decrease in sphingolipids disrupts the formation of myelin, causing nerve cells to become less efficient and eventually die. When sphingolipids are not made, an accumulation of toxic byproducts can also lead to nerve cell death. This gradual destruction of nerve cells results in loss of sensation and muscle weakness in people with hereditary sensory neuropathy type 1.
Type 2, Congenital sensory neuropathy
Hereditary sensory and autonomic neuropathy type II (HSAN2) is a condition that primarily affects the sensory nerve cells (sensory neurons) which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with HSAN2. In some affected people, the condition may also cause mild abnormalities of the autonomic nervous system, which controls involuntary body functions such as heart rate, digestion, and breathing. The signs and symptoms of HSAN2 typically begin in infancy or early childhood.
The first sign of HSAN2 is usually numbness in the hands and feet. Soon after, affected individuals lose the ability to feel pain or sense hot and cold. People with HSAN2 often develop open sores (ulcers) on their hands and feet. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may lead to amputation of the affected area. Unintentional self-injury is common in people with HSAN2, typically by biting the tongue, lips, or fingers. These injuries may lead to spontaneous amputation of the affected areas. Affected individuals often have injuries and fractures in their hands, feet, limbs, and joints that go untreated because of the inability to feel pain. Repeated injury can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.
The effects of HSAN2 on the autonomic nervous system are more variable. Some infants with HSAN2 have trouble sucking, which makes it difficult for them to eat. People with HSAN2 may experience episodes in which breathing slows or stops for short periods (apnea); digestive problems such as the backflow of stomach acids into the esophagus (gastroesophageal reflux); or slow eye blink or gag reflexes. Affected individuals may also have weak deep tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer.
Some people with HSAN2 experience a diminished sense of taste due to the loss of a type of taste bud on the tip of the tongue called lingual fungiform papillae.
Type 2, congenital sensory neuropathy (also historically known as Morvans disease), is characterized by onset of symptoms in early infancy or childhood. Upper & lower extremities are affected with chronic ulcerations and multiple injuries to fingers and feet. Pain sensation is affected predominantly and deep tendon reflexes are reduced. Autoamputation of the distal phalanges is common and so is neuropathic joint degeneration. The NCV shows reduced or absent sensory nerve action potentials and nerve biopsy shows total loss of myelinated fibers and reduced numbers of unmyelinated fibers. It is inherited as an autosomal recessive condition.
Genes related to Hereditary sensory and autonomic neuropathy Type 2:
There are two types of HSAN2, called HSAN2A and HSAN2B, each caused by mutations in a different gene. HSAN2A is caused by mutations in the WNK1 gene, and HSAN2B is caused by mutations in the RETREG1 gene (FAM134B). Although two different genes are involved, the signs and symptoms of HSAN2A and HSAN2B are the same.
The WNK1 gene provides instructions for making multiple versions (isoforms) of the WNK1 protein. HSAN2A is caused by mutations that affect a particular isoform called the WNK1/HSN2 protein. This protein is found in the cells of the nervous system, including nerve cells that transmit the sensations of pain, temperature, and touch (sensory neurons). The mutations involved in HSAN2A result in an abnormally short WNK1/HSN2 protein. Although the function of this protein is unknown, it is likely that the abnormally short version cannot function properly. People with HSAN2A have a reduction in the number of sensory neurons; however, the role that WNK1/HSN2 mutations play in that loss is unclear.
HSAN2B is caused by mutations in the RETREG1 gene. These mutations may lead to an abnormally short and nonfunctional protein. The RETREG1 protein is found in sensory and autonomic neurons. It is involved in the survival of neurons, particularly those that transmit pain signals, which are called nociceptive neurons. When the RETREG1 protein is nonfunctional, neurons die by a process of self-destruction called apoptosis.
The loss of neurons leads to the inability to feel pain, temperature, and touch sensations and to the impairment of the autonomic nervous system seen in people with HSAN2.
Type 3, Familial dysautonomia
Familial dysautonomia is a genetic disorder that affects the development and survival of certain nerve cells. The disorder disturbs cells in the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Familial dysautonomia is also called hereditary sensory and autonomic neuropathy, type III.
Problems related to this disorder first appear during infancy. Early signs and symptoms include poor muscle tone (hypotonia), feeding difficulties, poor growth, lack of tears, frequent lung infections, and difficulty maintaining body temperature. Older infants and young children with familial dysautonomia may hold their breath for prolonged periods of time, which may cause a bluish appearance of the skin or lips (cyanosis) or fainting. This breath-holding behavior usually stops by age 6. Developmental milestones, such as walking and speech, are usually delayed, although some affected individuals show no signs of developmental delay.
Additional signs and symptoms in school-age children include bed wetting, episodes of vomiting, reduced sensitivity to temperature changes and pain, poor balance, abnormal curvature of the spine (scoliosis), poor bone quality and increased risk of bone fractures, and kidney and heart problems. Affected individuals also have poor regulation of blood pressure. They may experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. They can also have episodes of high blood pressure when nervous or excited, or during vomiting incidents. About one-third of children with familial dysautonomia have learning disabilities, such as a short attention span, that require special education classes. By adulthood, affected individuals often have increasing difficulties with balance and walking unaided. Other problems that may appear in adolescence or early adulthood include lung damage due to repeated infections, impaired kidney function, and worsening vision due to the shrinking size (atrophy) of optic nerves, which carry information from the eyes to the brain.
Type 3, familial dysautonomia (FD) or Riley-Day syndrome, is an autosomal recessive disorder seen predominantly in Jews of eastern European descent. Patients present with sensory and autonomic disturbances. Newborns have absent or weak suck reflex, hypotonia and hypothermia. Delayed physical development, poor temperature and motor incoordination are seen in early childhood. Other features include reduced or absent tears, depressed deep tendon reflexes, absent corneal reflex, postural hypotension and relative indifference to pain. Scoliosis is frequent. Intelligence remains normal. Many patients die in infancy and childhood. Lack of flare with intradermal histamine is seen. Histopathology of peripheral nerve shows reduced number of myelinated and non-myelinated axons. The catecholamine endings are absent.
Genes related to Hereditary sensory and autonomic neuropathy Type 3:
Mutations in the IKBKAP gene cause familial dysautonomia.
The IKBKAP gene provides instructions for making a protein called IKK complex-associated protein (IKAP). This protein is found in a variety of cells throughout the body, including brain cells.
Nearly all individuals with familial dysautonomia have two copies of the same IKBKAP gene mutation in each cell. This mutation can disrupt how information in the IKBKAP gene is pieced together to make a blueprint for the production of IKAP protein. As a result of this error, a reduced amount of normal IKAP protein is produced. This mutation behaves inconsistently, however. Some cells produce near normal amounts of the protein, and other cells—particularly brain cells—have very little of the protein. Critical activities in brain cells are probably disrupted by reduced amounts or the absence of IKAP protein, leading to the signs and symptoms of familial dysautonomia.
Type 4, Congenital insensitivity to pain with anhidrosis
Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV), is characterized by insensitivity to pain, anhidrosis (the inability to sweat), and intellectual disability. The ability to sense all pain (including visceral pain) is absent, resulting in repeated injuries including: oral self-mutilation (biting of tongue, lips, and buccal mucosa); biting of fingertips; bruising, scarring, and infection of the skin; multiple bone fractures (many of which fail to heal properly); and recurrent joint dislocations resulting in joint deformity. Sense of touch, vibration, and position are normal. Anhidrosis predisposes to recurrent febrile episodes that are often the initial manifestation of CIPA. Hypothermia in cold environments also occurs. Intellectual disability of varying degree is observed in most affected individuals; hyperactivity and emotional lability are common.
Hereditary sensory neuropathy type IV (HSN4) is a rare genetic disorder characterized by the loss of sensation (sensory loss), especially in the feet and legs and, less severely, in the hands and forearms. The sensory loss is due to abnormal functioning of small, unmyelinated nerve fibers and portions of the spinal cord that control responses to pain and temperature as well as other involuntary or automatic body processes. Sweating is almost completely absent with this disorder. Intellectual disability is usually present.
Type 4, congenital insensitivity to pain with anhidrosis (CIPA), is an autosomal recessive condition and affected infants present with episodes of hyperthermia unrelated to environmental temperature, anhidrosis and insensitivity to pain. Palmar skin is thickened and charcot joints are commonly present. NCV shows motor and sensory nerve action potentials to be normal. The histopathology of peripheral nerve biopsy reveals absent small unmyelinated fibers and mitochondria are abnormally enlarged.
Management of Hereditary sensory and autonomic neuropathy Type 4:
Treatment of manifestations: Treatment is supportive and is best provided by specialists in pediatrics, orthopedics, dentistry, ophthalmology, and dermatology. For anhidrosis: Monitoring body temperature helps to institute timely measures to prevent/manage hyperthermia or hypothermia. For insensitivity to pain: Modify as much as reasonable a childs activities to prevent injuries. Inability to provide proper immobilization as a treatment for orthopedic injuries often delays healing; additionally, bracing and invasive orthopedic procedures increase the risk for infection. Methods used to prevent injuries to the lips, buccal mucosa, tongue, and teeth include tooth extraction, and/or filing (smoothing) of the sharp incisal edges of teeth, and/or use of a mouth guard. Skin care with moisturizers can help prevent palmar and plantar hyperkeratosis and cracking and secondary risk of infection; neurotrophic keratitis is best treated with routine care for dry eyes, prevention of corneal infection, and daily observation of the ocular surface. Interventions for behavioral, developmental and motor delays, as well as educational and social support for school-age children and adolescents, are recommended.
Prevention of secondary complications: Regular dental examinations and restriction of sweets to prevent dental caries; early treatment of dental caries and periodontal disease to prevent osteomyelitis of the mandible. During and following surgical procedures, potential complications to identify and manage promptly include hyper- or hypothermia and inadequate sedation, which may trigger unexpected movement and result in secondary injuries.
Type 5, Congenital insensitivity to pain with partial anhidrosis
Hereditary sensory and autonomic neuropathy type V (HSAN5) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with HSAN5.
The signs and symptoms of HSAN5 appear early, usually at birth or during infancy. People with HSAN5 lose the ability to feel pain, heat, and cold. Deep pain perception, the feeling of pain from injuries to bones, ligaments, or muscles, is especially affected in people with HSAN5. Because of the inability to feel deep pain, affected individuals suffer repeated severe injuries such as bone fractures and joint injuries that go unnoticed. Repeated trauma can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.
Type 5, congenital insensitivity to pain with partial anhidrosis, also manifests with congenital insensitivity to pain & anhidrosis. There is a selective absence of small myelinated fibers differentiating it from Type IV (CIPA).
Genes related to Hereditary sensory and autonomic neuropathy Type 5:
Mutations in the NGF gene cause HSAN5. The NGF gene provides instructions for making a protein called nerve growth factor beta (NGFβ) that is important in the development and survival of nerve cells (neurons), including sensory neurons. The NGFβ protein functions by attaching (binding) to its receptors, which are found on the surface of neurons. Binding of the NGFβ protein to its receptor transmits signals to the cell to grow and to mature and take on specialized functions (differentiate). This binding also blocks signals in the cell that initiate the process of self-destruction (apoptosis). Additionally, NGFβ signaling plays a role in pain sensation. Mutation of the NGF gene leads to the production of a protein that cannot bind to the receptor and does not transmit signals properly. Without the proper signaling, sensory neurons die and pain sensation is altered, resulting in the inability of people with HSAN5 to feel pain.
Type 6 -
Hereditary sensory and autonomic neuropathy type 6 (HSAN6) is a severe autosomal recessive disorder characterized by neonatal hypotonia, respiratory and feeding difficulties, lack of psychomotor development, and autonomic abnormalities including labile cardiovascular function, lack of corneal reflexes leading to corneal scarring, areflexia, and absent axonal flare response after intradermal histamine injection.Genes related to Hereditary sensory and autonomic neuropathy Type 6:
Mutations in the DST (Dystosin) gene are associated HSAN6. In two separate studies of families with presentations of HSAN6, the DST gene was found to be mutated, in one case with a truncating mutation, and in the other a non-sense or missense mutation. In the latter case, the authors proposed that homozygous truncating mutations result in a severe form of HSAN6, with congenital defects and early lethality, while heterozygosity for a truncating or missense mutation maintains enough dystosin expression and function to allow a normal lifespan, albeit with symptoms of HSAN6.DST is involved in maintaining cytoskeleton integrity and intracellular transport systems, each of which are critical to the normal function of the particularly long neurons found in the peripheral nervous system. Its believed that this disrupts the cells internal autophagy process, in which toxic proteins and other normally-occurring debris are captured and transported to the cell center for recycling or destruction. In neurons, autophagosomes, are generated at the ends of the neuron to carry the discardable material, and they are then transported toward center. With the intracellular transport system disrupted by a mutation in DST, the autophagosomes are unable to carry away the debris, which builds up at the ends of the neuron, leading to damage.
Type 7
Type 8
Genetics
Associated genes
Diagnosis
Treatment
References
https://www.jsaapd.com/abstractArticleContentBrowse/JSAAPD/1/4/3/26394/abstractArticle/Article
Further reading
GeneReviews/NIH/NCBI/UW entry on Hereditary Sensory and Autonomic Neuropathy IV
GeneReviews/NIH/NCBI/UW entry on Hereditary Sensory Neuropathy Type I
GeneReviews/NIH/NCBI/UW entry on Hereditary Sensory and Autonomic Neuropathy Type II
== External links == |
IRAK4 | IRAK-4 (interleukin-1 receptor-associated kinase 4), in the IRAK family, is a protein kinase involved in signaling innate immune responses from Toll-like receptors. It also supports signaling from T-cell receptors. IRAK4 contains domain structures which are similar to those of IRAK1, IRAK2, IRAKM and Pelle. IRAK4 is unique compared to IRAK1, IRAK2 and IRAKM in that it functions upstream of the other IRAKs, but is more similar to Pelle in this trait. IRAK4 has important clinical applications.
Animals without IRAK-4 are more susceptible to viruses and bacteria but completely resistant to LPS challenge.
History
The first IL-1 receptor-associated kinase (IRAK) was observed in 1994 through experiments with murine T helper cell lines D10N and EL-4. Two years later the first experimental member of this family of kinases, IRAK1, was cloned. In 2002, through database searches at the National Center for Biotechnology Information in an attempt to recognize novel members of the IRAK family, a human cDNA sequence which encoded a peptide sharing significant homology with IRAK1 was identified. This cDNA sequence was found to have five amino acid substitutions compared to IRAK1 and was termed IRAK4.IRAK4 was proposed to be the mammalian homolog of the Pelle gene found in Drosophila melanogaster and was proposed to require its kinase activity in order for it to function in activating NF-κB. It was also proposed by Li et al. that it might function upstream of other IRAKs and possibly cause a cascade of phosphorylation events through its function as an IRAK1 kinase. This idea of a cascade of phosphorylation events was supported by a study where an IRAK4 knockout in mice showed a more severe phenotype than other IRAK knockout experiments and signalling through Toll/IL-1 receptor (TIR) is virtually eliminated.In 2007 it was found that IRAK4 activity was necessary for activating signal pathways which lead to mitogen-activated protein kinases (MAPK), or Toll-like receptor-mediated immune responses (TLR), but was not essential to T-cell Receptor (TCR) signalling as was originally proposed.
Protein structure
IRAK4 is a threonine/serine protein kinase made up of 460 amino acids, which contains both a kinase domain and a death domain. Its kinase domain exhibits the typical bilobed structure of kinases, with the N-terminal lobe consisting of a five-stranded antiparallel beta-sheet and one alpha helix. The C-terminal lobe is composed mainly of a number of alpha helices. Also contained within IRAK4s N-terminal is an extension of twenty amino acids, which is unique to IRAK4 among kinases, even within the IRAK family. Situated where the two lobes meet is an ATP binding site, which is covered by a tyrosine gatekeeper. Tyrosine as a gatekeeper is believed to be unique to the IRAK family of kinases. The protein also contains three auto-phosphorylation sites, each of which when mutated results in a decrease in the kinase activity of IRAK4.A structure of the autophosphorylation of the activation loop has been determined in which the activation loop Thr345 of one monomer is sitting in the active site of another monomer in the crystal (PDB: 4U9A, 4U97).
Function, mechanism, signalling pathway
Members of interleukin-1 receptor (Il-1R) and the Toll-like receptor superfamily share an intracytoplasmic Toll-IL-1 receptor (TIR) domain, which mediates recruitment of the interleukin-1 receptor-associated kinase (IRAK) complex via TIR-containing adapter molecules. The TIR-IRAK signaling pathway appears to be crucial for protective immunity against specific bacteria but is redundant against most other microorganisms. IRAK4 is considered the “master IRAK” in the mammalian IRAK family because it is the only component in the IL-1/TLR signalling pathway that is absolutely crucial to its functioning. When one of these pathways is stimulated, the cell is triggered to release proinflammatory signals and to trigger innate immune actions. The loss of IRAK4, or its intrinsic kinase activity, can entirely stop signalling through these pathways.IRAK4 is involved in signal transduction pathways stimulated by the cellular receptors belonging to the Toll/Interleukin-1 receptor superfamily. The Toll-Like Receptors (TLRs) are stimulated by recognition of pathogen-associated molecular patterns (PAMPS), whereas members of the IL-1R family are stimulated by cytokines. Both play an essential role in the immune response. The ligand binding causes conformational changes to the intracellular domain which allows for the recruitment of scaffolding proteins. One of these proteins, MyD88, uses its death domains to recruit, orient, and activate IRAK4. IRAK2 can then be phosphorylated and joins with IRAK4 and MyD88 to form the myddosome complex, which further phosphorylates and recruits IRAK1. The myddosome complex and IRAK1 recruit and activate TNF receptor-associated factor 6 (TRAF6), a ubiquitin protein ligase. TRAF6 can polyubiquitinate IKK-γ as well as itself, which recruits TGF-β activated kinase 1 (TAK1) in order to activate its ability to phosphorylate IKK-β. These pathways both work to degrade IKKγ, which releases NFκB and free it for translocation into the nucleus. Additionally, TAK1 can activate JNK to induce a MAP kinase pathway which leads to AP-1-induced gene expression. Together, AP-1 and NFκB lead to increased cytokine transcription, adhesion molecule production, and release of second messengers of infection.
Central to all of these signalling pathways is the kinase IRAK4. Results show that IRAK4 is a crucial component in an animals response to IL-1. Animals deficient in this kinase were found to be lacking in the ability to recognize viral and bacterial invaders, and were completely resistant to lethal doses of lipopolysaccharide (LPS). This is due to IRAK4s function as both a structural protein and as a kinase. Both of these functions are required for the myddosome complex formation. Additionally, IRAK4 has been shown to be absolutely essential in a TLR signalling. IRAK4 deficient mice have a profoundly impaired ability to produce IL-6, TNF-α, and IL-12 in response to TLR ligands. However it is worthy of note that despite its importance to many immune signalling pathways, IRAK4 does not appear to be involved in TCR signalling.
Clinical significance
There are three components of evidence that illustrate IRAK4s involvement in TLR signalling. First, IRAK4 is the initial kinase near the TLR receptor to activate downstream effectors such as cytokines and chemokines in the inflammatory cascade. Second, deletion of the IRAK4 gene results in various cytokine response defects and finally, patients with IRAK4 deficiency have displayed defective immunity in response to IL-1, IL-8 and other TLR binding ligands. Considering IRAK4s downstream position of these signalling events, it is an important drug therapy target for various inflammatory disorders including rheumatoid arthritis, inflammatory bowel disease and other autoimmune diseases.
Prostate cancer
An important area of research currently being explored is the role the IRAK4 gene may play in the development of prostate cancer. There are several interacting factors that lead to the development of this disease however genetic susceptibility of chronic inflammation has been deemed one of the most important. It has been found that mutations in the IRAK4 gene can lead to dysfunctional TLR signalling and ultimately result in increased innate immune responses and therefore an increased inflammatory response. Over time, this can lead to the onset of prostate cancer.
Melanoma
Another interesting application of the IRAK4 gene was found in a study involving human melanoma patients. This research found that patients with melanin-cell tumors displayed an increase in the phosphorylation state of IRAK4. The siRNA inhibition of IRAK4 in mice displayed greater programmed cell death (PCD) and slowed tumor growth.IRAK4 is higher levels in some lines of melanoma. By reducing IRAK4 activity it may be possible to identify new chemotherapeutic agents to treat patients with advanced melanoma for which no effective treatment is available.
Pancreatic cancer
In a mice model, administering IRAK4 reduced inflammatory signaling, after which T-cells began to attack tumors and immunotherapy became more effective.
Drug target
A common concern with IRAK4 drug therapy or knockdown is if its absence would result in unbearable side effects considering IRAK4 plays an extremely central role in the TLR signalling pathway. Children with IRAK4 deficiency have been found to have decreased immunity to some specific bacterial infections yet not to viral, parasitic or other microbe infections. However, as these children enter adulthood and maternal antibodies are no longer present, susceptibility to infections becomes a rarity. In one study, no significant bacterial infections were documented in all investigated patients over the age of 14 with IRAK4 deficiency. This may mean that in later stages of life, IRAK4 inhibition could provide benefits against certain diseases while maintaining immunity.The next step in this area of research is the formation of safe IRAK4 inhibitors. There has been modest progress in the development of some potential inhibitors of IRAK4 in which their mechanism works by blocking its tyrosine gated ATP binding site. As of 2007 All potential drugs are in the early preclinical stages of development.Early-stage clinical trials of an IRAK4 inhibitor had started by 2019. Moreover, IRAK4 protein degraders have recently entered clinical trials, most notably one from Kymera Therapeutics.
References
External links
IRAK4+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
Overview of all the structural information available in the PDB for UniProt: Q9NWZ3 (Human Interleukin-1 receptor-associated kinase 4) at the PDBe-KB.
Overview of all the structural information available in the PDB for UniProt: Q8R4K2 (Mouse Interleukin-1 receptor-associated kinase 4) at the PDBe-KB. |
Cutaneous actinomycosis | Cutaneous actinomycosis is a chronic disease that affects the deep subcutaneous tissue of the skin. Caused by an anaerobic, Gram-positive, filamentous type of bacteria in the genus Actinomyces,: 270 invasion of the soft tissue leads to the formation of abnormal channels leading to the skin surface (external sinus tracts) that discharge pale yellow sulfur granules.This disease is uncommon, and has non-specific clinical features, making it difficult to diagnose.Cervicofacial, pulmonary/thoracic and gastrointestinal forms exist, yet cervicofacial disease accounts for two-thirds of reported infections.
See also
Skin lesion
== References == |
Congenital contractural arachnodactyly | Congenital contractural arachnodactyly (CCA), also known as Beals-Hecht syndrome, is a rare autosomal dominant congenital connective tissue disorder. As with Marfan syndrome, people with CCA typically have an arm span that is greater than their height and very long fingers and toes. However, Beals and Hecht discovered in 1972 that, unlike Marfans, CCA is caused by mutations to the fibrillin-2 (FBN2) gene rather than the fibrillin-1 (FBN1) gene.
Signs and symptoms
CCA is characterized by contractures of varying degrees, mainly involving the large joints, which are present in all affected children at birth. The contractures may be mild and tend to improve over time, but permanently bent fingers and toes (camptodactyly) are almost always present. In addition to long fingers and toes and a tall, slender body, people with CCA often have ears that appear to be crumpled, joint stiffness and underdeveloped muscles (muscular hypoplasia), and they may have curved spines (congenital kyphoscoliosis). If kyphoscoliosis is present, it often becomes progressively worse and may require surgery. In some cases, the blood vessel that distributes blood from the heart to the rest of the body (aorta) may be abnormally enlarged (aortic root dilatation).
Causes
Congenital contractural arachnodactyly may be the result of new mutations in the FBN2 gene or it may be inherited from a parent in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
Diagnosis
CCA may be diagnosed through the physical characteristics associated with the disease of long, slender body and contractures of multiple joints, as well as other symptoms, such as muscular hypoplasia. Molecular genetic tests may be run using sequence analysis or deletion/duplication analysis to look for mutations in the FBN2 gene. Prenatal testing may be used for pregnancies with a risk of CCA, such as a parent or sibling with the disease.
Management
Joint contractures are treated using physical therapy to increase mobility and to improve the effects of underdeveloped muscles. Braces and/or surgery may be required to correct kyphoscoliosis. Children born with CCA are usually tested using echocardiograms every two years until the risks of an enlarged aorta (aortic root dilation) have been ruled out. If this is detected, it is managed with standard care for this condition.
Prognosis
Life expectancy may be affected by the disease symptoms present but it is not usually shortened for those with this disease.
See also
Congenital contractural arachnodactyly in cattle
References
== External links == |
Fetishism | A fetish (derived from the French fétiche, which comes from the Portuguese feitiço, and this in turn from Latin facticius, artificial and facere, to make) is an object believed to have supernatural powers, or in particular, a human-made object that has power over others. Essentially, fetishism is the attribution of inherent value, or powers, to an object.
Historiography
The term fetish has evolved from an idiom used to describe a type of object created in the interaction between European travelers and Africans in the early modern period to an analytical term that played a central role in the perception and study of non-Western art in general and African art in particular.
William Pietz, who, in 1994, conducted an extensive ethno-historical study of the fetish, argues that the term originated in the coast of West Africa during the sixteenth and seventeenth centuries. Pietz distinguishes between, on the one hand, actual African objects that may be called fetishes in Europe, together with the indigenous theories of them, and on the other hand, "fetish", an idea, and an idea of a kind of object, to which the term above applies.According to Pietz, the post-colonial concept of "fetish" emerged from the encounter between Europeans and Africans in a very specific historical context and in response to African material culture.
He begins his thesis with an introduction to the complex history of the word:
My argument, then, is that the fetish could originate only in conjunction with the emergent articulation of the ideology of the commodity form that defined itself within and against the social values and religious ideologies of two radically different types of noncapitalist society, as they encountered each other in an ongoing cross-cultural situation. This process is indicated in the history of the word itself as it developed from the late medieval Portuguese feitiço, to the sixteenth-century pidgin Fetisso on the African coast, to various northern European versions of the word via the 1602 text of the Dutchman Pieter de Marees... The fetish, then, not only originated from, but remains specific to, the problem of the social value of material objects as revealed in situations formed by the encounter of radically heterogeneous social systems, and a study of the history of the idea of the fetish may be guided by identifying those themes that persist throughout the various discourses and disciplines that have appropriated the term.
Stallybrass concludes that "Pietz shows that the fetish as a concept was elaborated to demonize the supposedly arbitrary attachment of West Africans to material objects. The European subject was constituted in opposition to a demonized fetishism, through the disavowal of the object."
History
Initially, the Portuguese developed the concept of the fetish to refer to the objects used in religious practices by West African natives. The contemporary Portuguese feitiço may refer to more neutral terms such as charm, enchantment, or abracadabra, or more potentially offensive terms such as juju, witchcraft, witchery, conjuration or bewitchment.
The concept was popularized in Europe circa 1757, when Charles de Brosses used it in comparing West African religion to the magical aspects of ancient Egyptian religion. Later, Auguste Comte employed the concept in his theory of the evolution of religion, wherein he posited fetishism as the earliest (most primitive) stage, followed by polytheism and monotheism. However, ethnography and anthropology would classify some artifacts of monotheistic religions as fetishes.
The eighteenth-century intellectuals who articulated the theory of fetishism encountered this notion in descriptions of "Guinea" contained in such popular voyage collections as Ramusios Viaggio e Navigazioni (1550), de Brys India Orientalis (1597), Purchass Hakluytus Posthumus (1625), Churchills Collection of Voyages and Travels (1732), Astleys A New General Collection of Voyages and Travels (1746), and Prevosts Histoire generale des voyages (1748).The theory of fetishism was articulated at the end of the eighteenth century by G. W. F. Hegel in Lectures on the Philosophy of History. According to Hegel, Africans were incapable of abstract thought, their ideas and actions were governed by impulse, and therefore a fetish object could be anything that then was arbitrarily imbued with imaginary powers.In the 19th and 20th centuries, Tylor and McLennan, historians of religion, held that the concept of fetishism fostered a shift of attention away from the relationship between people and God, to focus instead on a relationship between people and material objects, and that this, in turn, allowed for the establishment of false models of causality for natural events. This they saw as religious fetishism for Santa Claus on Christmas day and does not consider the birth of Jesus a central problem historically and sociologically.
Practice
The use of the concept in the study of religion derives from studies of traditional West African religious beliefs, as well as from Vodun, which in turn derives from those beliefs.
Fetishes were commonly used in some Native American religions and practices. For example, the bear represented the shaman, the buffalo was the provider, the mountain lion was the warrior, and the wolf was the pathfinder the cause of the war.
Japan
Kato Genchi cited jewelry, swords, mirrors, and scarves as examples of fetishism in Shintoism. Kato stated that leaving behind cities and going into rural areas, he could find many traces of animism, fetishism, and phallicism.Kato Genchi stated that the Ten Sacred Treasures were fetishes and the Imperial Regalia of Japan retained the same traits, and pointed out the similarities with the Pusaka of the natives of the East Indies and the Tjurunga of the Central Australians. The Kusanagi no Tsurugi was believed to provide supernatural protection (blessings) through the spiritual experience of the divine sword, and the Kusanagi no Tsurugi was deified and enshrined at Atsuta in Owari Province, which is now the Atsuta Shrine.Akaruhime no Kami, the deity of Hiyurikuso Shrine, was said to be a red ball. In the Kami era, the jewel around Izanagi-no-Mikotos neck was deified and called Mikuratana-kami.William George Aston remarked that the sword at Atsuta Shrine was originally an offering and later became a sacred object, as an example of Fetishism. Sword was one of mitama-shiro (spirit representative, spirit-token), or more commonly known as the shintai (god-body). He observed that people tends to think of the mitama (spirit) of a deity first as the seat of his real presence, and second as the deity itself. Many people do not distinguish between mitama (spirit) and shintai (god-body), and some even confused shintai (god-body) with the gods real body. For example, cooking furnace (kamado) itself was worshipped as god. Noting the vagueness between highly imperfect symbol of deity and fetish worship, being worsened by the restricted uses of images (e.g., painting, sculpture), there was a strong tendency to even forget that there is a god by ascribing special virtues to certain physical objects.Roy Andrew Miller observed that the Kokutai no Hongi and the Imperial Rescript on Education were also often worshipped as fetishes, and were respectfully placed and kept in household altars (kamidana).
Minkisi
Made and used by the BaKongo of western DRC, a nkisi (plural minkisi) is a sculptural object that provides a local habitation for a spiritual personality. Though some minkisi have always been anthropomorphic, they were probably much less naturalistic or "realistic" before the arrival of the Europeans in the nineteenth century; Kongo figures are more naturalistic in the coastal areas than inland. As Europeans tend to think of spirits as objects of worship, idols become the objects of idolatry when worship was addressed to false gods. In this way, Europeans regarded minkisi as idols on the basis of false assumptions.
Europeans often called nkisi "fetishes" and sometimes "idols" because they are sometimes rendered in human form. Modern anthropology has generally referred to these objects either as "power objects" or as "charms".
In addressing the question of whether a nkisi is a fetish, William McGaffey writes that the Kongo ritual system as a whole,
bears a relationship similar to that which Marx supposed that "political economy" bore to capitalism as its "religion", but not for the reasons advanced by Bosman, the Enlightenment thinkers, and Hegel. The irrationally "animate" character of the ritual systems symbolic apparatus, including minkisi, divination devices, and witch-testing ordeals, obliquely expressed real relations of power among the participants in ritual. "Fetishism" is about relations among people, rather than the objects that mediate and disguise those relations.
Therefore, McGaffey concludes, to call a nkisi a fetish is to translate "certain Kongo realities into the categories developed in the emergent social sciences of nineteenth century, post-enlightenment Europe."
See also
Boli
References
External links
The Catholic Encyclopaedia: Fetishism
Andrew Lang, Fetishism and Spiritualism, The Making of Religion, (Chapter VIII), Longmans, Green, and C°, London, New York and Bombay, 1900, pp. 147–159. |
RAPADILINO syndrome | RAPADILINO syndrome is an autosomal recessive disorder characterized by:
RA: radial ray defect
PA: patellar aplasia, arched or cleft palate
DI: diarrhea, dislocated joints
LI: little (short stature), limb malformation
NO: slender nose, normal intelligenceIt is more prevalent in Finland than elsewhere in the world. It has been associated with the gene RECQL4. This is also associated with Rothmund-Thomson syndrome and Baller-Gerold syndrome.
References
External links
GeneReviews/NCBI/NIH/UW entry on Baller-Gerold Syndrome |
DSM-IV codes | DSM-IV codes are the classification found in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, also known as DSM-IV-TR, a manual published by the American Psychiatric Association (APA) that includes almost all currently recognized mental health disorders. The DSM-IV codes are thus used by mental health professionals to describe the features of a given mental disorder and indicate how the disorder can be distinguished from other, similar problems.The coding system utilized by the DSM-IV is designed to correspond with codes from the International Classification of Diseases, Ninth Revision, Clinical Modification, commonly referred to as the ICD-9-CM. Since early versions of the DSM did not correlate with ICD codes and updates of the publications for the ICD and the DSM are not simultaneous, some distinctions in the coding systems may still be present. For this reason, it is recommended that users of these manuals consult the appropriate reference when accessing diagnostic codes
Note that NOS is an abbreviation for Not Otherwise Specified, indicating a cluster of symptoms that do not clearly fit in any single diagnostic category. NOS is often a provisional diagnosis pending additional information or testing.
For an alphabetical list, see DSM-IV codes (alphabetical).
Disorders usually first diagnosed in infancy, childhood, or adolescence
Mental retardation
317 Mild mental retardation
318.0 Moderate mental retardation
318.1 Severe mental retardation
318.2 Profound mental retardation
319 Mental retardation; severity unspecified
Learning disorders
315.00 Reading disorder
315.1 Mathematics disorder
315.2 Disorder of written expression
315.9 Learning disorder NOS
Motor skills disorders
315.4 Developmental coordination disorder
Communication disorders
315.31 Expressive language disorder
315.32 Mixed receptive-expressive language disorder
315.39 Phonological disorder
307.0 Stuttering
307.9 Communication disorder NOS
Pervasive developmental disorders
299.00 Autistic Disorder
299.80 Retts Disorder
299.10 Childhood Disintegrative Disorder
299.80 Asperger Syndrome
299.80 PDD-NOS
Attention-deficit and disruptive behavior disorders
Attention-Deficit Hyperactivity Disorder
314.01 Combined subtype
314.01 Predominantly hyperactive-impulsive subtype
314.00 Predominantly inattentive subtype
314.9 Attention-Deficit Hyperactivity Disorder NOS
Conduct disorder
312.81 Childhood onset
312.82 Adolescent onset
312.89 Unspecified onset
313.81 Oppositional Defiant Disorder
312.9 Disruptive Behavior Disorder NOS
Feeding and eating disorders of infancy or early childhood
307.52 Pica
307.53 Rumination disorder
307.59 Feeding disorder of infancy or early childhood
Tic disorders
307.23 Tourettes Disorder
307.22 Chronic motor or vocal tic disorder
307.21 Transient tic disorder
307.20 Tic disorder NOS
Elimination disorders
307.6 Enuresis (not due to a general medical condition)
307.7 Encopresis, without constipation and overflow incontinence
787.6 Encopresis, with constipation and overflow incontinence
Other disorders of infancy, childhood, or adolescence
309.21 Separation anxiety disorder
313.23 Selective mutism
313.89 Reactive attachment disorder of infancy or early childhood
307.3 Stereotypic movement disorder
313.9 Disorder of infancy, childhood, or adolescence NOSTop
Delirium, dementia, and amnestic and other cognitive disorders
Delirium
293.0 Delirium due to... [indicate the general medical condition]
780.09 Delirium NOS
Dementia
Dementia of the Alzheimers Type, with early onset
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia of the Alzheimers Type, with late onset
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Vascular dementia
290.40 Uncomplicated
290.41 With delirium
290.42 With delusions
290.43 With depressed mood
Dementia due to HIV disease
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia due to head trauma
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia due to Parkinsons disease
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia due to Huntingtons disease
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia due to Picks disease
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia due to Creutzfeldt–Jakob disease
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
Dementia due to... [indicate other general medical condition]
294.10 Without behavioral disturbance
294.11 With behavioral disturbance
294.8 Dementia NOS
Amnestic disorders
294.0 Amnestic disorder due to... [indicate the general medical condition]
294.8 Amnestic disorder NOS
Other cognitive disorders
294.9 Cognitive disorder NOSTop
Mental disorders due to a general medical condition not elsewhere classified
293.89 Catatonic disorder due to... [indicate the general medical condition]
310.1 Personality change due to... [indicate the general medical condition]
(Subtypes: Labile, Disinhibited, Aggressive, Apathetic, Paranoid, Other, Combined, Unspecified)
293.9 Mental disorder NOS due to... [indicate the general medical condition]Top
Substance-related disorders
Alcohol-related disorders
Alcohol
305.00 Abuse
303.90 Dependence
291.89 -Induced anxiety disorder
291.89 -Induced mood disorder
291.1 -Induced persisting amnestic disorder
291.2 -Induced persisting dementia
291.5 -Induced psychotic disorder, with delusions
291.3 -Induced psychotic disorder, with hallucinations
291.89 -Induced sexual dysfunction
291.89 -Induced sleep disorder
303.00 Intoxication
291.0 Intoxication delirium
291.9 -Related disorder NOS
291.81 Withdrawal
291.0 Withdrawal delirium
Amphetamine (or amphetamine-like) related disorders
Amphetamine (or amphetamine-like)
305.70 Abuse
304.40 Dependence
292.89 -Induced anxiety disorder
292.84 -Induced mood disorder
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 -Induced sexual dysfunction
292.89 -Induced sleep disorder
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS
292.0 Withdrawal
Caffeine-related disorders
Caffeine
292.89 -Induced anxiety disorder
292.89 -Induced sleep disorder
305.90 Intoxication
292.9 -Related disorder NOS
293.9.10 consumption diversion
Cannabis-related disorders
Cannabis
305.20 Abuse
304.30 Dependence
292.89 -Induced anxiety disorder
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS
Cocaine-related disorders
Cocaine
305.60 Abuse
304.20 Dependence
292.89 -Induced anxiety disorder
292.84 -Induced mood disorder
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 -Induced sexual dysfunction
292.89 -Induced sleep disorder
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS
292.0 Withdrawal
Hallucinogen-related disorders
Hallucinogen
305.30 Abuse
304.50 Dependence
292.89 -Induced anxiety disorder
292.84 -Induced mood disorder
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 Intoxication
292.81 Intoxication delirium
292.89 -persisting perception disorder
292.9 -Related disorder NOS
Inhalant-related disorders
Inhalant
305.90 Abuse
304.60 Dependence
292.89 -Induced anxiety disorder
292.84 -Induced mood disorder
292.82 -Induced persisting dementia
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS
Nicotine-related disorders
Nicotine
305.1 Dependence
292.9 -Related disorder NOS
292.0 Withdrawal
Opioid-related disorders
Opioid
305.50 Abuse
304.00 Dependence
292.84 -Induced mood disorder
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 -Induced sexual dysfunction
292.89 -Induced sleep disorder
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS
292.0 Withdrawal
Phencyclidine (or phencyclidine-like) related disorders
Phencyclidine (or phencyclidine-like)
305.90 Abuse
304.60 Dependence
292.89 -Induced anxiety disorder
292.84 -Induced mood disorder
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS
Sedative-, hypnotic-, or anxiolytic-related disorders
Sedative, hypnotic, or anxiolytic
305.40 Abuse
304.10 Dependence
292.89 -Induced anxiety disorder
292.84 -Induced mood disorder
292.83 -Induced persisting amnestic disorder
292.82 -Induced persisting dementia
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 -Induced sexual dysfunction
292.89 -Induced sleep disorder
292.89 Intoxication
292.81 Intoxication delirium
292.9 -Related disorder NOS
292.0 Withdrawal
292.81 Withdrawal delirium
Polysubstance-related disorder
304.80 Polysubstance dependence
Other (or unknown) substance-related disorder
Other (or unknown) substance
305.90 Abuse
304.90 Dependence
292.89 -Induced anxiety disorder
292.81 -Induced delirium
292.84 -Induced mood disorder
292.83 -Induced persisting amnestic disorder
292.82 -Induced persisting dementia
292.11 -Induced psychotic disorder, with delusions
292.12 -Induced psychotic disorder, with hallucinations
292.89 -Induced sexual dysfunction
292.89 -Induced sleep disorder
292.89 Intoxication
292.9 -Related disorder NOS
292.0 Withdrawal
293.0 Delirium Due to ... [Indicate the General Medical Condition]Top
Schizophrenia and other psychotic disorders
Schizophrenia
295.20 Catatonic type
295.10 Disorganized type
295.30 Paranoid type
295.60 Residual type
295.90 Undifferentiated type
295.40 Schizophreniform disorder
295.70 Schizoaffective disorder
297.1 Delusional disorder
Erotomanic subtype
Grandiose subtype
Jealous subtype
Persecutory subtype
Somatic subtype
Mixed type
298.8 Brief psychotic disorder
297.3 Shared psychotic disorder
Psychotic disorder due to... [indicate the general medical condition]
293.81 With delusions
293.82 With hallucinations
298.9 Psychotic disorder NOSTop
Mood disorders
293.83 Mood Disorder Due to...[Indicate the General Medical Condition]
296.90 Mood Disorder NOS
Depressive disorders
300.4 Dysthymic disorder
Major depressive disorder
Major depressive disorder, recurrent
296.36 In full remission
296.35 In partial remission
296.31 Mild
296.32 Moderate
296.33 Severe without psychotic features
296.34 Severe with psychotic features
296.30 Unspecified
Major depressive disorder, single episode
296.26 In full remission
296.25 In partial remission
296.21 Mild
296.22 Moderate
296.23 Severe without psychotic features
296.24 Severe with psychotic features
296.20 Unspecified
311 Depressive disorder NOS
Bipolar disorders
Bipolar disorders
296.80 Bipolar disorder NOS
Bipolar I disorder, most recent episode depressed
296.56 In full remission
296.55 In partial remission
296.51 Mild
296.52 Moderate
296.53 Severe without psychotic features
296.54 Severe with psychotic features
296.50 Unspecified
296.40 Bipolar I disorder, most recent episode hypomanic
Bipolar I disorder, most recent episode manic
296.46 In full remission
296.45 In partial remission
296.41 Mild
296.42 Moderate
296.43 Severe without psychotic features
296.44 Severe with psychotic features
296.40 Unspecified
Bipolar I disorder, most recent episode mixed
296.66 In full remission
296.65 In partial remission
296.61 Mild
296.62 Moderate
296.63 Severe without psychotic features
296.64 Severe with psychotic features
296.60 Unspecified
296.7 Bipolar I disorder, most recent episode unspecified
Bipolar I disorder, single manic episode
296.06 In full remission
296.05 In partial remission
296.01 Mild
296.02 Moderate
296.03 Severe without psychotic features
296.04 Severe with psychotic features
296.00 Unspecified
296.89 Bipolar II disorder
301.13 Cyclothymic disorder
293.83 Mood disorder due to... [indicate the general medical condition]
296.90 Mood disorder NOSTop
Anxiety disorders
300.02 Generalized anxiety disorder
Panic disorder
300.21 With agoraphobia
300.01 Without agoraphobia
300.22 Agoraphobia without history of panic disorder
300.29 Specific phobia
300.23 Social phobia
300.3 Obsessive-compulsive disorder
309.81 Posttraumatic stress disorder
308.3 Acute stress disorder
293.84 Anxiety disorder due to a general medical condition
293.89 Anxiety disorder due to... [indicate the general medical condition]
300.00 Anxiety disorder NOSTop
Somatoform disorders
300.81 Somatization disorder
300.82 Undifferentiated somatoform disorder
300.11 Conversion disorder
Pain disorder
307.89 Associated with both psychological factors and a general medical condition
307.80 Associated with psychological factors
300.7 Hypochondriasis/Illness anxiety disorder
300.7 Body dysmorphic disorder
300.82 Somatoform disorder NOSTop
Factitious disorders
Factitious disorder
300.19 With combined psychological and physical signs and symptoms
300.19 With predominantly physical signs and symptoms
300.16 With predominantly psychological signs and symptoms
300.19 Factitious disorder NOSTop
Dissociative disorders
300.6 Depersonalization disorder
300.12 Dissociative amnesia
300.14 Dissociative identity disorder
300.15 Dissociative disorder not otherwise specified
Sexual and gender identity disorders
Sexual dysfunctions
625.8 Female hypoactive sexual desire disorder due to... [indicate the general medical condition]
608.89 Male hypoactive sexual desire disorder due to... [indicate the general medical condition]
302.71 Hypoactive sexual desire disorder
302.79 Sexual aversion disorder
302.72 Female sexual arousal disorder
302.72 Male erectile disorder
607.84 Male erectile disorder due to... [indicate the general medical condition]
302.73 Female orgasmic disorder
302.74 Male orgasmic disorder
302.75 Premature ejaculation
302.76 Dyspareunia (not due to a general medical condition)
625.0 Female dyspareunia due to... [indicate the general medical condition]
608.89 Male dyspareunia due to... [indicate the general medical condition]
306.51 Vaginismus (not due to a general medical condition)
625.8 Other female sexual dysfunction due to... [indicate the general medical condition]
608.89 Other male sexual dysfunction due to... [indicate the general medical condition]
302.70 Sexual dysfunction NOS
Paraphilias
302.4 Exhibitionism
302.81 Fetishism
302.89 Frotteurism
302.2 Pedophilia
302.83 Sexual masochism
302.84 Sexual sadism
302.3 Transvestic fetishism
302.82 Voyeurism
302.9 Paraphilia NOS (not otherwise specified)
Gender identity disorders
Gender identity disorder
302.85 In adolescents or adults
302.6 In children
302.6 Gender identity disorder NOS
302.9 Sexual disorder NOS
Eating disorders
307.1 Anorexia nervosa
307.51 Bulimia nervosa
307.50 Eating disorder not otherwise specified (EDNOS)Top
Sleep disorders
Primary sleep disorders
307.44 Primary hypersomnia
307.42 Primary insomnia
347 Narcolepsy
780.59 Breathing-related sleep disorder
307.45 Circadian rhythm sleep disorder
307.47 Dyssomnia NOS
327.03 Insomnia Related to Mood Disorder (ICD 9)
Parasomnias
307.47 Nightmare disorder
307.46 Sleep terror disorder
307.46 Sleepwalking disorder
307.47 Parasomnia NOS
Other sleep disorders
Sleep disorder
Sleep disorder due to... [indicate the general medical condition]
780.54 Hypersomnia type
780.52 Insomnia type
780.59 Mixed type
780.59 Parasomnia type
307.42 Insomnia related to... [indicate the Axis I or Axis II disorder]
307.44 Hypersomnia related to... [indicate the Axis I or Axis II disorder]Top
Impulse-Control Disorders Not Elsewhere Classified
312.34 Intermittent Explosive Disorder
312.32 Kleptomania
312.31 Pathological Gambling
312.33 Pyromania
312.39 Trichotillomania
312.30 Impulse-Control Disorder NOSTop
Adjustment disorders
Adjustment disorders
309.9 Unspecified
309.24 With anxiety
309.0 With depressed mood
309.3 With disturbance of conduct
309.28 With mixed anxiety and depressed mood
309.4 With mixed disturbance of emotions and conductTop
Personality disorders (Axis II)
Cluster A (odd or eccentric)
301.0 Paranoid personality disorder
301.20 Schizoid personality disorder
301.22 Schizotypal personality disorderCluster B (dramatic, emotional, or erratic)
301.7 Antisocial personality disorder
301.83 Borderline personality disorder
301.50 Histrionic personality disorder
301.81 Narcissistic personality disorderCluster C (anxious or fearful)
301.82 Avoidant personality disorder
301.6 Dependent personality disorder
301.4 Obsessive-compulsive personality disorderNOS
301.9 Personality disorder not otherwise specifiedTop
Additional codes
V62.3 Academic problem
V62.4 Acculturation problem
995.2 Adverse effects of medication NOS
780.9 Age-related cognitive decline
Antisocial behavior
V71.01 Adult antisocial behavior
V71.02 Child or adolescent antisocial behavior
V62.82 Bereavement
V62.89 Borderline intellectual functioning
313.82 Identity problem
Medication-induced
Movement disorder
333.90 Movement disorder NOS
333.1 Postural tremor
Neglect of child
V61.21 Neglect of child
995.5 Neglect of child (if focus of attention is on victim)
Neuroleptic-induced
333.99 Acute akathisia
333.7 Acute dystonia
332.1 Parkinsonism
333.82 Tardive dyskinesia
333.92 Neuroleptic malignant syndrome
V71.09 No diagnosis on Axis II
V71.09 No diagnosis or condition on Axis I
V15.81 Noncompliance with treatment
V62.2 Occupational problem
V61.20 Parent-child relational problem
V61.10 Partner relational problem
V62.89 Phase of life problem
Physical abuse
V61.1 Physical abuse of adult
995.81 Physical abuse of adult (if focus of attention is on victim)
V61.21 Physical abuse of child
995.5 Physical abuse of child (if focus of attention is on victim)
316 Psychological factors affecting medical condition
Relational problem
V62.81 Relational problem NOS
V61.9 Relational problem related to a mental disorder or general medical condition
V62.89 Religious or spiritual problem
V61.1 Sexual abuse of adult
995.83 Sexual abuse of adult (if focus of attention is on victim)
V61.21 Sexual abuse of child
995.53 Sexual abuse of child (if focus of attention is on victim)
V61.8 Sibling relational problem
300.9 Unspecified mental disorder (nonpsychotic)
799.9 Diagnosis deferred on Axis II
799.9 Diagnosis or condition deferred on Axis I
V65.2 Malingering
See also
Clinical coder
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, 1994 (DSM-IV).
DSM-5
List of ICD-9 codes 290–319: mental disorders
Relational disorder (proposed DSM-V new diagnosis)
Structured Clinical Interview for DSM-IV (SCID)
External links
The Diagnostic and Statistical Manual of Mental Disorders (DSM), published by the American Psychiatric Association (APA, via archive.org)
== References == |
Iniencephaly | Iniencephaly is a rare type of cephalic disorder characterised by three common characteristics: a defect to the occipital bone, spina bifida of the cervical vertebrae and retroflexion (backward bending) of the head on the cervical spine. Stillbirth is the most common outcome, with a few rare examples of live birth, after which death almost invariably occurs within a short time.
The disorder was first described by Étienne Geoffroy Saint-Hilaire in 1836. The name is derived from the Ancient Greek word ἰνίον inion, for the occipital bone/nape of the neck.
Classifications
There are two types of iniencephaly. The more severe group is iniencephaly apertus (open iniencephaly), involving the development of an encephalocele. In the other group, iniencephaly clausus (closed iniencephaly), the encephalocele is absent.
Signs and symptoms
The affected infant tends to be short, with a disproportionately large head. The fetal head of infants born with iniencephaly are hyperextended while the foramen magnum is enlarged and opens through the widened pedicles. The defective neural arches directly into the upper cervical reach of the spinal canal, causing the formation of a common cavity between most of the spinal cord and the brain. The skin of the anterior chest is connected directly to the face, bypassing the formation of a neck, while the scalp is directly connected to the skin of the back. Because of this, those born with this anomaly either have a highly shortened neck or no neck at all. This causes extreme retroflexion, or backward bending, of the head in a "star-gazing" fashion. The spine is severely distorted as well along with significant shortening due to marked lordosis. The vertebrae, especially cervical, are fused together in abnormal shapes and their numbers are reduced. The spinal cord is almost always defective while the ventricular system is often dilated and the cortex is thinned. Sometimes, in the case of iniencephaly apertus, an encephalocele (sac-like protrusions of the brain through an opening in the cranium) forms.
Additional symptoms
Additional symptoms include:
Causes
Though the iniencephaly is not genetic with its cause unknown, studies have shown that there are certain factors that can increase the risk of mothers giving birth to children with these anomalies.
Chromosomal abnormalities
Abnormalities in chromosomes such as trisomy 18, trisomy 13, and monosomy X have been shown to be tied to this disorder.
Environmental factors
Mothers with poor socioeconomic conditions, poor nutrition, low parity, and lack of folic acid supplementation, and/or hyperhomocysteinemia have shown to be at larger risk.
Drugs
Animal studies have shown that administration of the drugs vinblastine, streptonigrin, triparano, sulfonamide, tetracycline, antihistamines, and antitumor agents to pregnant mothers have resulted in offspring born with iniencephaly. The drug clomiphene, a drug commonly used for ovulation stimulation in fertility treatments, has also been seen to be associated with iniencephaly.
Obesity
Studies have shown that obesity of the mother increases the risk of neural tube disorders such as iniencephaly by 1.7 fold while severe obesity increases the risk by over 3 fold.
History of iniencephaly
Once a mother has given birth to a child with iniencephaly, risk of reoccurrence increases to 1-5%.
Pathogenesis
The exact pathogenesis of iniencephaly is still unknown though there are proposed theories, most of which view the neural tube malformation from the primary neural anomaly standpoint.
Marin-Padilla and MarinPadilla have proposed that the cause for the abnormalities has to do with a deficiency in the primary mesoderm. P. Erdinçler, et al. suggests from their findings that the cause of the anomaly is actually a defect in the occipital bone and rachischisis of the posterior vertebral arches leading to herniation of neural tissue through the opening in the bone during gestation.
Diagnosis
The most accurate method of diagnosis is prenatal screening through real-time fetal images. However, since maternal body habitus leads to diagnostic difficulties using this method, MRI and sonography are the most commonly used technique since there is no exposure to ionizing radiation. At the beginning of the second trimester, the central nervous system (CNS) and anatomic structures of the fetus can be clearly visualized and the characteristic malformations of iniencephaly, such as a shortened trunk, marked lordosis in the cervicothoracic vertebrae, absence or partial absence of the occipital squama, abnormal fusion of vertebrae, closed vertebral arches, formation of an encephalocele (for iniencephaly apertus), and dorsiflexion of the head in respect to the spine, can be precisely diagnosed as well as the severity and location established. Once established, further decisions can be made with regard to terminating the pregnancy or providing a plan of adequate postnatal care.
Differential diagnosis
Since many of the characteristics of iniencephaly, such as congenital retroflexion of the spine and fusion of the cervical vertebrae, are shared with other disorders, key differences are important to note.While anencephaly experiences a partial to total lack of the neurocranium, iniencephaly does not. In anencephaly, the retroflexed head is not covered with skin while in iniencephaly, the retroflexed head is covered with skin entirely. Cervical vertebrae are malformed and reduced in iniencephaly while they are almost normal in anencephaly.Even though KFS does experience malformed cervical vertebra due to failure of segmentation during early fetal development, there is not retroflexion of the head as seen in iniencephaly. While iniencephaly clausus is fatal, KFS is not and can be surgically corrected. Therefore, it is crucial to correctly diagnose KFS and not mistake it for iniencephaly clausus.
Prevention
Pregnant mothers are advised to take folic acid supplements to reduce risk of iniencephaly by up to 70%. Pregnant mothers are also advised not to take antiepileptic drugs, diuretics, antihistamines, and sulfa drugs, all of which have been associated with increased risk for neural tube defects.
Treatment
Since newborns with iniencephaly so rarely survive past childbirth, a standard treatment does not exist.
Prognosis
Iniencephaly of both types carry a lethal prognosis, sometimes even ending in spontaneous abortion or stillborns. Most infants die within hours of childbirth. There are only seven reported cases of relatively long-term survival of those born with iniencephaly.
Epidemiology
Iniencephaly is thought to make up around 1% of all fetal abnormalities, with an incidence rate estimated at 0.1 to 10 in 10,000 deliveries.
For unknown reasons, this disease seems to occur most often in newborn females (about 90%).
References
== External links == |
Enamel hypoplasia | Enamel hypoplasia is a defect of the teeth in which the enamel is deficient in quantity, caused by defective enamel matrix formation during enamel development, as a result of inherited and acquired systemic condition(s). It can be identified as missing tooth structure and may manifest as pits or grooves in the crown of the affected teeth, and in extreme cases, some portions of the crown of the tooth may have no enamel, exposing the dentin. It may be generalized across the dentition or localized to a few teeth. Defects are categorized by shape or location. Common categories are pit-form, plane-form, linear-form, and localised enamel hypoplasia. Hypoplastic lesions are found in areas of the teeth where the enamel was being actively formed during a systemic or local disturbance. Since the formation of enamel extends over a long period of time, defects may be confined to one well-defined area of the affected teeth. Knowledge of chronological development of deciduous and permanent teeth makes it possible to determine the approximate time at which the developmental disturbance occurred. Enamel hypoplasia varies substantially among populations and can be used to infer health and behavioural impacts from the past. Defects have also been found in a variety of non-human animals.
Causes
Enamel hypoplasia is believed to result from the dysfunction of ameloblasts—enamel-producing cells—either for a short period of time or throughout their lifespan. Enamel hypoplasia has a wide variety of known causes. Some causes are hereditary and others are from environmental exposure. The severity and localization of disease presentation is dependent on the timing and stage of tooth development in which the defective enamel formation occurred.
Hereditary causes of enamel hypoplasia include:
Primary abnormalities in enamel development, such as amelogenesis imperfecta
Certain dermatological conditions, such as Ehlers-Danlos syndrome
Other complex hereditary conditions such as Usher syndrome, Seckel syndrome, Treacher-Collins syndrome, Heimler syndrome & Ellis-Van Creveld syndromeEnvironmental causes of enamel hypoplasia include:
Nutritional deficits, such as Vitamin D, iron or calcium deficiency
Birth injury or preterm birth
Smoking during pregnancy
Trauma
Radiation
Certain infections (e.g. congenital syphilis, cytomegalovirus, congenital rubella)
Certain diseases (such as undiagnosed and untreated celiac disease, chicken pox, congenital syphilis)
High fever
Hypoxia (i.e. from severe cardiac defect)
Excessive fluoride exposure (dental fluorosis)
Tetracycline
Vitamin A, C, or D deficiency
Clinical relevance
Enamel hypoplasia is a risk factor for dental caries in children including early childhood caries (ECC), which continues to be a burden for many children. This association has been identified as significant and independent, and is believed that the formation of pits and missing enamel provides a suitable local environment for adhesion and colonization of cariogenic bacteria. Historically, enamel hypoplasia has been under-appreciated as a risk factor for ECC.
Developmental defects in enamel that affect tooth appearance in the esthetic zone (i.e. upper front teeth) may cause individuals to experience social embarrassment or anxiety regarding the appearance of their teeth.
Guidelines for Treatment of Enamel Hypoplasia
Dental sealants may be indicated for the prevention of caries in hypoplastic pit & fissure systems.
According to clinical trials, topical fluoride treatment in the form of gel or varnish is effective in preventing tooth decay in children with enamel defects. Treatment with other topical agents, such as calcium phosphate (CPP-ACP), may also be effective in the remineralization of areas with congenital or carious enamel defects.In decayed teeth with enamel defects, only bonded restorations (e.g. glass ionomer, polyacid-modified composite resin and not amalgam) should be placed and cavity margins should not be placed in areas of defective enamel as this may lead to marginal leakage and recurrent decay. Stainless steel crowns with conservative preparation may be an effective method to eliminate sensitivity and prevent further breakdown in teeth with enamel defects requiring full-coverage crowns.
Other conditions affecting enamel development
Hypomineralization or hypocalcification, as opposed to hypoplasia, refers to a decrease in the mineral content of the enamel, not the total amount present. It can vary in its presentation, and teeth may appear visually normal or highly translucent. Affected enamel is softer and more susceptible to acid, wear and decay.
Molar-incisor hypomineralization
Molar-incisor hypomineralization (MIH) is a condition in which there are areas of hypomineralized or hypomatured enamel on the crowns of permanent molars and incisors. In these cases, teeth may lose their weakened enamel shortly after eruption and are highly susceptible to dental caries. Affected teeth are highly sensitive to chemical and thermal irritants, and may also be difficult to obtain anesthesia. The causes of MIH are thought to be similar to those of other forms of enamel hypoplasia, but occur concurrently with crown development in the permanent molars and incisors (birth to approximately 3 years of age).
Turners hypoplasia
Turners hypoplasia or Turners tooth is a presentation of enamel hypoplasia that normally affects only a single tooth. Its causes can be the same as other forms of enamel hypoplasia, but it is most commonly associated with trauma to a primary maxillary central incisor and the subsequent developmental disturbance of the underlying permanent tooth. This may also result in dilaceration of the root of the permanent tooth.
References
== External links == |
Vocal cord paresis | Vocal cord paresis, also known as recurrent laryngeal nerve paralysis or vocal fold paralysis, is an injury to one or both recurrent laryngeal nerves (RLNs), which control all intrinsic muscles of the larynx except for the cricothyroid muscle. The RLN is important for speaking, breathing and swallowing.The primary larynx-related functions of the mainly efferent nerve fiber RLN, include the transmission of nerve signals to the muscles responsible for regulation of the vocal folds position and tension to enable vocalization, as well as the transmission of sensory nerve signals from the mucous membrane of the larynx to the brain.
A unilateral injury of the nerve typically results in hoarseness caused by a reduced mobility of one of the vocal folds. It may also cause minor shortages of breath as well as aspiration problems especially concerning liquids. A bilateral injury causes the vocal folds to impair the air flow resulting in breathing problems, stridor and snoring sounds, and fast physical exhaustion. This strongly depends on the median or paramedian position of the paralyzed vocal folds. Hoarseness rarely occurs in bilaterally paralyzed vocal folds.
Signs and symptoms
Typically, patients with vocal fold paresis or paralysis are able to identify the onset of their symptoms. The most commonly reported symptom patients with either vocal fold paresis or paralysis make is having a rough voice quality. It is important to note that the symptoms of vocal fold paresis are not specific to the condition and tend to be common symptoms of other voice disorders as well. Vocal fold bowing, decreased vocal fold mobility, especially decreased mobility of the arytenoid cartilage, are often observed in vocal fold paresis. Glottal insufficiency is another common symptom observed in vocal fold paresis. In this case, the vocal folds do not come together properly. Glottal insufficiency may be hard to identify, especially when the area above the vocal folds is hyperfunctional. Hyperfunction may also make it difficult to detect the presence of vocal fold paresis. Hyperfunction of the area above the vocal folds may be considered a sign of glottal insufficiency and potentially, vocal fold paresis.In some cases, glottal closure may appear to be normal, however, asymmetries in the vocal folds may still be present. Though voice qualities may appear normal in some cases of vocal fold paresis or paralysis, mild differences in tension between the two vocal folds of the larynx can result in changes of voice pitch, intensity and reduced vocal stamina.Patients with either vocal fold paresis or paralysis may exhibit a breathy voice quality. This voice quality results from the increased activity of the vocal folds to compensate for the immobility of the PCA muscle(s). Patients may need to use more effort than normal when speaking and may find that their voice quiets or grows tired after speaking for a long time. This is known as vocal fatigue. Patients may also complain about having a limited pitch range and trouble varying their pitch at quick rate. It is often difficult for the speaker to project their voice and speak loud enough to be heard in noisy environments, over background noise, or when speaking to someone from a distance. It is possible for symptoms to surface only in situations where the environmental acoustics are poor, such as outdoors. Patients may report feeling pain in the throat or experiencing bouts of choking. A patient presenting with diplophonia is of major concern as this typically means that the mass and tension of their vocal folds are asymmetrical which may also indicate vocal fold paresis.Swallowing difficulties (dysphagia) are not commonly seen in vocal fold paresis that results from RLN damage. Dysphagia may however, suggest SLN damage. Symptoms of sensory nerve damage include: chronic coughing, the feeling of having a lump in the throat (globus sensation), hypersensitivity or abnormal sensation, spasms of the vocal folds (laryngospasms), dysphagia, pain from vocal use, and voice loss in high pitch ranges. It is possible for both the RLN and the SLN to be damaged simultaneously, so the symptoms of RLN and SLN damage may be seen independently or alongside one another.If maladaptive compensatory strategies are used more and more to try to offset the voice difficulties, the vocal mechanisms will fatigue and the above symptoms will worsen.
Causes
There are a wide variety of possible causes of vocal fold (VF) paresis, including congenital (i.e. present at birth) causes, infectious causes, tumors, traumatic causes, endocrinologic diseases (i.e. thyroid disease), and systemic neurologic diseases.
Congenital
Congenital conditions that are implicated in VFP include neurological disorders like hydrocephalus and Arnold-Chiari malformation, dysmorphic neurological disorders such as Moebius syndrome or Goldenhar Syndrome, anatomical abnormalities such as a tracheoesophageal fistula, vascular anomalies (e.g. vascular ring) affecting the vocal mechanism, syndromes affecting brainstem function or atrophic diseases such as Charcot-Marie-Tooth.In the absence of imaging, either invasive (e.g. laryngoscopy) or non-invasive (e.g. computed tomography scan), congenital VFP can be detected in infants through the presence of stridor (i.e. a high-pitched wheezing resulting from a blockage in the larynx or trachea), difficulties feeding, an abnormal sounding cry or excessive hoarseness.Recovery from congenital VFP varies and is reliant on the severity of the condition. Some cases of VFP recover spontaneously, often within the first year. If the paresis is persistent, surgical options such as vocal fold injections or tracheotomy can be taken into consideration.
Infection
Many viral infections have been reported as a cause for VF paresis, including herpes simplex virus, Epstein-Barr virus, Varicella-Zoster, cytomegalovirus, HIV, West Nile virus, and upper respiratory infection. Bacterial infections have also been reported to cause VF paresis, such as syphilis and Lyme disease.
Tumors
When abnormal cells group together in the body, they are said to form a tumor. Tumors can be either malignant (cancerous) or benign (non-cancerous). Tumors may lead to paralysis of the vocal folds when they affect the recurrent laryngeal nerves (RLNs) either directly or indirectly:
RLN paralysis can be caused by tumors of the thyroid, lung, esophagus, and mediastinum.
Radiation as a treatment for malignant head and neck tumors can reduce the number of blood vessels in the treatment area and lead to scarring. In some cases, this can paralyze the vagus nerve, of which the RLNs are branches.
Tumors of the vagus nerve, called vagal neurilemmomas, can also paralyze the vocal folds.
Trauma
VF paresis can result from trauma to one of more laryngeal nerves during intubation, surgery (e.g. thyroidectomy, spine surgery, carotid endartectomy, vagal nerve stimulator implantation), injection of botulinum neurotoxin, or penetrating neck trauma.
Thyroid disease
Causes of VF paresis also include diseases of the thyroid gland, such as hypothyroidism, goiter, and thyroiditis.
Systemic neurologic diseases
Several neurological diseases can cause VF paresis including:
Myasthenia Gravis (MG), a rare neuromuscular autoimmune disease. MGs dominant characteristic is muscles weakness including facial, jaw, pharyngeal and laryngeal muscles.
Charcot-Marie-Tooth (CMT), a neurological heredity disease that affects both motor and sensory functions. CMT affects the nerve cells and interrupts the transmission of nerve impulses as it concerns the axons and the myelination of the nerve cells.
Multiple Sclerosis (MS), which is an autoimmune disease that damages the myelin sheet surrounding the axons of the cranial nerves and the spinal nerves. There are several types of MS depending on the course of the disease.
Spinocerebellar Degeneration, a term that refers to a rare yet diverse chronic disease that affects the brain and the spinal cord. Spinocerebellar Degeneration is usually an inherited progressive disease; however, toxicity and vitamin deficiency can result in the acquired type of cerebellar degeneration disease.Additionally, there are pieces of evidence that some Systemic Rheumatological Diseases such as sarcoidosis, rheumatoid, scleroderma can result in having VF paresis.
Cardiovascular
A rare cause of vocal cord paresis that often presents itself as unexplained hoarseness is cardiovocal syndrome or Ortners syndrome. Although it was originally identified in patients with left atrial enlargement, the definition has expanded to include aneurysms of the aortic arch, pulmonary hypertension due to mixed connective tissue disease, or aberrant subclavian artery syndrome among other causes of left recurrent laryngeal nerve palsy with cardiovascular origin.
Diagnosis
There are a variety of ways to diagnose vocal fold paralysis. Important indications of possible causes can be revealed in the patients medical history, which may inform which diagnostic approach is taken. Voice diagnostics are used to assess voice quality and vocal performance. Voice assessment is necessary to plan and estimate the success of a possible speech therapy.[12]An auditory-perceptual evaluation is conducted by a Speech-Language Pathologist (S-LP), and allows changes in voice quality to be monitored over time. There are two scales which can be used to subjectively measure voice quality: the GRBAS (grade, roughness, breathiness, asthenia, strain) and the CAPE-V (Consensus Auditory Perceptual Evaluation of Voice). The GRBAS is used to rate the patients voice quality on 5 dimensions: grade (overall severity), roughness, breathiness, asthenia (weakness) and strain. Each dimension will receive a severity rating from 0 (not present) to 3 (severe). This allows the S-LP to make a judgment about the overall severity of the voice quality. The CAPE-V is used in a similar manner, rating of the dimensions of voice quality on a subjective scale from 0–100, and using this to determine an overall severity score.In the presence of neural lesions with unknown cause, a thorough ENT endoscopy with additional imaging techniques (computed tomography (CT) of the chest, particularly in the case of left-sided paralyses, and magnetic resonance imaging (MRI) of the neck including the base of the skull and the brain, ultrasound examination of the neck) are performed to exclude tumors along the laryngeal nerves. When tumor formation is suspected, parts of the hypopharynx and the upper esophagus and passive mobility of the arytenoid cartilage are endoscopically examined under anesthesia.Voice diagnostics are used to assess voice quality and vocal performance. Voice assessment is necessary to plan and estimate the success of a possible speech therapy. In incompletely or only partially healed paralyses, stroboscopic larynx examinations yield a type of slow motion picture to assess tension and fine mobility of the vocal folds during vocalization. Stroboscopy and voice assessment are important to establish an individual treatment plan to improve the voice.
Breathing tests (spirometry, body plethysmography) are used to measure impairment of respiratory flow through the larynx, particularly in patients with bilateral paralysis.
Electromyography of the larynx muscles (larynx EMG), which measures the electrical activity of the larynx muscles via thin needle electrodes, allows better differentiation between a neural lesion and other causes of impaired mobility of the vocal fold and localization of the lesion along the nerve. The larynx EMG can, within limits, provide a prognosis of the development of a recurrent laryngeal nerve paralysis. Patients with a poor chance of healing can be identified at an early stage. Unfortunately, this advanced examination technique is not available in all treatment centers.
The treating physician must view all examination results combined and establish an individual diagnosis and treatment plan for each patient.
Classification
Vocal fold paresis refers to a partial loss of input to the nerve of the vocal folds. This loss of neural input leads to reduced vocal fold mobility. It is a condition with a variable profile, as the severity of the paresis can range on a wide continuum from minor to major loss of vocal fold mobility. Vocal fold paralysis, distinguished from vocal paresis, is the total loss of vocal fold mobility due to a lack of neural input to the vocal folds. These conditions result from continuous damage to the laryngeal nerves and often lead to vocal disability. Recurrent laryngeal nerve damage is the most common cause of vocal fold paresis. The RLN is responsible for motor input to the vocal folds. Physicians may also use the term recurrent laryngeal nerve paralysis. Additionally, superior laryngeal nerve damage (SLN) can also lead to vocal fold paresis. The SLN is responsible for sensory input to the vocal folds. Due to its variable nature, the progression of vocal fold paresis may fluctuate, so it may be characterized differently from one evaluation to the next. Fluctuating vocal fold paresis has been observed in neurodegenerative disorders like Guillain–Barré syndrome or myasthenia gravis.The posterior cricoarytenoid (PCA) is a muscle of the larynx that is responsible for pulling the vocal folds apart from one another. Vocal fold paresis describes the weakness of the PCA and an impairment to its functioning. Unilateral vocal fold paresis is the term used when there is damage to the RLN on one side of the body. In unilateral vocal fold paresis, there is a lack of nerve supply to one side of the vocal folds PCA muscle. This lack of nerve supply renders the arytenoid cartilage immobile. The RLN may be damaged during surgical procedures. The right RLN in particular, has a greater chance of being damaged during surgery due to its position in the neck. When both of the vocal folds PCA muscles lack a nerve supply, the term bilateral vocal fold paresis is used. With bilateral vocal fold paresis, a persons airway may become blocked as the muscles are unable to pull the vocal folds apart fully.
Treatment
The treatment of vocal fold paralysis varies depending on its cause and main symptoms. For example, if laryngeal nerve paralysis is caused by a tumor, suitable therapy should be initiated. In the absence of any additional pathology, the first step of clinical management should be observation to determine whether spontaneous nerve recovery will occur. Voice therapy with a speech-language pathologist is suitable at this time, to help manage compensatory vocal behaviours which may manifest in response to the paralysis.
Voice therapy
The overall goal of voice therapy is to narrow the glottis without causing hyperfunction of the surrounding muscles. In the past, forced adduction exercises were used to push the vocal folds together, but often resulted in additional stress on the vocal folds. Current methods focus more generally on improving abdominal support, muscle strength and agility.
Hard glottal attacks
Hard glottal attacks involve building up subglottal pressure (air pressure below the vocal folds) before letting out a vowel sound. Often, this method is beneficial for clients who compensate by use of a falsetto register.
Half-swallow boom
The half-swallow boom allows for a repositioning of the vocal folds by taking advantage of laryngeal positioning when swallowing. The client is asked to take a breath and then initiate the movement of swallowing, followed by forcefully saying "boom". When performed properly, the "boom" sounds loud and clear. Eventually, this sound can be generalized to other words and phrases.
Abdominal breathing
Training in breath support is essential for those clients who identify as professional voice users. Shifting the awareness of the breath to the belly (diaphragmatic breathing) aids in efficient vocal function, reducing the risk of hyperfunction and muscular tension.
Lip and tongue trills
Lip and tongue trills aid in the balance of resonance, as well as coordinate the muscles of respiration, phonation and articulation. In addition, subglottal pressure may increase during lip trills, and result in the generation greater vocal fold vibration.
Surgery
After 9 months of observation, should the paralysis not resolve and the patient be dissatisfied with the outcomes of voice therapy, the next option is temporary injection medialization. In this procedure, a variety of materials can be injected into the body of the vocal fold in order to bring it closer to the midline of the glottis. Materials such as Teflon, autologous fat, collagens acellular dermis, fascia, hydroxyapatite and hyaluronates are available to be used in the procedure. The choice of substance is dependent on several factors, taking into consideration the specific condition and preference of the patient as well as the clinical practice of the surgeon. The materials serve the purpose of filling up the vocal folds and increasing their volume. This allows the paralyzed vocal fold to make contact with the alternate fold, in order to more efficiently produce phonation. While injection augmentation has been long considered best practice, neither technique nor materials used have been standardized across clinicians. With this, results prove to be both safe and effective, but variable in their duration, lasting anywhere from 2 to 12 months.For patients with significant paralysis at 12 months post-onset, medialization thyroplasty may be suggested. This surgical procedure introduces a shim between the inner wall of the larynx and the soft tissue supporting the vocal fold. As a result, the paralyzed vocal fold is supported in a position closer to the midline of the glottis, and retains its ability to vibrate and phonate efficiently.In addition to medialization thyroplasty, arytenoid adduction can be performed to improve phonation results. This medical procedure consists of pulling the vocal processes of the arytenoid medially while monitoring the voicing quality being produced by the patient. When the best phonation appears to be achieved, the vocal processes are then maintained in place by a thread.A further surgical intervention used to mitigate vocal fold paresis is laryngeal reinnervation. This procedure restores nerve supply to the larynx and can be accomplished according to different techniques. Depending on the specific condition (i.e. bilateral versus unilateral vocal fold paralysis), these techniques include reconnecting parts of the RLN, supplying the laryngeal muscles with a donor nerve like the ansa cervicalis, or connecting the RLN to a donor nerve.
Post-surgical outcomes
In many cases, the surgical treatment options described above (temporary injection medialization, medialization thyroplasty, arytenoid adduction, and laryngeal reinnervation) have led to favourable outcomes as measured perceptually, acoustically, by laryngoscope, or via quality of life measures. However, none of these surgical interventions has been shown to be significantly better than the others.
Voice therapy after surgery
It is generally recommended that voice therapy start 1 to 2 months after surgery, when swelling has subsided. Post-surgical intervention is warranted to restore laryngeal muscle strength, agility and coordination.
Epidemiology
Due to the complex and controversial nature of this condition, epidemiological (incidence) reports vary significantly and more research in this area is needed. Instead of reporting the incidence of this condition within the general population, most studies are conducted within specialized voice disorder clinics. In such a setting, one study found that approximately 26% of patients are diagnosed with paralysis or paresis of the vocal folds. Yet, incidence rates as high as 80% for vocal fold paresis have been reported elsewhere. Yet another source reported only 71 cases of vocal fold paresis over 7 years. Incidence rates of vocal fold paresis after undergoing thyroid surgery have been reported between 0.3% and 13.2%, whereas these incidence rates are between 2% and 21.6% after undergoing spinal surgery.
See also
Puberphonia
References
== External links == |
Tracheobronchitis | Tracheobronchitis is inflammation of the trachea and bronchi. It is characterised by a cough, fever, and purulent (containing pus) sputum and is therefore suggestive of pneumonia. It is classified as a respiratory tract infection.Tracheobronchitis is often a hospital-acquired infection, particularly in an intensive care setting, associated with the use of mechanical ventilators, and the need for inserting a tracheal tube. In these cases it is known as ventilator-associated tracheobronchitis. The infection begins in the trachea where it colonises and spreads to the bronchi.
The characteristic increased sputum produced can give problems in the removal of the tracheal tube (extubation). Tracheobronchial infections are responsible for up to 80% of exacerbations in chronic obstructive pulmonary disease.
Causes
Ventilator-associated tracheobronchitis is a hospital-acquired infection usually contracted in an intensive care unit when a mechanical ventilator is used. The insertion of a tracheal tube can cause an infection in the trachea which then colonises and spreads to the bronchi. If there is further spread and development into the lungs this will give rise to ventilator-associated pneumonia. Antibiotics are recommended to prevent this development but only as a short term measure as antibiotic resistance is already high in some of the pathogens involved. This does not always progress to pneumonia.Fungal tracheobronchitis can be invasive into the lung tissue or pulmonary artery and cause a severe lung infection. The extra secreted mucus from tracheobronchitis plugs the airways allowing the fungal pathogens to lodge and multiply. Local damage to the tracheal wall that can be caused by mechanical ventilation is a risk factor for this. Respiratory failure may develop from this infection.Herpetic tracheobronchitis is caused by herpes simplex virus and causes small ulcers covered in exudate to form on the mucous membranes. The exudate contains necrotic cells from the mucosal epithelium.
The characteristic increased sputum produced can give problems in the removal of the tracheal tube (extubation). In the course of cystic fibrosis the lungs are affected. Thickened mucus secretions block the airways making infection possible. The recurrence of tracheobronchitis presents a major problem.In chronic obstructive pulmonary disease tracheobronchial infections are responsible for up to 80% of exacerbations.
In dogs
Tracheobronchitis often affects dogs particularly those confined in kennels where their persistent barking worsens the inflammation. This canine infectious tracheobronchitis is more usually known as kennel cough.
== References == |
Repetitive strain injury | A repetitive strain injury (RSI) is an injury to part of the musculoskeletal or nervous system caused by repetitive use, vibrations, compression or long periods in a fixed position. Other common names include repetitive stress disorders, cumulative trauma disorders (CTDs), and overuse syndrome.
Signs and symptoms
Some examples of symptoms experienced by patients with RSI are aching, pulsing pain, tingling and extremity weakness, initially presenting with intermittent discomfort and then with a higher degree of frequency.
Definition
Repetitive strain injury (RSI) and associative trauma orders are umbrella terms used to refer to several discrete conditions that can be associated with repetitive tasks, forceful exertions, vibrations, mechanical compression, sustained or awkward positions, or repetitive eccentric contractions. The exact terminology is controversial, but the terms now used by the United States Department of Labor and the National Institute of Occupational Safety and Health (NIOSH) are musculoskeletal disorders (MSDs) and work-related muscular skeletal disorders (WMDs).Examples of conditions that may sometimes be attributed to such causes include tendinosis (or less often tendinitis), carpal tunnel syndrome, cubital tunnel syndrome, De Quervain syndrome, thoracic outlet syndrome, intersection syndrome, golfers elbow (medial epicondylitis), tennis elbow (lateral epicondylitis), trigger finger (so-called stenosing tenosynovitis), radial tunnel syndrome, ulnar tunnel syndrome, and focal dystonia.A general worldwide increase since the 1970s in RSIs of the arms, hands, neck, and shoulder has been attributed to the widespread use in the workplace of keyboard entry devices, such as typewriters and computers, which require long periods of repetitive motions in a fixed posture. Extreme temperatures have also been reported as risk factor for RSI.
Risk factors
Occupational risk factors
Workers in certain fields are at risk of repetitive strains. Most occupational injuries are musculoskeletal disorders, and many of these are caused by cumulative trauma rather than a single event. Miners and poultry workers, for example, must make repeated motions which can cause tendon, muscular, and skeletal injuries. Jobs that involve repeated motion patterns or prolonged posture within a work cycle, or both, may be repetitive. Young athletes are predisposed to RSIs due to an underdeveloped musculoskeletal system.
Psychosocial factors
Factors such as personality differences to work-place organization problems. Certain workers may negatively perceive their work organization due to excessive work rate, long work hours, limited job control, and low social support. Previous studies shown elevated urinary catecholamines (stress-related chemicals) in workers with RSI. Pain related to RSI may evolve into chronic pain syndrome particularly for workers who do not have supports from co-workers and supervisors.
Non-occupational factors
Age and gender are important risk factors for RSIs. The risk of RSI increases with age. Women are more likely affected than men because of their smaller frame, lower muscle mass and strength, and due to endocrine influences. In addition, lifestyle choices such as smoking and alcohol consumption are recognizable risk factors for RSI. Recent scientific findings indicate that obesity and diabetes may predispose an individual to RSIs by creating a chronic low grade inflammatory response that prevents the body from effectively healing damaged tissues.
Diagnosis
RSIs are assessed using a number of objective clinical measures. These include effort-based tests such as grip and pinch strength, diagnostic tests such as Finkelsteins test for De Quervains tendinitis, Phalens contortion, Tinels percussion for carpal tunnel syndrome, and nerve conduction velocity tests that show nerve compression in the wrist. Various imaging techniques can also be used to show nerve compression such as x-ray for the wrist, and MRI for the thoracic outlet and cervico-brachial areas. Utilization of routine imaging is useful in early detection and treatment of overuse injuries in at risk populations, which is important in preventing long term adverse effects.
Treatment
There are no quick fixes for RSI. Early diagnosis is critical to limiting damage. For Upper Limb Repetitive Strain Injury (RSI), Occupational Therapists create interventions that include education to facilitate ergonomics. This will minimize the possibility of an upper limb strain injury by learning the correct approach during facilitating functional task movements. The RICE treatment is used as the first treatment for many muscle strains, ligament sprains, or other bruises and injuries. RICE is used immediately after an injury happens and for the first 24 to 48 hours after the injury. These modalities can help reduce the swelling and pain. Commonly prescribed treatments for early-stage RSIs include analgesics, myofeedback, biofeedback, physical therapy, relaxation, and ultrasound therapy. Low-grade RSIs can sometimes resolve themselves if treatments begin shortly after the onset of symptoms. However, some RSIs may require more aggressive intervention including surgery and can persist for years.Although there are no "quick fixes" for RSI, there are effective approaches to its treatment and prevention. One is that of ergonomics, the changing of ones environment (especially workplace equipment) to minimize repetitive strain.
General exercise has been shown to decrease the risk of developing RSI. Doctors sometimes recommend that those with RSI engage in specific strengthening exercises, for example to improve sitting posture, reduce excessive kyphosis, and potentially thoracic outlet syndrome. Modifications of posture and arm use are often recommended.
History
Although seemingly a modern phenomenon, RSIs have long been documented in the medical literature. In 1700, the Italian physician Bernardino Ramazzini first described RSI in more than 20 categories of industrial workers in Italy, including musicians and clerks. Carpal tunnel syndrome was first identified by the British surgeon James Paget in 1854. The April 1875 issue of The Graphic describes "telegraphic paralysis."The Swiss surgeon Fritz de Quervain first identified De Quervains tendinitis in Swiss factory workers in 1895. The French neurologist Jules Tinel (1879–1952) developed his percussion test for compression of the median nerve in 1900. The American surgeon George Phalen improved the understanding of the aetiology of carpal tunnel syndrome with his clinical experience of several hundred patients during the 1950s and 1960s.
Society
Specific sources of discomfort have been popularly referred to by terms such as Blackberry thumb, PlayStation thumb, Rubiks wrist or "cubers thumb", stylus finger, and ravers wrist, and Emacs pinky.
See also
Computer vision syndrome
Ergonomic keyboard
List of repetitive strain injury software
Maltron
Microsoft ergonomic keyboards
Citations
External links
Repetitive Strain Injuries at Curlie
Musculoskeletal disorders from the European Agency for Safety and Health at Work (EU-OSHA)
Amadio PC (January 2001). "Repetitive stress injury". J Bone Joint Surg Am. 83-A (1): 136–7, author reply 138–41. doi:10.2106/00004623-200101000-00018. PMID 11205849. |
Reactive airway disease | Reactive airway disease (RAD) is an informal label that physicians apply to patients with symptoms similar to those of asthma. An exact definition of the condition does not exist. Individuals who are typically labeled as having RAD generally have a history of wheezing, coughing, dyspnea, and production of sputum that may or may not be caused by asthma. Symptoms may also include, but are not limited to, coughing, shortness of breath, excess mucus in the bronchial tube, swollen mucous membrane in the bronchial tube, and/or hypersensitive bronchial tubes. Physicians most commonly label patients with RAD when they are hesitant about formally diagnosing a patient with asthma, which is most prevalent in the pediatric setting. While some physicians may use RAD and asthma synonymously, there is controversy over this usage.
More generally, there is controversy over the use of RAD as a label in the healthcare setting, largely due to the ambiguous definition that the term has. Since RAD is not recognized as a real clinical diagnosis, its meaning is highly inconsistent and may cause confusion and misdiagnosis within the medical community. There are also concerns with overtreatment and undertreatment with RAD amongst physicians, since there is little formality with the label. Other problems that healthcare workers have with the use of the RAD label include its exclusion in the International Statistical Classification of Diseases and Related Health Problems, which can lead to billing issues in hospitals and other health care facilities, and the creation of a fabricated sense of security when using it has a diagnosis.RAD can be confused with reactive airways dysfunction syndrome, an asthma-like disorder that results from high exposure to vapors, fumes, and/or smoke. Unlike RAD, reactive airways dysfunction syndrome is recognized by multiple societies as a real clinical syndrome, including the American Thoracic Society and the American College of Chest Physicians.
Terminology
The term reactive airway disease originally began to appear in medical literature in the 1980s in reference to asthmatic patients with hyperactive airways, which is a common feature of asthma. This feature is characterized by increased bronchoconstriction reactions in response to stimuli that should not elicit so strong of response. These stimuli can include methacholine, histamine, and distilled water. However, while this was how the term initially was introduced, RAD soon began to be used interchangeably with the term asthma itself, which has led to the current controversy over its place in medical diagnoses.More commonly, RAD is now mostly used by physicians when they are hesitant to diagnose a patient with asthma. This is most prominent in pediatric settings for a variety of reasons. While infants tend to wheeze more often than adults, only one third of them eventually go on to actually have asthma. Asthma and viral bronchiolitis can also be nearly identical to each other when presented in very young children, since they both consist of wheezing, coughing, and nasal congestion. In addition, typical tests used to accurately diagnose children with asthma, such as the bronchial challenge test, are not considered to be accurate for children under the age of five. This can be due to failure of very young children to cooperate. Diagnosing a child with asthma also carries a certain negative connotation, causing hesitancy from some physicians to do so. All of these factors lead physicians to label young children with RAD instead of asthma, since the disease is often only suspected and unable to be confirmed with pediatric patients.Physicians will generally label an adult with RAD if they have no prior diagnosis or history of asthma while exhibiting symptoms of wheezing, production of sputum, and/or the use of an inhaler. Symptoms may also include, but are not limited to, coughing, shortness of breath, excess mucus in the bronchial tube, swollen mucous membrane in the bronchial tube, and/or hypersensitive bronchial tubes. In order to make a formal asthma diagnosis in adult patients, there is requirement to have documentation of either airway hyperreactivity or some sort of reversible airway obstruction. If none of these symptoms are present in an adult patients medical history or documentation, the physician may label the patient with RAD instead of asthma in order to still indicate there is an airway issue without formal diagnosis.
Reactive airways dysfunction syndrome
While the acronyms are similar, reactive airway disease (RAD) and reactive airways dysfunction syndrome (RADS) are not the same.Reactive airways dysfunction syndrome was first identified by Stuart M. Brooks and colleagues in 1985 as an asthma-like syndrome developing after a single exposure to high levels of an irritating vapor, fume, or smoke. It can manifest in adults with exposure to high levels of chlorine, ammonia, acetic acid, or sulphur dioxide, creating symptoms like asthma. These symptoms can vary from mild to fatal and can even create long-term airway damage, depending on the amount of exposure and the concentration of chlorine. Patients that have been diagnosed with RADS will likely have methacholine airway hyperreactivity, yet other tests that also measure pulmonary functions may appear normal. Some experts classify RADS as occupational asthma. Those with exposure to highly irritating substances should receive treatment to mitigate harmful effects. Treatment for RADS is similar to treatment for other disorders that result from acute inhalation. Preexisting allergies can be a risk factor for developing RADS.The main difference between RAD and RADS is that RADS can occur after just one exposure to the inhalants and without any prior sensitization. In addition, although the symptoms of RADS are very similar to those of asthma, they may be resolved. While some physicians argue that RADS is also not a real clinical syndrome, it is more commonly recognized in legitimate associations than RAD. These associations include the American Thoracic Society and the American College of Chest Physicians.
Controversy over use
There remains controversy over the use of RAD as an unofficial diagnosis. With its use not only being limited to clinical lexicon, but also transitioning to clinical literature now, more physicians are now increasingly disapproving its use in the healthcare setting.One of the largest problems with the using RAD as a diagnostic label lies in the ambiguity of its meaning, as RAD has no true clinical definition. It is either not listed or redirects to "asthma" in all major medical journal or website. In addition to that, it is also not recognized in the American Academy of Pediatrics; the American Thoracic Society; or the National Heart Lung and Blood Institute. In addition, treatments for asthma, chronic bronchitis, emphysema, or pneumonia may not be prescribed under a label of reactive airway disease. In contrast, some physicians also fear overtreatment for RAD, as patients can be prescribed inhaled beta-agonists or inhaled corticosteroids, which are medications used for asthma. If an individual with RAD doesnt have asthma, there is no evidence these treatments are beneficial. As a result of its ambiguous place in the medical field, the symptoms used to characterize it are often inconsistent and can lead to confusion in a healthcare setting. This is a troubling issue for many physicians, as care can be made more complicated; many patients labeled with RAD do not ultimately have asthma and most RAD patients have never formally had their airway reactivity measured.In addition to the inconsistencies of its labeling, there is also no billing designation for RAD in the International Statistical Classification of Diseases and Related Health Problems, or the ICD, which can lead to problems for healthcare facilities. Searches in the ICD, point to content relating to asthma. Some medical professionals argue that using RAD as a diagnosis will only complicate research on asthma in the context of clinical research and epidemiology. There is also dispute that by giving physicians the ability to label a patient with RAD, it gives them a fabricated sense of security that they have made a diagnosis, when no real recognizable diagnosis has been concluded.
See also
Bronchiolitis
References
== External links == |
Chronic traumatic encephalopathy | Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repeated trauma to the head. The encephalopathy symptoms can include behavioral problems, mood problems, and problems with thinking. The disease often gets worse over time and can result in dementia. It is unclear if the risk of suicide is altered.Most documented cases have occurred in athletes involved in striking-based combat sports, such as boxing, kickboxing, mixed martial arts, and Muay Thai—hence its original name dementia pugilistica (Latin for "fistfighters dementia")—and contact sports such as American football, Australian rules football, professional wrestling, ice hockey, rugby, and association football (soccer), in semi-contact sports such as baseball and basketball, and military combat arms occupations. Other risk factors include being in the military, prior domestic violence, and repeated banging of the head. The exact amount of trauma required for the condition to occur is unknown, and as of 2022 definitive diagnosis can only occur at autopsy. The disease is classified as a tauopathy.There is no specific treatment for the disease. Rates of CTE have been found to be about 30% among those with a history of multiple head injuries; however, population rates are unclear. Research in brain damage as a result of repeated head injuries began in the 1920s, at which time the condition was known as dementia pugilistica or "fistfighters dementia", "boxers madness", or "punch drunk syndrome". It has been proposed that the rules of some sports be changed as a means of prevention.
Signs and symptoms
Symptoms of CTE, which occur in four stages, generally appear eight to ten years after an individual experiences repetitive mild traumatic brain injuries.First-stage symptoms are confusion, disorientation, dizziness, and headaches. Second-stage symptoms include memory loss, social instability, impulsive behavior, and poor judgment. Third and fourth stages include progressive dementia, movement disorders, hypomimia, speech impediments, sensory processing disorder, tremors, vertigo, deafness, depression and suicidality.Additional symptoms include dysarthria, dysphagia, cognitive disorders such as amnesia, and ocular abnormalities, such as ptosis. The condition manifests as dementia, or declining mental ability, problems with memory, dizzy spells or lack of balance to the point of not being able to walk under ones own power for a short time and/or Parkinsonism, or tremors and lack of coordination. It can also cause speech problems and an unsteady gait. Patients with CTE may be prone to inappropriate or explosive behavior and may display pathological jealousy or paranoia.
Cause
Most documented cases have occurred in athletes with mild repetitive head impacts (RHI) over an extended period of time. Evidence indicates that repetitive concussive and subconcussive blows to the head cause CTE. Specifically contact sports such as boxing, American football, Australian rules football, wrestling, mixed martial arts, ice hockey, rugby, and association football. In association football (soccer), whether this is just associated with prolific headers or other injuries is unclear as of 2017. Other potential risk factors include military personnel (repeated exposure to explosive charges or large caliber ordnance), domestic violence, and repeated banging of the head. The exact amount of trauma required for the condition to occur is unknown although it is believed that it may take years to develop.
Pathology
The neuropathological appearance of CTE is distinguished from other tauopathies, such as Alzheimers disease. The four clinical stages of observable CTE disability have been correlated with tau pathology in brain tissue, ranging in severity from focal perivascular epicenters of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions.The primary physical manifestations of CTE include a reduction in brain weight, associated with atrophy of the frontal and temporal cortices and medial temporal lobe. The lateral ventricles and the third ventricle are often enlarged, with rare instances of dilation of the fourth ventricle. Other physical manifestations of CTE include anterior cavum septi pellucidi and posterior fenestrations, pallor of the substantia nigra and locus ceruleus, and atrophy of the olfactory bulbs, thalamus, mammillary bodies, brainstem and cerebellum. As CTE progresses, there may be marked atrophy of the hippocampus, entorhinal cortex, and amygdala.On a microscopic scale, a pathognomonic CTE lesion involves p-tau aggregates in neurons, with or without thorn-shaped astrocytes, at the depths of the cortical sulcus around a small blood vessel, deep in the parenchyma, and not restricted to the subpial and superficial region of the sulcus; the pathognomonic lesion must include p-tau in neurons to distinguish CTE from ARTAG. Supporting features of CTE are: superficial neurofibrillary tangles (NFTs); p–tau in CA2 and CA4 hippocampus; p-tau in: mammillary bodies, hypothalamic nuclei, amygdala, nucleus accumbens, thalamus, midbrain tegmentum, nucleus basalis of Meynert, raphe nuclei, substantia nigra and locus coeruleus; p-tau thorn-shaped astrocytes (TSA) in the subpial region; p-tau dot-like neurites. Purely astrocytic perivascular p-tau pathology represents ARTAG and does not meet the criteria for CTE. Beta-amyloid is not a feature of CTE, however a person with CTE may have comorbid pathologies such as Alzheimers disease.A small group of individuals with CTE have chronic traumatic encephalomyopathy (CTEM), which is characterized by symptoms of motor-neuron disease and which mimics amyotrophic lateral sclerosis (ALS). Progressive muscle weakness and balance and gait problems (problems with walking) seem to be early signs of CTEM.Exosome vesicles created by the brain are potential biomarkers of TBI, including CTE.Loss of neurons, scarring of brain tissue, collection of proteinaceous senile plaques, hydrocephalus, attenuation of the corpus callosum, diffuse axonal injury, neurofibrillary tangles, and damage to the cerebellum are implicated in the syndrome. Neurofibrillary tangles have been found in the brains of dementia pugilistica patients, but not in the same distribution as is usually found in people with Alzheimers. One group examined slices of brain from patients having had multiple mild traumatic brain injuries and found changes in the cells cytoskeletons, which they suggested might be due to damage to cerebral blood vessels.Increased exposure to concussions and subconcussive blows is regarded as the most important risk factor. This exposure can depend on the total number of fights, number of knockout losses, the duration of career, fight frequency, age of retirement, and boxing style.
Diagnosis
Diagnosis of CTE cannot be made in living individuals; a clear diagnosis is only possible during an autopsy. Though there are signs and symptoms some researchers associate with CTE, there is no definitive test to prove the existence in a living person. Signs are also very similar to that of other neurological conditions such as Alzheimers.The lack of distinct biomarkers is the reason CTE cannot typically be diagnosed while a person is alive. Concussions are non-structural injuries and do not result in brain bleeding, which is why most concussions cannot be seen on routine neuroimaging tests such as CT or MRI. Acute concussion symptoms (those that occur shortly after an injury) should not be confused with CTE. Differentiating between prolonged post-concussion syndrome (PCS, where symptoms begin shortly after a concussion and last for weeks, months, and sometimes even years) and CTE symptoms can be difficult. Research studies are examining whether neuroimaging can detect subtle changes in axonal integrity and structural lesions that can occur in CTE. Recently, more progress in in-vivo diagnostic techniques for CTE has been made, using DTI, fMRI, MRI, and MRS imaging; however, more research needs to be done before any such techniques can be validated.PET tracers that bind specifically to tau protein are desired to aid diagnosis of CTE in living individuals. One candidate is the tracer [18F]FDDNP, which is retained in the brain in individuals with a number of dementing disorders such as Alzheimers disease, Down syndrome, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia, and Creutzfeldt–Jakob disease. In a small study of 5 retired NFL players with cognitive and mood symptoms, the PET scans revealed accumulation of the tracer in their brains. However, [18F]FDDNP binds to beta-amyloid and other proteins as well. Moreover, the sites in the brain where the tracer was retained were not consistent with the known neuropathology of CTE. A more promising candidate is the tracer [18F]-T807, which binds only to tau. It is being tested in several clinical trials.A putative biomarker for CTE is the presence in serum of autoantibodies against the brain. The autoantibodies were detected in football players who experienced a large number of head hits but no concussions, suggesting that even sub-concussive episodes may be damaging to the brain. The autoantibodies may enter the brain by means of a disrupted blood-brain barrier, and attack neuronal cells which are normally protected from an immune onslaught. Given the large numbers of neurons present in the brain (86 billion), and considering the poor penetration of antibodies across a normal blood-brain barrier, there is an extended period of time between the initial events (head hits) and the development of any signs or symptoms. Nevertheless, autoimmune changes in blood of players may constitute the earliest measurable event predicting CTE.According to 2017 study on brains of deceased gridiron football players, 99% of tested brains of NFL players, 88% of CFL players, 64% of semi-professional players, 91% of college football players, and 21% of high school football players had various stages of CTE. Players still alive are not able to be tested.
Imaging
Although the diagnosis of CTE cannot be determined by imaging, the effects of head trauma may be seen with the use of structural imaging. Imaging techniques include the use of magnetic resonance imaging, nuclear magnetic resonance spectroscopy, CT scan, single-photon emission computed tomography, Diffusion MRI, and Positron emission tomography (PET). One specific use of imaging is the use of a PET scan is to evaluate for tau deposition, which has been conducted on retired NFL players.
Prevention
The use of helmets and mouth-guards has been put forward as a possible preventative measure; though neither has significant research to support its use, both have been shown to reduce direct head trauma. Although there is no significant research to support the use of helmets to reduce the risk of concussions, there is evidence to support that helmet use reduces impact forces. Mouth guards have been shown to decrease dental injuries, but again have not shown significant evidence to reduce concussions. Because repeated impacts are thought to increase the likelihood of CTE development, a growing area of practice is improved recognition and treatment for concussions and other head trauma; removal from sport participation during recovery from these traumatic injuries is essential. Proper return-to-play protocol after possible brain injuries is also important in decreasing the significance of future impacts.Efforts are being made to change the rules of contact sports to reduce the frequency and severity of blows to the head. Examples of these rule changes are the evolution of tackling technique rules in American football, such as the banning of helmet-first tackles, and the addition of rules to protect defenseless players. Likewise, another growing area of debate is better implementation of rules already in place to protect athletes.Because of the concern that boxing may cause CTE, there is a movement among medical professionals to ban the sport. Medical professionals have called for such a ban as early as the 1950s.
Management
No cure exists for CTE, and because it cannot be tested for until an autopsy is performed, people cannot know if they have it. Treatment is supportive as with other forms of dementia. Those with CTE-related symptoms may receive medication and non-medication related treatments.
Epidemiology
Rates of disease have been found to be about 30% among those with a history of multiple head injuries. Population rates, however, are unclear.Professional level athletes are the largest group with CTE, due to frequent concussions and sub-concussive impacts from play in contact sport. These contact-sports include American football, Australian rules football, ice hockey, Rugby football (Rugby union and Rugby league), boxing, kickboxing, mixed martial arts, association football, and wrestling. In association football, only prolific headers are known to have developed CTE.Cases of CTE were also recorded in baseball.According to a 2017 study on brains of deceased gridiron football players, 99% of tested brains of NFL players, 88% of CFL players, 64% of semi-professional players, 91% of college football players, and 21% of high school football players had various stages of CTE.Other individuals diagnosed with CTE were those involved in military service, had a previous history of chronic seizures, were domestically abused, or were involved in activities resulting in repetitive head collisions.
History
CTE was originally studied in boxers in the 1920s as "punch-drunk syndrome." Punch-drunk syndrome was first described in 1928 by a forensic pathologist, Dr. Harrison Stanford Martland, who was the chief medical examiner of Essex County in Newark, New Jersey, in a Journal of the American Medical Association article, in which he noted the tremors, slowed movement, confusion and speech problems typical of the condition. The term "punch-drunk" was replaced with "dementia pugilistica" in 1937 by J.A. Millsbaugh, as he felt the term was condescending to former boxers. The initial diagnosis of dementia pugilistica was derived from the Latin word for boxer pugil (akin to pugnus fist, pugnāre to fight).Other terms for the condition have included chronic boxers encephalopathy, traumatic boxers encephalopathy, boxers dementia, pugilistic dementia, chronic traumatic brain injury associated with boxing (CTBI-B), and punch-drunk syndrome.The seminal work on the disease came from British neurologist Macdonald Critchley, who in 1949 wrote a paper titled "Punch-drunk syndromes: the chronic traumatic encephalopathy of boxers". CTE was first recognized as affecting individuals who took considerable blows to the head, but was believed to be confined to boxers and not other athletes. As evidence pertaining to the clinical and neuropathological consequences of repeated mild head trauma grew, it became clear that this pattern of neurodegeneration was not restricted to boxers, and the term chronic traumatic encephalopathy became most widely used.In 1990, a patient nicknamed Wilma was diagnosed postmortem with dementia pugilistica; she was the first woman diagnosed with dementia pugilistica from domestic violence.In 2002, American football player Mike Webster died following unusual and unexplained behavior. In 2005 Nigerian-American neuropathologist Bennet Omalu, along with colleagues in the Department of Pathology at the University of Pittsburgh, published their findings in a paper titled "Chronic Traumatic Encephalopathy in a National Football League Player", followed by a paper on a second case in 2006 describing similar pathology.In June 2007 professional wrestler Chris Benoit murdered his wife and son before committing suicide days after appearing on television. His autopsy revealed he was in very advanced stages of CTE with his brain being said to resemble that of an 87-year-old with advanced Alzheimers.
In 2008, the Sports Legacy Institute joined with the Boston University School of Medicine (BUSM) to form the Center for the Study of Traumatic Encephalopathy (now the BU CTE Center). Brain Injury Research Institute (BIRI) also studies the impact of concussions.In 2014, Patrick Grange of Albuquerque was the first US soccer player with CTE at autopsy. He was well known for his heading and had died in 2012.On April 7, 2021, former National Football League player Phillip Adams was found to have shot and killed six people, before killing himself a day later. A subsequent autopsy revealed at that the time of the shooting, Adams had an "unusually severe" case of chronic traumatic encephalopathy.
Research
In 2005, forensic pathologist Bennet Omalu, along with colleagues in the Department of Pathology at the University of Pittsburgh, published a paper, "Chronic Traumatic Encephalopathy in a National Football League Player", in the journal Neurosurgery, based on analysis of the brain of deceased former NFL center Mike Webster. This was then followed by a paper on a second case in 2006 describing similar pathology, based on findings in the brain of former NFL player Terry Long.In 2008, the Center for the Study of Traumatic Encephalopathy at the BU School of Medicine (now the BU CTE Center) started the VA-BU-CLF Brain Bank at the Bedford Veterans Administration Hospital to analyze the effects of CTE and other neurodegenerative diseases on the brain and spinal cord of athletes, military veterans, and civilians. To date, the VA-BU-CLF Brain Bank is the largest CTE tissue repository in the world, with over 1000 brain donors.On 21 December 2009, the National Football League Players Association announced that it would collaborate with the BU CTE Center to support the centers study of repetitive brain trauma in athletes. Additionally, in 2010 the National Football League gave the BU CTE Center a $1 million gift with no strings attached. In 2008, twelve living athletes (active and retired), including hockey players Pat LaFontaine and Noah Welch as well as former NFL star Ted Johnson, committed to donate their brains to VA-BU-CLF Brain Bank after their deaths. In 2009, NFL Pro Bowlers Matt Birk, Lofa Tatupu, and Sean Morey pledged to donate their brains to the VA-BU-CLF Brain Bank.In 2010, 20 more NFL players and former players pledged to join the VA-BU-CLF Brain Donation Registry, including Chicago Bears linebacker Hunter Hillenmeyer, Hall of Famer Mike Haynes, Pro Bowlers Zach Thomas, Kyle Turley, and Conrad Dobler, Super Bowl Champion Don Hasselbeck and former pro players Lew Carpenter, and Todd Hendricks. In 2010, professional wrestlers Mick Foley, Booker T and Matt Morgan also agreed to donate their brains upon their deaths. Also in 2010, MLS player Taylor Twellman, who had to retire from the New England Revolution because of post-concussion symptoms, agreed to donate his brain upon his death. As of 2010, the VA-BU-CLF Brain Donation Registry consists of over 250 current and former athletes.In 2011, former North Queensland Cowboys player Shaun Valentine became the first Australian National Rugby League player to agree to donate his brain upon his death, in response to recent concerns about the effects of concussions on Rugby League players, who do not use helmets. Also in 2011, boxer Micky Ward, whose career inspired the film The Fighter, agreed to donate his brain upon his death. In 2018, NASCAR driver Dale Earnhardt Jr., who retired in 2017 citing multiple concussions, became the first auto racing competitor agreeing to donate his brain upon his death.In related research, the Center for the Study of Retired Athletes, which is part of the Department of Exercise and Sport Science at the University of North Carolina at Chapel Hill, is conducting research funded by National Football League Charities to "study former football players, a population with a high prevalence of exposure to prior Mild Traumatic Brain Injury (MTBI) and sub-concussive impacts, in order to investigate the association between increased football exposure and recurrent MTBI and neurodegenerative disorders such as cognitive impairment and Alzheimers disease (AD)".In February 2011, former NFL player Dave Duerson committed suicide via a gunshot to his chest, thus leaving his brain intact. Duerson left text messages to loved ones asking that his brain be donated to research for CTE. The family got in touch with representatives of the Boston University center studying the condition, said Robert Stern, the co-director of the research group. Stern said Duersons gift was the first time of which he was aware that such a request had been made by someone who had committed suicide that was potentially linked to CTE. Stern and his colleagues found high levels of the protein tau in Duersons brain. These elevated levels, which were abnormally clumped and pooled along the brain sulci, are indicative of CTE.In July 2010, NHL enforcer Bob Probert died of heart failure. Before his death, he asked his wife to donate his brain to CTE research because it was noticed that Probert experienced a mental decline in his 40s. In March 2011, researchers at Boston University concluded that Probert had CTE upon analysis of the brain tissue he donated. He was the second NHL player from the program at the BU CTE Center to be diagnosed with CTE postmortem.The BU CTE Center has also found indications of links between amyotrophic lateral sclerosis (ALS) and CTE in athletes who have participated in contact sports. Tissue for the study was donated by twelve athletes and their families to the VA-BU-CLF Brain Bank at the Bedford, Massachusetts VA Medical Center.In 2013, President Barack Obama announced the creation of the Chronic Effects of Neurotrauma Consortium or CENC, a federally funded research project devised to address the long-term effects of mild traumatic brain injury in military service personnel (SMs) and veterans. The CENC is a multi-center collaboration linking premiere basic science, translational, and clinical neuroscience researchers from the DoD, VA, academic universities, and private research institutes to effectively address the scientific, diagnostic, and therapeutic ramifications of mild TBI and its long-term effects.Nearly 20% of the more than 2.5 million U.S. service members (SMs) deployed since 2003 to Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) have sustained at least one traumatic brain injury (TBI), predominantly mild TBI (mTBI), and almost 8% of all OEF/OIF Veterans demonstrate persistent post-TBI symptoms more than six months post-injury. Unlike those head injuries incurred in most sporting events, recent military head injuries are most often the result of blast wave exposure. After a competitive application process, a consortium led by Virginia Commonwealth University was awarded funding.The project principal investigator for the CENC is David Cifu, chairman and Herman J. Flax professor of the Department of Physical Medicine and Rehabilitation (PM&R) at Virginia Commonwealth University (VCU) in Richmond, Virginia, with co-principal investigators Ramon Diaz-Arrastia, Professor of Neurology, Uniformed Services University of the Health Sciences, and Rick L. Williams, statistician at RTI International.
In 2017, Aaron Hernandez, a former professional football player and convicted murderer, committed suicide at the age of 27 while in prison. His family donated his brain to the BU CTE Center. Ann McKee, the head of Center, concluded that "Hernandez had Stage 3 CTE, which researchers had never seen in a brain younger than 46 years old."
See also
Acquired brain injury
Brain damage
Concussions in American football
Concussions in rugby union
Brendan Schaub
Health issues in American football
List of NFL players with chronic traumatic encephalopathy
The Hit (Chuck Bednarik)
Traumatic brain injury
== References == |
Post-schizophrenic depression | Post-schizophrenic depression is a "depressive episode arising in the aftermath of a schizophrenic illness where some low-level schizophrenic symptoms may still be present." Someone that has post-schizophrenic depression experiences both symptoms of depression and can also continue showing mild symptoms of schizophrenia. Unfortunately, depression is a common symptom found in patients with schizophrenia and can fly under the radar for years before others become aware of its presence in a patient. However, very little research has been done on the subject, meaning there are few answers to how it should be systematically diagnosed, treated, or what course the illness will take. Some scientists would entirely deny the existence of post-schizophrenic depression, insisting it is a phase in schizophrenia as a whole. As of late, post-schizophrenic depression has become officially recognized as a syndrome and is considered a sub-type of schizophrenia.
Symptoms
Because the nature of acute schizophrenia is similar to depression, it is difficult to differentiate normal levels of depression in patients with schizophrenia from depressive levels in post-schizophrenic depression. "Prominent subjectively low mood, suggesting depression, and prominent blunting of affect, suggesting negative symptoms, are the two features which are most helpful in differentiating [schizophrenia and depression]." A number of researchers believe that depression is actually a symptom of schizophrenia that has been hidden by the psychosis. However, symptoms usually arise after the first psychotic episodes if they will arise at all. Officially, diagnosing post-schizophrenia depression in a patient requires for the patient to be experiencing a depressive episode of either short or long term following the overcoming of schizophrenia. The patient must still demonstrate some schizophrenic symptoms but those symptoms must no longer be the focus of the illness. Typically, the depressive symptoms are not severe enough to be classified as a severe depressive episode. Formally, diagnosis entails the patient having had schizophrenia within the past year, a number of schizophrenic symptoms, and depression being present for two weeks or more. Mild schizophrenic signs may be withdrawing socially, agitation or hostility, and irregular sleep such as in the case of insomnia and hypersomnia.
Causes
There is no clear cause to how certain patients with schizophrenia develop post-schizophrenic depression while others may surpass this stage. However, there are a few theories as to possible causes. Those with post-schizophrenic depression often experience social isolation due to their illness, which may increase depression levels. There is strong evidence of stigma-related isolation against those with mental illnesses in a variety of societies, especially those with schizophrenia as they are often viewed as dangerous and unpredictable. Because of this isolation and studies linking social isolation and depression, it is possible that patients under these stigmas eventually develop post-schizophrenic depression. Depression in patients with schizophrenia may also be caused by substance abuse, which is fairly common among those with schizophrenia, as depressants such as alcohol and cannabis can be relaxing. Furthermore, with what little information is currently known about post-schizophrenic depression, the onset may be caused by not giving patients with schizophrenia antipsychotic medications. After being taken off of antipsychotic medication, schizophrenic patients antidepressant medication had to be increased, while those under antipsychotic medication reported having fewer depressive symptoms, further giving reason to believe that a lack of antipsychotic medication in earlier stages of schizophrenia may lead to post-schizophrenic depression. However, some psychology professionals still push for the reduction of neuroleptic drugs, as there is a popular belief that post-schizophrenic depression is caused by neuroleptic treatment. Therapists are also believed to engage the depression in people with schizophrenia, having given too much psychotherapy after the patient had overcome their schizophrenic symptoms. Schizophrenia itself should not be overlooked as a key player in causing post-schizophrenic depression, though. A study done over a two-year time period shadowing patients with schizophrenia and monitoring their depression was unable to locate possible triggers such as the ones previously listed, so it is possible the nature of schizophrenia itself is the primary cause of post-schizophrenic depression.
Suicide
Those with post-schizophrenic depression are also commonly at risk for suicidal tendencies. There is a trend correlated between suicide and post-schizophrenic depression according to Mulholland and Coopers research in "The Symptoms of Depression in Schizophrenia and its Management." Furthermore, depression and schizophrenia have both been studied individually to try to determine if there is a correlation, and research has indicated that there is a very strong tendency for people with depression or schizophrenia to attempt suicide. Statistically, out of all patients with schizophrenia, "10%...commit suicide. Depressed patients with schizophrenia are at a particularly high risk for suicide the first few months after diagnosis and after hospital discharge." Risk factors increasing the chance of suicide are, from highest to lowest, previous depressive orders, previous suicide attempts, drug abuse, and several other factors. Surprisingly, the suicide risk actually decreased with the presence of hallucinations. The ICD-10 Classification of Mental and Behavioural Disorders officially recognizes suicide as being a prominent aspect of post-schizophrenic depression. Because of this drastic increase in suicide, it can be difficult to study post-schizophrenic depression as many of those affected take their own lives.
Treatment
For a number of years, scholars debated amongst themselves whether or not antipsychotic drugs had a tendency to increase depression or simply help the patient manage their mental illness. However, conclusive evidence points to antipsychotic drugs actually helping patients with their depression while simultaneously assisting in the suppression of schizophrenic episodes. Specifically risperidone, olanzapine, quetiapine, fluphenazine, haloperidol, and L-sulpiride have done the best in drug trials pertaining to people with schizophrenia. Along with antipsychotic drugs, post-schizophrenic patients may receive antidepressants to actively treat the depression. Drugs are certainly not the only answer, though. At the base of both depression and schizophrenia, social withdrawal is a shared symptom between the two. People with schizophrenia require a strong support system to be healthy, just as is the case with the rest the human population. The opportunity to become a working citizen is another way to ward off depression in patients with schizophrenia, helping them create social ties and a feeling of accomplishment.
References
== External links == |
Cryptorchidism | Cryptorchidism is the absence of one or both testes from the scrotum. The word is from Greek κρυπτός (kryptos) hidden and ὄρχις (orchis) testicle. It is the most common birth defect of the male genital tract. About 3% of full-term and 30% of premature infant boys are born with at least one undescended testis.
However, about 80% of cryptorchid testes descend by the first year of life (the majority within three months), making the true incidence of cryptorchidism around 1% overall. Cryptorchidism may develop after infancy, sometimes as late as young adulthood, but that is exceptional.
Cryptorchidism is distinct from monorchism, the condition of having only one testicle. Though the condition may occur on one or both sides, it more commonly affects the right testis.A testis absent from the normal scrotal position may be:
Anywhere along the "path of descent" from high in the posterior (retroperitoneal) abdomen, just below the kidney, to the inguinal ring
In the inguinal canal
Ectopic, having "wandered" from the path of descent, usually outside the inguinal canal and sometimes even under the skin of the thigh, the perineum, the opposite scrotum, or the femoral canal
Undeveloped (hypoplastic) or severely abnormal (dysgenetic)
Missing (also see anorchia).About two-thirds of cases without other abnormalities are unilateral; most of the other third involve both testes. In 90% of cases, an undescended testis can be felt in the inguinal canal. In a small minority of cases, missing testes may be found in the abdomen or appear to be nonexistent (truly "hidden").
Undescended testes are associated with reduced fertility, increased risk of testicular germ-cell tumors, and psychological problems when fully-grown. Undescended testes are also more susceptible to testicular torsion (and subsequent infarction) and inguinal hernias. Without intervention, an undescended testicle will usually descend during the first year of life, but to reduce these risks, undescended testes can be brought into the scrotum in infancy by a surgical procedure called an orchiopexy.Although cryptorchidism nearly always refers to congenital absence or maldescent, a testis observed in the scrotum in early infancy can occasionally "reascend" (move back up) into the inguinal canal. A testis that can readily move or be moved between the scrotum and canal is referred to as retractile.
Cryptorchidism, hypospadias, testicular cancer, and poor semen quality make up the syndrome known as testicular dysgenesis syndrome.
Signs and symptoms
Infertility
Many men who were born with undescended testes have reduced fertility, even after orchiopexy in infancy. The reduction with unilateral cryptorchidism is subtle, with a reported infertility rate of about 10%, compared with about 6% reported by the same study for the general population of adult men.
The fertility reduction after orchiopexy for bilateral cryptorchidism is more marked, about 38%, or six times that of the general population. The basis for the universal recommendation for early surgery is research showing degeneration of spermatogenic tissue and reduced spermatogonia counts after the second year of life in undescended testes. The degree to which this is prevented or improved by early orchiopexy is still uncertain.
Cancer risk
One of the strongest arguments for early orchiopexy is reducing the risk of testicular cancer. About one in 500 men born with one or both testes undescended develops testicular cancer, roughly a four- to 40-fold increased risk. The peak incidence occurs in the third and fourth decades of life. The risk is higher for intra-abdominal testes and somewhat lower for inguinal testes, but even the normally descended testis of a man whose other testis was undescended has about a 20% higher cancer risk than those of other men.The most common type of testicular cancer occurring in undescended testes is seminoma. It is usually treatable if caught early, so urologists often recommend that boys who had orchiopexy as infants be taught testicular self-examination, to recognize testicular masses and seek early medical care for them. Cancer developing in an intra-abdominal testis would be unlikely to be recognized before considerable growth and spread, and one of the advantages of orchiopexy is that a mass developing in a scrotal testis is far easier to recognize than an intra-abdominal mass.
Orchidopexy was originally thought to result in easier detection of testicular cancer, but did not lower the risk of actually developing cancer. However, recent data have shown a paradigm shift. The New England Journal of Medicine published in 2007 that orchidopexy performed before puberty resulted in a significantly reduced risk of testicular cancer than if done after puberty.The risk of malignancy in the undescended testis is four to 10 times higher than that in the general population and is about one in 80 with a unilateral undescended testis and one in 40 to one in 50 for bilateral undescended testes. The peak age for this tumor is 15–45 years old. The most common tumor developing in an undescended testis is a seminoma (65%); in contrast, after orchiopexy, seminomas represent only 30% of testicular tumors.
Causes
In most full-term infant boys with cryptorchidism but no other genital abnormalities, a cause cannot be found, making this a common, sporadic, unexplained (idiopathic) birth defect. A combination of genetics, maternal health, and other environmental factors may disrupt the hormones and physical changes that influence the development of the testicles.
Severely premature infants can be born before descent of testes. Low birth weight is also a known factor.
A contributing role of environmental chemicals called endocrine disruptors that interfere with normal fetal hormone balance has been proposed. The Mayo Clinic lists "parents exposure to some pesticides" as a known risk factor.
Risk factors may include exposure to regular alcohol consumption during pregnancy (five or more drinks per week, associated with a three-fold increase in cryptorchidism when compared to nondrinking mothers. Cigarette smoking is also a known risk factor.
Family history of undescended testicles or other problems of genital development
Cryptorchidism occurs at a much higher rate in a large number of congenital malformation syndromes. Among the more common are Down syndrome, Prader–Willi syndrome, and Noonan syndrome.
In vitro fertilization, use of cosmetics by the mother, and pre-eclampsia have also been recognized as risk factors for development of cryptorchidism.In 2008, a study was published that investigated the possible relationship between cryptorchidism and prenatal exposure to a chemical called phthalate (DEHP), which is used in the manufacture of plastics. The researchers found a significant association between higher levels of DEHP metabolites in pregnant mothers and several sex-related changes, including incomplete descent of the testes in their sons. According to the lead author of the study, a national survey found that 25% of U.S. women had phthalate levels similar to the levels that were found to be associated with sexual abnormalities.A 2010 study examined the prevalence of congenital cryptorchidism among offspring whose mothers had taken mild analgesics, primarily over-the-counter pain medications including ibuprofen (e.g. Advil) and paracetamol (acetaminophen). Combining the results from a survey of pregnant women prior to their due date in correlation with the health of their children and an ex vivo rat model, the study found that pregnant women who had been exposed to mild analgesics had a higher prevalence of baby boys born with congenital cryptorchidism.New insight into the testicular descent mechanism has been hypothesized by the concept of a male programming window derived from animal studies. According to this concept, testicular descent status is "set" during the period from eight to 14 weeks of gestation in humans. Undescended testis is a result of disruption in androgen levels only during this programming window.
Mechanism
Normal development
The testes begin as an immigration of primordial germ cells into testicular cords along the gonadal ridge in the abdomen of the early embryo. The interaction of several male genes organizes this developing gonad into a testis rather than an ovary by the second month of gestation. During the third to fifth months, the cells in the testes differentiate into testosterone-producing Leydig cells, and anti-Müllerian hormone-producing Sertoli cells. The germ cells in this environment become fetal spermatogonia. Male external genitalia develops during the third and fourth months of gestation and the fetus continues to grow, develop, and differentiate.
The testes remain high in the abdomen until the seventh month of gestation when they move from the abdomen through the inguinal canals into the two sides of the scrotum. Movement has been proposed to occur in two phases, under the control of somewhat different factors. The first phase, movement across the abdomen to the entrance of the inguinal canal, appears controlled (or at least greatly influenced) by anti-Müllerian hormone (AMH). The second phase, in which the testes move through the inguinal canal into the scrotum, is dependent on androgens (most importantly testosterone). In rodents, androgens induce the genitofemoral nerve to release calcitonin gene-related peptide, which produces rhythmic contractions of the gubernaculum, a ligament which connects the testis to the scrotum, but a similar mechanism has not been demonstrated in humans. Maldevelopment of the gubernaculum or deficiency or insensitivity to either AMH or androgen can, therefore, prevent the testes from descending into the scrotum. Some evidence suggests an additional paracrine hormone, referred to as descendin, may be secreted by the testes.
In many infants with inguinal testes, further descent of the testes into the scrotum occurs in the first six months of life. This is attributed to the postnatal surge of gonadotropins and testosterone that normally occurs between the first and fourth months of life.
Spermatogenesis continues after birth. In the third to fifth months of life, some of the fetal spermatogonia residing along the basement membrane become type A spermatogonia. More gradually, other fetal spermatogonia become type B spermatogonia and primary spermatocytes by the fifth year after birth. Spermatogenesis arrests at this stage until puberty.
Most normal-appearing undescended testes are also normal by microscopic examination, but reduced spermatogonia can be found. The tissue in undescended testes becomes more markedly abnormal ("degenerates") in microscopic appearance between two and four years after birth. Some evidence indicates early orchiopexy reduces this degeneration.
Pathophysiology
At least one contributing mechanism for reduced spermatogenesis in cryptorchid testes is temperature. The temperature of testes in the scrotum is at least a few degrees cooler than in the abdomen. Animal experiments in the middle of the 20th century suggested that raising the temperature could damage fertility. Some circumstantial evidence suggests tight underwear and other practices that raise the testicular temperature for prolonged periods can be associated with lower sperm counts. Nevertheless, research in recent decades suggests that the issue of fertility is more complex than a simple matter of temperature. Subtle or transient hormone deficiencies or other factors that lead to a lack of descent also may impair the development of spermatogenic tissue.
The inhibition of spermatogenesis by ordinary intra-abdominal temperature is so potent that continual suspension of normal testes tightly against the inguinal ring at the top of the scrotum by means of special "suspensory briefs" has been researched as a method of male contraception, and was referred to as "artificial cryptorchidism" by one report.
An additional factor contributing to infertility is the high rate of anomalies of the epididymis in boys with cryptorchidism (over 90% in some studies). Even after orchiopexy, these may also affect sperm maturation and motility at an older age.
Diagnosis
The most common diagnostic dilemma in otherwise normal boys is distinguishing a retractile testis from a testis that will not descend spontaneously into the scrotum. Retractile testes are more common than truly undescended testes and do not need to be operated on. In normal males, as the cremaster muscle relaxes or contracts, the testis moves lower or higher ("retracts") in the scrotum. This cremasteric reflex is much more active in infant boys than older men. A retractile testis high in the scrotum can be difficult to distinguish from a position in the lower inguinal canal. Though various maneuvers are used to do so, such as using a cross-legged position, soaping the examiners fingers, or examining in a warm bath, the benefit of surgery in these cases can be a matter of clinical judgment.
In the minority of cases with bilaterally nonpalpable testes, further testing to locate the testes, assess their function, and exclude additional problems is often useful. Scrotal ultrasound or magnetic resonance imaging performed and interpreted by a radiologist can often locate the testes while confirming absence of a uterus. At ultrasound, the undescended testis usually appears small, less echogenic than the contralateral normal testis and usually located in the inguinal region. With color Doppler ultrasonography, the vascularity of the undescended testis is poor.A karyotype can confirm or exclude forms of dysgenetic primary hypogonadism, such as Klinefelter syndrome or mixed gonadal dysgenesis. Hormone levels (especially gonadotropins and AMH) can help confirm that hormonally functional testes are worth attempting to rescue, as can stimulation with a few injections of human chorionic gonadotropin to elicit a rise of the testosterone level. Occasionally, these tests reveal an unsuspected and more complicated intersex condition.
In the even smaller minority of cryptorchid infants who have other obvious birth defects of the genitalia, further testing is crucial and has a high likelihood of detecting an intersex condition or other anatomic anomalies. Ambiguity can indicate either impaired androgen synthesis or reduced sensitivity. The presence of a uterus by pelvic ultrasound suggests either persistent Müllerian duct syndrome (AMH deficiency or insensitivity) or a severely virilized genetic female with congenital adrenal hyperplasia. An unambiguous micropenis, especially accompanied by hypoglycemia or jaundice, suggests congenital hypopituitarism.
Treatment
The primary management of cryptorchidism is watchful waiting, due to the high likelihood of self-resolution. Where this fails, orchiopexy is effective if inguinal testes have not descended after 4–6 months. Surgery is often performed by a pediatric urologist or pediatric surgeon, but in many communities still by a general urologist or surgeon.
When the undescended testis is in the inguinal canal, hormonal therapy is sometimes attempted and very occasionally successful. The most commonly used hormone therapy is human chorionic gonadotropin (hCG). A series of hCG injections (10 injections over five weeks is common) is given and the status of the testis/testes is reassessed at the end. Although many trials have been published, the reported success rates range widely, from roughly 5% to 50%, probably reflecting the varying criteria for distinguishing retractile testes from low inguinal testes. Hormone treatment does have the occasional incidental benefits of allowing confirmation of Leydig cell responsiveness (proven by a rise of the testosterone by the end of the injections) or inducing additional growth of a small penis (via the testosterone rise). Some surgeons have reported facilitation of surgery, perhaps by enhancing the size, vascularity, or healing of the tissue. A newer hormonal intervention used in Europe is the use of GnRH analogs such as nafarelin or buserelin; the success rates and putative mechanism of action are similar to hCG, but some surgeons have combined the two treatments and reported higher descent rates. Limited evidence suggests that germ cell count is slightly better after hormone treatment; whether this translates into better sperm counts and fertility rates at maturity has not been established. The cost of either type of hormone treatment is less than that of surgery and the chance of complications at appropriate doses is minimal. Nevertheless, despite the potential advantages of a trial of hormonal therapy, many surgeons do not consider the success rates high enough to be worth the trouble, since the surgery itself is usually simple and uncomplicated.
In cases where the testes are identified preoperatively in the inguinal canal, orchiopexy is often performed as an outpatient and has a very low complication rate. An incision is made over the inguinal canal. The testis with accompanying cord structure and blood supply is exposed, partially separated from the surrounding tissues ("mobilized"), and brought into the scrotum. It is sutured to the scrotal tissue or enclosed in a "subdartos pouch". The associated passage back into the inguinal canal, an inguinal hernia, is closed to prevent reascent.
In patients with intra-abdominal maldescended testis, laparoscopy is useful to see for oneself the pelvic structures, position of the testis and decide upon surgery (single or staged procedure ).
Surgery becomes more complicated if the blood supply is not ample and elastic enough to be stretched into the scrotum. In these cases, the supply may be divided, some vessels sacrificed with expectation of adequate collateral circulation. In the worst case, the testis must be "autotransplanted" into the scrotum, with all connecting blood vessels cut and reconnected (anastomosed).
When the testis is in the abdomen, the first stage of surgery is exploration to locate it, assess its viability, and determine the safest way to maintain or establish the blood supply. Multistage surgeries, or autotransplantation and anastomosis, are more often necessary in these situations. Just as often, intra-abdominal exploration discovers that the testis is nonexistent ("vanished"), or dysplastic and not salvageable.
The principal major complication of all types of orchiopexy is a loss of the blood supply to the testis, resulting in loss of the testis due to ischemic atrophy or fibrosis.
Other animals
Cryptorchidism is seen in all domestic animals, most commonly in stallions, boars, and canines. The prevalence of this condition can vary depending on species and breed. Evidence of this condition is more likely in companion animals and swine than ruminants. The cause of this condition can vary from a combination of genetics, environment, and epigenetics.
Dogs
Cryptorchidism is common in male dogs, occurring at a rate up to 10%. This condition is one of the most common congenital defects in purebred dogs (11%), with 14% reported in Siberian Huskies. Although the genetics are not fully understood, it is thought to be a recessive, and probably polygenetic, trait. Some have speculated that it is a sex-limited autosomal recessive trait; however, it is unlikely to be simple recessive. Dog testes usually descend by 10 days of age and it is considered to be cryptorchidism if they do not descend by the age of eight weeks. Cryptorchidism can be either bilateral (causing sterility) or unilateral, and inguinal or abdominal (or both). Because it is an inherited trait, affected dogs should not be bred and should be castrated. The parents should be considered carriers of the defect and a breeder should thoughtfully consider whether to breed the carrier parent or not. Littermates may be normal, carriers, or cryptorchid. Castration of the undescended teste(s) should be considered for cryptorchid dogs due to the high rate of testicular cancer, especially Sertoli cell tumors. The incidence of testicular cancer is 13.6 times higher in dogs with abdominally retained testicles compared with normal dogs. Testicular torsion is also more likely in retained testicles. Surgical correction is by palpation of the retained testicle and subsequent exploration of the inguinal canal or abdomen, but showing altered dogs is against AKC rules, making this correction pointless for breeding stock. Orchiopexy is an option for pet dogs that will not be used for breeding.
Commonly affected breeds include:
Alaskan Klee Kai
Boxer
Chihuahua
Dachshund (miniature)
Bulldog
Maltese
Miniature Schnauzer
Pekingese
Pomeranian
Poodle (toy and miniature)
Pug
Shetland Sheepdog
Siberian Husky
Whippet
Yorkshire Terrier
Cats
Cryptorchidism is rarer in cats than it is in dogs. In one study, 1.9% of intact male cats were cryptorchid. Persians are predisposed. Normally, the testicles are in the scrotum by the age of six to eight weeks. Male cats with one cryptorchid testicle may still be fertile; however, male cats with two cryptorchid testicles are most likely to be sterile. Urine spraying is one indication that a cat with no observable testicles may not be neutered; other signs are the presence of enlarged jowls, thickened facial and neck skin, and spines on the penis (which usually regress within six weeks after castration). Most cryptorchid cats present with an inguinal testicle.
Testicular tumors and testicular torsion are rare in cryptorchid cats, but castration is usually performed due to unwanted behavior such as urine spraying.
Horses
In horses, cryptorchidism is sufficiently common that affected males (ridglings) are routinely gelded.
Rarely, cryptorchidism is due to the presence of a congenital testicular tumor such as a teratoma, which has a tendency to grow large.
References
External links
Kidshealth.org: Cryptorchidism |
Cytomegalovirus | Cytomegalovirus (CMV) (from cyto- cell via Greek κύτος kútos- container + μέγας mégas big, megalo- + -virus via Latin vīrus poison) is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Betaherpesvirinae. Humans and other primates serve as natural hosts. The 11 species in this genus include human betaherpesvirus 5 (HCMV, human cytomegalovirus, HHV-5), which is the species that infects humans. Diseases associated with HHV-5 include mononucleosis and pneumonia. In the medical literature, most mentions of CMV without further specification refer implicitly to human CMV. Human CMV is the most studied of all cytomegaloviruses.MX2/MXB was identified as a restriction factor for herpesviruses, which acts at a very early stage of the replication cycle and MX2/MXB restriction of herpesvirus requires GTPase activity.
Taxonomy
Within the Herpesviridae, CMV belongs to the Betaherpesvirinae subfamily, which also includes the genera Muromegalovirus and Roseolovirus (human herpesvirus 6 and human betaherpesvirus 7). It is also related to other herpesviruses within the Alphaherpesvirinae subfamily, which includes herpes simplex viruses 1 and 2 and varicella-zoster virus, and the Gammaherpesvirinae subfamily, which includes Epstein–Barr virus and Kaposis sarcoma-associated herpesvirus.Several species of Cytomegalovirus have been identified and classified for different mammals. The most studied is Human cytomegalovirus (HCMV), which is also known as Human betaherpesvirus 5 (HHV-5). Other primate CMV species include Chimpanzee cytomegalovirus (CCMV) that infects chimpanzees and orangutans, and Simian cytomegalovirus (SCCMV) and Rhesus cytomegalovirus (RhCMV) that infect macaques; CCMV is known as both Panine beta herpesvirus 2 (PaHV-2) and Pongine betaherpesvirus 4 (PoHV-4). SCCMV is called cercopithecine betaherpesvirus 5 (CeHV-5) and RhCMV, Cercopithecine betaherpesvirus 8 (CeHV-8). A further two viruses found in the night monkey are tentatively placed in the genus Cytomegalovirus, and are called Herpesvirus aotus 1 and Herpesvirus aotus 3. Rodents also have viruses previously called cytomegaloviruses that are now reclassified under the genus Muromegalovirus; this genus contains Mouse cytomegalovirus (MCMV) is also known as Murid betaherpesvirus 1 (MuHV-1) and the closely related Murid betaherpesvirus 2 (MuHV-2) that is found in rats.
Species
The genus consists of these 11 species:
Aotine betaherpesvirus 1
Cebine betaherpesvirus 1
Cercopithecine betaherpesvirus 5
Human betaherpesvirus 5
Macacine betaherpesvirus 3
Macacine betaherpesvirus 8
Mandrilline betaherpesvirus 1
Panine betaherpesvirus 2
Papiine betaherpesvirus 3
Papiine betaherpesvirus 4
Saimiriine betaherpesvirus 4
Structure
Viruses in Cytomegalovirus are enveloped, with icosahedral, spherical to pleomorphic, and round geometries, and T=16 symmetry. The diameter is around 150–200 nm. Genomes are linear and nonsegmented, around 200 kb in length.
Genome
Herpesviruses have some of the largest genomes among human viruses, often encoding hundreds of proteins. For instance, the double‑stranded DNA (dsDNA) genome of wild-type HCMV strains has a size of around 235 kb and encodes at least 208 proteins. It is thus longer than all other human herpesviruses and one of the longest genomes of all human viruses in general. It has the characteristic herpesvirus class E genome architecture, consisting of two unique regions (unique long UL and unique short US), both flanked by a pair of inverted repeats (terminal/internal repeat long TRL/IRL and internal/terminal repeat short IRS/TRS). Both sets of repeats share a region of a few hundred bps, the so-called "a sequence"; the other regions of the repeats are sometimes referred to as "b sequence" and "c sequence".
Life cycle
Viral replication is nuclear and lysogenic. Entry into the host cell is achieved by attachment of the viral glycoproteins to host receptors, which mediates endocytosis. Replication follows the dsDNA bidirectional replication model. DNA templated transcription, with some alternative splicing mechanism is the method of transcription. Translation takes place by leaky scanning. The virus exits the host cell by nuclear egress, and budding. Humans and monkeys serve as the natural hosts. Transmission routes are dependent on coming into contact with bodily fluids (such as saliva, urine, and genital secretions) from an infected individual.
All herpesviruses share a characteristic ability to remain latent within the body over long periods. Although they may be found throughout the body, CMV infections are frequently associated with the salivary glands in humans and other mammals.
Genetic engineering
The CMV promoter is commonly included in vectors used in genetic engineering work conducted in mammalian cells, as it is a strong promoter and drives constitutive expression of genes under its control.
History
Cytomegalovirus was first observed by German pathologist Hugo Ribbert in 1881 when he noticed enlarged cells with enlarged nuclei present in the cells of an infant. Years later, between 1956 and 1957, Thomas Huckle Weller together with Smith and Rowe independently isolated the virus, known thereafter as "cytomegalovirus". In 1990, the first draft of human cytomegalovirus genome was published, the biggest contiguous genome sequenced at that time.
See also
CMV polyradiculomyelopathy
Human cytomegalovirus
References
External links
ICTV |
Steatocystoma simplex | Steatocystoma simplex is a skin condition characterized by a skin lesion that occurs with equal frequency in adult women and men, and is typically found on the face, trunk, or extremities.: 679 It is related to Steatocystoma multiplex.
== References == |
Generalized eruptive histiocytoma | Generalized eruptive histiocytoma (also known as "Eruptive histiocytoma," and "Generalized eruptive histiocytosis") is a rare cutaneous condition characterized by widespread, erythematous, essentially symmetrical papules, particularly involving the trunk and proximal extremities.: 717
See also
Non-X histiocytosis
List of cutaneous conditions
References
== External links == |
Proximal femoral focal deficiency | Proximal femoral focal deficiency (PFFD), also known as Congenital Femoral Deficiency (CFD), is a rare, non-hereditary birth defect that affects the pelvis, particularly the hip bone, and the proximal femur. The disorder may affect one side or both, with the hip being deformed and the leg shortened.
It is commonly linked with the absence or shortening of a leg bone (fibular hemimelia) and the absence of a kneecap. Other linked birth defects include the dislocation or instability of the joint between the femur and the kneecap, a shortened tibia or fibula, and foot deformities.
Causes
The cause of PFFD is uncertain. Two hypotheses have been advanced. The theory of sclerotome subtraction posits injury to neural crest cells that are the precursors to sensory nerves at the level of L4 and L5. Histologic studies of a fetus with unilateral PFFD have prompted an alternative hypothesis that PFFD is caused by a defect in maturation of chondrocytes (cartilage cells) at the growth plate. In either hypothesis, the agent causing the injury is usually not known. Thalidomide is known to cause PFFD when the mother is exposed to it in the fifth or sixth week of pregnancy, and it is speculated that exposure to other toxins during pregnancy may also be a cause. Other etiologies that have been suggested, but not proven, include anoxia, ischemia, radiation, infection, hormones, and mechanical force. PFFD occurs sporadically, and does not appear to be hereditary.
Diagnosis
Classifications
There are typically four classes (or types) of PFFD, ranging from class A to class D, as detailed by Aitken.Types of PFFD
Type A — The femur bone is slightly shorter on the proximal end (near the hip), and the femoral head (the ball of the thigh bone that goes into the hip socket) may not be solid enough to be seen on X-rays at birth, but later hardens (ossifies). This deformity is sometimes called congenital short femur, because the child’s anatomy from hip to knee is contiguous and similar to their peers except for the one shortened bone. In some cases, children with type A deformities will also have an externally rotated femur, which could lead to bowing of the legs (genu varum).
Type B — The femur bone is shorter on the proximal end (near the hip) and the defect affects both the femoral head (the ball) and the femoral shaft (the long part of the bone). This defect is more severe than type A deformities because it will not heal spontaneously and, at skeletal maturity, the proximal femur (lower part near the knee) will not connect with the femoral head.
Type C — The entire top half of the femur bone is absent, including the trochanters (the part of the bone in which muscles are attached to the upper thigh), and the femoral head. In type C deformities, the proximal femur is not connected to the hip in any way. In fact, many children with type C deformities also have acetabular dysplasia, a condition in which the acetabulum (hip socket) is shallow, abnormally shaped, and oriented outward.
Type D — This is the most severe form of proximal femoral focal deficiency, in which most of the femur bone is absent and only a small irregular piece of bone above the distal femoral epiphysis (the end of the femur bone at the knee) is present. In the pelvis, no acetabulum (hip socket) is present; instead the pelvic wall is flat on the affected side.
Treatment
Depending on the severity of the deformities, the treatment may include the amputation of the foot or part of the leg, lengthening of the femur, extension prosthesis, or custom shoe lifts. Amputation usually requires the use of prosthesis. Another alternative is a rotationplasty procedure, also known as Van Ness surgery. In this situation the foot and ankle are surgically removed, then attached to the femur. This creates a functional "knee joint". This allows the patient to be fit with a below knee prosthesis vs a traditional above knee prosthesis.In less severe cases, the use of an Ilizarov apparatus can be successful in conjunction with hip and knee surgeries (depending on the status of the femoral head/kneecap) to extend the femur length to normal ranges. This method of treatment can be problematic in that the Ilizarov might need to be applied both during early childhood (to keep the femur from being extremely short at the onset of growth) and after puberty (to match leg lengths after growth has ended). The clear benefit of this approach, however, is that no prosthetics are needed and at the conclusion of surgical procedures the patient will not be biologically or anatomically different from a person born without PFFD.In some cases the patient may not request treatment and instead elect to use a wheelchair or other aids to assist mobility.
References
== External links == |
Cystic eyeball | Congenital cystic eye (also known as CCE or cystic eyeball) is an extremely rare ocular malformation where the eye fails to develop correctly in utero and is replaced by benign, fluid-filled tissue. Its incidence is unknown, due to the very small number of cases reported. An audit by Duke-Elder of the medical literature from 1880 to 1963 discovered only 28 cases. The term was coined in 1937 by the renowned ophthalmologist Ida Mann.Embryologically, the defect is thought to occur around day 35 of gestation, when the vesicle fails to invaginate. Dysgenesis of the vesicle later in development may result in coloboma, a separate and less severe malformation of the ocular structures.
CCE is almost always unilateral, but at least 2 cases of bilateral involvement have been described. Patients may also present with skin appendages attached to the skin surrounding the eyes. Association with intracranial anomalies has been reported.
Treatment
Treatment of CCE is usually by enucleation, followed by insertion of an ocular implant and prosthesis.
References
== External links == |
Lupoid sycosis | Lupoid sycosis is a cutaneous condition that is characterized by a scarring form of deep folliculitis, typically affecting the beard area.
See also
Sycosis barbae
List of cutaneous conditions
== References == |
Aneurysm of sinus of Valsalva | Aneurysm of the aortic sinus, also known as the sinus of Valsalva, is a rare abnormality of the aorta, the largest artery in the body. The aorta normally has three small pouches that sit directly above the aortic valve (the sinuses of Valsalva), and an aneurysm of one of these sinuses is a thin-walled swelling. Aneurysms may affect the right (65–85%), non-coronary (10–30%), or rarely the left (< 5%) coronary sinus. These aneurysms may not cause any symptoms but if large can cause shortness of breath, palpitations or blackouts. Aortic sinus aneurysms can burst or rupture into adjacent cardiac chambers, which can lead to heart failure if untreated.
Aortic sinus aneurysms may occur in isolation, or may been seen in association with other diseases of the aorta including Marfan syndrome, Loeys-Dietz syndrome, and bicuspid aortic valve. They can be diagnosed using an echocardiogram or cardiac magnetic resonance imaging (MRI) scan. Treatment includes blood pressure control but surgical repair may be needed, especially if the aneurysm ruptures.
Symptoms and signs
If unruptured, sinus of Valsalva aneurysm (commonly abbreviated SVA or SOVA) is usually asymptomatic and typically goes undetected until symptoms appear or medical imaging is performed for other reasons. If symptoms do occur, the most common are shortness of breath, palpitations, myocardial ischemia, and syncope. Even less common, but more serious, presentations are embolic stroke and myocardial infarction due to blockage of a coronary artery by the aneurysm.A ruptured aneurysm typically leads to an aortocardiac shunt and progressively worsening heart failure.An aneurysm of the aortic sinus may rupture due to infective endocarditis involving the aortic wall and tertiary-stage syphilis.The manifestations appear depending on the site where the sinus has ruptured. For example, if the sinus ruptures in a low pressure area like the right atrium or right ventricle then a continuous type of murmur is heard. The murmur is located in the left parasternal region mainly confined to the lower sternum. It is also accompanied by a superficial thrill. A ruptured Sinus of Valsalva abscess represents a surgical emergency.
Causes
This type of aneurysm is typically congenital and may be associated with heart defects. It is sometimes associated with Marfan syndrome or Loeys–Dietz syndrome, but may also result from Ehlers–Danlos syndrome, bicuspid aortic valve, atherosclerosis, hypoplastic left heart syndrome, syphilis, cystic medial necrosis, chest injury, or infective endocarditis.
Diagnosis
The first step in diagnosis is typically transthoracic echocardiography. However, if surgery is planned or if the standard echocardiogram lacks sufficient detail, then one or more additional studies are recommended. These studies include transesophageal echocardiography, 3D echocardiography, CT Angiography and aortic angiography. Cardiac MRI may be another option.
Treatment
Medical therapy of aneurysm of the aortic sinus includes blood pressure control through the use of drugs, such as beta blockers.Another approach is surgical repair. The determination to perform surgery is usually based upon the diameter of the aortic root (with 5 centimeters being a rule of thumb - a normal size is 2-3 centimeters) and the rate of increase in its size (as determined through repeated echocardiography).An alternative to surgical repair or a ruptured aneurysm is percutaneous closure. In this technique, a wire is introduced via a small incision in the groin and advanced through the vascular system to the aneurysm. A closure device is advanced along the wire before being expanded to straddle the site of rupture.
Prognosis
If a sinus of Valsalva aneurysm ruptures, the life expectancy without treatment is approximately four years. Surgery carries a 1% risk of intra-operative death with higher risks associated with infected aneurysms, and 5- to 10-year survival rates following surgery range from 82-97%.
Epidemiology
Aneurysms of the sinuses of Valsalva are estimated to affect 0.09% of the population. Rupture of a sinus of Valsalva can occur at any age. Rupture is five times more likely to occur in those of far eastern than western ethnic backgrounds, and is twice as likely to occur in males than females.
History
The first description of sinus of Valsalva aneurysm was made in 1939.
See also
Aortic aneurysm
Thoracic aortic aneurysm
Abdominal aortic aneurysm
References
== External links == |
Syringomyelia | Syringomyelia is a generic term referring to a disorder in which a cyst or cavity forms within the spinal cord. Often, syringomyelia is used as a generic term before an etiology is determined. This cyst, called a syrinx, can expand and elongate over time, destroying the spinal cord. The damage may result in loss of feeling, paralysis, weakness, and stiffness in the back, shoulders, and extremities. Syringomyelia may also cause a loss of the ability to feel extremes of hot or cold, especially in the hands. It may also lead to a cape-like bilateral loss of pain and temperature sensation along the upper chest and arms. The combination of symptoms varies from one patient to another depending on the location of the syrinx within the spinal cord, as well as its extent.
Syringomyelia has a prevalence estimated at 8.4 cases per 100,000 people, with symptoms usually beginning in young adulthood. Signs of the disorder tend to develop slowly, although sudden onset may occur with coughing, straining, or myelopathy.
Signs and symptoms
Syringomyelia causes a wide variety of neuropathic symptoms, due to damage to the spinal cord. Patients may experience severe chronic pain, abnormal sensations and loss of sensation, particularly in the hands. Some patients experience paralysis or paresis, temporarily or permanently. A syrinx may also cause disruptions in the parasympathetic and sympathetic nervous systems, leading to abnormal body temperature or sweating, bowel control issues, or other problems. If the syrinx is higher up in the spinal cord or affecting the brainstem, as in syringobulbia, vocal cord paralysis, ipsilateral tongue wasting, trigeminal nerve sensory loss, and other signs may be present. Rarely, bladder stones can occur at the onset of weakness in the lower extremities.
Classically, syringomyelia spares the dorsal column/medial lemniscus of the spinal cord, leaving pressure, vibration, touch and proprioception intact in the upper extremities. Neuropathic arthropathy, also known as a Charcot joint, can occur, particularly in the shoulders, in patients with syringomyelia. The loss of sensory fibers to the joint is theorized to lead to degeneration of the joint over time.
Cause
Generally, there are two forms of syringomyelia: congenital and acquired. Syringomyelia is generally a chronic disorder that occurs over time, resulting in muscular atrophy. Acquired Syringomyelia can be caused by a serious physical trauma to the body such as in a road traffic accident. Syringomyelia can also be classified into communicating and noncommunicating forms. Communicating typically occurs due to lesions on the foramen magnum and noncommunicating occurring due to other spinal cord diseases.
Congenital
The first major form relates to an abnormality of the brain called an Arnold–Chiari malformation or Chiari malformation. This is the most common cause of syringomyelia, where the anatomic abnormality, which may be due to a small posterior fossa, causes the lower part of the cerebellum to protrude from its normal location in the back of the head into the cervical or neck portion of the spinal canal. A syrinx may then develop in the cervical region of the spinal cord. Here, symptoms usually begin between the ages of 25 and 40 and may worsen with straining, called a valsalva maneuver, or any activity that causes cerebrospinal fluid pressure to fluctuate suddenly. Some patients, however, may have long periods of stability. Some patients with this form of the disorder also have hydrocephalus, in which cerebrospinal fluid accumulates in the skull, or a condition called arachnoiditis, in which a covering of the spinal cord—the arachnoid membrane—is inflamed. Some cases of syringomyelia are familial, although this is rare.
Acquired
The second major form of syringomyelia occurs as a complication of trauma, meningitis, hemorrhage, a tumor, or arachnoiditis. Here, the syrinx or cyst develops in a segment of the spinal cord damaged by one of these conditions. The syrinx then starts to expand. This is sometimes referred to as noncommunicating syringomyelia. Symptoms may appear months or even years after the initial injury, starting with pain, weakness, and sensory impairment originating at the site of trauma.The primary symptom of post-traumatic syringomyelia (often referred to using the abbreviation of PTS) is pain, which may spread upward from the site of injury. Symptoms, such as pain, numbness, weakness, and disruption in temperature sensation, may be limited to one side of the body. Syringomyelia can also adversely affect sweating, sexual function, and, later, bladder and bowel control. A typical cause of PTS would be a car accident or similar trauma involving a whiplash injury.What can make PTS difficult to diagnose is the fact that symptoms can often first appear long after the actual cause of the syrinx occurred (e.g., a car accident occurring and then the patient first experiencing PTS symptoms such as pain, loss of sensation, and reduced ability on the skin to feel varying degrees of hot and cold a number of months after the car accident).
Pathogenesis
The pathogenesis of syringomyelia is debated. The cerebrospinal fluid also serves to cushion the brain. Excess cerebrospinal fluid in the central canal of the spinal cord is called hydromyelia. This term refers to increased cerebrospinal fluid that is contained within the ependyma of the central canal. When fluid dissects into the surrounding white matter forming a cystic cavity or syrinx, the term syringomyelia is applied. As these conditions coexist in the majority of cases, the term syringohydromyelia is applied. The terms are used interchangeably.It has been observed that obstruction of the cerebrospinal fluid spaces in the subarachnoid space can result in syrinx formation, and alleviation of the obstruction may improve symptoms. A number of pathological conditions can cause an obstruction of the normal cerebrospinal fluid spaces. These include Chiari malformation, spinal arachnoiditis, scoliosis, spinal vertebrae misalignment, spinal tumors, spina bifida, and others. The reasons that blockage of the cerebrospinal fluid space within the subarachnoid space can result in syrinx formation are not fully understood although a small posterior fossa is one known cause. It is unclear if syrinx fluid originates from bulk movement of cerebrospinal fluid into the spinal cord, from bulk transmural movement of blood fluids through the spinal vasculature into the syrinx, or from a combination of both. Recent work suggests that central nervous system compliance is the underlying problem for the central nervous system, and also that hydrocephalus and syringomyelia have related causes.
Diagnosis
Physicians now use magnetic resonance imaging (MRI) to diagnose syringomyelia. The MRI radiographer takes images of body anatomy, such as the brain and spinal cord, in vivid detail. This test will show the syrinx in the spine or any other conditions, such as the presence of a tumor. MRI is safe, painless, and informative and has greatly improved the diagnosis of syringomyelia.The physician may order additional tests to help confirm the diagnosis. One of these is called electromyography (EMG), which show possible lower motor neuron damage.Note this test isnt used diagnostically for injuries to the spine but to nerves and muscles.This would be part of a patients rehab routine. In addition, computed axial tomography (CT) scans of a patients head may reveal the presence of tumors and other abnormalities such as hydrocephalus.Like MRI and CT scans, another test, called a myelogram, uses radiographs and requires a contrast medium to be injected into the subarachnoid space. Since the introduction of MRI, this test is rarely necessary to diagnose syringomyelia.The possible causes are trauma, tumors, and congenital defects. It is most usually observed in the part of the spinal cord corresponding to the neck area. Symptoms are due to spinal cord damage and include pain, decreased sensation of touch, weakness, and loss of muscle tissue. The diagnosis is confirmed with a spinal CT, myelogram or MRI of the spinal cord. The cavity may be reduced by surgical decompression.Furthermore, evidence also suggests that impact injuries to the thorax area highly correlate with the occurrence of a cervical-located syrinx.
Treatment
Surgery
Treating syringomyelia sometimes requires surgery. Surgery involving the spinal cord carries certain risks, and as with any medical treatment, the potential benefits have to be weighed against the possible complications. On the other hand, delaying treatment can increase the risk of permanent damage. Evaluation of the condition is necessary because syringomyelia can remain stationary for long periods of time, and in some cases progress rapidly.The main goal of surgical intervention is to correct the condition which led to the formation of the syrinx. Draining the syrinx can also help, by preventing it from becoming worse, but the symptoms the syrinx has already caused may not go away.In cases involving an Arnold–Chiari malformation, the main goal of surgery is to provide more space for the cerebellum at the base of the skull and upper cervical spine, without entering the brain or spinal cord. This often causes the syrinx to shrink or disappear over time, as the normal flow of cerebrospinal fluid is restored. If syringomyelia is caused by a tumor, removing the tumor – if possible – is the treatment of choice.Most patients’ symptoms stabilize or have a modest improvement following surgery. Syringomyelia can come back, however, requiring additional surgeries which may be less effective.In some cases, including both communicating and non-communicating forms of the condition, a syrinx may require ongoing drainage. This is done with a shunt, which uses tubes and valves to let cerebrospinal fluid (CSF) drain from the syrinx into another cavity within the body (usually the abdomen). This type of shunt, called a ventriculoperitoneal shunt, is particularly useful in cases involving hydrocephalus. By continually draining the syrinx, a shunt can arrest the progression of symptoms and relieve pain, headache, and tightness.Many factors affect the decision to use a shunt. There are risks of injury to the spinal cord, infection, drainage becoming blocked, and bleeding, and they do not always achieve the intended results. Draining the fluid more quickly does not produce better outcomes, but for some syrinxes, a shunt is the only drainage option.In the case of trauma-related syringomyelia, the surgeon operates at the level of the initial injury. The syrinx collapses at surgery, but a tube or shunt is usually necessary to prevent it from returning.
Non-surgical interventions
Surgery is not always recommended for syringomyelia patients. While there is no medication which can cure the condition, for many patients, the main treatment is analgesia to manage the symptoms. Physicians specializing in pain management can develop a medication and treatment plan to ameliorate pain. Medications to combat any neuropathic pain symptoms such as shooting and stabbing pains (e.g. gabapentin or pregabalin) would be first-line choices. Opiates are usually prescribed for pain for management of this condition. Conversely, facet joint injections are not indicated for the treatment of syringomyelia.Radiation is rare, but may be used if a tumor is involved. In these cases, it can halt the extension of a cavity and may help to alleviate pain.Treatment is usually reserved for cases which are causing symptoms. Treatment may not provide enough benefits to be recommended for elderly patients, or when symptoms are stable instead of worsening. Whether treated or not, many patients are advised to avoid activities that involve straining.A conservative approach may be recommended, as the natural history of syringomyelia is not yet well understood. When surgery is not currently advised, patients are monitored with regular physical evaluations and MRIs.
Research
The precise causes of syringomyelia are still unknown, although blockage of the flow of cerebrospinal fluid has been known to be an important factor since the 1970s. Scientists in the UK and US continue to explore the mechanisms that lead to the formation of syrinxes in the spinal cord. It has been demonstrated that a block of the free flow of cerebrospinal fluid is a contributing factor in the pathogenesis of the disease. Duke University in America and Warwick University are conducting research to explore genetic features of syringomyelia.Surgical techniques are also being refined by the neurosurgical research community. Successful procedures expand the area around the cerebellum and spinal cord, improving the flow of cerebrospinal fluid and thereby reducing the syrinx.It is also important to understand the role of birth defects in the development of hindbrain malformations that can lead to syringomyelia, as syringomyelia is a feature of intrauterine life and is also associated with spina bifida. Learning when these defects occur during the development of the fetus can help with the understanding of this and similar disorders, and may lead to preventive treatment that can stop the formation of some birth abnormalities.Diagnostic technology is another area for continued research. MRI has enabled scientists to see the situation within the spine, including syringomyelia, before any symptoms appear. A new technology, known as dynamic MRI, allows investigators to view spinal fluid flow within the syrinx. CT scans allow physicians to see abnormalities in the brain, and other diagnostic tests have also improved greatly with the availability of new, non-toxic, contrast dyes.
See also
Brown-Séquard syndrome
Central cord syndrome
Dissociated sensory loss
Ependymoma, a type of tumors that are capable of causing syringomyelia
Otto Kahler, a neurologist in the late 1800s who published the first complete description of syringomyelia.
Peter McFarline, Australian sports writer who had syringomyelia
Scoliosis is sometimes caused by syringomyelia.
Chiari Malformation
Syringobulbia
Ehlers Danlos Syndrome
Ehlers-Danlos Society
Hypermobility spectrum disorder
References
External links
Syringomyelia at NINDS |
Acneiform eruption | Acneiform eruptions are a group of dermatoses including acne vulgaris, rosacea, folliculitis, and perioral dermatitis. Restated, acneiform eruptions are follicular eruptions characterized by papules and pustules resembling acne.
The hybrid term acneiform, literally, refers to an appearance similar to acne.The terminology used in this field can be complex, and occasionally contradictory. Some sources consider acne vulgaris part of the differential diagnosis for an acneiform eruption. Other sources classified acne vulgaris under acneiform eruption. MeSH explicitly excludes perioral dermatitis from the category of "acneiform eruptions", though it does group acneiform eruptions and perioral dermatitis together under "facial dermatoses".
See also
Drug eruption
List of cutaneous conditions
References
== External links == |
Complement 4 deficiency | Complement 4 deficiency is a genetic condition affecting complement component 4.It can present with lupus-like symptoms.
References
== External links == |
Carrions disease | Carrions disease is an infectious disease produced by Bartonella bacilliformis infection.
It is named after Daniel Alcides Carrión.
Signs and symptoms
The clinical symptoms of bartonellosis are pleomorphic and some patients from endemic areas may be asymptomatic. The two classical clinical presentations are the acute phase and the chronic phase, corresponding to the two different host cell types invaded by the bacterium (red blood cells and endothelial cells). An individual can be affected by either or both phases.
Acute phase
It is also called the hematic phase. The most common findings are fever (usually sustained, but with temperature no greater than 102 °F (39 °C)), pale appearance, malaise, painless liver enlargement, jaundice, enlarged lymph nodes, and enlarged spleen. This phase is characterized by severe hemolytic anemia and transient immunosuppression. The case fatality ratios of untreated patients exceeded 40% but reach around 90% when opportunistic infection with Salmonella spp. occurs. In a recent study, the attack rate was 13.8% (123 cases) and the case-fatality rate was 0.7%.Other symptoms include a headache, muscle aches, and general abdominal pain. Some studies have suggested a link between Carrions disease and heart murmurs due to the diseases impact on the circulatory system. In children, symptoms of anorexia, nausea, and vomiting have been investigated as possible symptoms of the disease.Most of the mortality of Carrions disease occurs during the acute phase. Studies vary in their estimates of mortality. In one study, mortality has been estimated as low as just 1% in studies of hospitalized patients, to as high as 88% in untreated, unhospitalized patients. In developed countries, where the disease rarely occurs, it is recommended to seek the advice of a specialist in infectious disease when diagnosed. Mortality is often thought to be due to subsequent infections due to the weakened immune symptoms and opportunistic pathogen invasion, or consequences of malnutrition due to weight loss in children. In a study focusing on pediatric and gestational effects of the disease, mortality rates for pregnant women with the acute phase were estimated at 40% and rates of spontaneous abortion in another 40%.
Chronic phase
It is also called the eruptive phase or tissue phase, in which the patients develop a cutaneous rash produced by a proliferation of endothelial cells and is known as "Peruvian warts" or "verruga peruana". Depending on the size and characteristics of the lesions, there are three types: miliary (1–4 mm), nodular or subdermic, and mular (>5mm). Miliary lesions are the most common. The lesions often ulcerate and bleed.The most common findings are bleeding of verrugas, fever, malaise, arthralgias (joint pain), anorexia, myalgias, pallor, lymphadenopathy, and liver and spleen enlargement.On microscopic examination, the chronic phase and its rash are produced by angioblastic hyperplasia, or the increased rates and volume of cell growth in the tissues that form blood vessels. This results in a loss of contact between cells and a loss of normal functioning.The chronic phase is the more common phase. Mortality during the chronic phase is very low.
Cause
Carrions disease is caused by Bartonella bacilliformis. Recent investigations show that Candidatus Bartonella ancashi may cause verruga peruana, although it may not meet all of Kochs postulates. There has been no experimental reproduction of the Peruvian wart in animals and there is little research on the diseases natural spread or impact in native animals.
Diagnosis
Diagnosis during the acute phase can be made by obtaining a peripheral blood smear with Giemsa stain, Columbia blood agar cultures, immunoblot, indirect immunofluorescence, and PCR. Diagnosis during the chronic phase can be made using a Warthin-Starry stain of wart biopsy, PCR, and immunoblot.
Treatment
Because Carrions disease is often comorbid with Salmonella infections, chloramphenicol has historically been the treatment of choice.Fluoroquinolones (such as ciprofloxacin) or chloramphenicol in adults and chloramphenicol plus beta-lactams in children are the antibiotic regimens of choice during the acute phase of Carrions disease. Chloramphenicol-resistant B. bacilliformis has been observed.During the eruptive phase, in which chloramphenicol is not useful, azithromycin, erythromycin, and ciprofloxacin have been used successfully for treatment. Rifampin or macrolides are also used to treat both adults and children.Because of the high rates of comorbid infections and conditions, multiple treatments are often required. These have included the use of corticosteroids for respiratory distress, red blood cell transfusions for anemia, pericardiectomies for pericardial tamponades, and other standard treatments.
== References == |
Polyneuropathy | Polyneuropathy (poly- + neuro- + -pathy) is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hands and feet and may progress to the arms and legs and sometimes to other parts of the body where it may affect the autonomic nervous system. It may be acute or chronic. A number of different disorders may cause polyneuropathy, including diabetes and some types of Guillain–Barré syndrome.
Classification
Polyneuropathies may be classified in different ways, such as by cause, by presentation, or by classes of polyneuropathy, in terms of which part of the nerve cell is affected mainly: the axon, the myelin sheath, or the cell body.
Distal axonopathy, is the result of interrupted function of the peripheral nerves. It is the most common response of neurons to metabolic or toxic disturbances, and may be caused by metabolic diseases such as diabetes, kidney failure, connective tissue disease, deficiency syndromes such as malnutrition and alcoholism, or the effects of toxins or drugs such as chemotherapy. They may be divided according to the type of axon affected (large-fiber, small-fiber, or both), the most distal portions of axons are usually the first to degenerate, and axonal atrophy advances slowly toward the nerves cell body. However, if the cause is removed, then regeneration is possible, although the prognosis depends on the duration and severity of the original stimulus. People with distal axonopathies usually present with sensorimotor disturbances such as amyotrophic lateral sclerosis
Myelinopathy, is due to a loss of myelin or of the Schwann cells. This demyelination slows down or completely blocks the conduction of action potentials through the axon of the nerve cell (neurapraxia). The most common cause is acute inflammatory demyelinating polyneuropathy AIDP, the most common form of Guillain–Barré syndrome (although other causes include chronic inflammatory demyelinating polyneuropathy )
Neuronopathy is the result of issues in the peripheral nervous system (PNS) neurons. They may be caused by motor neurone diseases, sensory neuronopathies, toxins, or autonomic dysfunction. Neurotoxins such as chemotherapy agents may cause neuronopathies.
Signs and symptoms
Among the signs/symptoms of polyneuropathy, which can be divided (into sensory and hereditary) and are consistent with the following:
Sensory polyneuropathy – ataxia, numbness, muscle wasting and paraesthesiae.
Hereditary polyneuropathy – scoliosis and hammer toes
Causes
The causes of polyneuropathy can be divided into hereditary and acquired and are therefore as follows:
Inherited -are hereditary motor neuropathies, Charcot–Marie–Tooth disease, and hereditary neuropathy with liability to pressure palsy
Acquired -are diabetes mellitus, vascular neuropathy, alcohol use disorder, and vitamin B12 deficiency
Pathophysiology
In regard to the pathophysiology of polyneuropathy, of course, the former depends on which polyneuropathy. For instance in the case of chronic inflammatory demyelinating polyneuropathy, one finds that it is an autoimmune disease. Here, T cells involvement has been demonstrated, while in terms of demyelination, antibodies alone are not capable.
Diagnosis
The diagnosis of polyneuropathies begins with a history and physical examination to ascertain the pattern of the disease process (such as-arms, legs, distal, proximal) if they fluctuate, and what deficits and pain are involved. If pain is a factor, determining where and how long the pain has been present is important, one also needs to know what disorders are present within the family and what diseases the person may have. Although diseases often are suggested by the physical examination and history alone, tests that may be employed include: electrodiagnostic testing, serum protein electrophoresis, nerve conduction studies, urinalysis, serum creatine kinase (CK) and antibody testing (nerve biopsy is sometimes done).Other tests may be used, especially tests for specific disorders associated with polyneuropathies, quality measures have been developed to diagnose patients with distal symmetrical polyneuropathy (DSP).
Differential diagnosis
In terms of the differential diagnosis for polyneuropathy one must look at the following:
Treatment
In the treatment of polyneuropathies one must ascertain and manage the cause, among management activities are: weight decrease, use of a walking aid, and occupational therapist assistance. Additionally, BP control in those with diabetes is helpful, while intravenous immunoglobulin is used for multifocal motor neuropathy.According to Lopate, et al., methylprednisolone is a viable treatment for chronic inflammatory demyelinative polyneuropathy (which can also be treated with intravenous immunoglobulin). The authors also indicate that prednisone has greater adverse effects in such treatment, as opposed to intermittent (high-doses) of the aforementioned medication.According to Wu, et al., in critical illness polyneuropathy supportive and preventive therapy are important for the affected individual, as well as, avoiding (or limiting) corticosteroids.
See also
References
Further reading
Dimachkie, Mazen M.; Barohn, Richard J. (7 April 2013). "Chronic Inflammatory Demyelinating Polyneuropathy". Current Treatment Options in Neurology. 15 (3): 350–366. doi:10.1007/s11940-013-0229-6. ISSN 1092-8480. PMC 3987657. PMID 23564314.
Katirji, Bashar; Kaminski, Henry J.; Ruff, Robert L. (2013-10-11). Neuromuscular Disorders in Clinical Practice. Springer Science & Business Media. ISBN 9781461465676. Retrieved 26 August 2016.
Said, Professor Gérard (2014). Peripheral Neuropathy & Neuropathic Pain: Into The Light. tfm Publishing Limited. p. 17. ISBN 9781910079027. Retrieved 3 August 2016.
== External links == |
Phantom pain | Phantom pain is a perception that an individual experiences relating to a limb or an organ that is not physically part of the body, either because it was removed or was never there in the first place. However, phantom limb sensations can also occur following nerve avulsion or spinal cord injury.
Sensations are recorded most frequently following the amputation of an arm or a leg, but may also occur following the removal of a breast, tooth, or an internal organ. Phantom limb pain is the feeling of pain in an absent limb or a portion of a limb. The pain sensation varies from individual to individual.
Phantom limb sensation is any sensory phenomenon (except pain) which is felt at an absent limb or a portion of the limb. It has been known that at least 80% of amputees experience phantom sensations at some time of their lives. Some experience some level of this phantom pain and feeling in the missing limb for the rest of their lives.
The term "phantom limb" was first coined by American neurologist Silas Weir Mitchell in 1871. Mitchell described that "thousands of spirit limbs were haunting as many good soldiers, every now and then tormenting them". However, in 1551, French military surgeon Ambroise Paré recorded the first documentation of phantom limb pain when he reported that, "For the patients, long after the amputation is made, say that they still feel pain in the amputated part".
Signs and symptoms
Phantom pain involves the sensation of pain in a part of the body that has been removed.
The onset of phantom pain can occur within the first few days of amputation. The sensation may come and go, but can be continuous. While the sensation often affects the part of the limb farthest from the body, such as the foot of an amputated leg, other body parts closer to the brain, such as the arm or hand, can still experience similar sensations. Sensations can be described as shooting, stabbing, boring, squeezing, throbbing or burning. Sensations on smaller limbs and digits such as toes or fingers tend to be less severe. Sometimes the sensation feels as if the phantom part is forced into an uncomfortable position. Overall, the sensations may be triggered by pressure on the remaining part of the limb or emotional stress.
Types
There are various types of sensations that may be felt:
Sensations related to the phantom limbs posture, length and volume e.g. feeling that the phantom limb is behaving just like a normal limb like sitting with the knee bent or feeling that the phantom limb is as heavy as the other limb. Sometimes, an amputee will experience a sensation called telescoping, the feeling that the phantom limb is gradually shortening over time.
Sensations of movement (e.g. feeling that the phantom foot is moving).
Sensations of touch, temperature, pressure and itchiness. Many amputees report of feeling heat, tingling, itchiness, and pain.
In less severe cases where small digits are amputated, the sensation can be described as a tingling feeling as opposed to a painful sensation.
Pathophysiology
The neurological basis and mechanisms for phantom limb pain are all derived from experimental theories and observations. Little is known about the true mechanism causing phantom pains, and many theories highly overlap. Historically, phantom pains were thought to originate from neuromas located at the stump tip. Traumatic neuromas, or non-tumor nerve injuries, often arise from surgeries and result from the abnormal growth of injured nerve fibers. Although stump neuromas contribute to phantom pains, they are not the sole cause. This is because patients with congenital limb deficiency can sometimes, although rarely, experience phantom pains. This suggests that there is a central representation of the limb responsible for painful sensations. Currently, theories are based on altered neurological pathways and cortical reorganization.
Peripheral mechanisms
Neuromas formed from injured nerve endings at the stump site are able to fire abnormal action potentials, and were historically thought to be the main cause of phantom limb pain. Although neuromas are able to contribute to phantom pain, pain is not completely eliminated when peripheral nerves are treated with conduction blocking agents. Physical stimulation of neuromas can increase C fiber activity, thus increasing phantom pain, but pain still persists once the neuromas have ceased firing action potentials. The peripheral nervous system is thought to have at most a modulation effect on phantom limb pain.
Spinal mechanisms
In addition to peripheral mechanisms, spinal mechanisms are thought to have an influencing role in phantom pains. Peripheral nerve injury can lead to the degeneration of C fibers in the dorsal horn of the spinal cord, and terminating A fibers may subsequently branch into the same lamina. If this occurs, A fiber inputs could be reported as noxious stimuli. Substance P, involved in the transmission of pain signals, is usually expressed by Aδ and C fibers, but following peripheral nerve damage, substance P is expressed by Aβ fibers. This leads to hyperexcitability of the spinal cord, which usually occurs only in the presence of noxious stimuli. Because patients with complete spinal cord injury have experienced phantom pains, there must be an underlying central mechanism responsible for the generation of phantom pains.
Central mechanisms
Under ordinary circumstances, the genetically determined circuitry in the brain remains largely stable throughout life. For much of the twentieth century, it was believed that no new neural circuits could be formed in the adult mammalian brain, but experiments from the 1980s onward cast this into doubt. For instance, functional MRI studies in amputees have shown that almost all patients have experienced motor cortical remapping. The majority of motor reorganization has occurred as a downward shift of the hand area of the cortex onto the area of face representation, especially the lips. Sometimes there is a side shift of the hand motor cortex to the ipsilateral cortex. In patients with phantom limb pain, the reorganization was great enough to cause a change in cortical lip representation into the hand areas only during lip movements. It has also been found that there is a high correlation between the magnitude of phantom limb pain and the extent to which the shift of the cortical representation of the mouth into the hand area in motor and somatosensory cortical reorganization has occurred. Additionally, as phantom pains in upper extremity amputees increased, there was a higher degree of medial shift of the facial motor representation. There are multiple theories that try to explain how cortical remapping occurs in amputees, but none have been supported to a great extent.
The neuromatrix
The neuromatrix theory proposes that there is an extensive network connecting the thalamus and the cortex, and the cortex and the limbic system. It is a theory that extends beyond body schema theory and incorporates the conscious awareness of oneself. This theory proposes that conscious awareness and the perception of self are generated in the brain via patterns of input that can be modified by different perceptual inputs. The network is genetically predetermined, and is modified throughout one’s lifetime by various sensory inputs to create a neurosignature. It is the neurosignature of a specific body part that determines how it is consciously perceived. The input systems contributing to the neurosignature are primarily the somatosensory, limbic, and thalamocortical systems. The neuromatrix theory aims to explain how certain activities associated with pain lead to the conscious perception of phantom pain. The persistence of the neurosignature, even after limb amputation, may be the cause of phantom sensations and pain. Phantom pain may arise from abnormal reorganization in the neuromatrix to a pre-existing pain state.Opposition to the neuromatrix theory exists largely because it fails to explain why relief from phantom sensations rarely eliminates phantom pains. It also does not address how sensations can spontaneously end and how some amputees do not experience phantom sensations at all. In addition, a major limitation of the neuromatrix theory is that it too broadly accounts for various aspects of phantom limb perception. It is also likely that it is too difficult to be tested empirically, especially when testing painless phantom sensations.
Management
Various methods have been used to treat phantom limb pain. Doctors may prescribe medications to reduce the pain. Some antidepressants or antiepileptics have been shown to have a beneficial effect on reducing phantom limb pain. Often physical methods such as light massage, electrical stimulation, and hot and cold therapy have been used with variable results.
There are many different treatment options for phantom limb pain that are actively being researched. Most treatments do not take into account the mechanisms underlying phantom pains, and are therefore ineffective. However, there are a few treatment options that have been shown to alleviate pain in some patients, but these treatment options usually have a success rate less than 30%. It is important to note that this rate of success does not exceed the placebo effect. It is also important to note that because the degree of cortical reorganization is proportional to phantom limb pains, any perturbations to the amputated regions may increase pain perception.
Mirror therapy
Mirror box therapy allows for illusions of movement and touch in a phantom limb by inducing somatosensory and motor pathway coupling between the phantom and real limb. Many patients experience pain as a result of a clenched phantom limb, and because phantom limbs are not under voluntary control, unclenching becomes impossible. This theory proposes that the phantom limb feels paralyzed because there is no feedback from the phantom back to the brain to inform it otherwise. Vilayanur S. Ramachandran believes that if the brain received visual feedback that the limb had moved, then the phantom limb would become unparalyzed.Although the use of mirror therapy has been shown to be effective in some cases there is still no widely accepted theory of how it works. According to 2017 paper that reviewed a wide range of studies of mirror therapy, "Research evidence suggests that a course of treatment (four weeks) of mirror therapy may reduce chronic pain. Contraindications and side effects are few. The mechanism of action of mirror therapy remains uncertain, with reintegration of motor and sensory systems, restored body image and control over fear-avoidance likely to influence outcome. The evidence for clinical efficacy of mirror therapy is encouraging, but not yet definitive. Nevertheless, mirror therapy is inexpensive, safe and easy for the patient to self-administer."Little research was published on MT before 2009, and much of the research since then has been of low quality. Out of 115 publications between 2012 and 2017 about using mirror therapy to treat phantom limb pain, a 2018 review, found only 15 studies whose scientific results should be considered. From these 15 studies, the reviewers concluded that "MT seems to be effective in relieving PLP, reducing the intensity and duration of daily pain episodes. It is a valid, simple, and inexpensive treatment for PLP."
Medication
Pharmacological techniques are often continued in conjunction with other treatment options. Doses of pain medications needed often drop substantially when combined with other techniques, but rarely are discontinued completely. Tricyclic antidepressants, such as amitriptyline, and sodium channel blockers, mainly carbamazepine, are often used to relieve chronic pain, and recently have been used in an attempt to reduce phantom pains. Pain relief may also be achieved through use of opioids, ketamine, calcitonin, and lidocaine.
Deep-brain stimulation
Deep brain stimulation is a surgical technique used to alleviate patients from phantom limb pain. Prior to surgery, patients undergo functional brain imaging techniques such as PET scans and functional MRI to determine an appropriate trajectory of where pain is originating. Surgery is then carried out under local anesthetic, because patient feedback during the operation is needed. In the study conducted by Bittar et al., a radiofrequency electrode with four contact points was placed on the brain. Once the electrode was in place, the contact locations were altered slightly according to where the patient felt the greatest relief from pain. Once the location of maximal relief was determined, the electrode was implanted and secured to the skull. After the primary surgery, a secondary surgery under general anesthesia was conducted. A subcutaneous pulse generator was implanted into a pectoral pocket below the clavicle to stimulate the electrode. It was found that all three patients studied had gained satisfactory pain relief from the deep brain stimulation. Pain had not been completely eliminated, but the intensity had been reduced by over 50% and the burning component had completely vanished.
Epidemiology
Phantom limb pain and phantom limb sensations are linked, but must be differentiated from one another. While phantom limb sensations are experienced by those with congenital limb deficiency, spinal cord injury, and amputation, phantom limb pain occurs almost exclusively as a result of amputation. Almost immediately following the amputation of a limb, 90–98% of patients report experiencing a phantom sensation. Nearly 75% of individuals experience the phantom as soon as anesthesia wears off, and the remaining 25% of patients experience phantoms within a few days or weeks. Of those experiencing innocuous sensations, a majority of patients also report distinct painful sensations.
Age and gender have not been shown to affect the onset or duration of phantom limb pain. Although it has not been fully explored, one investigation of lower limb amputation observed that as stump length decreased, there was a greater incidence of moderate and severe phantom pain.
See also
Phantom limb
Phantom eye syndrome
References
External links
MacLachlan, Malcolm; McDonald, Dympna; Waloch, Justine (2004), "Mirror Treatment of Lower Limb Phantom Pain: A Case Study", Disability and Rehabilitation, 26 (14/15): 901–904, doi:10.1080/09638280410001708913, PMID 15497919, S2CID 36325980Richardson, Cliff; Glenn, Sheila; Horgan, Maureen; Nurmikko, Turo (October 2007), "A Prospective Study of Factors Associated with the Presence of Phantom Limb Pain Six Months After Major Lower Limb Amputation in Patients with Peripheral Vascular Disease", The Journal of Pain, 8 (10): 793–801, doi:10.1016/j.jpain.2007.05.007, PMID 17631056Targeted Muscle Reinnervation |
Coeliac disease | Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barley. Classic symptoms include gastrointestinal problems such as chronic diarrhoea, abdominal distention, malabsorption, loss of appetite, and among children failure to grow normally. This often begins between six months and two years of age. Non-classic symptoms are more common, especially in people older than two years. There may be mild or absent gastrointestinal symptoms, a wide number of symptoms involving any part of the body, or no obvious symptoms. Coeliac disease was first described in childhood; however, it may develop at any age. It is associated with other autoimmune diseases, such as Type 1 diabetes mellitus and Hashimotos thyroiditis, among others.Coeliac disease is caused by a reaction to gluten, a group of various proteins found in wheat and in other grains such as barley and rye. Moderate quantities of oats, free of contamination with other gluten-containing grains, are usually tolerated. The occurrence of problems may depend on the variety of oat. It occurs in people who are genetically predisposed. Upon exposure to gluten, an abnormal immune response may lead to the production of several different autoantibodies that can affect a number of different organs. In the small bowel, this causes an inflammatory reaction and may produce shortening of the villi lining the small intestine (villous atrophy). This affects the absorption of nutrients, frequently leading to anaemia.Diagnosis is typically made by a combination of blood antibody tests and intestinal biopsies, helped by specific genetic testing. Making the diagnosis is not always straightforward. About 10% of the time, the autoantibodies in the blood are negative, and many people have only minor intestinal changes with normal villi. People may have severe symptoms and they may be investigated for years before a diagnosis is achieved. Increasingly, the diagnosis is being made in people without symptoms, as a result of screening. Evidence regarding the effects of screening, however, is not sufficient to determine its usefulness. While the disease is caused by a permanent intolerance to gluten proteins, it is distinct from wheat allergy, which is much more rare.The only known effective treatment is a strict lifelong gluten-free diet, which leads to recovery of the intestinal lining (mucous membrane), improves symptoms, and reduces the risk of developing complications in most people. If untreated, it may result in cancers such as intestinal lymphoma, and a slightly increased risk of early death. Rates vary between different regions of the world, from as few as 1 in 300 to as many as 1 in 40, with an average of between 1 in 100 and 1 in 170 people. It is estimated that 80% of cases remain undiagnosed, usually because of minimal or absent gastrointestinal complaints and lack of knowledge of symptoms and diagnostic criteria. Coeliac disease is slightly more common in women than in men.
Signs and symptoms
The classic symptoms of untreated coeliac disease include pale, loose, or greasy stools (steatorrhoea), and weight loss or failure to gain weight. Other common symptoms may be subtle or primarily occur in organs other than the bowel itself. It is also possible to have coeliac disease without any of the classic symptoms at all. This has been shown to comprise at least 43% of presentations in children. Further, many adults with subtle disease may only present with fatigue, anaemia or low bone mass. Many undiagnosed individuals who consider themselves asymptomatic are in fact not, but rather have become accustomed to living in a state of chronically compromised health. Indeed, after starting a gluten-free diet and subsequent improvement becomes evident, such individuals are often able to retrospectively recall and recognise prior symptoms of their untreated disease that they had mistakenly ignored.
Gastrointestinal
Diarrhoea that is characteristic of coeliac disease is chronic, sometimes pale, of large volume, and abnormally foul in odor. Abdominal pain, cramping, bloating with abdominal distension (thought to be the result of fermentative production of bowel gas), and mouth ulcers may be present. As the bowel becomes more damaged, a degree of lactose intolerance may develop. Frequently, the symptoms are ascribed to irritable bowel syndrome (IBS), only later to be recognised as coeliac disease. In populations of people with symptoms of IBS, a diagnosis of coeliac disease can be made in about 3.3% of cases, or four times more likely than in general. Screening them for coeliac disease is recommended by the National Institute for Health and Clinical Excellence (NICE), the British Society of Gastroenterology and the American College of Gastroenterology, but is of unclear benefit in North America.Coeliac disease leads to an increased risk of both adenocarcinoma and lymphoma of the small bowel (enteropathy-associated T-cell lymphoma (EATL) or other non-Hodgkin lymphomas). This risk is also higher in first-degree relatives such as siblings, parents and children. Whether a gluten-free diet brings this risk back to baseline is not clear. Long-standing and untreated disease may lead to other complications, such as ulcerative jejunitis (ulcer formation of the small bowel) and stricturing (narrowing as a result of scarring with obstruction of the bowel).
Malabsorption-related
The changes in the bowel reduce its ability to absorb nutrients, minerals, and the fat-soluble vitamins A, D, E, and K.
Malabsorption of carbohydrates and fats may cause weight loss (or failure to thrive or stunted growth in children) and fatigue or lack of energy.
Anaemia may develop in several ways: iron malabsorption may cause iron deficiency anaemia, and folic acid and vitamin B12 malabsorption may give rise to megaloblastic anaemia.
Calcium and vitamin D malabsorption (and compensatory secondary hyperparathyroidism) may cause osteopenia (decreased mineral content of the bone) or osteoporosis (bone weakening and risk of fragility fractures).
Selenium malabsorption in coeliac disease, combined with low selenium content in many gluten-free foods, confers a risk of selenium deficiency.
Copper and zinc deficiencies have also been associated with coeliac disease.
A small proportion have abnormal coagulation because of vitamin K deficiency and are at a slight risk of abnormal bleeding.
Miscellaneous
Coeliac disease has been linked with many conditions. In many cases, it is unclear whether the gluten-induced bowel disease is a causative factor or whether these conditions share a common predisposition.
IgA deficiency is present in 2.3% of people with coeliac disease, and is itself associated with a tenfold increased risk of coeliac disease. Other features of this condition are an increased risk of infections and autoimmune disease.
Dermatitis herpetiformis, an itchy cutaneous condition that has been linked to a transglutaminase enzyme in the skin, features small-bowel changes identical to those in coeliac disease and may respond to gluten withdrawal even if no gastrointestinal symptoms are present.
Growth failure and/or pubertal delay in later childhood can occur even without obvious bowel symptoms or severe malnutrition. Evaluation of growth failure often includes coeliac screening.
Pregnancy complications can occur if coeliac disease is pre-existing or later acquired, with significant outcomes including miscarriage, intrauterine growth restriction, low birthweight and preterm birth.
Hyposplenism (a small and underactive spleen) occurs in about a third of cases and may predispose to infection given the role of the spleen in protecting against harmful bacteria.
Abnormal liver function tests (randomly detected on blood tests) may be seen.Coeliac disease is associated with several other medical conditions, many of which are autoimmune disorders: diabetes mellitus type 1, hypothyroidism, primary biliary cholangitis, microscopic colitis, gluten ataxia, psoriasis, vitiligo, autoimmune hepatitis, primary sclerosing cholangitis, and more.
Cause
Coeliac disease is caused by an inflammatory reaction to gliadins and glutenins (gluten proteins) found in wheat and to similar proteins found in the crops of the tribe Triticeae (which includes other common grains such as barley and rye) and to the tribe Aveneae (oats). Wheat subspecies (such as spelt, durum, and Kamut) and wheat hybrids (such as triticale) also cause symptoms of coeliac disease.A small number of people with coeliac disease react to oats. Oat toxicity in coeliac people depends on the oat cultivar consumed because the prolamin genes, protein amino acid sequences, and the immunoreactivities of toxic prolamins are different in different oat varieties. Also, oats are frequently cross-contaminated with other grains containing gluten. The term "pure oats" refers to oats uncontaminated with other gluten-containing cereals. The long-term effects of pure oat consumption are still unclear, and further studies identifying the cultivars used are needed before making final recommendations on their inclusion in a gluten-free diet. Coeliac people who choose to consume oats need a more rigorous lifelong follow-up, possibly including periodic intestinal biopsies.
Other grains
Other cereals such as corn, millet, sorghum, teff, rice, and wild rice are safe for people with coeliac disease to consume, as well as noncereals such as amaranth, quinoa, and buckwheat. Noncereal carbohydrate-rich foods such as potatoes and bananas do not contain gluten and do not trigger symptoms.
Risk modifiers
There are various theories as to what determines whether a genetically susceptible individual will go on to develop coeliac disease. Major theories include surgery, pregnancy, infection and emotional stress.The eating of gluten early in a babys life does not appear to increase the risk of coeliac disease but later introduction after 6 months may increase it. There is uncertainty whether being breastfed reduces risk. Prolonging breastfeeding until the introduction of gluten-containing grains into the diet appears to be associated with a 50% reduced risk of developing coeliac disease in infancy; whether this persists into adulthood is not clear. These factors may just influence the timing of onset.
Pathophysiology
Coeliac disease appears to be multifactorial, both in that more than one genetic factor can cause the disease and in that more than one factor is necessary for the disease to manifest in a person.
Almost all people (95%) with coeliac disease have either the variant HLA-DQ2 allele or (less commonly) the HLA-DQ8 allele. However, about 20–30% of people without coeliac disease have also inherited either of these alleles. This suggests that additional factors are needed for coeliac disease to develop; that is, the predisposing HLA risk allele is necessary but not sufficient to develop coeliac disease. Furthermore, around 5% of those people who do develop coeliac disease do not have typical HLA-DQ2 or HLA-DQ8 alleles (see below).
Genetics
The vast majority of people with coeliac have one of two types (out of seven) of the HLA-DQ protein. HLA-DQ is part of the MHC class II antigen-presenting receptor (also called the human leukocyte antigen) system and distinguishes cells between self and non-self for the purposes of the immune system. The two subunits of the HLA-DQ protein are encoded by the HLA-DQA1 and HLA-DQB1 genes, located on the short arm of chromosome 6.
There are seven HLA-DQ variants (DQ2 and DQ4–DQ9). Over 95% of people with coeliac have the isoform of DQ2 or DQ8, which is inherited in families. The reason these genes produce an increase in the risk of coeliac disease is that the receptors formed by these genes bind to gliadin peptides more tightly than other forms of the antigen-presenting receptor. Therefore, these forms of the receptor are more likely to activate T lymphocytes and initiate the autoimmune process.
Most people with coeliac bear a two-gene HLA-DQ2 haplotype referred to as DQ2.5 haplotype. This haplotype is composed of two adjacent gene alleles, DQA1*0501 and DQB1*0201, which encode the two subunits, DQ α5 and DQ β2. In most individuals, this DQ2.5 isoform is encoded by one of two chromosomes 6 inherited from parents (DQ2.5cis). Most coeliacs inherit only one copy of this DQ2.5 haplotype, while some inherit it from both parents; the latter are especially at risk for coeliac disease as well as being more susceptible to severe complications.Some individuals inherit DQ2.5 from one parent and an additional portion of the haplotype (either DQB1*02 or DQA1*05) from the other parent, increasing risk. Less commonly, some individuals inherit the DQA1*05 allele from one parent and the DQB1*02 from the other parent (DQ2.5trans) (called a trans-haplotype association), and these individuals are at similar risk for coeliac disease as those with a single DQ2.5-bearing chromosome 6, but in this instance, the disease tends not to be familial. Among the 6% of European coeliacs that do not have DQ2.5 (cis or trans) or DQ8 (encoded by the haplotype DQA1*03:DQB1*0302), 4% have the DQ2.2 isoform, and the remaining 2% lack DQ2 or DQ8.The frequency of these genes varies geographically. DQ2.5 has high frequency in peoples of North and Western Europe (Basque Country and Ireland with highest frequencies) and portions of Africa and is associated with disease in India, but it is not found along portions of the West Pacific rim. DQ8 has a wider global distribution than DQ2.5 and is particularly common in South and Central America; up to 90% of individuals in certain Amerindian populations carry DQ8 and thus may display the coeliac phenotype.Other genetic factors have been repeatedly reported in coeliac disease; however, involvement in disease has variable geographic recognition. Only the HLA-DQ loci show a consistent involvement over the global population. Many of the loci detected have been found in association with other autoimmune diseases. One locus, the LPP or lipoma-preferred partner gene, is involved in the adhesion of extracellular matrix to the cell surface, and a minor variant (SNP = rs1464510) increases the risk of disease by approximately 30%. This gene strongly associates with coeliac disease (p < 10−39) in samples taken from a broad area of Europe and the US.The prevalence of coeliac disease genotypes in the modern population is not completely understood. Given the characteristics of the disease and its apparent strong heritability, it would normally be expected that the genotypes would undergo negative selection and to be absent in societies where agriculture has been practised the longest (compare with a similar condition, Lactose intolerance, which has been negatively selected so strongly that its prevalence went from ~100% in ancestral populations to less than 5% in some European countries). This expectation was first proposed by Simoons (1981). By now, however, it is apparent that this is not the case; on the contrary, there is evidence of positive selection in coeliac disease genotypes. It is suspected that some of them may have been beneficial by providing protection against bacterial infections.
Prolamins
The majority of the proteins in food responsible for the immune reaction in coeliac disease are the prolamins. These are storage proteins rich in proline (prol-) and glutamine (-amin) that dissolve in alcohols and are resistant to proteases and peptidases of the gut. Prolamins are found in cereal grains with different grains having different but related prolamins: wheat (gliadin), barley (hordein), rye (secalin) and oats (avenin). One region of α-gliadin stimulates membrane cells, enterocytes, of the intestine to allow larger molecules around the sealant between cells. Disruption of tight junctions allow peptides larger than three amino acids to enter the intestinal lining.
Membrane leaking permits peptides of gliadin that stimulate two levels of the immune response: the innate response, and the adaptive (T-helper cell-mediated) response. One protease-resistant peptide from α-gliadin contains a region that stimulates lymphocytes and results in the release of interleukin-15. This innate response to gliadin results in immune-system signalling that attracts inflammatory cells and increases the release of inflammatory chemicals. The strongest and most common adaptive response to gliadin is directed toward an α2-gliadin fragment of 33 amino acids in length.The response to the 33mer occurs in most coeliacs who have a DQ2 isoform. This peptide, when altered by intestinal transglutaminase, has a high density of overlapping T-cell epitopes. This increases the likelihood that the DQ2 isoform will bind, and stay bound to, peptide when recognised by T-cells. Gliadin in wheat is the best-understood member of this family, but other prolamins exist, and hordein (from barley), secalin (from rye), and avenin (from oats) may contribute to coeliac disease. Avenins toxicity in people with coeliac disease depends on the oat cultivar consumed, as prolamin genes, protein amino acid sequences, and the immunoreactivities of toxic prolamins vary among oat varieties.
Tissue transglutaminase
Anti-transglutaminase antibodies to the enzyme tissue transglutaminase (tTG) are found in the blood of the majority of people with classic symptoms and complete villous atrophy, but only in 70% of the cases with partial villous atrophy and 30% of the cases with minor mucosal lesions. Tissue transglutaminase modifies gluten peptides into a form that may stimulate the immune system more effectively. These peptides are modified by tTG in two ways, deamidation or transamidation.Deamidation is the reaction by which a glutamate residue is formed by cleavage of the epsilon-amino group of a glutamine side chain. Transamidation, which occurs three times more often than deamidation, is the cross-linking of a glutamine residue from the gliadin peptide to a lysine residue of tTg in a reaction that is catalysed by the transglutaminase. Crosslinking may occur either within or outside the active site of the enzyme. The latter case yields a permanently covalently linked complex between the gliadin and the tTg. This results in the formation of new epitopes believed to trigger the primary immune response by which the autoantibodies against tTg develop.Stored biopsies from people with suspected coeliac disease have revealed that autoantibody deposits in the subclinical coeliacs are detected prior to clinical disease. These deposits are also found in people who present with other autoimmune diseases, anaemia, or malabsorption phenomena at a much increased rate over the normal population. Endomysial components of antibodies (EMA) to tTG are believed to be directed toward cell-surface transglutaminase, and these antibodies are still used in confirming a coeliac disease diagnosis. However, a 2006 study showed that EMA-negative people with coeliac tend to be older males with more severe abdominal symptoms and a lower frequency of "atypical" symptoms, including autoimmune disease. In this study, the anti-tTG antibody deposits did not correlate with the severity of villous destruction. These findings, coupled with recent work showing that gliadin has an innate response component, suggest that gliadin may be more responsible for the primary manifestations of coeliac disease, whereas tTG is a bigger factor in secondary effects such as allergic responses and secondary autoimmune diseases. In a large percentage of people with coeliac, the anti-tTG antibodies also recognise a rotavirus protein called VP7. These antibodies stimulate monocyte proliferation, and rotavirus infection might explain some early steps in the cascade of immune cell proliferation.Indeed, earlier studies of rotavirus damage in the gut showed this causes villous atrophy. This suggests that viral proteins may take part in the initial flattening and stimulate self-crossreactive anti-VP7 production. Antibodies to VP7 may also slow healing until the gliadin-mediated tTG presentation provides a second source of crossreactive antibodies.
Other intestinal disorders may have biopsy that look like coeliac disease including lesions caused by Candida.
Villous atrophy and malabsorption
The inflammatory process, mediated by T cells, leads to disruption of the structure and function of the small bowels mucosal lining and causes malabsorption as it impairs the bodys ability to absorb nutrients, minerals, and fat-soluble vitamins A, D, E, and K from food. Lactose intolerance may be present due to the decreased bowel surface and reduced production of lactase but typically resolves once the condition is treated.
Alternative causes of this tissue damage have been proposed and involve the release of interleukin 15 and activation of the innate immune system by a shorter gluten peptide (p31–43/49). This would trigger killing of enterocytes by lymphocytes in the epithelium. The villous atrophy seen on biopsy may also be due to unrelated causes, such as tropical sprue, giardiasis and radiation enteritis. While positive serology and typical biopsy are highly suggestive of coeliac disease, lack of response to the diet may require these alternative diagnoses to be considered.
Diagnosis
Diagnosis is often difficult and as of 2019, there continues to be a lack of awareness among physicians about the variability of presentations of coeliac disease and the diagnostic criteria, such that most cases are diagnosed with great delay. It can take up to 12 years to receive a diagnosis from the onset of symptoms and the majority of those affected in most countries never receive it.Several tests can be used. The level of symptoms may determine the order of the tests, but all tests lose their usefulness if the person is already eating a gluten-free diet. Intestinal damage begins to heal within weeks of gluten being removed from the diet, and antibody levels decline over months. For those who have already started on a gluten-free diet, it may be necessary to perform a rechallenge with some gluten-containing food in one meal a day over 6 weeks before repeating the investigations.
Blood tests
Serological blood tests are the first-line investigation required to make a diagnosis of coeliac disease. Its sensitivity correlates with the degree of histological lesions. People who present with minor damage to the small intestine may have seronegative findings so many patients with coeliac disease often are missed. In patients with villous atrophy, anti-endomysial (EMA) antibodies of the immunoglobulin A (IgA) type can detect coeliac disease with a sensitivity and specificity of 90% and 99%, respectively. Serology for anti-transglutaminase antibodies (anti-tTG) was initially reported to have a higher sensitivity (99%) and specificity (>90%). However, it is now thought to have similar characteristics to anti-endomysial antibodies. Both anti-transglutaminase and anti-endomysial antibodies have high sensitivity to diagnose people with classic symptoms and complete villous atrophy, but they are only found in 30–89% of the cases with partial villous atrophy and in less than 50% of the people who have minor mucosal lesions (duodenal lymphocytosis) with normal villi.Tissue transglutaminase modifies gluten peptides into a form that may stimulate the immune system more effectively. These peptides are modified by tTG in two ways, deamidation or transamidation. Modern anti-tTG assays rely on a human recombinant protein as an antigen. tTG testing should be done first as it is an easier test to perform. An equivocal result on tTG testing should be followed by anti-endomysial antibodies.Guidelines recommend that a total serum IgA level is checked in parallel, as people with coeliac with IgA deficiency may be unable to produce the antibodies on which these tests depend ("false negative"). In those people, IgG antibodies against transglutaminase (IgG-tTG) may be diagnostic.If all these antibodies are negative, then anti-DGP antibodies (antibodies against deamidated gliadin peptides) should be determined. IgG class anti-DGP antibodies may be useful in people with IgA deficiency. In children younger than two years, anti-DGP antibodies perform better than anti-endomysial and anti-transglutaminase antibodies tests.Because of the major implications of a diagnosis of coeliac disease, professional guidelines recommend that a positive blood test is still followed by an endoscopy/gastroscopy and biopsy. A negative serology test may still be followed by a recommendation for endoscopy and duodenal biopsy if clinical suspicion remains high.Historically three other antibodies were measured: anti-reticulin (ARA), anti-gliadin (AGA) and anti-endomysial (EMA) antibodies. ARA testing, however, is not accurate enough for routine diagnostic use. Serology may be unreliable in young children, with anti-gliadin performing somewhat better than other tests in children under five. Serology tests are based on indirect immunofluorescence (reticulin, gliadin and endomysium) or ELISA (gliadin or tissue transglutaminase, tTG).Other antibodies such as anti–Saccharomyces cerevisiae antibodies occur in some people with coeliac disease but also occur in other autoimmune disorders and about 5% of those who donate blood.Antibody testing may be combined with HLA testing if the diagnosis is unclear. TGA and EMA testing are the most sensitive serum antibody tests, but as a negative HLA-DQ type excludes the diagnosis of coeliac disease, testing also for HLA-DQ2 or DQ8 maximises sensitivity and negative predictive values. In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) does not (as of 2015) recommend the use of HLA typing to rule out coeliac disease outside of a specialist setting, for example, in children who are not having a biopsy, or in patients who already have limited gluten ingestion and opt not to have a gluten challenge.
Endoscopy
An upper endoscopy with biopsy of the duodenum (beyond the duodenal bulb) or jejunum is performed to obtain multiple samples (four to eight) from the duodenum. Not all areas may be equally affected; if biopsies are taken from healthy bowel tissue, the result would be a false negative. Even in the same bioptic fragment, different degrees of
damage may be present.Most people with coeliac disease have a small intestine that appears to be normal on endoscopy before the biopsies are examined. However, five findings have been associated with high specificity for coeliac disease: scalloping of the small bowel folds (pictured), paucity in the folds, a mosaic pattern to the mucosa (described as a "cracked-mud" appearance), prominence of the submucosa blood vessels, and a nodular pattern to the mucosa.European guidelines suggest that in children and adolescents with symptoms compatible with coeliac disease, the diagnosis can be made without the need for intestinal biopsy if anti-tTG antibodies titres are very high (10 times the upper limit of normal).Until the 1970s, biopsies were obtained using metal capsules attached to a suction device. The capsule was swallowed and allowed to pass into the small intestine. After x-ray verification of its position, suction was applied to collect part of the intestinal wall inside the capsule. Often-utilised capsule systems were the Watson capsule and the Crosby–Kugler capsule. This method has now been largely replaced by fibre-optic endoscopy, which carries a higher sensitivity and a lower frequency of errors.Capsule endoscopy (CE) allows identification of typical mucosal changes observed in coeliac disease but has a lower sensitivity compared to regular endoscopy and histology. CE is therefore not the primary diagnostic tool for coeliac disease. However, CE can be used for diagnosing T-cell lymphoma, ulcerative jejunoileitis, and adenocarcinoma in refractory or complicated coeliac disease.
Pathology
The classic pathology changes of coeliac disease in the small bowel are categorised by |
Coeliac disease | the "Marsh classification":
Marsh stage 0: normal mucosa
Marsh stage 1: increased number of intra-epithelial lymphocytes (IELs), usually exceeding 20 per 100 enterocytes
Marsh stage 2: a proliferation of the crypts of Lieberkühn
Marsh stage 3: partial or complete villous atrophy and crypt hypertrophy
Marsh stage 4: hypoplasia of the small intestine architectureMarshs classification, introduced in 1992, was subsequently modified in 1999 to six stages, where the previous stage 3 was split in three substages. Further studies demonstrated that this system was not always reliable and that the changes observed in coeliac disease could be described in one of three stages:
A representing lymphocytic infiltration with normal villous appearance;
B1 describing partial villous atrophy; and
B2 describing complete villous atrophy.The changes classically improve or reverse after gluten is removed from the diet. However, most guidelines do not recommend a repeat biopsy unless there is no improvement in the symptoms on diet. In some cases, a deliberate gluten challenge, followed by a biopsy, may be conducted to confirm or refute the diagnosis. A normal biopsy and normal serology after challenge indicates the diagnosis may have been incorrect.In untreated coeliac disease, villous atrophy is more common in children younger than three years, but in older children and adults, it is common to find minor intestinal lesions (duodenal lymphocytosis) with normal intestinal villi.
Other diagnostic tests
At the time of diagnosis, further investigations may be performed to identify complications, such as iron deficiency (by full blood count and iron studies), folic acid and vitamin B12 deficiency and hypocalcaemia (low calcium levels, often due to decreased vitamin D levels). Thyroid function tests may be requested during blood tests to identify hypothyroidism, which is more common in people with coeliac disease.Osteopenia and osteoporosis, mildly and severely reduced bone mineral density, are often present in people with coeliac disease, and investigations to measure bone density may be performed at diagnosis, such as dual-energy X-ray absorptiometry (DXA) scanning, to identify the risk of fracture and need for bone protection medication.
Gluten withdrawal
Although blood antibody tests, biopsies, and genetic tests usually provide a clear diagnosis, occasionally the response to gluten withdrawal on a gluten-free diet is needed to support the diagnosis. Currently, gluten challenge is no longer required to confirm the diagnosis in patients with intestinal lesions compatible with coeliac disease and a positive response to a gluten-free diet. Nevertheless, in some cases, a gluten challenge with a subsequent biopsy may be useful to support the diagnosis, for example in people with a high suspicion for coeliac disease, without a biopsy confirmation, who have negative blood antibodies and are already on a gluten-free diet. Gluten challenge is discouraged before the age of 5 years and during pubertal growth. The alternative diagnosis of non-coeliac gluten sensitivity may be made where there is only symptomatic evidence of gluten sensitivity. Gastrointestinal and extraintestinal symptoms of people with non-coeliac gluten sensitivity can be similar to those of coeliac disease, and improve when gluten is removed from the diet, after coeliac disease and wheat allergy are reasonably excluded.Up to 30% of people often continue having or redeveloping symptoms after starting a gluten-free diet. A careful interpretation of the symptomatic response is needed, as a lack of response in a person with coeliac disease may be due to continued ingestion of small amounts of gluten, either voluntary or inadvertent, or be due to other commonly associated conditions such as small intestinal bacterial overgrowth (SIBO), lactose intolerance, fructose, sucrose, and sorbitol malabsorption, exocrine pancreatic insufficiency, and microscopic colitis, among others. In untreated coeliac disease, these are often transient conditions derived from the intestinal damage. They normally revert or improve several months after starting a gluten-free diet, but may need temporary interventions such as supplementation with pancreatic enzymes, dietary restrictions of lactose, fructose, sucrose or sorbitol containing foods, or treatment with oral antibiotics in the case of associated bacterial overgrowth. In addition to gluten withdrawal, some people need to follow a low-FODMAPs diet or avoid consumption of commercial gluten-free products, which are usually rich in preservatives and additives (such as sulfites, glutamates, nitrates and benzoates) and might have a role in triggering functional gastrointestinal symptoms.
Screening
There is debate as to the benefits of screening. As of 2017, the United States Preventive Services Task Force found insufficient evidence to make a recommendation among those without symptoms. In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) recommend testing for coeliac disease in first-degree relatives of those with the disease already confirmed, in people with persistent fatigue, abdominal or gastrointestinal symptoms, faltering growth, unexplained weight loss or iron, vitamin B12 or folate deficiency, severe mouth ulcers, and with diagnoses of type 1 diabetes, autoimmune thyroid disease, and with newly diagnosed chronic fatigue syndrome and irritable bowel syndrome. Dermatitis herpetiformis is included in other recommendations. The NICE also recommend offering serological testing for coeliac disease in people with metabolic bone disease (reduced bone mineral density or osteomalacia), unexplained neurological disorders (such as peripheral neuropathy and ataxia), fertility problems or recurrent miscarriage, persistently raised liver enzymes with unknown cause, dental enamel defects and with diagnose of Down syndrome or Turner syndrome.Some evidence has found that early detection may decrease the risk of developing health complications, such as osteoporosis, anaemia, and certain types of cancer, neurological disorders, cardiovascular diseases, and reproductive problems. They thus recommend screening in people with certain health problems.Serology has been proposed as a screening measure, because the presence of antibodies would detect some previously undiagnosed cases of coeliac disease and prevent its complications in those people. However, serologic tests have high sensitivity only in people with total villous atrophy and have a very low ability to detect cases with partial villous atrophy or minor intestinal lesions. Testing for coeliac disease may be offered to those with commonly associated conditions.
Treatment
Diet
At present, the only effective treatment is a lifelong gluten-free diet. No medication exists that prevents damage or prevents the body from attacking the gut when gluten is present. Strict adherence to the diet helps the intestines heal, leading to resolution of all symptoms in most cases and, depending on how soon the diet is begun, can also eliminate the heightened risk of osteoporosis and intestinal cancer and in some cases sterility. The diet can be cumbersome; failure to comply with the diet may cause relapse.
Dietitian input is generally requested to ensure the person is aware which foods contain gluten, which foods are safe, and how to have a balanced diet despite the limitations. In many countries, gluten-free products are available on prescription and may be reimbursed by health insurance plans. Gluten-free products are usually more expensive and harder to find than common gluten-containing foods. Since ready-made products often contain traces of gluten, some coeliacs may find it necessary to cook from scratch.The term "gluten-free" is generally used to indicate a supposed harmless level of gluten rather than a complete absence. The exact level at which gluten is harmless is uncertain and controversial. A recent systematic review tentatively concluded that consumption of less than 10 mg of gluten per day is unlikely to cause histological abnormalities, although it noted that few reliable studies had been done. Regulation of the label "gluten-free" varies. In the European Union, the European Commission issued regulations in 2009 limiting the use of "gluten-free" labels for food products to those with less than 20 mg/kg of gluten, and "very low gluten" labels for those with less than 100 mg/kg. In the United States, the FDA issued regulations in 2013 limiting the use of "gluten-free" labels for food products to those with less than 20 ppm of gluten. The current international Codex Alimentarius standard allows for 20 ppm of gluten in so-called "gluten-free" foods.Gluten-free diet improves healthcare-related quality of life, and strict adherence to the diet gives more benefit than incomplete adherence. Nevertheless, gluten-free diet doesnt completely normalise the quality of life.
Vaccination
Even though it is unclear if coeliac patients have a generally increased risk of infectious diseases, they should generally be encouraged to receive all common vaccines against vaccine preventable diseases (VPDs) as the general population. Moreover, some pathogens could be harmful to coeliac patients. According to the European Society for the Study of Celiac Disease (ESsCD), coeliac disease can be associated with hyposplenism or functional asplenia, which could result in impaired immunity to encapsulated bacteria, with an increased risk of such infections. For this reason, patients who are known to be hyposplenic should be administered at least the pneumococcal vaccine. However, the ESsCD states that it is not clear whether vaccination with the conjugated vaccine is preferable in this setting and whether additional vaccination against Haemophilus, meningococcus, and influenza should be considered if not previously given. However, Mårild et al. suggested considering additional vaccination against influenza because of an observed increased risk of hospital admission for this infection in celiac patients.
Refractory disease
Between 0.3% and 10% of affected people have refractory disease, which means that they have persistent villous atrophy on a gluten-free diet despite the lack of gluten exposure for more than 12 months. Nevertheless, inadvertent exposure to gluten is the main cause of persistent villous atrophy, and must be ruled out before a diagnosis of refractory disease is made. People with poor basic education and understanding of gluten-free diet often believe that they are strictly following the diet, but are making regular errors. Also, a lack of symptoms is not a reliable indicator of intestinal recuperation.If alternative causes of villous atrophy have been eliminated, steroids or immunosuppressants (such as azathioprine) may be considered in this scenario.Refractory coeliac disease should not be confused with the persistence of symptoms despite gluten withdrawal caused by transient conditions derived from the intestinal damage, which generally revert or improve several months after starting a gluten-free diet, such as small intestinal bacterial overgrowth, lactose intolerance, fructose, sucrose, and sorbitol malabsorption, exocrine pancreatic insufficiency, and microscopic colitis among others.
Epidemiology
Globally coeliac disease affects between 1 in 100 and 1 in 170 people. Rates, however, vary between different regions of the world from as few as 1 in 300 to as many as 1 in 40. In the United States it is thought to affect between 1 in 1750 (defined as clinical disease including dermatitis herpetiformis with limited digestive tract symptoms) to 1 in 105 (defined by presence of IgA TG in blood donors). Due to variable signs and symptoms it is believed that about 85% of people affected are undiagnosed. The percentage of people with clinically diagnosed disease (symptoms prompting diagnostic testing) is 0.05–0.27% in various studies. However, population studies from parts of Europe, India, South America, Australasia and the USA (using serology and biopsy) indicate that the percentage of people with the disease may be between 0.33 and 1.06% in children (but 5.66% in one study of children of the predisposed Sahrawi people) and 0.18–1.2% in adults. Among those in primary care populations who report gastrointestinal symptoms, the rate of coeliac disease is about 3%. In Australia, approximately 1 in 70 people have the disease. The rate amongst adult blood donors in Iran, Israel, Syria and Turkey is 0.60%, 0.64%, 1.61% and 1.15%, respectively.People of African, Japanese and Chinese descent are rarely diagnosed; this reflects a much lower prevalence of the genetic risk factors, such as HLA-B8. People of Indian ancestry seem to have a similar risk to those of Western Caucasian ancestry. Population studies also indicate that a large proportion of coeliacs remain undiagnosed; this is due, in part, to many clinicians being unfamiliar with the condition and also due to the fact it can be asymptomatic. Coeliac disease is slightly more common in women than in men. A large multicentre study in the U.S. found a prevalence of 0.75% in not-at-risk groups, rising to 1.8% in symptomatic people, 2.6% in second-degree relatives (like grandparents, aunt or uncle, grandchildren, etc.) of a person with coeliac disease and 4.5% in first-degree relatives (siblings, parents or children). This profile is similar to the prevalence in Europe. Other populations at increased risk for coeliac disease, with prevalence rates ranging from 5% to 10%, include individuals with Down and Turner syndromes, type 1 diabetes, and autoimmune thyroid disease, including both hyperthyroidism (overactive thyroid) and hypothyroidism (underactive thyroid).Historically, coeliac disease was thought to be rare, with a prevalence of about 0.02%. The reason for the recent increases in the number of reported cases is unclear. It may be at least in part due to changes in diagnostic practice. There also appears to be an approximately 4.5 fold true increase that may be due to less exposure to bacteria and other pathogens in Western environments. In the United States, the median age at diagnosis is 38 years. Roughly 20 percent of individuals with coeliac disease are diagnosed after 60 years of age.
History
The term "coeliac" is from the Greek κοιλιακός (koiliakós, "abdominal") and was introduced in the 19th century in a translation of what is generally regarded as an Ancient Greek description of the disease by Aretaeus of Cappadocia.Humans first started to cultivate grains in the Neolithic period (beginning about 9500 BCE) in the Fertile Crescent in Western Asia, and, likely, coeliac disease did not occur before this time. Aretaeus of Cappadocia, living in the second century in the same area, recorded a malabsorptive syndrome with chronic diarrhoea, causing a debilitation of the whole body. His "Cœliac Affection" (coeliac from Greek κοιλιακός koiliakos, "abdominal") gained the attention of Western medicine when Francis Adams presented a translation of Aretaeuss work at the Sydenham Society in 1856. The patient described in Aretaeus work had stomach pain and was atrophied, pale, feeble, and incapable of work. The diarrhoea manifested as loose stools that were white, malodorous, and flatulent, and the disease was intractable and liable to periodic return. The problem, Aretaeus believed, was a lack of heat in the stomach necessary to digest the food and a reduced ability to distribute the digestive products throughout the body, this incomplete digestion resulting in diarrhoea. He regarded this as an affliction of the old and more commonly affecting women, explicitly excluding children. The cause, according to Aretaeus, was sometimes either another chronic disease or even consuming "a copious draught of cold water."The paediatrician Samuel Gee gave the first modern-day description of the condition in children in a lecture at Hospital for Sick Children, Great Ormond Street, London, in 1887. Gee acknowledged earlier descriptions and terms for the disease and adopted the same term as Aretaeus (coeliac disease). He perceptively stated: "If the patient can be cured at all, it must be by means of diet." Gee recognised that milk intolerance is a problem with coeliac children and that highly starched foods should be avoided. However, he forbade rice, sago, fruit, and vegetables, which all would have been safe to eat, and he recommended raw meat as well as thin slices of toasted bread. Gee highlighted particular success with a child "who was fed upon a quart of the best Dutch mussels daily." However, the child could not bear this diet for more than one season.Christian Archibald Herter, an American physician, wrote a book in 1908 on children with coeliac disease, which he called "intestinal infantilism". He noted their growth was retarded and that fat was better tolerated than carbohydrate. The eponym Gee-Herter disease was sometimes used to acknowledge both contributions. Sidney V. Haas, an American paediatrician, reported positive effects of a diet of bananas in 1924. This diet remained in vogue until the actual cause of coeliac disease was determined.While a role for carbohydrates had been suspected, the link with wheat was not made until the 1940s by the Dutch paediatrician Dr Willem Karel Dicke. It is likely that clinical improvement of his patients during the Dutch famine of 1944 (during which flour was scarce) may have contributed to his discovery. Dicke noticed that the shortage of bread led to a significant drop in the death rate among children affected by coeliac disease from greater than 35% to essentially zero. He also reported that once wheat was again available after the conflict, the mortality rate soared to previous levels. The link with the gluten component of wheat was made in 1952 by a team from Birmingham, England. Villous atrophy was described by British physician John W. Paulley in 1954 on samples taken at surgery. This paved the way for biopsy samples taken by endoscopy.Throughout the 1960s, other features of coeliac disease were elucidated. Its hereditary character was recognised in 1965. In 1966, dermatitis herpetiformis was linked to gluten sensitivity.
Social and culture
May has been designated as "Coeliac Awareness Month" by several coeliac organisations.
Christian churches and the Eucharist
Speaking generally, the various denominations of Christians celebrate a Eucharist in which a wafer or small piece of sacramental bread from wheat bread is blessed and then eaten. A typical wafer weighs about half a gram. Wheat flour contains around 10 to 13% gluten, so a single communion wafer may have more than 50 mg of gluten, an amount that harms many people with coeliac, especially if consumed every day (see Diet above).
Many Christian churches offer their communicants gluten-free alternatives, usually in the form of a rice-based cracker or gluten-free bread. These include the United Methodist, Christian Reformed, Episcopal, the Anglican Church (Church of England, UK) and Lutheran. Catholics may receive from the Chalice alone, or ask for gluten-reduced hosts; gluten-free ones however are not considered to still be wheat bread and hence invalid matter.
Roman Catholic position
Roman Catholic doctrine states that for a valid Eucharist, the bread to be used at Mass must be made from wheat. Low-gluten hosts meet all of the Catholic Churchs requirements, but they are not entirely gluten free. Requests to use rice wafers have been denied.The issue is more complex for priests. As a celebrant, a priest is, for the fullness of the sacrifice of the Mass, absolutely required to receive under both species. On 24 July 2003, the Congregation for the Doctrine of the Faith stated, "Given the centrality of the celebration of the Eucharist in the life of a priest, one must proceed with great caution before admitting to Holy Orders those candidates unable to ingest gluten or alcohol without serious harm."By January 2004, extremely low-gluten Church-approved hosts had become available in the United States, Italy and Australia. As of July 2017, the Vatican still outlawed the use of gluten-free bread for Holy Communion.
Passover
The Jewish festival of Pesach (Passover) may present problems with its obligation to eat matzo, which is unleavened bread made in a strictly controlled manner from wheat, barley, spelt, oats, or rye. This rules out many other grains that are normally used as substitutes for people with gluten sensitivity, especially for Ashkenazi Jews, who also avoid rice. Many kosher-for-Passover products avoid grains altogether and are therefore gluten-free. Potato starch is the primary starch used to replace the grains.
Spelling
Coeliac disease is the preferred spelling in British English, while celiac disease is typically used in North American English.
Research directions
The search for environmental factors that could be responsible for genetically susceptible people becoming intolerant to gluten has resulted in increasing research activity looking at gastrointestinal infections. Research published in April 2017 suggests that an often-symptomless infection by a common strain of reovirus can increase sensitivity to foods such as gluten.Various treatment approaches are being studied, including some that would reduce the need for dieting. All are still under development, and are not expected to be available to the general public for a while.Three main approaches have been proposed as new therapeutic modalities for coeliac disease: gluten detoxification, modulation of the intestinal permeability, and modulation of the immune response.Using genetically engineered wheat species, or wheat species that have been selectively bred to be minimally immunogenic, may allow the consumption of wheat. This, however, could interfere with the effects that gliadin has on the quality of dough. Alternatively, gluten exposure can be minimised by the ingestion of a combination of enzymes (prolyl endopeptidase and a barley glutamine-specific cysteine endopeptidase (EP-B2)) that degrade the putative 33-mer peptide in the duodenum.Alternative treatments under investigation include the inhibition of zonulin, an endogenous signalling protein linked to increased permeability of the bowel wall and hence increased presentation of gliadin to the immune system. One inhibitor of this pathway is larazotide acetate, which is currently scheduled for phase 3 clinical trials. Other modifiers of other well-understood steps in the pathogenesis of coeliac disease, such as the action of HLA-DQ2 or tissue transglutaminase and the MICA/NKG2D interaction that may be involved in the killing of enterocytes.Attempts to modulate the immune response concerning coeliac disease are mostly still in phase I of clinical testing; one agent (CCX282-B) has been evaluated in a phase II clinical trial based on small-intestinal biopsies taken from people with coeliac disease before and after gluten exposure.Although popularly used as an alternative treatment for people with autism, there is no good evidence that a gluten-free diet is of benefit in the treatment of autism. In the subset of people who have gluten sensitivity there is limited evidence that suggests that a gluten free diet may improve some autistic behaviors.
References
External links
Coeliac disease at Curlie |
Lentigo maligna | Lentigo maligna is where melanocyte cells have become malignant and grow continuously along the stratum basale of the skin, but have not invaded below the epidermis. Lentigo maligna is not the same as lentigo maligna melanoma, as detailed below. It typically progresses very slowly and can remain in a non-invasive form for years.
It is normally found in the elderly (peak incidence in the 9th decade), on skin areas with high levels of sun exposure like the face and forearms. Incidence of evolution to lentigo maligna melanoma is low, about 2.2% to 5% in elderly patients.
It is also known as "Hutchinsons melanotic freckle". This is named for Jonathan Hutchinson. The word lentiginous comes from the latin for freckle.
Relation to melanoma
Lentigo maligna is a histopathological variant of melanoma in situ. Lentigo maligna is sometimes classified as a very early melanoma, and sometimes as a precursor to melanoma.When malignant melanocytes from a lentigo maligna have invaded below the epidermis, the condition is termed lentigo maligna melanoma.
Signs and symptoms
Characteristics include a blue/black stain of skin initially. Skin is thin, about 4-5 cell layers thick, which is often related to aging. Histological features include epidermal atrophy and increased number of melanocytes.
Diagnosis
First dilemma in diagnosis is recognition. As lentigo malignas often present on severely sun-damaged skin, it is frequently found amongst numerous pigmented lesions – thin seborrheic keratoses, lentigo senilis, lentigines. It is difficult to distinguish these lesions with the naked eye alone, and even with some difficulty using dermatoscopy. As the lentigo maligna is often very large, it often merges with, or encompasses other skin tumors – such as lentigines, melanocytic nevi, and seborrheic keratosis.
Second dilemma is the biopsy technique. Even though excisional biopsy (removing the entire lesion) is ideal, and advocated by pathologists; practical reason dictates that this should not be done. These tumors are often large and presenting on the facial area. Excision of such large tumor would be absolutely contraindicated if the lesions identity is uncertain. The preferred method of diagnosis is by using a punch biopsy, allowing the physician to sample multiple full thickness pieces of the tumor at multiple sites. While one section of the tumor might show benign melanocytic nevus, another section might show features concerning for severe cellular atypia. When cellular atypia is noted, a pathologist might indicate that the entire lesion should be removed. It is at this point that one can comfortably remove the entire lesion, and thus confirm the final diagnosis of lentigo maligna. The size of the punch biopsy can vary from 1 mm to 2 mm, but it is preferable to use a punch 1.5 mm or larger. Representative samples of the most atypical parts of the nevus should be biopsied, often guided by dermatoscopy.
Treatment
The best treatment of lentigo maligna is not clear as it has not been well studied.Standard excision is still being done by most surgeons. Unfortunately, the recurrence rate is high (up to 50%). This is due to the ill-defined visible surgical margin, and the facial location of the lesions (often forcing the surgeon to use a narrow surgical margin). The use of dermatoscopy can significantly improve the surgeons ability to identify the surgical margin. The narrow surgical margin used (smaller than the standard of care of 5 mm), combined with the limitation of the standard bread loafing technique of fixed tissue histology - result in a high "false negative" error rate, and frequent recurrences. Margin controlled (peripheral margins) is necessary to eliminate the false negative errors. If breadloafing is utilized, distances from sections should approach 0.1 mm to assure that the method approaches complete margin control.
Where the lesion is on the face and either large or 5mm margins are possible, a skin flap or skin graft may be indicated/required. Grafts have their own risks of failure and poor cosmetic outcomes. Flaps can require extensive incision resulting in long scars and may be better done by plastic surgeons (and possibly better again by those with extensive LM or "suspicious of early malignant melanoma" experience.
Mohs surgery has been done with cure rate reported to be 77%. The "double scalpel" peripheral margin controlled excision method approximates the Mohs method in margin control, but requires a pathologist intimately familiar with the complexity of managing the vertical margin on the thin peripheral sections and staining methods.Some melanocytic nevi, and melanoma-in-situ (lentigo maligna) have resolved with an experimental treatment, imiquimod (Aldara) topical cream, an immune enhancing agent. In view of the very poor cure rate with standard excision, some surgeons combine the two methods: surgical excision of the lesion, then three months treatment of the area with imiquimod cream.
Studies seem to conflict about the level of certainty associated with using imiquimod.Another treatment to be considered where standard margins cannot be achieved or cosmetics are a major consideration is ultra-soft x-ray/grenz-ray radiation.In the very elderly or those with otherwise limited life expectancy, the impact of major day surgery for excision with 5mm margins and large skin flap could be worse than doing nothing or the possibility of failed treatments with imiquimod or Grenz ray.
References
External links
Media related to Lentigo maligna at Wikimedia Commons
== External links == |
Hereditary stomatocytosis | Hereditary stomatocytosis describes a number of inherited, mostly autosomal dominant human conditions which affect the red blood cell and create the appearance of a slit-like area of central pallor (stomatocyte) among erythrocytes on peripheral blood smear. The erythrocytes cell membranes may abnormally leak sodium and/or potassium ions, causing abnormalities in cell volume. Hereditary stomatocytosis should be distinguished from acquired causes of stomatocytosis, including dilantin toxicity and alcoholism, as well as artifact from the process of preparing peripheral blood smears.: 237
Signs and symptoms
Stomatocytosis may present with signs and symptoms consistent with hemolytic anemia as a result of extravascular hemolysis and often intravascular hemolysis. These include fatigue and pallor, as well as signs of jaundice, splenomegaly and gallstone formation from prolonged hemolysis. Certain cases of hereditary stomatocytosis associated with genetic syndromes have additional symptoms that are unrelated to the hemolytic anemia.
Pathophysiology
The two varieties of stomatocytosis classified with respect to cellular hydration status are overhydrated (hydrocytosis) and dehydrated (xerocytosis).: 225–226 Hereditary xerocytosis is characterized by autosomal dominant mutations in PIEZO1, which encodes a cation channel whose mechanosensitive properties enable erythrocytes to deform as they pass through narrow capillaries by decreasing their intracellular volume. More rarely, hereditary xerocytosis may be caused by mutations in KCNN4, which encodes a calcium ion-sensitive potassium channel that mediates the potassium efflux triggered by a rise in intracellular Ca2+ via activated PIEZO1 channels. Hereditary xerocytosis occurs more commonly in African populations, and it exhibits complex interactions with other hereditary alterations of red blood cells, including sickle cell disease and malaria resistance.Osmosis leads to the red blood cell having a constant tendency to swell and burst. This tendency is countered by manipulating the flow of sodium and potassium ions. A pump forces sodium out of the cell and potassium in, and this action is balanced by a process called the passive leak. In overhydrated hereditary stomatocytoses, the passive leak is increased and the erythrocyte becomes swamped with salt and water. The affected erythrocytes have increased osmotic fragility. Haemolytic anaemia results. For as yet unknown reasons, the cells take on the shape of a cup, with a mouth-shaped (stoma) area of central pallor.
Overhydrated hereditary stomatocytosis is frequently linked to mutations in genes that encode components of the band 3 complex, such as RHAG. It is the altered band 3 protein complex which mediates the cation leaks that are characteristic of hydrocytotic hereditary stomatocytosis.Rare cases of hereditary spherocytosis can occur without cation leaks. These include cases of phytosterolemia nonleaky stomatocytosis, a disorder of lipid metabolism associated with mutations in ABCG5 and/or ABCG8, which encode sterol transporters. The resulting abnormal sterol composition of erythrocyte cell membranes causes them to appear as deformed stomatocytes on peripheral blood smear.
Diagnosis
Ektacytometry may be helpful in distinguishing different subtypes of hereditary stomatocytosis.
Variants
Haematologists have identified a number of variants. These can be classified as below.
Overhydrated hereditary stomatocytosis
Dehydrated hereditary stomatocytosis (hereditary xerocytosis; hereditary hyperphosphatidylcholine haemolytic anaemia)
Dehydrated hereditary stomatocytosis with perinatal edema and/or pseudohyperkalemia
Cryohydrocytosis
Blackburn variant
Familial pseudohyperkalaemia (not associated with hemolytic anemia)There are other families that do not fall neatly into any of these classifications.Stomatocytosis is also found as a hereditary disease in Alaskan malamute and miniature schnauzer dogs.
Treatment
At present there is no specific treatment. Many patients with haemolytic anaemia take folic acid (vitamin B9) since the greater turnover of cells consumes this vitamin. During crises transfusion may be required. Clotting problems can occur for which anticoagulation may be needed. Unlike hereditary spherocytosis, splenectomy is contraindicated.
References
Further reading
== External links == |
High-altitude cerebral edema | High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves disorientation, lethargy, and nausea among other symptoms. It occurs when the body fails to acclimatize while ascending to a high altitude.
It appears to be a vasogenic edema (fluid penetration of the blood–brain barrier), although cytotoxic edema (cellular retention of fluids) may play a role as well. Individuals with the condition must immediately descend to a lower altitude or coma and death can occur. Patients are usually given supplemental oxygen and dexamethasone as well.
HACE can be prevented by ascending to heights slowly to allow the body more time to acclimatize. Acetazolamide also helps prevent the condition. Untreated patients usually die within 48 hours. Those who receive treatment may take weeks to fully recover. It is a rare condition, occurring in less than one percent of people who ascend to 4,000 metres (13,000 ft). Although it was first described in 1913, little was known about the cause of the condition until MRI studies were performed in the 1990s.
Signs and symptoms
Early symptoms of HACE generally correspond with those of moderate to severe acute mountain sickness (AMS). Initial symptoms of HACE commonly include confusion, loss of consciousness, fever, ataxia, photophobia, rapid heart beat, lassitude, and an altered mental state. Those affected generally attempt to cease physical activities, regardless of their necessity for survival. Severe headaches develop and people lose the ability to sit up. Retinal venous dilation occurs in 59% of people with HACE. Rarer symptoms include brisk deep tendon reflexes, retinal hemorrhages, blurred vision, extension plantar reflexes, and ocular paralysis. Cranial nerve palsies occur in some unusual cases.In the bestselling 1996 non-fiction book Into Thin Air: A Personal Account of the Mt. Everest Disaster, Jon Krakauer describes the effects of HACE upon Dale Kruse, a forty-four-year-old dentist and one of the members of Scott Fischers team:
Kruse was having an incredibly difficult time simply trying to dress himself. He put his climbing harness on inside out, threaded it through the fly of his wind suit, and failed to fasten the buckle; fortunately, Fischer and Neal Beidleman noticed the screwup before Kruse started to descend. "If hed tried to rappel down the ropes like that," says Beidleman, "he would have immediately popped out of his harness and fallen to the bottom of the Lhotse Face."
"It was like I was very drunk," Kruse recollects. "I couldnt walk without stumbling, and completely lost the ability to think or speak. It was a really strange feeling. Id have some word in my mind, but I couldnt figure out how to bring it to my lips. So Scott and Neal had to get me dressed and make sure my harness was on correctly, then Scott lowered me down the fixed ropes." By the time Kruse arrived in Base Camp, he says, "it was still another three or four days before I could walk from my tent to the mess tent without stumbling all over the place."
Patients with HACE have an elevated white blood cell count, but otherwise their blood count and biochemistry are normal. If a lumbar puncture is performed, it will show normal cerebral spinal fluid and cell counts but an increase in pressure. In one study, CT scans of patients with HACE exhibited ventricle compression and low density in the cerebellum. Only a few autopsies have been performed on fatal cases of HACE; they showed swollen gyri, spongiosis of white matter, and compressed sulci. There was some variation between individuals, and the results may not be typical of HACE deaths.
Mechanism
Most people who travel to high altitudes acclimatize. Acclimatization precludes the development of HACE by maintaining adequate levels of cerebral oxygen. The primary cause of HACE is hypoxia (oxygen deprivation). This occurs after the body is exposed to a low-oxygen environment and before it acclimatizes. The rate of change from a normal oxygen environment and how little oxygen is in the new environment can be used to predict the chance of developing HACE. Prolonged exertion in low oxygen also causes serious hypocapnia, lower carbon dioxide in the bloodstream, which may play a role in HACE. These factors cause the brain to swell with fluid, resulting in severe impairment. If the swelling is untreated, it causes death by brain herniation.The brain swelling is likely a result of vasogenic edema, the penetration of the blood–brain barrier by fluids. This process has been observed in MRI studies. Hypoxia increases extracellular fluid, which passes through the vasogenic endothelium in the brain. The leaking may be caused by increased pressure, or it may be caused by inflammation that makes the endothelium vulnerable to leaking. An MRI study found microhemorrhages in the corpus callosum of HACE patients, and hypoxia may also cause microvascular permeability. It has been hypothesized that vascular endothelial growth factor may cause the vascular permeability at the root of HACE. MRI scans of patients with HACE showed increased T2 in the corpus callosum, although grey matter was unchanged. This demonstrated that the blood-brain barrier was broken by cerebral blood vessels, thus interfering with white matter metabolism. Another study looked at the brains of people with HACE several months after their recovery; it showed hemosiderin deposits in the corpus callosum, evidence of vascular permeability.While there is strong evidence that vasogenic edema plays a major role in HACE, cytotoxic edema, cellular retention of fluids, may contribute as well. Cytotoxic edema may be caused by the failure of cellular ion pumps, which results from hypoxia. Then intracellular sodium and osmolarity increase, and there is an influx of water that causes cellular swelling. After the failure of the ATPase pumps, free radicals form and cause damage that complicates the edema. Evidence against cytotoxic edema includes the high levels of hypoxemia (low bloodstream oxygen) needed to cause it.It is not known why some are more vulnerable to HACE than others. One theory is that variations in brain size play a role, but the increase in brain volume from edema does not likely cause cranial vault impingement. The presence of large sulci indicate the condition may be influenced by the brain tightly fitting. Elevated intracranial pressure is generally accepted to be a late effect of HACE. High central venous pressure may also occur late in the conditions progression.One study demonstrated that normal autorelation of cerebral blood flow does not cause HACE. What role the sympathetic nervous system plays in determining who gets HACE is unclear, but it may have an effect.Another theory about the cause of HACE is that hypoxia may induce nitrous oxide synthase. Vasodilation is caused by the release of nitric oxide and adenosine. This in turn can increase vascular permeability and causes edema. This may combine with low levels of cytokines to cause HACE.
Diagnosis
Generally, high-altitude pulmonary edema (HAPE) or AMS precede HACE. In patients with AMS, the onset of HACE is usually indicated by vomiting, headache that does not respond to non-steroidal anti-inflammatory drugs, hallucinations, and stupor. In some situations, however, AMS progresses to HACE without these symptoms. HACE must be distinguished from conditions with similar symptoms, including stroke, intoxication, psychosis, diabetic symptoms, meningitis, or ingestion of toxic substances. It should be the first diagnosis ruled out when sickness occurs while ascending to a high altitude.
Prevention
HACE is generally preventable by ascending gradually with frequent rest days while climbing or trekking. Not ascending more than 1,000 metres (3,300 ft) daily and not sleeping at a greater height than 300 metres (980 ft) more than the previous night is recommended. The risk of developing HACE is diminished if acetazolamide or dexamethasone are administered. Generally, the use of acetazolamide is preferred, but dexamethasone can be used for prevention if there are side effects or contraindications. Some individuals are more susceptible to HACE than others, and physical fitness is not preventive. Age and sex do not by themselves affect vulnerability to HACE.
Treatment
Patients with HACE should be brought to lower altitudes and provided supplemental oxygen, and rapid descent is sometimes needed to prevent mortality. Early recognition is important because as the condition progresses patients are unable to descend without assistance. Dexamethasone should also be administered, although it fails to ameliorate some symptoms that can be cured by descending to a lower altitude. It can also mask symptoms, and they sometimes resume upon discontinuation. Dexamethasones prevention of angiogenesis may explain why it treats HACE well. Three studies that examined how mice and rat brains react to hypoxia gave some credence to this idea.If available, supplemental oxygen can be used as an adjunctive therapy, or when descent is not possible. FiO2 should be titrated to maintain arterial oxygen saturation of greater than 90%, bearing in mind that oxygen supply is often limited in high altitude clinics/environments.In addition to oxygen therapy, a portable hyperbaric chamber (Gamow bag) can by used as a temporary measure in the treatment of HACE. These devices simulate a decrease in altitude of up to 7000 ft, but they are resource intensive and symptoms will often return after discontinuation of the device. Portable hyperbaric chambers should not be used in place of descent or evacuation to definitive care.Diuretics may be helpful, but pose risks outside of a hospital environment. Sildenafil and tadalafil may help HACE, but there is little evidence of their efficacy. Theophylline is also theorized to help the condition.Although AMS is not life-threatening, HACE is usually fatal within 24 hours if untreated. Without treatment, the patient will enter a coma and then die. In some cases, patients have died within a few hours, and a few have survived for two days. Descriptions of fatal cases often involve climbers who continue ascending while experiencing the conditions symptoms.
Prognosis
Recovery varies between days and weeks, but most recover in a few days. After the condition is successfully treated, it is possible for climbers to reascend. Dexamethesone should be discontinued, but continual acetazolamide is recommended. In one study, it took patients between one week and one month to display a normal CT scan following HACE.
Epidemiology
HACE occurs in 0.5% to 1% of people who climb or trek between 4,000 metres (13,000 ft) and 5,000 metres (16,000 ft). In some unusual cases, up to 30% of members of expeditions have had the condition. The condition is seldom seen below 3,000 metres (9,800 ft), but in some rare cases it has developed as low as 2,500 metres (8,200 ft). The condition generally does not occur until an individual has spent 48 hours at an altitude of 4,000 metres (13,000 ft).
History
HACE was first described by a medical officer stationed in Chile in 1913, but few took note of it. Later, access to air travel made the condition more common because it allowed more people access to high mountains, such as those in the Himalayas. One early description of HACE may have been published in 1969 after a group of Indian soldiers made a rapid ascent to almost 6,000 metres (20,000 ft). It is not definitely established whether they had HACE or acute decompression sickness. MRI has been used to study the effects of high altitude on the brain, providing the best evidence about the condition. A 1998 MRI study of nine climbers with HACE clearly demonstrated vasogenic edema.Data about HACE are lacking because it generally occurs in remote areas, far from hospitals and is generally rare. It is uncommon for doctors to be able to study victims within six days of the conditions development. Animal models of HACE have not been developed. Several genes are being examined for the role they may play in the development of the condition.Increased education and helicopter capabilities have combined to cut the number of deaths from the condition. Symptoms of HACE have been reported in many cases of deaths while descending Mount Everest, although HACE may not be the only problem they experienced. HACE also posed a threat to workers on the Qinghai–Tibet Railway.
References
Bibliography
Bärtsch, Peter; Swenson, Erik (2013). "Acute High-Altitude Illnesses". The New England Journal of Medicine. 368 (24): 2294–302. doi:10.1056/NEJMcp1214870. PMID 23758234.
Imray, Chris; Wright, Alex; Subudhi, Andrew; Roach, Robert (2010). "Acute Mountain Sickness: Pathophysiology, Prevention, and Treatment". Progress in Cardiovascular Diseases. 52 (6): 467–484. doi:10.1016/j.pcad.2010.02.003. PMID 20417340.
Rosenberg, Gary (2012). Molecular Physiology and Metabolism of the Nervous System (5 ed.). Oxford University Press. ISBN 978-0-19-539427-6.
Schoene, Robert (2008). "Illnesses at High Altitude". Chest. 134 (2): 402–16. doi:10.1378/chest.07-0561. PMID 18682459.
Schoene, Robert; Milledge, James; Luks, Andrew; West, John (2012). High Altitude Medicine and Physiology. CRC Press. ISBN 978-1-4441-5432-0.
Wilson, Mark; Newman, Stanton; Imray, Chris (2009). "The Cerebral Effects of Ascent to High Altitudes". Lancet Neurology. 8 (2): 175–91. doi:10.1016/S1474-4422(09)70014-6. PMID 19161909. S2CID 268646.
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Compensatory hyperhidrosis | Compensatory hyperhidrosis is a form of neuropathy. It is encountered in patients with myelopathy, thoracic disease, cerebrovascular disease, nerve trauma or after surgeries. The exact mechanism of the phenomenon is poorly understood. It is attributed to the perception in the hypothalamus (brain) that the body temperature is too high. The sweating is induced to reduce body heat.
Excessive sweating due to nervousness, anger, previous trauma or fear is called hyperhidrosis.
Compensatory hyperhidrosis is the most common side effect of endoscopic thoracic sympathectomy, a surgery to treat severe focal hyperhidrosis, often affecting just one part of the body. It may also be called rebound or reflex hyperhidrosis. In a small number of individuals, compensatory hyperhidrosis following sympathectomy is disruptive, because affected individuals may have to change sweat-soaked clothing two or three times a day.
According to Dr. Hooshmand, sympathectomy permanently damages the temperature regulatory system. The permanent destruction of thermoregulatory function of the sympathetic nervous system causes latent complications, e.g., RSD in contralateral extremity.Following surgery for axillary (armpit), palmar (palm) hyperhidrosis (see focal hyperhidrosis) and blushing, the body may sweat excessively at untreated areas, most commonly the lower back and trunk, but can be spread over the total body surface below the level of the cut. The upper part of the body, above the sympathetic chain transection, the body becomes anhidriotic, where the patient is unable to sweat or cool down, which further compromises the bodys thermoregulation and can lead to elevated core temperature, overheating and hyperthermia. Below the level of the sympathetic chain interruption, body temperature is significantly lower, creating a stark contrast that can be observed on thermal images. The difference in temperatures between the sympathetically under- and overactive regions can be as high as 10 Celsius.
Variations
Gustatory sweating or Freys syndrome is another presentation of autonomic neuropathy. Gustatory sweating is brought on while eating, thinking or talking about food that produces a strong salivary stimulus. It is thought that ANS fibres to salivary glands have become connected in error with the sweat glands after nerve regeneration. Apart from sweating in the anhidriotic area of the body, it can produce flushing, goosebumps, drop of body temperature - vasoconstriction and paresthesia. Aberrant gustatory sweating follows up to 73% of surgical sympathectomies and is particularly common after bilateral procedures. Facial sweating during salivation has also been described in diabetes mellitus, cluster headache, following chorda tympani injury, and following facial herpes zoster.Phantom sweating is another form of autonomic neuropathy. It can be observed in patients with nerve damage (following accidents), diabetes mellitus and as a result of sympathectomy. Phantom sweating is a sensation that one is sweating, while the skin remains dry. Affected people can not distinguish whether it is real sweating or just a sensation. The phenomena is experienced in the anhidriotic, denervated area of the body, presenting an abnormal sympathetic nervous system function.
Mechanism
The term compensatory is largely misleading, as it indicates that there is a compensatory mechanism that takes effect after sympathectomy, in which the body redirects the sweating from the palms or face to other areas of the body. Sweating after sympathetic surgery is a reflex cycle between the sympathetic system and the anterior portion of the hypothalamus. Reflex sweating will not happen if hand sweating can be stopped without interrupting sympathetic tone to the human brain.Compensatory hyperhidrosis is aberrant sympathetic nervous system functioning. The only study evaluating the total body sweat prior and shortly after sympathectomy concluded that patients produce more sweat after the surgery, just not so much in the areas treated by the surgery.
Epidemiology
Of people that have a sympathectomy, it is impossible to predict who will end up with a more severe version of this disorder, as there is no link to gender, age or weight. There is no test or screening process that would enable doctors to predict who is more susceptible.
== References == |
Desquamative gingivitis | Desquamative gingivitis is an erythematous (red), desquamatous (shedding) and ulcerated appearance of the gums. It is a descriptive term and can be caused by several different disorders.
Signs and symptoms
Desquamative gingivitis involves lesions of the free and attached gingiva. Unlike plaque-induced inflammation of the gums (normal marginal gingivitis), desquamative gingivitis extends beyond the marginal gingiva, involving the full width of the gingiva and sometimes the alveolar mucosa. The term "full width gingivitis" usually refers to the oral lesions of orofacial granulomatosis however. The color is another dissimilarity between typical marginal gingivitis and desquamative gingivitis, in the latter it is dusky red. Plasma cell gingivitis is another form of gingivitis which affects both the attached and free gingiva.
Cause
Caused by various autoimmune diseases as well as allergies. Erosive lichen planus, mucous membrane pemphigoid, pemphigus vulgaris, erythema exsudativum multiforme and lupus erythematosus.
Diagnosis
Differential diagnosis
Desquamative gingivitis is a descriptive clinical term, not a diagnosis. Dermatologic conditions cause about 75% of cases of desquamative gingivitis, and over 95% of the dermatologic cases are accounted for by either oral lichen planus or cicatricial pemphigoid. The exact cause of desquamative gingivitis cannot be determined about a third of cases.
Oral lichen planus
Cicatricial pemphigoid or less commonly bullous pemphigoid
Pemphigus vulgaris
Linear immunoglobulin A disease
Dermatitis herpetiformis
Lupus erythematosus
Chronic ulcerative stomatitis
Chronic bacterial, fungal, and viral infections
Reactions to medications, mouthwashes, and chewing gumRare causes include:
Crohn’s disease
Sarcoidosis
Leukemia
factitious (self inflicted) lesions
Squamous cell carcinoma (can be mistaken for desquamative gingivitis)
Treatment
Improving oral hygiene
Minimising irritation of the lesions
Specific therapies for the underlying disease (where available)
Local or systemic immunosuppressive or dapsone therapy (notably not corticosteroids)
History
This condition was first recognized and reported in 1894, but the term desquamative gingivitis was not coined until 1932.
References
== External links == |
Goldenhar syndrome | Goldenhar syndrome is a rare congenital defect characterized by incomplete development of the ear, nose, soft palate, lip and mandible on usually one side of the body. Common clinical manifestations include limbal dermoids, preauricular skin tags and strabismus. It is associated with anomalous development of the first branchial arch and second branchial arch.The term is sometimes used interchangeably with hemifacial microsomia, although this definition is usually reserved for cases without internal organ and vertebrae disruption.
It affects between 1 in 3,500 and 1 in 5,600 live births, with a male-to-female ratio of 3:2.
Signs and symptoms
Chief markers of Goldenhar syndrome are incomplete development of the ear, nose, soft palate, lip, and mandible on usually one side of the body. Additionally, some patients will have growing issues with internal organs, especially heart, kidneys and lungs. Typically, the organ will either not be present on one side or will be underdeveloped. While it is more usual for there to be problems on only one side, it has been known for defects to occur bilaterally (approximate incidence 10% of confirmed GS cases).Other problems can include severe scoliosis (twisting of the vertebrae), limbal dermoids and hearing loss (see hearing loss with craniofacial syndromes), and deafness or blindness in one or both ears/eyes. Granulosa cell tumors may be associated as well.
Causes
The cause of Goldenhar syndrome is largely unknown. However, it is thought to be multifactorial, although there may be a genetic component, which would account for certain familial patterns. It has been suggested that there is a branchial arch development issue late in the first trimester.An increase in Goldenhar syndrome in the children of Gulf War veterans has been suggested, but the difference was shown to be statistically insignificant.
Diagnosis
Diagnosis is based on clinical features. General features include unilateral facial asymmetry. Ocular abnormalities include limbal dermoids and strabismus. Otorhinolaryngological features include microtia, partial to complete atresia of external acoustic meatus, preauricular skin tags, deafness, and macrosomia. Skeletal abnormalities include mandibular deformities, scoliosis. Other organ abnormalities include cardiac defects and renal abnormalities.
Treatment
Treatment is usually confined to such surgical intervention as may be necessary to help the child to develop e.g. jaw distraction/bone grafts, ocular dermoid debulking (see below), repairing cleft palate/lip, repairing heart malformations or spinal surgery. Some patients with Goldenhar syndrome will require assistance as they grow by means of hearing aids or glasses. Stem cell grafting (womb tissue grafting) has been successfully used to "reprogram" eye dermoids, effectively halting the regrowth of eye dermoids. These tissues that grow on the eye are "mis-programmed" cells (sometimes tooth or nail cells instead of eye cells).
Epidemiology
Prevalence ranges from 1 in 3,500 to 5,600 live births. Male-female ratio is found to be 3:2.
Eponym
The condition was documented in 1952 by Belgian–American ophthalmologist Maurice Goldenhar (1924–2001).
References
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Oculopharyngodistal myopathy | Oculopharyngodistal myopathy is a rare genetic disorder characterized by progressive muscle weakness affecting various parts of the body.
Signs and symptoms
People with this condition exhibit symptoms susch as progressive muscle weakness affecting the eyes, face, and pharynx which consequently results in blepharoptosis, ophthalmoparesis, atrophy of the facial muscles, dysphagia, dysarthria, and muscle weakness and atrophy of the upper and lower distal limbs. These symptoms usually start during adulthood.On rare cases, hearing loss, severe proximal weakness and/or unilateral muscle weakness.
Complications
Complications vary depending on the symptoms and their severity, for example, muscle weakness might leave people unable to work on manual labor jobs.
Diagnosis
This condition can be diagnosed through physical examination and sequencing of the genes associated with the condition.
Genetics
There are four known genetic causes of this disorder:
1. Trinucleotide repeat expansion located in the 5-prime untranslated region of the LRP12 gene. (CGG)2. Trinucleotide repeat expansion located in the 5-prime untranslated region of the G1PC gene. (GGC)3. Trinucleotide repeat expansion located in the non-coding region of the NOTCH2NLC gene. (CGG)4. Trinucleotide repeat expansion located in the 5-prime untranslated region of the RILPL1 gene.All of these mutations are inherited/expressed in an autosomal dominant manner, meaning that for a person to exhibit the symptoms of this condition, they must inherit a copy of the mutated allele from at least one parent, although in other cases, the mutation might not have been inherited, but rather the result of a spontaneous error.
Prevalence
According to three OMIM pages for this condition, about 78 families across the world are known to have this condition, this includes both familial and sporadic cases with confirmed genetic basis (thus, potential to spread to offspring and turn it into a familial case). Most (if not all) of these families are of East Asian (Japanese and Chinese in particular) descent.
OMIM divided this condition into subtypes due to the different genetic causes and slightly different symptoms the three of them exhibit.
The following list comprises the number of families described in medical literature each of these subtypes has:
# 164310OCULOPHARYNGODISTAL MYOPATHY 1; OPDM1: 37 families
# 618940OCULOPHARYNGODISTAL MYOPATHY 2; OPDM2: 30 families
# 619473OCULOPHARYNGODISTAL MYOPATHY 3; OPDM3: 11 families.
History
This condition was first discovered in 1977 by E Sayotoshi et al. when they described an unspecified amount of people from 4 families who suffered from an "autosomal dominant, heredofamilial myopathy" which consisted in "slowly progressive ptosis and extraocular palsy, and weakness of the masseter, facial, and bulbar muscles, as well as distal involvement of the limbs starting around 40 years of age or later."In 2019, Hiroyuki Ishiura et al. discovered a heterozygous trinucleotide repeat expansion in the 5-prime untranslated region of the LRP12 gene in 5 patients with the condition, the trinucleotide sequence consisted of one C (cytosine) and two Gs (guanine). By using Southern blot analysis of leukocytes, it was revealed that the patients (on average) had expanded repeats ranging from 280 to 380 bp which was the equivalent of more than 90 repeats of CGG, when the LRP12 gene of 1,000 control subjects was tested with the same method, it was revealed that they (on average) had between 13 and 45 repeat units of the same nucleotides, with the exception of two out of the 1,000 controls, who had expanded repeats without any symptoms of the condition.In 2020, Deng et al. discovered beterozygous trinucleotide repeat expansions in the 5-prime untranslayed region of the GIPC1 gene of multiple affected members from 3 Chinese families, this trinucleotide sequence consisted of two Gs (guanine) and one C (cytosine). This mutation was later identified by the same team of researchers in 16 patients, of which 9 were Chinese and 7 were Japanese.In 2020, Ogasawara et al. discovered heterozygous trinucleotide repeat expansions in the non-coding region of the NOTCH2NLC gene of 7 un-related Japanese patients with the condition, the trinucleotide sequence consisted of one C (cytosine) and two Gs (guanine), all 5 patients had more than 100 repeats of the trinucleotide sequence, one of which had two expansions consisting of 217 and 674 repeats.
See also
Myopathy
Familial episodic pain syndrome
== References == |
Optic papillitis | Optic papillitis is a specific type of optic neuritis. Inflammation of the optic nerve head is called "papillitis" or "intraocular optic neuritis"; inflammation of the orbital portion of the nerve is called "retrobulbar optic neuritis" or "orbital optic neuritis". It is often associated with substantial losses in visual fields, pain on moving the globe, and sensitivity to light pressure on the globe. It is often an early sign of multiple sclerosis.Papillitis may have the same appearance as papilledema. However, papillitis may be unilateral, whereas papilledema is almost always bilateral. Papillitis can be differentiated from papilledema by an afferent pupillary defect (Marcus Gunn pupil), by its greater effect in decreasing visual acuity and color vision, and by the presence of a central scotoma. Papilledema that is not yet chronic will not have as dramatic an effect on vision. Because increased intracranial pressure can cause both papilledema and a sixth (abducens) nerve palsy, papilledema can be differentiated from papillitis if esotropia and loss of abduction are also present. However, esotropia may also develop secondarily in an eye that has lost vision from papillitis. Retrobulbar neuritis, an inflamed optic nerve, but with a normal-appearing nerve head, is associated with pain and the other findings of papillitis. Pseudopapilledema is a normal variant of the optic disk, in which the disk appears elevated, with indistinct margins and a normal vascular pattern. Pseudopapilledema sometimes occurs in hyperopic individuals.
Workup of the patient with papillitis includes lumbar puncture and cerebrospinal fluid analysis. B henselae infection can be detected by serology. MRI is the preferred imaging study. An abnormal MRI is associated with a worse visual outcome.
References
== External links == |
Progressive supranuclear palsy | Progressive supranuclear palsy (PSP) is a late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and cognitive impairment. PSP may be mistaken for other neurodegenerative diseases such as Parkinsons, frontotemporal dementia and Alzheimers. The cause of the condition is uncertain, but involves accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases.PSP affects about six people per 100,000. The first symptoms typically occur at 60–70 years of age. Males are slightly more likely to be affected than females. No association has been found between PSP and any particular race, location, or occupation.
Signs and symptoms
The initial symptoms in two-thirds of cases are loss of balance, lunging forward when mobilizing, fast walking, bumping into objects or people, and falls. Dementia symptoms are also initially seen in about one in five cases of frontotemporal dementia.Other common early symptoms are changes in personality, general slowing of movement, and visual symptoms. The most common behavioural symptoms in patients with PSP include apathy, disinhibition, anxiety, and dysphoria.Later symptoms and signs can include, but do not necessarily include dementia (typically including loss of inhibition and ability to organize information), slurring of speech, difficulty swallowing, and difficulty moving the eyes, particularly in the vertical direction. The latter accounts for some of the falls experienced by these patients, as they find it difficult to look up or down.Some of the other signs are poor eyelid function, contracture of the facial muscles, a backward tilt of the head with stiffening of the neck muscles, sleep disruption, urinary incontinence, and constipation. Some patients retain full cognitive function up to the end.The visual symptoms are of particular importance in the diagnosis of this disorder. Patients typically complain of difficulty reading due to the inability to look down well. The ophthalmoparesis experienced by these patients mainly concerns voluntary eye movement and the inability to make vertical saccades, which is often worse with downward saccades. Patients tend to have difficulty looking down (a downgaze palsy) followed by the addition of an upgaze palsy. This vertical gaze paresis will correct when the examiner passively rolls the patients head up and down as part of a test for the oculocephalic reflex. Involuntary eye movement, as elicited by Bells phenomenon, for instance, may be closer to normal. On close inspection, eye movements called "square-wave jerks" may be visible when the patient fixes at distance. These are fine movements, that can be mistaken for nystagmus, except that they are saccadic in nature, with no smooth phase. Although healthy individuals also make square-wave jerk movements, PSP patients make slower square-wave jerk movements, with smaller vertical components. Assessment of these square-wave jerks and diminished vertical saccades is especially useful for diagnosing progressive supranuclear palsy, because these movements set PSP patients apart from other parkinsonian patients. Difficulties with convergence (convergence insufficiency), where the eyes come closer together while focusing on something near, like the pages of a book, is typical. Because the eyes have trouble coming together to focus at short distances, the patient may complain of diplopia (double vision) when reading.A characteristic facial appearance known as “procerus sign”, with a wide-eye stare, furrowing of forehead with a frowning expression and deepening of other facial creases is diagnostic of PSP.
Cause
The cause of PSP is unknown. Fewer than 1% of those with PSP have a family member with the same disorder. A variant in the gene for tau protein called the H1 haplotype, located on chromosome 17 (rs1800547), has been linked to PSP. Nearly all people with PSP received a copy of that variant from each parent, but this is true of about two-thirds of the general population. Therefore, the H1 haplotype appears to be necessary but not sufficient to cause PSP. Other genes, as well as environmental toxins, are being investigated as other possible contributors to the cause of PSP.Additionally, the H2 haplotype, combined with vascular dysfunction, seems to be a factor of vascular progressive supranuclear palsy.Besides tauopathy, mitochondrial dysfunction seems to be a factor involved in PSP. Especially, mitochondrial complex I inhibitors (such as acetogenins and quinolines contained in Annonaceae, as well as rotenoids) are implicated in PSP-like brain injuries.
Pathophysiology
The affected brain cells are both neurons and glial cells. The neurons display neurofibrillary tangles (NFTs), which are clumps of tau protein, a normal part of a brain cells internal structural skeleton. These tangles are often different from those seen in Alzheimers disease, but may be structurally similar when they occur in the cerebral cortex. Their chemical composition is usually different, however, and is similar to that of tangles seen in corticobasal degeneration. Tufts of tau protein in astrocytes, or tufted astrocytes, are also considered diagnostic. Unlike globose NFTs, they may be more widespread in the cortex. Lewy bodies are seen in some cases, but whether this is a variant or an independent co-existing process is not clear, and in some cases, PSP can coexist with corticobasal degeneration, Parkinsons, and/or Alzheimers disease, particularly with older patients.The principal areas of the brain affected are the:
basal ganglia, particularly the subthalamic nucleus, substantia nigra, and globus pallidus
brainstem, particularly the tectum (the portion of the midbrain where "supranuclear" eye movement resides), as well as dopaminergic nuclei.
cerebral cortex, particularly that of the frontal lobes and the limbic system (similarly to frontotemporal degeneration)
dentate nucleus of the cerebellum
spinal cord, particularly the area where some control of the bladder and bowel residesSome consider PSP, corticobasal degeneration, and frontotemporal dementia to be variations of the same disease. Others consider them separate diseases. PSP has been shown occasionally to co-exist with Picks disease.
Diagnosis
Magnetic resonance imaging (MRI) is often used to diagnose PSP. MRI may show atrophy in the midbrain with preservation of the pons giving a "hummingbird" sign appearance and Mickey Mouse sign.
Types
Based on the pathological findings in confirmed cases of PSP, it is divided into the following categories:
classical Richardson syndrome (PSP-RS)
PSP-parkinsonism (PSP-P) and PSP-pure akinesia with gait freezing (PSP-PAGF)
frontal PSP, PSP-corticobasal syndrome (PSP-CBS), PSP-behavioural variant of frontotemporal dementia (PSP-bvFTD) and PSP-progressive non-fluent aphasia (PSP-PNFA)
PSP-C
PSP induced by AnnonaceaeRichardson syndrome is characterized by the typical features of PSP. In PSP-P features of Parkinson’s Disease overlap with the clinical presentation of PSP and follows a more benign course. In both PSP-P and PSP- PAGF distribution of abnormal tau is relatively restricted to the brain stem. Frontal PSP initially presents with behavioral and cognitive symptoms, with or without ophthalmoparesis and then evolve into typical PSP. The phenotypes of PSP-P and PSP-PAGF are sometimes referred as the ‘brain stem’ variants of PSP, as opposed to the ‘cortical’ variants which present with predominant cortical features including PSP-CBS, PSP-bvFTD, and PSP-PNFA. Cerebellar ataxia as the predominant early presenting feature is increasingly recognized as a very rare subtype of PSP (PSP-C) which is associated with severe neuronal loss with gliosis and higher densities of coiled bodies in the cerebellar dentate nucleus.
Differential diagnosis
PSP is frequently misdiagnosed as Parkinsons disease because they both involve slowed movements and gait difficulty, with PSP being one of a collection of diseases referred to as Parkinson plus syndromes. Both Parkinsons and PSP have an onset in late middle age and involve slowing and rigidity of movement. However, several distinguishing features exist. Tremor is very common with Parkinsons, but rare with PSP. Speech and swallowing difficulties are more common and severe with PSP and the abnormal eye movements of PSP are essentially absent with PD. A poor response to levodopa along with symmetrical onset can also help differentiate PSP from PD. Patients with the Richardson variant of PSP tend to have an upright posture or arched back, as opposed to the stooped-forward posture of other Parkinsonian disorders, although PSP-Parkinsonism (see below) can demonstrate a stooped posture. Early falls are also more common with PSP, especially with Richardson syndrome.PSP can also be misdiagnosed as Alzheimers disease because of the behavioral changes.Chronic traumatic encephalopathy shows many similarities with PSP.
Management
Treatment
No cure for PSP is known, and management is primarily supportive. PSP cases are often split into two subgroups, PSP-Richardson, the classic type, and PSP-Parkinsonism, where a short-term response to levodopa can be obtained. Dyskinesia is an occasional but rare complication of treatment. Amantadine is also sometimes helpful. After a few years the Parkinsonian variant tends to take on Richardson features. Other variants have been described. Botox can be used to treat neck dystonia and blepharospasm, but this can aggravate dysphagia.Two studies have suggested that rivastigmine may help with cognitive aspects, but the authors of both studies have suggested a larger sampling be used. There is some evidence that the hypnotic zolpidem may improve motor function and eye movements, but only from small-scale studies.
Rehabilitation
Patients with PSP usually seek or are referred to occupational therapy, speech-language pathology for motor speech changes typically a spastic-ataxic dysarthria, and physical therapy for balance and gait problems with reports of frequent falls. Evidence-based approaches to rehabilitation in PSP are lacking and, currently, the majority of research on the subject consists of case reports involving only a small number of patients.Case reports of rehabilitation programs for patients with PSP generally include limb-coordination activities, tilt-board balancing, gait training, strength training with progressive resistive exercises, and isokinetic exercises and stretching of the neck muscles. While some case reports suggest that physiotherapy can offer improvements in balance and gait of patients with PSP, the results cannot be generalized across all PSP patients, as each case report followed only one or two patients. The observations made from these case studies can be useful, however, in helping to guide future research concerning the effectiveness of balance and gait training programs in the management of PSP.Individuals with PSP are often referred to occupational therapists to help manage their condition and to help enhance their independence. This may include being taught to use mobility aids. Due to their tendency to fall backwards, the use of a walker, particularly one that can be weighted in the front, is recommended over a cane. The use of an appropriate mobility aid helps to decrease the individual’s risk of falls and makes them safer to ambulate independently in the community.
Due to their balance problems and irregular movements, individuals need to spend time learning how to safely transfer in their homes and in the community. This may include rising from and sitting in chairs safely.Due to the progressive nature of this disease, all individuals eventually lose their ability to walk and will need to progress to using a wheelchair. Severe dysphagia often follows, and at this point death is often a matter of months.
Prognosis
No effective treatment or cure has been found for PSP, although some of the symptoms can respond to nonspecific measures. The poor prognosis is predominantly attributed to the serious impact this condition has on the quality of life. The average age at symptoms onset is 63 and survival from onset averages seven years with a wide variance. Pneumonia is a frequent cause of death.
History
In 1877, Charcot described a 40-year-old woman who had rigid-akinetic parkinsonism, neck dystonia, dysarthria, and eye-movement problems. Chavany and others reported the clinical and pathologic features of a 50-year-old man with a rigid and akinetic form of parkinsonism with postural instability, neck dystonia, dysarthria, and staring gaze in 1951.
Progressive supranuclear palsy was first described as a distinct disorder by neurologists John Steele, John Richardson, and Jerzy Olszewski in 1963. They recognized the same clinical syndrome in 8 patients and described the autopsy findings in 6 of them in 1963.Progressive supranuclear palsy was not a “new” disease in 1963, as 22 well-documented case reports had been identified in the neurologic literature between 1877 and 1963. The unique frontal lobe cognitive changes of progressive supranuclear palsy (apathy, loss of spontaneity, slowing of thought processes, and loss of executive functions) were first described by Albert and colleagues in 1974.
Society and culture
There are several organizations around the world that support PSP patients and the research into PSP and related diseases, such as corticobasal degeneration (CBD) and multiple system atrophy (MSA).
Canada: PSP Society of Canada, a federally registered non-profit organization which serves patients and families dealing with PSP, CBD and MSA, set up in 2017 through the help of CurePSP in the USA
France: Association PSP France, a nonprofit patient association set up in 1996 through the help of PSPA in the UK. It also gives support to French speaking patients in Quebec, Morocco, Algeria, Belgium and Lebanon
UK: PSPA, a national charity for information, patient support and research of PSP and CBD, set up in 1995
Ireland: PSPAI, a body which aims to get PSP better known
US: CurePSP, a nonprofit organization for promoting awareness, care and research of PSP, CBD, MSA "and other prime of life neurodegenerative diseases"
In popular culture
In the 2020 American musical comedy-drama television series, Zoeys Extraordinary Playlist, the title characters father (Mitch Clarke, played by Peter Gallagher) has PSP and dies in the final episode of the first season.American singer Linda Ronstadt was diagnosed with PSP in 2019, subsequent to an initial diagnosis of Parkinsons disease in 2014.
See also
Lytico-bodig disease (Parkinsonism-Dementia Complex of Guam)
Annonacin
== References == |
8p23.1 duplication syndrome | 8p23.1 duplication syndrome is a rare genetic disorder caused by a duplication of a region from human chromosome 8. This duplication syndrome has an estimated prevalence of 1 in 64,000 births and is the reciprocal of the 8p23.1 deletion syndrome. The 8p23.1 duplication is associated with a variable phenotype including one or more of speech delay, developmental delay, mild dysmorphism, with prominent forehead and arched eyebrows, and congenital heart disease (CHD).
Presentation
The phenotypic data on 11 patients indicated that cases are not always ascertained for CHD but that CHD was the most common single feature found in 6 out of 11 individuals. Developmental delay and/or learning difficulties were found in 5 out of 11 cases, but one prenatal case was developing normally at 15 months of age (Case 1,). Three other prenatal cases could not yet be reliably assessed. A variable degree of facial dysmorphism was present in 5 out of 11 individuals. Partial toe syndactyly has been found in one mother and son diad and adrenal anomalies in two probands but not in the duplicated mother of one of them. The phenotype is compatible with independent adult life with varying degrees of support.
Duplication of the GATA4 transcription factor (OMIM: 600576) is believed to underlie the congenital heart disease and other genes, common to the duplication and deletion syndromes, can be regarded as candidates for the 8p23.1 duplication syndrome. These include the SOX7 transcription factor (OMIM: 612202) for both CHD and developmental delay and the TNKS gene (OMIM: 603303) for behavioural difficulties. The diaphragmatic hernia found in the 8p23.1 deletion syndrome has not been found in the 8p23.1 duplication syndrome to date.
The duplication may be associated with copy number changes of the adjacent olfactory receptor/defensin repeats (ORDRs) that predispose to the 8p23.1 deletion and duplication syndromes. High total copy numbers of these repeats have been associated with predisposition to psoriasis and low copy number with predisposition to Crohns disease.
Genetics
The duplication includes ~3.75 Mb between the distal and proximal ORDRs at either end of band 8p23.1. The copy number of the adjacent repeats may also be altered. The 8p23.1 duplication syndrome cannot be distinguished using conventional cytogenetics from high level copy number variation of the repeats themselves.Both de novo cases and families with transmitted duplications from parents of both sex are known. The duplication is believed to arise de novo as a result of non-allelic homologous recombination (NAHR) between the proximal and distal ORDRs. NAHR is also thought to give rise to the reciprocal microdeletion syndrome, the polymorphic inversion between the ORDRs and a variety of other large scale abnormalities involving the short arm of chromosome 8.
Diagnosis
Phenotypes
See also
Chromosome 8 (human)
References
External links
DECIPHER database description |
Brachygnathism | Brachygnathism, or colloquially parrot mouth, is the uneven alignment of the upper and lower teeth in animals. In serious cases, the upper teeth protrude beyond the lower teeth. Problem with parrot mouth occur if the molars at the back of the mouth are also uneven, resulting in large hooks forming on the upper molars and the rear of the lower back molars. Horses with parrot mouth often require dental treatment at least every six months to remove the hooks and maintain alignment.The equivalent conditions in humans are termed retrognathism or prognathism depending on whether the lower jaw is too far back or too far forward respectively.
See also
Horse teeth
Horse conformation
Veterinary dentistry
== References == |
Mixed affective state | A mixed affective state, formerly known as a mixed-manic or mixed episode, has been defined as a state wherein features unique to both depression and mania—such as episodes of despair, doubt, anguish, rage or homicidal ideation, suicidal ideation, splitting, racing thoughts, sensory overload, pressure of activity, and heightened irritability—occur either simultaneously or in very short succession.
Previously, the diagnostic criteria for both a manic and depressive episode had to be met in a consistent and sustained fashion, with symptoms enduring for at least a week (or any duration if psychiatric hospitalization was required), thereby restricting the official acknowledgement of mixed affective states to only a minority of patients with bipolar I disorder. In current DSM-5 nomenclature, however, a "mixed episode" no longer stands as an episode of illness unto itself; rather, the symptomology specifier "with mixed features" can be applied to any major affective episode (manic, hypomanic, or depressive), meaning that they are now officially recognized in patients with, in addition to bipolar I disorder, bipolar II disorder and, by convention, major depressive disorder. A depressive mixed state in a patient, however, even in the absence of discrete periods of mania or hypomania, effectively rules out unipolar depression.
Diagnostic criteria
As affirmed by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), the symptomology specifier "with mixed features" can be applied to manic episodes of bipolar I disorder, hypomanic episodes of either bipolar I disorder or bipolar II disorder and depressive episodes of either bipolar disorder or major depressive disorder, with at least three concurrent features of the opposite polarity being present. As a result, the presence of "mixed features" are now recognized in patients with bipolar II disorder and major depression; as earlier noted, however, although it is customary to withhold a diagnosis of a bipolar disorder until a manic or hypomanic episode appears, the presence of such features in a depressed patient even with no history of discrete mania or hypomania is strongly suggestive of the disorder.
Nevertheless, the DSM-5s narrower definition of mixed episodes may result in fewer patients meeting mixed criteria compared to DSM-IV. A call was made by Tohen in 2017 for introducing changes from a currently phenomenological to a target oriented approach to DSM-5 mixed mood criteria in order to achieve more personalized medical attention.Two features of both mania or hypomania and depression may superficially overlap and even resemble each other, namely "an increase in goal-directed activity" (psychomotor acceleration) vs. psychomotor agitation and "flight of ideas" and "racing thoughts" vs. depressive rumination. Attending to the patients experiences is very important. In the psychomotor agitation commonly seen in depression, the "nervous energy" is always overshadowed by a strong sense of exhaustion and manifests as purposeless movements (e.g., pacing, hand-wringing); in psychomotor acceleration, however, the excess in movement stems from an abundance of energy and is often channelled and purposeful. Likewise, in depressive rumination, the patient experiences the repetitive thoughts as heavy, leaden, and plodding; in psychic acceleration, however, (as seen in mania or hypomania) the thoughts move in a rapid progression, with many themes, rather than a singular one, being touched upon. Even when such experiences are accounted for on the basis of depression, the possibility does still exist, however, that the depressive episode may be complicated by other manic or hypomanic symptoms, in which case it is often prudent to attend to the patients personal and family history (e.g., family history of bipolar disorder, early age of onset) to determine whether or not the patient has bipolar disorder.
Treatment
Treatment of mixed states is typically based upon administration of mood stabilizing medication, which may include anticonvulsants such as valproic acid; atypical antipsychotics such as quetiapine, olanzapine, aripiprazole, and ziprasidone; or first-generation antipsychotics such as haloperidol. There is question of lithiums efficacy for treatment of mixed states due to conflicting conclusions drawn from various trials and research. Mood stabilizers work to reduce the manic symptoms associated with the mixed state, but they are not considered particularly effective for improving concurrent depressive symptoms.
See also
Post-traumatic stress disorder
Dopamine
Mania
Hyperthymic temperament
Cyclothymia
Narcissistic personality disorder
Borderline personality disorder
References
== External links == |
Schistosoma mansoni | Schistosoma mansoni is a water-borne parasite of humans, and belongs to the group of blood flukes (Schistosoma). The adult lives in the blood vessels (mesenteric veins) near the human intestine. It causes intestinal schistosomiasis (similar to S. japonicum, S. mekongi, S. guineensis, and S. intercalatum). Clinical symptoms are caused by the eggs. As the leading cause of schistosomiasis in the world, it is the most prevalent parasite in humans. It is classified as a neglected tropical disease. As of 2021, the World Health Organization reports that 236.6 million people have schistosomiasis and most of it is due to S. mansoni. It is found in Africa, the Middle East, the Caribbean, Brazil, Venezuela and Suriname.Unlike other flukes (trematodes) in which sexes are not separate (monoecious), schistosomes are unique in that adults are divided into males and females, thus, gonochoric. However, a permanent male-female pair, a condition called in copula, is required to become adults; for this, they are considered as hermaphrodites.
The life cycle of schistosomes includes two hosts: humans as definitive hosts, where the parasite undergoes sexual reproduction, and snails as intermediate hosts, where a series of asexual reproduction takes place. S. mansoni is transmitted through water, where freshwater snails of the genus Biomphalaria act as intermediate hosts. The larvae are able to live in water and infect the hosts by directly penetrating the skin. Prevention of infection is done by improved sanitation and killing the snails. Infection is treated with praziquantel.
S. mansoni was first noted by Theodor Maximillian Bilharz in Egypt in 1851, while discovering S. haematobium. Sir Patrick Manson identified it as unique species in 1902. Louis Westenra Sambon gave the name Schistosomum mansoni in 1907 in honour of Manson.
Structure
Adult
Schistosomes, unlike other trematodes, are long and cylindrical worms and are sexually dimorphic. The male S. mansoni is approximately 1 cm long (0.6–1.1 cm) and is 0.1 cm wide. It is white, and it has a funnel-shaped oral sucker at its anterior end followed by a second pediculated ventral sucker. The external part of the worm is composed of a double bilayer, which is continuously renewed as the outer layer, known as the membranocalyx, and is shed continuously. The tegument bears a large number of small tubercules. The suckers have small thorns in their inner part as well as in the buttons around them. The male genital apparatus is composed of 6 to 9 testicular masses, situated dorsally. There is one deferent canal beginning at each testicle, which is connected to a single deferent that dilates into a reservatory, the seminal vesicle, located at the beginning of the gynaecophoric canal. The copula happens through the coaptation of the male and female genital orifices.The female has a cylindrical body, longer and thinner than the males (1.2 to 1.6 cm long by 0.016 cm wide). It has the general appearance of a roundworm. The female parasite is darker, and it looks gray. The darker color is due to the presence of a pigment (hemozoin) in its digestive tube. This pigment is derived from the digestion of blood. The ovary is elongated and slightly lobulated and is located on the anterior half of the body. A short oviduct conducts to the ootype, which continues with the uterine tube. In this tube it is possible to find 1 to 2 eggs (rarely 3 to 4) but only 1 egg is observed in the ootype at any one time. The genital pore opens ventrally. The posterior two-thirds of the body contain the viteline glands and their winding canal, which unites with the oviduct a little before it reaches the ootype.The digestive tube begins at the anterior extremity of the worm, at the bottom of the oral sucker. The digestive tube is composed of an esophagus, which divides in two branches (right and left) and that reunite in a single cecum. The intestines end blindly, meaning that there is no anus.
Sex
S. mansoni and other schistosomes are the only flukes or flatworms that exhibit sex separation as they exist as male and female individuals as in dioecious animals. However, they are not truly dioecious since the adults live in permanent male-female pairs, a condition called in copula. Although they can be physically separated, isolated females cannot grow into sexually-mature adults. In copula starts in the liver only after which they can move to their final habitation, the inferior mesenteric veins. Individual females cannot enter the mesenteric veins. Sex organs, the gonads, are also incompletely separated and are interdependent between sexes. Egg-making organ, the vitelline gland in female does not develop in the absence of male. Male gametes, spermatozoa, are present in the oviduct. In males, there are rudimentary ovaries, oviduct, and oocytes (developing female gametes), as well as vitelline cells. Males also possess the genes for hermaphroditism in flukes. Thus, they are technically hermaphrodites.
Egg
The eggs are oval-shaped, measuring 115–175 µm long and 45–47 µm wide, and ~150 µm diameter on average. They have pointed spines towards the broader base on one side, i.e. lateral spines. This is an important diagnostic tool because co-infection with S. haematobium (having a terminal-spined eggs) is common, and they are hard to distinguish. When the eggs are released into the water, a lot of them are immature and unfertilised so that they do not hatch. When the eggs are larger than 160 µm in diameter, they also fail to hatch.
Larva
The miracidium (from the Greek word μειράκιον, meirakion, meaning youth) is pear-shaped, and gradually elongates as it ages. It measures about 136 μm long and 55 μm wide. The body is covered by anucleate epidermal plates separated by epidermal ridges. The epidermal cells give off numerous hair-like cilia on the body surface. There are 17–22 epidermal cells. Epidermal plate is absent only at the extreme anterior called apical papilla, or terebratorium, which contains numerous sensory organelles. Its internal body is almost fully filled with glycogen particles and vesicles.The cercaria has a characteristic bifurcated tail, classically called furcae (Latin for fork); hence, the name (derived from a Greek word κέρκος, kerkos, meaning tail). The tail is highly flexible and its beating propels the cercaria in water. It is about 0.2 mm long and 47 μm wide, somewhat loosely attached to the main body. The body is pear-shaped and measures 0.24 mm in length and 0.1 mm in width. Its tegument is fully covered with spine. A conspicuous oral sucker is at the apex. As a non-feeding larva, there are no elaborate digestive organs, only oesophagus is distinct. There are three pairs of mucin glands connected to laterally to the oral sucker at the region of the ventral sucker.
Physiology
Feeding and nutrition
Developing Schistosoma mansoni worms that have infected their definitive hosts, prior to the sexual pairing of males and females, require a nutrient source in order to properly develop from cercariae to adults. The developing parasites lyse host red blood cells to gain access to nutrients and also makes its own fungi from its waste it is hard to detect; the hemoglobin and amino acids the blood cells contain can be used by the worm to form proteins. While hemoglobin is digested intracellularly, initiated by salivary gland enzymes, iron waste products cannot be used by the worms, and are typically discarded via regurgitation.Kasschau et al. (1995) tested the effect of temperature and pH on the ability of developing S. mansoni to lyse red blood cells. The researchers found that the parasites were best able to destroy red blood cells for their nutrients at a pH of 5.1 and a temperature of 37 °C.
Locomotion
Schistosoma mansoni is locomotive in primarily two stages of its life cycle: as cercariae swimming freely through a body of freshwater to locate the epidermis of their human hosts, and as developing and fully-fledged adults, migrating throughout their primary host upon infection. Cercariae are attracted to the presence of fatty acids on the skin of their definitive host, and the parasite responds to changes in light and temperature in their freshwater medium to navigate towards the skin. Ressurreicao et al. (2015) tested the roles of various protein kinases in the ability of the parasite to navigate its medium and locate a penetrable host surface. Extracellular signal-regulated kinase and protein kinase C both respond to changes in medium temperature and light levels, and the stimulation of p38 mitogen-activated protein kinase, associated with recognition of parasite host surface, results in a glandular secretion that deteriorates the host epidermis, and allows the parasite to burrow into its host.
The parasites nervous system contains bilobed ganglia and several nerve cords which splay out to every surface of the body; serotonin is a transmitter distributed widely throughout the nervous system and plays an important role in nervous reception, and stimulating mobility.
Life cycle
Intermediate host
After the eggs of the human-dwelling parasite are emitted in the faeces and into the water, the ripe miracidium hatches out of the egg. The hatching happens in response to temperature, light and dilution of faeces with water. The miracidium searches for a suitable freshwater snail belonging to the genus Biomphalaria. In South America, the principal intermediate host is Biomphalaria glabrata, while B. straminea and B. tenagophila are less common. A land snail Achatina fulica was reported in 2010 to act as a host in Venezuela. In Africa, B. glabratra, B. pfeifferi, B. choanomphala and B. sudanica act as the hosts; but in Egypt, the main snail host is B. alexandrina.Miracidia directly penetrate the soft tissue of snail. Inside the snail, they lose their cilia and develop into mother sporocysts. The sporocysts rapidly multiply by asexual reproduction, each forming numerous daughter sporocysts. The daughter sporocysts move to the liver and gonads of the snail, where they undergo further growth. Within 2–4 weeks, they undergo metamorphosis and give rise to fork-tailed cercariae. Stimulated by light, hundreds of cercariae penetrate out of the snail into water.
Definitive host
The cercaria emerge from the snail during daylight and they propel themselves in water with the aid of their bifurcated tail, actively seeking out their final host. In water, they can live for up to 12 hours, and their maximum infectivity is between 1 and 9 hours after emergence. When they recognise human skin, they penetrate it within a very short time. This occurs in three stages, an initial attachment to the skin, followed by the creeping over the skin searching for a suitable penetration site, often a hair follicle, and finally penetration of the skin into the epidermis using cytolytic secretions from the cercarial post-acetabular, then pre-acetabular glands. On penetration, the head of the cercaria transforms into an endoparasitic larva, the schistosomule. Each schistosomule spends a few days in the skin and then enters the circulation starting at the dermal lymphatics and venules. Here, they feed on blood, regurgitating the haem as hemozoin. The schistosomule migrates to the lungs (5–7 days post-penetration) and then moves via circulation through the left side of the heart to the hepatoportal circulation (>15 days) where, if it meets a partner of the opposite sex, it develops into a sexually mature adult and the pair migrate to the mesenteric veins. Such pairings are monogamous.Male schistosomes undergo normal maturation and morphological development in the presence or absence of a female, although behavioural, physiological and antigenic differences between males from single-sex, as opposed to bisex, infections have been reported. On the other hand, female schistosomes do not mature without a male. Female schistosomes from single-sex infections are underdeveloped and exhibit an immature reproductive system. Although the maturation of the female worm seems to be dependent on the presence of the mature male, the stimuli for female growth and for reproductive development seem to be independent from each other.
The adult female worm resides within the adult male worms gynaecophoric canal, which is a modification of the ventral surface of the male, forming a groove. The paired worms move against the flow of blood to their final niche in the mesenteric circulation, where they begin egg production (>32 days). The S. mansoni parasites are found predominantly in the small inferior mesenteric blood vessels surrounding the large intestine and caecal region of the host. Each female lays approximately 300 eggs a day (one egg every 4.8 minutes), which are deposited on the endothelial lining of the venous capillary walls. Most of the body mass of female schistosomes is devoted to the reproductive system. The female converts the equivalent of almost her own body dry weight into eggs each day. The eggs move into the lumen of the hosts intestines and are released into the environment with the faeces.
Genome
Schistosoma mansoni has 8 pairs of chromosomes (2n = 16)—7 autosomal pairs and 1 sex pair. The female schistosome is heterogametic, or ZW, and the male is homogametic, or ZZ. Sex is determined in the zygote by a chromosomal mechanism. The genome is approximately 270 MB with a GC content of 34%, 4–8% highly repetitive sequence, 32–36% middle repetitive sequence and 60% single copy sequence. Numerous highly or moderately repetitive elements are identified, with at least 30% repetitive DNA. Chromosomes range in size from 18 to 73 MB and can be distinguished by size, shape, and C banding.In 2000, the first BAC library of Schistosome was constructed. In June 2003, a ~5x whole genome shotgun sequencing project was initiated at the Sanger Institute. Also in 2003, 163,000 ESTs (expressed sequence tags) were generated (by a consortium headed by the University of São Paulo) from six selected developmental stages of this parasite, resulting in 31,000 assembled sequences and an estimated 92% of the 14,000-gene complement.In 2009 the genomes of both S. mansoni and S. japonicum were published, with each describing 11,809 and 13,469 genes, respectively. S. mansoni genome has increased protease families and deficiencies in lipid anabolism; which are attributed its parasitic adaptation. Portease included the invadolysin (host penetration) and cathepsin (blood-feeding) gene families.In 2012, an improved version of the S. mansoni genome was published, which consisted of only 885 scaffolds and more than 81% of the bases organised into chromosomes.In 2019, Ittiprasert, Brindley and colleagues employed programmed CRISPR/Cas9 knockout of the gene encoding the T2 ribonuclease of the egg of Schistosoma mansoni, advancing functional genomics and reverse genetics in the study of schistosomes, and platyhelminths generally <https://doi.org/10.7554/eLife.41337>.
Pathology
Schistosome eggs, which may become lodged within the hosts tissues, are the major cause of pathology in schistosomiasis. Some of the deposited eggs reach the outside environment by passing through the wall of the intestine; the rest are swept into the circulation and are filtered out in the periportal tracts of the liver, resulting in periportal fibrosis. Onset of egg laying in humans is sometimes associated with an onset of fever (Katayama fever). This "acute schistosomiasis" is not, however, as important as the chronic forms of the disease. For S. mansoni and S. japonicum, these are "intestinal" and "hepatic schistosomiasis", associated with formation of granulomas around trapped eggs lodged in the intestinal wall or in the liver, respectively. The hepatic form of the disease is the most important, granulomas here giving rise to fibrosis of the liver and hepatosplenomegaly in severe cases. Symptoms and signs depend on the number and location of eggs trapped in the tissues. Initially, the inflammatory reaction is readily reversible. In the latter stages of the disease, the pathology is associated with collagen deposition and fibrosis, resulting in organ damage that may be only partially reversible.Granuloma formation is initiated by antigens secreted by the miracidium through microscopic pores within the rigid egg shell, and the immune response to granuloma, rather than the direct action of egg antigens, causes the symptoms. The granulomas formed around the eggs impair blood flow in the liver and, as a consequence, induce portal hypertension. With time, collateral circulation is formed and the eggs disseminate into the lungs, where they cause more granulomas, pulmonary arteritis and, later, cor pulmonale. A contributory factor to portal hypertension is Symmers fibrosis, which develops around branches of the portal veins. This fibrosis occurs only many years after the infection and is presumed to be caused in part by soluble egg antigens and various immune cells that react to them.Recent research has shown that granuloma size is consistent with levels of IL-13, which plays a prominent role in granuloma formation and granuloma size. IL-13 receptor α 2 (IL-13Rα2) binds IL-13 with high affinity and blocks the effects of IL-13. Thus, this receptor is essential in preventing the progression of schistosomiasis from the acute to the chronic (and deadly) stage of disease. Synthetic IL-13Rα2 given to mice has resulted in significant decreases in granuloma size, implicating IL-13Rα2 as an important target in schistosomiasis.S. mansoni infection often occurs alongside those of viral hepatitis, either hepatitis B virus (HBV) or hepatitis C virus (HCV). This is due to high prevalence of schistosomiasis in areas where chronic viral hepatitis is prevalent. One important factor was the development of large reservoir of infection due to extensive schistosomiasis control programs that used intravenously administered tartar emetic since the 1960s. Co-infection is known to cause earlier liver deterioration and more severe illness.
Evasion of host immunity
Adult and larval worms migrate through the hosts blood circulation avoiding the hosts immune system. The worms have many tools that help in this evasion, including the tegument, antioxidant proteins, and defenses against host membrane attack complex (MAC). The tegument coats the worm and acts as a physical barrier to host antibodies and complement. Host immune defenses are capable of producing superoxide, but these are counterattacked by antioxidant proteins produced by the parasite. Schistosomes have four superoxide dismutases, and levels of these proteins increase as the schistosome grows. Antioxidant pathways were first recognised as a chokepoints for schistosomes, and later extended to other trematodes and cestodes. Targeting of this pathway with different inhibitors of the central antioxidant enzyme thioredoxin glutathione reductase (TGR) results in reduced viability of worms. Decay accelerating factor (DAF) protein is present on the parasite tegument and protects host cells by blocking formation of MAC. In addition, schistosomes have six homologues of human CD59 which are strong inhibitors of MAC.
Diagnosis
The presence of S. mansoni is detected by microscopic examination of parasite eggs in stool. A staining method called Kato-Katz technique is used for stool examination. It involves methylene blue-stained cellophane soaked in glycerine or glass slides. A bit costlier technique called formalin-ether concentration technique (FECT) is often used in combination with the direct faecal smear for higher accuracy. Serological and immunological tests are also available. Antibodies and antigens can be detected in the blood using ELISA to identify infection. Adult worm antigens can be detected by indirect haemagglutination assays (IHAs). Polymerase chain reaction (PCR) is also used for detecting the parasite DNA. Circulating cathodic antigen (CCA) in urine can be tested with lateral flow immune-chromatographic reagent strip and point-of-care (POC) tests.Egg detection and immunologic tests are not that sensitive. Polymerase chain reaction (PCR) based testing is accurate and rapid. They, however, are not frequency used in countries were the disease is common due to the cost of the equipment and the technical experience required to run them. Using a microscope to detect eggs costs about US$0.40 per test well PCR is about $US7 per test as of 2019. Loop-mediated isothermal amplification (LAMP) are being studied as they are lower cost. LAMP testing is not commercially available as of 2019.
Treatment
The standard drug for S. mansoni infection is praziquantel at a dose of 40 mg/kg. Oxamniquine is also used.
Epidemiology
As of WHO report in 2016, 206.5 million people worldwide are having schistosomiasis due to different species of Schistosoma. More than 105 million people were given medical treatment. S. mansoni is the major species causing an annual death of about 130,000. It is endemic in 55 countries and most prevalent in Africa, the Middle East, the Caribbean, Brazil, Venezuela and Suriname. About 80-85% of schistosomiasis is found in sub-Saharan Africa, where S. haematobium, S. intercalatum and S. mansoni are endemic. Approximately 393 million Africans are at risk of infection from S. mansoni, of which about 55 million are infected at any moment. Annual death due to S. mansoni is about 130,000. The prevalence rate in different countries of Africa are: 73.9% in northern Ethiopia, 37.9% in western Ethiopia, 56% in Nigeria, 60.5% in Kenya, 64.3% in Tanzania, 19.8% in Ghana, and 53.8% in Côte dIvoire. In Egypt, 60% of the population in the Northern and Eastern parts of the Nile Delta and only 6% in the Southern part are infected.S. mansoni is commonly found in places with poor sanitation. Because of the parasites fecal-oral transmission, bodies of water that contain human waste can be infectious. Water that contains large populations of the intermediate host snail species is more likely to cause infection. Young children living in these areas are at greatest risk because of their tendency to swim and bathe in cercaria-infected waters longer than adults
. Anyone travelling to the areas described above, and who is exposed to contaminated water, is at risk of schistosomiasis.
History
The intermediate hosts Biomphalaria snails are estimated to originate in South America 95–110 million years ago. But the parasites Schistosoma originated in Asia. In Africa, the progenitor species evolved into modern S. mansoni and S. haematobium around 2–5 million years ago.A German physician Theodor Maximillian Bilharz was the first to discover the parasite in 1851, while working at Kasr el-Aini Hospital, a medical school in Cairo. Bilharz recovered them from autopsies of dead soldiers, and noticed two distinct parasites. He described one of them as Distomum haematobium (now S. haematobium) in 1852, but failed to identify the other. In one of his letters to his mentor Karl Theordor von Siebold, he mentioned some of the eggs were different in having terminal spines while some had lateral spines. Terminal-spined eggs are unique to S. haematobium, while lateral spines are found only in S. mansoni. Bilharz also noted that the adult flukes were different in anatomy and number eggs they produced. He introduced the terms bilharzia and bilharziasis for the name of the infection in 1856. A German zoologist David Friedrich Weinland corrected the genus name to Schistosoma in 1858; and introduced the disease name as schistosomiasis.The species distinction was first recognised by Patrick Manson at the London School of Hygiene & Tropical Medicine. Manson identified lateral-spined eggs in the faeces of a colonial officer earlier posted to the West Indies, and concluded that there were two species of Schistosoma. An Italian-British physician Louis Westenra Sambon gave the new names Schistosomum haematobium and Schistosomum mansoni in 1907, the latter to honour Manson. Sambon only gave partial description using a male worm. In 1908, a Brazilian physician Manuel Augusto Pirajá da Silva gave a complete description of male and female worms, including the lateral-spined eggs. Pirajá da Silva obtained specimens from three necropsies and eggs from 20 stool examinations in Bahia. He gave the name S. americanum. The species identity was confirmed in 1907 by British parasitologist Robert Thomson Leiper, identifying the specific snail host, and distinguishing the egg structure, thereby establishing the life cycle.
References
External links
Media related to Schistosoma mansoni at Wikimedia Commons
Disease info at CDC
Species profile at Animal Diversity Web
Profile at WormBase |
Kimuras disease | Kimuras disease is a benign rare chronic inflammatory disorder. Its primary symptoms are subdermal lesions in the head or neck or painless unilateral inflammation of cervical lymph nodes.
Cause
Its cause remains unknown. Reasons such as an allergic reaction, tetanus toxoid vaccination, or an alteration of immune regulation are suspected. Other theories like persistent antigenic stimulation following arthropod bites and parasitic or candidal infection have also been proposed. To date, none of these theories has been substantiated.
Pathophysiology
The pathophysiology of Kimuras disease remains unknown, although an allergic reaction, trauma, and an autoimmune process have all been implicated as possible causes. The disease is manifested by an abnormal proliferation of lymphoid follicles and vascular endothelium. Peripheral eosinophilia and the presence of eosinophils in the inflammatory infiltrate suggest it may be a hypersensitivity reaction. Some evidence has indicated TH2 lymphocytes may also play a role, but further investigation is needed.Kimuras disease is generally limited to the skin, lymph nodes, and salivary glands, but patients with Kimuras disease and nephrotic syndrome have been reported. The basis of this possible association is unclear.
Diagnosis
An open biopsy is the chief means by which this disease is diagnosed."Lymphoid nodules with discrete germinal centers can occupy an area extending from the reticular dermis to the fascia and muscle. Follicular hyperplasia, marked eosinophilic infiltrate and eosinophilic abscesses, and the proliferation of postcapillary venules are characteristic histological findings. [18] Centrally, thick-walled vessels are present with hobnail endothelial cells. Immunohistochemical evaluation of the lymphoid nodules demonstrates a polymorphous infiltrate without clonality. [12, 27] Reports have also demonstrated the presence of plasmacytoid dendritic cells in a lesion of Kimura disease. [40] Histopathological examination is an effective way to establish the diagnosis."
Treatment
Observation is acceptable if the lesions are neither symptomatic nor disfiguring. Intralesional or oral steroids can shrink the nodules, but seldom result in cure. Cyclosporine has been reported to induce remission in patients with Kimuras disease, but recurrence of the lesions has been observed once this therapy is stopped.Cetirizine is an effective agent in treating its symptoms. Cetirizines properties of being effective both in the treatment of pruritus (itching) and as an anti-inflammatory agent make it suitable for the treatment of the pruritus associated with these lesions. In a 2005 study, the American College of Rheumatology conducted treatments initially using prednisone, followed by steroid dosages and azathioprine, omeprazole, and calcium and vitamin D supplements over the course of two years. The skin condition of the patient began to improve and the skin lesions lessened. However, symptoms of cushingoid and hirsutism were observed before the patient was removed from the courses of steroids and placed on 10 mg/day of cetirizine to prevent skin lesions; an agent suitable for the treatment of pruritus associated with such lesions. Asymptomatically, the patients skin lesions disappeared after treatment with cetirizine, blood eosinophil counts became normal, corticosteroid effects were resolved, and a remission began within a period of two months. The inhibition of eosinophils may be the key to treatment of Kimuras disease due to the role of eosinophils, rather than other cells with regards to the lesions of the skin.Radiotherapy has been used to treat recurrent or persistent lesions. However, considering the benign nature of this disease, radiation should be considered only in cases of recurrent, disfiguring lesions.Surgery has been considered the mainstay of therapy. However, recurrence after surgery is common.In 2011, an eight-year-old boy had presented with a firm, nontender, nonfluctuating 15- to 12-cm mass on the left side of the neck involving the lateral region of the neck and jaw and a 5- to 7-cm mass on the right side of his neck. He had an eosinophil concentration of 36% (absolute count: 8172/mL), his IgE level was 9187 IU/mL. He was diagnosed with Kimuras disease. Initially treated with corticosteroids, he was given a single dose of intravenous immunoglobulin (IVIG) as a steroid-sparing agent after the disease flared while tapering prednisone. After IVIG administration, improvement was rapid, both left and right cervical masses diminished to less than 1 cm and his eosinophil and IgE levels returned to normal range. He has been free of disease during a six-year follow-up. IVIG may have value in the treatment of Kimuras disease.A study is going on to assess the efficacy of tacrolimus on Kimuras disease. One case has so far been described. A patient with refractory Kimuras disease after surgery and treatment with prednisone was treated with tacrolimus. Tacrolimus (FK-506) was administered at an initial dosage of 1 mg every 12 hours, and FK-506 concentration in the blood was monitored monthly. FK-506 blood concentration was controlled within 5 to 15 μg/L. After 6 months, the dosage of tacrolimus was reduced to 0.5 mg daily for another 2 months and then treatment was stopped. Swelling of the bilateral salivary glands disappeared within the first week. No serious side effects were noted and the disease has not recurred in the 2 years of follow-up. Tacrolimus may be an effective treatment for patients with Kimuras disease, but more research is needed to determine its long-term efficacy and safety, as well as its mechanism of action.
Prevalence
Kimuras disease is said to be predominantly seen in males of Asian descent. However, a study of 21 cases in the United States showed no racial preference, of 18 males and three females (male/female ratio 6:1), 8 to 64 years of age (mean, 32 years), and seven Caucasians, six Blacks, six Asians, one Hispanic, and an Arab were included.Assessing the prevalence is difficult. The medical literature alone holds over 500 case reports and series (typically two, three cases) from the 1980s to early 2017 in English, excluding the existing Chinese, Japanese, and Korean medical reports that add more cases.
History
The first known report of Kimuras disease was from China in 1937, when Kimm and Szeto identified seven cases of the condition. It first received its name in 1948 when Kimura and others noted a change in the surrounding blood vessels and referred to it as "unusual granulation combined with hyperplastic changes in lymphoid tissue."
See also
Kikuchis disease
List of cutaneous conditions
References
== External links == |
Monilethrix | Monilethrix (also referred to as beaded hair) is a rare autosomal dominant hair disease that results in short, fragile, broken hair that appears beaded. It comes from the Latin word for necklace (monile) and the Greek word for hair (thrix). Hair becomes brittle, and breaks off at the thinner parts between the beads. It appears as a thinning or baldness of hair and was first described in 1897 by Walter Smith
Signs and symptoms
Some indicators of monilethrix are small bumps on the skin, mainly on the scalp, neck and arms. In most cases, firm, dark papules, covered with dark scales and crusts appears on the skin, especially the scalp. The affected individual would have beaded hair strands. The possible areas for the hair loss are the eyebrows, eyelashes, limbs, and pubic region. Hair strands are usually dull, dry, and brittle. The strands are prone to mild to severe breakage, causing onset alopecia, especially during pregnancy. Fingernail and toenails tend to appear abnormal. The onset for this disease varies from person to person. The frequency of monilethrix is currently unknown.
Presentation
Newborns are not born with Monilethrix; it usually develops within the first few months of life. The presentation may be of alopecia (baldness). Individuals vary in severity of symptoms. Nail deformities may also be present as well as hair follicle keratosis and follicular hyperkeratosis. Depending on severity it can effect hair on all areas of the body including head hair, arm and leg hair, pubic hair, underarm hair, eyebrows, and eyelashes. The hair is seen under a microscope with bumps in the hair strand. These cause the hair to be brittle and break in the thinner sections. Severe cases of monilethrix can also effect finger and toe nails causing abnormal growth. Monilethrix can also cause keratosis pilaris (small bumps on the skin). Less severe cases of Monilethrix may only affect certain parts of the scalp, usually the back of the head and neck.
Diagnosis
Monilethrix may be diagnosed with trichoscopy and other forms of dermoscopy. Light microscopic examination is diagnostic and reveals elliptical nodes of normal thickness and intermittent constrictions, internodes at which the hair easily breaks. Under examination, the hair is beaded. The beading is the result of a periodic narrowing of the shaft with nodes separated by about 0.7 mm. In general, there is a tendency for spontaneous improvement with time, especially during puberty and pregnancy, but the condition never disappears completely.
Genetics
Monilethrix is caused by mutations affecting the genes KRTHB1 (KRT81), KRTHB3 (KRT83), or KRTHB6 (KRT86) which code for type II hair cortex keratins. The disorder is inherited in an autosomal dominant manner. This means that the defective gene(s) responsible for the disorder is located on an autosome, and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. If an affected parent and an unaffected parent have children, 75% of the time they will be affected by Monilethrix. It can be equally present in both males and females.
Treatment
No specific treatment exists for monilethrix. Spontaneous resolution following puberty has occurred in some cases. In affected females, the condition improves during pregnancy. Genetic counseling will be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
Epidemiology
Currently, the frequency for this disease is unknown and affects both men and women. Signs and symptoms either show up spontaneously at birth or around the age of 2. The symptoms may change or remain the same throughout ones life, but are usually present after the first few months after birth.
See also
List of cutaneous conditions
List of conditions caused by problems with junctional proteins
List of cutaneous conditions caused by mutations in keratins
References
== External links == |
Sepiapterin reductase deficiency | Sepiapterin reductase deficiency is an inherited pediatric disorder characterized by movement problems, and most commonly displayed as a pattern of involuntary sustained muscle contractions known as dystonia. Symptoms are usually present within the first year of age, but diagnosis is delayed due to physicians lack of awareness and the specialized diagnostic procedures. Individuals with this disorder also have delayed motor skills development including sitting, crawling, and need assistance when walking. Additional symptoms of this disorder include intellectual disability, excessive sleeping, mood swings, and an abnormally small head size. SR deficiency is a very rare condition. The first case was diagnosed in 2001, and since then there have been approximately 30 reported cases. At this time, the condition seems to be treatable, but the lack of overall awareness and the need for a series of atypical procedures used to diagnose this condition pose a dilemma.
Signs and symptoms
Cognitive problems
Intellectual disability: Delay in cognitive development
Extreme mood swings
Language delay
Motor problems
Dystonia: involuntary muscle contractions
Axial hypotonia: low muscle tone and strength
Dysarthria: impairment in muscles used for speech
Muscle stiffness and tremors
Seizures
Coordination and balance impairment
Oculogyric crises: abnormal rotation of the eyesThe oculogyric crises usually occur in the later half of the day and during these episodes patients undergo extreme agitation and irritability along with uncontrolled head and neck movements. Apart from the aforementioned symptoms, patients can also display parkinsonism, sleep disturbances, small head size (microcephaly), behavioral abnormalities, weakness, drooling, and gastrointestinal symptoms.
Causes
This disorder occurs through a mutation in the SPR gene, which is responsible for encoding the sepiapterin reductase enzyme. The enzyme is involved in the last step of producing tetrahydrobiopterin, better known as BH4. BH4 is involved in the processing of amino acids and the production of neurotransmitters, specifically that of dopamine and serotonin which are primarily used in transmission of signals between nerve cells in the brain. The mutation in the SPR gene interferes with the production of the enzyme by producing enzymes with little or no function at all. This interference results in a lack of BH4 specifically in the brain. The lack of BH4 only occurs in the brain because other parts of the body adapt and utilize alternate pathways for the production of BH4. The mutation in the SPR gene leads to nonfunctional sepiapterin reductase enzymes, which results in a lack of BH4 and ultimately disrupts the production of dopamine and serotonin in the brain. The disruption of dopamine and serotonin production leads to the visible symptoms present in patients suffering from sepiapterin reductase deficiency. SR deficiency is considered an inherited autosomal recessive condition disorder because each parent carries one copy of the mutated gene, but typically do not show any signs or symptoms of the condition.
Diagnosis
CSF neurotransmitter screening
The diagnosis of SR deficiency is based on the analysis of the pterins and biogenic amines found in the cerebrospinal fluid (CSF) of the brain. The pterin compound functions as a cofactor in enzyme catalysis and biogenic amines which include adrenaline, dopamine, and serotonin have functions that vary from the control of homeostasis to the management of cognitive tasks. This analysis reveals decreased concentrations of homovanillic acid (HVA), 5-hydroxyindolacetic acid (HIAA), and elevated levels of 7,8-dihydrobiopterin, a compound produced in the synthesis of neurotransmitters. Sepiapterin is not detected by the regularly used methods applied in the investigation of biogenic monoamine metabolites in the cerebrospinal fluid. It must be determined by specialized methods that work by indicating a marked and abnormal increase of sepiapterin in cerebrospinal fluid. Confirmation of the diagnosis occurs by demonstrating high levels of CSF sepiapterin and a marked decrease of SR activity of the fibroblasts along with SPR gene molecular analysis.
Treatment
Levodopa and Carbidopa
SR deficiency is currently being treated using a combination therapy of levodopa and carbidopa. These treatments are also used for individuals suffering from Parkinsons. The treatment is noninvasive and only requires the patient to take oral tablets 3 or 4 times a day, where the dosage of levodopa and carbidopa is determined by the severity of the symptoms. Levodopa is in a class of medications called central nervous system agents where its main function is to become dopamine in the brain. Carbidopa is in a class of medications called decarboxylase inhibitors and it works by preventing levodopa from being broken down before it reaches the brain. This treatment is effective in mitigating motor symptoms, but it does not totally eradicate them and it is not as effective on cognitive problems. Patients who have been diagnosed with SR deficiency and have undergone this treatment have shown improvements with most motor impairments including oculogyric crises, dystonia, balance, and coordination.
Case Studies
Autosomal Recessive DOPA-responsive Dystonia
The diagnosis of sepiapterin reductase deficiency in a patient at the age of 14 years was delayed by an earlier diagnosis of an initially unclassified form of methylmalonic aciduria at the age of 2. At that time the hypotonia and delayed development were not considered to be suggestive of a neurotransmitter defect. The clinically relevant diagnosis was only made following the onset of dystonia with diurnal variation, when the patient was a teenager. Variability in occurrence and severity of other symptoms of the condition, such as hypotonia, ataxia, tremors, spasticity, bulbar involvement, oculogyric crises, and cognitive impairment, is comparable with autosomal dominant GTPCH and tyrosine hydroxylase deficiency, which are both classified as forms of DOPA-responsive dystonia.
Homozygous Mutation causing Parkinsonism
Hypotonia and Parkinsonism were present in two Turkish siblings, brother and sister. By using exome sequencing, which sequences a selective coding region of the genome, researchers have found a homozygous five-nucleotide deletion in the SPR gene which confirmed both siblings were homozygous. It is predicted that this mutation leads to premature translational termination. Translation is the biological process through which proteins are manufactured. The homozygous mutation of the SPR gene in these two siblings exhibiting early-onset Parkinsonism showcases that SPR gene mutations can vary in combinations of clinical symptoms and movement. These differences result in a wider spectrum for the disease phenotype and increases the genetic heterogeneity causing difficulties in diagnosing the disease.
Quantification of Sepiapterin in CSF
This study examined the clinical history of the CSF and urine of two Greek siblings who were both diagnosed with SR deficiency. Both siblings displayed delayed psychomotor development and a movement disorder. The diagnosis was confirmed by measuring the SR enzyme activity and mutation analysis. The mutation analysis of the gene was performed using genomic DNA isolated from blood samples. The results concluded that both patients have low concentrations of HVA and HIAA and high concentrations of sepiapterin in the CSF, but neopterin and biopterin were abnormal in only one sibling. The results of this research indicates that when diagnosing the SR deficiency, the quantification of sepiapterin in the CSF is more important and indicative of SR deficiency than using neopterin and biopterin alone. The results also show that the urine concentrations of neurotransmitter metabolites are abnormal in patients with this disorder. This finding may provide an initial and easier indication of the deficiency before CSF analysis is performed.
Figures
See also
Succinic semialdehyde dehydrogenase deficiency
Neurotransmitter
Parkinsons disease
Cerebral palsy
Enzyme
Biochemistry
References
External links
SR deficiency Genetics Home Reference
SR deficiency National Institute of Health |
Stretch marks | Stretch marks, also known as striae () or striae distensae, are a form of scarring on the skin with an off-color hue. Over time they may diminish, but will not disappear completely. Striae are caused by tearing of the dermis during periods of rapid growth of the body, such as during puberty or pregnancy, in which they usually form during the last trimester. Usually on the stomach, these striae also commonly occur on the breasts, thighs, hips, lower back, and buttocks. Pregnancy-related striae are known as striae gravidarum. Striae may also be influenced by the hormonal changes associated with puberty, pregnancy, bodybuilding, or hormone replacement therapy.
There is no evidence that creams used during pregnancy prevent stretch marks. Once they have formed there is no clearly effective treatment, though various methods have been attempted and studied.
Signs and symptoms
Striae, or "stretch marks", begin as reddish or purple lesions, which can appear anywhere on the body, but are most likely to appear in places where larger amounts of fat are stored; the most common places are the abdomen (especially near the navel), breasts, upper arms, underarms, back, thighs (both inner and outer), hips, and buttocks. Over time, they tend to atrophy and lose pigmentation. The affected areas appear empty, and are soft to the touch.Stretch marks occur in the dermis, the resilient middle tissue layer that helps the skin retain its shape. No stretch marks will form as long as there is support within the dermis; stretching plays a role in where the marks occur and in what direction they run, however, there are a number of contributing factors (see: "Causes", below) to their formation.They can (but do not always) cause a burning and itching sensation, as well as emotional distress. They pose no health risk in and of themselves, and do not compromise the bodys ability to function normally and repair itself, however, they are often considered a cosmetic nuisance. Young women are generally affected the most and often seek treatment for them from a dermatologist and following pregnancy.
Causes
Stretch marks appear to be caused by stretching of the skin. This is especially true when there is an increase in cortisone – an increase in cortisone levels can increase the probability or severity of stretch marks by reducing the skins pliability. More specifically, it affects the dermis by preventing the fibroblasts from forming collagen and elastin fibers necessary to keep rapidly growing skin taut; this can create a lack of supportive material as the skin is stretched, and lead to dermal and epidermal tearing, which in turn can produce scarring in the form of stretch marks. This is particularly the case when there is new tissue growth (which can interfere with the underlying physical support of the dermis or epidermis, by displacing the supportive tissue).Examples of cases where stretch marks are common, also given by the Mayo Clinic, include weight gain (in the form of fat and/or muscle), pregnancy, and adolescent growth spurts, though it is also noted that some medications, as well as other medical conditions and diseases, may increase the likelihood of stretch marks appearing. In the case of medication, the Clinic points to "corticosteroid creams, lotions and pills and chronic use of oral or systemic steroids" as a common contributing factor. Medical conditions that can contribute to stretch marks include Ehlers-Danlos syndrome, Cushings syndrome, Marfan syndrome, and "adrenal gland diseases".
Pregnancy
Pregnancy stretch marks, also known as striae gravidarum, are a specific form of scarring of the skin of the abdominal area due to rapid expansion of the uterus as well as sudden weight gain during pregnancy. About 90% of pregnant women are affected.A number of additional factors appear to promote the appearance of stretchmarks: one study of 324 women, done just after they had given birth, demonstrated that low maternal age, high body mass index, weight gain over 15 kg (33 pounds) and higher neonatal birth weight were independently correlated with the occurrence of striae. Teenagers were found to be at the highest risk of developing severe striae.These skin marks are symptoms of pregnancy caused by the tearing of the dermis, resulting in atrophy and loss of rete ridges. These scars often appear as reddish or bluish streaks on the abdomen, and can also appear on the breasts and thighs. Some of these striae disappear with time, while others remain as permanent discolorations of the body.Mechanical distension and rapidly developing areas of the body during pregnancy (such as the abdomen, breasts, and thighs) are most commonly associated with striae formation. Some have suggested that relaxin and estrogen combined with higher levels of cortisol during pregnancy can cause an accumulation of mucopolysaccharides, which increases water absorption of connective tissue, making it prime for tearing under mechanical stress. There also seems to be an association between higher body mass indices and in women with bigger babies and the incidence and severity of striae. Also, younger women seem to be at higher risk of developing striae during pregnancy.The prevalence and severity of striae gravidarum varies among populations. The current literature suggest that in the general population of the US, there is a 50%-90% prevalence of striae associated with pregnancy, partly as a result of the normal hormonal changes of pregnancy and partly due to stretching of skin fibers. Many women experience striae gravidarum during their first pregnancy. Nearly 45% percent of women develop striae gravidarum before 24 weeks of gestation. Many women who develop lesions during the first pregnancy do not develop them during later pregnancies. Genetic factors such as genealogy and race also seem to be predictive in the appearance of striae.
Prevention
Collagen and elastin are proteins in the skin that contribute to the skins strength, resilience, flexibility, and help skin that has been stretched to recover its original state. Boosting the production of collagen and elastin helps prevent stretch marks from occurring. Stretch marks can also derive from nutritional deficiencies. Consuming foods that contribute to the skins health, such as zinc-rich foods, foods high in vitamin A, C, D, and protein rich foods, can help suppress stretch marks. A systematic review has not found evidence that creams and oils are useful for preventing or reducing stretch marks in pregnancy. The safety in pregnancy of one ingredient, Centella asiatica, has been questioned. Evidence on treatments for reducing the appearance of the scars after pregnancy is limited.
Treatment
There are no clearly useful treatments for stretch marks, although there are many different suggestions on how to remove them or lessen their appearance.Various efforts that have been tried including laser treatments, glycolic acid, and microdermabrasion. Tretinoin (0.1% w/w), which is a retinoid, has found to be effective on early stretch marks in several studies. Hyaluronic acid also improves the appearance of stretch marks. Topical tretinoin is categorized by the FDA as a known teratogen (causing malformations in fetuses) in animals, without adequate human studies on safety in pregnancy.Carboxytherapy is a known procedure; however, there is a lack of evidence to support how effective it is.
History
Since ancient times, pregnant women have sought remedies to prevent stretch marks during pregnancy. Both ancient Greeks and Romans used olive oil, while Ethiopians and Somalis used frankincense.Striae were first recognized by Roederer in 1773, and were later histologically described by Troisier and Ménétrier in 1889. In 1936, Nardelli made the first morphologically correct descriptions.
Terminology
Medical terminology for these kinds of markings includes striae atrophicae, vergetures, stria distensae, striae cutis distensae, lineae atrophicae, linea albicante, or simply striae.
References
== External links == |
Caudal regression syndrome | Caudal regression syndrome, or sacral agenesis (or hypoplasia of the sacrum), is a rare birth defect. It is a congenital disorder in which the fetal development of the lower spine—the caudal partition of the spine—is abnormal. It occurs at a rate of approximately one per 60,000 live births.Some babies are born with very small differences compared to typical development, and others have significant changes. Most grow up to be otherwise typical adults who have difficulty with walking and incontinence.
Signs and symptoms
This condition exists in a variety of forms, ranging from partial absence of the tail bone regions of the spine to absence of the lower vertebrae, pelvis and parts of the thoracic and/or lumbar areas of the spine. In some cases where only a small part of the spine is absent, there may be no outward sign of the condition. In cases where more substantial areas of the spine are absent, there may be fused, webbed or smaller lower extremities and paralysis. Bowel and bladder control is usually affected.
Cause
The condition arises from some factor or set of factors present during approximately the 3rd week to 7th week of fetal development. Formation of the sacrum/lower back and corresponding nervous system is usually nearing completion by the 4th week of development. Due to abnormal gastrulation, the mesoderm migration is disturbed. This disturbance results in symptoms varying from minor lesions of the lower vertebrae to more severe symptoms such as complete fusion of the lower limbs. While the exact cause is unknown, it has been speculated that the condition has a combination of environmental and genetic causes, and that various types of the condition may have differing causes.Sacral agenesis syndrome (a type of caudal regression syndrome involving agenesis of the lumbar spine, sacrum, and coccyx, and hypoplasia of the lower extremities) is a well-established congenital anomaly associated with maternal diabetes mellitus. Other causes are presumably involved, as demonstrated by the rare overall incidence of caudal regression syndrome (1:60,000) compared to diabetes; however, the condition does have a greatly increased incidence among infants born to mothers with diabetes, estimated at 1 in 350 newborns of mothers with diabetes.The dominant inherited sacral agenesis (also referred to as Currarino syndrome) is very often correlated with a mutation in the Hb9 (also called HlxB9) gene (shown by Sally Ann Lynch, 1995, Nature Genetics).It was previously thought to be related to sirenomelia ("Mermaid syndrome") but has now been determined not to be related to this condition.
Prognosis
There are four levels (or types) of malformation. The least severe indicates partial deformation (unilateral) of the sacrum. The second level indicates a bilateral (uniform) deformation. The most severe types involve a total absence of the sacrum.Depending on the type of sacral agenesis, bowel or urinary bladder deficiencies may be present. A permanent colostomy may be necessary in the case of imperforate anus. Incontinence may also require some type of continence control system (e.g., self-catheterization) be utilized. The condition often impacts the formation of the knees, legs or feet that is sometimes addressed through surgery. For some with tightly webbed, bent knees or knees that are fused straight, disarticulation surgery at the knee may be a viable option to maximize mobility options.Before more comprehensive medical treatment was available, full amputation of the legs at the hip was often performed. More recently, the amputation (actually a disarticulation because no cutting of the bone is involved) is done at the knee for those who have bent knee positions and webbing between thigh and calf to enable more ease of mobility and better seating. Some children with knee disarticulation use prosthetic legs to walk. Prosthetics for children without substantial hip and trunk control is usually abandoned in favor of faster and easier wheelchair mobility as the childs weight and age increase. Children may walk on their hands and generally are able to climb and move about to accomplish whatever they need and want to accomplish. Children more mildly affected may have normal gait and no need for assistive devices for walking. Others may walk with bracing or crutches.There is typically no cognitive impairment associated with this disability. Adults with this disability live independently, attend college, and have careers in various fields. In 2012, Spencer West, a man with sacral agenesis and both legs amputated, climbed Mount Kilimanjaro using only his hands. In 2021, athlete Zion Clark broke the Guinness World Record 20m running on hands.
Society and culture
Notable people
Zion Clark, American track athlete and wrestler, 2022 Guinness World Record holder (20m hand sprint in 4.78 seconds)
Rebecca Dubber, New Zealand para-swimmer and Rio 2016 Paralympic bronze medalist
Kenny Easterday, played a fictionalized version of himself in the film Kenny
Johnny Eck, American freak show performer
Kurt Fearnley, Australian wheelchair racer
Chloé Cooper Jones, American philosopher and author
Bobby Martin, American footballer
Kevin McKee, two-times Olympic champion and two-times world champion in sledge hockey
Sainimili Naivalu, Fijian wheelchair table tennis medallist and disability rights activists
Victoria Pendergast, first female Australian sit-skier at Winter Paralympics
Jessica Rogers, American wheelchair racer and swimmer, founder and President of iSACRA (International Caudal Regression Syndrome Association)
Rose Siggins, actress (American Horror Story: Freak Show)
References
== External links == |
Inflammatory bowel disease | Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, Crohns disease and ulcerative colitis being the principal types. Crohns disease affects the small intestine and large intestine, as well as the mouth, esophagus, stomach and the anus, whereas ulcerative colitis primarily affects the colon and the rectum.IBD also occurs in dogs and is thought to arise from a combination of host genetics, intestinal microenvironment, environmental components and the immune system. There is an ongoing discussion, however, that the term "chronic enteropathy" might be better to use than "inflammatory bowel disease" in dogs because it differs from IBD in humans in how the dogs respond to treatment. For example, many dogs respond to only dietary changes compared to humans with IBD, who often need immunosuppressive treatment. Some dogs may also need immunosuppressant or antibiotic treatment when dietary changes are not enough. After having excluded other diseases that can lead to vomiting, diarrhea, and abdominal pain in dogs, intestinal biopsies are often performed to investigate what kind of inflammation is occurring (lymphoplasmacytic, eosinophilic, or granulomatous). In dogs, low levels of cobalamin in the blood have been shown to be a risk factor for negative outcome.
Signs and symptoms
In spite of Crohns and UC being very different diseases, both may present with any of the following symptoms: abdominal pain, diarrhea, rectal bleeding, severe internal cramps/muscle spasms in the region of the pelvis and weight loss. Anemia is the most prevalent extraintestinal complication of inflammatory bowel disease. Associated complaints or diseases include arthritis, pyoderma gangrenosum, primary sclerosing cholangitis, and non-thyroidal illness syndrome (NTIS). Associations with deep vein thrombosis (DVT) and bronchiolitis obliterans organizing pneumonia (BOOP) have also been reported. Diagnosis is generally by assessment of inflammatory markers in stool followed by colonoscopy with biopsy of pathological lesions.
Causes
IBD is a complex disease which arises as a result of the interaction of environmental and genetic factors leading to immunological responses and inflammation in the intestine.
Diet
People living with IBD are very interested in diet, but little is known about the impact of diet on these patients. Recent reviews underlined the important role of nutritional counselling in IBD patients. Patients should be encouraged to adopt diets that are best supported by evidence and involve monitoring for the objective resolution of inflammation.A 2022 study found that diets with increased intake of fruits and vegetables, reduction of processed meats and refined carbohydrates, and preference of water for hydration were associated with lower risk of active symptoms with IBD, although increased intake of fruits and vegetables alone did not reduce risk of symptoms with Crohns disease.Dietary patterns are associated with a risk for ulcerative colitis. In particular, subjects who were in the highest tertile of the healthy dietary pattern had a 79% lower risk of ulcerative colitis.Gluten sensitivity is common in IBD and associated with having flareups. Gluten sensitivity was reported in 23.6 and 27.3% of Crohns disease and ulcerative colitis patients, respectively.A diet high in protein, particularly animal protein, and/or high in sugar may be associated with increased risk of inflammatory bowel disease and relapses.
Microbiota
As a result of microbial symbiosis and immunity, alterations in the gut microbiome may contribute to inflammatory gut diseases. IBD-affected individuals have been found to have 30–50 percent reduced biodiversity of commensal bacteria, such as decreases in Bacillota (namely Lachnospiraceae) and Bacteroidota. Further evidence of the role of gut flora in the cause of inflammatory bowel disease is that IBD-affected individuals are more likely to have been prescribed antibiotics in the 2–5 year period before their diagnosis than unaffected individuals. The enteral bacteria can be altered by environmental factors, such as concentrated milk fats (a common ingredient of processed foods and confectionery) or oral medications such as antibiotics and oral iron preparations. The mucosal microbiota in the large intestine of IBD patients with active inflammation was found to be associated with pro-inflammatory changes to the host epigenome. However, large international studies have failed to identify a single microbial biomarker of IBD indicating its not driven by any single micro-organism.
Breach of intestinal barrier
Loss of integrity of the intestinal epithelium plays a key pathogenic role in IBD. Dysfunction of the innate immune system as a result of abnormal signaling through immune receptors called toll-like receptors (TLRs)—which activates an immune response to molecules that are broadly shared by multiple pathogens—contributes to acute and chronic inflammatory processes in IBD colitis and associated cancer. Changes in the composition of the intestinal microbiota are an important environmental factor in the development of IBD. Detrimental changes in the intestinal microbiota induce an inappropriate (uncontrolled) immune response that results in damage to the intestinal epithelium. Breaches in this critical barrier (the intestinal epithelium) allow further infiltration of microbiota that, in turn, elicit further immune responses. IBD is a multifactorial disease that is nonetheless driven in part by an exaggerated immune response to gut microbiota that causes defects in epithelial barrier function.
Oxidative stress and DNA damage
Pereira et al. reviewed evidence from numerous studies indicating that oxidative stress and DNA damage likely have a role in the pathophysiology of IBD. Oxidative DNA damage as measured by 8-OHdG levels was found to be significantly increased in patients with IBD compared to control patients, and in inflamed mucosa compared with non-inflamed mucosa.
Genetics
A genetic component to IBD has been recognized for over a century. Research that has contributed to understanding of the genetics include studies of ethnic groups (e.g., Ashkenazi Jews, Irish), familial clustering, epidemiological studies, and twin studies. With the advent of molecular genetics, understanding of the genetic basis has expanded considerably, particularly in the past decade. The first gene linked to IBD was NOD2 in 2001. Genome-wide association studies have since added to understanding of the genomics and pathogenesis of the disease. More than 200 single nucleotide polymorphisms (SNPs or "snips") are now known to be associated with susceptibility to IBD. One of the largest genetic studies of IBD was published in 2012 . The analysis explained more of the variance in Crohns disease and ulcerative colitis than previously reported. The results suggested that commensal microbiota are altered in such a way that they act as pathogens in inflammatory bowel diseases. Other studies show that mutations in IBD-associated genes might interfere with the cellular activity and interactions with the microbiome that promote normal immune responses. Many studies identified that microRNAs dysregulation involved in IBD and to promote colorectal cancer. By 2020, single-cell RNA sequencing analysis was launched by a small consortium using IBD patient biopsy material in a search for therapeutic targets.
Diagnosis
The diagnosis is usually confirmed by biopsies on colonoscopy. Fecal calprotectin is useful as an initial investigation, which may suggest the possibility of IBD, as this test is sensitive but not specific for IBD.
Differential diagnosis
Other diseases may cause an increased excretion of fecal calprotectin, such as infectious diarrhea, untreated coeliac disease, necrotizing enterocolitis, intestinal cystic fibrosis and neoplastic pediatric tumor cells.Conditions with similar symptoms as Crohns disease includes intestinal tuberculosis, Behçets disease, ulcerative colitis, nonsteroidal anti-inflammatory drug enteropathy, irritable bowel syndrome and coeliac disease.Conditions with similar symptoms as ulcerative colitis includes acute self-limiting colitis, amebic colitis, schistosomiasis, Crohns disease, colon cancer, irritable bowel syndrome, intestinal tuberculosis and nonsteroidal anti-inflammatory drug enteropathy.Liver function tests are often elevated in inflammatory bowel disease, and are often mild and generally return spontaneously to normal levels. The most relevant mechanisms of elevated liver functions tests in IBD are drug-induced hepatotoxicity and fatty liver.
Classification
The chief types of inflammatory bowel disease are Crohns disease and ulcerative colitis (UC). Inflammatory bowel diseases fall into the class of autoimmune diseases, in which the bodys own immune system attacks elements of the digestive system.Accounting for fewer cases are other forms of IBD, which are not always classified as typical IBD:
Microscopic colitis subdivided into collagenous colitis and lymphocytic colitis
Diversion colitis
Behçets disease
Early Onset IBD
Indeterminate colitisNo disease specific markers are currently known in the blood, enabling the reliable separation of Crohns disease and ulcerative colitis patients. The way doctors can tell the difference between Crohns disease and UC is the location and nature of the inflammatory changes. Crohns can affect any part of the gastrointestinal tract, from mouth to anus (skip lesions), although a majority of the cases start in the terminal ileum. Ulcerative colitis, in contrast, is restricted to the colon and the rectum. Microscopically, ulcerative colitis is restricted to the mucosa (epithelial lining of the gut), while Crohns disease affects the full thickness of the bowel wall ("transmural lesions"). Lastly, Crohns disease and ulcerative colitis present with extra-intestinal manifestations (such as liver problems, arthritis, skin manifestations and eye problems) in different proportions.In 10–15% of cases, a definitive diagnosis neither of Crohns disease nor of ulcerative colitis can be made because of idiosyncrasies in the presentation. In this case, a diagnosis of indeterminate colitis may be made. Although a recognised definition, not all centres refer to this.
Treatment
Surgery
CD and UC are chronic inflammatory diseases, and are not medically curable. However, ulcerative colitis can in most cases be cured by proctocolectomy, although this may not eliminate extra-intestinal symptoms. An ileostomy will collect feces in a bag. Alternatively, a pouch can be created from the small intestine; this serves as the rectum and prevents the need for a permanent ileostomy. Between one-quarter and one-half of patients with ileo-anal pouches do have to manage occasional or chronic pouchitis.Surgery cannot cure Crohns disease but may be needed to treat complications such as abscesses, strictures or fistulae. Severe cases may require surgery, such as bowel resection, strictureplasty or a temporary or permanent colostomy or ileostomy. In Crohns disease, surgery involves removing the worst inflamed segments of the intestine and connecting the healthy regions, but unfortunately, it does not cure Crohns or eliminate the disease. At some point after the first surgery, Crohns disease can recur in the healthy parts of the intestine, usually at the resection site. (For example, if a patient with Crohns disease has an ileocecal anastomosis, in which the caecum and terminal ileum are removed and the ileum is joined to the ascending colon, their Crohns will nearly always flare-up near the anastomosis or in the rest of the ascending colon).
Medical therapies
Medical treatment of IBD is individualised to each patient. The choice of which drugs to use and by which route to administer them (oral, rectal, injection, infusion) depends on factors including the type, distribution, and severity of the patients disease, as well as other historical and biochemical prognostic factors, and patient preferences. For example, mesalazine is more useful in ulcerative colitis than in Crohns disease. Generally, depending on the level of severity, IBD may require immunosuppression to control the symptoms, with drugs such as prednisone, tumor necrosis factor inhibitors (TNF inhibitors), azathioprine, methotrexate, or 6-mercaptopurine.Steroids, such as the glucocorticoid prednisone, are frequently used to control disease flares and were once acceptable as a maintenance drug. Biological therapy for inflammatory bowel disease, especially the TNF inhibitors, are used in people with more severe or resistant Crohns disease and sometimes in ulcerative colitis.Treatment is usually started by administering drugs with high anti-inflammatory effects, such as prednisone. Once the inflammation is successfully controlled, another drug to keep the disease in remission, such as mesalazine in UC, is the main treatment. If further treatment is required, a combination of an immunosuppressive drug (such as azathioprine) with mesalazine (which may also have an anti-inflammatory effect) may be needed, depending on the patient. Controlled release budesonide is used for mild ileal Crohns disease.
Nutritional and dietetic therapies
Exclusive enteral nutrition is a first-line therapy in pediatric Crohns disease with weaker data in adults.: 331 Evidence supporting exclusive enteral nutrition in ulcerative colitis is lacking.: 333 Nutritional deficiencies play a prominent role in IBD. Malabsorption, diarrhea, and GI blood loss are common features of IBD. Deficiencies of B vitamins, fat-soluble vitamins, essential fatty acids, and key minerals such as magnesium, zinc, and selenium are extremely common and benefit from replacement therapy. Dietary interventions, including certain exclusion diets like the specific carbohydrate diet (SCD) can be beneficial for symptom management. Dietary fiber interventions, such as psyillium supplementation (a mixture of soluble and insoluble fibers), may relieve symptoms as well as induce/maintain remission by altering the microbiome composition of the GI tract, thereby improving regulation of immune function, reducing inflammation, and helping to restore the intestinal mucosal lining.Anaemia is commonly present in both ulcerative colitis and Crohns disease. Due to raised levels of inflammatory cytokines which lead to the increased expression of hepcidin, parenteral iron is the preferred treatment option as it bypasses the gastrointestinal system, has lower incidence of adverse events and enables quicker treatment. Hepcidin itself is also an anti-inflammatory agent. In the murine model very low levels of iron restrict hepcidin synthesis, worsening the inflammation that is present. Enteral nutrition has been found to be efficient to improve hemoglobin level in patients with inflammatory bowel disease, especially combined with erythropoietin.
Microbiome
There is preliminary evidence of an infectious contribution to inflammatory bowel disease in some patients that may benefit from antibiotic therapy, such as with rifaximin. The evidence for a benefit of rifaximin is mostly limited to Crohns disease with less convincing evidence supporting use in ulcerative colitis.Fecal microbiota transplant is a relatively new treatment option for IBD which has attracted attention since 2010. Some preliminary studies have suggested benefits similar to those in Clostridium difficile infection but a review of use in IBD shows that FMT is safe, but of variable efficacy. A 2014 review stated that more randomized controlled trials were needed.
Alternative medicine
Complementary and alternative medicine approaches have been used in inflammatory bowel disorders. Evidence from controlled studies of these therapies has been reviewed; risk of bias was quite heterogeneous. The best supportive evidence was found for herbal therapy, with Plantago ovata and curcumin in UC maintenance therapy, wormwood in CD, mind/body therapy and self-intervention in UC, and acupuncture in UC and CD.
Novel approaches
Stem cell therapy is undergoing research as a possible treatment for IBD. A review of studies suggests a promising role, although there are substantial challenges, including cost and characterization of effects, which limit the current use in clinical practice.
Psychological interventions
Currently, there is no evidence to recommend psychological treatment, such as psychotherapy, stress management and patients education, to all adults with IBD in general. These treatments had no effect on quality of life, emotional well-being and disease activity. The need for these approaches should be individually assessed and further researched to identify subgroups and determine type of therapy that may benefit individuals with IBD. In adolescents population such treatments may be beneficial on quality of life and depression, although only short-term effects have been found, which also imposes the need for further research.
Treatment standards
Crohns and Colitis Australia, the peak body for IBD in Australia, where prevalence is one of the highest in the world, reviewed the quality of care for patients admitted to Australian hospitals. They found that only one hospital met accepted standards for multidisciplinary care, but that care was improved with the availability of even minimal specialised services.
Prognosis
While IBD can limit quality of life because of pain, vomiting, and diarrhea, it is rarely fatal on its own. Fatalities due to complications such as toxic megacolon, bowel perforation and surgical complications are also rare.. Fatigue is a common symptom of IBD and can be a burden.Around one-third of individuals with IBD experience persistent gastrointestinal symptoms similar to irritable bowel syndrome (IBS) in the absence of objective evidence of disease activity. Despite enduring the side-effects of long-term therapies, this cohort has a quality of life that is not significantly different to that of individuals with uncontrolled, objectively active disease, and escalation of therapy to biological agents is typically ineffective in resolving their symptoms. The cause of these IBS-like symptoms is unclear, but it has been suggested that changes in the gut-brain axis, epithelial barrier dysfunction, and the gut flora may be partially responsible.While patients of IBD do have an increased risk of colorectal cancer, this is usually caught much earlier than the general population in routine surveillance of the colon by colonoscopy, and therefore patients are much more likely to survive.New evidence suggests that patients with IBD may have an elevated risk of endothelial dysfunction and coronary artery disease.The goal of treatment is toward achieving remission, after which the patient is usually switched to a lighter drug with fewer potential side effects. Every so often, an acute resurgence of the original symptoms may appear; this is known as a "flare-up". Depending on the circumstances, it may go away on its own or require medication. The time between flare-ups may be anywhere from weeks to years, and varies wildly between patients – a few have never experienced a flare-up.Life with IBD can be challenging; however, many with the conditionlead relatively normal lives. IBD carries a psychological burden due to stigmatization of being diagnosed, leading to high levels of anxiety, depression, and a general reduction in the quality of life. Although living with IBD can be difficult, there are numerous resources available to help families navigate the ins and out of IBD, such as the Crohns and Colitis Foundation of America (CCFA).
Epidemiology
IBD resulted in a global total of 51,000 deaths in 2013 and 55,000 deaths in 1990. The increased incidence of IBD since World War 2 has been correlated to the increase in meat consumption worldwide, supporting the claim that animal protein intake is associated with IBD. However, there are many environmental risk factors that have been linked to the increased and decreased risk of IBD, such as smoking, air pollution and greenspace, urbanization and Westernization. Inflammatory bowel diseases are increasing in Europe. Incidence and prevalence of IBD has risen steadily for the last decades in Asia, which could be related changes in diet and other environmental factors.Around 0.8% of people in the UK have IBD. Similarly, around 270,000 (0.7%) of people in Canada have IBD, with that number expected to rise to 400,000 (1%) by 2030.
Research
The following treatment strategies are not used routinely, but appear promising in some forms of inflammatory bowel disease.
Initial reports suggest that "helminthic therapy" may not only prevent but even control IBD: a drink with roughly 2,500 ova of the Trichuris suis helminth taken twice monthly decreased symptoms markedly in many patients. It is even speculated that an effective "immunization" procedure could be developed—by ingesting the cocktail at an early age.Prebiotics and probiotics are focusing increasing interest as treatments for IBD. Currently, there is evidence to support the use of certain probiotics in addition to standard treatments in people with ulcerative colitis but there is no sufficient data to recommend probiotics in people with Crohns disease. Both single strain and multi-strain probiotics have been researched for mild to moderate cases of ulcerative colitis. The most clinically researched multi-strain probiotic with over 70 human trials is the De Simone Formulation. Further research is required to identify specific probiotic strains or their combinations and prebiotic substances for therapies of intestinal inflammation.Currently, the probiotic strain, frequency, dose and duration of the probiotic therapy are not established. In severely ill people with IBD there is a risk of the passage of viable bacteria from the gastrointestinal tract to the internal organs (bacterial translocation) and subsequent bacteremia, which can cause serious adverse health consequences. Live bacteria might not be essential because of beneficial effects of probiotics seems to be mediated by their DNA and by secreted soluble factors, and their therapeutic effects may be obtained by systemic administration rather than oral administration.In 2005 New Scientist published a joint study by Bristol University and the University of Bath on the apparent healing power of cannabis on IBD. Reports that cannabis eased IBD symptoms indicated the possible existence of cannabinoid receptors in the intestinal lining, which respond to molecules in the plant-derived chemicals. CB1 cannabinoid receptors – which are known to be present in the brain – exist in the endothelial cells which line the gut, it is thought that they are involved in repairing the lining of the gut when damaged.The team deliberately damaged the cells to cause inflammation of the gut lining and then added synthetically produced cannabinoids; the result was that gut started to heal: the broken cells were repaired and brought back closer together to mend the tears. It is believed that in a healthy gut, natural endogenous cannabinoids are released from endothelial cells when they are injured, which then bind to the CB1 receptors. The process appears to set off a wound-healing reaction, and when people use cannabis, the cannabinoids bind to these receptors in the same way.Previous studies have shown that CB1 receptors located on the nerve cells in the gut respond to cannabinoids by slowing gut motility, therefore reducing the painful muscle contractions associated with diarrhea. CB2, another cannabinoid receptor predominantly expressed by immune cells, was detected in the gut of people with IBD at a higher concentration. These receptors, which also respond to chemicals in cannabis, appear to be associated with apoptosis – programmed cell death – and may have a role in suppressing the overactive immune system and reducing inflammation by mopping up excess cells.Activation of the endocannabinoid system was found efficient in ameliorating colitis and increasing the survival rate of mice, and reducing remote organ changes induced by colitis, further suggest that modulation of this system is a potential therapeutic approach for IBDs and the associated remote organ lesions.Alicaforsen is a first generation antisense oligodeoxynucleotide designed to bind specifically to the human ICAM-1 messenger RNA through Watson-Crick base pair interactions in order to subdue expression of ICAM-1. ICAM-1 propagates an inflammatory response promoting the extravasation and activation of leukocytes (white blood cells) into inflamed tissue. Increased expression of ICAM-1 has been observed within the inflamed intestinal mucosa of people with ulcerative colitis, pouchitis and Crohns, where ICAM-1 over production correlated with disease activity. This suggests that ICAM-1 is a potential therapeutic target in the treatment of these diseases.Cannabinoid CB2 receptor agonists are found to decrease the induction of ICAM-1 and VCAM-1 surface expression in human brain tissues and primary human brain endothelial cells (BMVEC) exposed to various pro-inflammatory mediators.In 2014, an alliance among the Broad Institute, Amgen and Massachusetts General Hospital formed with the intention to "collect and analyze patient DNA samples to identify and further validate genetic targets."In 2015, a meta-analysis on 938 IBD patients and 953 controls, IBD was significantly associated with having higher odds of vitamin D deficiency.Gram-positive bacteria present in the lumen could be associated with extending the time of relapse for ulcerative colitis.Bidirectional pathways between depression and IBD have been suggested and psychological processes have been demonstrated to influence self-perceived physical and psychological health over time. IBD-disease activity may impact quality of life and over time may significantly affect individuals mental well-being, which may be related to the increased risk to develop anxiety and/or depression. On the other hand, psychological distress may also influence IBD activity.Higher rates of anxiety and depression are observed among those with IBD compared to healthy individuals, which correlated with disease severity. Moreover, anxiety and depression rates increase during active disease compared with inactive phases.
See also
Inflammatory bowel disease-22
World Inflammatory Bowel Disease Day
References
External links
Inflammatory bowel disease at Curlie |
Winchester syndrome | Winchester syndrome is a rare hereditary connective tissue disease described in 1969, of which the main characteristics are short stature, marked contractures of joints, opacities in the cornea, coarse facial features, dissolution of the carpal and tarsal bones (in the hands and feet, respectively), and osteoporosis. Winchester syndrome was once considered to be related to a similar condition, multicentric osteolysis, nodulosis, and arthropathy (MONA). However, it was discovered that the two are caused by mutations found in different genes; however they mostly produce the same phenotype or clinical picture. Appearances resemble rheumatoid arthritis. Increased uronic acid is demonstrated in cultured fibroblasts from the skin and to a lesser degree in both parents. Despite initial tests not showing increased mucopolysaccharide excretion, the disease was regarded as a mucopolysaccharidosis. Winchester syndrome is thought to be inherited as an autosomal recessive trait.
Symptoms
Symptoms of Winchester or MONA syndrome begin with the deterioration of bone within the hands and feet. This loss of bone causes pain, pathological fractures and limited mobility. The abnormalities of the bone spread to other areas of the body, mostly the joints. This causes arthropathy: stiffening of the joints (contractures) and swollen joints. Many people develop osteopenia and osteoporosis throughout their entire body. The bone and joint manifestations characteristically start in the hands and feet then spread to the larger joints eventually like elbows and shoulders in the upper extremities and knees and hips in the lower extremities. Due to the damage to the bones, many affected individuals suffer from bone fractures, arthritis and occasionally short stature. Many individuals experience leathery skin where the skin appears dark and thick. Excessive hair growth is known to be found in these darker areas of the skin (hypertrichosis). The eyes may develop a white or clear covering the cornea (corneal opacities) which can cause problems with vision.
Mechanism
Winchester syndrome is believed to be inherited through autosomal recessive inheritance. It believed that this disease is caused by a nonlysosomal connective-tissue disturbance. The protein inactivation mutation is found on the matrix metalloproteinase 2 gene (MMP2). MM2 is responsible for bone remodeling. Bone remodeling is the process in which old bone is destroyed so that new bone can be created to replace it. This mutation causes a multicentric osteolysis and arthritis syndrome. It is hypothesized that the loss of an upstream MMP-2 protein activator MT1-MMP, results in decreased MMP-2 activity without affecting MMP2. The inactivating homoallelic mutation of MT1-MMP can be seen at the surface of fibroblasts. It was determined that fibroblasts lacking MT1-MMP lack the ability to degrade type I collagen which leads to anomalous function.
Diagnosis
In 1989, a set of diagnostic criteria were created for the diagnosing of Winchester syndrome. The typical diagnosis criteria begin with skeletal radiological test results and two of the defining symptoms, such as short stature, coarse facial features, hyperpigmentation, or excessive hair growth. The typical tests that are performed are x-ray and magnetic resonance imaging. A complete skeletal radiographic survey is mandatory for diagnosis of Winchester or MONA syndrome together with a detailed musculoskeletal examination and craniofacial morphology assessment. It appears that Winchester syndrome is more common in women than men. Winchester syndrome is very rare. There have only been a few individuals worldwide who were reported to have this disorder.
Treatment
There is no known cure for Winchester syndrome; however, there are many therapies that can aid in the treatment of symptoms. Such treatments can include medications: anti-inflammatories, muscle relaxants, and antibiotics. Many individuals will require physical therapy to promote movement and use of the limbs affected by the syndrome. Bisphosphonates have been used to improve bone quality and density or at least halt the progression of bone damages or osteolysis. Genetic counseling is typically prescribed for families to help aid in the understanding of the disease. There are a few clinical trials available to participate in. The prognosis for patients diagnosed with Winchester syndrome is positive. It has been reported that several affected individuals have lived to middle age; however, the disease is progressive and mobility will become limited towards the end of life. Eventually, the contractures will remain even with medical intervention, such as surgery.
Research
In 2005, a patient with Winchester syndrome was shown to have mutations in the matrix metalloproteinase 2 (MMP2) gene. A 2006 study showed other mutations found in the MMP2 gene. This has led to the belief that there are many similar diseases within this family of mutations. As of 2007, it was found that these mutations are also found in Torg and Nodulosis-arthropathy-osteolysis syndrome (NAO). This means that Torg, NAO, and Winchester syndrome are allelic disorders. In 2014, a new case of Winchester syndrome was reported. According to a recently published article, it was discovered that multicentric osteolysis, nodulosis, and arthropathy (MONA) and Winchester syndrome are different diseases. Mutations in MMPS and MT1-MMP result in similar but distinctly different "vanishing bone" syndromes.
See also
Multicentric carpotarsal osteolysis syndrome
References
== External links == |
Hemothorax | A hemothorax (derived from hemo- [blood] + thorax [chest], plural hemothoraces) is an accumulation of blood within the pleural cavity. The symptoms of a hemothorax may include chest pain and difficulty breathing, while the clinical signs may include reduced breath sounds on the affected side and a rapid heart rate. Hemothoraces are usually caused by an injury, but they may occur spontaneously due to cancer invading the pleural cavity, as a result of a blood clotting disorder, as an unusual manifestation of endometriosis, in response to a collapsed lung, or rarely in association with other conditions.
Hemothoraces are usually diagnosed using a chest X-ray, but they can be identified using other forms of imaging including ultrasound, a CT scan, or an MRI. They can be differentiated from other forms of fluid within the pleural cavity by analysing a sample of the fluid, and are defined as having a hematocrit of greater than 50% that of the persons blood. Hemothoraces may be treated by draining the blood using a chest tube. Surgery may be required if the bleeding continues. If treated, the prognosis is usually good. Complications of a hemothorax include infection within the pleural cavity and the formation of scar tissue.
Background
The lungs are surrounded by two layers of tissue called the pulmonary pleurae. In most healthy people, these two layers are tightly apposed, separated only by a small amount of pleural fluid. In certain disease states, the space between these two layers, called the pleural cavity, swells with fluid. This accumulation of fluid in the pleural cavity is called pleural effusion. Pleural effusions are given specific names depending on the nature of the fluid: hydrothorax for serous fluid, pyothorax for pus, hemothorax for blood, and urinothorax for urine.
Signs and symptoms
Signs and symptoms include anxiety, rapid breathing, restlessness, shock, and pale, cool, clammy skin. When the affected area is percussed, a dull feeling may be observed. Neck veins may be flat and breathing sounds reduced. It can also cause a collapsed lung (atelectasis). Massive hemothorax, often defined as over 1.5 liters of blood initially when an intercostal drain is placed, or a bleeding rate greater than .2 liters/hr, can result in shock with two causes: massive bleeding resulting from hypovolemic shock, and venous pressure from the retained blood, impairing blood flow.
Causes
Hemothoraces are classified in three broad categories according to the cause and in order of frequency: traumatic, iatrogenic, or nontraumatic. All three categories have the potential to affect major arteries and result in death by blood loss.
Traumatic
Hemothorax is most often caused by blunt or penetrating trauma to the chest. In blunt traumatic cases, hemothorax typically occurs when rib fracture damages the intercostal vessels or the intraparenchymal pulmonary vessel, while in penetrating trauma, hemothorax occurs due to injuries directly affecting blood vessels in the thoracic wall, lung parenchyma, or the heart. If large blood vessels such as the aorta are damaged, the blood loss can be massive. Minor chest trauma can cause hemothorax when the bloods ability to clot is diminished as result either of anticoagulant medications or when there are bleeding disorders such as hemophilia.
Iatrogenic
Iatrogenic hemothorax can occur as a complication of heart and lung surgery, for example the rupture of lung arteries caused by the placement of catheters, thoracotomy, thoracostomy, or thoracentesis. The most common iatrogenic causes include subclavian venous catheterizations and chest tube placements, with an occurrence rate of around 1% Sometimes, a Swan-Ganz catheter causes rupture of the pulmonary artery, causing a massive hemothorax. It can also be caused by other procedures like pleural, lung, or transbronchial biopsies, CPR, Nuss procedure, or endoscopic treatment of esophageal varices. Iatrogenic hemothorax is more common in people who have chronic kidney disease in the intensive care unit.
Nontraumatic
Less frequently, hemothoraces may occur spontaneously. Nontraumatic hemothoraces most frequently occur as a complication of some forms of cancer if the tumour invades the pleural space. Cancers responsible for hemothoraces include angiosarcomas, schwannomas, mesothelioma, thymomas, germ cell tumours, and lung cancer. Significant hemothoraces can occur with spontaneous rupture of small vessels when the bloods ability to clot is diminished as result of anticoagulant medications. In cases caused by anticoagulant therapy, the hemothorax becomes noticeable 4–7 days after anticoagulant therapy is started. In cases of hemothorax complicating pulmonary embolism treatment, the hemothorax is usually on the side of the original embolism. Those with an abnormal accumulation of air within the pleural space (a pneumothorax) can bleed into the cavity, which occurs in about 5% of cases of spontaneous pneumothorax, especially when lung bullae rupture. The resulting combination of air and blood within the pleural space is known as a hemopneumothorax. Bone growth in exostosis can create sharp edges, which can result in hemothorax by damaging adjacent arteries. It can occur postpartum due to the change in thoracic pressure during labor.
Vascular
Vascular causes of hemothorax include rupture of the descending aorta, in which case it initially involves the left pleural and mediastinal area due to the close vicinity of the pleural cavity. Rarely, a rupture of the thoracic aorta can result in a hemothorax, but the bleeding usually occurs in the pericardial space. Spontaneous tearing of blood vessels is more likely to occur in those with disorders that weaken blood vessels such as some forms of Ehlers-Danlos syndrome, disorders that lead to malformed blood vessels as seen in Rendu-Osler-Weber syndrome, or in bleeding disorders such as hemophilia and Glanzmann thromboastenia. Other rare causes of hemothorax include neurofibromatosis type 1 and extramedullary hematopoiesis.
Catamenial
Rarely, hemothoraces can arise due to extrapelvic endometriosis, a condition in which tissue similar to the lining that normally covers the inside of the uterus forms in unusual locations outside the pelvis. Endometriotic tissue that implants on the pleural surface can bleed in response to the hormonal changes of the menstrual cycle, causing what is known as a catamenial hemothorax as part of thoracic endometriosis along with catamenial pneumothorax, catamenial hemoptysis, and lung nodules of endometriosis. Catamenial hemothorax represents 14% of cases of thoracic endometriosis syndrome while catamenial pneumothorax is seen in 73%, catamenial hemoptysis in 7%, and pulmonary nodules in 6%.
Mechanism
When a hemothorax occurs, blood enters the pleural cavity. The blood loss from the circulation has several effects. Firstly, as blood builds up within the pleural cavity, it begins to interfere with the normal movement of the lungs, preventing one or both lungs from fully expanding and thereby interfering with the normal transfer of oxygen and carbon dioxide to and from the blood. Secondly, blood that has been lost into the pleural cavity can no longer be circulated. Hemothoraces can lead to significant blood loss – each half of the thorax can hold more than 1500 milliliters of blood, representing more than 25% of an average adults total blood volume. The body may struggle to cope with this blood loss, and tries to compensate by maintaining blood pressure by forcing the heart to pump harder and faster, and by squeezing or constricting small blood vessels in the arms and legs. These compensatory mechanisms can be recognised by a rapid resting heart rate and cool fingers and toes.If the blood within the pleural cavity is not removed, it will eventually clot. This clot tends to stick the parietal and visceral pleura together and has the potential to lead to scarring within the pleura, which if extensive leads to the condition known as a fibrothorax. Following the initial loss of blood, a small hemothorax may irritate the pleura, causing additional fluid to seep out, leading to a bloodstained pleural effusion. Furthermore, as enzymes in the pleural fluid begin to break down the clot, the protein concentration of the pleural fluid increases. As a result, the osmotic pressure of the pleural cavity increases, causing fluid to leak into the pleural cavity from the surrounding tissues.
Diagnosis
Hemothoraces are most commonly detected using a chest X-ray, although ultrasound is sometimes used in an emergency setting. It can be suspected in any person with any form of chest trauma. However, plain X-rays may miss smaller hemothoraces while other imaging modalities such as computed tomography (CT), or magnetic resonance imaging may be more sensitive. In cases where the nature of an effusion is in doubt, a sample of fluid can be aspirated and analysed in a procedure called thoracentesis. Physical examination is used initially. Auscultation has been reported to have an accuracy of nearly 100% in diagnosing hemopneumothorax.
Chest X-ray
A chest X-ray is the most common technique used to diagnosis a hemothorax. X-rays should ideally be taken in an upright position (an erect chest X-ray), but may be performed with the person lying on their back (supine) if an erect chest X-ray is not feasible. On an erect chest X-ray, a hemothorax is suggested by blunting of the costophrenic angle or partial or complete opacification of the affected half of the thorax. On a supine film the blood tends to layer in the pleural space, but can be appreciated as a haziness of one half of the thorax relative to the other. A small hemothorax may be missed on a chest X-ray as several hundred milliliters of blood can be hidden by the diaphragm and abdominal viscera on an erect film. Supine X-rays are even less sensitive and as much as one liter of blood can be missed on a supine film.
Other methods
Ultrasonography may be used to detect hemothorax and other pleural effusions. This technique is of particular use in the critical care and trauma settings as it provides rapid, reliable results at the bedside. Ultrasound is more sensitive than chest x-ray in detecting hemothorax. Ultrasound can cause issues in people who are morbidly obese or have subcutaneous emphysema. When CT is unavailable in the current setting or the person cannot be moved to the scan, ultrasound is used.Computed tomography (CT or CAT) scans may be useful for diagnosing retained hemothorax as this form of imaging can detect much smaller amounts of fluid than a plain chest X-ray. However, CT is less used as a primary means of diagnosis within the trauma setting, as these scans require a critically ill person to be transported to a scanner, are slower, and require the subject to remain supine.Magnetic resonance imaging (MRI) can be used to differentiate between a hemothorax and other forms of pleural effusion, and can suggest how long the hemothorax has been present for. Fresh blood can be seen as a fluid with low T1 but high T2 signals, while blood that has been present for more than a few hours displays both low T1 and T2 signals. MRI is used infrequently in the trauma setting due to the prolonged time required to perform an MRI, and the deterioration in image quality that occurs with motion.
Thoracentesis
Although imaging techniques can demonstrate that fluid is present within the pleural space, it may be unclear what this fluid represents. To establish the nature of the fluid, a sample can be removed by inserting a needle into the pleural cavity in a procedure known as a thoracentesis or pleural tap. In this context, the most important assessment of the pleural fluid is the percentage by volume that is taken up by red blood cells (the hematocrit) A hemothorax is defined as having a hematocrit of at least 50% of that found in the affected persons blood, although the hematocrit of a chronic hemothorax may be between 25 and 50% if additional fluid has been secreted by the pleura. Pleural fluid can dilute hemothoraces in as low as 3–4 days. The red blood cells in the effusion spontaneously break down. Distinguishing the pleural fluid from blood by colour is impossible when the hematocrit value is over 5%. For these reasons, even if there is a hematocrit value under 50%, further investigations can be done in order to figure out if there is a source of bleeding. Hematocrit can be roughly calculated by dividing the red blood cell count of the pleural fluid by 100,000. Thoracentesis is the test most commonly used to diagnose a hemothorax in animals. Hemothorax can itself be a rare complication of thoracentesis if the intercostal artery is punctured.
Treatment
The treatment of a hemothorax depends largely on the extent of bleeding. While small hemothoraces may require little in the way of treatment, larger hemothoraces may require fluid resuscitation to replace the blood that has been lost, drainage of the blood within the pleural space using a procedure known as a tube thoracostomy, and potentially surgery in the form of a thoracotomy or video-assisted thoracoscopic surgery (VATS) to prevent further bleeding. Occasionally, transcatheter arterial embolization may be used to stop ongoing arterial bleeding. Additional treatment options include antibiotics to reduce the risk of infection and fibrinolytic therapy to break down clotted blood within the pleural space.
Thoracostomy
Blood in the cavity can be removed by inserting a drain (chest tube) in a procedure called a tube thoracostomy. This procedure is indicated for most causes of hemothorax, but should be avoided in aortic rupture which should be managed with immediate surgery. The thoracostomy tube is usually placed between the ribs in the sixth or seventh intercostal space at the mid-axillary line. It is important to avoid a chest tube becoming obstructed by clotted blood as obstruction prevents adequate drainage of the pleural space. Clotting occurs as the clotting cascade is activated when the blood leaves the blood vessels and comes into contact with the pleural surface, injured lung or chest wall, or the thoracostomy tube. Inadequate drainage may lead to a retained hemothorax, increasing the risk of infection within the pleural space (empyema) or the formation of scar tissue (fibrothorax). Thoracostomy tubes with a diameter of 24–36 F (large-bore tubes) should be used, as these reduce the risk of blood clots obstructing the tube. Manual manipulation of chest tubes (referred to as milking, stripping, or tapping) is commonly performed to maintain an open tube, but no conclusive evidence has demonstrated that this improves drainage. If a chest tube does become obstructed, the tube can be cleared using open or closed techniques. Tubes should be removed as soon as drainage has stopped, as prolonged tube placement increases the risk of empyema.
Surgery
About 10–20% of traumatic hemothoraces require surgical management. Larger hemothoraces, or those that continue to bleed following drainage, may require surgery. This surgery may take the form of a traditional open-chest procedure (a thoracotomy), but may be performed using video-associated thoracoscopic surgery (VATS). While there is no universally accepted cutoff for the volume of blood loss required before surgery is indicated, generally accepted indications include more than 1500 mL of blood drained from a thoracostomy, bleeding rate of over 500mL/hr in the first hour followed by over 200 mL, hemodynamic instability, or the need for repeat blood transfusions. VATS is less invasive and cheaper than an open thoracotomy, and can reduce the length of hospital stay, but a thoracotomy may be preferred when hypovolemic shock is present, in order to watch bleeding. The procedure should ideally be performed within 72 hours of the injury as delay may increase the risk of complications. In clotted hemothorax, VATS is the generally preferred procedure to remove the clot, and is indicated if the hemothorax fills 1/3 or more of a hemithorax. The ideal time to remove a clot using VATS is at 48–96 hours, but can be attempted up to nine days after the injury.
Other
Thoracentesis is no longer used in the treatment of hemothorax, although it may still be used to treat small hemothoraces. In catamenial hemothorax, the bleeding is typically self-limiting and mild. Most people with the condition are stable and can be treated with hormonal therapies. They are only partially effective. Surgical removal of the endometrial tissue may be necessary in recurrent cases. However, the disease frequently recurs. Resuscitation with intravenous fluids or with blood products may be required. In fulminant cases, transfusions may be administered before admission to the hospital. Clotting abnormalities, such as those caused by anticoagulant medications, should be reversed. Prophylactic antibiotics are given for 24 hours in the case of trauma. Blood clots may be retained within the pleural cavity despite chest tube drainage. They are a risk factor for complications like fibrothorax and empyema. Such retained clots should be removed, preferably with video-assisted thoracoscopic surgery (VATS). If VATS is unavailable, an alternative is fibrinolytic therapy such as streptokinase or urokinase given directly into the pleural space seven to ten days after the injury. The issues with fibrinolytic therapy include having a high cost and lengthened hospital stay. Residual clot that does not dissipate in response to fibrinolytics may require surgical removal in the form of decortication.
Prognosis
The prognosis following a hemothorax depends on its size, the treatment given, and the underlying cause. While small hemothoraces may cause little in the way of problems, in severe cases an untreated hemothorax may be rapidly fatal due to uncontrolled blood loss. If left untreated, the accumulation of blood may put pressure on the mediastinum and the trachea, limiting the hearts ability to fill. However, if treated, the prognosis following a traumatic hemothorax is usually favourable and dependent on other non-thoracic injuries that have been sustained at the same time, the age of the person, and the need for mechanical ventilation. Hemothoraces caused by benign conditions such as endometriosis have a good prognosis, while those caused by neurofibromatosis type 1 has a 36% rate of death, and those caused by aortic rupture are often fatal. Penetrating trauma is significantly less common, and has a much higher death rate, with up to 90% dying before arriving at the hospital. Gunshot wounds are associated with a higher death rates compared to stab wounds. In cases of penetrating trauma involving the heart, less than 1% survive.
Complications
Complications can occur following a hemothorax, and are more likely to occur if the blood has not been adequately drained from the pleural cavity. Blood that remains within the pleural space can become infected, and is known as an empyema. It occurs in 3–4% of traumatic cases, and 27-33% of retained hemothoraces. It is more likely in people who develop shock, had a contaminated pleural space during the injury, persistent bronchopleural fistulae, and lung contusions. The likelihood of it can be reduced by keeping thoracostomy tubes sterile and by keeping the pleural surfaces close together to prevent fluid or blood from accumulating between the surfaces. The retained blood can irritate the pleura, causing scar tissue (adhesions) to form. If extensive, this scar tissue can encase the lung, restricting movement of the chest wall, and is then referred to as a fibrothorax. Less than 1 percent of cases go on to develop a fibrothorax. Cases with hemopneumothorax or infection more often develop fibrothorax. After the chest tube is removed, over 10% of cases develop pleural effusions that are mostly self-limited and leave no lasting complications. In such cases, thoracentesis is performed to eliminate the possibility of an infection being present. Other potential complications include atelectasis, lung infection, pneumothorax, sepsis, respiratory distress, hypotension, tachycardia, pneumonia, adhesions, and impaired lung function.
Epidemiology
Trauma to the thorax results in approximately 16,000 to 30,000 deaths every year. There are about 300,000 cases of hemothorax in the U.S every year. Polytrauma (injury to multiple body systems) involves chest injuries in 60% of cases and commonly leads to hemothorax. In a case study, 37% of people hospitalized for blunt chest trauma had traumatic hemothorax. Hemothorax commonly occurs with a displaced rib fracture.
Other animals
Horses
In horses, hemothorax is uncommon and usually traumatic. It may occur along with pneumothorax. It is mainly diagnosed by ultrasound. Treatment involves supportive care, correction of the underlying cause, and occasionally drainage. The prognosis is variable.
Hemothorax is usually caused by trauma to the thorax. It can result from any injury that involves the pleural, intercostal, intervertebral, cardiac, or thoracic wall muscle. It can rarely be caused by diaphragmatic rupture that results in abdominal herniation. Hemothorax can be caused be cancers involving the thoracic, pulmonary, and mediastinal wall. The most common cancer resulting in hemothorax is a hemangiosarcoma.Clinical signs and symptoms may be variable and cause-dependant. They may include rapid breathing, pain, and shallow breathing in cases with a rib fracture. In the case of extensive bleeding, signs of hypovolemia may occur, and rapid death may result within hours. In less acute cases with slower bleeding, anemia and hypoproteinemia may gradually develop.Ultrasound can detect blood in the pleural cavity. Blood in the thorax is shown by a uniform area without flocculation. Pleural effusions without blood are usually hypoechoic. Echogenicity is indicated by cellular debris and/or fibrin. Bloody pleural effusions are shows by a swirling, hyperechoic pattern. When a stethoscope is used (auscultation), the heartbeat sounds are faint. When percussion is performed, it produces a dull area. However, especially in traumatic cases, percussion may be painful. Although nonspecific, physical examinations may show reduced lung sounds and muffled, widespread heart sounds. Similar signs and symptoms may occur when other fluids are in the pleural cavity.Treatment includes correction of the underlying cause. Drainage is not always required, but can be performed in case of infection or fluid levels resulting in respiratory compromise. However, drainage in contraindicated in cases caused by clotting disorders. Additionally, broad spectrum antibiotics can be given in the case of open trauma or pulmonary rupture. Supportive care may be required. It may include intranasal oxygen, painkillers, blood transfusions, and fluids. In order to avoid fluid overload, fluids are given slowly.The prognosis significantly depends on the underlying cause of the hemothorax. In cases caused by uncomplicated thoracic trauma, the prognosis may be good, but the prognosis is worse in cases that are complicated by pleuritis. Cases caused by cancer or clotting disorders have a poor prognosis, as do cases with massive bleeding due to injury to the heart or very large blood vessels.
References
== External links == |
Reflex syncope | Reflex syncope is a brief loss of consciousness due to a neurologically induced drop in blood pressure and/or a decrease in heart rate. Before an affected person passes out, there may be sweating, a decreased ability to see, or ringing in the ears. Occasionally, the person may twitch while unconscious. Complications of reflex syncope include injury due to a fall.Reflex syncope is divided into three types: vasovagal, situational, and carotid sinus. Vasovagal syncope is typically triggered by seeing blood, pain, emotional stress, or prolonged standing. Situational syncope is often triggered by urination, swallowing, or coughing. Carotid sinus syncope is due to pressure on the carotid sinus in the neck. The underlying mechanism involves the nervous system slowing the heart rate and dilating blood vessels, resulting in low blood pressure and thus not enough blood flow to the brain. Diagnosis is based on the symptoms after ruling out other possible causes.Recovery from a reflex syncope episode happens without specific treatment. Prevention of episodes involves avoiding a persons triggers. Drinking sufficient fluids, salt, and exercise may also be useful. If this is insufficient for treating vasovagal syncope, medications such as midodrine or fludrocortisone may be tried. Occasionally, a cardiac pacemaker may be used as treatment. Reflex syncope affects at least 1 in 1,000 people per year. It is the most common type of syncope, making up more than 50% of all cases.
Signs and symptoms
Episodes of vasovagal syncope are typically recurrent and usually occur when the predisposed person is exposed to a specific trigger. Before losing consciousness, the individual frequently experiences early signs or symptoms such as lightheadedness, nausea, the feeling of being extremely hot or cold (accompanied by sweating), ringing in the ears, an uncomfortable feeling in the heart, fuzzy thoughts, confusion, a slight inability to speak or form words (sometimes combined with mild stuttering), weakness and visual disturbances such as lights seeming too bright, fuzzy or tunnel vision, black cloud-like spots in vision, and a feeling of nervousness can occur as well. The symptoms may become more intense over several seconds to several minutes before the loss of consciousness (if it is lost). Onset usually occurs when a person is sitting up or standing.When people lose consciousness, they fall down (unless prevented from doing so) and, when in this position, effective blood flow to the brain is immediately restored, allowing the person to regain consciousness. If the person does not fall into a fully flat, supine position, and the head remains elevated above the trunk, a state similar to a seizure may result from the bloods inability to return quickly to the brain, and the neurons in the body will fire off and generally cause muscles to twitch very slightly but mostly remain very tense.The autonomic nervous systems physiological state (see below) leading to loss of consciousness may persist for several minutes, so
If patients try to sit or stand when they wake up, they may pass out again
The person may be nauseated, pale, and sweaty for several minutes or hours
Causes
Reflex syncope occurs in response to a trigger due to dysfunction of the heart rate and blood pressure regulating mechanism. When heart rate slows or blood pressure drops, the resulting lack of blood to the brain causes fainting.
Vasovagal
Typical triggers include:
Prolonged standing
Emotional stress
Pain
The sight of blood
Fear of needles
Time varying magnetic field (i.e. transcranial magnetic stimulation)
Situational
After or during urination (micturition syncope)
Straining, such as to have a bowel movement
Coughing
Swallowing
Lifting a heavy weight
Carotid sinus
Pressing upon a certain spot in the neck. This may happen when wearing a tight collar, shaving, or turning the head.
Pathophysiology
Regardless of the trigger, the mechanism of syncope is similar in the various vasovagal syncope syndromes. The nucleus tractus solitarii of the brainstem is activated directly or indirectly by the triggering stimulus, resulting in simultaneous enhancement of parasympathetic nervous system (vagal) tone and withdrawal of sympathetic nervous system tone.This results in a spectrum of hemodynamic responses:
On one end of the spectrum is the cardioinhibitory response, characterized by a drop in heart rate (negative chronotropic effect) and in contractility (negative inotropic effect) leading to a decrease in cardiac output that is significant enough to result in a loss of consciousness. It is thought that this response results primarily from enhancement in parasympathetic tone.
On the other end of the spectrum is the vasodepressor response, caused by a drop in blood pressure (to as low as 80/20) without much change in heart rate. This phenomenon occurs due to dilation of the blood vessels, probably as a result of withdrawal of sympathetic nervous system tone.
The majority of people with vasovagal syncope have a mixed response somewhere between these two ends of the spectrum.One account for these physiological responses is the Bezold-Jarisch reflex.
Vasovagal syncope may be part of an evolved response, specifically, the fight-or-flight response.
Diagnosis
In addition to the mechanism described above, a number of other medical conditions may cause syncope. Making the correct diagnosis for loss of consciousness is difficult. The core of the diagnosis of vasovagal syncope rests upon a clear description of a typical pattern of triggers, symptoms, and time course.It is pertinent to differentiate lightheadedness, seizures, vertigo, and low blood sugar as other causes.
In people with recurrent vasovagal syncope, diagnostic accuracy can often be improved with one of the following diagnostic tests:
A tilt table test (results should be interpreted in the context of patients clinical presentations and with an understanding of the sensitivity and specificity of the test)
Implantation of an insertable loop recorder
A Holter monitor or event monitor
An echocardiogram
An electrophysiology study
Treatment
Treatment for reflex syncope focuses on avoidance of triggers, restoring blood flow to the brain during an impending episode, and measures that interrupt or prevent the pathophysiologic mechanism described above.
Lifestyle changes
The cornerstone of treatment is avoidance of triggers known to cause syncope in that person. However, research has shown that people show great reductions in vasovagal syncope through exposure-based exercises with therapists if the trigger is mental or emotional, e.g., sight of blood. However, if the trigger is a specific drug, then avoidance is the only treatment.
A technique known as "applied tension" may be additionally useful in those who have syncope with exposure to blood. The technique is done by tightening the skeletal muscles for about 15 seconds when the exposure occurs and then slowing releasing them. This is then repeated every 30 seconds for a few minutes.
Because vasovagal syncope causes a decrease in blood pressure, relaxing the entire body as a mode of avoidance is not favorable. A person can move or cross their legs and tighten leg muscles to keep blood pressure from dropping so significantly before an injection.
Before known triggering events, the affected person may increase consumption of salt and fluids to increase blood volume. Sports drinks or drinks with electrolytes may be helpful.
People should be educated on how to respond to further episodes of syncope, especially if they experience prodromal warning signs: they should lie down and raise their legs, or at least lower their head to increase blood flow to the brain. At the very least, upon the onset of initial symptoms the patient should try to relocate to a safe, perhaps cushioned, location in case of losing consciousness. Positioning themselves in a way where the impact from falling or collapsing would be minimized is ideal. The safe area should be within close proximity, since, time is of the essence and these symptoms usually climax to loss of consciousness within a matter of minutes. If the individual has lost consciousness, he or she should be laid down in the recovery position. Tight clothing should be loosened. If the inciting factor is known, it should be removed if possible (for instance, the cause of pain).
Wearing graded compression stockings may be helpful.
Medications
Certain medications may also be helpful:
Beta blockers (β-adrenergic antagonists) were once the most common medication given; however, they have been shown to be ineffective in a variety of studies and are thus no longer prescribed. In addition, they may cause the syncope by lowering the blood pressure and heart rate.
Medications which may be effective include: CNS stimulants fludrocortisone, midodrine, SSRIs such as paroxetine or sertraline, disopyramide, and, in health-care settings where a syncope is anticipated, atropine or epinephrine (adrenaline).
For people with the cardioinhibitory form of vasovagal syncope, implantation of a permanent pacemaker may be beneficial or even curative.Types of long-term therapy for vasovagal syncope include
Preload agents
Vasoconstrictors
Anticholinergic agents
Negative cardiac inotropes
Central agents
Mechanical device
Discontinuation of medications known to lower blood pressure may be helpful, but stopping antihypertensive drugs can also be dangerous in some people. Taking antihypertensive drugs may worsen the syncope, as the hypertension may have been the bodys way to compensate for the low blood pressure.
Prognosis
Brief periods of unconsciousness usually cause no lasting harm to health. Reflex syncope can occur in otherwise healthy individuals, and has many possible causes, often trivial ones such as prolonged standing with the legs locked.The main danger of vasovagal syncope (or dizzy spells from vertigo) is the risk of injury by falling while unconscious. Medication therapy could possibly prevent future vasovagal responses; however, for some individuals medication is ineffective and they will continue to have fainting episodes.
See also
Orthostatic hypotension
Orthostatic intolerance
Postural orthostatic tachycardia syndrome
Roemheld Syndrome
== References == |
Juvenile polyposis syndrome | Juvenile polyposis syndrome is an autosomal dominant genetic condition characterized by the appearance of multiple juvenile polyps in the gastrointestinal tract. Polyps are abnormal growths arising from a mucous membrane. These usually begin appearing before age 20, but the term juvenile refers to the type of polyp (i.e benign hamartoma, as opposed to adenoma for example), not to the age of the affected person. While the majority of the polyps found in juvenile polyposis syndrome are non-neoplastic, hamartomatous, self-limiting and benign, there is an increased risk of adenocarcinoma.
Solitary juvenile polyps most commonly occur in the rectum and present with rectal bleeding. The World Health Organization criteria for diagnosis of juvenile polyposis syndrome are one of either:
More than five juvenile polyps in the colon or rectum; or
Juvenile polyps throughout the gastrointestinal tract; or
Any number of juvenile polyps in a person with a family history of juvenile polyposis.
Signs and symptoms
Age of onset is variable. The term juvenile in the title of juvenile polyposis syndrome refers to the histological type of the polyps rather than the age of onset.
Affected individuals may present with rectal bleeding, abdominal pain, diarrhea or anemia. On colonoscopy or sigmoidoscopy polyps that vary in shape or size are present. The polyps can be sessile or pedunculated hamartomatous polyps.
Genetics
Juvenile polyposis syndrome can occur sporadically in families or be inherited in an autosomal dominant manner.Two genes associated with juvenile polyposis syndrome are BMPR1A and SMAD4. Gene testing may be useful when trying to ascertain which non-symptomatic family members may be at risk of developing polyps, however having a known familial mutation would be unlikely to change the course of treatment. A known mutation may also be of use for affected individuals when they decide to start a family as it allows them reproductive choices.While mutations in the gene PTEN were also thought to have caused juvenile polyposis syndrome, it is now thought that mutations in this gene cause a similar clinical picture to juvenile polyposis syndrome but are actually affected with Cowden syndrome or other phenotypes of the PTEN hamartoma tumor syndrome.
Screening
People with juvenile polyps may require yearly upper and lower endoscopies with polyp excision and cytology. Their siblings may also need to be screened regularly.
Treatment
Malignant transformation of polyps requires surgical colectomy.
Prognosis
Most juvenile polyps are benign; however, malignancy can occur. The cumulative lifetime risk of colorectal cancer is 39% in patients with juvenile polyposis syndrome.
References
Further reading
Larsen Haidle J, Howe JR (September 29, 2011). Juvenile Polyposis Syndrome. University of Washington, Seattle. PMID 20301642. NBK1469. In Pagon RA, Bird TD, Dolan CR, et al., eds. (1993). GeneReviews [Internet]. Seattle WA: University of Washington, Seattle. PMID 20301295.
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Primary pigmented nodular adrenocortical disease | Primary pigmented nodular adrenocortical disease (PPNAD) was first coined in 1984 by Carney et al. it often occurs in association with Carney complex (CNC). CNC is a rare syndrome that involves the formation of abnormal tumours that cause endocrine hyperactivity.
PPNAD arises due to the enlargement of the cortex of the adrenal glands, resulting in Cushings syndrome that is independent of the pituitary hormone ACTH.
Signs and symptoms
PPNAD is a rare cause of high cortisol levels in the blood and often manifests as ACTH-independent Cushings syndrome. The effects of PPNAD can often be cyclical so the symptoms of Cushings syndrome will not always be as severe, which may complicate diagnosis. The classic symptoms of Cushings syndrome include rapid central weight gain, a puffy red face and a buffalo hump at the back of the neck due to fat deposits. Skin changes in Cushings syndrome include thinning and bruising easily, developing striae and hyperpigmentation at skin folds. The hormonal changes can lead to hirsutism, males developing breast tissue, females no longer having periods and both sexes may become infertile. High cortisol levels can lead to psychological disturbances such as anxiety or depression and insomnia. Bone health can deteriorate, leading to an increased fracture risk in people with Cushings syndrome. PPNAD is unique as it often causes Cushings at a young age, in children and adolescents. In addition to the other symptoms of Cushings syndrome, the patient may have a short stature due to interrupted growth because of ACTH suppression.In 90% of people with PPNAD it is associated with Carney Complex. Carney Complex is usually inherited, however it can also occur sporadically. A visible sign of Carney complex is abnormal skin hyperpigmentation. There may also be myxomas which can appear as lumps in the skin and breast as well as often being present in the heart, which can lead to multiple cardiovascular problems. The majority of people with PPNAD will have some of these signs/symptoms due to the strong association between PPNAD and Carney Complex.
Causes
PPNAD, the endocrine manifestation that comes from Carney Complex (CNC), can be syndromic or isolated. The main cause of isolated PPNAD is a mutation of PRKAR1α, located at 17q22-24, which is the gene encoding the regulatory R1α subunit of protein kinase A. Germline heterozygous PRKAR1α inactivation mutations are present in 80% of CNC patients affected by Cushings syndrome. There are over 117 mutations of the PRKAR1α gene that can cause CNC, with many of these mutations producing premature stop codons, thus resulting in the complete loss of PRKAR1α protein. CNC patients have also been discovered with an unusually shortened PRKAR1α protein, detected in tumours and leukocytes, following a splice-site mutation, which causes exon-6 skipping. Therefore, both haploinsufficiency and the complete loss of PRKAR1α can lead to the increased PKA activity observed in PPNAD patients, due to the disruption of the cAMP signalling pathway.Sahut-Barnola et al. used a mouse model to cre-lox knockout the Prkar1a gene specifically from cells of the adrenal cortex and observed that the mice subsequently developed Cushing syndrome that is independent of the pituitary. They also observed that the mutation caused increased PKA activity.The R1α loss caused the adult adrenal gland became hyperactive and hyperplastic on both sides, as seemingly the foetal adrenal cells within it were not maintained and thus expanded. This established tumoral growths. This mouse KO model phenocopies what happens in human cases of PPNAD.Inactivation of PDE11A4, located at 2q31-5, has also been identified in PPNAD patients without PRKAR1α mutations. PDE11A4 is the gene encoding phosphodiesterase 11A4, another participant of the cAMP signalling pathway.
Diagnosis
Diagnosis usually occurs upon investigation of a cause for already suspected Cushings syndrome. High levels of cortisol observed in patients with PPNAD are not suppressed upon administration of dexamethasone (dexamethasone suppression test), and upon MRI or CT imaging, the pituitary will show no abnormalities. Measuring ACTH will confirm that the cause of the patients Cushings syndrome is ACTH independent. The nature of Cushings syndrome itself is periodic, which can make diagnosing PPNAD increasingly difficult.Diagnosis of PPNAD can be difficult to determine preoperatively as CT scan findings can be variable i.e. appear normal or suggest unilateral adrenal lesions therefore impeding the correct diagnosis. NP-59 scintigraphy may be particularly useful in identifying the bilateral nature of the disease.Gene studies are not necessary for diagnosis as there are clear gross and histological diagnostic markers, as the nodules can usually be seen clearly in both cases A positive family history of PPNAD has been shown to be associated with abnormal histological findings, e.g. mitotic figures, which may further hinder diagnosis. At the point where abdominal CT scanning and pituitary fossa MRI show no clear abnormalities, adrenalectomy may be performed.
Treatment
After diagnosis, it is important for patients to be continually monitored. The most common treatment for PPNAD is bilateral laparoscopic adrenalectomy; the process by which both adrenal glands are removed by a small incision.
Patients who have received this treatment will be prescribed mineralocorticoid and glucocorticoid steroids as they are no longer being naturally produced.
This is a treatment which has been used and refined since 1984.
References
== External links == |
Blind loop syndrome | Blind loop syndrome (BLS), also known as stagnant loop syndrome, is a state that occurs when the normal bacterial flora of the small intestine proliferates to numbers that cause significant derangement to the normal physiological processes of digestion and absorption. In some cases of blind loop syndrome, overgrowth of pathogenic non-commensal bacteria has also been noted. It has long been understood that from birth, and throughout life, large amounts of bacteria reside symbiotically within animal gastrointestinal tracts such as the human gastrointestinal tract. The understanding of this gut flora has even led to novel treatments for bowel irregularity that utilize so called "probiotics" or good bacteria that aid in normal digestion.
The problem of BLS arises when the bacterial colonies residing in the upper gastrointestinal tract begin to grow out of control or are altered in their makeup thereby creating a burden on the normal physiological processes occurring in the small intestine. This results in problems, among others, of: vitamin B12 deficiency, fat malabsorption and steatorrhea, fat-soluble vitamin deficiencies and intestinal wall injury.
Symptoms and signs
Most of the symptoms of BLS are non specific but nevertheless warrant the utmost attention. These include:
Loss of appetite
Nausea
Flatulence
Diarrhea
Fullness after a meal
Fatty stools (steatorrhea)
Unintentional weight loss
Generalised weaknessAs a result of the concomitant vitamin and mineral deficiencies that occur as a result of the malabsorption associated with BLS patients with advanced cases should be investigated for:
Vitamin B12 deficiency
Folate deficiency
Iron deficiency
Vitamin E deficiency
Causes
Blind loop syndrome is a complication of surgical operations of the abdomen, as well as inflammatory bowel disease or scleroderma. Another cause is jejunoileal diverticula.
Pathophysiology
The overgrowth of bacteria in the small intestine is prevented by various mechanical and chemical factors which include the constant peristaltic movement of contents along the length of the gastrointestinal tract and the antibacterial properties of gastric secretions, pancreatic secretions and bile.It follows that a disruption of any of these factors could lead to bacterial overgrowth and indeed BLS has been found to occur in persons with anatomical anomalies that result in stagnation. BLS has also been associated with achlorhydria, dysmotility, fistulae, and strictures. Chronic or high dose opioid therapy may contribute to BLS by reducing gastric motility.Due to the disruption of digestive processes by the overgrowth of intestinal bacteria; malabsorption of bile salts, fat and fat-soluble vitamins, protein and carbohydrates results in damage to the mucosal lining of the intestine by bacteria or via the production of toxic metabolites.
Diagnosis
A physical examination may reveal a mass or distention of the abdomen.Tests which may be useful for diagnosis include:
Abdominal x-ray
Abdominal CT scan
Contrast enema study
Treatment
The treatment of BLS follows two basic principles. When a patient presents with symptoms of BLS, the treating physician basically has two recognized options for management:
Test-and-treat
Treat empirically
Test-and-treat method
Although it would seem to be the better way to go in terms of management, there has been recent criticism on the need for such testing because of reliability issues. However, it must be stated that there are options such as the glucose breath test and jejunal aspiration the explanations of which are beyond the scope of this current article.
Treating empirically
The "treat empirically" route also has its difficulties, which have all come under wide debate and study. Recommendations are varied but seem to find some common ground around the notion that treatment should be individualized to the specific circumstances under which a patient has developed BLS since these circumstances affect the complex microbial make up of the affected bowel.Tetracyclines have been the mainstay of treatment for BLS, but recent studies have concluded Rifaximin to be very effective in the treatment of BLS. One study by Di Stefano et al., however, concluded Metronidazole to be more effective than Rifaximin in the treatment of BLS.
Surgical management
Surgical management is reserved for fixing anatomical causes of bowel obstruction that interfere with normal function once they are amenable to such intervention. These conditions include:
Strictures
Fistulae
Diverticula
References
== External links == |
Unibrow | A unibrow (or jacco brow or monobrow; called synophrys in medicine) is a single eyebrow created when the two eyebrows meet in the middle above the bridge of the nose. The hair above the bridge of the nose is of the same color and thickness as the eyebrows, such that they converge to form one uninterrupted line of hair.
History
The word monobrow first appeared in print in 1968, and the adjectival form monobrowed followed in 1973, in Martin Amis novel The Rachel Papers. The first known use of the word unibrow was in 1981.
Culture and beauty
Oman
A unibrow is considered as a sign of beauty by Baluchi Omanis. Its popularity causes women to draw a black line joining the brows as a part of their routine makeup to fake a unibrow. A study found the prevalence of synophrys to be at 11.87% in the Omani population.
Tajikistan
In Tajikistan, a unibrow is viewed as an attractive quality in both men and women. For women, it is associated with virginity and purity and, in men, virility. If there is no unibrow present, or if it is weak, it is commonplace for women to use a kohl liner or a modern kajal pen to simulate a unibrow.
Elsewhere
The unibrow has largely been seen as undesirable in the Americas and Europe, with the hairs often plucked, shaved, or waxed away.
The artist Frida Kahlo was famous for her unibrow, which she often depicted in self-portraits. Greek-Cypriot model Sophia Hadjipanteli is also known for her unibrow.It is also the trademark of NBA player Anthony Davis, football player Marouane Fellaini and YouTuber ElectroBOOM. Famous boxer Roberto Elizondo also famously sported a unibrow during his professional boxing fighting days.Bert, Herry Monster, and Oscar the Grouch from Sesame Street, Muppets Sam Eagle, Statler and Animal, Tim Lockwood from Cloudy with a Chance of Meatballs, Spanky Ham from Drawn Together, Squilliam Fancyson from SpongeBob SquarePants, Helga Pataki from Hey Arnold!, and Baby Gerald from The Simpsons are fictional characters with a unibrow.
Medicine
Genetics
The unibrow is a genetic trait. It is associated with the PAX3 gene.
Medical conditions
A unibrow is part of normal human variation, but can also stem from developmental disorders. A unibrow is a recognized feature of Cornelia De Lange syndrome, a genetic disorder whose main features include moderate to severe learning difficulties, limb abnormalities such as oligodactyly (fewer than normal fingers or toes), and phocomelia (malformed limbs), and facial abnormalities including a long philtrum (the slight depression/line between the nose and mouth).
Other medical conditions associated with a unibrow include:
Waardenburg syndrome;
Patau syndrome;
Smith-Lemli-Opitz syndrome;
Sanfilippo syndrome;
3p deletion syndrome;
Chromosome Deletion Dillan 4p Syndrome (Wolf–Hirschhorn syndrome);
Gorlin syndrome (Basal Cell Nevus Syndrome);
Cornelia de Lange Syndrome
Frontometaphyseal dysplasia;
ATRX syndrome;
Chromosome 9q34 Microdeletion Syndrome or Kleefstra syndrome.
17q12 microduplication syndrome
See also
Glabella
References
External links
Media related to Unibrows at Wikimedia Commons |
Erythema dyschromicum perstans | Erythema dyschromicum perstans (also known as ashy dermatosis, and dermatosis cinecienta) is an uncommon skin condition with peak age of onset being young adults, but it may also be seen in children or adults of any age. EDP is characterized by hyperpigmented macules that are ash-grey in color and may vary in size and shape. While agents such as certain medications, radiographic contrast, pesticides, infection with parasites, and HIV have been implicated in the occurrence of this disease, the cause of this skin disease remains unknown.
EDP initially presents as grey or blue-brown circumferential or irregularly shaped macules or patches that appear. While the lesions of EDP are generally non-elevated, they may initially have a slight raised red margin as they first begin to appear. These lesions usually arise in a symmetric distribution and involve the trunk, but also commonly spread to the face and extremities. EDP does not usually have symptoms beside the macules and patches of discolored skin; however, some itching in these areas may occur.
Because EDP is an uncommon disease of the skin, it is important to consider other skin diseases that may resemble erythema dyschromicum perstans, such as infectious diseases (i.e. leprosy or pinta), reaction to drugs, post inflammatory hyperpigmentation, or lichen planus pigmentosus.
There is no cure for EDP. While multiple various topical and systemic therapies have been tried, none have been consistently successful. In children, spontaneous resolution of EDP over the course of months to years is possible; however, this outcome is less likely if EDP presents in adulthood.: 224
See also
Lichen planus
List of cutaneous conditions
References
== External links == |
Beaus lines | Beaus lines are deep grooved lines that run from side to side on the fingernail or the toenail. They may look like indentations or ridges in the nail plate.: 657 This condition of the nail was named by a French physician, Joseph Honoré Simon Beau (1806–1865), who first described it in 1846.
Signs and symptoms
Beaus lines are horizontal, going across the nailline, and should not be confused with vertical ridges going from the bottom (cuticle) of the nail out to the fingertip. These vertical lines are usually a natural consequence of aging and are harmless.Beaus lines should also be distinguished from Muehrckes lines of the fingernails. While Beaus lines are actual ridges and indentations in the nail plate, Muehrcke lines are areas of hypopigmentation without palpable ridges; they affect the underlying nail bed, and not the nail itself. Beaus lines should also be distinguished from Mees lines of the fingernails, which are areas of discoloration in the nail plate.
As the nail grows out, the ridge in the nail can be seen to move upwards until it reaches the fingertip. When it reaches this point the fingertips can become sore for a few days due to the nail bed being exposed by the mis-shapen nail.
Causes
There are several causes of Beaus lines. It is believed that there is a temporary cessation of cell division in the nail matrix. This may be caused by an infection or problem in the nail fold, where the nail begins to form, or it may be caused by an injury to that area. Some other reasons for these lines include trauma, coronary occlusion, hypocalcaemia, and skin disease. They may be a sign of systemic disease, or may also be caused by an illness of the body, as well as drugs used in chemotherapy, or malnutrition. Beaus lines can also be seen one to two months after the onset of fever in children with Kawasaki disease. Conditions also associated with Beaus lines include uncontrolled diabetes and peripheral vascular disease, as well as illnesses associated with a high fever, such as scarlet fever, measles, mumps and pneumonia. Beaus lines can also be a sign of zinc deficiency.
A researcher found Beaus lines in the fingernails of two of six divers following a deep saturation dive to a pressure equal to 305 metres (1,001 ft) of sea water, and in six of six divers following a similar dive to 335 metres (1,099 ft). They have also been seen in Ötzi the Iceman.
Human nails grow at a rate which varies with many factors: age, and the finger or toe in question as well as nutrition. However, typically in healthy populations fingernails grow at about 0.1 mm/day and toenails at about 0.05 mm/day.
See also
List of cutaneous conditions
References
External links
Image of Beaus Lines from docetaxel chemotherapy |
Exanthem | An exanthem is a widespread rash occurring on the outside of the body and usually occurring in children. An exanthem can be caused by toxins, drugs, or microorganisms, or can result from autoimmune disease.
The term exanthem is from the Greek ἐξάνθημα, exánthēma, a breaking out. It can be contrasted with enanthems which occur inside the body, such as on mucous membranes.
Infectious exanthem
In 1905, the Russian-French physician Léon Cheinisse (1871–1924), proposed a numbered classification of the six most common childhood exanthems.Of these six "classical" infectious childhood exanthems, four are viral. Numbers were provided in 1905.The four viral exanthema have much in common, and are often studied together as a class. They are:
Scarlet fever, or "second disease", is associated with the bacterium Streptococcus pyogenes. Fourth disease, also known as "Dukes disease" is a condition whose existence is not widely accepted today. It was described in 1900 and is postulated to be related to the bacterium Staphylococcus aureus.In 1979 and 2001 a possible "seventh diease" was postulated following reports of a condition in Japan also referred to as acute febrile infantile mucocutaneous lymph node syndrome (MCLS).Many other common viruses apart from the ones mentioned above can also produce an exanthem as part of their presentation, though they are not considered part of the classic numbered list:
Varicella zoster virus (chickenpox or shingles)
Mumps
rhinovirus (the common cold)
unilateral laterothoracic exanthem of childhood
Some types of viral haemorrhagic fever are also known to produce a systemic rash of this kind during the progression of the disease.
Tick-borne diseases like Rocky Mountain spotted fever produce a rash that may become extensive enough so as to be classified as exanthemous in as many as 90% of children with the disease.
See also
List of cutaneous conditions
References
External links
Overview at About.com
Definition at MedTerms
Differential diagnosis
Dermatology Quiz Includes photo, diagnosis, and treatment of unilateral laterothoracic exanthem (ULE). |
Early myoclonic encephalopathy | Early myoclonic encephalopathy (EME) is a rare neonatal-onset epilepsy developmental and epileptic encephalopathy (DEE) with an onset at neonatal period or during the first 3 months of life. It is marked by the presence of myoclonic seizures but multiple seizure types may occur. The electroencephalographic recording is abnormal with eitherusually a suppression-burst pattern or other significantly abnormal patterns. On most occasions the seizures are drug-resistant. After several months, the seizure pattern may develop into infantile spasms syndrome (West syndrome). The neurological exam is abnormal with a significant risk of early death. Various genetic and metabolic disorders are responsible. At present, EME and Ohtahara syndrome are recorded as distinct patterns in the categorization of epilepsies but both neonatal-onset epilepsy syndromes are considered to be merged in one unique entity. It is a severe type of epilepsy syndrome associated with high level of resistance to treatment and a high risk for cognitive impairment. The myoclonic seizures could be seen in other epilepsy syndromes. Multiple types of childhood epilepsies are usually mentioned as myoclonic epilepsies when the myoclonic seizures are a predominant feature.
Signs and symptoms
It is characterized by early-onset myoclonic seizures that can vary from erratic movements of a single limb or a part of the face (focal) to bilateral myoclonic movement of the whole body. The myoclonus may occur at any time (sleep, wakefulneess) from few times per day to very frequent or even continuous myoclonus. The symptoms may start appearing as early as a few hours after birth and up to three months of age. Around three-fourths of affected children present with neonatal seizure. Other seizure types such as focal or generalized tonic seizures, epileptic spasms or other epileptic manifestations may occur at the course of the disease. The distinctive feature of the phenotype is severe progressive encephalopathy with delay in development and abnormal neurological examination delay (hypotonia, lethargy, poor eye contact, difficulties in feeding) usually being present even before the onset of other symptoms. Head circumference is usually normal at onset but microcephaly may develop over time. Family history is usually normal.
Causes
There are varied etiologies related to EME that are mainly genetic abnormalities (mutations), brain structure abnormalities, or inborn metabolic defects. Another common reason rather than structural brain abnormality is inborn metabolic defects. Sometimes a metabolic disorder that affects how the brain works may lead to EME. While most of these metabolic disorders cannot be reversed, sometimes treating the underlying disorder can help. Vitamin-responsive epileptic encephalopathies are rare but significant reasons.
Genetics
A growing number of genetic aetiologies have been linked to the phenotype of EME and Otahara syndrome and diagnosis by genetic testing can nowadays be achieved in around 50 percent of cases. Some examples of well described genetic aetiologies include: KCNQ2- DEE. • SCN2A-DEE • STXBP1-DEE. • CDKL5-DEE• KCNT1-DEE and UBA5-DEE.
Acquired
No acquired aetiologies are known for EME although etiology remains unknown for a small percentage of patients after genetic, metabolic, and imaging workup. Some acquired conditions may share some features with EME and should be differentiated from it. These include hypoxic-ischaemic encephalopathy, central nervous system infections, acute metabolic disturbances or acute vascular events.
Mechanism
Pathology results in EME consist of multifocal changes in white matter, imperfect lamination of the deep cortical layers, astrocytic proliferation, and demyelination.
Diagnosis
Electroencephalogram (EEG) is usually characterized by a burst suppression pattern. Subsequently it may transition to hypsarrhythmia, a chaotic pattern on EEG, or other severely abnormal EEG patterns. Neuroimaging is useful in assessing a possible underlying structural causality that might cause EME. MRI findings depend on the underlying etiology and may be normal or not at diagnosis.
Prevention
Early identification of metabolism error defects is very essential in prevention as the traditional antiepileptic drug are usually not very effective, proper treatment aiming to the conditions can prevent neurological worsening. Genetic counselling is critical given the high prevalence of genetic mutations and early genetic testing also helps to avoid unnecessary procedures and unsuccessful treatment. The families who are at risk, prophylactic treatment is suggested as it may stop the seizure and help in recovering the neurodevelopmental consequences.
Management
Antiepileptic drugs are used to treat EME, but it is difficult to control seizures with anti-epileptic drugs alone. Phenobarbital, valproate, pyridoxine, zonisamide, and benzodiazepines have all been used but with inadequate usefulness in seizure control. Some patients show favorable response to sodium channel agents, often at high dose. There are various means to add on the treatment when seizures are resistant. A ketogenic diet can be useful in controlling seizures. Surgery is also a treatment option. In epilepsy surgery (focal resection or hemispherectomy) the part of the brain which creates the abnormal electrical current through the brain must be resected, but the surgery is very complicated and needs to be performed by expert surgeons in epilepsy reference centers. None of these treatments, with the exception of some metabolic disorders with specific treatments available, have shown any efficacy at avoid long-term consequences of the disease.
Prognosis
The prognosis is usually poor. Mortality rate is high during early infancy and almost half of the children die by 2 years of age. In the patient with severe phenotype, even when optimal treatment is initiated promptly, the prognosis remains poor. Most of the survivors suffer from psychomotor impairment and develop electroclinical features of other epilepsy syndromes (i.e Lennox- Gastaut syndrome). In patients with reduced phenotype, if there is early treatment initiated the better developmental outcome can be observed.
Epidemiology
The prevalence estimates among EME are of <1 / 1 000 000.
References
== External links == |
Neorickettsia helminthoeca | Neorickettsia helminthoeca is a bacterium in the Neorickettsia genus that causes Salmon poisoning disease.
Salmon poisoning disease
Salmon poisoning disease (SPD) is a fatal disease of dogs and other canids caused by a rickettsial bacterium, Neorickettsia helminthoeca. It results from eating raw salmon, trout, or salamander and is common in the Pacific Northwest. These fish and amphibians are infected with the larvae of a fluke, Nanophyetus salmincola through an intermediate host, the snail Oxytrema plicifer. The larvae attaches to the intestine of the dog and the rickettsial bacteria are released, causing severe gastrointestinal disease and systemic infection.
Neorickettsia elokominica, carried by the same fluke, causes a similar disease known as Elokomin fluke fever (EFF) in canids, bears, raccoons, and ferrets.
Symptoms
Symptoms of SPD begin about one week after eating the salmon and include vomiting, diarrhea, loss of appetite, depression, high fever, and enlarged lymph nodes. Untreated, mortality reaches 90 percent. Death occurs seven to ten days after symptoms begin.EFF has less severe symptoms than SPD, with less gastrointestinal signs and more lymph node involvement. The mortality in untreated cases is about 10 percent.A similar disease has been identified in Brazil.
Diagnosis
Diagnosis is through finding the fluke eggs microscopically in a stool sample. A needle aspiration biopsy of an enlarged lymph node will reveal rickettsial organisms within macrophages in many cases. The rickettsial infection can be successfully treated with tetracycline, and the fluke infection can be treated with fenbendazole.
== References == |
Atopic dermatitis | Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis). It results in itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which often thickens over time. While the condition may occur at any age, it typically starts in childhood, with changing severity over the years. In children under one year of age, much of the body may be affected. As children get older, the areas on the insides of the knees and elbows are most commonly affected. In adults, the hands and feet are most commonly affected. Scratching the affected areas worsens the symptoms, and those affected have an increased risk of skin infections. Many people with atopic dermatitis develop hay fever or asthma.The cause is unknown but believed to involve genetics, immune system dysfunction, environmental exposures, and difficulties with the permeability of the skin. If one identical twin is affected, the other has an 85% chance of having the condition. Those who live in cities and dry climates are more commonly affected. Exposure to certain chemicals or frequent hand washing makes symptoms worse. While emotional stress may make the symptoms worse, it is not a cause. The disorder is not contagious. A diagnosis is typically based on the signs and symptoms. Other diseases that must be excluded before making a diagnosis include contact dermatitis, psoriasis, and seborrheic dermatitis.Treatment involves avoiding things that make the condition worse, daily bathing with application of a moisturising cream afterwards, applying steroid creams when flares occur, and medications to help with itchiness. Things that commonly make it worse include wool clothing, soaps, perfumes, chlorine, dust, and cigarette smoke. Phototherapy may be useful in some people. Steroid pills or creams based on calcineurin inhibitors may occasionally be used if other measures are not effective. Antibiotics (either by mouth or topically) may be needed if a bacterial infection develops. Dietary changes are only needed if food allergies are suspected.Atopic dermatitis affects about 20% of people at some point in their lives. It is more common in younger children. Females are slightly more affected than males. Many people outgrow the condition. Atopic dermatitis is sometimes called eczema, a term that also refers to a larger group of skin conditions. Other names include "infantile eczema", "flexural eczema", "prurigo Besnier", "allergic eczema", and "neurodermatitis".
Signs and symptoms
People with AD often have dry and scaly skin that spans the entire body, except perhaps the diaper area, and intensely itchy red, splotchy, raised lesions to form in the bends of the arms or legs, face, and neck.AD commonly affects the eyelids, where signs such as Dennie-Morgan infraorbital fold, infra-auricular fissure, and periorbital pigmentation can be seen. Postinflammatory hyperpigmentation on the neck gives the classic "dirty neck" appearance. Lichenification, excoriation, and erosion or crusting on the trunk may indicate secondary infection. Flexural distribution with ill-defined edges with or without hyperlinearity on the wrist, finger knuckles, ankle, feet, and hands are also commonly seen.
Causes
The cause of AD is not known, although some evidence indicates genetic, environmental, and immunologic factors.
Climate
Low humidity, and low temperature increase the prevalence and risk of flares in patients with atopic dermatitis.
Genetics
Many people with AD have a family history or a personal history of atopy. Atopy is an immediate-onset allergic reaction (type-1 hypersensitivity reaction mediated by IgE) that may manifest as asthma, food allergies, AD, or hay fever. Up to 80% of people with atopic dermatitis have elevated total or allergen-specific IgE levels.About 30% of people with atopic dermatitis have mutations in the gene for the production of filaggrin (FLG), which increase the risk for early onset of atopic dermatitis and developing asthma.
Hygiene hypothesis
According to the hygiene hypothesis, early childhood exposure to certain microorganisms (such as gut flora and helminth parasites) protects against allergic diseases by contributing to the development of the immune system. This exposure is limited in a modern "sanitary" environment, and the incorrectly developed immune system is prone to develop allergies to harmless substances.
Some support exists for this hypothesis with respect to AD. Those exposed to dogs while growing up have a lower risk of atopic dermatitis. Also, epidemiological studies support a protective role for helminths against AD. Likewise, children with poor hygiene are at a lower risk for developing AD, as are children who drink unpasteurized milk.
Allergens
In a small percentage of cases, atopic dermatitis is caused by sensitization to foods. Also, exposure to allergens, either from food or the environment, can exacerbate existing atopic dermatitis. Exposure to dust mites, for example, is believed to contribute to ones risk of developing AD. A diet high in fruits seems to have a protective effect against AD, whereas the opposite seems true for fast foods. Atopic dermatitis sometimes appears associated with celiac disease and nonceliac gluten sensitivity, and the improvement with a gluten-free diet (GFD) indicates that gluten is a causative agent in these cases.
Role of Staphylococcus aureus
Colonization of the skin by the bacterium S. aureus is extremely prevalent in those with atopic dermatitis. Abnormalities in the skin barrier of persons with AD are exploited by S. aureus to trigger cytokine expression, thus aggravating the condition.
Hard water
Atopic dermatitis in children may be linked to the level of calcium carbonate or "hardness" of household water, when used to drink. So far, these findings have been supported in children from the United Kingdom, Spain, and Japan.
Pathophysiology
Excessive type 2 inflammation underlies the pathophysiology of atopic dermatitis.Disruption of the epidermal barrier is thought to play an integral role in the pathogenesis of AD. Disruptions of the epidermal barrier allows allergens to penetrate the epidermis to deeper layers of the skin. This leads to activation of epidermal inflammatory dendritic and innate lymphoid cells which subsequently attracts Th2 CD4+ helper T cells to the skin. This dysregulated Th2 inflammatory response is thought to lead to the eczematous lesions. The Th2 helper T cells become activated, leading to the release of inflammatory cytokines including IL-4, IL-13 and IL-31 which activate downstream Janus kinase (Jak) pathways. The active Jak pathways lead to inflammation and downstream activation of plasma cells and B lymphocytes which release antigen specific IgE contributing to further inflammation. Other CD4+ helper T-cell pathways thought to be involved in atopic dermatitis inflammation include the Th1, Th17, and Th22 pathways. Some specific CD4+ helper T-cell inflammatory pathways are more commonly activated in specific ethnic groups with AD (for example, the Th-2 and Th-17 pathways are commonly activated in Asian people) possibly explaining the differences in phenotypic presentation of atopic dermatitis in specific populations.Mutations in the filaggrin gene, FLG, also cause impairment in the skin barrier that contributes to the pathogenesis of AD. Filaggrin is produced by epidermal skin cells (keratinocytes) in the horny layer of the epidermis. Filaggrin stimulates skin cells to release moisturizing factors and lipid matrix material, which cause adhesion of adjacent keratinocytes and contributes to the skin barrier. A loss-of-function mutation of filaggrin causes loss of this lipid matrix and external moisturizing factors, subsequently leading to disruption of the skin barrier. The disrupted skin barrier leads to transdermal water loss (leading to the xerosis or dry skin commonly seen in AD) and antigen and allergen penetration of the epidermal layer. Filaggrin mutations are also associated with a decrease in natural antimicrobial peptides found on the skin; subsequently leading to disruption of skin flora and bacterial overgrowth (commonly Staphylococcus aureus overgrowth or colonization).Atopic dermatitis is also associated with the release of pruritogens (molecules that stimulate pruritus or itching) in the skin. Keratinocytes, mast cells, eosinophils and T-cells release pruritogens in the skin; leading to activation of Aδ fibers and Group C nerve fibers in the epidermis and dermis contributing to sensations of pruritus and pain. The pruritogens include the Th2 cytokines IL-4, IL-13, IL-31, histamine, and various neuropeptides. Mechanical stimulation from scratching lesions can also lead to the release of pruritogens contributing to the itch scratch cycle whereby there is increased pruritus or itch after scratching a lesion. Chronic scratching of lesions can cause thickening or lichenification of the skin or prurigo nodularis (generalized nodules that are severely itchy).
Diagnosis
AD is typically diagnosed clinically, meaning it is based on signs and symptoms alone, without special testing. Several different criteria developed for research have also been validated to aid in diagnosis. Of these, the UK Diagnostic Criteria, based on the work of Hanifin and Rajka, has been the most widely validated.
Treatments
No cure for AD is known, although treatments may reduce the severity and frequency of flares.
Humidity
A humidifier can be used to prevent low indoor humidity during winter (especially with indoor heating), and dry season. And a dehumidifier can be used during seasons with excessive humidity.
Applying moisturisers may prevent the skin from drying out and decrease the need for other medications. Affected persons often report that improvement of skin hydration parallels with improvement in AD symptoms.
Lifestyle
Health professionals often recommend that persons with AD bathe regularly in lukewarm baths, especially in salt water, to moisten their skin. Avoiding woolen clothing is usually good for those with AD. Likewise silk, silver-coated clothing may help. Dilute bleach baths have also been reported effective at managing AD.
Diet
The role of vitamin D on atopic dermatitis is not clear, but some evidence shows that vitamin D supplementation may improve its symptoms.Studies have investigated the role of long-chain polyunsaturated fatty acid (LCPUFA) supplementation and LCPUFA status in the prevention and treatment of AD, but the results are controversial. Whether the nutritional intake of n-3 fatty acids has a clear preventive or therapeutic role, or if n-6 fatty acids consumption promotes atopic diseases is unclear.Several probiotics seem to have a positive effect, with a roughly 20% reduction in the rate of AD. The best evidence is for multiple strains of bacteria.In people with celiac disease or nonceliac gluten sensitivity, a gluten-free diet improves their symptoms and prevents the occurrence of new outbreaks.
Medication
Topical corticosteroids, such as hydrocortisone, have proven effective in managing AD. If topical corticosteroids and moisturisers fail, short-term treatment with topical calcineurin inhibitors such as tacrolimus or pimecrolimus may be tried, although their use is controversial, as some studies indicate that they increase the risk of developing skin cancer or lymphoma. A 2007 meta-analysis showed that topical pimecrolimus is not as effective as corticosteroids and tacrolimus. A 2015 meta-analysis, though, indicated that topical tacrolimus and pimecrolimus are more effective than low-dose topical corticosteroids, and found no evidence for increased risk of malignancy or skin atrophy. In 2016, crisaborole, an inhibitor of PDE-4, was approved as a topical treatment for mild-to-moderate eczema.Other medications used for AD include systemic immunosuppressants such as ciclosporin, methotrexate, interferon gamma-1b, mycophenolate mofetil, and azathioprine. Antidepressants and naltrexone may be used to control pruritus (itchiness). Leukotriene inhibitors such as monteleukast are of unclear benefit as of 2018.In 2017, the monoclonal antibody(mAb) dupilumab under the trade name Dupixent was approved to treat moderate-to-severe eczema.
In 2021, an additional monoclonal antibody, tralokinumab, was approved in the EU & UK with the trade name Adtralza then later in the US as Adbry for similarly severe cases. Another monoclonal antibody treatment, lebrikizumab, is in phase 3 trials in the US; the drug has been granted Fast Track Designation by the FDA, and Eli Lilly and Company is expected to apply for FDA approval of the drug in the second half of 2022.Some JAK inhibitors such as abrocitinib, trade name Cibinquo, and upadacitinib, trade name Rinvoq, have been approved in the US for the treatment of moderate-to-severe eczema as of January 2022.
Tentative, low-quality evidence indicates that allergy immunotherapy is effective in AD. This treatment consists of a series of injections or drops under the tongue of a solution containing the allergen.Antibiotics, either by mouth or applied topically, are commonly used to target overgrowth of S. aureus in the skin of people with AD, but a 2019 meta-analysis found no clear evidence of benefit.
Light
A more novel form of treatment involves exposure to broad- or narrow-band ultraviolet (UV) light. UV radiation exposure has been found to have a localized immunomodulatory effect on affected tissues and may be used to decrease the severity and frequency of flares. In particular, the usage of UVA1 is more effective in treating acute flares, whereas narrow-band UVB is more effective in long-term management scenarios. However, UV radiation has also been implicated in various types of skin cancer, and thus UV treatment is not without risk. UV phototherapy is not indicated in young adults and children due to this risk of skin cancer with prolonged use or exposure.
Alternative medicine
While several Chinese herbal medicines are intended for treating atopic eczema, no conclusive evidence shows that these treatments, taken by mouth or applied topically, reduce the severity of eczema in children or adults.
Epidemiology
Since the beginning of the 20th century, many inflammatory skin disorders have become more common; AD is a classic example of such a disease. It now affects 15–30% of children and 2–10% of adults in developed countries, and in the United States has nearly tripled in the past 30–40 years. Over 15 million American adults and children have AD.
Research
Evidence suggests that IL-4 is central in the pathogenesis of AD. Therefore, a rationale exists for targeting IL-4 with IL-4 inhibitors. People with atopic dermatitis are more likely to have Staphylococcus aureus living on them. The role this plays in pathogenesis is yet to be determined.
See also
Sweat allergy
References
External links
NIH Handout on Health: Atopic Dermatitis
DermAtlas 9
"Atopic Dermatitis". Genetics Home Reference. U.S. National Library of Medicine. |
Pityriasis rubra pilaris | Pityriasis rubra pilaris refers to a group of chronic disorders characterized by reddish orange, scaling plaques and keratotic follicular papules.: 442 Symptoms may include reddish-orange patches (Latin: rubra) on the skin, severe flaking (Latin: pityriasis), uncomfortable itching, thickening of the skin on the feet and hands, and thickened bumps around hair follicles (Latin: pilus for hair). For some, early symptoms may also include generalized swelling of the legs, feet and other parts of the body. PRP has a varied clinical progression and a varied rate of improvement. There is currently no known cause or cure for PRP.
It was first described by Marie-Guillaume-Alphonse Devergie in 1856, and the condition is also known as Devergies disease.
Diagnosis
Classification
Dr. W.A.D. Griffiths, from Great Britain, classified six forms of PRP in the early 1980s. At this time, the causes of PRP are still unknown and symptoms can be difficult to diagnose. Frequently, more than one medical professional will be consulted before an accurate PRP diagnosis is made.Dermatologists have identified both an acquired form and an inherited form (familial) of PRP and have described them in medical journals. The acquired form usually shows a spontaneous or gradual remission of symptoms within several years although long-term symptoms may continue for years. The inherited form starts early in childhood with persistent long-term symptoms into adulthood.Although most people who develop PRP are over age 50, individuals of any age, race, and nationality can be affected. Women and men seem to be equally affected.
Treatment
Treatment with emollients is used to relieve symptoms of cracking and dryness. Application of lubricants under plastic occlusion before bedtime appears to aid removal of scales on hands and feet. Other topical options include: topical corticosteroids alone, or combined with keratolytics, such as urea and vitamin D3 analogues.
The most effective therapy is long term use of oral retinoids, such as acitretin and isotretinoin. Other effective systemic approaches include: methotrexate, cyclosporin and corticosteroids. There are also reports that the monoclonal antibody ustekinumab (which blocks IL-23/ IL-12) may be effective.
See also
List of cutaneous conditions
Footnotes
Further reading
Dr. Griffith (June 1998). "Pityriasis rubra pilaris". In Champion R.H.; Burton J.L.; Burns D.A.; Breathnach S.M. (eds.). Textbook of Dermatology. Vol. 2 (6th ed.). pp. 1539–1545. ISBN 0-632-05064-0.
== External links == |
Purpura | Purpura () is a condition of red or purple discolored spots on the skin that do not blanch on applying pressure. The spots are caused by bleeding underneath the skin secondary to platelet disorders, vascular disorders, coagulation disorders, or other causes. They measure 3–10 mm, whereas petechiae measure less than 3 mm, and ecchymoses greater than 1 cm.Purpura is common with typhus and can be present with meningitis caused by meningococci or septicaemia. In particular, meningococcus (Neisseria meningitidis), a Gram-negative diplococcus organism, releases endotoxin when it lyses. Endotoxin activates the Hageman factor (clotting factor XII), which causes disseminated intravascular coagulation (DIC). The DIC is what appears as a rash on the affected individual.
Classification
Purpura are a common and nonspecific medical sign; however, the underlying mechanism commonly involves one of:
Platelet disorders (thrombocytopenic purpura)
Primary thrombocytopenic purpura
Secondary thrombocytopenic purpura
Post-transfusion purpura
Vascular disorders (nonthrombocytopenic purpura)
Microvascular injury, as seen in senile (old age) purpura, when blood vessels are more easily damaged
Hypertensive states
Deficient vascular support
Vasculitis, as in the case of Henoch–Schönlein purpura
Coagulation disorders
Disseminated intravascular coagulation (DIC)
Scurvy (vitamin C deficiency) – defect in collagen synthesis due to lack of hydroxylation of procollagen results in weakened capillary walls and cells
Meningococcemia
Clumping fibrillary protein deposits caused by Amyloidosis
Cocaine use with concomitant use of the one-time chemotherapy drug and now veterinary deworming agent levamisole can cause purpura of the ears, face, trunk, or extremities, sometimes needing reconstructive surgery. Levamisole is purportedly a common cutting agent.
Decomposition of blood vessels including purpura is a symptom of acute radiation poisoning in excess of 2 Grays of radiation exposure. This is an uncommon cause in general, but is commonly seen in victims of nuclear disaster.Cases of psychogenic purpura are also described in the medical literature, some claimed to be due to "autoerythrocyte sensitization". Other studies suggest the local (cutaneous) activity of tissue plasminogen activator can be increased in psychogenic purpura, leading to substantial amounts of localized plasmin activity, rapid degradation of fibrin clots, and resultant bleeding. Petechial rash is also characteristic of a rickettsial infection.
Etymology and pronunciation
The word purpura () comes from Latin purpura, "purple", which came from ancient Greek πορφύρα. Purpura is a mass noun naming the condition or state, not the name of an individual spot (thus there is no *pupurum, *purpura or *purpura, *purpurae count declension).
See also
Bruise, which is a hematoma caused by trauma
Petechia, which is a small type of hematoma (<3 mm)
Ecchymosis, which is a large type of hematoma (>1 cm)
Purpura secondary to clotting disorders
Purpura hemorrhagica in horses
Pigmented purpuric dermatosis
Schamberg disease (progressive pigmentary purpura)
References
External links
Evaluating the Child with Purpura from American Academy of Family Physicians |
Peritonsillar abscess | Peritonsillar abscess (PTA), also known as quinsy, is an accumulation of pus due to an infection behind the tonsil. Symptoms include fever, throat pain, trouble opening the mouth, and a change to the voice. Pain is usually worse on one side. Complications may include blockage of the airway or aspiration pneumonitis.PTA is typically due to infection by a number of types of bacteria. Often it follows streptococcal pharyngitis. They do not typically occur in those who have had a tonsillectomy. Diagnosis is usually based on the symptoms. Medical imaging may be done to rule out complications.Treatment is by removing the pus, antibiotics, sufficient fluids, and pain medication. Steroids may also be useful. Admission to hospital is generally not needed. In the United States about 3 per 10,000 people per year are affected. Young adults are most commonly affected.
Signs and symptoms
Physical signs of a peritonsillar abscess include redness and swelling in the tonsillar area of the affected side and swelling of the jugulodigastric lymph nodes. The uvula may be displaced towards the unaffected side.Unlike tonsillitis, which is more common in children, PTA has a more even age spread, from children to adults. Symptoms start appearing two to eight days before the formation of an abscess. A progressively severe sore throat on one side and pain during swallowing (odynophagia) usually are the earliest symptoms. As the abscess develops, persistent pain in the peritonsillar area, fever, a general sense of feeling unwell, headache, and a distortion of vowels informally known as "hot potato voice" may appear. Neck pain associated with tender, swollen lymph nodes, referred ear pain and foul breath are also common. While these signs may be present in tonsillitis itself, a PTA should be specifically considered if there is limited ability to open the mouth (trismus).
Complications
While most people recover uneventfully, there is a wide range of possible complications. These may include:
Retropharyngeal abscess
Extension of abscess in other deep neck spaces leading to airway compromise (see Ludwigs angina)
Airway obstruction
Aspiration pneumonitis
Lung abscess (following rupture)
Sepsis
Life-threatening hemorrhage (following erosion or septic necrosis into the carotid sheath of the neck)
Glomerulonephritis and rheumatic fever (chronic complications of strep throat)Difficulty swallowing can lead to decreased oral intake and dehydration.
Causes
PTA usually arises as a complication of an untreated or partially treated episode of acute tonsillitis. The infection, in these cases, spreads to the peritonsillar area (peritonsillitis). This region comprises loose connective tissue and is hence susceptible to formation of an abscess. PTA can also occur de novo. Both aerobic and anaerobic bacteria can be causative. Commonly involved aerobic pathogens include Streptococcus, Staphylococcus and Haemophilus. The most common anaerobic species include Fusobacterium necrophorum, Peptostreptococcus, Prevotella species, and Bacteroides.
Diagnosis
Diagnosis is usually based on the symptoms. Medical imaging may be done to rule out complications. Medical imaging may include CT scan, MRI, or ultrasound is also useful in diagnosis.
Treatment
Medical treatment with antibiotics, volume repletion with fluids, and pain medication is usually adequate, although in cases where airway obstruction or systemic sepsis occurs, surgical drainage may be necessary. Steroids may also be useful. Admission to hospital is generally not needed.
Medication
The infection is frequently penicillin resistant. There are a number of antibiotics options including amoxicillin/clavulanate, clindamycin, or metronidazole in combination with benzylpenicillin (penicillin G) or penicillin V. Piperacillin/tazobactam may also be used.
Surgery
The pus can be removed by a number of methods including needle aspiration, incision and drainage, and tonsillectomy. Incision and drainage may be associated with a lower chance of recurrence than needle aspiration but the evidence is very uncertain. Needle aspiration may be less painful but again the evidence is very uncertain.Treatment can also be given while a patient is under anesthesia, but this is usually reserved for children or anxious patients. Tonsillectomy can be indicated if a patient has recurring peritonsillar abscesses or a history of tonsillitis. For patients with their first peritonsillar abscess most ENT-surgeons prefer to "wait and observe" before recommending tonsillectomy.
Epidemiology
It is a commonly encountered otorhinolaryngological (ENT) emergency.The number of new cases per year of peritonsillar abscess in the United States has been estimated approximately at 30 cases per 100,000 people. In a study in Northern Ireland, the number of new cases was 10 cases per 100,000 people per year.
In Denmark, the number of new cases is higher and reaches 41 cases per 100,000 people per year. Younger children who develop a peritonsillar abscess are often immunocompromised and in them, the infection can cause airway obstruction.
Etymology
The condition is often referred to as "quincy", "quinsy", or "quinsey", anglicised versions of the French word esquinancie which was originally rendered as squinsey and subsequently quinsy.
Notable cases
Sultan Tekish of Kwarezm
Osceola
Michel de Montaigne
Pope Adrian IV
Dan Minogue, the captain/coach of Australian Rules football team Richmond was rumoured to be dead a week before the 1920 VFL Grand Final, but in fact, was in his hometown of Bendigo recovering from quinsy.
George Washington was believed to have died of complications arising from quinsy, but is now thought to have died from epiglottitis.
James Gregory of the band The Ordinary Boys almost died from quinsy because it was left untreated for so long before emergency treatment was started.
Eiichiro Oda, author of the best-selling One Piece manga, was hospitalized due to complications.
Ian Maclaren died of complications from quinsy while on a lecture tour of the United States.The ancient Roman goddess Angerona was claimed to cure quinsy (Latin angina) in humans and sheep.
References
== External links == |
Dens invaginatus | Dens invaginatus (DI), also known as tooth within a tooth, is a rare dental malformation where there is an infolding of enamel into dentine. The prevalence of condition is 0.3 - 10%, affecting more males than females. The condition is presented in two forms, coronal and radicular, with the coronal form being more common.
DI is a malformation of teeth most likely resulting from an infolding of the dental papilla during tooth development or invagination of all layers of the enamel organ in dental papillae. Affected teeth show a deep infolding of enamel and dentine starting from the foramen coecum or even the tip of the cusps and which may extend deep into the root. Teeth most affected are maxillary lateral incisors (80%), followed by maxillary canines (20%). Bilateral occurrence is not uncommon (25%).
Signs and symptoms
Tooth affected by this condition has a higher risk of developing caries and periradicular pathology. The thin layer of the infolding enamel could be chipped off easily, providing entrance for microorganisms into the tooth canal. This can cause abscess formation, displacement of dental structures (i.e. teeth). Preventive measures should be taken.
Cause
Cause of DI is unclear. However, there are several theories:
Infection
Trauma
Growth pressure of the dental arches during odontogenesis
Rapid proliferation of the internal enamel epithelium invades the underlying dental papilla
Diagnosis
During clinical examination, abnormally shaped tooth can be observed. Teeth with this condition can have a conical shape or deep pit on the lingual side or have an exaggerated talon cusp.
Although examination may reveal a fissure on the surface of anterior tooth, radiographic examination is the way. On a periapical radiograph, the invagination lesion will appear as a radiolucent pocket. It is usually seen beneath the cingulum or incisal edge. Larger lesions can appear as fissures. A radio-opaque could be shown. Pulp may be involved and the root canal could have complex anatomy. Two periapical radiographs are often required to make sure that it is not a masked lesion.
Cone beam computed tomography (CBCT) is useful in diagnosing DI. It provides clinicians a detailed 3D image and could aid treatment planning. Feasibility of root canal treatment or apical surgery or other procedures could be assessed.
Oehlers classification
Class I - Partial invagination. It is limited to the crown of tooth. The lesion does not extend pass the cementoenamel junction (CEJ) or the pulp.
Class II - Partial invagination. It extends beyond the crown and CEJ. Pulp may be involved but remain within the root anatomy. There is no communication of the lesion with periodontal ligament (PDL).
Class IIIa - Complete invagination. It extends through root and communicates with PDL. It usually does not involve the pulp but can cause anatomical malformation.
Class IIIb - Complete invagination. It extends through the root and communicates with PDL through apical foramen. Pulpal anatomy may not be directly involved but can cause disruption to the dental anatomy.
Histology
No irregularities in the dentin below invagination
Strains of vital tissue or fine canals that communicates with the pulp could be found
Enamel lining irregularly structured
External and internal enamel have different structures
Management
Preventative treatment - e.g. oral hygiene instructions, fissure sealant
Intentional replantation
Root canal treatment with mineral trioxde aggregate
Periapical surgery with retrograde filling
Extraction
References
== External links == |
Encephalocele | Encephalocele is a neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull. These defects are caused by failure of the neural tube to close completely during fetal development. Encephaloceles cause a groove down the middle of the skull, or between the forehead and nose, or on the back side of the skull. The severity of encephalocele varies, depending on its location.
Signs and symptoms
Encephaloceles are often accompanied by craniofacial abnormalities or other brain malformations. Symptoms may include neurologic problems, hydrocephalus (cerebrospinal fluid accumulated in the brain), spastic quadriplegia (paralysis of the limbs), microcephaly (an abnormally small head), ataxia (uncoordinated muscle movement), developmental delay, vision problems, mental and growth retardation, and seizures.
Causes
Since its earliest cited case in the 16th century, many generations of scientists have attempted to explain the cause. Little has been revealed in the centuries to follow. Although the exact cause is unknown, encephaloceles are caused by failure of the neural tube to close completely during fetal development. Both environmental and genetic factors have been seen to contribute to the cause of encephaloceles. Some studies have revealed a higher occurrence in female embryos, suggesting a genetic cause. Research has indicated that teratogens (substances known to cause birth defects), trypan blue (a stain used to color dead tissues or cells blue), and arsenic may damage the developing fetus and cause encephaloceles.Proper levels of folic acid have been shown to help prevent such defects when taken before pregnancy, and early in pregnancy.Occipital encephaloceles are frequently accompanied by hydrocephalus, as seen in 60-90% of patients.
Diagnosis
Usually encephaloceles are noticeable deformities and are diagnosed immediately after birth, but a small encephalocele in the nasal or forehead region can go undetected. Various physical and mental developmental delays can indicate the presence of encephaloceles.
Classifications
Encephaloceles of the face are generally classified as nasofrontal, nasoethmoidal, or naso-orbital, however, there can be some overlap in the type of encephalocele. They can also appear along any part of the cranial vault, as they result from abnormal closure of cranial bones; the most common location for encephaloceles is the occipital region. If the bulging portion contains only cerebrospinal fluid and the overlying membrane, it may be called a meningocele. If brain tissue is present, it may be referred to as a meningoencephalocele. When the head size or occipitofrontal circumference is smaller than the herniating sac, then it is termed as giant encephalocele.Separation of the neural and surface ectoderm causes apoptosis in the midline. A disturbance in this separation process at the final closure due to the lack of apoptosis is considered to be a critical aspect of nasofrontal and nasoethmoidal encephalocele.
Prevention
It is recommended that women take a multivitamin with 400 micrograms of folic acid daily to reduce the likelihood of any type of neural tube defects before and during the first 28 days after conception.
Treatment
A series of steps involved in reconstructive surgery of a frontal encephalocele. The same child is in all the images.
Currently, the only effective treatment for encephaloceles is reparative surgery, generally performed during infancy. The extent to which it can be corrected depends on the location and size of the encephaloceles; however, large protrusions can be removed without causing major disability. Surgery repositions the bulging area back into the skull, removes the protrusions, and corrects the deformities, typically relieving pressure that can delay normal brain development. Occasionally, shunts are placed to drain excess cerebrospinal fluid from the brain.The goals of treatment include:
closure of open skin defects to prevent infection and desiccation of brain tissue
removal of nonfunctional extracranial cerebral tissue with water-tight closure of the dura
total craniofacial reconstruction with particular emphasis on avoiding the long-nose deformity (nasal elongation that results from depression of the cribiform plate and nasal placode). Without proper management, the long-nose deformity can be more obvious after repair.
Recovery
Recovery is difficult to predict prior to surgery, and depends on the type of brain tissue involved and location of the encephaloceles. If surgery is successful, and developmental delays have not occurred, a patient can develop normally. Where neurologic and developmental damage has occurred, the specialists will focus on minimizing both mental and physical disabilities.In general, when the bulging material consists of primarily cerebrospinal fluid, a complete recovery can occur. When a large amount of brain tissue is present in the encephaloceles, there is a higher chance of perioperative complication.
Epidemiology
Encephaloceles occur rarely, at a rate of one per 5,000 live births worldwide. Encephaloceles of the back of the head are more common in Europe and North America, while encephaloceles on the front of the head more frequently occur in Southeast Asia, Africa, Malaysia, and Russia. Ethnic, genetic, and environmental factors, as well as parental age, can all affect the likelihood of encephaloceles. The condition can occur in families with a family history of spina bifida.
Notable cases
The Facemakers: Operation Smile is a documentary co-produced by the Discovery Channel and BBC 1 in conjunction with century films aired on 21 June 2000. The Facemakers documents the remarkable changes that occurred in the lives of three children as a result of Operation Smiles visit to Davao City in the Philippines in 1999. One child in particular, Abel Gastardo, had a condition too severe to be treated during the time of the mission. Abel had a rare nasofrontal facial encephalocele, an extreme protrusion of brain tissue from the front of his skull. The documentary follows Abel to the United States seven months later to receive corrective surgery. He was brought over by Operation Smile to receive the major surgery in Virginia, at the Childrens Hospital of the Kings Daughters. The other facial defects within the fifty-minute programme consisted of children with facial cleft and cleft lip and palate which may be associated with encephalocele.
In November 2006, there was an hour-long documentary on the British television network Channel 4 about Facing the World, an organization that helps children with severe facial disfigurements in developing countries. One of the children featured on the documentary was Ney, a Cambodian boy who had a severe form of encephalocele, wherein part of his brain protruded through his face.
On December 4, 2012, Dr. Meara again led a cranio-facial surgical team to remove the encephalocele of an infant, Dominic Gundrum, the son of a Wisconsin Court of Appeals judge and his wife. The surgery also closed the babys skull, repaired a Tessier facial cleft, and brought the babys facial features together.
See also
Cephalic disorder
Knobloch syndrome
References
9. Chaturvedi J, Goyal N, Arora RK, Govil N. Giant occipitocervical encephalocele. J Neurosci Rural Pract 2018;9:414-6
External links
encephaloceles at NINDS |
Nuchal fibroma | Nuchal-type fibroma is a rare benign proliferation involving the dermis and subcutaneous tissues, that is a collection of dense, hypocellular bundles of collagen with entrapped adipocytes and increased numbers of small nerves. It is no longer called a nuchal fibroma, but instead a "nuchal-type fibroma" since it develops in other anatomic sites. There is no known etiology. The World Health Organization, 2020, classified nuchal fibromas as a specific tumor form in the category of benign fibroblastic and myofibroblastic tumors.
Signs and symptoms
These lesions are generally asymptomatic, although patients give a long history of a solitary, superficial mass. The mass is usually in the neck (hence the name "nuchal-type"), but it can be seen in the extremities, lumbosacral area, buttocks, and face.
There is a strong association with diabetes mellitus and Gardner syndrome; in fact, it may be the initial manifestation of Gardner syndrome.
Pathology
The tumors are unencapsulated and poorly circumscribed, showing a firm, white cut surface. Most tumors are about 3.5 cm, but can be up to 8 cm.
By microscopic examination, there are haphazardly arranged thick collagen fibers, with a low cellularity and no pleomorphism. There are usually entrapped fat cells, skeletal muscle, and peripheral nerves. The may be perineural fibrosis. The elastic fibers may be altered, which is why an elastofibroma is considered in the differential diagnosis.
Immunohistochemistry
The tumor cells are strongly positive for vimentin, CD34, and sometimes with CD99. There is often (up to 2/3rds) a nuclear reaction with β-catenin.
Diagnosis
Differential diagnoses
The differential diagnosis includes elastofibroma, fibrolipoma, desmoid-type fibromatoses, and nuchal fibrocartilaginous pseudotumor.
Management
Simple excision is curative. However, in patients with Gardner syndrome, up to 45% will develop desmoid-type fibromatosis at other sites, and so this should be searched for and excluded. Patients can develop a recurrence, so follow-up is required.
Epidemiology
This is a rare tumor, presenting over a wide age range, but usually in the 3rd to 5th decades of life. There is a slight male predilection, although this is not seen in syndrome associated patients. The most common site is the posterior neck, but may also be seen in other sites (extremities, lumbosacral area, buttocks, face).
See also
Fibrous Lesions
References
Further reading
Lester D. R. Thompson; Bruce M. Wenig (2011). Diagnostic Pathology: Head and Neck: Published by Amirsys. Hagerstown, MD: Lippincott Williams & Wilkins. pp. 8:44–45. ISBN 978-1-931884-61-7. |
Lichen myxedematosus | Lichen myxedematosus is a group of cutaneous disorders considered mucinoses.: 183 Conditions included in this group are:: 183
Generalized lichen myxedematosus
Localized lichen myxedematosusDiscrete papular lichen myxedematosus
Acral persistent papular mucinosis
Self-healing papular mucinosisSelf-healing juvenile cutaneous mucinosisPapular mucinosis of infancy
Atypical lichen myxedematosus
Atypical tuberous myxedema
See also
List of cutaneous conditions
References
== External links == |
WDR45 | WD repeat domain phosphoinositide-interacting protein 4 (WIPI-4) is a protein that in humans is encoded by the WDR45 gene. Mutations in this gene cause a distinct form of Neurodegeneration with brain iron accumulation (NBIA) called Beta-propeller protein-associated neurodegeneration (BPAN).
Function
WIPI-4 is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation.
This gene WDR45 has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined.
Role in disease
De novo loss of function mutations in WDR45 were identified by exome sequencing in 20 patients with progressive neurodegeneration and evidence of iron on brain MRI scans. The mutations cause an X-linked dominant form of NBIA now called Beta-propeller protein-associated neurodegeneration (BPAN). A name for the disease before the gene was identified was called static encephalopathy of childhood with neurodegeneration in adulthood (SENDA), though this term is no longer used. There are no current treatments for BPAN, though medications and therapies can be used to treat symptoms.
See also
WIPI protein family
References
== Further reading == |
Fiddlers neck | Fiddlers neck is an occupational disease that affects violin and viola players.It is a cutaneous condition usually characterized by redness, thickening, and inflammation on the left side of the neck below the angle of the jaw where the instrument is held. Acne-like lesions and cysts may form at the site due to foreign body reactions, and infections may also occur due to poor hygiene. The primary causes of fiddlers neck are constant friction and local pressure. It is well known among professional orchestra musicians but is "not well recognized by dermatologists", and a red mark on the left side of the neck under the jaw "functions as an identifying sign" of a violinist or violist "in public without seeing the instrument".
Although the presence of fiddlers neck is sometimes used as an indicator of a violinists skill, or battle scars from constant practice, many violinists never develop fiddlers neck, due to differences in skin sensitivity, playing habits, and the materials used in the construction of the instrument. An accomplished professional player could practice hard their whole life and never develop fiddlers neck.
Signs and symptoms
Fiddlers neck usually involves highly localized lichenification, mild hyperpigmentation, and erythema where the chin rest or instrument body presses against the skin of the neck. Other signs and symptoms include scale buildup, cyst and scar formation, papules and pustules related to local infection, and focal edema. In Blum & Ritters study in West Germany (1990), they found that 27% of their population had only minor issues, 72% had a palpable mass at the site, and 23% reported pain and other signs of inflammation such as hyperthermia, pulsation, and cystic, pustular, or papular lesions. Size of masses were an average of 2 cm in diameter ranging up to 4 cm, some being associated with purulent drainage, continuous discharge, and crusting. Dystrophic calcinosis cutis has also been reported. Other serious sequelae include sialolithiasis of the submandibular gland and adenolymphoma of the parotid gland.The histopathology of fiddlers neck frequently shows hyperkeratosis and acanthosis, along with plugging of follicles. Histiocytic infiltration with granulomas to foreign body and follicular cysts are also common. Foreign body granulomas are thought to derive from abrasion of the wooden surface of the chin rest and its absorption into the superficial dermis. The location and complex mechanism of causation for fiddlers neck give rise to a wider spectrum of skin changes when compared to contact dermatitis from more common irritants. Fiddlers neck can be differentiated from rosacea and sarcoid reaction with granulomas.
Causes
The proximal causes of fiddlers neck are friction and pressure, but both repetitive shearing stress and occlusion with consequent trapping of sweat give rise to progressive damage. This damage along with poor hygiene predisposes the area to local infection, and such infection can progress to scarring and other long-term effects. Hot weather is reported to exacerbate fiddlers neck, as are tiredness, playing emotional music, and playing in smaller groups where individual stress is higher. Type I hypersensitivity reactions may also be involved, particularly to rosewood and ebony in the chinrest and tailpiece, as well as to varnish of the instrument body when chinrests are not used and to rosin deposits on the instrument and on chin cloths. Nickel or other metal allergies are common causes if the chin rest has a metal clip that comes into constant contact with the skin. Rosin exposure in particular may lead to abietic acid dermatitis.
Diagnosis
Differential diagnoses
The differential diagnoses of fiddlers neck include branchial cleft cyst, disease of the salivary glands, tumors of the parotid gland, psoriasis, lichen planus, contact dermatitis, herpes simplex and similar infections, and insect bites and stings especially from fleas.
Treatment
Treatment for fiddlers neck is unnecessary if it is painless and shows minimal swelling, particularly since minor cases are taken as a mark of pride. But fiddlers neck may lead to worse disorders. The primary methods of treatment involve adjustments to playing of the instrument:
good hygiene for the affected area and for the instrument
use of a clean cotton cloth that is changed frequently
use of a comfortable pad to absorb sweat and reduce friction between the instrument and skin
use of a shoulder rest to reduce pressure below the jaw
a suitable chin rest, especially one carved or molded for the individual
covering or changing potentially allergenic materials on the instrument.
shifting the chin rest to the center of the body over the tailpiece
smoothing coarse surfaces to reduce abrasion
for males, growing a beard to avoid folliculitisSurgery is necessary for sialolithiasis, parotid tumors, and cysts. Cervical lymph nodes that are larger than 1 cm must be biopsied. Connective tissue can be removed by excision when a non-inflamed mass is large, and there is generally little recurrence. Infections should be treated conservatively, and causative species should be identified through smear and culture for appropriate antibiotic selection. Reduction of playing time may be helpful for cases without inflammation, but in 30% of cases this did not improve the symptoms.
Prevalence
Fiddlers neck does not usually form unless the musician is practicing or playing for more than a few hours each day, and only seems to develop after a few years of serious playing. Thus, when not infected or otherwise problematic, fiddlers neck may be known as a benign practice mark and may be worn proudly as an indication of long hours of practice. Blum & Ritter (1990) found that 62% of 523 professional violinists and violists in West Germany experienced fiddlers neck, with the percentage among violists being higher (67%) than among violinists (59%). Viola players are believed to be more predisposed to developing fiddlers neck than violinists because the viola is larger and heavier, but this has not been empirically confirmed.The development of fiddlers neck does not depend on preexisting skin problems, and Blum & Ritter find that only 23% of men and 14% of women in their study reported cutaneous disorders in other parts of the face (mainly acne and eczema) that were independent of playing the violin or viola. Fiddlers neck may exacerbate existing acne, but acne may also be limited solely to the lesion and not appear elsewhere. Nonetheless, musicians with underlying dermatologic diseases like acne and eczema are more endangered by fiddlers neck than others. Males may develop folliculitis or boils due to involvement of beard hair.
References
== External links == |
Dysphagia lusoria | Dysphagia lusoria (or Bayford-Autenrieth dysphagia) is an abnormal condition characterized by difficulty in swallowing caused by an aberrant right subclavian artery. It was discovered by David Bayford in 1761 and first reported in a paper by the same in 1787.
Pathophysiology
During development of aortic arch, if the proximal portion of the right fourth arch disappears instead of distal portion, the right subclavian artery will arise as the last branch of aortic arch. It then courses behind the esophagus (or rarely in front of esophagus, or even in front of trachea) to supply blood to right arm. This causes pressure on esophagus and results in dysphagia. It can sometimes result in upper gastrointestinal tract bleeding.
Investigation of choice - CT angiography
Treatment
Surgical repair is performed. Reconstruction or ligation of aberrant right subclavian artery by sternotomy/by neck approach.
Eponym
David Bayford called it dysphagia lusoria because in Latin, lusus naturæ means sports of nature or natural anomaly. Bayford-Autenrieth dysphagia is eponym for Bayford and Autenrieth.
See also
Aberrant subclavian artery
Ortners syndrome
References
== External links == |
Haemodialysis-associated amyloidosis | Amyloidosis is the accumulation on misfolded protein fibers in the body. This is very common condition associated with many of the chronic illness.
Haemodialysis-associated amyloidosis is a form of systemic amyloidosis associated with chronic kidney failure. Even if this is common in CKD patients with chronic regular dialysis, it can be also seen in patient with CKD but have never dialysed too.
Presentation
Long-term haemodialysis results in a gradual accumulation of β2 microglobulin, a serum protein, in the blood. It accumulates because it is unable to cross the dialysis filter.
Affected individuals usually present after 5 years of dialysis rarely before that. The tendency of haemodialysis-associated amyloidosis is to be articular in general affecting the joints.
Diagnosis
Prevention
The mainstay of management of the dialysis related amyloidosis is the prevention than the other type of treatment methods. Because most of the medical and surgical managements for this condition may not prevent the symptoms completely. Therefore we have to take adequate precautions to prevent future dialysis disequilibrium syndrome in CKD patients.
There are several steps in prevention of dialysis related amyloidosis.
Use of high flux dialyzers
Use of Beta 2 globulin absorber
Preserve the residual kidney functions
Early kidney transplant
In addition low copper dialysis is theorized to prevent or delay onset.
Management
Management of haemodialysis associated amyloidosis is symptomatic. Although there are lot of methods to prevent and delay the complications, probably the steroids and analgesics may helpful in the management of the condition.
However there are some surgical procedure to reduce the pain.
See also
Hepatoerythropoietic porphyria
List of cutaneous conditions
References
External links
https://academic.oup.com/ndt/article-pdf/13/suppl_1/58/9896967/130058.pdf |
Morphea | Morphea is a form of scleroderma that involves isolated patches of hardened skin on the face, hands, and feet, or anywhere else on the body, with no internal organ involvement.: 130
Signs and symptoms
Morphea most often presents as macules or plaques a few centimeters in diameter, but also may occur as bands or in guttate lesions or nodules.: 171 Morphea is a thickening and hardening of the skin and subcutaneous tissues from excessive collagen deposition. Morphea includes specific conditions ranging from very small plaques only involving the skin to widespread disease causing functional and cosmetic deformities. Morphea discriminates from systemic sclerosis by its supposed lack of internal organ involvement. This classification scheme does not include the mixed form of morphea in which different morphologies of skin lesions are present in the same individual. Up to 15% of morphea patients may fall into this previously unrecognized category.
Cause
Physicians and scientists do not know what causes morphea. Case reports and observational studies suggest there is a higher frequency of family history of autoimmune diseases in patients with morphea. Tests for autoantibodies associated with morphea have shown results in higher frequencies of anti-histone and anti-topoisomerase IIa antibodies. Case reports of morphea co-existing with other systemic autoimmune diseases such as primary biliary cirrhosis, vitiligo, and systemic lupus erythematosus lend support to morphea as an autoimmune disease.Borrelia burgdorferi infection may be relevant for the induction of a distinct autoimmune type of scleroderma; it may be called "Borrelia-associated early onset morphea" and is characterized by the combination of disease onset at younger age, infection with B. burgdorferi, and evident autoimmune phenomena as reflected by high-titer antinuclear antibodies.
Diagnosis
Classification
Morphea–lichen sclerosus et atrophicus overlap is characterized by both lesions of morphea and lichen sclerosus et atrophicus, most commonly seen in women.: 171
Generalized morphea is characterized by widespread indurated plaques and pigmentary changes, sometimes associated with muscle atrophy, but without visceral involvement.: 171
Morphea profunda involves deep subcutaneous tissue, including fascia, and there is a clinical overlap with eosinophilic fasciitis, eosinophilia-myalgia syndrome, and the Spanish toxic oil syndrome.: 171 Morphea profunda shows little response to corticosteroids and tends to run a more chronic debilitating course.: 171
Pansclerotic morphea is manifested by sclerosis of the dermis, panniculus, fascia, muscle, and at times, the bone, all causing disabling limitation of motion of joints.: 171
Linear scleroderma is a type of localised scleroderma which is an autoimmune disease characterized by a line of thickened skin which can affect the bones and muscles underneath it. It most often occurs in the arms, legs, or forehead, and may occur in more than one area. It is also most likely to be on just one side of the body. Linear scleroderma generally first appears in young children.
Frontal linear scleroderma (also known as en coup de sabre or morphea en coup de sabre) is a type of linear scleroderma characterized by a linear band of atrophy and a furrow in the skin that occurs in the frontal or frontoparietal scalp. Multiple lesions of en coup de sabre may coexist in a single patient, with one report suggesting that the lesions followed Blaschkos lines. It gets its name from the perceived similarity to a sabre wound.
Atrophoderma of Pasini and Pierini (also known as "Dyschromic and atrophic variation of scleroderma," "Morphea plana atrophica," "Sclérodermie atrophique demblée") is a disease characterized by large lesions with a sharp peripheral border dropping into a depression with no outpouching, which, on biopsy, elastin is normal, while collagen may be thickened. Atrophoderma of Pasini and Pierini affects less than 200,000 Americans and is classified as a rare disease by http://rarediseases.info.nih.gov. The disease results in round or oval patches of hyper-pigmented skin. The darkened skin patches may sometimes have a bluish or purplish hue when they first appear and are often smooth to the touch and hairless.
Treatment
Throughout the years, many different treatments have been tried for morphea including topical, intra-lesional, and systemic corticosteroids. Antimalarials such as hydroxychloroquine or chloroquine have been used. Other immunomodulators such as methotrexate, topical tacrolimus, and penicillamine have been tried. Children and teenagers with active morphea (linear scleroderma, generalised morphea and mixed morphea: linear and circumscribed) may experience greater improvement of disease activity or damage with oral methotrexate plus prednisone than with placebo plus prednisone. Some have tried prescription vitamin-D with success. Ultraviolet A (UVA) light, with or without psoralens have also been tried. UVA-1, a more specific wavelength of UVA light, is able to penetrate the deeper portions of the skin and thus, thought to soften the plaques in morphea by acting in two fashions: by causing a systemic immunosuppression from UV light, or by inducing enzymes that naturally degrade the collagen matrix in the skin as part of natural sun-aging of the skin. [1] However, there is limited evidence that UVA‐1 (50 J/cm2), low‐dose UVA‐1 (20 J/cm2), and narrowband UVB differ from each other in effectiveness in treating children and adults with active morphea.
Epidemiology
Morphea is a form of scleroderma that is more common in women than men, in a ratio 3:1. Morphea occurs in childhood as well as in adult life.
Morphea is an uncommon condition that is thought to affect 2 to 4 in 100,000 people. Adequate studies on the incidence and prevalence have not been performed. Morphea also may be under-reported, as physicians may be unaware of this disorder, and smaller morphea plaques may be less often referred to a dermatologist or rheumatologist.
See also
List of cutaneous conditions
References
Further reading
JAMA Dermatology Patient Page. Morphea (Localized Scleroderma. Nicole M. Fett, MD. JAMA Dermatol. 2013;149(9):1124. doi:10.1001/jamadermatol.2013.5079. September 2013
== External links == |
Nonvenereal endemic syphilis | Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by the endemicum subspecies of the spirochete Treponema pallidum. Bejel is one of the "endemic treponematoses" (endemic infections caused by spiral-shaped bacteria called treponemes), a group that also includes yaws and pinta. Typically, endemic trepanematoses begin with localized lesions on the skin or mucous membranes. Pinta is limited to affecting the skin, whereas bejel and yaws are considered to be invasive because they can also cause disease in bone and other internal tissues.
Signs and symptoms
Bejel usually begins in childhood as a small patch on the mucosa, often on the interior of the mouth, followed by the appearance of raised, eroding lesions on the limbs and trunk. Periostitis (inflammation) of the leg bones is commonly seen, and gummas of the nose and soft palate develop in later stages.
Causes
Although the organism that causes bejel, Treponema pallidum endemicum, is morphologically and serologically indistinguishable from Treponema pallidum pallidum, which causes venereal syphilis, transmission of bejel is not venereal in nature, generally resulting from mouth-to-mouth contact or sharing of domestic utensils, and the courses of the two diseases are somewhat different.
Diagnosis
The diagnosis of bejel is based on the geographic history of the patient as well as laboratory testing of material from the lesions (dark-field microscopy). The responsible spirochaete is readily identifiable on sight in a microscope as a treponema.
Treatment
It is treatable with penicillin or other antibiotics, resulting in a complete recovery.
Epidemiology
Bejel is mainly found in arid countries of the eastern Mediterranean region and in West Africa, where it is known as sahel. (Sahel disease should be distinguished from "Sahel", the geographical band between the Northern Sahara and Southern Sudan.)
See also
Pinta (disease)
Syphilis
Yaws
References
== External links == |
Diabetes | Diabetes mellitus, commonly known as diabetes, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased appetite. If left untreated, diabetes can cause many health complications. Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death. Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, damage to the nerves, damage to the eyes and cognitive impairment.Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not responding properly to the insulin produced. Insulin is a hormone which is responsible for helping glucose from food get into cells to be used for energy. There are three main types of diabetes mellitus:
Type 1 diabetes results from failure of the pancreas to produce enough insulin due to loss of beta cells. This form was previously referred to as "insulin-dependent diabetes mellitus" or "juvenile diabetes". The loss of beta cells is caused by an autoimmune response. The cause of this autoimmune response is unknown. Although Type 1 diabetes usually appears during childhood or adolescence, it can also develop in adults.
Type 2 diabetes begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses, a lack of insulin may also develop. This form was previously referred to as "non insulin-dependent diabetes mellitus" or "adult-onset diabetes". Type 2 diabetes is more common in older adults, but a significant increase in the prevalence of obesity among children has led to more cases of type 2 diabetes in younger people. The most common cause is a combination of excessive body weight and insufficient exercise.
Gestational diabetes is the third main form, and occurs when pregnant women without a previous history of diabetes develop high blood sugar levels. In women with gestational diabetes, blood sugar usually returns to normal soon after delivery. However, women who had gestational diabetes during pregnancy have a higher risk of developing type 2 diabetes later in life.Type 1 diabetes must be managed with insulin injections. Prevention and treatment of type 2 diabetes involves maintaining a healthy diet, regular physical exercise, a normal body weight, and avoiding use of tobacco. Type 2 diabetes may be treated with oral antidiabetic medications, with or without insulin. Control of blood pressure and maintaining proper foot and eye care are important for people with the disease. Insulin and some oral medications can cause low blood sugar (hypoglycemia). Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 diabetes. Gestational diabetes usually resolves after the birth of the baby.As of 2019, an estimated 463 million people had diabetes worldwide (8.8% of the adult population), with type 2 diabetes making up about 90% of the cases. Rates are similar in women and men. Trends suggest that rates will continue to rise. Diabetes at least doubles a persons risk of early death. In 2019, diabetes resulted in approximately 4.2 million deaths. It is the 7th leading cause of death globally. The global economic cost of diabetes-related health expenditure in 2017 was estimated at US$727 billion. In the United States, diabetes cost nearly US$327 billion in 2017. Average medical expenditures among people with diabetes are about 2.3 times higher.
Signs and symptoms
The classic symptoms of untreated diabetes are unintended weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger). Symptoms may develop rapidly (weeks or months) in type 1 diabetes, while they usually develop much more slowly and may be subtle or absent in type 2 diabetes.Several other signs and symptoms can mark the onset of diabetes although they are not specific to the disease. In addition to the known symptoms listed above, they include blurred vision, headache, fatigue, slow healing of cuts, and itchy skin. Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. Long-term vision loss can also be caused by diabetic retinopathy. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.
Diabetic emergencies
People with diabetes (usually but not exclusively in type 1 diabetes) may also experience diabetic ketoacidosis (DKA), a metabolic disturbance characterized by nausea, vomiting and abdominal pain, the smell of acetone on the breath, deep breathing known as Kussmaul breathing, and in severe cases a decreased level of consciousness. DKA requires emergency treatment in hospital. A rarer but more dangerous condition is hyperosmolar hyperglycemic state (HHS), which is more common in type 2 diabetes and is mainly the result of dehydration caused by high blood sugars.Treatment-related low blood sugar (hypoglycemia) is common in people with type 1 and also type 2 diabetes depending on the medication being used. Most cases are mild and are not considered medical emergencies. Effects can range from feelings of unease, sweating, trembling, and increased appetite in mild cases to more serious effects such as confusion, changes in behavior such as aggressiveness, seizures, unconsciousness, and rarely permanent brain damage or death in severe cases. Rapid breathing, sweating, and cold, pale skin are characteristic of low blood sugar but not definitive. Mild to moderate cases are self-treated by eating or drinking something high in rapidly absorbed carbohydrates. Severe cases can lead to unconsciousness and must be treated with intravenous glucose or injections with glucagon.
Complications
All forms of diabetes increase the risk of long-term complications. These typically develop after many years (10–20) but may be the first symptom in those who have otherwise not received a diagnosis before that time.The major long-term complications relate to damage to blood vessels. Diabetes doubles the risk of cardiovascular disease and about 75% of deaths in people with diabetes are due to coronary artery disease. Other macrovascular diseases include stroke, and peripheral artery disease. These complications are also a strong risk factor for severe COVID-19 illness.The primary complications of diabetes due to damage in small blood vessels include damage to the eyes, kidneys, and nerves. Damage to the eyes, known as diabetic retinopathy, is caused by damage to the blood vessels in the retina of the eye, and can result in gradual vision loss and eventual blindness. Diabetes also increases the risk of having glaucoma, cataracts, and other eye problems. It is recommended that people with diabetes visit an eye doctor once a year. Damage to the kidneys, known as diabetic nephropathy, can lead to tissue scarring, urine protein loss, and eventually chronic kidney disease, sometimes requiring dialysis or kidney transplantation. Damage to the nerves of the body, known as diabetic neuropathy, is the most common complication of diabetes. The symptoms can include numbness, tingling, sudomotor dysfunction, pain, and altered pain sensation, which can lead to damage to the skin. Diabetes-related foot problems (such as diabetic foot ulcers) may occur, and can be difficult to treat, occasionally requiring amputation. Additionally, proximal diabetic neuropathy causes painful muscle atrophy and weakness.
There is a link between cognitive deficit and diabetes. Compared to those without diabetes, those with the disease have a 1.2 to 1.5-fold greater rate of decline in cognitive function. Having diabetes, especially when on insulin, increases the risk of falls in older people.
Causes
Diabetes mellitus is classified into six categories: type 1 diabetes, type 2 diabetes, hybrid forms of diabetes, hyperglycemia first detected during pregnancy, "unclassified diabetes", and "other specific types". "Hybrid forms of diabetes" include slowly evolving, immune-mediated diabetes of adults and ketosis-prone type 2 diabetes. "Hyperglycemia first detected during pregnancy" includes gestational diabetes mellitus and diabetes mellitus in pregnancy (type 1 or type 2 diabetes first diagnosed during pregnancy). The "other specific types" are a collection of a few dozen individual causes. Diabetes is a more variable disease than once thought and people may have combinations of forms.
Type 1
Type 1 diabetes is characterized by loss of the insulin-producing beta cells of the pancreatic islets, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of an immune-mediated nature, in which a T cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin. It causes approximately 10% of diabetes mellitus cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Although it has been called "juvenile diabetes" due to the frequent onset in children, the majority of individuals living with type 1 diabetes are now adults."Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis and should not be used. Still, type 1 diabetes can be accompanied by irregular and unpredictable high blood sugar levels, and the potential for diabetic ketoacidosis or serious low blood sugar levels. Other complications include an impaired counterregulatory response to low blood sugar, infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addisons disease). These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type 1 diabetes.
Type 1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors, such as a viral infection or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans. Among dietary factors, data suggest that gliadin (a protein present in gluten) may play a role in the development of type 1 diabetes, but the mechanism is not fully understood.Type 1 diabetes can occur at any age, and a significant proportion is diagnosed during adulthood. Latent autoimmune diabetes of adults (LADA) is the diagnostic term applied when type 1 diabetes develops in adults; it has a slower onset than the same condition in children. Given this difference, some use the unofficial term "type 1.5 diabetes" for this condition. Adults with LADA are frequently initially misdiagnosed as having type 2 diabetes, based on age rather than a cause.
Type 2
Type 2 diabetes is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion. The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus cases due to a known defect are classified separately. Type 2 diabetes is the most common type of diabetes mellitus. Many people with type 2 diabetes have evidence of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) before meeting the criteria for type 2 diabetes. The progression of prediabetes to overt type 2 diabetes can be slowed or reversed by lifestyle changes or medications that improve insulin sensitivity or reduce the livers glucose production.Type 2 diabetes is primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity (defined by a body mass index of greater than 30), lack of physical activity, poor diet, stress, and urbanization. Excess body fat is associated with 30% of cases in people of Chinese and Japanese descent, 60–80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders. Even those who are not obese may have a high waist–hip ratio.Dietary factors such as sugar-sweetened drinks are associated with an increased risk. The type of fats in the diet is also important, with saturated fat and trans fats increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk. Eating white rice excessively may increase the risk of diabetes, especially in Chinese and Japanese people. Lack of physical activity may increase the risk of diabetes in some people.Adverse childhood experiences, including abuse, neglect, and household difficulties, increase the likelihood of type 2 diabetes later in life by 32%, with neglect having the strongest effect.Antipsychotic medication side effects (specifically metabolic abnormalities, dyslipidemia and weight gain) and unhealthy lifestyles (including poor diet and decreased physical activity), are potential risk factors.
Gestational diabetes
Gestational diabetes resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2–10% of all pregnancies and may improve or disappear after delivery. It is recommended that all pregnant women get tested starting around 24–28 weeks gestation. It is most often diagnosed in the second or third trimester because of the increase in insulin-antagonist hormone levels that occurs at this time. However, after pregnancy approximately 5–10% of women with gestational diabetes are found to have another form of diabetes, most commonly type 2. Gestational diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy. Management may include dietary changes, blood glucose monitoring, and in some cases, insulin may be required.Though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital heart and central nervous system abnormalities, and skeletal muscle malformations. Increased levels of insulin in a fetuss blood may inhibit fetal surfactant production and cause infant respiratory distress syndrome. A high blood bilirubin level may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Labor induction may be indicated with decreased placental function. A caesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.
Other types
Maturity onset diabetes of the young (MODY) is a rare autosomal dominant inherited form of diabetes, due to one of several single-gene mutations causing defects in insulin production. It is significantly less common than the three main types, constituting 1–2% of all cases. The name of this disease refers to early hypotheses as to its nature. Being due to a defective gene, this disease varies in age at presentation and in severity according to the specific gene defect; thus, there are at least 13 subtypes of MODY. People with MODY often can control it without using insulin.Some cases of diabetes are caused by the bodys tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type 2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells, whereas others increase insulin resistance (especially glucocorticoids which can provoke "steroid diabetes"). The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (ICD-10 code E12), was deprecated by the World Health Organization (WHO) when the current taxonomy was introduced in 1999.
Yet another form of diabetes that people may develop is double diabetes. This is when a type 1 diabetic becomes insulin resistant, the hallmark for type 2 diabetes or has a family history for type 2 diabetes. It was first discovered in 1990 or 1991.
The following is a list of disorders that may increase the risk of diabetes:
Pathophysiology
Insulin is the principal hormone that regulates the uptake of glucose from the blood into most cells of the body, especially liver, adipose tissue and muscle, except smooth muscle, in which insulin acts via the IGF-1. Therefore, deficiency of insulin or the insensitivity of its receptors play a central role in all forms of diabetes mellitus.The body obtains glucose from three main sources: the intestinal absorption of food; the breakdown of glycogen (glycogenolysis), the storage form of glucose found in the liver; and gluconeogenesis, the generation of glucose from non-carbohydrate substrates in the body. Insulin plays a critical role in regulating glucose levels in the body. Insulin can inhibit the breakdown of glycogen or the process of gluconeogenesis, it can stimulate the transport of glucose into fat and muscle cells, and it can stimulate the storage of glucose in the form of glycogen.Insulin is released into the blood by beta cells (β-cells), found in the islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the bodys cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Lower glucose levels result in decreased insulin release from the beta cells and in the breakdown of glycogen to glucose. This process is mainly controlled by the hormone glucagon, which acts in the opposite manner to insulin.If the amount of insulin available is insufficient, or if cells respond poorly to the effects of insulin (insulin resistance), or if the insulin itself is defective, then glucose is not absorbed properly by the body cells that require it, and is not stored appropriately in the liver and muscles. The net effect is persistently high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as metabolic acidosis in cases of complete insulin deficiency.When glucose concentration in the blood remains high over time, the kidneys reach a threshold of reabsorption, and the body excretes glucose in the urine (glycosuria). This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume is replaced osmotically from water in body cells and other body compartments, causing dehydration and increased thirst (polydipsia). In addition, intracellular glucose deficiency stimulates appetite leading to excessive food intake (polyphagia).
Diagnosis
Diabetes mellitus is diagnosed with a test for the glucose content in the blood, and is diagnosed by demonstrating any one of the following:
Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL). For this test, blood is taken after a period of fasting, i.e. in the morning before breakfast, after the patient had sufficient time to fast overnight.
Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) two hours after a 75 gram oral glucose load as in a glucose tolerance test (OGTT)
Symptoms of high blood sugar and plasma glucose ≥ 11.1 mmol/L (200 mg/dL) either while fasting or not fasting
Glycated hemoglobin (HbA1C) ≥ 48 mmol/mol (≥ 6.5 DCCT %).A positive result, in the absence of unequivocal high blood sugar, should be confirmed by a repeat of any of the above methods on a different day. It is preferable to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test. According to the current definition, two fasting glucose measurements above 7.0 mmol/L (126 mg/dL) is considered diagnostic for diabetes mellitus.
Per the WHO, people with fasting glucose levels from 6.1 to 6.9 mmol/L (110 to 125 mg/dL) are considered to have impaired fasting glucose. People with plasma glucose at or above 7.8 mmol/L (140 mg/dL), but not over 11.1 mmol/L (200 mg/dL), two hours after a 75 gram oral glucose load are considered to have impaired glucose tolerance. Of these two prediabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus, as well as cardiovascular disease. The American Diabetes Association (ADA) since 2003 uses a slightly different range for impaired fasting glucose of 5.6 to 6.9 mmol/L (100 to 125 mg/dL).Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.
Prevention
There is no known preventive measure for type 1 diabetes. Type 2 diabetes—which accounts for 85–90% of all cases worldwide—can often be prevented or delayed by maintaining a normal body weight, engaging in physical activity, and eating a healthy diet. Higher levels of physical activity (more than 90 minutes per day) reduce the risk of diabetes by 28%. Dietary changes known to be effective in helping to prevent diabetes include maintaining a diet rich in whole grains and fiber, and choosing good fats, such as the polyunsaturated fats found in nuts, vegetable oils, and fish. Limiting sugary beverages and eating less red meat and other sources of saturated fat can also help prevent diabetes. Tobacco smoking is also associated with an increased risk of diabetes and its complications, so smoking cessation can be an important preventive measure as well.The relationship between type 2 diabetes and the main modifiable risk factors (excess weight, unhealthy diet, physical inactivity and tobacco use) is similar in all regions of the world. There is growing evidence that the underlying determinants of diabetes are a reflection of the major forces driving social, economic and cultural change: globalization, urbanization, population aging, and the general health policy environment.
Management
Diabetes management concentrates on keeping blood sugar levels as close to normal, without causing low blood sugar. This can usually be accomplished with dietary changes, exercise, weight loss, and use of appropriate medications (insulin, oral medications).
Learning about the disease and actively participating in the treatment is important, since complications are far less common and less severe in people who have well-managed blood sugar levels. Per the American College of Physicians, the goal of treatment is an HbA1C level of 7-8%. Attention is also paid to other health problems that may accelerate the negative effects of diabetes. These include smoking, high blood pressure, metabolic syndrome obesity, and lack of regular exercise. Specialized footwear is widely used to reduce the risk of diabetic foot ulcers by relieving the pressure on the foot.The principles of managing diabetes may be similar across the general population with diabetes, however some considerations may need to be addressed when tailoring intervention, mainly in special populations.
Considering those with severe mental illness, the efficacy of type 2 diabetes self-management interventions is still poorly explored, with insufficient scientific evidence to show whether these interventions have similar results to those observed in general population.
Lifestyle
People with diabetes can benefit from education about the disease and treatment, dietary changes, and exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.Weight loss can prevent progression from prediabetes to diabetes type 2, decrease the risk of cardiovascular disease, or result in a partial remission in people with diabetes. No single dietary pattern is best for all people with diabetes. Healthy dietary patterns, such as the Mediterranean diet, low-carbohydrate diet, or DASH diet, are often recommended, although evidence does not support one over the others. According to the ADA, "reducing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia", and for individuals with type 2 diabetes who cannot meet the glycemic targets or where reducing anti-glycemic medications is a priority, low or very-low carbohydrate diets are a viable approach. For overweight people with type 2 diabetes, any diet that achieves weight loss is effective.
Medications
Glucose control
Most medications used to treat diabetes act by lowering blood sugar levels through different mechanisms. There is broad consensus that when people with diabetes maintain tight glucose control – keeping the glucose levels in their blood within normal ranges – they experience fewer complications, such as kidney problems or eye problems. There is however debate as to whether this is appropriate and cost effective for people later in life in whom the risk of hypoglycemia may be more significant.There are a number of different classes of anti-diabetic medications. Type 1 diabetes requires treatment with insulin, ideally using a "basal bolus" regimen that most closely matches normal insulin release: long-acting insulin for the basal rate and short-acting insulin with meals. Type 2 diabetes is generally treated with medication that is taken by mouth (e.g. metformin) although some eventually require injectable treatment with insulin or GLP-1 agonists.Metformin is generally recommended as a first-line treatment for type 2 diabetes, as there is good evidence that it decreases mortality. It works by decreasing the livers production of glucose. Several other groups of drugs, mostly given by mouth, may also decrease blood sugar in type 2 diabetes. These include agents that increase insulin release (sulfonylureas), agents that decrease absorption of sugar from the intestines (acarbose), agents that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4) that inactivates incretins such as GLP-1 and GIP (sitagliptin), agents that make the body more sensitive to insulin (thiazolidinedione) and agents that increase the excretion of glucose in the urine (SGLT2 inhibitors). When insulin is used in type 2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications. Doses of insulin are then increased until glucose targets are reached.
Blood pressure lowering
Cardiovascular disease is a serious complication associated with diabetes, and many international guidelines recommend blood pressure treatment targets that are lower than 140/90 mmHg for people with diabetes. However, there is only limited evidence regarding what the lower targets should be. A 2016 systematic review found potential harm to treating to targets lower than 140 mmHg, and a subsequent systematic review in 2019 found no evidence of additional benefit from blood pressure lowering to between 130 – 140mmHg, although there was an increased risk of adverse events.2015 American Diabetes Association recommendations are that people with diabetes and albuminuria should receive an inhibitor of the renin-angiotensin system to reduce the risks of progression to end-stage renal disease, cardiovascular events, and death. There is some evidence that angiotensin converting enzyme inhibitors (ACEIs) are superior to other inhibitors of the renin-angiotensin system such as angiotensin receptor blockers (ARBs), or aliskiren in preventing cardiovascular disease. Although a more recent review found similar effects of ACEIs and ARBs on major cardiovascular and renal outcomes. There is no evidence that combining ACEIs and ARBs provides additional benefits.
Aspirin
The use of aspirin to prevent cardiovascular disease in diabetes is controversial. Aspirin is recommended by some in people at high risk of cardiovascular disease, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes. 2015 American Diabetes Association recommendations for aspirin use (based on expert consensus or clinical experience) are that low-dose aspirin use is reasonable in adults with diabetes who are at intermediate risk of cardiovascular disease (10-year cardiovascular disease risk, 5–10%). National guidelines for England and Wales by the National Institute for Health and Care Excellence (NICE) recommend against the use of aspirin in people with type 1 or type 2 diabetes who do not have confirmed cardiovascular disease.
Surgery
Weight loss surgery in those with obesity and type 2 diabetes is often an effective measure. Many are able to maintain normal blood sugar levels with little or no medications following surgery and long-term mortality is decreased. There is, however, a short-term mortality risk of less than 1% from the surgery. The body mass index cutoffs for when surgery is appropriate are not yet clear. It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.A pancre |
Diabetes | as transplant is occasionally considered for people with type 1 diabetes who have severe complications of their disease, including end stage kidney disease requiring kidney transplantation.
Self-management and support
In countries using a general practitioner system, such as the United Kingdom, care may take place mainly outside hospitals, with hospital-based specialist care used only in case of complications, difficult blood sugar control, or research projects. In other circumstances, general practitioners and specialists share care in a team approach. Home telehealth support can be an effective management technique.The use of technology to deliver educational programs for adults with type 2 diabetes includes computer-based self-management interventions to collect for tailored responses to facilitate self-management. There is no adequate evidence to support effects on cholesterol, blood pressure, behavioral change (such as physical activity levels and dietary), depression, weight and health-related quality of life, nor in other biological, cognitive or emotional outcomes.
Epidemiology
In 2017, 425 million people had diabetes worldwide, up from an estimated 382 million people in 2013 and from 108 million in 1980. Accounting for the shifting age structure of the global population, the prevalence of diabetes is 8.8% among adults, nearly double the rate of 4.7% in 1980. Type 2 makes up about 90% of the cases. Some data indicate rates are roughly equal in women and men, but male excess in diabetes has been found in many populations with higher type 2 incidence, possibly due to sex-related differences in insulin sensitivity, consequences of obesity and regional body fat deposition, and other contributing factors such as high blood pressure, tobacco smoking, and alcohol intake.The WHO estimates that diabetes resulted in 1.5 million deaths in 2012, making it the 8th leading cause of death. However another 2.2 million deaths worldwide were attributable to high blood glucose and the increased risks of cardiovascular disease and other associated complications (e.g. kidney failure), which often lead to premature death and are often listed as the underlying cause on death certificates rather than diabetes. For example, in 2017, the International Diabetes Federation (IDF) estimated that diabetes resulted in 4.0 million deaths worldwide, using modeling to estimate the total number of deaths that could be directly or indirectly attributed to diabetes.Diabetes occurs throughout the world but is more common (especially type 2) in more developed countries. The greatest increase in rates has however been seen in low- and middle-income countries, where more than 80% of diabetic deaths occur. The fastest prevalence increase is expected to occur in Asia and Africa, where most people with diabetes will probably live in 2030. The increase in rates in developing countries follows the trend of urbanization and lifestyle changes, including increasingly sedentary lifestyles, less physically demanding work and the global nutrition transition, marked by increased intake of foods that are high energy-dense but nutrient-poor (often high in sugar and saturated fats, sometimes referred to as the "Western-style" diet). The global number of diabetes cases might increase by 48% between 2017 and 2045.
History
Diabetes was one of the first diseases described, with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine." The Ebers papyrus includes a recommendation for a drink to take in such cases. The first described cases are believed to have been type 1 diabetes. Indian physicians around the same time identified the disease and classified it as madhumeha or "honey urine", noting the urine would attract ants.The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Apollonius of Memphis. The disease was considered rare during the time of the Roman empire, with Galen commenting he had only seen two cases during his career. This is possibly due to the diet and lifestyle of the ancients, or because the clinical symptoms were observed during the advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea urinosa).The earliest surviving work with a detailed reference to diabetes is that of Aretaeus of Cappadocia (2nd or early 3rd century CE). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness, reflecting the beliefs of the "Pneumatic School". He hypothesized a correlation between diabetes and other diseases, and he discussed differential diagnosis from the snakebite, which also provokes excessive thirst. His work remained unknown in the West until 1552, when the first Latin edition was published in Venice.Two types of diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400–500 CE with one type being associated with youth and another type with being overweight. Effective treatment was not developed until the early part of the 20th century when Canadians Frederick Banting and Charles Herbert Best isolated and purified insulin in 1921 and 1922. This was followed by the development of the long-acting insulin NPH in the 1940s.
Etymology
The word diabetes ( or ) comes from Latin diabētēs, which in turn comes from Ancient Greek διαβήτης (diabētēs), which literally means "a passer through; a siphon". Ancient Greek physician Aretaeus of Cappadocia (fl. 1st century CE) used that word, with the intended meaning "excessive discharge of urine", as the name for the disease. Ultimately, the word comes from Greek διαβαίνειν (diabainein), meaning "to pass through", which is composed of δια- (dia-), meaning "through" and βαίνειν (bainein), meaning "to go". The word "diabetes" is first recorded in English, in the form diabete, in a medical text written around 1425.
The word mellitus ( or ) comes from the classical Latin word mellītus, meaning "mellite" (i.e. sweetened with honey; honey-sweet). The Latin word comes from mell-, which comes from mel, meaning "honey"; sweetness; pleasant thing, and the suffix -ītus, whose meaning is the same as that of the English suffix "-ite". It was Thomas Willis who in 1675 added "mellitus" to the word "diabetes" as a designation for the disease, when he noticed the urine of a person with diabetes had a sweet taste (glycosuria). This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and Persians.
Society and culture
The 1989 "St. Vincent Declaration" was the result of international efforts to improve the care accorded to those with diabetes. Doing so is important not only in terms of quality of life and life expectancy but also economically – expenses due to diabetes have been shown to be a major drain on health – and productivity-related resources for healthcare systems and governments.
Several countries established more and less successful national diabetes programmes to improve treatment of the disease.People with diabetes who have neuropathic symptoms such as numbness or tingling in feet or hands are twice as likely to be unemployed as those without the symptoms.In 2010, diabetes-related emergency room (ER) visit rates in the United States were higher among people from the lowest income communities (526 per 10,000 population) than from the highest income communities (236 per 10,000 population). Approximately 9.4% of diabetes-related ER visits were for the uninsured.
Naming
The term "type 1 diabetes" has replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes mellitus. Likewise, the term "type 2 diabetes" has replaced several former terms, including adult-onset diabetes, obesity-related diabetes, and noninsulin-dependent diabetes mellitus. Beyond these two types, there is no agreed-upon standard nomenclature.Diabetes mellitus is also occasionally known as "sugar diabetes" to differentiate it from diabetes insipidus.
Other animals
In animals, diabetes is most commonly encountered in dogs and cats. Middle-aged animals are most commonly affected. Female dogs are twice as likely to be affected as males, while according to some sources, male cats are more prone than females. In both species, all breeds may be affected, but some small dog breeds are particularly likely to develop diabetes, such as Miniature Poodles.Feline diabetes is strikingly similar to human type 2 diabetes. The Burmese, Russian Blue, Abyssinian, and Norwegian Forest cat breeds are at higher risk than other breeds. Overweight cats are also at higher risk.The symptoms may relate to fluid loss and polyuria, but the course may also be insidious. Diabetic animals are more prone to infections. The long-term complications recognized in humans are much rarer in animals. The principles of treatment (weight loss, oral antidiabetics, subcutaneous insulin) and management of emergencies (e.g. ketoacidosis) are similar to those in humans.
References
External links
American Diabetes Association
IDF Diabetes Atlas
National Diabetes Education Program
ADAs Standards of Medical Care in Diabetes 2019
Polonsky KS (October 2012). "The past 200 years in diabetes". The New England Journal of Medicine. 367 (14): 1332–1340. doi:10.1056/NEJMra1110560. PMID 23034021. S2CID 9456681.
"Diabetes". MedlinePlus. U.S. National Library of Medicine. |
Coagulation factor VII | Coagulation factor VII (EC 3.4.21.21, formerly known as proconvertin) is one of the proteins that causes blood to clot in the coagulation cascade, and in humans is coded for by the gene F7. It is an enzyme of the serine protease class. Once bound to tissue factor released from damaged tissues, it is converted to factor VIIa (or blood-coagulation factor VIIa, activated blood coagulation factor VII), which in turn activates factor IX and factor X.
Using genetic recombination a recombinant factor VIIa (eptacog alfa) (trade names include NovoSeven) has been approved by the FDA for the control of bleeding in hemophilia. It is sometimes used unlicensed in severe uncontrollable bleeding, although there have been safety concerns. A biosimilar form of recombinant activated factor VII (AryoSeven) is also available, but does not play any considerable role in the market.
In April 2020, the US FDA approved a new rFVIIa product, eptacog beta (SEVENFACT), the first bypassing agent (BPA) approved in more than 2 decades. As an rFVIIa product, eptacog beta works in a complex with tissue factor to activate factor X to Xa, thereby bypassing FVIII and FIX. The activation of Factor X to Xa initiates the coagulation cascade’s common pathway, leading to clot formation at the site of hemorrhage. Activated FVII binds to endothelial protein C receptor (EPCR), which enhances hemostasis.14 One study showed that eptacog beta binds to EPCR with 25% to 30% more affinity than eptacog alfa, displacing protein C from EPCR binding sites and downregulating activated protein C generation, contributing to its hemostatic effect.
Physiology
The main role of factor VII (FVII) is to initiate the process of coagulation in conjunction with tissue factor (TF/factor III). Tissue factor is found on the outside of blood vessels - normally not exposed to the bloodstream. Upon vessel injury, tissue factor is exposed to the blood and circulating factor VII. Once bound to TF, FVII is activated to FVIIa by different proteases, among which are thrombin (factor IIa), factor Xa, IXa, XIIa, and the FVIIa-TF complex itself. The complex of factor VIIa with TF catalyzes the conversion of factor IX and factor X into the active proteases, factor IXa and factor Xa, respectively.The action of the factor is impeded by tissue factor pathway inhibitor (TFPI), which is released almost immediately after initiation of coagulation. Factor VII, which was discovered around 1950, is vitamin K-dependent and produced in the liver. Use of warfarin or similar anticoagulants decreases hepatic synthesis of FVII.
Structure
Factor VII shares a common domain architecture with factors IX and X.
Genetics
The gene for factor VII is located on chromosome 13 (13q34).
Role in disease
Factor VII deficiency (congenital proconvertin deficiency) is rare and inherited recessively. It presents as a hemophilia-like bleeding disorder. It is treated with recombinant factor VIIa (NovoSeven or AryoSeven). Gene therapy approaches for treating FVII deficiency are very promising ()
Medical uses
Recombinant factor VIIa, marketed under the trade names AryoSeven and NovoSeven, is used for people with hemophilia (with Factor VIII or IX deficiency) who have developed antibodies against replacement coagulation factor.
It has also been used in the setting of uncontrollable hemorrhage, but its role in this setting is controversial with insufficient evidence to support its use outside of clinical trials. The first report of its use in hemorrhage was in an Israeli soldier with uncontrollable bleeding in 1999. Risks of its use include an increase in arterial thrombosis. However, animal studies have not shown complications as seen in humans, in fact same of the studies show a better prognosis. In the military settings it is used as an off label intervention in complications related to disseminated intravascular coagulation related haemorrhage caused by penetrating trauma.Recombinant human factor VII while initially looking promising in intracerebral hemorrhage failed to show benefit following further study and this is no longer recommended.
Interactions
Factor VII has been shown to interact with tissue factor and protein kinase C.
References
Further reading
External links
Official website
The MEROPS online database for peptidases and their inhibitors: S01.215
CHES - Comprehensive Health Education Services LLC - Factor VII treatment and awareness [1] |
Auditory processing disorder | Auditory processing disorder (APD), rarely known as King-Kopetzky syndrome or auditory disability with normal hearing (ADN), is a neurodevelopmental disorder affecting the way the brain processes auditory information. Individuals with APD usually have normal structure and function of the outer, middle, and inner ear (peripheral hearing). However, they cannot process the information they hear in the same way as others do, which leads to difficulties in recognizing and interpreting sounds, especially the sounds composing speech. It is thought that these difficulties arise from dysfunction in the central nervous system. It is highly prevalent in individuals with other neurodevelopmental disorders, such as Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorders, Dyslexia, and Sensory Processing Disorder.
The American Academy of Audiology notes that APD is diagnosed by difficulties in one or more auditory processes known to reflect the function of the central auditory nervous system. It can affect both children and adults. Although the actual prevalence is currently unknown, it has been estimated to be 2–7% in children in US and UK populations. APD can continue into adulthood. Cooper and Gates (1991) estimated the prevalence of adult APD to be 10 to 20%. It has been reported that males are twice as likely to be affected by the disorder as females, and that prevalence is higher in the elderly and increases with age.Neurodevelopmental forms of APD are differentiable from aphasia in that aphasia is by definition caused by acquired brain injury, but acquired epileptic aphasia has been viewed as a form of APD.
Signs and symptoms
Many people experience problems with learning and day-to-day tasks with difficulties over time. Adults with this disorder can experience the signs and symptoms below:
talk louder than necessary
talk softer than necessary
have trouble remembering a list or sequence
often need words or sentences repeated
have poor ability to memorize information learned by listening
interpret words too literally
need assistance hearing clearly in noisy environments
rely on accommodation and modification strategies
find or request a quiet work space away from others
request written material when attending oral presentations
ask for directions to be given one step at a time
Relation to attention deficit hyperactivity disorder
It has been discovered that APD and ADHD present overlapping symptoms. Below is a ranked order of behavioral symptoms that are most frequently observed in each disorder. Professionals evaluated the overlap of symptoms between the two disorders. The order below is of symptoms that are almost always observed. This chart shows that although the symptoms listed are different, it is easy to get confused between many of them.
There is a co-occurrence between ADHD and APD. A systematic review published in 2018 detailed one study that showed 10% of children with APD have confirmed or suspected ADHD. It also stated that it is sometimes difficult to distinguish the two, since characteristics and symptoms between APD and ADHD tend to overlap. The systematic review mentioned here described this overlap between APD and other behavioral disorders and whether or not it was easy to distinguish those children that solely had auditory processing disorder.
Relation to specific language impairment and developmental dyslexia
There has been considerable debate over the relationship between APD and Specific language impairment (SLI).
SLI is diagnosed when a child has difficulties with understanding or producing spoken language for no obvious cause. The problems cannot be explained in terms of peripheral hearing loss. The child is typically late in starting to talk, and may have problems in producing speech sounds clearly, and in producing or understanding complex sentences. Some theoretical accounts of SLI regard it as the result of auditory processing problems. However, this view of SLI is not universally accepted, and others regard the main difficulties in SLI as stemming from problems with higher-level aspects of language processing. Where a child has both auditory and language problems, it can be difficult to sort out the causality at play.Similarly with developmental dyslexia, researchers continue to explore the hypothesis that reading problems emerge as a downstream consequence of difficulties in rapid auditory processing. Again, cause and effect can be hard to unravel. This is one reason why some experts have recommended using non-verbal auditory tests to diagnose APD. Specifically regarding neurological factors, dyslexia has been linked to polymicrogyria which causes cell migrational problems. Children that have polymicrogyri almost always present with deficits on APD testing. It has also been suggested that APD may be related to cluttering, a fluency disorder marked by word and phrase repetitions.
It has been found that a higher than expected proportion of individuals diagnosed with SLI and dyslexia on the basis of language and reading tests also perform poorly on tests in which auditory processing skills are tested. APD can be assessed using tests that involve identifying, repeating or discriminating speech, and a child may do poorly because of primary language problems. In a study comparing children with a diagnosis of dyslexia and those with a diagnosis of APD, they found the two groups could not be distinguished. Analogous results were observed in studies comparing children diagnosed with SLI or APD, the two groups presenting with similar diagnostic criteria. As such, the diagnosis a child receives may depend on which specialist they consult: the same child who might be diagnosed with APD by an audiologist may instead be diagnosed with SLI by a speech-language therapist or with dyslexia by a psychologist.
Causes
Acquired
Acquired APD can be caused by any damage to or dysfunction of the central auditory nervous system and can cause auditory processing problems. For an overview of neurological aspects of APD, see T. D. Griffiths 2002 article "Central Auditory Pathologies".
Genetics
Some studies have indicated an increased prevalence of a family history of hearing impairment in these patients. The pattern of results is suggestive that auditory processing disorder may be related to conditions of autosomal dominant inheritance. The ability to listen to and comprehend multiple messages at the same time is a trait that is heavily influenced by our genes, say federal researchers. These "short circuits in the wiring" sometimes run in families or result from a difficult birth, just like any learning disability. Auditory processing disorder can be associated with conditions affected by genetic traits, such as various developmental disorders. Inheritance of auditory processing disorder refers to whether the condition is inherited from your parents or "runs" in families. Central auditory processing disorder may be hereditary neurological traits from the mother or the father.
Developmental
In the majority of cases of developmental APD, the cause is unknown. An exception is acquired epileptic aphasia or Landau-Kleffner syndrome, where a childs development regresses, with language comprehension severely affected. The child is often thought to be deaf, but normal peripheral hearing is found. In other cases, suspected or known causes of APD in children include delay in myelin maturation, ectopic (misplaced) cells in the auditory cortical areas, or genetic predisposition. In a family with autosomal dominant epilepsy, seizures which affected the left temporal lobe seemed to cause problems with auditory processing. In another extended family with a high rate of APD, genetic analysis showed a haplotype in chromosome 12 that fully co-segregated with language impairment.Hearing begins in utero, but the central auditory system continues to develop for at least the first decade. There is considerable interest in the idea that disruption to hearing during a sensitive period may have long-term consequences for auditory development. One study showed thalamocortical connectivity in vitro was associated with a time sensitive developmental window and required a specific cell adhesion molecule (lcam5) for proper brain plasticity to occur. This points to connectivity between the thalamus and cortex shortly after being able to hear (in vitro) as at least one critical period for auditory processing. Another study showed that rats reared in a single tone environment during critical periods of development had permanently impaired auditory processing. Bad auditory experiences, such as temporary deafness by cochlear removal in rats leads to neuron shrinkage. In a study looking at attention in APD patients, children with one ear blocked developed a strong right-ear advantage but were not able to modulate that advantage during directed-attention tasks.In the 1980s and 1990s, there was considerable interest in the role of chronic Otitis media (middle ear disease or glue ear) in causing APD and related language and literacy problems. Otitis media with effusion is a very common childhood disease that causes a fluctuating conductive hearing loss, and there was concern this may disrupt auditory development if it occurred during a sensitive period. Consistent with this, in a sample of young children with chronic ear infections recruited from a hospital otolargyngology department, increased rates of auditory difficulties were found later in childhood. However, this kind of study will have sampling bias because children with otitis media will be more likely to be referred to hospital departments if they are experiencing developmental difficulties. Compared with hospital studies, epidemiological studies, which assesses a whole population for otitis media and then evaluate outcomes, have found much weaker evidence for long-term impacts of otitis media on language outcomes.
Somatic
It seems that somatic anxiety (that is, physical symptoms of anxiety such as butterflies in the stomach or cotton mouth) and situations of stress may be determinants of speech-hearing disability.
Diagnosis
Questionnaires can be used for the identification of persons with possible auditory processing disorders, as these address common problems of listening. They can help in the decision for pursuing clinical evaluation. One of the most common listening problems is speech recognition in the presence of background noise. According to the respondents who participated in a study by Neijenhuis, de Wit, and Luinge (2017), the following symptoms are characteristic in children with listening difficulties, and they are typically problematic with adolescents and adults. They include:
Difficulty hearing in noise
Auditory attention problems
Better understanding in one on one situations
Difficulties in noise localization
Difficulties in remembering oral informationAccording to the New Zealand Guidelines on Auditory Processing Disorders (2017) a checklist of key symptoms of APD or comorbidities that can be used to identify individuals who should be referred for audiological and APD assessment includes, among others:
Difficulty following spoken directions unless they are brief and simple
Difficulty attending to and remembering spoken information
Slowness in processing spoken information
Difficulty understanding in the presence of other sounds
Overwhelmed by complex or "busy" auditory environments e.g. classrooms, shopping malls
Poor listening skills
Insensitivity to tone of voice or other nuances of speech
Acquired brain injury
History of frequent or persistent middle ear disease (otitis media, glue ear).
Difficulty with language, reading or spelling
Suspicion or diagnosis of dyslexia
Suspicion or diagnosis of language disorder or delayFinally, the New Zealand guidelines state that behavioral checklists and questionnaires should only be used to provide guidance for referrals, for information gathering (for example, prior to assessment or as outcome measures for interventions), and as measures to describe the functional impact of auditory processing disorder. They are not designed for the purpose of diagnosing auditory processing disorders. The New Zealand guidelines indicate that a number of questionnaires have been developed to identify children who might benefit from evaluation of their problems in listening. Examples of available questionnaires include the Fishers Auditory Problems Checklist, the Childrens Auditory Performance Scale, the Screening Instrument for Targeting Educational Risk, and the Auditory Processing Domains Questionnaire among others. All of the previous questionnaires were designed for children and none are useful for adolescents and adults.The University of Cincinnati Auditory Processing Inventory (UCAPI) was designed for use with adolescents and adults seeking testing for evaluation of problems with listening and/or to be used following diagnosis of an auditory processing disorder to determine the subjects status. Following a model described by Zoppo et al. (2015) a 34-item questionnaire was developed that investigates auditory processing abilities in each of the six common areas of complaint in APD (listening and concentration, understanding speech, following spoken instructions, attention, and other.) The final questionnaire was standardized on normally-achieving young adults ranging from 18 to 27 years of age. Validation data was acquired from subjects with language-learning or auditory processing disorders who were either self-reported or confirmed by diagnostic testing. A UCAPI total score is calculated by combining the totals from the six listening conditions and provides an overall value to categorize listening abilities. Additionally, analysis of the scores from the six listening conditions provides an auditory profile for the subject. Each listening condition can then be utilized by the professional in making recommendation for diagnosing problem of learning through listening and treatment decisions. The UCAPI provides information on listening problems in various populations that can aid examiners in making recommendations for assessment and management.APD has been defined anatomically in terms of the integrity of the auditory areas of the nervous system. However, children with symptoms of APD typically have no evidence of neurological disease and the diagnosis is made on the basis of performance on behavioral auditory tests. Auditory processing is "what we do with what we hear", and in APD there is a mismatch between peripheral hearing ability (which is typically normal) and ability to interpret or discriminate sounds. Thus in those with no signs of neurological impairment, APD is diagnosed on the basis of auditory tests. There is, however, no consensus as to which tests should be used for diagnosis, as evidenced by the succession of task force reports that have appeared in recent years. The first of these occurred in 1996. This was followed by a conference organized by the American Academy of Audiology.Experts attempting to define diagnostic criteria have to grapple with the problem that a child may do poorly on an auditory test for reasons other than poor auditory perception: for instance, failure could be due to inattention, difficulty in coping with task demands, or limited language ability. In an attempt to rule out at least some of these factors, the American Academy of Audiology conference explicitly advocated that for APD to be diagnosed, the child must have a modality-specific problem, i.e. affecting auditory but not visual processing. However, a committee of the American Speech-Language-Hearing Association subsequently rejected modality-specificity as a defining characteristic of auditory processing disorders.
Definitions
in 2005 The American Speech-Language-Hearing Association (ASHA) published "Central Auditory Processing Disorders" as an update to the 1996 "Central Auditory Processing: Current Status of Research and Implications for Clinical Practice". The American Academy of Audiology has released more current practice guidelines related to the disorder. ASHA formally defines APA as "a difficulty in the efficiency and effectiveness by which the central nervous system (CNS) utilizes auditory information."In 2018, the British Society of Audiology published a position statement and practice guidance on auditory processing disorder (APD) updated its definition of APD. According to the Society, APD refers to the inability to process speech and on-speech sounds.Auditory processing disorder can be developmental or acquired. It may result from ear infections, head injuries or neurodevelopmental delays that affect processing of auditory information. This can include problems with: "...sound localization and lateralization (see also binaural fusion); auditory discrimination; auditory pattern recognition; temporal aspects of audition, including temporal integration, temporal discrimination (e.g., temporal gap detection), temporal ordering, and temporal masking; auditory performance in competing acoustic signals (including dichotic listening); and auditory performance with degraded acoustic signals".The Committee of UK Medical Professionals Steering the UK Auditory Processing Disorder Research Program have developed the following working definition of auditory processing disorder: "APD results from impaired neural function and is characterized by poor recognition, discrimination, separation, grouping, localization, or ordering of speech sounds. It does not solely result from a deficit in general attention, language or other cognitive processes."
Types of testing
The SCAN-C for children and SCAN-A for adolescents and adults are the most common tools for screening and diagnosing APD in the USA. Both tests are standardized on a large number of subjects and include validation data on subjects with auditory processing disorders. The SCAN test batteries include screening tests: norm-based criterion-referenced scores; diagnostic tests: scaled scores, percentile ranks and ear advantage scores for all tests except the Gap Detection test. The four tests include four subsets on which the subject scores are derived include: discrimination of monaurally presented single words against background noise (speech in noise), acoustically degraded single words (filtered words), dichotically presented single words and sentences.
Random Gap Detection Test (RGDT) is also a standardized test. It assesses an individuals gap detection threshold of tones and white noise. The exam includes stimuli at four different frequencies (500, 1000, 2000, and 4000 Hz) and white noise clicks of 50 ms duration. It is a useful test because it provides an index of auditory temporal resolution. In children, an overall gap detection threshold greater than 20 ms means they have failed and may have an auditory processing disorder based on abnormal perception of sound in the time domain.
Gaps in Noise Test (GIN) also measures temporal resolution by testing the patients gap detection threshold in white noise.
Pitch Patterns Sequence Test (PPT) and Duration Patterns Sequence Test (DPT) measure auditory pattern identification. The PPS has s series of three tones presented at either of two pitches (high or low). Meanwhile, the DPS has a series of three tones that vary in duration rather than pitch (long or short). Patients are then asked to describe the pattern of pitches presented.
Masking Level Difference (MLD) at 500 Hz measures overlapping temporal processing, binaural processing, and low-redundancy by measuring the difference in threshold of an auditory stimulus when a masking noise is presented in and out of phase.
The Staggered Spondaic Word Test (SSW) is one of the oldest tests for APD developed by Jack Katz. Although it has fallen into some disuse by audiologists as it is complicated to score, it is one of the quickest and most sensitive tests to determine APD.
Modality-specificity and controversies
The issue of modality-specificity has led to considerable debate among experts in this field. Cacace and McFarland have argued that APD should be defined as a modality-specific perceptual dysfunction that is not due to peripheral hearing loss. They criticise more inclusive conceptualizations of APD as lacking diagnostic specificity. A requirement for modality-specificity could potentially avoid including children whose poor auditory performance is due to general factors such as poor attention or memory. Others, however, have argued that a modality-specific approach is too narrow, and that it would miss children who had genuine perceptual problems affecting both visual and auditory processing. It is also impractical, as audiologists do not have access to standardized tests that are visual analogs of auditory tests. The debate over this issue remains unresolved between modality-specific researchers such as Cacace, and associations such as the American Speech-Language-Hearing Association (among others). It is clear, however, that a modality-specific approach will diagnose fewer children with APD than a modality-general one, and that the latter approach runs a risk of including children who fail auditory tests for reasons other than poor auditory processing. Although modality-specific testing has been advocated for well over a decade, the visual analog of APD testing has met with sustained resistance from the fields of optometry and ophthalmology.Another controversy concerns the fact that most traditional tests of APD use verbal materials. The British Society of Audiology has embraced Moores (2006) recommendation that tests for APD should assess processing of non-speech sounds. The concern is that if verbal materials are used to test for APD, then children may fail because of limited language ability. An analogy may be drawn with trying to listen to sounds in a foreign language. It is much harder to distinguish between sounds or to remember a sequence of words in a language you do not know well: the problem is not an auditory one, but rather due to lack of expertise in the language.In recent years there have been additional criticisms of some popular tests for diagnosis of APD. Tests that use tape-recorded American English have been shown to over-identify APD in speakers of other forms of English. Performance on a battery of non-verbal auditory tests devised by the Medical Research Councils Institute of Hearing Research was found to be heavily influenced by non-sensory task demands, and indices of APD had low reliability when this was controlled for. This research undermines the validity of APD as a distinct entity in its own right and suggests that the use of the term "disorder" itself is unwarranted. In a recent review of such diagnostic issues, it was recommended that children with suspected auditory processing impairments receive a holistic psychometric assessment including general intellectual ability, auditory memory, and attention, phonological processing, language, and literacy. The authors state that "a clearer understanding of the relative contributions of perceptual and non-sensory, unimodal and supramodal factors to performance on psychoacoustic tests may well be the key to unravelling the clinical presentation of these individuals."Depending on how it is defined, APD may share common symptoms with ADD/ADHD, specific language impairment, and autism spectrum disorders. A review showed substantial evidence for atypical processing of auditory information in children with autism. Dawes and Bishop noted how specialists in audiology and speech-language pathology often adopted different approaches to child assessment, and they concluded their review as follows: "We regard it as crucial that these different professional groups work together in carrying out assessment, treatment and management of children and undertaking cross-disciplinary research." In practice, this seems rare.To ensure that APD is correctly diagnosed, the examiners must differentiate APD from other disorders with similar symptoms. Factors that should be taken into account during the diagnosis are: attention, auditory neuropathy, fatigue, hearing and sensitivity, intellectual and developmental age, medications, motivation, motor skills, native language and language experience, response strategies and decision-making style, and visual acuity.It should also be noted that children under the age of seven cannot be evaluated correctly because their language and auditory processes are still developing. In addition, the presence of APD cannot be evaluated when a childs primary language is not English.
Characteristics
The American Speech-Language-Hearing Association state that children with (central) auditory processing disorder often:
have trouble paying attention to and remembering information presented orally, and may cope better with visually acquired information
have problems carrying out multi-step directions given orally; need to hear only one direction at a time
have poor listening skills
need more time to process information
have difficulty learning a new language
have difficulty understanding jokes, sarcasm, and learning songs or nursery rhymes
have language difficulties (e.g., they confuse syllable sequences and have problems developing vocabulary and understanding language)
have difficulty with reading, comprehension, spelling, and vocabularyAPD can manifest as problems determining the direction of sounds, difficulty perceiving differences between speech sounds and the sequencing of these sounds into meaningful words, confusing similar sounds such as "hat" with "bat", "there" with "where", etc. Fewer words may be perceived than were actually said, as there can be problems detecting the gaps between words, creating the sense that someone is speaking unfamiliar or nonsense words. In addition, it is common for APD to cause speech errors involving the distortion and substitution of consonant sounds. Those with APD may have problems relating what has been said with its meaning, despite obvious recognition that a word has been said, as well as repetition of the word. Background noise, such as the sound of a radio, television or a noisy bar can make it difficult to impossible to understand speech, since spoken words may sound distorted either into irrelevant words or words that dont exist, depending on the severity of the auditory processing disorder. Using a telephone can be problematic for someone with auditory processing disorder, in comparison with someone with normal auditory processing, due to low quality audio, poor signal, intermittent sounds and the chopping of words. Many who have auditory processing disorder subconsciously develop visual coping strategies, such as lip reading, reading body language, and eye contact, to compensate for their auditory deficit, and these coping strategies are not available when using a telephone.As noted above, the status of APD as a distinct disorder has been queried, especially by speech-language pathologists and psychologists, who note the overlap between clinical profiles of children diagnosed with APD and those with other forms of specific learning disability. Many audiologists, however, would dispute that APD is just an alternative label for dyslexia, SLI, or ADHD, noting that although it often co-occurs with these conditions, it can be found in isolation.
Subcategories
Based on sensitized measures of auditory dysfunction and on psychological assessment, patients can be subdivided into seven subcategories:
middle ear dysfunction
mild cochlear pathology
central/medial olivocochlear efferent system (MOCS) auditory dysfunction
purely psychological problems
multiple auditory pathologies
combined auditory dysfunction and psychological problems
unknownDifferent subgroups may represent different pathogenic and aetiological factors. Thus, subcategorization provides further understanding of the basis of auditory processing disorder, and hence may guide the rehabilitative management of these patients. This was suggested by Professor Dafydd Stephens and F Zhao at the Welsh Hearing Institute, Cardiff University.
Treatment
Treatment of APD typically focuses on three primary areas: changing learning environment, developing higher-order skills to compensate for the disorder, and remediation of the auditory deficit itself. However, there is a lack of well-conducted evaluations of intervention using randomized controlled trial methodology. Most evidence for effectiveness adopts weaker standards of evidence, such as showing that performance improves after training. This does not control for possible influences of practice, maturation, or placebo effects. Recent research has shown that practice with basic auditory processing tasks (i.e. auditory training) may improve performance on auditory processing measures and phonemic awareness measures. Changes after auditory training have also been recorded at the physiological level. Many of these tasks are incorporated into computer-based auditory training programs such as Earobics and Fast ForWord, an adaptive software available at home and in clinics worldwide, but overall, evidence for effectiveness of these computerised interventions in improving language and literacy is not impressive. One small-scale uncontrolled study reported successful outcomes for children with APD using auditory training software.Treating additional issues related to APD can result in success. For example, treatment for phonological disorders (difficulty in speech) can result in success in terms of both the phonological disorder as well as APD. In one study, speech therapy improved auditory evoked potentials (a measure of brain activity in the auditory portions of the brain).While there is evidence that language training is effective for improving APD, there is no current research supporting the following APD treatments:
Auditory Integration Training typically involves a child attending two 30-minute sessions per day for ten days.
Lindamood-Bell Learning Processes (particularly, the Visualizing and Verbalizing program)
Physical activities that require frequent crossing of the midline (e.g., occupational therapy)
Sound Field Amplification
Neuro-Sensory Educational Therapy
NeurofeedbackHowever, use of an individual FM transmitter/receiver system by teachers and students has been shown to produce significant improvements with children over time.
History
Samuel J. Kopetzky first described the condition in 1948. P. F. King, first discussed the etiological factors behind it in 1954. Helmer Rudolph Myklebusts 1954 study, "Auditory Disorders in Children". suggested auditory processing disorder was separate from language learning difficulties. His work sparked interest in auditory deficits after acquired brain lesions affecting the temporal lobes and led to additional work looking at the physiological basis of auditory processing, but it was not until the late seventies and early eighties that research began on APD in depth.
In 1977, the first conference on the topic of APD was organized by Robert W. Keith, Ph.D. at the University of Cincinnati. The proceedings of that conference was published by Grune and Stratton under the title "Central Auditory Dysfunction" (Keith RW Ed.) That conference started a new series of studies focusing on APD in children. Virtually all tests currently used to diagnose APD originate from this work. These early researchers also invented many of the auditory training approaches, including interhemispheric transfer training and interaural intensity difference training. This period gave us a rough understanding of the causes and possible treatment options for APD.
Much of the work in the late nineties and 2000s has been looking to refining testing, developing more sophisticated treatment options, and looking for genetic risk factors for APD. Scientists have worked on improving behavioral tests of auditory function, neuroimaging, electroacoustic, and electrophysiologic testing. Working with new technology has led to a number of software programs for auditory training. With global awareness of mental disorders and increasing understanding of neuroscience, auditory processing is more in the public and academic consciousness than ever before.
See also
Amblyaudia
Auditory verbal agnosia
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Auditory processing disorder | Cocktail party effect
Cortical deafness
Dafydd Stephens
Echoic memory
Hearing loss
Language processing
List of eponymous diseases
Music-specific disorders
Selective auditory attention
Selective mutism
Sensory processing disorders
Spatial hearing loss
References
External links
Auditory processing disorder: An overview for the clinician
American Speech-Language-Hearing Association (ASHA) |
Subsets and Splits