page_title
stringlengths 1
91
| page_text
stringlengths 0
34.2k
|
|---|---|
Laryngeal paralysis | Laryngeal paralysis in animals is a condition in which the nerves and muscles that control the movements of one or both arytenoid cartilages of the larynx cease to function, and instead of opening during aspiration and closing during swallowing, the arytenoids remain stationary in a somewhat neutral position. Specifically, the muscle that causes abduction of the arytenoid cartilage, the cricoarytenoideus dorsalis muscle, ceases to function. This leads to inadequate ventilation during exercise and during thermoregulatory panting as well as incomplete protection of the airway during swallowing.
One of the most common forms of laryngeal paralysis develops in geriatric medium to large breed dogs, in particular the Labrador retriever, but also some other breeds. This had been traditionally known as idiopathic laryngeal paralysis ("ILP": idiopathic means "of unknown cause"), and was believed to be a result of a condition affecting the nerves of the larynx (bilateral mononeuropathy of the recurrent laryngeal nerves). However investigations into ILP by two groups in Michigan and Tennessee between 2005 - 2013 showed that the condition was not limited to, or specifically a result of, dysfunction of the laryngeal nerves. Instead it was the most visible symptom of a slowly progressing polyneuropathy of old age, which also affected other nerves in the body. This finding, now generally believed correct following further research, has led to the proposed renaming of this type of laryngeal paralysis from "Idiopathic laryngeal paralysis" ("ILP") to "Geriatric onset laryngeal paralysis polyneuropathy" ("GOLPP").
Animals affected by laryngeal paralysis have reduced tolerance for exercise and heat and an increased risk of aspiration pneumonia. The condition is not generally regarded as causing pain, other than physical distress and anxiety caused by any difficulty in breathing or emotional distress from any difficulty with physical movement. Where laryngeal paralysis is related to a general progressive polyneuropathy, as in GOLPP, the nervous system will gradually degenerate causing increasing difficulty in management of the limbs (especially rear limbs), swallowing and breathing, and eventually in most cases euthanasia. Laryngeal paralysis is fairly common in large breed and geriatric dogs, particularly in the Labrador retriever, is rarely found in cats, and can also occur in horses where it is referred to as roaring, roarers syndrome, or medically as laryngeal hemiplegia or recurrent laryngeal neuropathy (RLN). Laryngeal paralysis can be unilateral or bilateral depending upon dysfunction of one or both arytenoid cartilages.
Causes
In most cases, the cause of laryngeal paralysis is unknown or idiopathic. However, the disorder may arise secondary to general neuropathies, generalized neuromuscular diseases, muscular diseases, neoplasia either in the cervical (neck) region or the cranial mediastinum, or trauma. This acquired form occurs predominantly in middle-aged to old large breed or giant breed dogs such as the Labrador Retriever, golden retriever, Siberian Husky, Newfoundland, and St. Bernard. Usually these dogs are born with a normal larynx, but over time the nerves and muscles that control the laryngeal cartilages lose function.Laryngeal paralysis may also be congenital in some breeds (e.g. Bouvier des Flandres, Dalmatians, Siberian huskies, and bulldogs), appearing in dogs between two and six months of age. Affected puppies may have difficulty swallowing and breathing, they may gag frequently, and their bark often sounds abnormal. In Dalmatians it is part of another condition called laryngeal paralysis-polyneuropathy complex. Affected puppies should not be used for breeding.Choke collars are not thought to be a significant risk factor for this disorder. However, after LP is diagnosed it is usually recommended to stop using a collar or anything else around the dogs neck and to switch to a harness instead.
Signs
Signs of laryngeal paralysis include voice change (the dogs bark becomes hoarse-sounding), gagging or coughing (often during or after eating or drinking), exercise intolerance, inspiratory stridor (noisy breathing on inspiration), difficulty breathing, and in severe cases cyanosis or syncope (fainting). Secondary problems may also occur, including aspiration or edema in the lungs, though often the problem remains an upper respiratory problem. Affected dogs are vulnerable to heat stroke and heat exhaustion due to their limited ability to cool themselves down by panting, but the disorder itself can be mistaken for heat stroke.
Signs may occur at any time, but initially owners may only notice that their dogs bark sounds different, that their dog cant run as much as before, or that the dog has trouble in hot weather in unilateral cases because the unaffected side can compensate for the paralysed side. However most unilateral cases will eventually progress to include both sides of the larynx, a more serious problem with symptoms appearing more often.
Signs are usually worse in hot and humid weather, during exercise, during times of stress or excitement, and in obese pets. Acute or late-stage symptoms are usually unmistakable and require immediate emergency treatment.
Diagnosis
This condition is usually diagnosed by direct examination of the larynx under light sedation, which also allows checking for benign or malignant tumors. Tests, such as thoracic radiographs, CT-scans, or echocardiography, are sometimes needed to rule out heart, lung, or mediastinal diseases or other possible causes of the symptoms often seen with LP. Some vets may also recommend running a thyroid profile since LP can be a symptom or complication of hypothyroidism.
Treatment
Mild cases are managed by limiting activity, keeping a healthy body weight, and avoiding exposure to high ambient temperatures. Mild sedatives can be used to decrease anxiety and panting and therefore improve respiration. Corticosteroids may also be administered in acute cases to decrease inflammation and edema of the larynx.
Severe acute symptoms, such as difficulty breathing, hyperthermia, or aspiration pneumonia, must be stabilized with sedatives and oxygen therapy and may require steroid or antibiotic medications. Sometimes a tracheotomy is required to allow delivery of oxygen. Once the patient is stabilized, surgical treatment may be beneficial especially when paralysis occurs in both arytenoid cartilages (bilateral paralysis). The surgery (aretynoid lateralization, or a "laryngeal tieback") consists of suturing one of the aretynoid cartilages in a maximally abducted (open) position. This reduces the signs associated with inadequate ventilation (such as exercise intolerance or overheating) but may exacerbate the risk of aspiration and consequent pneumonia. Tying back only one of the arytenoid cartilages instead of both helps reduce the risk of aspiration. Afterwards the dog will still sound hoarse, and will need to be managed in the same way as those with mild cases of LP.
Recent studies have found that many dogs with laryngeal paralysis have decreased motility of their esophagus. Animals with a history of regurgitation or vomiting should be fully evaluated for esophageal or other gastrointestinal disorders. Dogs with megaesophagus or other conditions causing frequent vomiting or regurgitation are at high risk for aspiration pneumonia after laryngeal tie-back. Permanent tracheostomy is an alternative surgical option for these dogs to palliate their clinical signs.
Complications of surgical treatment
Besides complications of surgery and anesthesia in general, there may be drainage, swelling, or redness of the incision, gagging or coughing during eating or drinking, or pneumonia due to aspiration of food or liquids. Undesirable complications are estimated to occur in 10-30% of cases. If medical therapy is unsuccessful and surgery cannot be performed due to concurrent disease (such as heart or lung problems) or cost, euthanasia may be necessary if the animals quality of life is considered unacceptable due to the disease.
References
Stanley BJ, et al. Esophageal dysfunction in dogs with idiopathic laryngeal paralysis: A controlled cohort study. Veterinary Surgery 39(2), pg. 139–149, February 2010.
External links
Support for LP
Article about LP |
Bacillary peliosis | Bacillary peliosis is a form of peliosis hepatis that has been associated with bacteria in the genus Bartonella.
== References == |
Erythema multiforme | Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands.It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the superficial microvasculature of the skin and oral mucous membrane that usually follows an infection or drug exposure. It is an uncommon disorder, with peak incidence in the second and third decades of life. The disorder has various forms or presentations, which its name reflects (multiforme, "multiform", from multi- + formis). Target lesions are a typical manifestation. Two types, one mild to moderate and one severe, are recognized (erythema multiforme minor and erythema multiforme major).
Erythema multiforme was first described by von Hebra in 1860.
Signs and symptoms
The condition varies from a mild, self-limited rash (E. multiforme minor) to a severe, life-threatening form known as erythema multiforme major (or erythema multiforme majus) that also involves mucous membranes.
Consensus classification:
Erythema multiforme minor—typical targets or raised, edematous papules distributed acrally
Erythema multiforme major—typical targets or raised, edematous papules distributed acrally with involvement of one or more mucous membranes; epidermal detachment involves less than 10% of total body surface areaStevens–Johnson syndrome and toxic epidermal necrolysis used to be considered part of the erythema multiforme spectrum, but that is no longer the case.The mild form usually presents with mildly itchy (but itching can be very severe), pink-red blotches, symmetrically arranged and starting on the extremities. It often takes on the classical "target lesion" appearance, with a pink-red ring around a pale center. Resolution within 7–10 days is the norm.
Individuals with persistent (chronic) erythema multiforme will often have a lesion form at an injury site, e.g. a minor scratch or abrasion, within a week. Irritation or even pressure from clothing will cause the erythema sore to continue to expand along its margins for weeks or months, long after the original sore at the center heals.
Causes
Many suspected etiologic factors have been reported to cause EM.
Infections: bacterial (including Bacillus Calmette–Guérin (BCG) vaccination, haemolytic Streptococci, legionellosis, leprosy, Neisseria meningitidis, Mycobacterium, Pneumococcus, Salmonella species, Staphylococcus species, Mycoplasma pneumoniae), chlamydial.
Fungal (Coccidioides immitis)
Parasitic (Trichomonas species, Toxoplasma gondii),
Viral (especially Herpes simplex)
Drug reactions, most commonly to: antibiotics (including, sulphonamides, penicillin), anticonvulsants (phenytoin, barbiturates), aspirin, modafinil, antituberculoids, and allopurinol and many others.
Physical factors: radiotherapy, cold, sunlight
Others: collagen diseases, vasculitides, non-Hodgkin lymphoma, leukaemia, multiple myeloma, myeloid metaplasia, polycythemiaEM minor is regarded as being triggered by HSV in almost all cases. A herpetic etiology also accounts for 55% of cases of EM major. Among the other infections, Mycoplasma infection appears to be a common cause.
Herpes simplex virus suppression and even prophylaxis (with acyclovir) has been shown to prevent recurrent erythema multiforme eruption.
Treatment
Erythema multiforme is frequently self-limiting and requires no treatment. The appropriateness of glucocorticoid therapy can be uncertain, because it is difficult to determine if the course will be a resolving one.
See also
Erythema multiforme major
Erythema multiforme minor
Toxic epidermal necrolysis
Stevens–Johnson syndrome
References
== External links == |
Cryofibrinogenemic purpura | Cryofibrinogenemic purpura is a skin condition that manifests as painful purpura with slow healing ulcerations and edema of both feet during winter months.: 823
See also
Cryofibrinogenemia
Skin lesion
== References == |
Congenital malaria | Congenital malaria is an extremely rare condition which occurs due to transplacental transmission of maternal infection.Clinical features include fever, irritability, feeding problems, anemia, hepatosplenomegaly and jaundice. Clinical features commence only after three weeks due to the protective effect of transplacentally transmitted antibodies.
References
External links
(P37.3) Congenital falciparum malaria
(P37.4) Other congenital malaria |
Alveolar soft part sarcoma | Alveolar soft part sarcoma, abbreviated ASPS, is a very rare type of soft-tissue sarcoma, that grows slowly and whose cell of origin is unknown.
ASPS arises mainly in children and young adults and can migrate (metastasize) into other parts of the body, typically the lungs and the brain. Typically, ASPS arises in muscles and deep soft tissue of the thigh or the leg (lower extremities), but can also appear in the upper extremities (hands, neck, and head). While ASPS is a soft tissue sarcoma, it can also spread and grow inside the bones.
Etymology
The term alveolar comes from the microscopic pattern, visible during the analysis of slides of ASPS under the microscope in histopathology. The tumor cells seem to be arranged in the same pattern as the cells of the small air sacks (alveoli) in the lungs. However, this is just a structural similarity. ASPS was first described and characterized in 1952.ASPS is a sarcoma, and that indicates that this cancer initially arises from tissue of embryonic mesenchymal origin. (The fertilized egg divides and redivides forming a sphere. Early in embryogenesis, dimples appear in the poles of the sphere and burrow through the sphere forming an inner passage that will ultimately form the gut. Malignancies arising from cells that were originally part of the outer layer of the sphere and those that were part of the embryonic tunnel are termed carcinomas; malignancies arising from the cells between the outer layer and the inner burrow are termed sarcomas.)
Causes
Chromosomal analysis of ASPS shows the breaking and joining of two chromosomes in the tumor cells. A piece of chromosome X breaks and is joined to chromosome 17. This translocation creates a fusion between two genes named ASPL and TFE3, which results in the formation of an aberrant protein (termed fusion protein) that is not found in normal cells. Two sorts of fusions between chromosome X and chromosome 17 are found in different ASPS tumors: type one and type two.
Dr. Marc Ladanyi at Memorial Sloan-Kettering Cancer Center, in New York City, has pioneered this work. The resultant fusion protein ASPL–TFE3 is a rogue transcription factor that is the driver of aberrant cellular behavior including uncontrolled cell division and enhanced angiogenesis.
Diagnosis
ASPS may exist in the patient’s body for a long time before being diagnosed. It can grow large and push aside surrounding tissues for a long time before causing any discomfort. Therefore, ASPS symptoms may either be a painless swelling, or a soreness caused by compressed nerves or muscles, affecting the range of motion in the area.
Pathology
The definitive diagnosis of ASPS is based on its appearance under the microscope (i.e., its histomorphology), and presence of the characteristic chromosomal translocation (i.e., cytogenetics).
ASPS histomorphologic features include an alveolar-like pattern at low magnification and the presence of large cells with abundant eosinophilic cytoplasm and eccentric nuclei. Calcifications are commonly present, as may be seen with slow-growing neoplasms.
Prognosis
Although ASPS displays a relatively indolent course, the ultimate prognosis is poor and is often characterized by late metastases.
Epidemiology
ASPS is an extremely rare cancer. While sarcomas comprise about 1% of all newly diagnosed cancers, and 15% of all childhood cancers, ASPS comprises less than 1% of sarcomas. According to the American Cancer Society, about 9530 new cases of soft tissue sarcoma will be diagnosed in the USA in 2006. This predicts under 100 new cases of ASPS. Such low numbers of occurrence seriously impede the search for a cure by making it hard to gather any meaningful statistics about the disease. As a result, finding the best treatment option often involves making a lot of educated guesses.
Research
The first xenograft model of ASPS (for type one) was established in mice by David Vistica at the National Cancer Institute in Frederick, MD in 2009. The same authors subsequently generated the first publicly available ASPS cell line (designated ASPS-1).An important advance involved demonstrating that the ASPL–TFE3 fusion protein (a transcription factor) enhanced expression of the receptor tyrosine kinase c-MET, making ASPS sensitive to small-molecule kinase inhibitor such as sunitinib.Current clinical trials are exploring the utility of kinase inhibitors (targeting growth factor pathways and angiogenesis); checkpoint inhibitors and cellular immunotherapies in the treatment of ASPS.Researchers at the Huntsman Cancer Institute (HCI) in Utah demonstrated that ASPS might be driven in part by lactate both being used as a fuel and driving angiogenesis.In terms of origin, it was recently demonstrated that although ASPS generally arises in muscle tissue, the cells do not express muscle markers at the mRNA level and more closely resemble mesenchymal stromal cells.
References
== External links == |
Undervirilization | Undervirilization is a medical term describing the state of a male whose body, especially the genitalia, shows evidence of below-normal prenatal (less commonly pubertal) androgen effects.
See virilization for a more detailed description of the normal process and newborn status.
See also
Sexual differentiation
Defeminization and masculinization
Defeminization
Feminization
== References == |
Venous lake | A venous lake (also known as phlebectasis) is a generally solitary, soft, compressible, dark blue to violaceous, 0.2- to 1-cm papule commonly found on sun-exposed surfaces of the vermilion border of the lip, face and ears. Lesions generally occur among the elderly.Though these lesions may resemble nodular melanoma, the lack of induration, slow growth, and lightening appearance upon diascopy suggest against it, and indicate a vascular lesion. Additionally, lack of pulsation distinguishes this lesion of the lower lip from a tortuous segment of the inferior labial artery.
Cause
The cause is unknown; however it is thought to be associated with sun exposure, leading to a dilated blood-filled vascular channel "...lined with a singled layer of flattened endothelial cells and a thin wall of fibrous tissue filled with red blood cells."
Treatment
Treatment may be requested for cosmetic reasons. Traditional techniques such as surgical excision are effective but will leave a scar. Laser therapy has become the mainstay of therapy.
Published research suggests that the Long Pulsed Nd:YAG laser is a very effective, with a clearance rate of 94% following a single treatment. In this study no scarring or other complications were reported.
History
The term was coined by American physician William Bennett Bean.
Images
See also
List of cutaneous conditions
Footnotes
== External links == |
Simyra (moth) | Simyra is a genus of moths of the family Noctuidae. The genus was described by Ochsenheimer in 1816.
Species
Simyra nervosa (Denis & Schiffermüller, 1775) central and southern Europe
Simyra albovenosa (Goeze, 1781) Europe, Turkey, northern Iran, Transcaucasia, Central Asia, southern Siberia
Simyra dentinosa Freyer, 1838 south-eastern Europe, Turkey, Caucasus, Transcaucasia, Lebanon, Syria, Israel, Egypt, Iran
Simyra albicosta Hampson, 1909 Nilgiri Mountains of India
Simyra capillata Wallengren, 1875 South Africa
Simyra confusa (Walker, 1856) Sri Lanka, Arabia
Simyra conspersa Moore, 1881 Punjab, Sikkim, Bengal
Simyra renimaculata (Osthelder, 1932) Turkey
Simyra saepestriata (Alphéraky, 1895) Japan, Korea, Mongolia
Simyra sincera Warren, 1914
Simyra splendida Staudinger, 1888 Turkestan, Tibet, southern Siberia, Korea
Simyra insularis (Herrich-Schäffer, 1868) Ontario, New York, Massachusetts, Kansas, California, New Mexico, Cuba
Simyra unifacta Dyar, 1912 Mexico
== References == |
Diffuse leprosy of Lucio and Latapí | The diffuse leprosy of Lucio and Latapí, also known as diffuse lepromatous leprosy or "pretty leprosy" is a clinical variety of lepromatous leprosy. It was first described by Lucio and Alvarado in 1852 and re-identified by Latapí in 1936. It is common in Mexico (23% of leprosy cases) and in Costa Rica and very rare in other countries.
History
The spotted or lazarine leprosy was first described by Ladislao de la Pascua in 1844. Lucio and Alvarado published a description of the disease with the same names in 1852. Latapí re-described it in 1938 and reported it as spotted leprosy of Lucio in 1948. It was named the diffuse leprosy of Lucio and Latapí in 1963 by Frenken.
The underlying pathology was explained by Chévez-Zamora as a diffuse generalised cutaneous infiltration. He named it pure and primitive diffuse lepromatosis, upon which necrotising lesions develop. He proposed the name Fenómeno de Lucio or erythema necrotisans for these lesions.
Clinical features
This condition is characterized by:
a diffuse infiltration of all the skin which never transforms into nodule
a complete alopecia of eyebrows and eyelashes and body hair
an anhydrotic and dysesthesic zones of the skin
a peculiar type of lepra reaction named Lucios phenomenon or necrotic erythemaLucios phenomenon consists of well-shaped erythematous spots which later become necrotic with scabs, ulcerations and scars. These lesions are usually located on the lower extremities and may be extensive. They are frequently painful and rarely fatal.
Pathology
The main pathological features of this disease are a vasculitis affecting all cutaneous vessels.
There are by five characteristic features:
colonisation of endothelial cells by acid-fast bacilli
endothelial proliferation and marked thickening of vessel walls to the point of obliteration
angiogenesis
vascular ectasia
thrombosis of the superficial and mid-dermal blood vesselsThe likely pathogenesis is endothelial cell injury due to colonization/invasion followed by proliferation, angiogensis, thrombosis and vessel ectasia.
Treatment
Lucios phenomenon is treated by anti-leprosy therapy (dapsone, rifampin, and clofazimine), optimal wound care, and treatment for bacteremia including antibiotics. In severe cases exchange transfusion may be helpful.
== References == |
Fat embolism syndrome | Fat embolism syndrome occurs when fat enters the blood stream (fat embolism) and results in symptoms. Symptoms generally begin within a day. This may include a petechial rash, decreased level of consciousness, and shortness of breath. Other symptoms may include fever and decreased urine output. The risk of death is about 10%.Fat embolism most commonly occurs as a result of fractures of bones such as the femur or pelvis. Other potential causes include pancreatitis, orthopedic surgery, bone marrow transplant, and liposuction. The underlying mechanism involved widespread inflammation. Diagnosis is based on symptoms.Treatment is mostly supportive care. This may involve oxygen therapy, intravenous fluids, albumin, and mechanical ventilation. While small amounts of fat commonly occur in the blood after a bone fracture, fat embolism syndrome is rare. The condition was first diagnosed in 1862 by Zenker.
Signs and symptoms
Symptoms of fat embolism syndrome (FES) can start from 12 hours to 3 days after diagnosis of the underlying clinical disease. The three most characteristic features are: respiratory distress, neurological features, and skin petechiae. Respiratory distress (present in 75% of the cases) can vary from mild distress which requires supplemental oxygen to severe distress which requires mechanical ventilation. For neurologic features, those who have FES may become lethargic, restless, with a drop in Glasgow Coma Scale (GCS) due to cerebral oedema rather than cerebral ischaemia. Therefore, neurological signs are not lateralised to one side of the body. In the severe form of cerebral odema, a person may become unresponsive. Petechiae rash usually happens in 50% of the patients. Such skin manifestation is temporary and can disappear within one day. The fat embolism syndrome can be divided into three types:
Subclinical FES - It manifests as reduced partial pressure of oxygen (PaO2) on arterial blood gas (ABG) with deranged blood parameters (reduced haemoglobin or thrombocytopenia) associated with fever, pain, discomfort, tachypnoea, tachycardia. However, there is no respiratory distress. However, it is often confused with post-operative symptoms of fever, pain, and discomfort.
Subacute FES (non-fulminant FES) - The three characteristic features of fat embolism are present: respiratory distress, neurological signs, and skin petechiae. Petechiae are seen on the chest, axilla, shoulder, and mouth. Occulsion of dermal capillaries by the fat emboli result in petechial rash. Petechiae rash occurs in 50 to 60% of the cases. Neurologic signs such as confusion, stupor, and coma may be present. These are usually temporary and do not happen on one side of the body. Respiratory distress can be mild and tends to improve on the third day. Retinal changes similar to Purtschers retinopathy may also be present. Retinal changes happens in 50% of the patients with FES. These are the cotton wool exudates and small haemorrhages along the retinal vessels and macula.
Fulminant FES - This type of FES is much rarer than the above two types. It usually happens within the first few hours of the injury. The three characteristics of FES existed in the most severe form. Cause of death is usually due to acute right heart failure.
Causes
Orthopaedic injuries especially fractures of the long bones are the most common cause of fat embolism syndrome (FES). The rates of fat embolism in long bone fractures vary from 1% to 30%. The mortality rate of fat-embolism syndrome is approximately 10–20%. However, fat globules have been detected in 67% of those with orthopaedic trauma and can reach as high as 95% if the blood is sampled near the fracture site. As the early operative fixation of long bone fractures became a common practice, the incidence of FES has been reduced to between 0.9% and 11%.
Other rare causes of fat embolism syndrome are:
Severe burns
Liver injury
Closed chest cardiac massage (during cardiopulmonary resuscitation)
Bone marrow transplantation
Liposuction
Parenteral lipid infusion
Decompression sickness
Extracorporeal circulation
Acute haemorrhagic pancreatitis
Alcoholic liver disease
Prolonged corticosteriod therapy
Sickle cell disease
Carbon tetrachloride poisoning
Osteomyelitis
Pathophysiology
Once fat emboli enter the blood circulation, they can lodge at various sites of the body, most commonly in the lungs (up to 75% of cases). However, it can also enter the brain, skin, eyes, kidneys, liver, and heart circulation, causing capillary damage, and subsequently cause organ damage in these areas. There are two theories that describe the formation of a fat embolus:
Mechanical theory - Following trauma, fat is released directly from the bone marrow into the circulation. This is because after trauma, an elevated pressure in the medullary cavity (central cavity of the bone where the bone marrow are stored) causes the release of fat globules into the venous system supplying the bone. Since venous blood returns to the right heart and is pumped to the lungs for reoxygenation, the fat globules often get lodged in the pulmonary circulation. Fat globules may also pass through lung circulation back into the left ventricle of the heart to be pumped throughout the body in the systemic circulation. They may also reach the systemic circulation through a patent foramen ovale (a hole communicating the right atrium directly to the left atrium of the heart). If fat globules obstruct 80% of the lung capillary network, the resulting back pressure on the right heart increases workload and causes right heart dilatation through cor pulmonale, leading to acute right heart failure.
Biochemical theory - Following trauma, an inflammation causes bone marrow to liberate fatty acids into the venous circulation. This is achieved through the increased activity of lipoprotein lipase which break down triglycerides into free fatty acids. Both the release of fatty acids and the inflammation causes damage to the capillary beds of the lungs and other organs, causing interstitial lung disease, chemical pneumonitis, and acute respiratory distress syndrome (ARDS). This theory can help to explain non-traumatic causes of fat embolism.
Diagnosis
Fat embolism is presence of fat particles in the micro-circulation of the body. Meanwhile, fat embolism syndrome is the clinical manifestation as the result of fat particles lodging in the body micro-circulation. There are three major diagnostic criteria proposed for fat embolism syndrome, however, none of them are validated and accepted universally. However, Gurd and Wilsons criteria for fat embolism become more commonly used when compared to the other two diagnostic criteria.
Gurd and Wilsons criteria
Major criteria
Axillary or subconjunctival petechiae
Hypoxaemia PaO2 <60 mm Hg, FIO2 = 0.4
Central nervous system depression disproportionate to hypoxaemia
Pulmonary oedemaMinor criteria
Tachycardia more than 110 beats per minute
Pyrexia more than 38.5 °C
Fat globules present in urine
Changes in renal function (reduced urine output)
Drop in haemoglobin values (more than 20% of the value upon admission)
Drop in haematocrit values
Drop in platelet values (more than 50% of the value upon admission)
Increasing erythrocyte sedimentation rate (ESR) (greater than 71 mm per hour)
Fat globules present in the sputum
Emboli present in the retina on fundoscopyA least two positive major criteria plus one minor criteria or four positive minor criteria are suggestive of fat embolism syndrome. Fat embolism syndrome is a clinical diagnosis. There are no laboratory tests sensitive or specific enough to diagnose FES. Such laboratory tests are only used to support the clinical diagnosis only. Chest X-ray may show diffuse interstitial infiltrates while chest CT scan will show diffuse vascular congestion and pulmonary oedema. Bronchoalveolar lavage has been proposed to look for fat droplets in alveolar macrophages however it is time-consuming and is not specific to fat embolism syndrome. Looking for fat globules in sputum and urine is also not specific enough to diagnose FES.
Prevention
For those treated conservatively with immobilisation of long bone fractures, the incidence of FES is 22%. Early operative fixation of long bone fractures can reduce the incidence of FES especially with the usage of internal fixation devices. Patients undergoing urgent fixation of long bone fractures has a rate of 7% of acute respiratory distress syndrome (ARDS) when compared to those undergoing fixation after 24 hours (39% with ARDS). However, movement of the fracture ends of the long bones during the operative fixation can cause transient increase of fat emboli in the blood circulation. Cytokines are persistently elevated if the long bone fractures is treated conservatively using immobilisation. The cytokine levels would return to normal after operative fixation. Although ream nailing increases pressure in the medullary cavity of the long bones, it does not increase the rates of FES. Other methods such as drilling of holes in the bony cortex, lavaging bone marrow prior to fixation, and the use of tourniquets to prevent embolisation have not been shown to reduce the rates of FES.Corticosteroid therapy such as methylprednisolone (6 to 90 mg/kg) has been proposed for the treatment of FES, however, it is controversial. Corticosteroid can be used to limit free fatty acid levels, stabilising membranes, and inhibit leukocyte aggregation. A meta-analysis conducted in 2009 reported prophylactic corticosteroids can reduce the risk of FES by 77%. However, there is no difference in mortality, infection, and avascular necrosis when compared to the control group. However, a randomised trial conducted in 2004 reported no differences in FES incidence when comparing treatment with the control group. Administration of corticosteroids for 2 to 3 days is not associated with increased rates of infection. However, there is insufficient data to support the use of methyprednisolone once FES is established.Heparin has been used in the prevention of venous thrombosis in post-operative patients; however its regular use in those with FES has been contraindicated due to increase risk of bleeding in those with polytrauma. Placement of inferior vena cava filters has been proposed to reduce the amount of emboli going into the lung vascular system, however, this method has not been studied in detail.
Treatment
Once FES develops, the person should be admitted into intensive care unit (ICU), preferably with central venous pressure (CVP) monitoring. CVP monitoring would be helpful to guide the volume resuscitation. Supportive treatment is the only proven treatment method. Supplemental oxygen can be given if a person has mild respiratory distress. However, if a person has severe respiratory distress, either continuous positive pressure ventilation (CPAP), or mechanical ventilation using positive end-expiratory pressure (PEEP) may be indicated. Fluid replacement is required to prevent shock. Volume resuscitation with human albumin is recommended because it can restore blood volume in the circulatory system while also binds to free fatty acids in order to reduce lung injuries. In severe cases, dobutamine should be used to support the right ventricular failure. Frequent Glasgow coma scale (GCS) charting is required to assess the neurological progression of a person with FES. A placement of intracranial pressure monitor may be helpful to direct the treatment of cerebral odema.
History
In 1861, Zenker first reported on the autopsy findings of fat droplets found in the lungs of a railway worker who died due to severe thoraco-abdominal crush injury. In 1873, Bergmann diagnosed fat embolism clinically in a patient with fractured femur. In 1970, Gurd defined the characteristics of this phenomenon. Gurd later modified the fat embolism criteria together with Wilson, thus producing Gurd and Wilsons criteria for fat embolism syndrome in 1974. In 1983, Schonfeld suggested a scoring system for the diagnosis of fat embolism syndrome. In 1987, Lindeque proposed another scoring system that diagnose fat embolism syndrome by using respiratory changes alone. However, none of them have become universally accepted in the medical community.In 2015, Singaporean couple Pua Hak Chuan and Tan Hui Zhen were charged with the abuse and murder of Annie Ee Yu Lian, who died due to multiple physical abuse which lasted for eight months before her death. The cause of death was revealed to be acute fat embolism, which resulted from the blunt force impact caused by the beatings, which led to the fatty tissue entering the bloodstream and eventually entering the blood vessels in the lungs, which led to a blockage and cut off the circulation of oxygenated blood and led to Ees death by respiratory and cardiac failure. Two years later, for reduced charges of voluntarily causing grievous hurt with a weapon, Tan was sentenced to 16 years and six months in jail while Pua received 14 years imprisonment and 14 strokes of the cane.
References
Further reading
== External links == |
Atonic seizure | An atonic seizure (also called drop seizure, akinetic seizure, astatic seizure, or drop attack) is a type of seizure that consists of partial or complete loss of muscle tone that is caused by temporary alterations in brain function. These seizures are brief – usually less than fifteen seconds. They usually begin in childhood and may persist into adulthood. The seizure itself causes no physical injury, but the loss of control, predominantly in trunk muscles, can result in direct injury from falling. Electroencephalography can be used to confirm diagnosis. It is rare and can be indicative of Lennox–Gastaut syndrome (see Henri Gastaut).
Atonic seizures can occur while standing, walking, or sitting, and are often noticeable by a head drop (relaxing of the neck muscles). Fall injuries may result in impact to the face or head. As with common epileptic occurrences, no first aid is needed post-seizure, except in the instances where falling injuries have occurred. In some cases, a person may become temporarily paralyzed in part of his or her body. This usually does not last longer than 3 minutes.
Treatment
There is no general treatment for patients with a seizure disorder. Each treatment plan is specifically tailored to the individual patient based on their diagnosis and symptoms. Treatment options may include medical therapy, nerve stimulation, dietary therapy, or surgery, as appropriate. Clinical trials may also be a valuable treatment alternative.
Usually, anticonvulsants are given based on other symptoms and / or associated problems.
Because the areas of the cerebellum which determine increases and decreases in muscle tone are close together, people experiencing atonic seizures are most likely experiencing myoclonic ones too, at some point. This may play a role in therapy and diagnostic.One surgical approach, selective posterior callostomy, can greatly decrease instances of drop attacks and improve function and behavior in patients with intellectual disability.
References
== External links == |
Idiopathic pulmonary haemosiderosis | Idiopathic pulmonary haemosiderosis (IPH) is a lung disease of unknown cause that is characterized by alveolar capillary bleeding and accumulation of haemosiderin in the lungs. It is rare, with an incidence between 0.24 and 1.23 cases per million people.
Pathophysiology
Being idiopathic, IPH by definition has an unknown cause. It is thought to be an immune-mediated disease. The lung bleeding causes accumulation of iron, which in itself causes additional lung damage. Meanwhile, there is insufficient iron for inclusion into the haemoglobin molecules inside red blood cells which carry oxygen to body tissues for cellular respiration.Idiopathic pulmonary haemosiderosis can occur either as a primary lung disorder or as the sequela to other pulmonary, cardiovascular or immune system disorder.
PH1 involves PH with circulating anti-GBM antibodies.
PH2 involves PH with immune complex disease such as systemic lupus erythematosus, SLE.
PH3 involves no demonstrable immune system involvement.A distinct subset of patients with pulmonary hemosiderosis has hypersensitivity to cows milk which result in formation of IgG antibodies against basement membrane. This is called Heiner syndrome. Mechanism of haemorrhage is similar to that observed in Goodpasture syndrome.
Related or similar conditions
There are many pulmonary problems that may seem to mimic haemosiderosis but do not necessarily include the deposits of iron into the lung. The deposition of iron in the lungs, occurring in the form of haemosiderin, is the defining characteristic of this illness. These other conditions may occur separately or together with haemosiderosis.
Pulmonary fibrosis
Adult respiratory distress syndrome (ARDS)
Immune complex disease
intra-alveolar bleeding
Diagnosis
Clinically, IPH manifests as a triad of haemoptysis, diffuse parenchymal infiltrates on chest radiographs, and iron deficiency anaemia. It is diagnosed at an average age of 4.5 plus or minus 3.5 years, and it is twice as common in females. The clinical course of IPH is exceedingly variable, and most of the patients continue to have episodes of pulmonary haemorrhage despite therapy. Death may occur suddenly from acute pulmonary haemorrhage or after progressive pulmonary insufficiency resulting in chronic respiratory failure.
Treatment
Corticosteroids are the mainstay of treatment of IPH, though they are controversial and lack clear evidence in their favour. They are thought to decrease the frequency of haemorrhage, while other studies suggest that they do not have any effect on the course or prognosis of this disease. In either case, steroid therapy has significant side effects. Small trials have investigated the use of other medications, but none has emerged as a clear standard of care. This includes immune modulators such as hydroxychloroquine, azathioprine, and cyclophosphamide. 6-mercaptopurine as a long-term therapy may prevent pulmonary haemorrhage. A 2007 scientific letter reports preliminary success in preventing pulmonary haemorrhage with the anti-oxidant N-acetylcysteine.
Prognosis
Death may occur rapidly with acute, massive pulmonary bleeding or over longer periods as the result of continued pulmonary failure and right heart failure. Historically, patients had an average survival of 2.5 years after diagnosis, but today 86% may survive beyond five years.
History
The condition was first described as "brown lung induration" by Rudolf Virchow in 1864 in patients after their death. Wilhelm Ceelen later correlated his findings to the clinical symptoms of two children who died of IPH in 1931. The first living patient was diagnosed by Jan Waldenström in 1944. It has been given several names, including:
Haemosiderin accumulation
Pulmonary haemosiderosis
Brown induration of lung
Essential brown induration of lung
Ceelen-Gellerstedt syndrome (after physicians Wilhelm Ceelen and Nils Gellerstedt)
References
External links
Hemosiderosis at eMedicine |
Phlegmasia alba dolens | Phlegmasia alba dolens (also colloquially known as milk leg or white leg; not to be confused with phlegmasia cerulea dolens) is part of a spectrum of diseases related to deep vein thrombosis. Historically, it was commonly seen during pregnancy and in mothers who have just given birth. In cases of pregnancy, it is most often seen during the third trimester, resulting from a compression of the left common iliac vein against the pelvic rim by the enlarged uterus. Today, this disease is most commonly (40% of the time) related to some form of underlying malignancy. Hypercoagulability (a propensity to clot formation) is a well-known state that occurs in many cancer states. The incidence of this disease is not well reported.
Cause
The disease presumably begins with a deep vein thrombosis that progresses to total occlusion of the deep venous system. It is at this stage that it is called phlegmasia alba dolens. It is a sudden (acute) process. The leg, then, must rely on the superficial venous system for drainage. The superficial system is not adequate to handle the large volume of blood being delivered to the leg via the arterial system. The result is edema, pain and a white appearance (alba) of the leg.
The next step in the disease progression is occlusion of the superficial venous system, thereby preventing all venous outflow from the extremity. At this stage it is called phlegmasia cerulea dolens. The leg becomes more swollen and increasingly more painful. Additionally, the edema and loss of venous outflow impedes the arterial inflow. Ischemia with progression to gangrene are potential consequences. Phlegmasia alba dolens is distinguished, clinically, from phlegmasia cerulea dolens in that there is no ischemia and congestion. In severe cases of venous obstruction the arterial pulse may gradually disappear and venous gangrene may ensue.
Diagnosis
The condition can be identified clinically & as early as possible to prevent further deterioration & complications like embolism, ischaemic necrosis, and gangrene. The diagnosis is confirmed with Doppler ultrasound of the veins of the affected leg, and occasionally other imaging modalities.
Treatment
The mainstay of the treatment of deep vein thrombosis is with anticoagulation, but in very large DVTs various other modalities may be used to reduce the risk of complications. This may be surgical thrombectomy or catheter-directed thrombolysis.
Etymology
Phlegmasia alba dolens literally means "painful white edema". It received the name "milk leg" because it was once thought to be caused by the metastasis of milk.
References
== External links == |
Comedo | A comedo is a clogged hair follicle (pore) in the skin. Keratin (skin debris) combines with oil to block the follicle. A comedo can be open (blackhead) or closed by skin (whitehead) and occur with or without acne. The word "comedo" comes from the Latin comedere, meaning "to eat up", and was historically used to describe parasitic worms; in modern medical terminology, it is used to suggest the worm-like appearance of the expressed material.The chronic inflammatory condition that usually includes comedones, inflamed papules, and pustules (pimples) is called acne. Infection causes inflammation and the development of pus. Whether a skin condition classifies as acne depends on the number of comedones and infection. Comedones should not be confused with sebaceous filaments.
Comedo-type ductal carcinoma in situ (DCIS) is not related to the skin conditions discussed here. DCIS is a noninvasive form of breast cancer, but comedo-type DCIS may be more aggressive, so may be more likely to become invasive.
Causes
Oil production in the sebaceous glands increases during puberty, causing comedones and acne to be common in adolescents. Acne is also found premenstrually and in women with polycystic ovarian syndrome. Smoking may worsen acne.Oxidation rather than poor hygiene or dirt causes blackheads to be black. Washing or scrubbing the skin too much could make it worse, by irritating the skin. Touching and picking at comedones might cause irritation and spread infection. What effect shaving has on the development of comedones or acne is unclear.Some skin products might increase comedones by blocking pores, and greasy hair products (such as pomades) can worsen acne. Skin products that claim to not clog pores may be labeled noncomedogenic or nonacnegenic. Make-up and skin products that are oil-free and water-based may be less likely to cause acne. Whether dietary factors or sun exposure make comedones better, worse, or neither is unknown.A hair that does not emerge normally, an ingrown hair, can also block the pore and cause a bulge or lead to infection (causing inflammation and pus).Genes may play a role in the chances of developing acne. Comedones may be more common in some ethnic groups. People of Latino and recent African descent may experience more inflammation in comedones, more comedonal acne, and earlier onset of inflammation.
Pathophysiology
Comedones are associated with the pilosebaceous unit, which includes a hair follicle and sebaceous gland. These units are mostly on the face, neck, upper chest, shoulders, and back. Excess keratin combined with sebum can plug the opening of the follicle. This small plug is called a microcomedo. Androgens increase sebum (oil) production. If sebum continues to build up behind the plug, it can enlarge and form a visible comedo.A comedone may be open to the air ("blackhead") or closed by skin ("whitehead"). Being open to the air causes oxidation, which turns it black. Cutibacterium acnes is the suspected infectious agent in acne. It can proliferate in sebum and cause inflamed pustules (pimples) characteristic of acne. Nodules are inflamed, painful, deep bumps under the skin.Comedones that are 1 mm or larger are called macrocomedones. They are closed comedones and are more frequent on the face than neck.Solar comedones (sometimes called senile comedones) are related to many years of exposure to the sun, usually on the cheeks, not to acne-related pathophysiology.
Management
Using nonoily cleansers and mild soap may not cause as much irritation to the skin as regular soap. Blackheads can be removed across an area with commercially available pore-cleansing strips (which can still damage the skin by leaving the pores wide open and ripping excess skin) or the more aggressive cyanoacrylate method used by dermatologists.Squeezing blackheads and whiteheads can remove them, but can also damage the skin. Doing so increases the risk of causing or transmitting infection and scarring, as well as potentially pushing any infection deeper into the skin. Comedo extractors are used with careful hygiene in beauty salons and by dermatologists, usually after using steam or warm water.Complementary medicine options for acne in general have not been shown to be effective in trials. These include aloe vera, pyridoxine (vitamin B6), fruit-derived acids, kampo (Japanese herbal medicine), ayurvedic herbal treatments, and acupuncture.Some acne treatments target infection specifically, but some treatments are aimed at the formation of comedones, as well. Others remove the dead layers of the skin and may help clear blocked pores.Dermatologists can often extract open comedones with minimal skin trauma, but closed comedones are more difficult. Laser treatment for acne might reduce comedones, but dermabrasion and laser therapy have also been known to cause scarring.Macrocomedones (1 mm or larger) can be removed by a dermatologist using surgical instruments or cauterized with a device that uses light. The acne drug isotretinoin can cause severe flare-ups of macrocomedones, so dermatologists recommend removal before starting the drug and during treatment.Some research suggests that the common acne medications retinoids and azelaic acid are beneficial and do not cause increased pigmentation of the skin. If using a retinoid, sunscreen is recommended.
Rare conditions
Favre–Racouchot syndrome occurs in sun-damaged skin and includes open and closed comedones.Nevus comedonicus or comedo nevus is a benign hamartoma (birthmark) of the pilosebaceous unit around the oil-producing gland in the skin. It has widened open hair follicles with dark keratin plugs that resemble comedones, but they are not actually comedones.Dowling–Degos disease is a genetic pigment disorder that includes comedo-like lesions and scars.Familial dyskeratotic comedones are a rare autosomal-dominant genetic condition, with keratotic (tough) papules and comedo-like lesions.
References
External links
Rines, George Edwin, ed. (1920). "Comedones" . Encyclopedia Americana.
What causes blackheads, Treatment and Prevention Archived 2020-01-27 at the Wayback Machine |
Monkeypox | Monkeypox is an infectious viral disease that can occur in humans and some other animals. Symptoms include fever, swollen lymph nodes, and a rash that forms blisters and then crusts over. The time from exposure to onset of symptoms ranges from five to twenty-one days. The duration of symptoms is typically two to four weeks. There may be mild symptoms, and it may occur without any symptoms being known. The classic presentation of fever and muscle pains, followed by swollen glands, with lesions all at the same stage, has not been found to be common to all outbreaks. Cases may be severe, especially in children, pregnant women or people with suppressed immune systems.The disease is caused by the monkeypox virus, a zoonotic virus in the genus Orthopoxvirus. The variola virus, the causative agent of smallpox, is also in this genus. Of the two types in humans, clade II (formerly West African clade) causes a less severe disease than the Central African (Congo basin) type. It may spread from infected animals by handling infected meat or via bites or scratches. Human-to-human transmission can occur through exposure to infected body fluids or contaminated objects, by small droplets, and possibly through the airborne route. People can spread the virus from the onset of symptoms until all the lesions have scabbed and fallen off; with some evidence of spread for more than a week after lesions have crusted. Diagnosis can be confirmed by testing a lesion for the viruss DNA.There is no known cure. A study in 1988 found that the smallpox vaccine was around 85% protective in preventing infection in close contacts and in lessening the severity of the disease. A newer smallpox and monkeypox vaccine based on modified vaccinia Ankara has been approved, but with limited availability. Other measures include regular hand washing and avoiding sick people and animals. Antiviral drugs, cidofovir and tecovirimat, vaccinia immune globulin and the smallpox vaccine may be used during outbreaks. The illness is usually mild and most of those infected will recover within a few weeks without treatment. Estimates of the risk of death vary from 1% to 10%, although few deaths as a consequence of monkeypox have been recorded since 2017.Several species of mammals are suspected to act as a natural reservoir of the virus. Although it was once thought to be uncommon in humans, the quantity and severity of outbreaks has significantly increased since the 1980s, possibly as a result of waning immunity since the stopping of routine smallpox vaccination. The first cases in humans were found in 1970 in the Democratic Republic of the Congo (DRC). There have been sporadic cases in Central and West Africa, and it is endemic in the DRC. The 2022 monkeypox outbreak represents the first incidence of widespread community transmission outside of Africa, which was initially identified in the United Kingdom in May 2022, with subsequent cases confirmed in at least 74 countries in all continents except Antarctica. On 23 July 2022, the World Health Organization (WHO) declared the outbreak a Public Health Emergency of International Concern (PHEIC) with more than 53,000 reported cases in 75 countries and territories.
Signs and symptoms
It is possible for a person to be infected with monkeypox without showing any symptoms. Monkeypox symptoms tend to begin 5 to 21 days after infection, with early symptoms including headache, muscle pains, fever and fatigue, initially resembling influenza. Within a few days of the fever, lesions characteristically appear on the face before appearing on the trunk then elsewhere such as palms of the hands and soles of the feet. The disease can resemble chickenpox, measles and smallpox but is distinguished by the presence of swollen glands which may appear behind the ear, below the jaw, in the neck or in the groin, before the onset of the rash. Many cases in the 2022 monkeypox outbreak presented with genital and peri-anal lesions, fever, swollen lymph nodes, and pain when swallowing, with some patients manifesting only single sores from the disease.Three-quarters of affected people have lesions on the palms and soles, more than two-thirds in the mouth, a third on the genitals and one in five have lesions in the eyes. They begin as small flat spots, before becoming small bumps which then fill with at first clear fluid and then yellow fluid, which subsequently burst and scab over, persisting for around ten days. There may be a few lesions or several thousand, sometimes merging to produce large lesions. After healing, the lesions may leave pale marks before becoming dark scars.An unwell person may remain so for two to four weeks.
Complications
Complications include secondary infections, pneumonia, sepsis, encephalitis, and loss of vision with severe eye infection. If infection occurs during pregnancy, still birth or birth defects may occur. The disease may be milder in people vaccinated against smallpox in childhood. Patel and colleagues, in the BMJ, demonstrate that this virus can produce severe symptoms, particularly in HIV-positive people. The descriptive case series reveal that symptoms can be so severe that hospitalization is required in 10% of cases. The study also shows that 75% of patients (15 out of 20 participants) admitted to the hospital were HIV-positive individuals. Overall, the study depict a new variety of clinical manifestations including proctitis and rectal perforation. The pictures of genital lesions published in the BMJ show the severity of monkeypox, which is often described as causing moderate symptoms.
In other animals
The disease has also been reported in dormice, tree squirrels, rope squirrels and non human primates. Rodents such as rats and mice are likely susceptible but not known.
Signs and symptoms in animals vary among different species. Monkeypox infected Gambian pouched rats may have mild symptoms. During the 2003 US outbreak, affected prairie dogs presented with fever, cough, sore eyes, poor feeding and rash. Non-human primates present similarly. They may have breathing problems, facial swelling, mouth ulcers and swollen glands. In cynomolgus monkeys, the time from exposure to symptoms was noted to be around a week. Rabbits and rodents typically present with fever, cough, runny nose, sore eyes and swollen glands. They develop small bumps that fill with yellow fluid and may have patches of hair loss and pneumonia.
Spread among animals occurs via the fecal-oral route and through the nose, through wounds and eating infected meat. Death is more likely in baby monkeys. The CDC recommend that animals exposed to monkeypox be quarantined for six weeks.
Causes
Monkeypox in both humans and animals is caused by infection with the monkeypox virus – a double-stranded DNA virus in the genus Orthopoxvirus, family Poxviridae. The virus was first identified in captive monkeys and is found mainly in tropical rainforest regions of Central and West Africa. The two subtypes of virus are clade I and clade II (formerly Congo Basin and West African clades, matching the geographical areas).In addition to monkeys, the virus has been identified in Gambian pouched rats (Cricetomys gambianus), dormice (Graphiurus spp.) and African squirrels (Heliosciurus, and Funisciurus). The use of these animals as food may be an important source of transmission to humans.
Transmission
Humans can be infected by an animal via a bite or scratch, bush meat preparation, or by contact with an infected animal’s bodily fluids or lesion material. The virus is thought to enter the body through broken skin, the respiratory tract, or the mucous membranes of the eyes, nose, or mouth.Once a human is infected, transmission to other humans is common, with family members and hospital staff at particularly high risk of infection. The virus can spread by respiratory (airborne) contact or by direct contact with an infected persons bodily fluids or during pregnancy from mother to fetus. There are indications that transmission can occur during sexual contact, with infectious monkeypox virus able to be isolated from semen samples. Prolonged shedding in seminal fluids has raised the possibility of a genital reservoir for monkeypox virus. It is not known if the virus can spread through vaginal fluids.The virus can also spread via fomites or through indirect contact with lesion material, such as through contaminated bedding, even with standard personal protective equipment, likely through inhalation. Risk factors for transmission include sharing a bed or room, or using the same utensils as an infected person. Increased transmission risk is associated with factors involving the introduction of virus to the oral mucosa. It is not yet known if people without symptoms of monkeypox can spread the virus.Further research about the transmission of the strain responsible for the 2022 outbreak is ongoing, but it is not thought to be different from other strains of the clade II.
People living with HIV
According to a CDC report, 41% of cases of monkeypox were among HIV-positive patients (136 out of 334 patients) between May and July 2022. The New England Journal of Medicine (NEJM) also looked at more than 500 cases from different countries and found that 41% of them were among HIV patients. In addition, a study published in The Lancet that looked at nearly 200 cases in Barcelona and Madrid discovered that 40% were HIV-positive. Patel and colleagues observed 197 patients from sexual health centres in south London between May and July 2022. They reported 35.5% patients had HIV-1 co-infection. 91.4% of these participants were receiving antiretroviral therapy and 78.6% had an undetectable HIV-1 viral load (<200 copies). The median CD4 count was 664 cells (interquartile range 522-894 cells). The proportion of HIV-positive individuals in these reports is significantly higher than the HIV rate among men who have sex with other men. The reasons for this heavy overrepresentation of men living with HIV among monkeypox cases are not fully understood yet.
Diagnosis
Clinical differential diagnosis must consider other rash illnesses, such as chickenpox, measles, bacterial skin infections, scabies, syphilis and medication-associated allergies. Lymphadenopathy during the prodromal stage of illness can distinguish monkeypox from chickenpox or smallpox. Diagnosis can be verified by testing for the virus.Polymerase chain reaction (PCR) testing of samples from skin lesions is the preferred laboratory test. PCR blood tests are usually inconclusive because the virus remains in blood only a short time. To interpret test results, information is required on date of onset of fever, date of onset of rash, date of specimen collection, current stage of rash, and patient age.
Prevention
Vaccination against smallpox is assumed to protect against human monkeypox infection because they are closely related viruses, and the vaccine protects animals from experimental lethal monkeypox challenges. This has not been conclusively demonstrated in humans because routine smallpox vaccination was discontinued following the eradication of smallpox.Smallpox vaccine has been reported to reduce the risk of monkeypox among previously vaccinated persons in Africa. The decrease in immunity to poxviruses in exposed populations is a factor in the prevalence of monkeypox. It is attributed to waning cross-protective immunity among those vaccinated before 1980, when mass smallpox vaccinations were discontinued, and to the gradually increasing proportion of unvaccinated individuals.The United States Centers for Disease Control and Prevention (CDC) recommends that persons investigating monkeypox outbreaks and involved in caring for infected individuals or animals should receive a smallpox vaccination to protect against monkeypox. Persons who have had close or intimate contact with individuals or animals confirmed to have monkeypox should also be vaccinated. However, the CDC does not recommend pre-exposure vaccination for unexposed veterinarians, veterinary staff, or animal control officers, unless such persons are involved in field investigations. No smallpox or monkeypox vaccine has been approved for use during pregnancy. The CDC recommends that healthcare providers don a full set of personal protective equipment (PPE) before caring for an infected person. This includes a gown, mask, goggles, and a disposable filtering respirator (such as an N95). An infected person should be isolated in preferably a negative air pressure room or at least a private exam room to keep others from possible contact.Monkeypox prevention cannot be simplified to just providing a vaccine. There are more pressing challenges to address, such as access to treatment, veracity and availability of information, and quality of health care. Public health messaging is perhaps the most important challenge. The multiple levels of interconnectivity and negotiated social meanings inherent to the disease require cooperation between medical professionals and patients to achieve correct public health communication. Therefore, Scalvini argues in the BMJ that it is necessary a "new ethic of shared responsibility" to educate people about dangers and give people from underprivileged groups the tools they need to make better decisions.
Treatment
In the European Union and the United States, tecovirimat is approved for the treatment of several poxviruses, including monkeypox. BMJ Best Practice recommends tecovirimat or the smallpox treatment brincidofovir as the first line antiviral treatment if required, alongside supportive care (including antipyretic, fluid balance and oxygenation). Empirical antibiotic therapy or aciclovir may be used if secondary bacterial or varicella zoster infection is suspected, respectively.
Outcome
After healing, the scabs may leave pale marks before becoming darker scars. The risk of death in those infected ranges from 0% to 11%, depending on the type of monkeypox and location in the world. Fatality rates have been reported as around 3.6% in West Africa and 10.6% in Central Africa. Most reported deaths have occurred in young children and people with HIV infection.
Epidemiology
In 1970, monkeypox was first associated with an illness as a disease in humans in the Democratic Republic of the Congo (formerly Zaire), in the town of Basankusu, Équateur Province.
Although it was once thought to be uncommon in humans, cases increased since the 1980s, possibly as a result of waning immunity since the stopping of routine smallpox vaccination.Between 1981 and 1986 WHO surveillance in DRC/Zaire recorded 338 confirmed cases and 33 deaths (CFR 9.8%). In 1996–1997, a second outbreak of human illness was identified in DRC/Zaire and between 1991 and 1999, 511 cases were reported in DRC/Zaire. Clade I of disease remains endemic in DRC and has a higher CFR than the other genetic clade in Western Africa.By May 2022, the case fatality rate (CFR) of past outbreaks was around 3%–6%, while the CFR of the 2022 outbreak remains below 1%. No human-to-human transmission was documented until the 2022 monkeypox outbreak in Europe. Clade II had an outbreak – the first outbreak of monkeypox outside of Africa – in Midwestern United States among owners of pet prairie dogs in 2003. Seventy-one people were reportedly infected, of whom none died.As of 2018, monkeypox was traditionally restricted to the ecology of tropical rainforests. although the pattern was broken in 2005, when 49 cases were reported in Sudan (areas now South Sudan), with no fatalities. The genetic analysis suggested that the virus did not originate in Sudan but was imported, most likely from DRC.Many more monkeypox cases have been reported in Central and West Africa, and in the Democratic Republic of Congo in particular: 2000 cases per year are known between 2011 and 2014. The collected data is often incomplete and unconfirmed, which hinders realistic estimations of the number of cases of monkeypox over time. Nevertheless, it was suggested that the number of reported monkeypox cases had increased and the geographical occurrence broadened as of 2018.
2003 U.S. outbreak
In May 2003, a young child became ill with fever and rash after being bitten by a prairie dog purchased at a local swap meet near Milwaukee, Wisconsin. In total, 71 cases of monkeypox were reported through June 20, 2003. All cases were traced to Gambian pouched rats imported from Accra, Ghana, in April 2003 by a Texas exotic animal distributor. No deaths resulted. Electron microscopy and serologic studies were used to confirm that the disease was human monkeypox.People with monkeypox typically experienced prodromal symptoms of fever, headaches, muscle aches, chills, and drenching sweats. Roughly one-third of infected people had nonproductive coughs. This prodromal phase was followed 1–10 days later by the development of a papular rash that typically progressed through stages of vesiculation, pustulation, umbilication, and crusting. In some people, early lesions had become ulcerated.Rash distribution and lesions occurred on head, trunk, and extremities. Many of the people had initial and satellite lesions on palms, soles, and extremities. Rashes were generalized in some people. After onset of the rash, people generally manifested rash lesions in different stages. Everyone affected reported direct or close contact with prairie dogs, later found to be infected with the monkeypox virus.
2017–2019 Nigeria outbreak
According to the Nigeria Centre for Disease Control (NCDC), between 1971 and 1978, only 10 human monkeypox infections were reported in the country.In September 2017, human monkeypox re-emerged in Nigeria, 39 years since it had been last reported. The subsequent 2017–18 Nigerian human monkeypox outbreak was, at that time, the largest ever outbreak of clade II of the virus, with 118 confirmed cases. Unlike previous outbreaks of this clade, infection was predominantly among young male adults and human-to-human transmission appears to have readily occurred. Seven deaths (5 male, 2 female, case fatality rate of 6%) were reported, including a baby and four HIV/AIDS patients. Additionally, a pregnant woman in her second trimester had a spontaneous miscarriage due to monkeypox infection.The Niger Delta University Teaching Hospital reported that a substantial number of its young adult cases had concomitant genital ulcers, syphilis and HIV infection.
Monkeypox spread around southeast and south Nigeria with some states and the federal government of Nigeria seeking ways to contain it. By December 2017 it spread to Akwa Ibom, Abia, Bayelsa, Benue, Cross River, Delta, Edo, Ekiti, Enugu, Imo, Lagos, Nasarawa, Oyo, Plateau, Rivers and Federal Capital Territory. The outbreak started in September 2017 and remained ongoing across multiple states as of May 2019.
The Centers for Disease Control and Prevention reported cases of American travelers contracting Monkeypox upon return from Lagos and Ibadan. Agam Rao, a medical officer in the Division of Pathogens and High Consequence Pathology at the CDC, said that since 2018 all cases reported outside Africa have come from Nigeria.In a 2021 article Oyewale Tomori pointed out that the number of monkeypox infections in Nigeria through 2021 was likely to be under-represented, because much of the Nigerian population had been avoiding healthcare facilities due to fear of contracting COVID-19.In May 2022, the Nigerian government released a report stating that between 2017 and 2022, 558 cases were confirmed across 32 states and the Federal Capital Territory. The Rivers State was the most affected by monkeypox followed by Bayelsa and Lagos. There were 8 deaths reported, making for a 3.5% Case Fatality Ratio. In 2022, NCDC implemented a National Technical Working Group for reporting and monitoring infections, strengthening response capacity.
2018 and 2019 United Kingdom cases
In September 2018, the United Kingdoms first case of monkeypox was recorded. The person, a Nigerian national, is believed to have contracted monkeypox in Nigeria before travelling to the United Kingdom. According to Public Health England, the person was staying in a naval base in Cornwall before being moved to the Royal Free Hospitals specialised infectious disease unit. People who had been in contact with the person since he contracted the disease were contacted.A second case was confirmed in the town of Blackpool, with a further case that of a medical worker who cared for the case from Blackpool. A fourth case occurred on 3 December 2019, when monkeypox was diagnosed in a person in south west England. They were travelling to the UK from Nigeria.
2019 Singapore case
On 8 May 2019, a 38-year-old man who travelled from Nigeria was hospitalised in an isolation ward at the National Centre for Infectious Diseases in Singapore, after being confirmed as the countrys first case of monkeypox. As a result, 22 people were quarantined. The case may have been linked to a simultaneous outbreak in Nigeria.
2021 cases in United Kingdom, United States
On 24 May in the UK, three cases of monkeypox from a single household were identified by Public Health Wales. The cases were also announced by Health Secretary Matt Hancock while addressing MPs. The index case was diagnosed on 24 May after traveling from Nigeria. The second case was reported on 2 June, and the third on 24 June. One of the three patients, an adult female, was treated with tecovirimat. On day 7 of tecovirimat, she was discharged from hospital to complete her second week of treatment at home.On 14 July in the US, an American returning from a trip in Nigeria was diagnosed with monkeypox. Subsequent testing identified the virus as belonging to clade II. The patient was hospitalized and treated with tecovirimat and was discharged after 32 days, at which time monkeypox virus DNA could no longer be detected in residual skin lesions.
2022 outbreak
History
Monkeypox was first identified as a distinct illness in 1958 among laboratory monkeys in Copenhagen, Denmark.
The first documented cases in humans was in 1970, in six unvaccinated children during the smallpox eradication efforts; the first being a 9-month old boy in the Democratic Republic of the Congo (formerly Zaire). The others, including three who were playmates, were in Liberia and Sierra Leone. It was noted to be less easily transmissible than smallpox. From 1981 to 1986, over 300 cases of human monkeypox were reported in the DRC, the majority being due to contact with animals. In 1996, the disease reemerged in the DRC with 88% of cases resulting from human-to-human transmission. Small viral outbreaks with a death rate in the range of 10% and a secondary human-to-human infection rate of about the same amount occur routinely in equatorial Central and West Africa. In humans, the disease remained confined to the rain forests of Western and Central Africa until 2003, when an outbreak of monkeypox occurred in the US. All cases were traced to sick rodents imported from Ghana. Local prairie dogs caught the infection and passed it onto their owners. The disease was found to be mild and there were no deaths. Between 1970 and 2019 the disease was reported in 10 African countries; mostly in Central and West Africa.In 2018, cases of monkeypox were diagnosed in the UK in two unrelated travellers from Nigeria. That year the first human-to-human transmission outside of Africa was confirmed in the UK. This person was a healthcare worker who possibly contracted the disease from contaminated bedlinen. Cases were also reported in travellers to Israel and Singapore. The UK saw further cases in 2019 and 2021.In June 2022, the World Health Organization announced that it would find a new name for the disease, in line with its policy to avoid misleading associations with specific regions or animals.On 31 July 2022, the first death from monkeypox was recorded in India: a 22-year-old man who had returned from the UAE died.
See also
2003 Midwest monkeypox outbreak
2022 monkeypox outbreak
2022 monkeypox outbreak in Canada
2022 monkeypox outbreak in the United States
2022 monkeypox outbreak in the United Kingdom
References
External links
CDC – Monkeypox Fact Sheet
WHO – Monkeypox Fact Sheet
Virology.net Picturebook: Monkeypox
"Could Monkeypox Take Over Where Smallpox Left Off? Smallpox may be gone, but its viral cousins – monkeypox and cowpox – are staging a comeback". Scientific American, March 4, 2013.
More than 80 cases confirmed in 12 countries, May 23, 2022.
Monkeypox DNA sequencing hints virus circulating since 2017, June 7, 2022.
MonkeypoxTracker – Monkeypox statistics visualization site
PoxApp - the monkeypox app – Assess skin lesions and symptoms with artificial intelligence developed by Stanford University |
Macrophagic myofasciitis | Macrophagic myofasciitis (MMF) is a histopathological finding involving inflammatory microphage formations with aluminium-containing crystal inclusions and associated microscopic muscle necrosis in biopsy samples of the deltoid muscle. Based on the presence of aluminium and the common practice of administering vaccines into the deltoid, it has been proposed that the abnormalities are a result of immunisation with aluminium adjuvant-containing vaccines. The findings were observed in a minority of persons being evaluated for "diffuse myalgias, arthralgias or muscle weakness" who underwent deltoid muscle biopsies. The individuals had a history of receiving aluminium-containing vaccines, administered months to several years prior to observation of MMF histopathology, however this link is tenuous and unsustainable. It has been subsequently proposed that macrophagic myofasciitis is in fact a systemic disorder where various diseases develop in association and as consequence of vaccination with aluminium-containing vaccines in susceptible individuals, however, the World Health Organization has concluded that "[t]here is no evidence to suggest that MMF is a specific illness", and that "[t]he current evidence neither establishes nor excludes a generalized disorder affecting other organs."
Description
MMF was first described in 1998 by a consortium of French myopathologists as an emerging condition of unknown cause characterised by a defining lesion observed upon muscle biopsy. MMF was identified in patients affected by myalgia and fatigue. MMF was judged a consequence of a switch to intramuscular injection and the deltoid muscle being the preferred site of both vaccine injection and biopsy in France (while other sites were preferred for biopsy in other countries) and the commencement of HBV vaccination in French adults. Similar lesions could be detected in babies and children upon biopsy of the quadriceps as this is the site of vaccine administration in this group. MMF could also be experimentally reproduced in animals, with regression over time. It has been proposed that in a small portion of the population, vaccination results in persistence of aluminium-compound particles in macrophages in association with myalgia, fatigue, and cognitive dysfunction. A MMF disorder has been compared to autoimmune/inflammatory syndrome induced by adjuvants. A case-controlled study in France found those with MMF were more likely to have received aluminium-containing vaccines. MMF was also associated with fatigue “and related functional limitations", with fatigue more common in the beginning of the malady that led to the biopsy. However, neither myalgia, arthralgia, nor any other symptoms or risk factors were identified as specific to those with MMF.Many of those with MMF had previously been treated for malaria with chloroquine or hydroxychloroquine.As of 2009, with few exceptions, MMF had only been reported in France.
== References == |
Tonsil carcinoma | Carcinoma of the tonsil is a type of squamous cell carcinoma. The tonsil is the most common site of squamous cell carcinoma in the oropharynx. It comprises 23.1% of all malignancies of the oropharynx. The tumors frequently present at advanced stages, and around 70% of patients present with metastasis to the cervical lymph nodes.
. The most reported complaints include sore throat, otalgia or dysphagia. Some patients may complain of feeling the presence of a lump in the throat. Approximately 20% patients present with a node in the neck as the only symptom.Main risk factors of developing carcinoma tonsil include tobacco smoking and regular intake of high amount of alcohol. It has also been linked to human papilloma virus (HPV type HPV16). Other risk factors include poor maintenance of oral hygiene, a genetic predisposition leading to inclination towards development of throat cancer, immunocompromised states (such as post solid-organ transplant), and chronic exposure to agents such as asbestos and perchloroethylene in certain occupations, radiation therapy and dietary factors.
Signs and symptoms
The early lesions are usually asymptomatic. The patients presenting with an advanced stage of the disease comprises around 66–77% of the cases.
The most important signs include a lump in the neck when palpated and weight loss.
People may also present with fatigue as a symptom.The primary tumor does not have readily discernible signs or symptoms as they grow within the tonsillar capsule. It is difficult to notice anything suspicious on examination of the tonsil other than slight enlargement or the development of firmness around the area.
The carcinoma may occur in one or more sites deep within the tonsillar crypts. It may be accompanied by the enlargement of the tonsil. The affected tonsil grows into the oropharyngeal space making it noticeable by the patient in the form of a neck mass mostly in the jugulodigastric region.
As the tonsils consist of a rich network of lymphatics, the carcinoma may metastasize to the neck lymph nodes which many are cystic.
Extension of tumor to skull or mediastinum can occur.
The additional symptoms include a painful throat, dysphagia, otalgia (due to cranial nerve involvement), foreign body sensation, bleeding, fixation of tongue (infiltration of deep muscles) and trismus (if the pterygoid muscle is involved in the parapharyngeal space).On the other hand, the tumor may also present as a deep red or white fungating wound growing outwards, breaking the skin surface with a central ulceration. This wound-like ulcer fails to heal (non-healing) leading to bleeding and throat pain and other associated symptoms.During biopsy, the lesion may show three signs: gritty texture, firmness and cystification owing to keratinization, fibrosis and necrosis respectively.Cervical lymphydenopathy may be present.
Cause
Smoking and alcohol abuse are the major risk factors. Viral causes have recently been taken under consideration as one of the risk factors. Viruses such as Epstein-Barr virus (EBV) (majorly involved in causing nasopharyngeal carcinoma) and human papilloma virus are included in this category. Chewing of betel nut (Areca catechu) quid has been directly associated to cause oral cancers. It has also been stated under the FDA poisonous plant data base by the U.S Food and Drug Administration
An unbalanced diet, deficit in fruits and vegetables has shown to increase the risk of cancer.
Pathophysiology
Metastasis to regional lymphnodes is common as the tonsil has a rich supply of lymphatics giving way to the tumor cells to metastasis to other lymph nodes (commonly the lymph nodes of neck) and cause lymphydenopathy. The cervical lyphydenopathy can be ipsilateral (70% or more patients) or bilateral (30% and fewer patients). The carcinoma of tonsil usually spreads through the cervical lymph node levels II, III, IV, V, and retropharyngeal lymph nodes.The fourth edition of WHO s classification of head and neck tumors subdivides squamous cell carcinoma of the tonsil into two types: HPV positive or negative. HPV positive tumors arise from the deep lymphoid tissue of the tonsillar crypts and are non-keratinizing. On the other hand HPV negative tumors develop from the tonsillar surface epithelium and hence have keratinizing dysplasia.
Routes of metastasis
Metastasis is common in tonsillar carcinoma. It largely depends on the stage of the cancer and the route through with the cancer cells metastasize.
The cancer cells may spread to adjacent structures, to lymphatics or to distant locations in the body producing secondary tumors.
Local
The tumor may spread locally to soft palate and pillars, base of tongue, pharyngeal wall and hypopharynx. It may invade pterygoid muscles and mandible, resulting in pain and trismus. Parapharyngeal space may also get invaded.
Lymphatic
50% of patients have initial cervical node involvement at the time of presentation. Jugulardigastric nodes are the first to be involved.
Distant metastasis
The occurrence of distant metastasis varies extensively, ranging between 4–31% in clinical studies.
Factors influencing the incidence of distant metastasis are:
Location of primary tumor.
Initial staging
Histological differentiation
Loco-regional control of the primary tumor.The records of 471 male patients with tonsillar carcinoma seen at the Veterans Administration Medical Center, Hines, Illinois, have been reviewed to establish the incidence and site of distant metastasis. All the patients were histological diagnosed and proven cases of tonsillar carcinoma. 72 (15%) out of 471 patients and 33 (29%) of 155 autopsied patients were reported to have distant metastasis.
Squamous cell carcinoma was the most common reported cell type (88%); cases with Lymphoepithelioma had the highest incidence of distant metastasis. The most common anatomical sites of incidence of distant metastasis include lung, liver and bones.
Thorough investigation of these organs is highly recommended before treatment as well as during follow ups.
Diagnosis
The first step to diagnosing tonsil carcinoma is to obtain an accurate history from the patient. The physician will also examine the patient for any indicative physical signs. A few tests then, maybe conducted depending on the progress of the disease or if the doctor feels the need for. The tests include:
Fine needle aspiration, blood tests, MRI, x-rays and PET scan.
Staging
The staging of a tumor mass is based on TNM staging.T staging is the based on the tumor mass. The N staging is based on the extent of spread of cancer to the lymph nodes. Finally, the M stage indicates if the cancer has spread beyond the head and neck or not.
T Staging
The basis of deciding the T stage depends on physical examination and imaging of the tumor.
N staging
This stage is decided through the assessment of the lymph nodes.
M staging
Based on the examination of the entire body.
FInally, the stage is decided by concluding the above results and referring the following chart:
Treatment
The treatment for tonsil carcinoma includes the following methods:
Radiotherapy
Early radio-sensitive tumors are treated by radiotherapy along with irradiation of cervical nodes. The radiation uses high-energy X-rays, electron beams, or radioactive isotopes to destroy cancer cells.
Chemotherapy
Induction chemotherapy is the treatment adapted for shrinking the tonsil tumor. It is given prior to other treatments, hence, the term induction. After the therapy is completed, the patient is asked to rest and is evaluated over a period of time. Then the patient is given chemo-radiation therapy (a combination of chemotherapy and radiation) to completely destroy the tumor cells.
Surgery
If radiation and chemotherapy are unable to destroy the tumor, surgical intervention is considered. Excision of the tonsil can be done for early superficial lesions. Large lesions and those which invade bone require wide surgical excision with hemimandibulectomy and neck dissection (Commando operation)
Combination therapy
Surgery may be combined with pre- or post operative radiation.
Chemotherapy may be given as an adjunct to surgery or radiation.
Prognosis
Prognosis is determined by various factors such as stage, Human Papilloma Virus (HPV) status, Lymph infiltration of cancer cells, spread of cancer cells beyond the lymph node capsule, margins of the tumor and the extent of metastasis.
Many factors are unique to each individual patient and may affect the chances of success of the treatment.
Factors determining the prognosis of tonsillar carcinoma are as follows:
HPV status
Tonsillar carcinoma can be either HPV related or HPV unrelated. It is shown that cases which are HPV positive have a better prognosis than those with HPV negative oropharyngeal cancer.
Stage
The stage at which the cancer presents itself affects the type of definitive treatment, chance of cure, recurrence of cancer and survival rate of the patient. Generally the patient presents very late due to the lack of definitive symptoms in the early stages of the disease. Nearly three fourths of the patients present in Stage III or later.The stages of oropharyngeal cancer are as follows:
• Stage 0 (carcinoma in situ): This stage indicates a good prognosis as most patients with stage 0 survive for a long period without the requirement of an intensive treatment. Although, the patient must cease smoking as it can increase the risk of developing a new cancer.• Stage I and II: Most patients presenting at this stage receive successful treatment, showing a good prognosis. The modes of treatment for this stage include chemotherapy, surgery, radiation therapy or chemoradiation. The main treatment at this stage is radiation, targeting the tumor and the cervical lymph nodes. Surgical removal of the tumor and lymphadenectomy of the cervical (neck) lymph nodes can also be taken up at the main treatment method instead of radiation. And remaining cancer cells post surgery are treated with chemoradiation.• Stage III and IVA: In this stage the cancer cells metastasize into the local tissues and cervical lymph nodes. The treatment used in these cases is chemo radiation. Any remaining cancer cells post chemoradiation are surgically removed. Lymphadenectomy may also be done after treatment with chemoradiation if the cancer cells have infiltrated the cervical lymph nodes. Another method of treatment includes, first, surgical removal of tumor as well as cervical lymph nodes followed by chemoradiation or radiation to decrease the chances of recurrence.• Stage IVB: In this stage the cancer has already undergone distant metastasis, hence showing poor prognosis. The treatment includes chemotherapy, cetuximab or both. Radiation may be used to aid in relieving symptoms arising from the cancer and also to prevent further development of complications.
Lymphatic infiltration
Nearly half of the patients with anterior pillar lesions and three fourths of the patients with tonsillar fossa lesions have nodal metastasis at the time of presentation itself. Metastasis of cancer cells to cervical lymph nodes diminishes the chance of cure. Specially, if there is evidence of metastasis of cancer cells beyond the lymph node capsule. Though, some data indicates that the metastasis of cancer cells outside the lymph node capsule is a bad prognosis for HPV-unrelated oropharynx cancer than it is for HPV-related oropharynx.
Tumor extension
Extension of the tumor to the base of tongue reduces the chances of cure drastically. It also increases the chances of recurrence after treatment.
Metastasis
Spread of cancer cells to local structures like tissues, vessels, large nerves and lymphatics worsens a patients prognosis.A study that analyzed the survival rate in HPV-related oropharynx carcinoma to that in HPV-unrelated oropharynx carcinoma. The study revealed that based on the HPV status of the patient, for STAGE III and STAGE IV oropharynx carcinoma, there was a discrepancy in survival after three years.
The survival was 82% in HPV positive and then also 57% in HPV negative cancers.
References
== External links == |
Rheumatoid arthritis | Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves and blood. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.While the cause of rheumatoid arthritis is not clear, it is believed to involve a combination of genetic and environmental factors. The underlying mechanism involves the bodys immune system attacking the joints. This results in inflammation and thickening of the joint capsule. It also affects the underlying bone and cartilage. The diagnosis is made mostly on the basis of a persons signs and symptoms. X-rays and laboratory testing may support a diagnosis or exclude other diseases with similar symptoms. Other diseases that may present similarly include systemic lupus erythematosus, psoriatic arthritis, and fibromyalgia among others.The goals of treatment are to reduce pain, decrease inflammation, and improve a persons overall functioning. This may be helped by balancing rest and exercise, the use of splints and braces, or the use of assistive devices. Pain medications, steroids, and NSAIDs are frequently used to help with symptoms. Disease-modifying antirheumatic drugs (DMARDs), such as hydroxychloroquine and methotrexate, may be used to try to slow the progression of disease. Biological DMARDs may be used when disease does not respond to other treatments. However, they may have a greater rate of adverse effects. Surgery to repair, replace, or fuse joints may help in certain situations.RA affects about 24.5 million people as of 2015. This is between 0.5 and 1% of adults in the developed world with 5 and 50 per 100,000 people newly developing the condition each year. Onset is most frequent during middle age and women are affected 2.5 times as frequently as men. It resulted in 38,000 deaths in 2013, up from 28,000 deaths in 1990. The first recognized description of RA was made in 1800 by Dr. Augustin Jacob Landré-Beauvais (1772–1840) of Paris. The term rheumatoid arthritis is based on the Greek for watery and inflamed joints.
Signs and symptoms
RA primarily affects joints, but it also affects other organs in more than 15–25% of cases. Associated problems include cardiovascular disease, osteoporosis, interstitial lung disease, infection, cancer, feeling tired, depression, mental difficulties, and trouble working.
Joints
Arthritis of joints involves inflammation of the synovial membrane. Joints become swollen, tender and warm, and stiffness limits their movement. With time, multiple joints are affected (polyarthritis). Most commonly involved are the small joints of the hands, feet and cervical spine, but larger joints like the shoulder and knee can also be involved.: 1098 Synovitis can lead to tethering of tissue with loss of movement and erosion of the joint surface causing deformity and loss of function. The fibroblast-like synoviocytes (FLS), highly specialized mesenchymal cells found in the synovial membrane, have an active and prominent role in these pathogenic processes of the rheumatic joints.RA typically manifests with signs of inflammation, with the affected joints being swollen, warm, painful and stiff, particularly early in the morning on waking or following prolonged inactivity. Increased stiffness early in the morning is often a prominent feature of the disease and typically lasts for more than an hour. Gentle movements may relieve symptoms in early stages of the disease. These signs help distinguish rheumatoid from non-inflammatory problems of the joints, such as osteoarthritis. In arthritis of non-inflammatory causes, signs of inflammation and early morning stiffness are less prominent.
The pain associated with RA is induced at the site of inflammation and classified as nociceptive as opposed to neuropathic. The joints are often affected in a fairly symmetrical fashion, although this is not specific, and the initial presentation may be asymmetrical.: 1098 As the pathology progresses the inflammatory activity leads to tendon tethering and erosion and destruction of the joint surface, which impairs range of movement and leads to deformity. The fingers may develop almost any deformity depending on which joints are most involved. Specific deformities, which also occur in osteoarthritis, include ulnar deviation, boutonniere deformity (also "buttonhole deformity", flexion of proximal interphalangeal joint and extension of distal interphalangeal joint of the hand), swan neck deformity (hyperextension at proximal interphalangeal joint and flexion at distal interphalangeal joint) and "Z-thumb." "Z-thumb" or "Z-deformity" consists of hyperextension of the interphalangeal joint, fixed flexion and subluxation of the metacarpophalangeal joint and gives a "Z" appearance to the thumb.: 1098 The hammer toe deformity may be seen. In the worst case, joints are known as arthritis mutilans due to the mutilating nature of the deformities.
Skin
The rheumatoid nodule, which is sometimes in the skin, is the most common non-joint feature and occurs in 30% of people who have RA. It is a type of inflammatory reaction known to pathologists as a "necrotizing granuloma". The initial pathologic process in nodule formation is unknown but may be essentially the same as the synovitis, since similar structural features occur in both. The nodule has a central area of fibrinoid necrosis that may be fissured and which corresponds to the fibrin-rich necrotic material found in and around an affected synovial space. Surrounding the necrosis is a layer of palisading macrophages and fibroblasts, corresponding to the intimal layer in synovium and a cuff of connective tissue containing clusters of lymphocytes and plasma cells, corresponding to the subintimal zone in synovitis. The typical rheumatoid nodule may be a few millimetres to a few centimetres in diameter and is usually found over bony prominences, such as the elbow, the heel, the knuckles, or other areas that sustain repeated mechanical stress. Nodules are associated with a positive RF (rheumatoid factor) titer, ACPA, and severe erosive arthritis. Rarely, these can occur in internal organs or at diverse sites on the body.Several forms of vasculitis occur in RA, but are mostly seen with long-standing and untreated disease. The most common presentation is due to involvement of small- and medium-sized vessels. Rheumatoid vasculitis can thus commonly present with skin ulceration and vasculitic nerve infarction known as mononeuritis multiplex.Other, rather rare, skin associated symptoms include pyoderma gangrenosum, Sweets syndrome, drug reactions, erythema nodosum, lobe panniculitis, atrophy of finger skin, palmar erythema, and skin fragility (often worsened by corticosteroid use).Diffuse alopecia areata (Diffuse AA) occurs more commonly in people with rheumatoid arthritis. RA is also seen more often in those with relatives who have AA.
Lungs
Lung fibrosis is a recognized complication of rheumatoid arthritis. It is also a rare but well-recognized consequence of therapy (for example with methotrexate and leflunomide). Caplans syndrome describes lung nodules in individuals with RA and additional exposure to coal dust. Exudative pleural effusions are also associated with RA.
Heart and blood vessels
People with RA are more prone to atherosclerosis, and risk of myocardial infarction (heart attack) and stroke is markedly increased.
Other possible complications that may arise include: pericarditis, endocarditis, left ventricular failure, valvulitis and fibrosis. Many people with RA do not experience the same chest pain that others feel when they have angina or myocardial infarction. To reduce cardiovascular risk, it is crucial to maintain optimal control of the inflammation caused by RA (which may be involved in causing the cardiovascular risk), and to use exercise and medications appropriately to reduce other cardiovascular risk factors such as blood lipids and blood pressure. Doctors who treat people with RA should be sensitive to cardiovascular risk when prescribing anti-inflammatory medications, and may want to consider prescribing routine use of low doses of aspirin if the gastrointestinal effects are tolerable.
Blood
Anemia is by far the most common abnormality of the blood cells which can be caused by a variety of mechanisms. The chronic inflammation caused by RA leads to raised hepcidin levels, leading to anemia of chronic disease where iron is poorly absorbed and also sequestered into macrophages. The red cells are of normal size and color (normocytic and normochromic). A low white blood cell count usually only occurs in people with Feltys syndrome with an enlarged liver and spleen. The mechanism of neutropenia is complex. An increased platelet count occurs when inflammation is uncontrolled.
Other
Kidneys
Renal amyloidosis can occur as a consequence of untreated chronic inflammation. Treatment with penicillamine or gold salts such as sodium aurothiomalate are recognized causes of membranous nephropathy.
Eyes
The eye can be directly affected in the form of episcleritis or scleritis, which when severe can very rarely progress to perforating scleromalacia. Rather more common is the indirect effect of keratoconjunctivitis sicca, which is a dryness of eyes and mouth caused by lymphocyte infiltration of lacrimal and salivary glands. When severe, dryness of the cornea can lead to keratitis and loss of vision as well as being painful. Preventive treatment of severe dryness with measures such as nasolacrimal duct blockage is important.
Liver
Liver problems in people with rheumatoid arthritis may be due to the underlying disease process or as a result of the medications used to treat the disease. A coexisting autoimmune liver disease, such as primary biliary cirrhosis or autoimmune hepatitis may also cause problems.
Neurological
Peripheral neuropathy and mononeuritis multiplex may occur. The most common problem is carpal tunnel syndrome caused by compression of the median nerve by swelling around the wrist. Rheumatoid disease of the spine can lead to myelopathy. Atlanto-axial subluxation can occur, owing to erosion of the odontoid process and/or transverse ligaments in the cervical spines connection to the skull. Such an erosion (>3mm) can give rise to vertebrae slipping over one another and compressing the spinal cord. Clumsiness is initially experienced, but without due care, this can progress to quadriplegia or even death.
Constitutional symptoms
Constitutional symptoms including fatigue, low grade fever, malaise, morning stiffness, loss of appetite and loss of weight are common systemic manifestations seen in people with active RA.
Bones
Local osteoporosis occurs in RA around inflamed joints. It is postulated to be partially caused by inflammatory cytokines. More general osteoporosis is probably contributed to by immobility, systemic cytokine effects, local cytokine release in bone marrow and corticosteroid therapy.
Cancer
The incidence of lymphoma is increased, although it is uncommon and associated with the chronic inflammation, not the treatment of RA. The risk of non-melanoma skin cancer is increased in people with RA compared to the general population, an association possibly due to the use of immunosuppression agents for treating RA.
Teeth
Periodontitis and tooth loss are common in people with rheumatoid arthritis.
Risk factors
RA is a systemic (whole body) autoimmune disease. Some genetic and environmental factors affect the risk for RA.
Genetic
Worldwide, RA affects approximately 1% of the adult population and occurs one in 1000 children. Studies show RA primarily affects individuals between the ages of 40–60 years and is seen more commonly in females. A family history of RA increases the risk around three to five times; as of 2016, it was estimated that genetics may account for between 40 and 65% of cases of seropositive RA, but only around 20% for seronegative RA. RA is strongly associated with genes of the inherited tissue type major histocompatibility complex (MHC) antigen. HLA-DR4 is the major genetic factor implicated – the relative importance varies across ethnic groups.Genome-wide association studies examining single-nucleotide polymorphisms have found around one hundred alleles associated with RA risk. Risk alleles within the HLA (particularly HLA-DRB1) genes harbor more risk than other loci. The HLA encodes proteins which controls recognition of self versus nonself molecules. Other risk loci include genes affecting co-stimulatory immune pathways, for example CD28 and CD40, cytokine signaling, lymphocyte receptor activation threshold (e.g., PTPN22), and innate immune activation appear to have less influence than HLA mutations.
Environmental
There are established epigenetic and environmental risk factors for RA. Smoking is an established risk factor for RA in Caucasian populations, increasing the risk three times compared to non-smokers, particularly in men, heavy smokers, and those who are rheumatoid factor positive. Modest alcohol consumption may be protective.Silica exposure has been linked to RA.
Vitamin D deficiency
There are claims that patients that have lower vitamin D levels by 8-10 ng/mL are at risk for rheumatoid arthritis.
Negative findings
No infectious agent has been consistently linked with RA and there is no evidence of disease clustering to indicate its infectious cause, but periodontal disease has been consistently associated with RA.The many negative findings suggest that either the trigger varies, or that it might, in fact, be a chance event inherent with the immune response.
Pathophysiology
RA primarily starts as a state of persistent cellular activation leading to autoimmunity and immune complexes in joints and other organs where it manifests. The clinical manifestations of disease are primarily inflammation of the synovial membrane and joint damage, and the fibroblast-like synoviocytes play a key role in these pathogenic processes. Three phases of progression of RA are an initiation phase (due to non-specific inflammation), an amplification phase (due to T cell activation), and chronic inflammatory phase, with tissue injury resulting from the cytokines, IL–1, TNF-alpha, and IL–6.
Non-specific inflammation
Factors allowing an abnormal immune response, once initiated, become permanent and chronic. These factors are genetic disorders which change regulation of the adaptive immune response. Genetic factors interact with environmental risk factors for RA, with cigarette smoking as the most clearly defined risk factor.Other environmental and hormonal factors may explain higher risks for women, including onset after childbirth and hormonal medications. A possibility for increased susceptibility is that negative feedback mechanisms – which normally maintain tolerance – are overtaken by positive feedback mechanisms for certain antigens, such as IgG Fc bound by rheumatoid factor and citrullinated fibrinogen bound by antibodies to citrullinated peptides (ACPA - Anti–citrullinated protein antibody). A debate on the relative roles of B-cell produced immune complexes and T cell products in inflammation in RA has continued for 30 years, but neither cell is necessary at the site of inflammation, only autoantibodies to IgGFc, known as rheumatoid factors and ACPA, with ACPA having an 80% specificity for diagnosing RA. As with other autoimmune diseases, people with RA have abnormally glycosylated antibodies, which are believed to promote joint inflammation.
Amplification in the synovium
Once the generalized abnormal immune response has become established – which may take several years before any symptoms occur – plasma cells derived from B lymphocytes produce rheumatoid factors and ACPA of the IgG and IgM classes in large quantities. These activate macrophages through Fc receptor and complement binding, which is part of the intense inflammation in RA. Binding of an autoreactive antibody to the Fc receptors is mediated through the antibodys N-glycans, which are altered to promote inflammation in people with RA.This contributes to local inflammation in a joint, specifically the synovium with edema, vasodilation and entry of activated T-cells, mainly CD4 in microscopically nodular aggregates and CD8 in microscopically diffuse infiltrates. Synovial macrophages and dendritic cells function as antigen-presenting cells by expressing MHC class II molecules, which establishes the immune reaction in the tissue.
Chronic inflammation
The disease progresses by forming granulation tissue at the edges of the synovial lining, pannus with extensive angiogenesis and enzymes causing tissue damage. The fibroblast-like synoviocytes have a prominent role in these pathogenic processes. The synovium thickens, cartilage and underlying bone disintegrate, and the joint deteriorates, with raised calprotectin levels serving as a biomarker of these events. Importantly inflammatory events are not limited to synovium but it appear to be systemic, evidence suggest that alterations in T helper profile favoring inflammation such as inflammatory IL-17A producing T helper cells and pathogenic Th17 cells are come from both memory and effector compartment in RA patients peripheral blood.Cytokines and chemokines attract and accumulate immune cells, i.e. activated T- and B cells, monocytes and macrophages from activated fibroblast-like synoviocytes, in the joint space. By signalling through RANKL and RANK, they eventually trigger osteoclast production, which degrades bone tissue. The fibroblast-like synoviocytes that are present in the synovium during rheumatoid arthritis display altered phenotype compared to the cells present in normal tissues. The aggressive phenotype of fibroblast-like synoviocytes in rheumatoid arthritis and the effect these cells have on the microenvironment of the joint can be summarized into hallmarks that distinguish them from healthy fibroblast-like synoviocytes. These hallmark features of fibroblast-like synoviocytes in rheumatoid arthritis are divided into 7 cell-intrinsic hallmarks and 4 cell-extrinsic hallmarks. The cell-intrinsic hallmarks are: reduced apoptosis, impaired contact inhibition, increased migratory invasive potential, changed epigenetic landscape, temporal and spatial heterogeneity, genomic instability and mutations, and reprogrammed cellular metabolism. The cell-extrinsic hallmarks of FLS in RA are: promotes osteoclastogenesis and bone erosion, contributes to cartilage degradation, induces synovial angiogenesis, and recruits and stimulates immune cells.
Diagnosis
Imaging
X-rays of the hands and feet are generally performed when many joints affected. In RA, there may be no changes in the early stages of the disease or the x-ray may show osteopenia near the joint, soft tissue swelling, and a smaller than normal joint space. As the disease advances, there may be bony erosions and subluxation. Other medical imaging techniques such as magnetic resonance imaging (MRI) and ultrasound are also used in RA.Technical advances in ultrasonography like high-frequency transducers (10 MHz or higher) have improved the spatial resolution of ultrasound images depicting 20% more erosions than conventional radiography. Color Doppler and power Doppler ultrasound are useful in assessing the degree of synovial inflammation as they can show vascular signals of active synovitis. This is important, since in the early stages of RA, the synovium is primarily affected, and synovitis seems to be the best predictive marker of future joint damage.
Blood tests
When RA is clinically suspected, a physician may test for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs measured as anti-CCP antibodies).
It is positive in 75–85%, but a negative RF or CCP antibody does not rule out RA, rather, the arthritis is called seronegative, which is in about 15–25% of people with RA. During the first year of illness, rheumatoid factor is more likely to be negative with some individuals becoming seropositive over time. RF is a non-specific antibody and seen in about 10% of healthy people, in many other chronic infections like hepatitis C, and chronic autoimmune diseases such as Sjögrens syndrome and systemic lupus erythematosus. Therefore, the test is not specific for RA.Hence, new serological tests check for anti-citrullinated protein antibodies ACPAs. These tests are again positive in 61–75% of all RA cases, but with a specificity of around 95%. As with RF, ACPAs are many times present before symptoms have started.The by far most common clinical test for ACPAs is the anti-cyclic citrullinated peptide (anti CCP) ELISA. In 2008 a serological point-of-care test for the early detection of RA combined the detection of RF and anti-MCV with a sensitivity of 72% and specificity of 99.7%.To improve the diagnostic capture rate in the early detection of patients with RA and to risk stratify these individuals, the rheumatology field continues to seek complementary markers to both RF and anti-CCP. 14-3-3η (YWHAH) is one such marker that complements RF and anti-CCP, along with other serological measures like c-reactive protein. In a systematic review, 14-3-3η has been described as a welcome addition to the rheumatology field. The authors indicate that the serum based 14-3-η marker is additive to the armamentarium of existing tools available to clinicians, and that there is adequate clinical evidence to support its clinical benefits.Other blood tests are usually done to differentiate from other causes of arthritis, like the erythrocyte sedimentation rate (ESR), C-reactive protein, full blood count, kidney function, liver enzymes and other immunological tests (e.g., antinuclear antibody/ANA) are all performed at this stage. Elevated ferritin levels can reveal hemochromatosis, a mimic of RA, or be a sign of Stills disease, a seronegative, usually juvenile, variant of rheumatoid arthritis.
Classification criteria
In 2010, the 2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria were introduced.The new criteria are not diagnostic criteria, but are classification criteria to identify disease with a high likelihood of developing a chronic form. However a score of 6 or greater unequivocally classifies a person with a diagnosis of rheumatoid arthritis.These new classification criteria overruled the "old" ACR criteria of 1987 and are adapted for early RA diagnosis. The "new" classification criteria, jointly published by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) establish a point value between 0 and 10. Four areas are covered in the diagnosis:
joint involvement, designating the metacarpophalangeal joints, proximal interphalangeal joints, the interphalangeal joint of the thumb, second through fifth metatarsophalangeal joint and wrist as small joints, and shoulders, elbows, hip joints, knees, and ankles as large joints:
Involvement of 1 large joint gives 0 points
Involvement of 2–10 large joints gives 1 point
Involvement of 1–3 small joints (with or without involvement of large joints) gives 2 points
Involvement of 4–10 small joints (with or without involvement of large joints) gives 3 points
Involvement of more than 10 joints (with involvement of at least 1 small joint) gives 5 points
serological parameters – including the rheumatoid factor as well as ACPA – "ACPA" stands for "anti-citrullinated protein antibody":
Negative RF and negative ACPA gives 0 points
Low-positive RF or low-positive ACPA gives 2 points
High-positive RF or high-positive ACPA gives 3 points
acute phase reactants: 1 point for elevated erythrocyte sedimentation rate, ESR, or elevated CRP value (c-reactive protein)
duration of arthritis: 1 point for symptoms lasting six weeks or longerThe new criteria accommodate to the growing understanding of RA and the improvements in diagnosing RA and disease treatment. In the "new" criteria, serology and autoimmune diagnostics carries major weight, as ACPA detection is appropriate to diagnose the disease in an early state, before joints destructions occur. Destruction of the joints viewed in radiological images was a significant point of the ACR criteria from 1987. This criterion no longer is regarded to be relevant, as this is just the type of damage that treatment is meant to avoid.
Differential diagnoses
Several other medical conditions can resemble RA, and need to be distinguished from it at the time of diagnosis:
Crystal induced arthritis (gout, and pseudogout) – usually involves particular joints (knee, MTP1, heels) and can be distinguished with an aspiration of joint fluid if in doubt. Redness, asymmetric distribution of affected joints, pain occurs at night and the starting pain is less than an hour with gout.
Osteoarthritis – distinguished with X-rays of the affected joints and blood tests, older age, starting pain less than an hour, asymmetric distribution of affected joints and pain worsens when using joint for longer periods.
Systemic lupus erythematosus (SLE) – distinguished by specific clinical symptoms and blood tests (antibodies against double-stranded DNA)
One of the several types of psoriatic arthritis resembles RA – nail changes and skin symptoms distinguish between them
Lyme disease causes erosive arthritis and may closely resemble RA – it may be distinguished by blood test in endemic areas
Reactive arthritis – asymmetrically involves heel, sacroiliac joints and large joints of the leg. It is usually associated with urethritis, conjunctivitis, iritis, painless buccal ulcers, and keratoderma blennorrhagica.
Axial spondyloarthritis (including ankylosing spondylitis) – this involves the spine, although an RA-like symmetrical small-joint polyarthritis may occur in the context of this condition.
Hepatitis C – RA-like symmetrical small-joint polyarthritis may occur in the context of this condition. Hepatitis C may also induce rheumatoid factor auto-antibodies.Rarer causes which usually behave differently but may cause joint pains:
Sarcoidosis, amyloidosis, and Whipples disease can also resemble RA.
Hemochromatosis may cause hand joint arthritis.
Acute rheumatic fever can be differentiated by a migratory pattern of joint involvement and evidence of antecedent streptococcal infection.
Bacterial arthritis (such as by Streptococcus) is usually asymmetric, while RA usually involves both sides of the body symmetrically.
Gonococcal arthritis (a bacterial arthritis) is also initially migratory and can involve tendons around the wrists and ankles.Sometimes arthritis is in an undifferentiated stage (i.e. none of the above criteria is positive), even if synovitis is witnessed and assessed with ultrasound imaging.
Difficult-to-treat
Rheumatoid arthritis (D2T RA) is a specific classification RA by the European League against Rheumatism (EULAR).Signs of illness:
Persistence of signs and symptoms
Drug resistance
Does not respond on two or more biological treatments
Does not respond on anti-rheumatic drugs with different mechanism of actionFactors contributing to difficult-to-treat disease:
Genetic risk factors
Environmental factors (diet, smoking, physical activity)
Overweight and obese
Genetic factors
Genetic factors such as HLA-DR1B1, TRAF1, PSORS1C1 and microRNA 146a are associated with difficult to treat rheumatoid arthritis, other gene polymorphisms seem to be correlated with response to biologic modifying anti-rheumatic drugs (bDMARDs). Next one is FOXO3A gene region been reported as associated with worst disorder. The minor allele at FOXO3A summon a differential response |
Rheumatoid arthritis | of monocytes in RA patients. FOXO3A can provide an increase of pro-inflammatory cytokines, including TNFα. Possible gene polymorphism: STAT4, PTPN2, PSORS1C1 and TRAF3IP2 genes had been correlated with response to TNF inhibitors.
HLA-DR1 and HLA-DRB1 gene
The HLA-DRB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex is the human version of the major histocompatibility complex (MHC). Currently, have been identified at least 2479 different versions of the HLA-DRB1 gene. The presence of HLA-DRB1 alleles seems to predict radiographic damage, which may be partially mediated by ACPA development, and also elevated sera inflammatory levels and high swollen joint count. HLA-DR1 is encoded by the most risk allele HLA-DRB1 which share a conserved 5-aminoacid sequence that is correlated with the development of anti-citrullinated protein antibodies. HLA-DRB1 gene have more strong correlation with disease development. Susceptibility to and outcome for rheumatoid arthritis (RA) may associate with particular HLA-DR alleles, but these alleles vary among ethnic groups and geographic areas.
MicroRNAs
MicroRNAs are a factor in the development of that type of disease. MicroRNAs usually operate as a negative regulator of the expression of target proteins and their increased concentration after biologic treatment (bDMARDs) or after anti-rheumatic drugs. Level of miRNA before and after anti-TNFa/DMRADs combination therapy are potential novel biomarkers for predicting and monitoring outcome. For instance, some of them were found significantly upregulated by anti-TNFa/DMRADs combination therapy. For example, miRNA-16-5p, miRNA-23-3p, miRNA125b-5p, miRNA-126-3p, miRNA-146a-5p, miRNA-223-3p. Curious fact is that only responder patients showed an increase in those miRNAs after therapy, and paralleled the reduction of TNFα, interleukin (IL)-6, IL-17, rheumatoid factor (RF), and C-reactive protein (CRP).
Monitoring progression
Many tools can be used to monitor remission in rheumatoid arthritis.
DAS28: Disease Activity Score of 28 joints (DAS28) is widely used as an indicator of RA disease activity and response to treatment. Joints included are (bilaterally): proximal interphalangeal joints (10 joints), metacarpophalangeal joints (10), wrists (2), elbows (2), shoulders (2) and knees (2). When looking at these joints, both the number of joints with tenderness upon touching (TEN28) and swelling (SW28) are counted. The erythrocyte sedimentation rate (ESR) is measured and the affected person makes a subjective assessment (SA) of disease activity during the preceding 7 days on a scale between 0 and 100, where 0 is "no activity" and 100 is "highest activity possible". With these parameters, DAS28 is calculated as:
D
A
S
28
=
0.56
×
T
E
N
28
+
0.28
×
S
W
28
+
0.70
×
ln
(
E
S
R
)
+
0.014
×
S
A
{\displaystyle DAS28=0.56\times {\sqrt {TEN28}}+0.28\times {\sqrt {SW28}}+0.70\times \ln(ESR)+0.014\times SA}
From this, the disease activity of the affected person can be classified as follows:
It is not always a reliable indicator of treatment effect. One major limitation is that low-grade synovitis may be missed.
Other: Other tools to monitor remission in rheumatoid arthritis are: ACR-EULAR Provisional Definition of Remission of Rheumatoid arthritis, Simplified Disease Activity Index and Clinical Disease Activity Index. Some scores do not require input from a healthcare professional and allow self-monitoring by the person, like HAQ-DI.
Prevention
There is no known prevention for the condition other than the reduction of risk factors.
Supplementation
Evidence suggests that increasing vitamin D levels to the range of 40–60 ng/mL could reduce the risk of rheumatoid arthritis.
Management
There is no cure for RA, but treatments can improve symptoms and slow the progress of the disease. Disease-modifying treatment has the best results when it is started early and aggressively. The results of a recent systematic review found that combination therapy with tumor necrosis factor (TNF) and non-TNF biologics plus methotrexate (MTX) resulted in improved disease control, Disease Activity Score (DAS)-defined remission, and functional capacity compared with a single treatment of either methotrexate or a biologic alone.The goals of treatment are to minimize symptoms such as pain and swelling, to prevent bone deformity (for example, bone erosions visible in X-rays), and to maintain day-to-day functioning. This is primarily addressed with disease-modifying antirheumatic drugs (DMARDs); dosed physical activity; analgesics and physical therapy may be used to help manage pain. RA should generally be treated with at least one specific anti-rheumatic medication. The use of benzodiazepines (such as diazepam) to treat the pain is not recommended as it does not appear to help and is associated with risks.
Lifestyle
Regular exercise is recommended as both safe and useful to maintain muscle strength and overall physical function. Physical activity is beneficial for people with rheumatoid arthritis who experience fatigue, although there was little to no evidence to suggest that exercise may have an impact on physical function in the long term, a study found that carefully dosed exercise has shown significant improvements in patients with RA. Moderate effects have been found for aerobic exercises and resistance training on cardiovascular fitness and muscle strength in RA. Furthermore, physical activity had no detrimental side effects like increased disease activity in any exercise dimension. It is uncertain if eating or avoiding specific foods or other specific dietary measures help improve symptoms. Occupational therapy has a positive role to play in improving functional ability in people with rheumatoid arthritis. Weak evidence supports the use of wax baths (thermotherapy) to treat arthritis in the hands.Educational approaches that inform people about tools and strategies available to help them cope with rheumatoid arthritis may improve a persons psychological status and level of depression in the shorter-term. The use of extra-depth shoes and molded insoles may reduce pain during weight-bearing activities such as walking. Insoles may also prevent the progression of bunions.
Disease-modifying agents
Disease-modifying antirheumatic drugs (DMARDs) are the primary treatment for RA. They are a diverse collection of drugs, grouped by use and convention. They have been found to improve symptoms, decrease joint damage, and improve overall functional abilities. DMARDs should be started early in the disease as they result in disease remission in approximately half of people and improved outcomes overall.The following drugs are considered DMARDs: methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, TNF inhibitors (certolizumab, adalimumab, infliximab and etanercept), abatacept, and anakinra. Additionally, rituximab and tocilizumab are monoclonal antibodies and are also DMARDs. Use of tocilizumab is associated with a risk of increased cholesterol levels.The most commonly used agent is methotrexate with other frequently used agents including sulfasalazine and leflunomide. Leflunomide is effective when used from 6–12 months, with similar effectiveness to methotrexate when used for 2 years. Sulfasalazine also appears to be most effective in the short-term treatment of rheumatoid arthritis.Hydroxychloroquine, in addition to its low toxicity profile, is considered effective for treatment of moderate RA treatment.Agents may be used in combination, however, people may experience greater side effects. Methotrexate is the most important and useful DMARD and is usually the first treatment. A combined approach with methotrexate and biologics improves ACR50, HAQ scores and RA remission rates. Triple therapy consisting of methotrexate, sulfasalazine and hydroxychloroquine may also effectively control disease activity. Adverse effects should be monitored regularly with toxicity including gastrointestinal, hematologic, pulmonary, and hepatic. Side effects such as nausea, vomiting or abdominal pain can be reduced by taking folic acid.A 2015 Cochrane review found rituximab with methotrexate to be effective in improving symptoms compared to methotrexate alone. Rituximab works by decreasing levels of B-cells (immune cell that is involved in inflammation). People taking rituximab had improved pain, function, reduced disease activity and reduced joint damage based on x-ray images. After 6 months, 21% more people had improvement in their symptoms using rituximab and methotrexate.Biological agents should generally be used only if methotrexate and other conventional agents are not effective after a trial of three months. They are associated with a higher rate of serious infections as compared to other DMARDs. Biological DMARD agents used to treat rheumatoid arthritis include: tumor necrosis factor alpha inhibitors (TNF inhibitors) such as infliximab; interleukin 1 blockers such as anakinra, monoclonal antibodies against B cells such as rituximab, interleukin 6 blockers such as tocilizumab, and T cell co-stimulation blockers such as abatacept. They are often used in combination with either methotrexate or leflunomide. Biologic monotherapy or tofacitinib with methotrexate may improve ACR50, RA remission rates and function. Abatacept should not be used at the same time as other biologics. In those who are well controlled (low disease activity) on TNF inhibitors, decreasing the dose does not appear to affect overall function. Discontinuation of TNF inhibitors (as opposed to gradually lowering the dose) by people with low disease activity may lead to increased disease activity and may affect remission, damage that is visible on an x-ray, and a persons function. People should be screened for latent tuberculosis before starting any TNF inhibitor therapy to avoid reactivation of tuberculosis.TNF inhibitors and methotrexate appear to have similar effectiveness when used alone and better results are obtained when used together. Golimumab is effective when used with methotraxate. TNF inhibitors may have equivalent effectiveness with etanercept appearing to be the safest. Injecting etanercept, in addition to methotrexate twice a week may improve ACR50 and decrease radiographic progression for up to 3 years. Abatacept appears effective for RA with 20% more people improving with treatment than without but long term safety studies are yet unavailable. Adalimumab slows the time for the radiographic progression when used for 52 weeks. However, there is a lack of evidence to distinguish between the biologics available for RA. Issues with the biologics include their high cost and association with infections including tuberculosis. Use of biological agents may reduce fatigue. The mechanism of how biologics reduce fatigue is unclear.
Gold (sodium aurothiomalate) and cyclosporin
Sodium aurothiomalate (gold) and cyclosporin are less commonly used due to more common adverse effects. However, cyclosporin was found to be effective in the progressive RA when used up to one year.
Anti-inflammatory and analgesic agents
Glucocorticoids can be used in the short term and at the lowest dose possible for flare-ups and while waiting for slow-onset drugs to take effect. Combination of glucocorticoids and conventional therapy has shown a decrease in rate of erosion of bones. Steroids may be injected into affected joints during the initial period of RA, prior to the use of DMARDs or oral steroids.Non-NSAID drugs to relieve pain, like paracetamol may be used to help relieve the pain symptoms; they do not change the underlying disease. The use of paracetamol may be associated with the risk of developing ulcers.NSAIDs reduce both pain and stiffness in those with RA but do not affect the underlying disease and appear to have no effect on peoples long term disease course and thus are no longer first line agents. NSAIDs should be used with caution in those with gastrointestinal, cardiovascular, or kidney problems. Rofecoxib was withdrawn from the global market as its long-term use was associated to an increased risk of heart attacks and strokes. Use of methotrexate together with NSAIDs is safe, if adequate monitoring is done. COX-2 inhibitors, such as celecoxib, and NSAIDs are equally effective. A 2004 Cochrane review found that people preferred NSAIDs over paracetamol. However, it is yet to be clinically determined whether NSAIDs are more effective than paracetamol.The neuromodulator agents topical capsaicin may be reasonable to use in an attempt to reduce pain. Nefopam by mouth and cannabis are not recommended as of 2012 as the risks of use appear to be greater than the benefits.Limited evidence suggests the use of weak oral opioids but the adverse effects may outweigh the benefits.Alternatively, physical therapy has been tested and shown as an effective aid in reducing pain in patients with RA. As most RA is detected early and treated aggressively, physical therapy plays more of a preventative and compensatory role, aiding in pain management alongside regular rheumatic therapy.
Surgery
Especially for affected fingers, hands, and wrists, synovectomy may be needed to prevent pain or tendon rupture when drug treatment has failed. Severely affected joints may require joint replacement surgery, such as knee replacement. Postoperatively, physiotherapy is always necessary.: 1080, 1103 There is insufficient evidence to support surgical treatment on arthritic shoulders.
Physiotherapy
For people with RA, physiotherapy may be used together with medical management. This may include cold and heat application, electronic stimulation, and hydrotherapy. Although medications improve symptoms of RA, muscle function is not regained when disease activity is controlled.Physiotherapy promotes physical activity. In RA, physical activity like exercise in the appropriate dosage (frequency, intensity, time, type, volume, progression) and physical activity promotion is effective in improving cardiovascular fitness, muscle strength, and maintaining a long term active lifestyle. In the short term, resistance exercises, with or without range of motion exercises, improve self-reported hand functions. Physical activity promotion according to the public health recommendations should be an integral part of standard care for people with RA and other arthritic diseases. Additionally, the combination of physical activities and cryotherapy show its efficacy on the disease activity and pain relief. The combination of aerobic activity and cryotherapy may be an innovative therapeutic strategy to improve the aerobic capacity in arthritis patients and consequently reduce their cardiovascular risk while minimizing pain and disease activity.
Compression gloves
Compression gloves are handwear designed to help prevent the occurrence of various medical disorders relating to blood circulation in the wrists and hands. They can be used to treat the symptoms of arthritis, though the medical benefits may be limited.
Alternative medicine
In general, there is not enough evidence to support any complementary health approaches for RA, with safety concerns for some of them. Some mind and body practices and dietary supplements may help people with symptoms and therefore may be beneficial additions to conventional treatments, but there is not enough evidence to draw conclusions. A systematic review of CAM modalities (excluding fish oil) found that " The available evidence does not support their current use in the management of RA.". Studies showing beneficial effects in RA on a wide variety of CAM modalities are often affected by publication bias and are generally not high quality evidence such as randomized controlled trials (RCTs).A 2005 Cochrane review states that low level laser therapy can be tried to improve pain and morning stiffness due to rheumatoid arthritis as there are few side-effects.There is limited evidence that Tai Chi might improve the range of motion of a joint in persons with rheumatoid arthritis. The evidence for acupuncture is inconclusive with it appearing to be equivalent to sham acupuncture.A Cochrane review in 2002 showed some benefits of the electrical stimulation as a rehabilitation intervention to improve the power of the hand grip and help to resist fatigue. D‐penicillamine may provide similar benefits as DMARDs but it is also highly toxic. Low-quality evidence suggests the use of therapeutic ultrasound on arthritic hands. Potential benefits include increased grip strength, reduced morning stiffness and number of swollen joints. There is tentative evidence of benefit of transcutaneous electrical nerve stimulation (TENS) in RA. Acupuncture‐like TENS (AL-TENS) may decrease pain intensity and improve muscle power scores.Low-quality evidence suggests people with active RA may benefit from assistive technology. This may include less discomfort and difficulty such as when using an eye drop device. Balance training is of unclear benefits.
Dietary supplements
Fatty acids
There has been a growing interest in the role of long-chain omega-3 polyunsaturated fatty acids to reduce inflammation and alleviate the symptoms of RA. Metabolism of omega-3 polyunsaturated fatty acids produces docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which inhibits pro-inflammatory eicosanoids and cytokines (TNF-a, IL-1b and IL-6), decreasing both lymphocyte proliferation and reactive oxygen species. These studies showed evidence for significant clinical improvements on RA in inflammatory status and articular index. Gamma-linolenic acid, an omega-6 fatty acid, may reduce pain, tender joint count and stiffness, and is generally safe. For omega-3 polyunsaturated fatty acids (found in fish oil, flax oil and hemp oil), a meta-analysis reported a favorable effect on pain, although confidence in the effect was considered moderate. The same review reported less inflammation but no difference in joint function. A review examined the effect of marine oil omega-3 fatty acids on pro-inflammatory eicosanoid concentrations; leukotriene4 (LTB4) was lowered in people with rheumatoid arthritis but not in those with non-autoimmune chronic diseases. (LTB4) increases vascular permeabiltity and stimulates other inflammatory substances. A third meta-analysis looked at fish consumption. The result was a weak, non-statistically significant inverse association between fish consumption and RA. A fourth review limited inclusion to trials in which people eat ≥2.7 g/day for more than three months. Use of pain relief medication was decreased, but improvements in tender or swollen joints, morning stiffness and physical function were not changed. Collectively, the current evidence is not strong enough to determine that supplementation with omega-3 fatty acids or regular consumption of fish are effective treatments for rheumatoid arthritis.
Diets
Patients with RA often claim that their symptoms are alleviated by special diets or by simple elimination of certain foods. In contrast, some foods might provoke hypersensitivity responses, which may increase symptoms of RA.The Dong diet has been suggested for a benefit in RA. This diet is rich in oils, seafood, vegetables, and rice which improve symptoms of RA. It eliminates citrus fruits, chocolate, dairy produce, flour products, alcohol, additives, spices, fizzy drinks, and red meat which are implicated in the aggravation of symptoms.The Mediterranean diet is a well‐balanced, nutritionally adequate diet that encompasses all the food groups. This diet is rich in fresh fruits and vegetables, whole grains, seafood, nuts and legumes, and olive oil. In contrast, it limits red meat, sugary foods, and dairy, in small portions of yogurt and cheese. The foods in this category parallel the Dong Diet closely and show evidence of overlap. There is beneficial effect in using a Mediterranean diet and Dong diet for a reduction in the number of tender joints, stiffness, and pain.Vitamins
Adequate Vitamin concentrations may provide an important defence against the increased oxidant stress in patients with RA. Here we look at the effects of vitamins E, C and B on the management of RA.
In general vitamin E deficiency enhances components of the inflammatory response and suppresses components of the immune response. Molecular studies have demonstrated that the formation of the pro-inflammatory prostaglandin E2 is inhibited 95% by aspirin when combined with vitamin E compared to control. This suggests that vitamin E supplementation reduces the need for high dosage of aspirin needed by patients with RA to relieve joint symptoms. This can offer double benefits because lowering the dose of aspirin can also reduce the gastric irritation side effect for patients. Even though there is no evidence of only taking vitamin E supplementation alone, I believe patients with RA should be encouraged to increase their consumption of vitamin E rich cereals, fruit, and vegetables.
Vitamin C is necessary for the growth and development of all body tissues and plays an important role in antioxidant defences. In animal studies biochemical markers of antioxidant defence mechanisms were increased with vitamin C supplementation and infiltration of inflammatory cells into synovial fluid were decreased. From these studies I can conclude that vitamin C supplementation may be more effective for the pain associated with RA however long-term use might aggravate onset of osteoarthritis.
Vitamin B6 and B9 play a role in RA management as well. Studies have shown that low plasma levels of pyridoxal-5-phosphate, the metabolically active form of vitamin B6, have been reported in RA patients, which may be associated with the elevated TNF-a production. Folate supplies are also decreased in RA patients who are taking Methotrexate, an anti-rheumatic drug. We see that folate supplementation can reduce the mucosal and gastrointestinal side effects of low dose Methotrexate in patients with RA. This works in a similar pattern to aspirin and vitamin E supplementation. Therefore, RA patients should be advised to consume dietary sources of vitamin B6 and B9 up to the dietary reference value, until further research is undertaken into the toxicity and effectiveness of large dose supplementation.
Food containing high source of vitamin E to help treat Rheumatoid Arthritis include almonds, avocados, spinach, sunflower seeds and peanut butter. Vitamin C foods include oranges, orange juice, strawberry, broccoli, brussel sprouts and potatoes. Brown rice, barley, and fish contain sources of vitamin B6 and B9. Lastly, Vitamin D can be included in the diet by incorporating tuna, salmon, orange juice and almond Milk into diet.Minerals
Minerals including fluoride, iron, calcium, and zinc have been studied in the role of RA management. The effects of fluoride supplementation in preventing RA-induced bone loss were examined in a randomized control trial. Results suggest that fluoride therapy may increase vertebral bone mass in RA patients.Approximately, one-third of cases of anaemia in RA patients may be caused by depletion of iron stores. A major cause for iron deficiency anaemia is the poor dietary intake. Deferioxamine, an iron-chelating agent, which has possible anti-inflammatory properties, causes haemoglobin and serum iron levels to increases. This shows that iron stores are needed within the body and an adequate dietary intake to meet the recommended intakes should be encouraged, even though there is no evidence for additional routine supplementation for patients with RA.
Studies have examined the effect of calcium supplementation on bone mineral density among subjects taking corticosteroids. A study of calcium combined with vitamin D3 in RA patients taking low-dose corticosteroids demonstrated a reduction in bone mineral density loss in both the spine and trochanter, but not the femoral neck. However, no change was seen in BMD with calcium and vitamin D3 supplementation in RA patients not receiving corticosteroids. Therefore, there is little evidence to support calcium and vitamin D supplementation in corticosteroid receiving RA patients.
Lastly, low levels of serum zinc have been reported in patients with RA which may be caused by elevated IL-1b levels. However, Zinc supplementations yield contradictory results and at present do not support a therapeutic use of zinc.
Food containing high source of fluoride to help treat Rheumatoid Arthritis include tomatoes, oranges, bell peppers and grapefruit, which you should eat in moderation. Iron can be incorporated into the diet by eating seafood, spinach, and peas. Moderate amounts of calcium should be included into the diet by having milk, cheese, dairy products, curly kale, okra, bread and fortified flour products such as cereals.
Herbal
The American College of Rheumatology states that no herbal medicines have health claims supported by high-quality evidence and thus they do not recommend their use. There is no scientific basis to suggest that herbal supplements advertised as "natural" are safer for use than conventional medications as both are chemicals. Herbal medications, although labelled "natural", may be toxic or fatal if consumed.
Due to the false belief that herbal supplements are always safe, there is sometimes a hesitancy to report their use which may increase the risk of adverse reaction.The following are under investigation for treatments for RA, based on preliminary promising results (not recommended for clinical use yet): boswellic acid, curcumin, devils claw, Euonymus alatus, and thunder god vine (Tripterygium wilfordii). NCCIH has noted that, "In particular, the herb thunder god vine (Tripterygium wilfordii) can have serious side effects."There is conflicting evidence on the role of erythropoiesis-stimulating agents for treatment of anemia in persons with rheumatoid arthritis.
Pregnancy
More than 75% of women with rheumatoid arthritis have symptoms improve during pregnancy but might have symptoms worsen after delivery. Methotrexate and leflunomide are teratogenic (harmful to foetus) and not used in pregnancy. It is recommended women of childbearing age should use contraceptives to avoid pregnancy and to discontinue its use if pregnancy is planned. Low dose of prednisolone, hydroxychloroquine and sulfasalazine are considered safe in pregnant persons with rheumatoid arthritis. Prednisolone should be used with caution as the side effects include infections and fractures.
Vaccinations
People with RA have an increased risk of infections and mortality and recommended vaccinations can reduce these risks. The inactivated influenza vaccine should be received annually. The pneumococcal vaccine should be administered twice for people under the age 65 and once for those over 65. Lastly, the live-attenuated zoster vaccine should be administered once after the age 60, but is not recommended in people on a tumor necrosis factor alpha blocker.
Prognosis
The course of the disease varies greatly. Some people have mild short-term symptoms, but in most the disease is progressive for life. Around 25% will have subcutaneous nodules (known as rheumatoid nodules); this is associated with a poor prognosis.
Prognostic factors
Poor prognostic factors include,
Persistent synovitis
Early erosive disease
Extra-articular findings (including subcutaneous rheumatoid nodules)
Positive serum RF findings
Positive serum anti-CCP autoantibodies
Positive serum 14-3-3η (YWHAH) levels above 0.5 ng/ml
Carriership of HLA-DR4 "Shared Epitope" alleles
Family history of RA
Poor functional status
Socioeconomic factors
Elevated acute phase response (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP])
Increased clinical severity.
Mortality
RA reduces lifespan on average from three to twelve years. Young age at onset, long disease duration, the presence of other health problems, and characteristics of severe RA—such as poor functional ability or overall health status, a lot of joint damage on x-rays, the need for hospitalisation or involvement of organs other than the joints—have been shown to associate with higher mortality. Positive responses to treatment may indicate a better prognosis. A 2005 study by the Mayo Clinic noted that individuals with RA have a doubled risk of heart disease, independent of other risk factors such as |
Rheumatoid arthritis | diabetes, excessive alcohol use, and elevated cholesterol, blood pressure and body mass index. The mechanism by which RA causes this increased risk remains unknown; the presence of chronic inflammation has been proposed as a contributing factor. It is possible that the use of new biologic drug therapies extend the lifespan of people with RA and reduce the risk and progression of atherosclerosis. This is based on cohort and registry studies, and still remains hypothetical. It is still uncertain whether biologics improve vascular function in RA or not. There was an increase in total cholesterol and HDLc levels and no improvement of the atherogenic index.
Epidemiology
RA affects between 0.5 and 1% of adults in the developed world with between 5 and 50 per 100,000 people newly developing the condition each year. In 2010 it resulted in about 49,000 deaths globally.Onset is uncommon under the age of 15 and from then on the incidence rises with age until the age of 80. Women are affected three to five times as often as men.The age at which the disease most commonly starts is in women between 40 and 50 years of age, and for men somewhat later. RA is a chronic disease, and although rarely, a spontaneous remission may occur, the natural course is almost invariably one of the persistent symptoms, waxing and waning in intensity, and a progressive deterioration of joint structures leading to deformations and disability.There is an association between periodontitis and rheumatoid arthritis (RA), hypothesised to lead to enhanced generation of RA-related autoantibodies. Oral bacteria that invade the blood may also contribute to chronic inflammatory responses and generation of autoantibodies.
History
The first recognized description of RA in modern medicine was in 1800 by the French physician Dr Augustin Jacob Landré-Beauvais (1772–1840) who was based in the famed Salpêtrière Hospital in Paris. The name "rheumatoid arthritis" itself was coined in 1859 by British rheumatologist Dr Alfred Baring Garrod.The art of Peter Paul Rubens may possibly depict the effects of RA. In his later paintings, his rendered hands show, in the opinion of some physicians, increasing deformity consistent with the symptoms of the disease. RA appears to some to have been depicted in 16th-century paintings. However, it is generally recognized in art historical circles that the painting of hands in the 16th and 17th century followed certain stylized conventions, most clearly seen in the Mannerist movement. It was conventional, for instance, to show the upheld right hand of Christ in what now appears a deformed posture. These conventions are easily misinterpreted as portrayals of disease.Historic (though not necessarily effective) treatments for RA have also included: rest, ice, compression and elevation, apple diet, nutmeg, some light exercise every now and then, nettles, bee venom, copper bracelets, rhubarb diet, extractions of teeth, fasting, honey, vitamins, insulin, magnets, and electroconvulsive therapy (ECT).
Etymology
Rheumatoid arthritis is derived from the Greek word ῥεύμα-rheuma (nom.), ῥεύματος-rheumatos (gen.) ("flow, current"). The suffix -oid ("resembling") gives the translation as joint inflammation that resembles rheumatic fever. Rhuma which means watery discharge might refer to the fact that the joints are swollen or that the disease may be made worse by wet weather.
Research
Meta-analysis found an association between periodontal disease and RA, but the mechanism of this association remains unclear. Two bacterial species associated with periodontitis are implicated as mediators of protein citrullination in the gums of people with RA.Vitamin D deficiency is more common in people with rheumatoid arthritis than in the general population. However, whether vitamin D deficiency is a cause or a consequence of the disease remains unclear. One meta-analysis found that vitamin D levels are low in people with rheumatoid arthritis and that vitamin D status correlates inversely with prevalence of rheumatoid arthritis, suggesting that vitamin D deficiency is associated with susceptibility to rheumatoid arthritis.The fibroblast-like synoviocytes have a prominent role in the pathogenic processes of the rheumatic joints, and therapies that target these cells are emerging as promising therapeutic tools, raising hope for future applications in rheumatoid arthritis.Possible links with intestinal barrier dysfunction are investigated.
References
External links
Rheumatoid arthritis at Curlie
"Rheumatoid Arthritis". MedlinePlus. U.S. National Library of Medicine. |
Black hairy tongue | Black hairy tongue syndrome (BHT) is a condition of the tongue in which the small bumps on the tongue elongate with black or brown discoloration, giving a black and hairy appearance. The appearance may be alarming, but it is a harmless condition. Predisposing factors include smoking, xerostomia (dry mouth), soft diet, poor oral hygiene and certain medications. Management is facilitated by improving oral hygiene, especially scraping or brushing the tongue.
Signs and symptoms
Hairy tongue largely occurs in the central part of the dorsal tongue, just anterior (in front) of the circumvallate papillae, although sometimes the entire dorsal surface may be involved. Discoloration usually accompanies hairy tongue, and may be yellow, brown or black. Apart from the appearance, the condition is typically asymptomatic, but sometimes people may experience a gagging sensation or a bad taste. There may also be associated oral malodor (intra-oral halitosis).The term "melanoglossia is also used to refer to there being black discolorations on the tongue without "hairs", which are also harmless and unrelated to black hairy tongue.
Causes
The cause is uncertain, but it is thought to be caused by accumulation of epithelial squames and proliferation of chromogenic (i.e., color-producing) microorganisms. There may be an increase in keratin production or a decrease in normal desquamation (shedding of surface epithelial cells). Many people with BHT are heavy smokers. Other possible associated factors are poor oral hygiene, general debilitation, hyposalivation (i.e., decreased salivary flow rate), radiotherapy, overgrowth of fungal or bacterial organisms, and a soft diet. Occasionally, BHT may be caused by the use of antimicrobial medications (e.g., tetracyclines), or oxidizing mouthwashes or antacids. A soft diet may be involved as normally food has an abrasive action on the tongue, which keeps the filiform papillae short. Pellagra, a condition caused by niacin (vitamin B3) deficiency, may cause a thick greyish fur to develop on the dorsal tongue, along with other oral signs.Transient surface discoloration of the tongue and other soft tissues in the mouth can occur in the absence of hairy tongue. Causes include smoking (or betel chewing), some foods and beverages (e.g., coffee, tea or liquorice), and certain medications (e.g., chlorhexidine, iron salts, or bismuth subsalicylate (Pepto-Bismol)).
Diagnosis
Diagnosis is usually made on the clinical appearance without the need for a tissue biopsy. However, when biopsies have been taken, the histologic appearance is one of marked elongation and hyperparakeratosis of the filiform papillae and numerous bacteria growing on the epithelial surface.Hairy tongue may be confused with hairy leukoplakia, however the latter usually occurs on the sides of the tongue and is associated with an opportunistic infection with Epstein–Barr virus on a background immunocompromise (almost always human immunodeficiency virus infection but rarely other conditions which suppress the immune system).
Classification
Hairy tongue (lingua villosa) refers to a marked accumulation of keratin on the filiform papillae on the dorsal surface of the tongue, giving a hair-like appearance. Black tongue (lingua nigra) refers to a black discoloration of the tongue, which may or may not be associated with hairy tongue. However, the elongated papillae of hairy tongue usually develop discoloration due to growth of pigment producing bacteria and staining from food. Hence the term black hairy tongue, although hairy tongue may also be discolored yellow or brown. Transient, surface discoloration that is not associated with hairy tongue can be brushed off. Drug-induced black hairy tongue specifically refers to BHT that develops because of medication.
Treatment
Treatment is by reassurance, as the condition is benign, and then by correction of any predisposing factors. This may be cessation of smoking or cessation/substitution of implicated medications or mouthwashes. Generally direct measures to return the tongue to its normal appearance involve improving oral hygiene, especially scraping or brushing the tongue before sleep. This promotes desquamation of the hyperparakeratotic papillae. Keratolytic agents (chemicals to remove keratin) such as podophyllin are successful, but carry safety concerns. Other reported successful measures include sodium bicarbonate mouthrinses, eating pineapple, sucking on a peach stone and chewing gum.
Prognosis
BHT is a benign condition, but people who are affected may be distressed at the appearance and possible halitosis, and therefore treatment is indicated.
Epidemiology
Hairy tongue occurs in about 0.5% of adults. However, the prevalence is variable depending on the population studied.
References
== External links == |
Ganglioneuroma | Ganglioneuroma is a rare and benign tumor of the autonomic nerve fibers arising from neural crest sympathogonia, which are completely undifferentiated cells of the sympathetic nervous system. However, ganglioneuromas themselves are fully differentiated neuronal tumors that do not contain immature elements.Ganglioneuromas most frequently occur in the abdomen, however these tumors can grow anywhere sympathetic nervous tissue is found. Other common locations include the adrenal gland, paraspinal retroperitoneum, posterior mediastinum, head, and neck. It is contained within the neuroblastic tumors group, which includes: Ganglioneuroma (benign), Ganglioneuroblastoma (intermediate), Neuroblastoma (aggressive).
Symptoms and signs
A ganglioneuroma is typically asymptomatic, and is typically only discovered when being examined or treated for another condition. Any symptoms will depend upon the tumors location and the nearby organs affected.For example, a tumor in the chest area may cause breathing difficulty, chest pain, and trachea compression. If the tumor is located lower in the abdomen, it may cause abdominal pain and bloating. A tumor near the spinal cord may cause spinal deformity or spinal compression, leading to pain and loss of muscle control or sensation in the legs and/or arms.These tumors may produce certain hormones, which can cause diarrhea, an enlarged clitoris (in females), high blood pressure, increased body hair, and sweating.
Cause
There are no known risk factors for ganglioneuromas. However, the tumors may be associated with some genetic problems, such as neurofibromatosis type 1.
Pathology
Pathologically, ganglioneuromas are composed of ganglion cells, Schwann cells and fibrous tissue. Ganglioneuromas are solid, firm tumours that typically are white when seen with the naked eye.
Diagnosis
Ganglioneuromas can be diagnosed visually by a CT scan, MRI scan, or an ultrasound of the head, abdomen, or pelvis. Blood and urine tests may be done to determine if the tumor is secreting hormones or other circulating chemicals. A biopsy of the tumor may be required to confirm the diagnosis.
Treatment
Because ganglioneuromas are benign, treatment may not be necessary, as it would expose patients to more risk than leaving it alone.If there are symptoms or major physical deformity, treatment usually consists of surgery to remove the tumor.
Prognosis
Most ganglioneuromas are noncancerous, thus expected outcome is usually good. However, a ganglioneuroma may become cancerous and spread to other areas, or it may regrow after removal.If the tumor has been present for a long time and has pressed on the spinal cord or caused other symptoms, it may have caused irreversible damage that cannot be corrected with the surgical removal of the tumor. Compression of the spinal cord may result in paralysis, especially if the cause is not detected promptly.
References
== External links == |
Rheumatoid lung disease | Rheumatoid lung disease is a disease of the lung associated with RA, rheumatoid arthritis. Rheumatoid lung disease is characterized by pleural effusion, pulmonary fibrosis, lung nodules and pulmonary hypertension. Common symptoms associated with the disease include shortness of breath, cough, chest pain and fever. It is estimated that about one quarter of people with rheumatoid arthritis develop this disease, which are more likely to develop among elderly men with a history of smoking.Rheumatoid lung is separate from but often associated with Interstitial lung disease(ILD).
Signs and symptoms
Most common:
Chest Pain
Cough
Fever
Shortness of breath
Joint pain, stiffness, swelling
Skin nodulesPeople may not present with all these symptoms or none at all.
From most to least common:
Pleural involvement (pleurisy, effusions)
Pulmonary parenchymal nodules, more common in men than in women
Rheumatoid-associated interstitial lung disease
Bronchiolitis obliterans organizing pneumonia
Obliterative bronchiolitis (obstructive lung disease/bronchiectasis)
Rheumatoid-associated pulmonary hypertension
Pulmonary vasculitis/arteritis
Shrinking lung syndrome
Miscellaneous: MTX, cricoarytenoid arthritis, infection, cancer
Causes
The exact cause of rheumatoid lung disease is unknown. However, associated factors could be due largely to smoking. Sometimes, the medicines used to treat rheumatoid arthritis, especially methotrexate, may result in lung disease.Prevention:
Stop smoking: Chemicals found in cigarettes can irritate already delicate lung tissue, leading to further complications.
Having regular checkups: The doctor could listen to lungs and monitor breathing, because lung problems that are detected early can be easier to treat.
Mechanism
RA is a complex and poorly understood disease.
However, the characteristic presence of antibodies to citrullinated proteins (anti-CCP) suggests that there are pathogenic mechanisms unique to RA. Recent studies suggest a link between smoking, HLA-DRBSE, anti-CCP and RA. Smoking has long been linked to RA and worsens articular disease as well as rheumatoid lung disease. Exposure to cigarette smoke leads to the activation of PADI enzymes that deaminate arginine to citrulline, producing autoantigens like citrullinated collagen and fibrinogen. Autoantigenic peptides containing citrulline residues are preferentially bound by HLA-DRB SE proteins and are presented to T cells, which interact with CCP-specific B cells found at sites containing autoantigen and produce inflammatory cytokines and autoantibodies, which accelerate disease. Bacterial or viral infections of the respiratory tract may also exacerbate pulmonary inflammation and rheumatoid lung disease.
Diagnosis
The diagnosis of RA was formerly based on detection of rheumatoid factor (RF). However, RF is also associated with other autoimmune diseases. The detection of anti-CCP is currently considered the most specific marker of RA. The diagnosis of rheumatoid lung disease is based on evaluation of pulmonary function, radiology, serology and lung biopsy. High resolution CT scans are preferred to chest X-rays due to their sensitivity and specificity.Associated doctors to diagnosis this properly would be a Rheumatologists or Pulmonologist.
Within a physical examination doctors could find possible indications, such as hearing crackles (rales) when listening to the lungs with a stethoscope. Or, there may be decreased breath sounds, wheezing, a rubbing sound, or normal breath sounds. When listening to the heart, there may be abnormal heart sounds. Bronchoscopic, video-assisted, or open lung biopsy allows the histological characterization of pulmonary lesions, which can distinguish rheumatoid lung disease from other interstitial lung diseases.The following tests may also show signs of rheumatoid lung disease:
Chest x-ray may show:
pleural effusion
lower zone predominant reticular or reticulonodular pattern
volume loss in advanced disease
skeletal changes, e.g. erosion of clavicles, glenohumeral erosive arthropathy, superior rib notching
Chest CT or HRCT features include:
pleural thickening or effusion
interstitial fibrosis
bronchiectasis
bronchiolitis obliterans
large rheumatoid nodules
single or multiple
tend to be based peripherally
may cavitate (necrobiotic lung nodules)
cavitation of a peripheral nodule can lead to pneumothorax or haemopneumothorax.
follicular bronchiolitis
small centrilobular nodules or tree-in-bud
rare
Caplan syndrome
Echocardiogram (may show pulmonary hypertension)
Lung biopsy (bronchoscopic, video-assisted, or open), which may show pulmonary lesions
Lung function tests
Needle inserted into the fluid around the lung (thoracentesis)
Blood tests for rheumatoid arthritis
Treatment
Many people with this condition have no symptoms. Treatment is aimed at the health problems causing the lung problem and the complications caused by the disorder.Fast-acting drugs for RA include aspirin and corticosteroids, which alleviate pain and reduce inflammation. Slow-acting drugs termed disease modifying antirheumatic drugs (DMARDs), include gold, methotrexate and hydroxychloroquine (Plaquenil), which promote disease remission and prevent progressive joint destruction. In patients with less severe RA, pain relievers, anti-inflammatory drugs and physical rest are sufficient to improve quality of life. In patients with joint deformity, surgery is the only alternative for recovering articular function.Prognosis is related to the underlying disorder and the type and severity of lung disease. In severe cases, lung transplantation can be considered. This is more common in cases of bronchiolitis obliterans, pulmonary fibrosis, or pulmonary hypertension. Most complications are not fatal, but does reduce life expectancy to an estimated 5 to 10 years.
Epidemiology
The prevalence of RA is around 0.3–1.2% (0.92% of Americans). Women are 2–3 times more susceptible than men. The prevalence of rheumatoid lung disease in patients with RA depends on the method used for diagnosis: chest X rays (5%), high resolution CT scans (10–40%).A study showed 582 patients with RA and 603 subjects without RA were followed for a mean of 16.4 and 19.3 years, respectively. The lifetime risk of developing ILD was 7.7% for RA patients and 0.9% for subjects without RA. The risk of developing ILD was higher in patients with older age at RA onset, among male patients and for individuals with parameters that indicate more severe RA.
Survival of RA patients diagnosed with ILD was worse compared to RA patients without ILD. ILD contributed approximately 13% to the excess mortality of patients with RA patients when compared to the general population.
History
Rheumatoid Lung was first described in 1948.1948, they published several cases of patients with RA who had severe erosive joint disease who also developed an interstitial lung and suggested there may be an association between the inflammatory joint disease and interstitial lung disease.1953, Anthony Caplan described rheumatoid nodules within the lung parenchyma, associated with pneumoconiosis in coal miners, who were exposed to coal dust.1954, rheumatoid lung nodules were found in patients with RA who were not exposed to coal dust and without pneumoconiosis.
1955 there was a short case series of about 10 patients with RA whose autopsies showed that the pleural disease was much higher in rheumatoid patients than in the general population, and much higher than what they had previously seen clinically.
1961, Cudkowicz described the first pulmonary function tests and lung biopsies were done in RA patients.
Research
According to a recent study, the main risk factors for RA-ILD are advancing age, male sex, greater RA disease activity, rheumatoid factor (RF) positivity, and elevated titers of anticitrullinated protein antibodies such as anticyclic citrullinated peptide. Cigarette smoking also appears to increase risk of RA-ILD, especially in patients with human leukocyte antigen DRB1.A recently published retrospective study by a team from Beijing Chao-Yang Hospital in Beijing, China, supported three of the risk factors listed for RA-ILD and identified an additional risk factor. In that study of 550 RA patients, logistic regression analysis of data collected on the 237 (43%) with ILD revealed that age, smoking, RF positivity, and elevated lactate dehydrogenase closely correlated with ILD.Recent studies have identified risk factors for disease progression and mortality. A retrospective study of 167 patients with RA-ILD determined that the usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) was a risk factor for progression, as were severe disease upon diagnosis and rate of change in pulmonary function test results in the first 6 months after diagnosis.
A study of 59 RA-ILD patients found no median survival difference between those with the UIP pattern and those without it. But the UIP group had more deaths, hospital admissions, need for supplemental oxygen, and decline in lung function.
== References == |
Infantile acropustulosis | Infantile acropustulosis is an intensely itchy vesicopustular eruption of the hands and feet.: 205 Involvement of scabies has been suggested.infantile acropustulosis is characterized by itchy papules and vesicles that are similar to those found in scabies "mosquito like bites" but there is absence of the typical burrowing with S like burrows on the skin and can occur in small babies as opposed to scabies mostly found on children and young adults.
See also
Acropustulosis
List of cutaneous conditions
References
== External links == |
Traction alopecia | Traction alopecia is a type of hair loss caused by a pulling force being applied to the hair.This commonly results from a person frequently wearing their hair in a particularly tight ponytail, pigtails, or braids. It is also seen occasionally in long-haired people who use barrettes to keep hair out of their faces. Traction alopecia is recession of the hairline due to chronic traction, or hair pulling, and is characterized by a fringe along the marginal hairline on physical exam. Even though this "fringe sign" is considered a useful clinical marker of this condition, cases of frontal fibrosing alopecia presenting with an unusual retention of the hairline (pseudo-fringe sign) have been described.
Cause
It is commonly seen with certain hair styles or braiding patterns that pull the hairline forcefully towards the vertex of the scalp, and has been reported more often in African American women (as some wear their hair tightly pulled back), in whom it can cause scarring. It has also been seen in female ballerinas, and in cultural traditions where the hair is voluntarily not cut in religious obeisance, the latter caused by progressively increasing weight of the hair itself. Traction alopecia is mechanical in cause, rather than androgenic, and treatment is typically not pharmaceutical. Management includes cessation of the chronic traction, cosmeses, with surgical restoration reserved for more severe cases.Traction alopecia is a substantial risk in hair weaves, which can be worn either to conceal hair loss, or purely for cosmetic purposes. The former involves creating a braid around the head below the existing hairline, to which an extended-wear hairpiece, or wig, is attached. Since the hair of the braid is still growing, it requires frequent maintenance, which involves the hairpiece being removed, the natural hair braided again, and the piece snugly reattached. The tight braiding and snug hairpiece cause tension on the hair that is already at risk for falling out. Traction Alopecia is one of the most common causes of hair loss in African American women.
Sikh men are also susceptible to traction alopecia if the hair under the turban is tied too tightly for many years.Other causes include:
Hairstyle. Although the aforementioned style is one of the culprits, hairstyles such as dreadlocks and single (extension) braids can also have the same effect. Men and women who have had traction alopecia have found that the hair loss occurs most at the hair line—primarily around the temples and the sides of their heads.
Headgear. Compressive safety helmets worn tightly and closely to the scalp are a cause of traction alopecia. The lining of tightly fitted safety helmets like those worn for activities such as motorcycling, cycling, skiing and snowboarding are responsible for the constant rubbing and tugging of localised areas of the hair and scalp. Frequent wearers or those who use such helmets for prolonged periods seem more likely to develop traction alopecia.
Chemicals. A condition known as CCCA (central cicatricial centrifugal alopecia), seen almost exclusively in African American women, can cause extensive hair loss. It is caused by a combination of too much stress (traction) on the hair and the use of harsh relaxers and dyes.
See also
Croydon facelift
Cicatricial alopecia
List of cutaneous conditions
References
External links
Causes of Hairloss Archived 2021-01-12 at the Wayback Machine |
Macrocytic anemia | The term macrocytic is from Greek words meaning "large cell". A macrocytic class of anemia is an anemia (defined as blood with an insufficient concentration of hemoglobin) in which the red blood cells (erythrocytes) are larger than their normal volume. The normal erythrocyte volume in humans is about 80 to 100 femtoliters (fL= 10−15 L). In metric terms the size is given in equivalent cubic micrometers (1 μm3 = 1 fL). The condition of having erythrocytes which (on average) are too large, is called macrocytosis. In contrast, in microcytic anemia, the erythrocytes are smaller than normal.
In a macrocytic anemia, the larger red cells are always associated with insufficient numbers of cells and often also insufficient hemoglobin content per cell. Both of these factors work to the opposite effect of larger cell size, to finally result in a total blood hemoglobin concentration that is less than normal (i.e., anemia).
Macrocytic anemia is not a disease in the sense of having a single pathology but, rather, is a condition. As such, it is the class name for a set of pathologies that all produce somewhat the same red blood cell abnormality. Different pathologies result in macrocytic-type anemias. Some of these pathologies produce slightly different sets of appearances in blood cells that are detectable from red and white cell morphology, and others are only detectable with chemical testing.
Causes
Megaloblastic anemias
Megaloblastic anemias represent a type of macrocytic anemia characterized by certain morphologic abnormalities noted on a peripheral blood smear examination. These abnormalities include the presence of enlarged oval shaped red blood cells (macroovalocytes) and hypersegmented neutrophils (defined as a neutrophil with six or more lobes). Hypersegmented neutrophils may be seen in the absence of macroovalocytes as hypersegmentation of neutrophils is an early sign of megaloblastic anemia and may precede the appearance of macroovalocytes; they may also be seen in other anemias (e.g., iron deficiency anemia) and thus are suggestive of megaloblastic anemia but not specific for it. An increased red cell distribution width (anisocytosis) also suggests megaloblastosis and is commonly seen in Vitamin B12 deficiency and folic acid deficiency. This type of anemia is caused by impaired DNA synthesis and repair, often from deficient thymidine production. Thiamine responsive megaloblastic anemia syndrome also causes megaloblastic anemia.The red blood cells grow larger because they cannot produce DNA quickly enough to divide at the right time as they grow and thus grow too large before division. Additional causes of megaloblastic anemia include medications that interfere with DNA synthesis or with the absorption or metabolism of Vitamin B12 or folate such as methotrexate, sulfasalazine, metformin, anticonvulsant medications (e.g., valproic acid or phenytoin), certain antibiotics (e.g., trimethoprim/sulfamethoxazole), antiretroviral medications, cholestyramine, triamterene, and nitrous oxide.
Non-Megaloblastic anemias
Red cell membrane disorders producing codocytes
Other disorders which cause macrocytosis without DNA replication problems (i.e., non-megaloblastic macrocytic anemias), are disorders associated with increased red cell membrane surface area, such as pathologies of the liver and spleen which produce codocytes or "target cells" which have a central collection of hemoglobin surrounded by a pallor (a thin area) then followed by a thicker collection of hemoglobin at the rim of the cell.
Alcohol
Round macrocytes which are not codocytes are produced in chronic alcoholism (which produces a mild macrocytosis even in the absence of vitamin deficiency), apparently as a direct toxic effect of alcohol specifically on the bone marrow. Excessive alcohol consumption is one of the most common causes of macrocytosis and non-megaloblastic macrocytic anemia.
Association with rapid red cell turnover and reticulocytosis
Mild macrocytosis is a common finding associated with rapid blood restoration or production, since in general, "fresh" or newly produced red cells (reticulocytes) are larger than the mean (average) size, due to slow shrinkage of normal cells over a normal red cell circulating lifetime. Thus, chronic obstructive pulmonary disease (COPD), in which red cells are rapidly produced in response to low oxygen levels in the blood, often produces mild macrocytosis. The macrocytosis associated with COPD is also attributed to excess cell water secondary to carbon dioxide retention. Also, rapid blood replacement from the marrow after a traumatic blood loss, or rapid red blood cell turnover from rapid hemolysis (G6PD deficiency), also often produces mild macrocytosis in the associated anemia.
Diagnosis
Several tests can help to elucidate the underlying cause of a persons macrocytic anemia. A peripheral blood smear is often recommended as a first step in the evaluation to determine if the macrocytic anemia has megaloblastic features since the causes of megaloblastic and non-megaloblastic macrocytic anemia differ and making this distinction can narrow the list of differential diagnoses.For non-megaloblastic macrocytic anemias, a reticulocyte count may be helpful. Non-megaloblastic macrocytic anemias with a low reticulocyte count (indicating a poor bone marrow response to the anemia) suggest liver disease (e.g., cirrhosis), hypothyroidism, toxic effects of alcohol on the bone marrow, or myelodysplasia. In contrast, non-megaloblastic macrocytic anemias associated with a high reticulocyte count (reticulocytosis) may be caused by hemolysis or bleeding.For megaloblastic macrocytic anemias, useful tests may include serum levels of Vitamin B12, methylmalonic acid, and homocysteine. If there is no clear evidence of Vitamin B12 or folic acid deficiency, additional causes of megaloblastic anemia include copper deficiency, medications, and certain inborn errors of metabolism.
Epidemiology
Macrocytic anemias have several causes but with the implementation of folic acid fortification in North America, folic acid deficiency has become a rare cause of megaloblastic macrocytic anemia in that part of the world. In this region, Vitamin B12 deficiency is a far more common cause of megaloblastic macrocytic anemia. In countries that have not put such practices into place — including most European nations — folic acid deficiency remains a common cause of macrocytic anemia.
See also
List of circulatory system conditions
References
== External links == |
Primordial dwarfism | Primordial dwarfism (PD) is a form of dwarfism that results in a smaller body size in all stages of life beginning from before birth. More specifically, primordial dwarfism is a diagnostic category including specific types of profoundly proportionate dwarfism, in which individuals are extremely small for their age, even as a fetus. Most individuals with primordial dwarfism are not diagnosed until they are about 3–5 years of age.
Medical professionals typically diagnose the fetus as being small for gestational age, or as showing intrauterine growth restriction when an ultrasound is conducted. Typically, people with primordial dwarfism are born with very low birth weights. After birth, growth continues at a much slower rate, leaving individuals with primordial dwarfism perpetually years behind their peers in stature and in weight.
Most cases of short stature are caused by skeletal or endocrine disorders. The five subtypes of primordial dwarfism are among the most severe forms of the 200 types of dwarfism.
There are as yet no effective treatments for primordial dwarfism. It is rare for individuals affected by primordial dwarfism to live past the age of 30. In the case of microcephalic osteodysplastic primordial dwarfism type II (MOPDII), there can be increased risk of vascular problems, which may cause premature death.
Causes
It is known that PD is caused by inheriting a mutant gene from each parent. The lack of normal growth in the disorder is not due to a deficiency of growth hormone, as in hypopituitary dwarfism. Administering growth hormone, therefore, has little or no effect on the growth of the individual with primordial dwarfism, except in the case of Russell–Silver syndrome (RSS). Individuals with RSS respond favorably to growth hormone treatment. Children with RSS that are treated with growth hormone before puberty may achieve several inches of additional height. In January 2008, it was published that mutations in the pericentrin gene (PCNT) were found to cause primordial dwarfism. Pericentrin has a role in cell division, proper chromosome segregation and cytokinesis.
Another gene that has been implicated in this condition is DNA2. Mutations in this gene have been implicated in Seckel syndrome.
Diagnosis
Since primordial dwarfism disorders are extremely rare, misdiagnosis is common. Because children with PD do not grow like other children, poor nutrition, a metabolic disorder, or a digestive disorder may be diagnosed initially. The correct diagnosis of PD may not be made until the child is 5 years old and it becomes apparent that the child has severe dwarfism.
Types
Notable cases
Jyoti Amge - Indian actress, worlds shortest woman since her 18th birthday on 16 December 2011
Caroline Crachami – known as the "Sicilian Fairy", displayed in the Hunterian Museum in Scotland
Chandra Bahadur Dangi – smallest man of all time
Nelson de la Rosa – actor linked to the USA baseball team Boston Red Sox
Aditya Dev – worlds smallest bodybuilder
Bridgette Jordan and Brad Jordan – siblings
Khagendra Thapa Magar – worlds shortest man from his 18th birthday on 14 October 2010 to 13 June 2011
Gul Mohammed – former smallest man of all time
He Pingping – worlds shortest ambulatory man until his death in 2010
Weng Weng – Filipino actor and martial artist
Lucía Zárate – Mexican entertainer and first person identified to have MOPD II
See also
Gigantism
Dwarfism
Psychogenic dwarfism
List of people with dwarfism
== References == |
Pemphigus vegetans | Pemphigus vegetans is a localized form of pemphigus vulgaris.
in which there is a localized vegetating papillomatous response. The eroded areas do not heal like usual but form papillomatous growth and vegetation.
Accounts for 1-2% of pemphigus cases and is a relatively benign variant of pemphigus vulgaris.
Two forms are recognized:
Pemphigus vegetans of Neumann is a localized disease of pemphigus vulgaris slightly more extensive than pemphigus vegetans of Hallopeau. : 568 This type is more common and characterized by early lesions similar to Pemphigus Vulgaris with large bullae and erosive areas. Healing is through formation of granulation tissue. It is named for the Austrian Dermatologist, Isidor Neumann.
Pemphigus vegetans of Hallopeau is a disease of localized pemphigus vulgaris. : 568 It is named for François Henri Hallopeau. This type is less aggressive and has pustules not bullae. These pustules heal by verrucous hyperkeratotic vegetations.
See also
List of cutaneous conditions
Pemphigus
List of conditions caused by problems with junctional proteins
References
== External links == |
Chondromalacia patellae | Chondromalacia patellae (also known as CMP) is an inflammation of the underside of the patella and softening of the cartilage.
The cartilage under the kneecap is a natural shock absorber, and overuse, injury, and many other factors can cause increased deterioration and breakdown of the cartilage. The cartilage is no longer smooth and therefore movement and use is very painful. While it often affects young individuals engaged in active sports, it also afflicts older adults who overwork their knees.Chondromalacia patellae is sometimes used synonymously with patellofemoral pain syndrome. However, there is general consensus that patellofemoral pain syndrome applies only to individuals without cartilage damage. This condition is also known as Chondrosis. The term literally translates to softening (malakia) of cartilage (chondros) behind patella in Greek.
Cause
The condition may result from acute injury to the patella or chronic friction between the patella and a groove in the femur through which it passes during knee flexion. Possible causes include a tight iliotibial band, neuromas, bursitis, overuse, malalignment, core instability, and patellar maltracking.Pain at the front or inner side of the knee is common in adults of all ages especially when engaging in soccer, gymnastics, cycling, rowing, tennis, ballet, basketball, horseback riding, volleyball, running, combat sports, figure skating, snowboarding, skateboarding and even swimming. The pain is typically felt after prolonged sitting. Skateboarders most commonly experience this injury in their non-dominant foot due to the constant kicking and twisting required of it. Swimmers acquire it doing the breaststroke, which demands an unusual motion of the knee. People who are involved in an active lifestyle with high impact on the knees are at greatest risk. Proper management of physical activity may help prevent worsening of the condition. Athletes are advised to talk to a physician for further medical diagnosis, as symptoms may be similar to more serious problems within the knee. Tests are not necessarily needed for diagnosis, but in some situations they may confirm diagnosis or rule out other causes for pain. Commonly used tests are blood tests, MRI scans, and arthroscopy.While the term chondromalacia sometimes refers to abnormal-appearing cartilage anywhere in the body, it most commonly denotes irritation of the underside of the kneecap (or "patella"). The patellas posterior surface is covered with a layer of smooth cartilage, which the base of the femur normally glides smoothly against when the knee is bent. However, in some individuals the kneecap tends to rub against one side of the knee joint, irritating the cartilage and causing knee pain.
Diagnosis
When investigating a possible diagnosis of chondromalacia, a physician will carry out a complete examination of the affected knee. The physician will palpate the patella and surrounding tissue, feel the joint to observe when and how the distress manifests and obtains a list of symptoms and clinical history. The following tests or procedures may be used to refine the diagnosis:
A knee X-ray and/or blood test – this can assist to exclude certain types of arthritis or inflammation.
Magnetic Resonance Imaging (MRI) – to observe cartilage condition and assess deterioration
Arthroscopy – a low invasive approach to image the inside of the knee joint by inserting an endoscope into the knee joint.
Treatment
In the absence of cartilage damage, pain at the front of the knee due to overuse can be managed with a combination of RICE (rest, ice, compression, elevation), anti-inflammatory medications, and physiotherapy.Usually chondromalacia develops without swelling or bruising and most individuals benefit from rest and adherence to an appropriate physical therapy program. Allowing inflammation to subside while avoiding irritating activities for several weeks is followed by a gradual resumption. Cross-training activities such as swimming – using strokes other than the breaststroke – can help to maintain general fitness and body composition. This is beneficial until a physical therapy program emphasizing strengthening and flexibility of the hip and thigh muscles can be undertaken. Use of nonsteroidal anti-inflammatory medication is also helpful to minimize the swelling amplifying patellar pain. Treatment with surgery is declining in popularity due to positive non-surgical outcomes and the relative ineffectiveness of surgical intervention.
See also
Knee
Knee pain
Patellofemoral pain syndrome
Knee osteoarthritis
Plica syndrome
Iliotibial band syndrome
References
External links
Plica Syndrome at eMedicine |
Persistent hyperplastic primary vitreous | Persistent hyperplastic primary vitreous (PHPV), also known as persistent fetal vasculature (PFV), is a rare congenital developmental anomaly of the eye that results following failure of the embryological, primary vitreous and hyaloid vasculature to regress. It can be present in three forms: purely anterior (persistent tunica vasculosa lentis and persistent posterior fetal fibrovascular sheath of the lens), purely posterior (falciform retinal septum and ablatio falcicormis congenita) and a combination of both. Most examples of PHPV are unilateral and non-hereditary. When bilateral, PHPV may follow an autosomal recessive or autosomal dominant inheritance pattern.
Symptoms
The primary vitreous used in formation of the eye during fetal development remains in the eye upon birth and is hazy and scarred. The symptoms are leukocoria, strabismus, nystagmus and blurred vision, blindness.
Causes
Trisomy 13 (Patau syndrome)
Norrie disease
Walker-Warburg syndrome
Autosomal dominant
Autosomal recessive
Diagnosis
Causes a white reflex in the affected eye (leukocoria), prompting further investigation.
Treatment
Pars plana lensectomy with or without vitrectomy and trabeculectomy.
See also
Persistent tunica vasculosa lentis
References
External links
GeneReviews/NIH/NCBI/UW entry on NDP-Related Retinopathies |
Congenital hereditary endothelial dystrophy | Congenital hereditary corneal dystrophy (CHED) is a form of corneal endothelial dystrophy that presents at birth.
CHED was previously subclassified into two subtypes: CHED1 and CHED2. However in 2015, the International Classification of Corneal Dystrophies (IC3D) renamed the condition "CHED1" to become posterior polymorphous corneal dystrophy, and renamed the condition "CHED2" to become, simply, CHED. Consequently, the scope of this article is restricted to the condition currently referred to as CHED
Signs and symptoms
CHED presents congenitally, but has a stationary course. The cornea exhibits a variable degree of clouding: from a diffuse haze, to a "ground glass" appearance, with occasional focal gray spots. The cornea thickens to between two and three times is normal thickness. Rarely, sub-epithelial band keratopathy and elevated intraocular pressure occur. Patients have blurred vision and nystagmus, however it is rare for the condition to be associated with either epiphora or photophobia with this.
Genetics
CHED exhibits autosomal recessive inheritance, with 80% of cases linked to mutations in SLC4A11 gene. The SLC4A11 gene encodes solute carrier family 4, sodium borate transporter, member 11.
Pathology
Histologically, the Descemets membrane in CHED becomes diffusely thickened and laminated. Multiple layers of basement membrane-like material appear to form on the posterior part of Descemets membrane. The endothelial cells are sparse - they become atrophic and degenerated, with many vacuoles. The corneal stroma becomes severely disorganised; the lamellar arrangement of the fibrils becomes disrupted.
Diagnosis
Management
Management of CHED primarily involves corneal transplantation. The age that corneal transplantation is required is variable, however, it is usually necessary fairly early in life.
See also
Posterior polymorphous corneal dystrophy (for the condition previously referred to as CHED1)
Corneal dystrophy
== References == |
Pulseless electrical activity | Pulseless electrical activity (PEA) refers to cardiac arrest in which the electrocardiogram shows a heart rhythm that should produce a pulse, but does not. Pulseless electrical activity is found initially in about 55% of people in cardiac arrest.Under normal circumstances, electrical activation of muscle cells precedes mechanical contraction of the heart (known as electromechanical coupling). In PEA, there is electrical activity but insufficient cardiac output to generate a pulse and supply blood to the organs, whether the heart itself is failing to contract or otherwise. While PEA is classified as a form of cardiac arrest, significant cardiac output may still be present, which may be determined and best visualized by bedside ultrasound (echocardiography).
Cardiopulmonary resuscitation (CPR) is the first treatment for PEA, while potential underlying causes are identified and treated. The medication epinephrine (aka adrenaline) may be administered. Survival is about 20%.
Signs and symptoms
Pulseless electrical activity leads to a loss of cardiac output, and the blood supply to the brain is interrupted. As a result, PEA is usually noticed when a person loses consciousness and stops breathing spontaneously. This is confirmed by examining the airway for obstruction, observing the chest for respiratory movement, and feeling the pulse (usually at the carotid artery) for a period of 10 seconds.
Causes
These possible causes are remembered as the 6 Hs and the 6 Ts. See Hs and Ts
Hypovolemia
Hypoxia
Hydrogen ions (Acidosis)
Hyperkalemia or Hypokalemia
Hypoglycemia
Hypothermia
Tablets or Toxins
Cardiac Tamponade
Tension pneumothorax
Thrombosis (e.g., myocardial infarction, pulmonary embolism)
Tachycardia
Trauma (e.g., hypovolemia from blood loss)The possible mechanisms by which the above conditions can cause pulseless in PEA are the same as those recognized as producing circulatory shock states. These are (1) impairment of cardiac filling, (2) impaired pumping effectiveness of the heart, (3) circulatory obstruction and (4) pathological vasodilation causing loss of vascular resistance and excess capacitance. More than one mechanism may be involved in any given case.
Diagnosis
The absence of a pulse confirms a clinical diagnosis of cardiac arrest, but PEA can only be distinguished from other causes of cardiac arrest with a device capable of electrocardiography (ECG/EKG). In PEA, there is organised or semi-organised electrical activity in the heart as opposed to asystole (flatline) or to the disorganised electrical activity of either ventricular fibrillation or ventricular tachycardia.
Treatment
Cardiac resuscitation guidelines (ACLS/BCLS) advise that cardiopulmonary resuscitation should be initiated promptly to maintain cardiac output until the PEA can be corrected. The approach in treatment of PEA is to treat the underlying cause, if known (e.g. relieving a tension pneumothorax). Where an underlying cause for PEA cannot be determined and/or reversed, the treatment of pulseless electrical activity is similar to that for asystole. There is no evidence that external cardiac compression can increase cardiac output in any of the many scenarios of PEA, such as hemorrhage, in which impairment of cardiac filling is the underlying mechanism producing loss of a detectable pulse.A priority in resuscitation is placement of an intravenous or intraosseous line for administration of medications. The mainstay of drug therapy for PEA is epinephrine (adrenaline) 1 mg every 3–5 minutes. Although previously the use of atropine was recommended in the treatment of PEA/asystole, this recommendation was withdrawn in 2010 by the American Heart Association due to lack of evidence for therapeutic benefit. Epinephrine too has a limited evidence base, and it is recommended on the basis of its mechanism of action.Sodium bicarbonate 1meq per kilogram may be considered in this rhythm as well, although there is little evidence to support this practice. Its routine use is not recommended for patients in this context, except in special situations (e.g. preexisting metabolic acidosis, hyperkalemia, tricyclic antidepressant overdose).All of these drugs should be administered along with appropriate CPR techniques. Defibrillators cannot be used to correct this rhythm, as the problem lies in the response of the myocardial tissue to electrical impulses.
References
== External links == |
Hawkinsinuria | Hawkinsinuria is an autosomal dominant metabolic disorder affecting the metabolism of tyrosine.Normally, the breakdown of the amino acid tyrosine involves the conversion of 4-hydroxyphenylpyruvate to homogentisate by 4-hydroxyphenylpyruvate dioxygenase. Complete deficiency of this enzyme would lead to tyrosinemia III. In rare cases, however, the enzyme is still able to produce the reactive intermediate 1,2-epoxyphenyl acetic acid, but is unable to convert this intermediate to homogentisate. The intermediate then spontaneously reacts with glutathione to form 2-L-cystein-S-yl-1,4-dihydroxy-cyclohex-5-en-1-yl acetic acid (hawkinsin).Patients present with metabolic acidosis during the first year of life, and growth arrest around the time of weaning off breast milk. Treatment involves a diet containing a low amount of phenylalanine and tyrosine. Tolerance toward these amino acids normalizes as the patients get older. Then only a chlorine-like smell of the urine indicates the presence of the condition. Patients have a normal life and do not require treatment or a special diet.The production of hawkinsin is the result of a gain-of-function mutation. Inheritance of hawkinsinuria is therefore autosomal dominant (presence of a single mutated copy of the gene causes the condition). The gene affected is the HPD gene encoding 4-hydroxyphenylpyruvic acid dioxygenase, on chromosome 12q24. It is unusual in that most other inborn errors of metabolism are caused by loss-of-function mutations, and hence have recessive inheritance (condition occurs only if both copies are mutated).
See also
4-Hydroxyphenylpyruvate dioxygenase
References
== External links == |
Lithium toxicity | Lithium toxicity, also known as lithium overdose, is the condition of having too much lithium. Symptoms may include a tremor, increased reflexes, trouble walking, kidney problems, and an altered level of consciousness. Some symptoms may last for a year after levels return to normal. Complications may include serotonin syndrome.Lithium toxicity can occur due to excessive intake or decreased excretion. Excessive intake may be either a suicide attempt or accidental. Decreased excretion may occur as a result of dehydration such as from vomiting or diarrhea, a low sodium diet, or from kidney problems. The diagnosis is generally based on symptoms and supported by a lithium level of greater than 1.2 mEq/L.Gastric lavage and whole bowel irrigation may be useful if done early. Activated charcoal is not effective. For severe toxicity hemodialysis is recommended. The risk of death is generally low. Acute toxicity generally has better outcomes than chronic toxicity. In the United States about 5,000 cases are reported to poison control centers a year. Lithium toxicity was first described in 1898.
Signs and symptoms
Symptoms of lithium toxicity can be mild, moderate, or severe.Mild symptoms include nausea, feeling tired, and tremor occur at a level of 1.5 to 2.5 mEq/L. Moderate symptoms include confusion, an increased heart rate, and low muscle tone occur at a level of 2.5 to 3.5 mEq/L. Severe symptoms include coma, seizures, low blood pressure and increased body temperature which occur at a lithium concentration greater than 3.5 mEq/L. When lithium overdoses produce neurological deficits or cardiac toxicity, the symptoms are considered serious and can be fatal.
Acute toxicity
In acute toxicity, people have primarily gastrointestinal symptoms such as vomiting and diarrhea, which may result in volume depletion. During acute toxicity, lithium distributes later into the central nervous system causing dizziness and other mild neurological symptoms.
Chronic toxicity
In chronic toxicity, people have primarily neurological symptoms which include nystagmus, tremor, hyperreflexia, ataxia, and change in mental status. During chronic toxicity, the gastrointestinal symptoms seen in acute toxicity are less prominent. The symptoms are often vague and nonspecific.
Acute on chronic toxicity
In acute on chronic toxicity, people have symptoms of both acute and chronic toxicity.
Complications
People who survive an intoxication episode may develop persistent health problems. This group of persistent health symptoms are called syndrome of irreversible lithium-effectuated neurotoxicity (SILENT). The syndrome presents with irreversible neurological and neuro-psychiatric effects. The neurological signs are cerebellar dysfunction, extrapyramidal symptoms, and brainstem dysfunction. The neuro-psychiatric findings present with memory deficits, cognitive deficits, and sub-cortical dementia. For a diagnosis, the syndrome requires the absence of prior symptoms and persistence of symptoms for greater than 2 months after cessation of lithium.
Pathophysiology
Lithium is readily absorbed from the gastrointestinal tract. It is distributed to the body with higher levels in the kidney, thyroid, and bone as compared to other tissues. Since lithium is almost exclusively excreted by the kidneys, people with preexisting chronic kidney disease are at high risk of developing lithium intoxication. The drug itself is also known to be nephrotoxic, opening up the possibility of spontaneous emergence of toxicity at doses that were previously well-tolerated. Lithium toxicity can be mistaken for other syndromes associated with antipsychotic use, such as serotonin syndrome because lithium increases serotonin metabolites in the cerebrospinal fluid.There are several drug interactions with lithium. Interactions can occur from typical antipsychotics or atypical antipsychotics. In particular, certain drugs enhance lithium levels by increasing renal re-absorption at the proximal tubule. These drugs are angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs and thiazide diuretics.
Diagnosis
The diagnosis is generally based on symptoms and supported by a lithium level blood level. Blood levels are most useful six to twelve hours after the last dose. The normal serum lithium level in those on treatment is between 0.6-1.2 mEq/L. Some blood tubes contain lithium heparin which may result in falsely positive results.When lithium toxicity is suspected tests may include:
fingerstick glucose
serum lithium concentration
basic metabolic panel to assess renal function
serum acetaminophen and salicylate concentrations to rule out other sources of acute ingestion
urine pregnancy tests to ensure management does not cause abortionImaging tests are not helpful.
Treatment
If the persons lithium toxicity is mild or moderate, lithium dosage is reduced or stopped entirely. If the toxicity is severe, lithium may need to be removed from the body. The removal of lithium is done in a hospital emergency department. It may involve:
Gastric lavage. A tube is placed through the nose or mouth into the stomach. The tube is used to remove lithium that has not been digested yet. It may also be used to put medicines directly into the stomach to help stop lithium from being absorbed.
Use of an artificial kidney to clean the blood (dialysis). This is usually done only in the most severe cases.
Diuretic medications such as furosemide and hydration via intravenous normal saline appear to be effective in speeding the removal of lithium and also rehydrate patients whove lost fluids.
Hemodialysis. Hemodialysis is widely advocated as a means of reducing the risk of permanent neurological sequelae following lithium poisoning. Although hemodialysis clearly enhances the elimination of lithium, it is unclear whether this translates into improved patient outcomes.People may be sent home once their lithium level is less than 1.5 mEq/L and they have no symptoms.
See also
Biology and pharmacology of chemical elements
Diabetes insipidus
== References == |
Meningococcal disease | Meningococcal disease describes infections caused by the bacterium Neisseria meningitidis (also termed meningococcus). It has a high mortality rate if untreated but is vaccine-preventable. While best known as a cause of meningitis, it can also result in sepsis, which is an even more damaging and dangerous condition. Meningitis and meningococcemia are major causes of illness, death, and disability in both developed and under-developed countries.
There are approximately 2,600 cases of bacterial meningitis per year in the United States, and on average 333,000 cases in developing countries. The case fatality rate ranges between 10 and 20 percent. The incidence of endemic meningococcal disease during the last 13 years ranges from 1 to 5 per 100,000 in developed countries, and from 10 to 25 per 100,000 in developing countries. During epidemics the incidence of meningococcal disease approaches 100 per 100,000. Meningococcal vaccines have sharply reduced the incidence of the disease in developed countries.
The diseases pathogenesis is not fully understood. Neisseria meningitidis colonises a substantial proportion of the general population harmlessly, but in a very small percentage of individuals it can invade the bloodstream, affecting the entire body, most notably limbs and brain, causing serious illness. Over the past few years, experts have made an intensive effort to understand specific aspects of meningococcal biology and host interactions; however, the development of improved treatments and effective vaccines is expected to depend on novel efforts by workers in many different fields.While meningococcal disease is not as contagious as the common cold (which is spread through casual contact), it can be transmitted through saliva and occasionally through close, prolonged general contact with an infected person.
Types
Meningococcemia
Meningococcemia, like many other gram-negative blood infections, can cause disseminated intravascular coagulation (DIC), which is the inappropriate clotting of blood within the vessels. DIC can cause ischemic tissue damage when upstream thrombi obstruct blood flow and haemorrhage because clotting factors are exhausted. Small bleeds into the skin cause the characteristic petechial rash, which appears with a star-like shape. This is due to the release of toxins into the blood that break down the walls of blood vessels. A rash can develop under the skin due to blood leakage that may leave red or brownish pinprick spots, which can develop into purple bruising. Meningococcal rash can usually be confirmed by a glass test in which the rash does not fade away under pressure.
Meningitis
Meningococcal meningitis is a form of bacterial meningitis. Meningitis is a disease caused by inflammation and irritation of the meninges, the membranes surrounding the brain and spinal cord. In meningococcal meningitis this is caused by the bacteria invading the cerebrospinal fluid and circulating through the central nervous system. Sub-Saharan Africa, the Americas, Western Europe, the UK, and Ireland still face many challenges combating this disease.
Other types
As with any gram-negative bacterium, N. meningitidis can infect a variety of sites.Meningococcal pneumonia can appear during influenza pandemics and in military camps. This is a multilobar, rapidly evolving pneumonia, sometimes associated with septic shock. With prompt treatment, the prognosis is excellent. Another alternative is dexamethasone with vancomycin and meropenem. Pericarditis can appear, either as a septic pericarditis with grave prognosis or as a reactive pericarditis in the wake of meningitis or septicaemia.
Signs and symptoms
Meningitis
The patient with meningococcal meningitis typically presents with high fever, nuchal rigidity (stiff neck), Kernigs sign, severe headache, vomiting, purpura, photophobia, and sometimes chills, altered mental status, or seizures. Diarrhea or respiratory symptoms are less common. Petechiae are often also present, but do not always occur, so their absence should not be used against the diagnosis of meningococcal disease. Anyone with symptoms of meningococcal meningitis should receive intravenous antibiotics before the results of lumbar puncture, as delay in treatment worsens the prognosis.
Meningococcemia
Symptoms of meningococcemia are, at least initially, similar to those of influenza. Typically, the first symptoms include fever, nausea, myalgia, headache, arthralgia, chills, diarrhea, stiff neck, and malaise. Later symptoms include septic shock, purpura, hypotension, cyanosis, petechiae, seizures, anxiety, and multiple organ dysfunction syndrome. Acute respiratory distress syndrome and altered mental status may also occur. The petechial rash appear with the star-like shape. Meningococcal sepsis has a greater mortality rate than meningococcal meningitis, but the risk of neurologic sequelae is much lower.
Pathogenesis
Meningococcal disease causes life-threatening meningitis and sepsis conditions. In the case of meningitis, bacteria attack the lining between the brain and skull called the meninges. Infected fluid from the meninges then passes into the spinal cord, causing symptoms including stiff neck, fever and rashes. The meninges (and sometimes the brain itself) begin to swell, which affects the central nervous system.Even with antibiotics, approximately 1 in 10 people who have meningococcal meningitis will die; however, about as many survivors of the disease lose a limb or their hearing, or experience permanent brain damage. The sepsis type of infection is much more deadly, and results in a severe blood poisoning called meningococcal sepsis that affects the entire body. In this case, bacterial toxins rupture blood vessels and can rapidly shut down vital organs. Within hours, patients health can change from seemingly good to mortally ill.The N. meningitidis bacterium is surrounded by a slimy outer coat that contains disease-causing endotoxin. While many bacteria produce endotoxin, the levels produced by meningococcal bacteria are 100 to 1,000 times greater (and accordingly more lethal) than normal. As the bacteria multiply and move through the bloodstream, it sheds concentrated amounts of toxin. The endotoxin directly affects the heart, reducing its ability to circulate blood, and also causes pressure on blood vessels throughout the body. As some blood vessels start to hemorrhage, major organs like the lungs and kidneys are damaged.Patients with meningococcal disease are treated with a large dose of antibiotic. The systemic antibiotic flowing through the bloodstream rapidly kills the bacteria but, as the bacteria are killed, even more toxin is released. It takes up to several days for the toxin to be neutralized from the body by using continuous liquid treatment and antibiotic therapy.
Prevention
The most important form of prevention is a vaccine against N. meningitidis. Different countries have different strains of the bacteria and therefore use different vaccines. Twelve serogroups (strains) exist with six having the potential to cause a major epidemic - A, B, C, X, Y and W135 are responsible for virtually all cases of the disease in humans. Vaccines are currently available against all six strains, including the newest vaccine against serogroup B. The first vaccine to prevent meningococcal serogroup B (meningitis B) disease was approved by the European Commission on 22 January 2013. The vaccine is manufactured by GlaxoSmithKline and sold under the trade name Bexsero. Bexsero is for use in all age groups from two months of age and older.Menveo and Mencevax of GlaxoSmithKline Vaccines, Menactra and Menomune of Sanofi-Aventis, and NmVac4-A/C/Y/W-135 (has not been licensed in the US) of JN-International Medical Corporation, are the commonly used vaccines. Vaccines offer significant protection from three to five years (plain polysaccharide vaccine Menomune, Mencevax and NmVac-4) to more than eight years (conjugate vaccine Menactra).
Vaccinations
Children
Children 2–10 years of age who are at high risk for meningococcal disease such as certain chronic medical conditions and travel to or reside in countries with hyperendemic or epidemic meningococcal disease should receive primary immunization. Although safety and efficacy of the vaccine have not been established in children younger than 2 years of age and under outbreak control, the unconjugated vaccine can be considered.
Adolescents
Primary immunization against meningococcal disease with meningitis A, C, Y and W-135 vaccines is recommended for all young adolescents at 11–12 years of age and all unvaccinated older adolescents at 15 years of age. Although conjugate vaccines are the preferred meningococcal vaccine in adolescents 11 years of age or older, polysaccharide vaccines are an acceptable alternative if the conjugated vaccine is unavailable.
Adults
Primary immunization with meningitis A, C, Y and W-135 vaccines is recommended for college students who plan to live in dormitories, although the risk for meningococcal disease for college students 18–24 years of age is similar to that of the general population of similar age.Routine primary immunization against meningococcal disease is recommended for most adults living in areas where meningococcal disease is endemic or who are planning to travel to such areas. Although conjugate vaccines are the preferred meningococcal vaccine in adults 55 years of age or younger, polysaccharide vaccines are an acceptable alternative for adults in this age group if the conjugated vaccine is unavailable. Since safety and efficacy of conjugate vaccines in adults older than 55 years of age have not been established to date, polysaccharide vaccines should be used for primary immunization in this group.
Medical staff
Health care people should receive routine immunization against meningococcal disease for laboratory personnel who are routinely exposed to isolates of N. meningitidis. Laboratory personnel and medical staff are at risk of exposure to N. meningitides or to patients with meningococcal disease. Hospital Infection Control Practices Advisory Committee (HICPAC) recommendations regarding immunization of health-care workers that routine vaccination of health-care personnel is recommended, Any individual 11–55 years of age who wishes to reduce their risk of meningococcal disease may receive meningitis A, C, Y and W-135 vaccines and those older than 55 years of age. Under certain circumstances if unvaccinated health-care personnel cannot get vaccinated and who have intensive contact with oropharyngeal secretions of infected patients and who do not use proper precautions should receive anti-infective prophylaxis against meningococcal infection (i.e., 2-day regimen of oral rifampicin or a single dose of IM ceftriaxone or a single dose of oral ciprofloxacin).
USA Military recruits
Because the risk of meningococcal disease is increased among USAs military recruits, all military recruits routinely receive primary immunization against the disease.
Travelers
Immunization against meningococcal disease is not a requirement for entry into any country, unlike Yellow fever. Only Saudi Arabia requires that travelers to that country for the annual Hajj and Umrah pilgrimage have a certificate of vaccination against meningococcal disease, issued not more than 3 years and not less than 10 days before arrival in Saudi Arabia.Travelers to or residents of areas where N. meningitidis is highly endemic or epidemic are at risk of exposure should receive primary immunization against meningococcal disease.
HIV-infected individuals
HIV-infected individuals are likely to be at increased risk for meningococcal disease; HIV-infected individuals who wish to reduce their risk of meningococcal disease may receive primary immunization against meningococcal disease. Although efficacy of meningitis A, C, Y and W-135 vaccines have not been evaluated in HIV-infected individuals to date, HIV-infected individuals 11–55 years of age may receive primary immunization with the conjugated vaccine. Vaccination against meningitis does not decrease CD4+ T-cell counts or increase viral load in HIV-infected individuals, and there has been no evidence that the vaccines adversely affect survival.
Close contacts
Protective levels of anticapsular antibodies are not achieved until 7–14 days following administration of a meningococcal vaccine, vaccination cannot prevent early onset disease in these contacts and usually is not recommended following sporadic cases of invasive meningococcal disease. Unlike developed countries, in sub-Saharan Africa and other under developed countries, entire families live in a single room of a house.Meningococcal infection is usually introduced into a household by an asymptomatic person. Carriage then spreads through the household, reaching infants usually after one or more other household members have been infected. Disease is most likely to occur in infants and young children who lack immunity to the strain of organism circulating and who subsequently acquire carriage of an invasive strain.By preventing susceptible contacts from acquiring infection by directly inhibiting colonization. Close contacts are defined as those persons who could have had intimate contact with the patients oral secretions such as through kissing or sharing of food or drink. The importance of the carrier state in meningococcal disease is well known. In developed countries the disease transmission usually occurs in day care, schools and large gatherings where usually disease transmission could occur. Because the meningococcal organism is transmitted by respiratory droplets and is susceptible to drying, it has been postulated that close contact is necessary for transmission. Therefore, the disease transmission to other susceptible person cannot be prevented. Meningitis occurs sporadically throughout the year, and since the organism has no known reservoir outside of man, asymptomatic carriers are usually the source of transmission.Additionally, basic hygiene measures, such as handwashing and not sharing drinking cups, can reduce the incidence of infection by limiting exposure. When a case is confirmed, all close contacts with the infected person can be offered antibiotics to reduce the likelihood of the infection spreading to other people. However, rifampin-resistant strains have been reported and the indiscriminate use of antibiotics contributes to this problem. Chemoprophylaxis is commonly used to those close contacts who are at highest risk of carrying the pathogenic strains. Since vaccine duration is unknown, mass select vaccinations may be the most cost-effective means for controlling the transmission of the meningococcal disease, rather than mass routine vaccination schedules.
Chronic medical conditions
Persons with component deficiencies in the final common complement pathway (C3, C5-C9) are more susceptible to N. meningitidis infection than complement-satisfactory persons, and it was estimated that the risk of infection is 7000 times higher in such individuals. In addition, complement component-deficient populations frequently experience frequent meningococcal disease since their immune response to natural infection may be less complete than that of complement non-deficient persons.Inherited properdin deficiency also is related, with an increased risk of contracting meningococcal disease. Persons with functional or anatomic asplenia may not efficiently clear encapsulated Neisseria meningitidis from the bloodstream Persons with other conditions associated with immunosuppression also may be at increased risk of developing meningococcal disease.
Antibiotics
An updated 2013 Cochrane review investigated the effectiveness of different antibiotics for prophylaxis against meningococcal disease and eradication of N. meningitidis particularly in people at risk of being carriers. The systematic review included 24 studies with 6,885 participants. During follow up no cases of meningococcal disease were reported and thus true antibiotic preventative measures could not be directly assessed. However, the data suggested that rifampin, ceftriaxone, ciprofloxacin and penicillin were equally effective for the eradication of N. meningitidis in potential carriers, although rifampin was associated with resistance to the antibiotic following treatment. Eighteen studies provided data on side effects and reported they were minimal but included nausea, abdominal pain, dizziness and pain at injection site.
Disease outbreak control
Meningitis A, C, Y and W-135 vaccines can be used for large-scale vaccination programs when an outbreak of meningococcal disease occurs in Africa and other regions of the world. Whenever sporadic or cluster cases or outbreaks of meningococcal disease occur in the US, chemoprophylaxis is the principal means of preventing secondary cases in household and other close contacts of individuals with invasive disease. Meningitis A, C, Y and W-135 vaccines rarely may be used as an adjunct to chemoprophylaxis,1 but only in situations where there is an ongoing risk of exposure (e.g., when cluster cases or outbreaks occur) and when a serogroup contained in the vaccine is involved.It is important that clinicians promptly report all cases of suspected or confirmed meningococcal disease to local public health authorities and that the serogroup of the meningococcal strain involved be identified. The effectiveness of mass vaccination programs depends on early and accurate recognition of outbreaks. When a suspected outbreak of meningococcal disease occurs, public health authorities will then determine whether mass vaccinations (with or without mass chemoprophylaxis) is indicated and delineate the target population to be vaccinated based on risk assessment.
Treatment
When meningococcal disease is suspected, treatment must be started immediately and should not be delayed while waiting for investigations. Treatment in primary care usually involves prompt intramuscular administration of benzylpenicillin, and then an urgent transfer to hospital (hopefully, an academic level I medical center, or at least a hospital with round the clock neurological care, ideally with neurological intensive and critical care units) for further care. Once in the hospital, the antibiotics of choice are usually IV broad spectrum 3rd generation cephalosporins, e.g., cefotaxime or ceftriaxone. Benzylpenicillin and chloramphenicol are also effective. Supportive measures include IV fluids, oxygen, inotropic support, e.g., dopamine or dobutamine and management of raised intracranial pressure. Steroid therapy may help in some adult patients, but is unlikely to affect long term outcomes.There is some debate on which antibiotic is most effective at treating the illness. A systematic review compared two antibiotics. There was one trial: an open label (not blinded) non-inferiority trial of 510 people comparing two different types of antibiotics; ceftriaxone (in which there were 14 deaths out of 247), and chloramphenicol (12 deaths out of 256). There were no reported side effects. Both antibiotics were considered equally effective. Antibiotic choice should be based on local antibiotic resistance information.
Prognosis
Complications
Complications following meningococcal disease can be divided into early and late groups. Early complications include: raised intracranial pressure, disseminated intravascular coagulation, seizures, circulatory collapse and organ failure. Later complications are: deafness, blindness, lasting neurological deficits, reduced IQ, and gangrene leading to amputations.
Epidemiology
Africa
The importance of meningitis disease is as significant in Africa as HIV, TB and malaria. Cases of meningococcemia leading to severe meningoencephalitis are common among young children and the elderly. Deaths occurring in less than 24 hours are more likely during the disease epidemic seasons in Africa and Sub-Saharan Africa is hit by meningitis disease outbreaks throughout the epidemic season. It may be that climate change contributes significantly the spread of the disease in Benin, Burkina Faso, Cameroon, the Central African Republic, Chad, Côte dIvoire, the Democratic Republic of the Congo, Ethiopia, Ghana, Mali, Niger, Nigeria and Togo. This is an area of Africa where the disease is endemic: meningitis is "silently" present, and there are always a few cases. When the number of cases passes five per population of 100,000 in one week, teams are on alert. Epidemic levels are reached when there have been 100 cases per 100,000 populations over several weeks.Further complicating efforts to halt the spread of meningitis in Africa is the fact that extremely dry, dusty weather conditions which characterize Niger and Burkina Faso from December to June favor the development of epidemics. Overcrowded villages are breeding grounds for bacterial transmission and lead to a high prevalence of respiratory tract infections, which leave the body more susceptible to infection, encouraging the spread of meningitis. IRIN Africa news has been providing the number of deaths for each country since 1995, and a mass vaccination campaign following a community outbreak of meningococcal disease in Florida was done by the CDC.
Florida
As of June 2022, there is an ongoing outbreak of the disease in Florida. The CDC has identified 26 cases of the disease. Seven deaths have been attributed to the disease.
History and etymology
From the Greek meninx (membrane) + kokkos (berry), meningococcal disease was first described by Gaspard Vieusseux during an outbreak in Geneva in 1805. In 1884, Italian pathologists Ettore Marchiafava and Angelo Celli described intracellular micrococci in cerebrospinal fluid, and in 1887, Anton Wiechselbaum identified the meningococcus (designated as Diplococcus intracellularis meningitidis) in cerebrospinal fluid and established the connection between the organism and epidemic meningitis.
See also
Endocarditis
Pathogenic bacteria
Waterhouse–Friderichsen syndrome
African meningitis belt
2009–10 West African meningitis outbreak
Meningococcal vaccine
Meningitis Vaccine Project
References
Further reading
Centers for Disease Control and Prevention (2012). "Ch. 13: Meningococcal Disease". In Atkinson W, Wolfe S, Hamborsky J (eds.). Epidemiology and Prevention of Vaccine-Preventable Diseases (12th ed.). Washington DC: Public Health Foundation. pp. 193–204. Archived from the original on 10 March 2017.
External links
DermAtlas -1886809878 |
Opsoclonus myoclonus syndrome | Opsoclonus myoclonus syndrome (OMS), also known as opsoclonus-myoclonus-ataxia (OMA), is a rare neurological disorder of unknown cause which appears to be the result of an autoimmune process involving the nervous system. It is an extremely rare condition, affecting as few as 1 in 10,000,000 people per year. It affects 2 to 3% of children with neuroblastoma and has been reported to occur with celiac disease and diseases of neurologic and autonomic dysfunction.
Signs and symptoms
Symptoms include:
opsoclonus (rapid, involuntary, multivectorial (horizontal and vertical), unpredictable, conjugate fast eye movements without intersaccadic [quick rotation of the eyes] intervals)
myoclonus (brief, involuntary twitching of a muscle or a group of muscles)
cerebellar ataxia, both truncal and appendicular
aphasia (a language disorder in which there is an impairment of speech and of comprehension of speech, caused by brain damage)
mutism (a language disorder in which a person does not speak despite evidence of speech ability in the past, often part of a larger neurological or psychiatric disorder)
lethargy
irritability or malaise
drooling
strabismus (a condition in which the eyes are not properly aligned with each other)
vomiting
sleep disturbances
emotional disturbances (including fits of rage)About half of all OMS cases occur in association with neuroblastoma (a cancer of the sympathetic nervous system usually occurring in infants and children).
Disease course and clinical subtypes
In most cases, OMS starts with an acute flare-up of physical symptoms within days or weeks, but some less obvious symptoms such as irritability and malaise may begin weeks or months earlier.
Cause
In children, most cases are associated with neuroblastoma and most of the others are suspected to be associated with a low-grade neuroblastoma that spontaneously regressed before detection. In adults, most cases are associated with breast carcinoma or small-cell lung carcinoma. It is one of the few paraneoplastic (meaning indirectly caused by cancer) syndromes that occurs in both children and adults, although the mechanism of immune dysfunction underlying the adult syndrome is probably quite different.It is hypothesized that a viral infection (perhaps St. Louis encephalitis, Chikungunya, Epstein-Barr, Coxsackie B, enterovirus, or just a flu) causes the remaining cases, though a direct connection has not been proven. Rare cases of Opsoclonus myoclonus syndrome associated with Lyme disease have also been reported.OMS is not generally considered an infectious disease. OMS is not passed on genetically.
Diagnosis
Because OMS is so rare and occurs at an average age of 19 months (6 to 36 months), a diagnosis can be slow. Some cases have been diagnosed as having been caused by a virus. After a diagnosis of OMS is made, an associated neuroblastoma is discovered in half of cases, with median delay of 3 months.The interictal EEG pattern is usually normal.
Treatment
There is no known definitive cure for OMS. However, several drugs have proven to be effective in their treatment.
Some of medication used to treat the symptoms are:
ACTH has shown improvements in symptoms but can result in an incomplete recovery with residual deficits.
Corticosteroids (such as prednisone or methylprednisolone) used at high dosages (500 mg - 2 g per day intravenously for a course of 3 to 5 days) can accelerate regression of symptoms. Subsequent very gradual tapering with pills generally follows. Most patients require high doses for months to years before tapering.
Intravenous Immunoglobulins (IVIg) are often used with varying results.
Several other immunosuppressive drugs, such as cyclophosphamide and azathioprine, may be helpful in some cases.
Chemotherapy for neuroblastoma may be effective, although data is contradictory and unconvincing at this point in time.
Rituximab has been used with encouraging results.
Other medications are used to treat symptoms without influencing the nature of the disease (symptomatic treatment):
Trazodone can be useful against irritability and sleep problems
Additional treatment options include plasmapheresis for severe, steroid-unresponsive relapses.The National Organization for Rare Disorders (NORD) recommends FLAIR therapy consisting of a three-agent protocol involving front-loaded high-dose ACTH, IVIg, and rituximab that was developed by the National Pediatric Myoclonus Center, and has the best-documented outcomes. Almost all patients (80-90%) show improvement with this treatment and the relapse rate appears to be about 20%.A more detailed summary of current treatment options can be found at Treatment Options
The following medications should probably be avoided:
Midazolam - Can cause irritability.
Melatonin - Is known to stimulate the immune system.
Also, see "An Innovative Approach to the Problem of Sedating Children with Opsoclonus-Myoclonus Syndrome". Pranzatelli Abstracts. for more details
Prognosis
Currently, there are no clinically established laboratory investigations available to predict prognosis or therapeutic response.Tumors in children who develop OMS tend to be more mature, showing favorable histology and absence of n-myc oncogene amplification than similar tumors in children without symptoms of OMS. Involvement of local lymph nodes is common, but these children rarely have distant metastases and their prognosis, in terms of direct morbidity and mortality effects from the tumor, is excellent. The three-year survival rate for children with non-metastatic neuroblastoma and OMS was 100% according to Childrens Cancer Group data (gathered from 675 patients diagnosed between 1980 and 1994); three-year survival in comparable patients with OMS was 77%. Although the symptoms of OMS are typically steroid-responsive and recovery from acute symptoms of OMS can be quite good, children often experience lifelong neurologic sequelae that impair motor, cognitive, language, and behavioral development.Most children will experience a relapsing form of OMS, though a minority will have a monophasic course and may be more likely to recover without residual deficits. Viral infection may play a role in the reactivation of disease in some patients who had previously experienced remission, possibly by expanding the memory B cell population. Studies have generally asserted that 70-80% of children with OMS will have long-term neurologic, cognitive, behavioral, developmental, and academic impairment. Since neurologic and developmental difficulties have not been reported as a consequence of neuroblastoma or its treatment, it is thought that these are exclusively due to the immune mechanism underlying OMS.One study concludes that: "Patients with OMA and neuroblastoma have excellent survival but a high risk of neurologic sequelae. Favourable disease stage correlates with a higher risk for development of neurologic sequelae. The role of anti-neuronal antibodies in late sequelae of OMA needs further clarification".Another study states that: "Residual behavioral, language, and cognitive problems occurred in the majority".
Research
The National Institute of Neurological Disorders and Stroke (NINDS) conducts and supports research on various movement disorders, including opsoclonus myoclonus. These studies are focused on finding ways to prevent, treat, and cure these disorders, as well as increasing knowledge about them.
Nomenclature
OMS was first described by Marcel Kinsbourne in 1962. (The term Opsoclonus was coined by Orzechowski in 1913, but it was classically described and associated with neuroblastoma by Kinsbourne). Other names for OMS include:
Dancing Eyes-Dancing Feet syndrome
Dancing Eyes syndrome (see also Nystagmus)
Kinsbourne syndrome
Myoclonic Encephalopathy of Infants (MEI), not to be confused with Early myoclonic encephalopathy (EME)
Opsoclonic Cerebellopathy
Opsoclonus-Myoclonus-Ataxia (OMA)
Paraneoplastic Opsoclonus-Myoclonus Ataxia (POMA)
References
Further reading
== External links == |
Sensory processing disorder | Sensory processing disorder (SPD, formerly known as sensory integration dysfunction) is a condition in which multisensory input is not adequately processed in order to provide appropriate responses to the demands of the environment. Sensory processing disorder is present in many people with autism spectrum disorder and attention deficit hyperactivity disorder. Individuals with SPD may inadequately process visual, auditory, olfactory (smell), gustatory (taste), tactile (touch), vestibular (balance), proprioception (body awareness), and interoception (internal body senses) sensory stimuli.
Sensory integration was defined by occupational therapist Anna Jean Ayres in 1972 as "the neurological process that organizes sensation from ones own body and from the environment and makes it possible to use the body effectively within the environment". Sensory processing disorder has been characterized as the source of significant problems in organizing sensation coming from the body and the environment and is manifested by difficulties in the performance in one or more of the main areas of life: productivity, leisure and play or activities of daily living.Sources debate whether SPD is an independent disorder or represents the observed symptoms of various other, more well-established, disorders. SPD is not included in the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, and the American Academy of Pediatrics has recommended in 2012 that pediatricians not use SPD as a stand-alone diagnosis.
Signs and symptoms
Sensory integration difficulties or sensory processing disorder (SPD) are characterized by persistent challenges with neurological processing of sensory stimuli that interfere with a persons ability to participate in everyday life. Such challenges can appear in one or several sensory systems of the somatosensory system, vestibular system, proprioceptive system, interoceptive system, auditory system, visual system, olfactory system, and gustatory system.While many people can present one or two symptoms, sensory processing disorder has to have a clear functional impact on the persons life:
Signs of over-responsivity, including, for example, dislike of textures such as those found in fabrics, foods, grooming products or other materials found in daily living, to which most people would not react, and serious discomfort, sickness or threat induced by normal sounds, lights, ambient temperature, movements, smells, tastes, or even inner sensations such as heartbeat.Signs of under-responsivity, including sluggishness and lack of responsiveness.
Sensory cravings, including, for example, fidgeting, impulsiveness, and/or seeking or making loud, disturbing noises; and sensorimotor-based problems, including slow and uncoordinated movements or poor handwriting.
Sensory discrimination problems, which might manifest themselves in behaviors such as things constantly dropped.Symptoms may vary according to the disorders type and subtype present.
Relationship to other disorders
Sensory integration and processing difficulties can be a feature of a number of disorders, including anxiety problems, attention deficit hyperactivity disorder (ADHD), food intolerances, behavioral disorders, and particularly, autism spectrum disorders. This pattern of comorbidities poses a significant challenge to those who claim that SPD is an identifiably specific disorder, rather than simply a term given to a set of symptoms common to other disorders.Two studies have provided preliminary evidence suggesting that there may be measurable neurological differences between children diagnosed with SPD and control children classified as neurotypical or children diagnosed with autism. Despite this evidence, that SPD researchers have yet to agree on a proven, standardized diagnostic tool undermines researchers ability to define the boundaries of the disorder and makes correlational studies, like those on structural brain abnormalities, less convincing.
Causes
The exact cause of SPD is not known. However, it is known that the midbrain and brainstem regions of the central nervous system are early centers in the processing pathway for multisensory integration; these brain regions are involved in processes including coordination, attention, arousal, and autonomic function. After sensory information passes through these centers, it is then routed to brain regions responsible for emotions, memory, and higher level cognitive functions. Damage in any part of the brain involved in multisensory processing can cause difficulties in adequately processing stimuli in a functional way.
Mechanism
Research in sensory processing in 2007, is focused on finding the genetic and neurological causes of SPD. Electroencephalography (EEG), measuring event-related potential (ERP) and magnetoencephalography (MEG) are traditionally used to explore the causes behind the behaviors observed in SPD.
Differences in tactile and auditory over-responsivity show moderate genetic influences, with tactile over-responsivity demonstrating greater heritability. Differences in auditory latency (the time between the input is received and when reaction is observed in the brain), hypersensitivity to vibration in the Pacinian corpuscles receptor pathways and other alterations in unimodal and multisensory processing have been detected in autism populations.People with sensory processing deficits appear to have less sensory gating than typical subjects, and atypical neural integration of sensory input. In people with sensory over-responsivity, different neural generators activate, causing the automatic association of causally related sensory inputs that occurs at this early sensory-perceptual stage to not function properly. People with sensory over-responsivity might have increased D2 receptor in the striatum, related to aversion to tactile stimuli and reduced habituation. In animal models, prenatal stress significantly increased tactile avoidance.Recent research has also found an abnormal white matter microstructure in children with SPD, compared with typical children and those with other developmental disorders such as autism and ADHD.One hypothesis is that multisensory stimulation may activate a higher-level system in the frontal cortex that involves attention and cognitive processing, rather than the automatic integration of multisensory stimuli observed in typically developing adults in the auditory cortex.
Diagnosis
Sensory processing disorder is accepted in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-3R). It is not recognized as a mental disorder in medical manuals such as the ICD-10 or the DSM-5.Diagnosis is primarily arrived at by the use of standardized tests, standardized questionnaires, expert observational scales, and free-play observation at an occupational therapy gym. Observation of functional activities might be carried at school and home as well.Though diagnosis in most of the world is done by an occupational therapist, in some countries diagnosis is made by certified professionals, such as psychologists, learning specialists, physiotherapists and/or speech and language therapists. Some countries recommend to have a full psychological and neurological evaluation if symptoms are too severe.
Standardized tests
Sensory Integration and Praxis Test (SIPT)
Evaluation of Ayres Sensory Integration (EASI) – in development
DeGangi-Berk Test of Sensory Integration (TSI)
Test of Sensory Functions in Infants (TSFI)
Standardized questionnaires
Sensory Profile (SP)
Infant/Toddler Sensory Profile
Adolescent/Adult Sensory Profile
Sensory Profile School Companion
Indicators of Developmental Risk Signals (INDIPCD-R)
Sensory Processing Measure (SPM)
Sensory Processing Measure Preeschool (SPM-P)
Classification
Sensory integration and processing difficulties
Construct-related evidence relating to sensory integration and processing difficulties from Ayres early research emerged from factor analysis of the earliest test the SCISIT and Mulligans 1998 "Patterns of Sensory Integration Dysfunctions: A Confirmatory Factor Analysis". Sensory integration and processing patterns recognised in the research support a classification of difficulties related to:
Sensory registration and perception (discrimination)
Sensory reactivity (modulation)
Praxis (meaning "to do")
Postural, ocular and bilateral integration
Sensory processing disorder (SPD)
Proponents of a new nosology SPD have instead proposed three categories: sensory modulation disorder, sensory-based motor disorders and sensory discrimination disorders (as defined in the Diagnostic Classification of Mental Health and Developmental Disorders in Infancy and Early Childhood).
1. Sensory modulation disorder (SMD)
Sensory modulation refers to a complex central nervous system process by which neural messages that convey information about the intensity, frequency, duration, complexity, and novelty of sensory stimuli are adjusted.SMD consists of three subtypes:
Sensory over-responsivity.
Sensory under-responsivity
Sensory craving/seeking.
2. Sensory-based motor disorder (SBMD)
According to proponents, sensory-based motor disorder shows motor output that is disorganized as a result of incorrect processing of sensory information affecting postural control challenges, resulting in postural disorder, or developmental coordination disorder.The SBMD subtypes are:
Dyspraxia
Postural disorder
3. Sensory discrimination disorder (SDD)
Sensory discrimination disorder involves the incorrect processing of sensory information. The SDD subtypes are:
Visual
Auditory
Tactile
Gustatory (taste)
Olfactory (smell)
Vestibular (balance, head position and movement in space)
Proprioceptive (feeling of where parts of the body are located in space, muscle sensation)
Interoception (inner body sensations).
Treatment
Sensory integration therapy
Typically offered as part of occupational therapy, ASI that places a child in a room specifically designed to stimulate and challenge all of the senses to elicit functional adaptive responses. Occupational Therapy is defined by the American Occupational Therapy Association (AOTA) as "Occupational therapy practitioners in pediatric settings work with children and their families, caregivers and teachers to promote participation in meaningful activities and occupations". In childhood, these occupations may include play, school and learning self-care tasks. The following link provides information from AOTAs website regarding Occupational Therapy working with children and youth: https://www.aota.org/~/media/Corporate/Files/AboutOT/Professionals/WhatIsOT/CY/Fact-Sheets/Children%20and%20Youth%20fact%20sheet.ashx. An entry level Occupational Therapist can provide treatment for sensory processing disorder however, more advanced clinical training exists to target the underlying neuro-biological processes involved. The following link is a fact sheet regarding the role of Occupational Therapy in treating sensory processing disorder: https://www.aota.org/-/media/corporate/files/aboutot/professionals/whatisot/cy/fact-sheets/factsheet_sensoryintegration.pdf
Although Ayres initially developed her assessment tools and intervention methods to support children with sensory integration and processing challenges, the theory is relevant beyond childhood.Sensory integration therapy is driven by four main principles:
Just right challenge (the child must be able to successfully meet the challenges that are presented through playful activities)
Adaptive response (the child adapts their behavior with new and useful strategies in response to the challenges presented)
Active engagement (the child will want to participate because the activities are fun)
Child directed (the childs preferences are used to initiate therapeutic experiences within the session)Serious questions have been raised as to the effectiveness of this therapy particularly in medical journals where the requirements for a treatment to be effective is much higher and developed than its occupational therapy counter parts which often advocate the effectiveness of the treatment.
Sensory processing therapy
This therapy retains all of the above-mentioned four principles and adds:
Intensity (person attends therapy daily for a prolonged period of time)
Developmental approach (therapist adapts to the developmental age of the person, against actual age)
Test-retest systematic evaluation (all clients are evaluated before and after)
Process driven vs. activity driven (therapist focuses on the "just right" emotional connection and the process that reinforces the relationship)
Parent education (parent education sessions are scheduled into the therapy process)
"Joie de vivre" (happiness of life is therapys main goal, attained through social participation, self-regulation, and self-esteem)
Combination of best practice interventions (is often accompanied by integrated listening system therapy, floor time, and electronic media such as Xbox Kinect, Nintendo Wii, Makoto II machine training and others)While occupational therapists using a sensory integration frame of reference work on increasing a childs ability to adequately process sensory input, other OTs may focus on environmental accommodations that parents and school staff can use to enhance the childs function at home, school, and in the community. These may include selecting soft, tag-free clothing, avoiding fluorescent lighting, and providing ear plugs for "emergency" use (such as for fire drills).
Evaluation of treatment effectiveness
A 2019 review found sensory integration therapy to be effective for autism spectrum disorder. Another study from 2018 backs up the intervention for children with special needs, Additionally, the American Occupational Therapy Association supports the intervention.In its overall review of the treatment effectiveness literature, Aetna concluded that "The effectiveness of these therapies is unproven", while the American Academy of Pediatrics concluded that "parents should be informed that the amount of research regarding the effectiveness of sensory integration therapy is limited and inconclusive." A 2015 review concluded that SIT techniques exist "outside the bounds of established evidence-based practice" and that SIT is "quite possibly a misuse of limited resources."
Epidemiology
It has been estimated by proponents that up to 16.5% of elementary school aged children present elevated SOR behaviors in the tactile or auditory modalities. This figure is larger than what previous studies with smaller samples had shown: an estimate of 5–13% of elementary school aged children. Critics have noted that such a high incidence for just one of the subtypes of SPD raises questions about the degree to which SPD is a specific and clearly identifiable disorder.Proponents have also claimed that adults may also show signs of sensory processing difficulties and would benefit for sensory processing therapies, although this work has yet to distinguish between those with SPD symptoms alone vs adults whose processing abnormalities are associated with other disorders, such as autism spectrum disorder.
Society
The American Occupational Therapy Association (AOTA) and British Royal College of Occupational Therapy (RCOT) support the use of a variety of methods of sensory integration for those with sensory integration and processing difficulties. Both organization recognise the need for further research about Ayres Sensory Integration and related approaches. In the USA this important to increase insurance coverage for related therapies. AOTA and RCOT have made efforts to educate the public about sensory Integration and related approaches. AOTAs practice guidelines and RCOTs informed view "Sensory Integration and sensory-based interventions" currently support the use of sensory integration therapy and interprofessional education and collaboration in order to optimize treatment for those with sensory integration and processing difficulties. The AOTA provides several resources pertaining to sensory integration therapy, some of which includes a fact sheet, new research, and continuing education opportunities.
Controversy
There are concerns regarding the validity of the diagnosis. SPD is not included in the DSM-5 or ICD-10, the most widely used diagnostic sources in healthcare. The American Academy of Pediatrics (AAP) in 2012 stated that there is no universally accepted framework for diagnosis and recommends caution against using any "sensory" type therapies unless as a part of a comprehensive treatment plan. The AAP has plans to review its policy, though those efforts are still in the early stages.A 2015 review of research on Sensory Integration Therapy (SIT) concluded that SIT is "ineffective and that its theoretical underpinnings and assessment practices are unvalidated", that SIT techniques exist "outside the bounds of established evidence-based practice", and that SIT is "quite possibly a misuse of limited resources".Some sources point that sensory issues are an important concern, but not a diagnosis in themselves.Critics have noted that what proponents claim are symptoms of SPD are both broad and, in some cases, represent very common, and not necessarily abnormal or atypical, childhood characteristics. Where these traits become grounds for a diagnosis is generally in combination with other more specific symptoms or when the child gets old enough to explain that the reasons behind their behavior are specifically sensory.
Manuals
SPD is in Stanley Greenspans Diagnostic Manual for Infancy and Early Childhood and as Regulation Disorders of Sensory Processing part of The Zero to Threes Diagnostic Classification.
Is not recognized as a stand-alone diagnosis in the manuals ICD-10 or in the recently updated DSM-5, but unusual reactivity to sensory input or unusual interest in sensory aspects is included as a possible but not necessary criterion for the diagnosis of autism.
History
Sensory processing disorder as a specific form of atypical functioning was first described by occupational therapist Anna Jean Ayres (1920–1989).
Original model
Ayress theoretical framework for what she called Sensory Integration Dysfunction was developed after six factor analytic studies of populations of children with learning disabilities, perceptual motor disabilities and normal developing children.
Ayres created the following nosology based on the patterns that appeared on her factor analysis:
Dyspraxia: poor motor planning (more related to the vestibular system and proprioception)
Poor bilateral integration: inadequate use of both sides of the body simultaneously
Tactile defensiveness: negative reaction to tactile stimuli
Visual perceptual deficits: poor form and space perception and visual motor functions
Somatodyspraxia: poor motor planning (related to poor information coming from the tactile and proprioceptive systems)
Auditory-language problemsBoth visual perceptual and auditory language deficits were thought to possess a strong cognitive component and a weak relationship to underlying sensory processing deficits, so they are not considered central deficits in many models of sensory processing.In 1998, Mulligan found a similar pattern of deficits in a confirmatory factor analytic study.
Quadrant model
Dunns nosology uses two criteria: response type (passive vs. active) and sensory threshold to the stimuli (low or high) creating four subtypes or quadrants:
High neurological thresholdsLow registration: high threshold with passive response. Individuals who do not pick up on sensations and therefore partake in passive behavior.
Sensation seeking: high threshold and active response. Those who actively seek out a rich sensory filled environment.Low neurological thresholdSensitivity to stimuli: low threshold with passive response. Individuals who become distracted and uncomfortable when exposed to sensation but do not actively limit or avoid exposure to the sensation.
Sensation avoiding: low threshold and active response. Individuals actively limit their exposure to sensations and are therefore high self regulators.
Sensory processing model
In Millers nosology "sensory integration dysfunction" was renamed into "Sensory processing disorder" to facilitate coordinated research work with other fields such as neurology since "the use of the term sensory integration often applies to a neurophysiologic cellular process rather than a behavioral response to sensory input as connoted by Ayres."The sensory processing models nosology divides SPD in three subtypes: modulation, motor based and discrimination problems.
See also
== References == |
Urethral diverticulum | A urethral diverticulum is a condition where the urethra or the periurethral glands push into the connective tissue layers (fascia) that surround it.
Signs and symptoms
Urethral diverticula are often asymptomatic and symptoms that are present tend to be nonspecific. They can co-occur with cancer, in approximately 6-9% of cases, most commonly adenocarcinoma, but also including squamous cell carcinoma and transitional cell carcinoma. Approximately 10% of cases co-occur with kidney stones.There are 2 types of urethral diverticulums. Congenital and acquired. In infancy usually the urethral diverticulum is congenital but in rare instances acquired urethral diverticulum can be seen in infancy specially following traumatic catheterization.Common symptoms of urethral diverticulum include incontinence, urinary frequency and urgency, pain during sex, and pain during urination. Other symptoms include pain localized to the urethra or pelvis and frequent urinary tract infection.When urethral diverticulum becomes severe, a painful mass can sometimes be felt inside the introitus of the vagina, which can discharge pus. If the mass is hard or bleeds, complications like cancer or kidney stones may be present.
Causes
Few urethral diverticula are present at birth; the vast majority are acquired. Acquired urethral diverticula can be caused by trauma and/or infection. When the peri-urethral ducts become infected repeatedly, they can become blocked and eventually cause a diverticulum. They are usually found in the middle of the urethra or the end farthest from the bladder.Congenital urethral diverticula can arise from several embryological sources. These include defects in the primordial folds and remnants of Gartners duct.
Pathology
Histopathologically, several characteristics are frequently visible in urethral diverticula. These include nephrogenic adenoma, chronic inflammation associated with fibrosis around the glands, small or absent epithelium, chronic cystitis, cystitis cystica, cystitis glandularis, squamous metaplasia, and adenomatous metaplasia.Approximately 1/3 of diverticula are compound or multiple, and some can extend to surround the urethra.
Diagnosis
Urethral diverticulum is often an incidental finding. It can be diagnosed using magnetic resonance imaging and/or micturating cystourethrography. Other studies that can be used to diagnose urethral diverticulum include intravenous urography, urethroscopy, and/or ultrasound. Conditions that should be distinguished from urethral diverticulum in a differential diagnosis include overactive bladder, Gartners duct cyst, Gartners duct abscess, ectopic caeco-ureterocele, interstitial cystitis, pelvic inflammatory disease, endometriosis, and cancer.
Treatment
The primary treatment for urethral diverticulum is surgical. In women the surgery is conducted transvaginally, usually when there is no acute inflammation to better aid dissection of the delicate tissues.
Prognosis
Left untreated, urethral diverticulum can cause significant morbidity (sickness).During surgery, there is a risk for complications due to the highly vascular nature of the tissue. The urethral sphincters and its smooth muscle, as well as the neck of the bladder, can be injured regardless of the surgical approach. Other complications from surgery can include urinary incontinence, stress incontinence, a urethrovaginal fistula, or recurrent diverticula. Horseshoe-shaped diverticula and diverticula that completely surround the urethra are both associated with worse outcomes, as are those located close to the bladder, and large (over 3–4 cm) diverticula.
Epidemiology
The incidence of urethral diverticulum has been increasing in the 2000s, likely due to increasing diagnosis and detection of the condition. It is estimated to be present in as low as 0.02% of all women and as high as 6% of all women, and 40% of women with lower urinary tract symptoms. Most symptomatic urethral diverticula are present in women from 30 to 60 years old.84% of periurethral masses are due to urethral diverticula.
In men
Urethral diverticulum can occur in men, and can cause complications including kidney stones and urinary tract infections.
== References == |
Stroke | A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functioning properly.Signs and symptoms of a stroke may include an inability to move or feel on one side of the body, problems understanding or speaking, dizziness, or loss of vision to one side. Signs and symptoms often appear soon after the stroke has occurred. If symptoms last less than one or two hours, the stroke is a transient ischemic attack (TIA), also called a mini-stroke. A hemorrhagic stroke may also be associated with a severe headache. The symptoms of a stroke can be permanent. Long-term complications may include pneumonia and loss of bladder control.The main risk factor for stroke is high blood pressure. Other risk factors include high blood cholesterol, tobacco smoking, obesity, diabetes mellitus, a previous TIA, end-stage kidney disease, and atrial fibrillation. An ischemic stroke is typically caused by blockage of a blood vessel, though there are also less common causes. A hemorrhagic stroke is caused by either bleeding directly into the brain or into the space between the brains membranes. Bleeding may occur due to a ruptured brain aneurysm. Diagnosis is typically based on a physical exam and supported by medical imaging such as a CT scan or MRI scan. A CT scan can rule out bleeding, but may not necessarily rule out ischemia, which early on typically does not show up on a CT scan. Other tests such as an electrocardiogram (ECG) and blood tests are done to determine risk factors and rule out other possible causes. Low blood sugar may cause similar symptoms.Prevention includes decreasing risk factors, surgery to open up the arteries to the brain in those with problematic carotid narrowing, and warfarin in people with atrial fibrillation. Aspirin or statins may be recommended by physicians for prevention. A stroke or TIA often requires emergency care. An ischemic stroke, if detected within three to four and half hours, may be treatable with a medication that can break down the clot. Some hemorrhagic strokes benefit from surgery. Treatment to attempt recovery of lost function is called stroke rehabilitation, and ideally takes place in a stroke unit; however, these are not available in much of the world.In 2013, approximately 6.9 million people had an ischemic stroke and 3.4 million people had a hemorrhagic stroke. In 2015, there were about 42.4 million people who had previously had a stroke and were still alive. Between 1990 and 2010 the number of strokes which occurred each year decreased by approximately 10% in the developed world and increased by 10% in the developing world. In 2015, stroke was the second most frequent cause of death after coronary artery disease, accounting for 6.3 million deaths (11% of the total). About 3.0 million deaths resulted from ischemic stroke while 3.3 million deaths resulted from hemorrhagic stroke. About half of people who have had a stroke live less than one year. Overall, two thirds of strokes occurred in those over 65 years old.
Classification
Strokes can be classified into two major categories: ischemic and hemorrhagic. Ischemic strokes are caused by interruption of the blood supply to the brain, while hemorrhagic strokes result from the rupture of a blood vessel or an abnormal vascular structure. About 87% of strokes are ischemic, the rest being hemorrhagic. Bleeding can develop inside areas of ischemia, a condition known as "hemorrhagic transformation." It is unknown how many hemorrhagic strokes actually start as ischemic strokes.
Definition
In the 1970s the World Health Organization defined stroke as a "neurological deficit of cerebrovascular cause that persists beyond 24 hours or is interrupted by death within 24 hours", although the word "stroke" is centuries old. This definition was supposed to reflect the reversibility of tissue damage and was devised for the purpose, with the time frame of 24 hours being chosen arbitrarily. The 24-hour limit divides stroke from transient ischemic attack, which is a related syndrome of stroke symptoms that resolve completely within 24 hours. With the availability of treatments that can reduce stroke severity when given early, many now prefer alternative terminology, such as brain attack and acute ischemic cerebrovascular syndrome (modeled after heart attack and acute coronary syndrome, respectively), to reflect the urgency of stroke symptoms and the need to act swiftly.
Ischemic
In an ischemic stroke, blood supply to part of the brain is decreased, leading to dysfunction of the brain tissue in that area. There are four reasons why this might happen:
Thrombosis (obstruction of a blood vessel by a blood clot forming locally)
Embolism (obstruction due to an embolus from elsewhere in the body),
Systemic hypoperfusion (general decrease in blood supply, e.g., in shock)
Cerebral venous sinus thrombosis.A stroke without an obvious explanation is termed cryptogenic (of unknown origin); this constitutes 30–40% of all ischemic strokes.There are various classification systems for acute ischemic stroke. The Oxford Community Stroke Project classification (OCSP, also known as the Bamford or Oxford classification) relies primarily on the initial symptoms; based on the extent of the symptoms, the stroke episode is classified as total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), lacunar infarct (LACI) or posterior circulation infarct (POCI). These four entities predict the extent of the stroke, the area of the brain that is affected, the underlying cause, and the prognosis. The TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification is based on clinical symptoms as well as results of further investigations; on this basis, a stroke is classified as being due to (1) thrombosis or embolism due to atherosclerosis of a large artery, (2) an embolism originating in the heart, (3) complete blockage of a small blood vessel, (4) other determined cause, (5) undetermined cause (two possible causes, no cause identified, or incomplete investigation). Users of stimulants such as cocaine and methamphetamine are at a high risk for ischemic strokes.
Hemorrhagic
There are two main types of hemorrhagic stroke:
Intracerebral hemorrhage, which is basically bleeding within the brain itself (when an artery in the brain bursts, flooding the surrounding tissue with blood), due to either intraparenchymal hemorrhage (bleeding within the brain tissue) or intraventricular hemorrhage (bleeding within the brains ventricular system).
Subarachnoid hemorrhage, which is basically bleeding that occurs outside of the brain tissue but still within the skull, and precisely between the arachnoid mater and pia mater (the delicate innermost layer of the three layers of the meninges that surround the brain).The above two main types of hemorrhagic stroke are also two different forms of intracranial hemorrhage, which is the accumulation of blood anywhere within the cranial vault; but the other forms of intracranial hemorrhage, such as epidural hematoma (bleeding between the skull and the dura mater, which is the thick outermost layer of the meninges that surround the brain) and subdural hematoma (bleeding in the subdural space), are not considered "hemorrhagic strokes".Hemorrhagic strokes may occur on the background of alterations to the blood vessels in the brain, such as cerebral amyloid angiopathy, cerebral arteriovenous malformation and an intracranial aneurysm, which can cause intraparenchymal or subarachnoid hemorrhage.In addition to neurological impairment, hemorrhagic strokes usually cause specific symptoms (for instance, subarachnoid hemorrhage classically causes a severe headache known as a thunderclap headache) or reveal evidence of a previous head injury.
Signs and symptoms
Stroke symptoms typically start suddenly, over seconds to minutes, and in most cases do not progress further. The symptoms depend on the area of the brain affected. The more extensive the area of the brain affected, the more functions that are likely to be lost. Some forms of stroke can cause additional symptoms. For example, in intracranial hemorrhage, the affected area may compress other structures. Most forms of stroke are not associated with a headache, apart from subarachnoid hemorrhage and cerebral venous thrombosis and occasionally intracerebral hemorrhage.
Early recognition
Various systems have been proposed to increase recognition of stroke. Different findings are able to predict the presence or absence of stroke to different degrees. Sudden-onset face weakness, arm drift (i.e., if a person, when asked to raise both arms, involuntarily lets one arm drift downward) and abnormal speech are the findings most likely to lead to the correct identification of a case of stroke, increasing the likelihood by 5.5 when at least one of these is present. Similarly, when all three of these are absent, the likelihood of stroke is decreased (– likelihood ratio of 0.39). While these findings are not perfect for diagnosing stroke, the fact that they can be evaluated relatively rapidly and easily make them very valuable in the acute setting.
A mnemonic to remember the warning signs of stroke is FAST (facial droop, arm weakness, speech difficulty, and time to call emergency services), as advocated by the Department of Health (United Kingdom) and the Stroke Association, the American Stroke Association, the National Stroke Association (US), the Los Angeles Prehospital Stroke Screen (LAPSS) and the Cincinnati Prehospital Stroke Scale (CPSS). Use of these scales is recommended by professional guidelines. FAST is less reliable in the recognition of posterior circulation strokes.For people referred to the emergency room, early recognition of stroke is deemed important as this can expedite diagnostic tests and treatments. A scoring system called ROSIER (recognition of stroke in the emergency room) is recommended for this purpose; it is based on features from the medical history and physical examination.
Subtypes
If the area of the brain affected includes one of the three prominent central nervous system pathways—the spinothalamic tract, corticospinal tract, and the dorsal column–medial lemniscus pathway, symptoms may include:
hemiplegia and muscle weakness of the face
numbness
reduction in sensory or vibratory sensation
initial flaccidity (reduced muscle tone), replaced by spasticity (increased muscle tone), excessive reflexes, and obligatory synergies.In most cases, the symptoms affect only one side of the body (unilateral). Depending on the part of the brain affected, the defect in the brain is usually on the opposite side of the body. However, since these pathways also travel in the spinal cord and any lesion there can also produce these symptoms, the presence of any one of these symptoms does not necessarily indicate a stroke. In addition to the above CNS pathways, the brainstem gives rise to most of the twelve cranial nerves. A brainstem stroke affecting the brainstem and brain, therefore, can produce symptoms relating to deficits in these cranial nerves:
altered smell, taste, hearing, or vision (total or partial)
drooping of eyelid (ptosis) and weakness of ocular muscles
decreased reflexes: gag, swallow, pupil reactivity to light
decreased sensation and muscle weakness of the face
balance problems and nystagmus
altered breathing and heart rate
weakness in sternocleidomastoid muscle with inability to turn head to one side
weakness in tongue (inability to stick out the tongue or move it from side to side)If the cerebral cortex is involved, the CNS pathways can again be affected, but also can produce the following symptoms:
aphasia (difficulty with verbal expression, auditory comprehension, reading and writing; Brocas or Wernickes area typically involved)
dysarthria (motor speech disorder resulting from neurological injury)
apraxia (altered voluntary movements)
visual field defect
memory deficits (involvement of temporal lobe)
hemineglect (involvement of parietal lobe)
disorganized thinking, confusion, hypersexual gestures (with involvement of frontal lobe)
lack of insight of his or her, usually stroke-related, disabilityIf the cerebellum is involved, ataxia might be present and this includes:
altered walking gait
altered movement coordination
vertigo and or disequilibrium
Associated symptoms
Loss of consciousness, headache, and vomiting usually occur more often in hemorrhagic stroke than in thrombosis because of the increased intracranial pressure from the leaking blood compressing the brain.
If symptoms are maximal at onset, the cause is more likely to be a subarachnoid hemorrhage or an embolic stroke.
Causes
Thrombotic stroke
In thrombotic stroke, a thrombus (blood clot) usually forms around atherosclerotic plaques. Since blockage of the artery is gradual, onset of symptomatic thrombotic strokes is slower than that of a hemorrhagic stroke. A thrombus itself (even if it does not completely block the blood vessel) can lead to an embolic stroke (see below) if the thrombus breaks off and travels in the bloodstream, at which point it is called an embolus. Two types of thrombosis can cause stroke:
Large vessel disease involves the common and internal carotid arteries, the vertebral artery, and the Circle of Willis. Diseases that may form thrombi in the large vessels include (in descending incidence): atherosclerosis, vasoconstriction (tightening of the artery), aortic, carotid or vertebral artery dissection, various inflammatory diseases of the blood vessel wall (Takayasu arteritis, giant cell arteritis, vasculitis), noninflammatory vasculopathy, Moyamoya disease and fibromuscular dysplasia.
Small vessel disease involves the smaller arteries inside the brain: branches of the circle of Willis, middle cerebral artery, stem, and arteries arising from the distal vertebral and basilar artery. Diseases that may form thrombi in the small vessels include (in descending incidence): lipohyalinosis (build-up of fatty hyaline matter in the blood vessel as a result of high blood pressure and aging) and fibrinoid degeneration (a stroke involving these vessels is known as a lacunar stroke) and microatheroma (small atherosclerotic plaques).Anemia causes increase blood flow in the blood circulatory system. This causes the endothelial cells of the blood vessels to express adhesion factors which encourages the clotting of blood and formation of thrombus. Sickle-cell anemia, which can cause blood cells to clump up and block blood vessels, can also lead to stroke. A stroke is the second leading cause of death in people under 20 with sickle-cell anemia. Air pollution may also increase stroke risk.
Embolic stroke
An embolic stroke refers to an arterial embolism (a blockage of an artery) by an embolus, a traveling particle or debris in the arterial bloodstream originating from elsewhere. An embolus is most frequently a thrombus, but it can also be a number of other substances including fat (e.g., from bone marrow in a broken bone), air, cancer cells or clumps of bacteria (usually from infectious endocarditis).Because an embolus arises from elsewhere, local therapy solves the problem only temporarily. Thus, the source of the embolus must be identified. Because the embolic blockage is sudden in onset, symptoms usually are maximal at the start. Also, symptoms may be transient as the embolus is partially resorbed and moves to a different location or dissipates altogether.
Emboli most commonly arise from the heart (especially in atrial fibrillation) but may originate from elsewhere in the arterial tree. In paradoxical embolism, a deep vein thrombosis embolizes through an atrial or ventricular septal defect in the heart into the brain.Causes of stroke related to the heart can be distinguished between high and low-risk:
High risk: atrial fibrillation and paroxysmal atrial fibrillation, rheumatic disease of the mitral or aortic valve disease, artificial heart valves, known cardiac thrombus of the atrium or ventricle, sick sinus syndrome, sustained atrial flutter, recent myocardial infarction, chronic myocardial infarction together with ejection fraction <28 percent, symptomatic congestive heart failure with ejection fraction <30 percent, dilated cardiomyopathy, Libman-Sacks endocarditis, Marantic endocarditis, infective endocarditis, papillary fibroelastoma, left atrial myxoma and coronary artery bypass graft (CABG) surgery.
Low risk/potential: calcification of the annulus (ring) of the mitral valve, patent foramen ovale (PFO), atrial septal aneurysm, atrial septal aneurysm with patent foramen ovale, left ventricular aneurysm without thrombus, isolated left atrial "smoke" on echocardiography (no mitral stenosis or atrial fibrillation), complex atheroma in the ascending aorta or proximal arch.Among those who have a complete blockage of one of the carotid arteries, the risk of stroke on that side is about one percent per year.A special form of embolic stroke is the embolic stroke of undetermined source (ESUS). This subset of cryptogenic stroke is defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources. About one out of six ischemic strokes could be classified as ESUS.
Cerebral hypoperfusion
Cerebral hypoperfusion is the reduction of blood flow to all parts of the brain. The reduction could be to a particular part of the brain depending on the cause. It is most commonly due to heart failure from cardiac arrest or arrhythmias, or from reduced cardiac output as a result of myocardial infarction, pulmonary embolism, pericardial effusion, or bleeding. Hypoxemia (low blood oxygen content) may precipitate the hypoperfusion. Because the reduction in blood flow is global, all parts of the brain may be affected, especially vulnerable "watershed" areas—border zone regions supplied by the major cerebral arteries. A watershed stroke refers to the condition when the blood supply to these areas is compromised. Blood flow to these areas does not necessarily stop, but instead it may lessen to the point where brain damage can occur.
Venous thrombosis
Cerebral venous sinus thrombosis leads to stroke due to locally increased venous pressure, which exceeds the pressure generated by the arteries. Infarcts are more likely to undergo hemorrhagic transformation (leaking of blood into the damaged area) than other types of ischemic stroke.
Intracerebral hemorrhage
It generally occurs in small arteries or arterioles and is commonly due to hypertension, intracranial vascular malformations (including cavernous angiomas or arteriovenous malformations), cerebral amyloid angiopathy, or infarcts into which secondary hemorrhage has occurred. Other potential causes are trauma, bleeding disorders, amyloid angiopathy, illicit drug use (e.g., amphetamines or cocaine). The hematoma enlarges until pressure from surrounding tissue limits its growth, or until it decompresses by emptying into the ventricular system, CSF or the pial surface. A third of intracerebral bleed is into the brains ventricles. ICH has a mortality rate of 44 percent after 30 days, higher than ischemic stroke or subarachnoid hemorrhage (which technically may also be classified as a type of stroke).
Other
Other causes may include spasm of an artery. This may occur due to cocaine.
Silent stroke
A silent stroke is a stroke that does not have any outward symptoms, and people are typically unaware they have had a stroke. Despite not causing identifiable symptoms, a silent stroke still damages the brain and places the person at increased risk for both transient ischemic attack and major stroke in the future. Conversely, those who have had a major stroke are also at risk of having silent strokes. In a broad study in 1998, more than 11 million people were estimated to have experienced a stroke in the United States. Approximately 770,000 of these strokes were symptomatic and 11 million were first-ever silent MRI infarcts or hemorrhages. Silent strokes typically cause lesions which are detected via the use of neuroimaging such as MRI. Silent strokes are estimated to occur at five times the rate of symptomatic strokes. The risk of silent stroke increases with age, but may also affect younger adults and children, especially those with acute anemia.
Pathophysiology
Ischemic
Ischemic stroke occurs because of a loss of blood supply to part of the brain, initiating the ischemic cascade. Atherosclerosis may disrupt the blood supply by narrowing the lumen of blood vessels leading to a reduction of blood flow by causing the formation of blood clots within the vessel or by releasing showers of small emboli through the disintegration of atherosclerotic plaques. Embolic infarction occurs when emboli formed elsewhere in the circulatory system, typically in the heart as a consequence of atrial fibrillation, or in the carotid arteries, break off, enter the cerebral circulation, then lodge in and block brain blood vessels. Since blood vessels in the brain are now blocked, the brain becomes low in energy, and thus it resorts to using anaerobic metabolism within the region of brain tissue affected by ischemia. Anaerobic metabolism produces less adenosine triphosphate (ATP) but releases a by-product called lactic acid. Lactic acid is an irritant which could potentially destroy cells since it is an acid and disrupts the normal acid-base balance in the brain. The ischemia area is referred to as the "ischemic penumbra".As oxygen or glucose becomes depleted in ischemic brain tissue, the production of high energy phosphate compounds such as adenosine triphosphate (ATP) fails, leading to failure of energy-dependent processes (such as ion pumping) necessary for tissue cell survival. This sets off a series of interrelated events that result in cellular injury and death. A major cause of neuronal injury is the release of the excitatory neurotransmitter glutamate. The concentration of glutamate outside the cells of the nervous system is normally kept low by so-called uptake carriers, which are powered by the concentration gradients of ions (mainly Na+) across the cell membrane. However, stroke cuts off the supply of oxygen and glucose which powers the ion pumps maintaining these gradients. As a result, the transmembrane ion gradients run down, and glutamate transporters reverse their direction, releasing glutamate into the extracellular space. Glutamate acts on receptors in nerve cells (especially NMDA receptors), producing an influx of calcium which activates enzymes that digest the cells proteins, lipids, and nuclear material. Calcium influx can also lead to the failure of mitochondria, which can lead further toward energy depletion and may trigger cell death due to programmed cell death.Ischemia also induces production of oxygen free radicals and other reactive oxygen species. These react with and damage a number of cellular and extracellular elements. Damage to the blood vessel lining or endothelium may occur. These processes are the same for any type of ischemic tissue and are referred to collectively as the ischemic cascade. However, brain tissue is especially vulnerable to ischemia since it has little respiratory reserve and is completely dependent on aerobic metabolism, unlike most other organs.
Hemorrhagic
Hemorrhagic strokes are classified based on their underlying pathology. Some causes of hemorrhagic stroke are hypertensive hemorrhage, ruptured aneurysm, ruptured AV fistula, transformation of prior ischemic infarction, and drug-induced bleeding. They result in tissue injury by causing compression of tissue from an expanding hematoma or hematomas. In addition, the pressure may lead to a loss of blood supply to affected tissue with resulting infarction, and the blood released by brain hemorrhage appears to have direct toxic effects on brain tissue and vasculature. Inflammation contributes to the secondary brain injury after hemorrhage.
Diagnosis
Stroke is diagnosed through several techniques: a neurological examination (such as the NIHSS), CT scans (most often without contrast enhancements) or MRI scans, Doppler ultrasound, and arteriography. The diagnosis of stroke itself is clinical, with assistance from the imaging techniques. Imaging techniques also assist in determining the subtypes and cause of stroke. There is yet no commonly used blood test for the stroke diagnosis itself, though blood tests may be of help in finding out the likely cause of stroke. In deceased people, an autopsy of stroke may help establishing the time between stroke onset and death.
Physical examination
A physical examination, including taking a medical history of the symptoms and a neurological status, helps giving an evaluation of the location and severity of a stroke. It can give a standard score on e.g., the NIH stroke scale.
Imaging
For diagnosing ischemic (blockage) stroke in the emergency setting:
CT scans (without contrast enhancements)sensitivity= 16% (less than 10% within first 3 hours of symptom onset)
specificity= 96%MRI scansensitivity= 83%
specificity= 98%For diagnosing hemorrhagic stroke in the emergency setting:
CT scans (without contrast enhancements)sensitivity= 89%
specificity= 100%MRI scansensitivity= 81%
specificity= 100%For detecting chronic hemorrhages, an MRI scan is more sensitive.For the assessment of stable stroke, nuclear medicine scans SPECT and PET/CT may be helpful. SPECT documents cerebral blood flow, whereas PET with an FDG isotope shows cerebral glucose metabolism.
CT scans may not detect an ischemic stroke, especially if it is small, of recent onset, or in the brainstem or cerebellum areas (posterior circulation infarct). MRI is better at detecting a posterior circulation infarct with diffusion-weighted imaging. A CT scan is used more to rule out certain stroke mimics and detect bleeding. The presence of leptomeningeal collateral circulation in the brain is associated with better clinical outcomes after recanalization treatment. Cerebrovascular reserve capacity is another factor that affects stroke outcome – it is the amount of increase in cerebral blood flow after a purposeful stimulation of blood flow by the physician, such as by giving inhaled carbon dioxide or intravenous acetazolamide. The increase in blood flow can be measured by PET scan or transcranial doppler sonography. However, in people with obstruction of the internal carotid artery of one side, the presence of leptomeningeal collateral circulation is associated with reduced cerebral reserve capacity.
Underlying cause
When a stroke has been diagnosed, various other studies may be performed to determine the underlying cause. With the current treatment and diagnosis options available, it is of particular importance to determine whether there is a peripheral source of emboli. Test selection may vary since the cause of stroke varies with age, comorbidity and the clinical presentation. The following are commonly used techniques:
an ultrasound/doppler study of the carotid arteries (to detect carotid stenosis) or dissection of the precerebral arteries;
an electrocardiogram (ECG) and echocardiogram (to identify arrhythmias and resultant clots in the heart which may spread to the brain vessels through the bloodstream);
a Holter monitor study to identify intermittent abnormal heart rhythms;
an angiogram of the cerebral vasculature (if a bleed is thought to have originated from an aneurysm or arteriovenous malformation);
blood tests to determine if blood cholesterol is high, if there is an abnormal tendency to bleed, and if some rarer processes such as homocystinuria might be involved.For hemorrhagic strokes, a CT or MRI scan with intravascular contrast may be able to identify abnormalities in the brain arteries (such as aneurysms) or other sources of bleeding, and structural MRI if this shows no cause. If this too does not identify an underlying reason for the bleeding, invasive cerebral angiography could be performed but this requires access to the bloodstream with an intravascular catheter and can cause further strokes as well as complications at the insertion site and this investigation is therefore reserved for specific situations. If there are symptoms suggesting that the hemorrhage might have occurred as a result of venous throm |
Stroke | bosis, CT or MRI venography can be used to examine the cerebral veins.
Misdiagnosis
Among people with ischemic strokes, misdiagnosis occurs 2 to 26% of the time. A "stroke chameleon" (SC) is stroke which is diagnosed as something else.People not having a stroke may also be misdiagnosed as a stroke. Giving thrombolytics (clot-busting) in such cases causes intracerebral bleeding 1 to 2% of the time, which is less than that of people with strokes. This unnecessary treatment adds to health care costs. Even so, the AHA/ASA guidelines state that starting intravenous tPA in possible mimics is preferred to delaying treatment for additional testing.Women, African-Americans, Hispanic-Americans, Asian and Pacific Islanders are more often misdiagnosed for a condition other than stroke when in fact having a stroke. In addition, adults under 44 years of age are seven times more likely to have a stroke missed than are adults over 75 years of age. This is especially the case for younger people with posterior circulation infarcts. Some medical centers have used hyperacute MRI in experimental studies for persons initially thought to have a low likelihood of stroke. And in some of these persons, strokes have been found which were then treated with thrombolytic medication.
Prevention
Given the disease burden of strokes, prevention is an important public health concern. Primary prevention is less effective than secondary prevention (as judged by the number needed to treat to prevent one stroke per year). Recent guidelines detail the evidence for primary prevention in stroke. In those who are otherwise healthy, aspirin does not appear beneficial and thus is not recommended. In people who have had a myocardial infarction or those with a high cardiovascular risk, it provides some protection against a first stroke. In those who have previously had a stroke, treatment with medications such as aspirin, clopidogrel, and dipyridamole may be beneficial. The U.S. Preventive Services Task Force (USPSTF) recommends against screening for carotid artery stenosis in those without symptoms.
Risk factors
The most important modifiable risk factors for stroke are high blood pressure and atrial fibrillation although the size of the effect is small; 833 people have to be treated for 1 year to prevent one stroke. Other modifiable risk factors include high blood cholesterol levels, diabetes mellitus, end-stage kidney disease, cigarette smoking (active and passive), heavy alcohol use, drug use, lack of physical activity, obesity, processed red meat consumption, and unhealthy diet. Smoking just one cigarette per day increases the risk more than 30%. Alcohol use could predispose to ischemic stroke, as well as intracerebral and subarachnoid hemorrhage via multiple mechanisms (for example, via hypertension, atrial fibrillation, rebound thrombocytosis and platelet aggregation and clotting disturbances). Drugs, most commonly amphetamines and cocaine, can induce stroke through damage to the blood vessels in the brain and acute hypertension. Migraine with aura doubles a persons risk for ischemic stroke. Untreated, celiac disease regardless of the presence of symptoms can be an underlying cause of stroke, both in children and adults.High levels of physical activity reduce the risk of stroke by about 26%. There is a lack of high quality studies looking at promotional efforts to improve lifestyle factors. Nonetheless, given the large body of circumstantial evidence, best medical management for stroke includes advice on diet, exercise, smoking and alcohol use. Medication is the most common method of stroke prevention; carotid endarterectomy can be a useful surgical method of preventing stroke.
Blood pressure
High blood pressure accounts for 35–50% of stroke risk. Blood pressure reduction of 10 mmHg systolic or 5 mmHg diastolic reduces the risk of stroke by ~40%. Lowering blood pressure has been conclusively shown to prevent both ischemic and hemorrhagic strokes. It is equally important in secondary prevention. Even people older than 80 years and those with isolated systolic hypertension benefit from antihypertensive therapy. The available evidence does not show large differences in stroke prevention between antihypertensive drugs—therefore, other factors such as protection against other forms of cardiovascular disease and cost should be considered. The routine use of beta-blockers following a stroke or TIA has not been shown to result in benefits.
Blood lipids
High cholesterol levels have been inconsistently associated with (ischemic) stroke. Statins have been shown to reduce the risk of stroke by about 15%. Since earlier meta-analyses of other lipid-lowering drugs did not show a decreased risk, statins might exert their effect through mechanisms other than their lipid-lowering effects.
Diabetes mellitus
Diabetes mellitus increases the risk of stroke by 2 to 3 times. While intensive blood sugar control has been shown to reduce small blood vessel complications such as kidney damage and damage to the retina of the eye it has not been shown to reduce large blood vessel complications such as stroke.
Anticoagulation drugs
Oral anticoagulants such as warfarin have been the mainstay of stroke prevention for over 50 years. However, several studies have shown that aspirin and other antiplatelets are highly effective in secondary prevention after a stroke or transient ischemic attack. Low doses of aspirin (for example 75–150 mg) are as effective as high doses but have fewer side effects; the lowest effective dose remains unknown. Thienopyridines (clopidogrel, ticlopidine) might be slightly more effective than aspirin and have a decreased risk of gastrointestinal bleeding, but are more expensive. Both aspirin and clopidogrel may be useful in the first few weeks after a minor stroke or high risk TIA. Clopidogrel has less side effects than ticlopidine. Dipyridamole can be added to aspirin therapy to provide a small additional benefit, even though headache is a common side effect. Low-dose aspirin is also effective for stroke prevention after having a myocardial infarction.Those with atrial fibrillation have a 5% a year risk of stroke, and this risk is higher in those with valvular atrial fibrillation. Depending on the stroke risk, anticoagulation with medications such as warfarin or aspirin is useful for prevention. Except in people with atrial fibrillation, oral anticoagulants are not advised for stroke prevention—any benefit is offset by bleeding risk.In primary prevention, however, antiplatelet drugs did not reduce the risk of ischemic stroke but increased the risk of major bleeding. Further studies are needed to investigate a possible protective effect of aspirin against ischemic stroke in women.
Surgery
Carotid endarterectomy or carotid angioplasty can be used to remove atherosclerotic narrowing of the carotid artery. There is evidence supporting this procedure in selected cases. Endarterectomy for a significant stenosis has been shown to be useful in preventing further strokes in those who have already had one. Carotid artery stenting has not been shown to be equally useful. People are selected for surgery based on age, gender, degree of stenosis, time since symptoms and the persons preferences. Surgery is most efficient when not delayed too long—the risk of recurrent stroke in a person who has a 50% or greater stenosis is up to 20% after 5 years, but endarterectomy reduces this risk to around 5%. The number of procedures needed to cure one person was 5 for early surgery (within two weeks after the initial stroke), but 125 if delayed longer than 12 weeks.Screening for carotid artery narrowing has not been shown to be a useful test in the general population. Studies of surgical intervention for carotid artery stenosis without symptoms have shown only a small decrease in the risk of stroke. To be beneficial, the complication rate of the surgery should be kept below 4%. Even then, for 100 surgeries, 5 people will benefit by avoiding stroke, 3 will develop stroke despite surgery, 3 will develop stroke or die due to the surgery itself, and 89 will remain stroke-free but would also have done so without intervention.
Diet
Nutrition, specifically the Mediterranean-style diet, has the potential for decreasing the risk of having a stroke by more than half. It does not appear that lowering levels of homocysteine with folic acid affects the risk of stroke.
Women
A number of specific recommendations have been made for women including taking aspirin after the 11th week of pregnancy if there is a history of previous chronic high blood pressure and taking blood pressure medications during pregnancy if the blood pressure is greater than 150 mmHg systolic or greater than 100 mmHg diastolic. In those who have previously had preeclampsia other risk factors should be treated more aggressively.
Previous stroke or TIA
Keeping blood pressure below 140/90 mmHg is recommended. Anticoagulation can prevent recurrent ischemic strokes. Among people with nonvalvular atrial fibrillation, anticoagulation can reduce stroke by 60% while antiplatelet agents can reduce stroke by 20%. However, a recent meta-analysis suggests harm from anticoagulation started early after an embolic stroke. Stroke prevention treatment for atrial fibrillation is determined according to the CHA2DS2–VASc score. The most widely used anticoagulant to prevent thromboembolic stroke in people with nonvalvular atrial fibrillation is the oral agent warfarin while a number of newer agents including dabigatran are alternatives which do not require prothrombin time monitoring.Anticoagulants, when used following stroke, should not be stopped for dental procedures.If studies show carotid artery stenosis, and the person has a degree of residual function on the affected side, carotid endarterectomy (surgical removal of the stenosis) may decrease the risk of recurrence if performed rapidly after stroke.
Management
Ischemic stroke
Aspirin reduces the overall risk of recurrence by 13% with greater benefit early on. Definitive therapy within the first few hours is aimed at removing the blockage by breaking the clot down (thrombolysis), or by removing it mechanically (thrombectomy). The philosophical premise underlying the importance of rapid stroke intervention was summed up as Time is Brain! in the early 1990s. Years later, that same idea, that rapid cerebral blood flow restoration results in fewer brain cells dying, has been proved and quantified.Tight blood sugar control in the first few hours does not improve outcomes and may cause harm. High blood pressure is also not typically lowered as this has not been found to be helpful. Cerebrolysin, a mixture of pig-derived neurotrophic factors used to treat acute ischemic stroke in many Asian and European countries, does not improve outcomes and may increase the risk of severe adverse events.
Thrombolysis
Thrombolysis, such as with recombinant tissue plasminogen activator (rtPA), in acute ischemic stroke, when given within three hours of symptom onset, results in an overall benefit of 10% with respect to living without disability. It does not, however, improve chances of survival. Benefit is greater the earlier it is used. Between three and four and a half hours the effects are less clear. The AHA/ASA recommend it for certain people in this time frame. A 2014 review found a 5% increase in the number of people living without disability at three to six months; however, there was a 2% increased risk of death in the short term. After four and a half hours thrombolysis worsens outcomes. These benefits or lack of benefits occurred regardless of the age of the person treated. There is no reliable way to determine who will have an intracranial bleed post-treatment versus who will not. In those with findings of savable tissue on medical imaging between 4.5 hours and 9 hours or who wake up with a stroke, alteplase results in some benefit.Its use is endorsed by the American Heart Association, the American College of Emergency Physicians and the American Academy of Neurology as the recommended treatment for acute stroke within three hours of onset of symptoms as long as there are no other contraindications (such as abnormal lab values, high blood pressure, or recent surgery). This position for tPA is based upon the findings of two studies by one group of investigators which showed that tPA improves the chances for a good neurological outcome. When administered within the first three hours thrombolysis improves functional outcome without affecting mortality. 6.4% of people with large strokes developed substantial brain bleeding as a complication from being given tPA thus part of the reason for increased short term mortality. The American Academy of Emergency Medicine had previously stated that objective evidence regarding the applicability of tPA for acute ischemic stroke was insufficient. In 2013 the American College of Emergency Medicine refuted this position, acknowledging the body of evidence for the use of tPA in ischemic stroke; but debate continues. Intra-arterial fibrinolysis, where a catheter is passed up an artery into the brain and the medication is injected at the site of thrombosis, has been found to improve outcomes in people with acute ischemic stroke.
Endovascular treatment
Mechanical removal of the blood clot causing the ischemic stroke, called mechanical thrombectomy, is a potential treatment for occlusion of a large artery, such as the middle cerebral artery. In 2015, one review demonstrated the safety and efficacy of this procedure if performed within 12 hours of the onset of symptoms. It did not change the risk of death, but reduced disability compared to the use of intravenous thrombolysis which is generally used in people evaluated for mechanical thrombectomy. Certain cases may benefit from thrombectomy up to 24 hours after the onset of symptoms.
Craniectomy
Strokes affecting large portions of the brain can cause significant brain swelling with secondary brain injury in surrounding tissue. This phenomenon is mainly encountered in strokes affecting brain tissue dependent upon the middle cerebral artery for blood supply and is also called "malignant cerebral infarction" because it carries a dismal prognosis. Relief of the pressure may be attempted with medication, but some require hemicraniectomy, the temporary surgical removal of the skull on one side of the head. This decreases the risk of death, although some people – who would otherwise have died – survive with disability.
Hemorrhagic stroke
People with intracerebral hemorrhage require supportive care, including blood pressure control if required. People are monitored for changes in the level of consciousness, and their blood sugar and oxygenation are kept at optimum levels. Anticoagulants and antithrombotics can make bleeding worse and are generally discontinued (and reversed if possible). A proportion may benefit from neurosurgical intervention to remove the blood and treat the underlying cause, but this depends on the location and the size of the hemorrhage as well as patient-related factors, and ongoing research is being conducted into the question as to which people with intracerebral hemorrhage may benefit.In subarachnoid hemorrhage, early treatment for underlying cerebral aneurysms may reduce the risk of further hemorrhages. Depending on the site of the aneurysm this may be by surgery that involves opening the skull or endovascularly (through the blood vessels).
Stroke unit
Ideally, people who have had a stroke are admitted to a "stroke unit", a ward or dedicated area in a hospital staffed by nurses and therapists with experience in stroke treatment. It has been shown that people admitted to a stroke unit have a higher chance of surviving than those admitted elsewhere in hospital, even if they are being cared for by doctors without experience in stroke. Nursing care is fundamental in maintaining skin care, feeding, hydration, positioning, and monitoring vital signs such as temperature, pulse, and blood pressure.
Rehabilitation
Stroke rehabilitation is the process by which those with disabling strokes undergo treatment to help them return to normal life as much as possible by regaining and relearning the skills of everyday living. It also aims to help the survivor understand and adapt to difficulties, prevent secondary complications, and educate family members to play a supporting role. Stroke rehabilitation should begin almost immediately with a multidisciplinary approach. The rehabilitation team may involve physicians trained in rehabilitation medicine, neurologists, clinical pharmacists, nursing staff, physiotherapists, occupational therapists, speech-language pathologists, and orthotists. Some teams may also include psychologists and social workers, since at least one-third of affected people manifests post stroke depression. Validated instruments such as the Barthel scale may be used to assess the likelihood of a person who has had a stroke being able to manage at home with or without support subsequent to discharge from a hospital.Stroke rehabilitation should be started as quickly as possible and can last anywhere from a few days to over a year. Most return of function is seen in the first few months, and then improvement falls off with the "window" considered officially by U.S. state rehabilitation units and others to be closed after six months, with little chance of further improvement. However, some people have reported that they continue to improve for years, regaining and strengthening abilities like writing, walking, running, and talking. Daily rehabilitation exercises should continue to be part of the daily routine for people who have had a stroke. Complete recovery is unusual but not impossible and most people will improve to some extent: proper diet and exercise are known to help the brain to recover.
Spatial neglect
The current body of evidence is uncertain on the efficacy of cognitive rehabilitation for reducing the disabling effects of neglect and increasing independence remains unproven. However, there is limited evidence that cognitive rehabilitation may have an immediate beneficial effect on tests of neglect. Overall, no rehabilitation approach can be supported by evidence for spatial neglect.
Automobile driving
The current body of evidence is uncertain whether the use of rehabilitation can improve on-road driving skills following stroke. There is limited evidence that training on a driving simulator will improve performance on recognizing road signs after training. The findings are based on low-quality evidence as further research is needed involving large numbers of participants.
Yoga
Based on low quality evidence, it is currently uncertain whether yoga has a significant benefit for stroke rehabilitation on measures of quality of life, balance, strength, endurance, pain, and disability scores. Yoga may reduce anxiety and could be included as part of patient-centred stroke rehabilitation. Further research is needed assessing the benefits and safety of yoga in stroke rehabilitation.
Action observation for upper limbs
The latest scientific evidence indicates that action observation is beneficial in improving upper limb motor function and dependence in activities of daily living in patients with stroke. Thus, action observation therapy is generally associated with better arm and hand function, with no significant adverse events. The findings are based on low to moderate quality evidence.
Cognitive rehabilitation for attention deficits
The current body of scientific evidence is uncertain on the effectiveness of cognitive rehabilitation for attention deficits in patients following stroke. While there may be an immediate effect after treatment on attention, the findings are based on low to moderate quality and small number of studies. Further research is needed to assess whether the effect can be sustained in day-to-day tasks requiring attention.
Motor imagery for gait rehabilitation
The latest evidence supports the short-term benefits of motor imagery (MI) on walking speed in individuals who have had a stroke, in comparison to other therapies. MI does not improve motor function after stroke and does not seem to cause significant adverse events. The findings are based on low-quality evidence as further research is needed to estimate the effect of MI on walking endurance and the dependence on personal assistance.
Physical and occupational therapy
Physical and occupational therapy have overlapping areas of expertise; however, physical therapy focuses on joint range of motion and strength by performing exercises and relearning functional tasks such as bed mobility, transferring, walking and other gross motor functions. Physiotherapists can also work with people who have had a stroke to improve awareness and use of the hemiplegic side. Rehabilitation involves working on the ability to produce strong movements or the ability to perform tasks using normal patterns. Emphasis is often concentrated on functional tasks and peoples goals. One example physiotherapists employ to promote motor learning involves constraint-induced movement therapy. Through continuous practice the person relearns to use and adapt the hemiplegic limb during functional activities to create lasting permanent changes. Physical therapy is effective for recovery of function and mobility after stroke. Occupational therapy is involved in training to help relearn everyday activities known as the activities of daily living (ADLs) such as eating, drinking, dressing, bathing, cooking, reading and writing, and toileting. Approaches to helping people with urinary incontinence include physical therapy, cognitive therapy, and specialized interventions with experienced medical professionals, however, it is not clear how effective these approaches are at improving urinary incontinence following a stroke.Treatment of spasticity related to stroke often involves early mobilizations, commonly performed by a physiotherapist, combined with elongation of spastic muscles and sustained stretching through various different positions. Gaining initial improvement in range of motion is often achieved through rhythmic rotational patterns associated with the affected limb. After full range has been achieved by the therapist, the limb should be positioned in the lengthened positions to prevent against further contractures, skin breakdown, and disuse of the limb with the use of splints or other tools to stabilize the joint. Cold in the form of ice wraps or ice packs have been proven to briefly reduce spasticity by temporarily dampening neural firing rates. Electrical stimulation to the antagonist muscles or vibrations has also been used with some success. Physical therapy is sometimes suggested for people who experience sexual dysfunction following a stroke.
Interventions for age-related visual problems in patients with stroke
With the prevalence of vision problems increasing with age in stroke patients, the overall effect of interventions for age-related visual problems is currently uncertain. It is also not sure whether people with stroke respond differently from the general population when treating eye problems. Further research in this area is needed as current body of evidence is very low quality.
Speech and language therapy
Speech and language therapy is appropriate for people with the speech production disorders: dysarthria and apraxia of speech, aphasia, cognitive-communication impairments, and problems with swallowing. Speech and language therapy for aphasia following stroke compared to no therapy improves functional communication, reading, writing and expressive language. There may be benefit in high intensity and high doses over a longer period, but these higher intensity doses may not be acceptable to everyone.People who have had a stroke may have particular problems, such as dysphagia, which can cause swallowed material to pass into the lungs and cause aspiration pneumonia. The condition may improve with time, but in the interim, a nasogastric tube may be inserted, enabling liquid food to be given directly into the stomach. If swallowing is still deemed unsafe, then a percutaneous endoscopic gastrostomy (PEG) tube is passed and this can remain indefinitely. Swallowing therapy has mixed results as of 2018.
Devices
Often, assistive technology such as wheelchairs, walkers and canes may be beneficial. Many mobility problems can be improved by the use of ankle foot orthoses.
Physical fitness
A stroke can also reduce peoples general fitness. Reduced fitness can reduce capacity for rehabilitation as well as general health. Physical exercises as part of a rehabilitation program following a stroke appear safe. Cardiorespiratory fitness training that involves walking in rehabilitation can improve speed, tolerance and independence during walking, and may improve balance. There are inadequate long-term data about the effects of exercise and training on death, dependence and disability after a stroke. The future areas of research may concentrate on the optimal exercise prescription and long-term health benefits of exercise. The effect of physical training on cognition also may be studied further.
The ability to walk independently in their community, indoors or outdoors, is important following stroke. Although no negative effects have been reported, it is unclear if outcomes can improve with these walking programs when compared to usual treatment.
Other therapy methods
Some current and future therapy methods include the use of virtual reality and video games for rehabilitation. These forms of rehabilitation offer potential for motivating people to perform specific therapy tasks that many other forms do not. While virtual reality and interactive video gaming are not more effective than conventional therapy for improving upper limb function, when used in conjunction with usual care these approaches may improve upper limb function and ADL function. There are inadequate data on the effect of virtual reality and interactive video gaming on gait speed, balance, participation and quality of life. Many clinics and hospitals are adopting the use of these off-the-shelf devices for exercise, social interaction, and rehabilitation because they are affordable, accessible and can be used within the clinic and home.Mirror therapy is associated with improved motor function of the upper extremity in people who have had a stroke.Other non-invasive rehabilitation methods used to augment physical therapy of motor function in people recovering from a stroke include transcranial magnetic stimulation and transcranial direct-current stimulation. and robotic therapies. Constraint‐induced movement therapy (CIMT), mental practice, mirror therapy, interventions for sensory impairment, virtual reality and a relatively high dose of repetitive task practice may be effective in improving upper limb function. However, further primary research, specifically of CIMT, mental practice, mirror therapy and virtual reality is needed.
Orthotics
Clinical studies confirm the importance of orthoses in stroke rehabilitation. The orthosis supports the therapeutic applications and also helps to mobilize the patient at an early stage. With the help of an orthosis, physiological standing and walking can be learned again, and late health consequences caused by a wrong gait pattern can be prevented. A treatment with an orthosis can therefore be used to support the therapy.
Self-management
A stroke can affect the ability to live independently and with quality. Self-management programs are a special training that educates stroke survivors about stroke and its consequences, helps them acquire skills to cope with their challenges, and helps them set and meet their own goals during their recovery process. These programs are tailored to the target audience, and led by someone trained and expert in stroke and its consequences (most commonly professionals, but also stroke survivors and peers). A 2016 review reported that these programs improve the quality of life after stroke, without negative effects. People with stroke felt more empowered, happy and satisfied with life after participating in this training.
Prognosis
Disability affects 75% of stroke survivors enough to decrease their ability to work.
Stroke can affect people physically, mentally, emotionally, or a combination of the three. The results of stroke vary widely depending on size and location of the lesion.
Physical effects
Some of the physical disabilities that can result from stroke include muscle weakness, numbness, pressure sores, pneumonia, incontinence, apraxia (inability to perform learned movements), difficulties carrying out daily activities, appetite loss, speech loss, vision loss and pain. If the stroke is severe enough, or in a certain location such as parts of the brainstem, coma or death can result. Up to 10% of people following a stroke develop seizures, most commonly in the week subsequent to the event; the severity of the stroke increases the likelihood of a seizure. An estimated 15% of people experience urinary incontinence for more than a year following a stroke. 50% of people have a decline in sexual function (sexual dysfunction) following a stroke.
Emotional and mental effects
Emotional and mental dysfunctions correspond to areas in the brain that have been damaged. Emotional problems following a stroke can be due to direct damage to emotional centers in the brain or from frustration and difficulty adapting to new limitations. Post-stroke emotional difficulties include anxiety, panic attacks, flat affect (failure to express emotions), mania, apathy and psychosis. Other difficulties may include a decreased ability to communicate emotions through facial expression, body language and voice.Disruption in self-identity, relationships with others, and emotional well-being can lead to social consequences after stroke due to the lack of ability to communicate. Many people who experience communication impairments after a stroke find it more difficult to cope with the social issues rather than physical impairments. Broader aspects of care must address the emotional impact speech impairment has on those who experience difficulties with speech after a stroke. Those who experience a stroke are at risk of paralysis which could result in a self disturbed body image which may also lead to other social issues.30 to 50% of stroke survivors develop post-stroke depression, which is characterized by lethargy, irritability, sleep disturbances, lowered self-esteem and withdrawal.Depression can reduce motivation and worsen outcome, but can be treated with social and family support, psychotherapy and, in severe cases, antidepressants. Psychotherapy sessions may have a small effect on improving mood and preventing depression after a stroke, however psychotherapy does not appear to be effective at treating depression after a stroke. Antidepressant medications may be useful for treating depression after a stroke |
Stroke | .Emotional lability, another consequence of stroke, causes the person to switch quickly between emotional highs and lows and to express emotions inappropriately, for instance with an excess of laughing or crying with little or no provocation. While these expressions of emotion usually correspond to the persons actual emotions, a more severe form of emotional lability causes the affected person to laugh and cry pathologically, without regard to context or emotion. Some people show the opposite of what they feel, for example crying when they are happy. Emotional lability occurs in about 20% of those who have had a stroke. Those with a right hemisphere stroke are more likely to have an empathy problems which can make communication harder.Cognitive deficits resulting from stroke include perceptual disorders, aphasia, dementia, and problems with attention and memory. A stroke survivor may be unaware of their own disabilities, a condition called anosognosia. In a condition called hemispatial neglect, the affected person is unable to attend to anything on the side of space opposite to the damaged hemisphere. Cognitive and psychological outcome after a stroke can be affected by the age at which the stroke happened, pre-stroke baseline intellectual functioning, psychiatric history and whether there is pre-existing brain pathology.
Epidemiology
Stroke was the second most frequent cause of death worldwide in 2011, accounting for 6.2 million deaths (~11% of the total). Approximately 17 million people had a stroke in 2010 and 33 million people have previously had a stroke and were still alive. Between 1990 and 2010 the number of strokes decreased by approximately 10% in the developed world and increased by 10% in the developing world. Overall, two-thirds of strokes occurred in those over 65 years old. South Asians are at particularly high risk of stroke, accounting for 40% of global stroke deaths. Incidence of ischemic stroke is ten times more frequent than haemorrhagic stroke.It is ranked after heart disease and before cancer. In the United States stroke is a leading cause of disability, and recently declined from the third leading to the fourth leading cause of death. Geographic disparities in stroke incidence have been observed, including the existence of a "stroke belt" in the southeastern United States, but causes of these disparities have not been explained.
The risk of stroke increases exponentially from 30 years of age, and the cause varies by age. Advanced age is one of the most significant stroke risk factors. 95% of strokes occur in people age 45 and older, and two-thirds of strokes occur in those over the age of 65.A persons risk of dying if he or she does have a stroke also increases with age. However, stroke can occur at any age, including in childhood.Family members may have a genetic tendency for stroke or share a lifestyle that contributes to stroke. Higher levels of Von Willebrand factor are more common amongst people who have had ischemic stroke for the first time. The results of this study found that the only significant genetic factor was the persons blood type. Having had a stroke in the past greatly increases ones risk of future strokes.
Men are 25% more likely to develop strokes than women, yet 60% of deaths from stroke occur in women. Since women live longer, they are older on average when they have their strokes and thus more often killed. Some risk factors for stroke apply only to women. Primary among these are pregnancy, childbirth, menopause, and the treatment thereof (HRT).
History
Episodes of stroke and familial stroke have been reported from the 2nd millennium BC onward in ancient Mesopotamia and Persia. Hippocrates (460 to 370 BC) was first to describe the phenomenon of sudden paralysis that is often associated with ischemia. Apoplexy, from the Greek word meaning "struck down with violence", first appeared in Hippocratic writings to describe this phenomenon.
The word stroke was used as a synonym for apoplectic seizure as early as 1599, and is a fairly literal translation of the Greek term. The term apoplectic stroke is an archaic, nonspecific term, for a cerebrovascular accident accompanied by haemorrhage or haemorrhagic stroke. Martin Luther was described as having an apoplectic stroke that deprived him of his speech shortly before his death in 1546.In 1658, in his Apoplexia, Johann Jacob Wepfer (1620–1695) identified the cause of hemorrhagic stroke when he suggested that people who had died of apoplexy had bleeding in their brains.
Wepfer also identified the main arteries supplying the brain, the vertebral and carotid arteries, and identified the cause of a type of ischemic stroke known as a cerebral infarction when he suggested that apoplexy might be caused by a blockage to those vessels. Rudolf Virchow first described the mechanism of thromboembolism as a major factor.The term cerebrovascular accident was introduced in 1927, reflecting a "growing awareness and acceptance of vascular theories and (...) recognition of the consequences of a sudden disruption in the vascular supply of the brain". Its use is now discouraged by a number of neurology textbooks, reasoning that the connotation of fortuitousness carried by the word accident insufficiently highlights the modifiability of the underlying risk factors. Cerebrovascular insult may be used interchangeably.The term brain attack was introduced for use to underline the acute nature of stroke according to the American Stroke Association, which has used the term since 1990, and is used colloquially to refer to both ischemic as well as hemorrhagic stroke.
Research
As of 2017, angioplasty and stents were under preliminary clinical research to determine the possible therapeutic advantages of these procedures in comparison to therapy with statins, antithrombotics, or antihypertensive drugs.
See also
References
Further reading
External links
Stroke at Curlie
DRAGON Score for Post-Thrombolysis Archived 2020-10-27 at the Wayback Machine
THRIVE score for stroke outcome Archived 2016-09-13 at the Wayback Machine
National Institute of Neurological Disorders and Stroke |
Coral dermatitis | Coral dermatitis is a cutaneous condition caused by injury from the exoskeleton of certain corals.: 430
See also
Skin lesion
== References == |
Halo nevus | Halo nevus (also known as "Leukoderma acquisitum centrifugum," "Perinevoid vitiligo," and "Sutton nevus": 689 ) is a mole that is surrounded by a depigmented ring or halo.
Presentation
Halo nevi are also known as Suttons nevi, or leukoderma acquisitum centrifugum. Halo nevi are named such because they are a mole (nevus) that is surrounded by an area of depigmentation that resembles a halo.
Halo nevi are associated with vitiligo. Sometimes the pale (hypopigmented) areas will spontaneously regress, and pigment returns.
Causes
The formation of a halo surrounding a nevi is believed to occur when certain white blood cells called CD8+ T lymphocytes destroy the pigment-producing cells of the skin (melanocytes). The cause for the attack is unknown.
Diagnosis
Treatment
As halo nevi are only of cosmetic significance, no treatment is required, and patients will be asymptomatic. Although halo nevi are harmless, it is important to monitor the lesion on regular basis. Watch out for any changes in appearance of existing or new halo nevi. If there is any change in appearance or is associated with pain, itch, and infection, a doctor should be consulted immediately to exclude the possibility of melanoma.
Epidemiology
Halo nevi are estimated to be present in approximately 1% of the general population, and are found to be more prevalent in people with vitiligo, malignant melanoma, or Turner syndrome. All races and sexes are equally susceptible to this disease, although a familial tendency has been reported. The average age of onset is in a persons teenage years.
See also
Nevus
List of cutaneous conditions
References
== External links == |
Emphysematous cystitis | Emphysematous cystitis is a rare type of infection of the bladder wall by gas-forming bacteria or fungi. The most frequent offending organism is E. coli. Other gram negative bacteria, including Klebsiella and Proteus are also commonly isolated. Fungi, such as Candida, have also been reported as causative organisms. Citrobacter and Enterococci have also been found to cause emphysematous cystitis. Although it is a rare type of bladder infection, it is the most common type of all gas-forming bladder infections. The condition is characterized by the formation of air bubbles in and around the bladder wall. The gas found in the bladder consists of nitrogen, hydrogen, oxygen, and carbon dioxide. The disease most commonly affects elderly diabetic and immunocompromised patients. The first case was identified in a post-mortem examination in 1888.
Signs and symptoms
Signs and symptoms of emphysematous cystitis include air in the bladder wall, altered mental status, severe abdominal pain, weakness, dark urine, dysuria, fever, lethargy, vomiting, as well as white blood cells and bacteria in the urine. Where some patients may be asymptomatic, others may present with septic shock. Symptoms can vary greatly from patient to patient, which makes the disease difficult to diagnose. In some cases of emphysematous cystitis, patients do not even claim to have any urinary symptoms. Urinary symptoms can include blood in the urine, increased urinary frequency, urgency, occasional incontinence, difficulty voiding, and burning sensation. Emphysematous cystitis is often indicated in patients who have air in the urine. In some cases, emphysematous cystitis can cause thickening of the bladder wall. Clinical subcutaneous emphysema is a rare complication of emphysematous cystitis that has a poor prognosis.
Risk factors
Risk factors include catheter use and chronic urinary tract infections, being female, diabetes mellitus, neurogenic bladder, and being in an immunocompromised state. In 50% of cases, patients are elderly and diabetic. Obstruction of the urinary tract as well as urinary stasis, often brought on by paralysis of the urinary tract, are also major risk factors in addition to diabetes. Transplant recipients have also been found to be at risk. Introduction of infection from external means was discovered in one case study where a male with no history of diabetes or abnormalities to his immune system had recently undergone a transrectal ultrasound needle-guided prostate biopsy contracted a severe case of sepsis, which led to a case of Emphysematous cystitis. The patient went on to develop disseminated intravascular coagulopathy and acute respiratory distress syndrome. After a stay in Intensive Care undergoing broad-spectrum antibiotic therapy, the patient was eventually discharged in stable condition. Patients diagnosed with Emphysematous Cystitis are also commonly diagnosed with urinary tract infections and sepsis. Cases of Emphysematous Cystitis in a clinical study have shown to progress quickly and are life-threatening and sometimes fatal due to inflammation caused by gas forming organisms.
Diagnosis
Due to the atypical presentation and rarity of the infection, it takes a physician longer to diagnose than more common types of bladder infections. Diagnosis requires a personalized investigation with consideration to risk factors and symptoms. Radiology of the abdominal or pubic region has proven to be an important tool in reaching a definitive diagnosis of conditions causing gas in the urinary tract. Computer tomography, or CT scans, are of most help due to their high sensitivity in detecting gas and air bubbles. However, radiology is normally not the first tool used to diagnose. Most diagnoses are made by chance after imaging examination. Sometimes, even when patients dont show symptoms, their Emphysematous cystitis infection level can be very advanced already. Gas in the bladder wall will often have the appearance of cobblestone or a “beaded necklace” with the use of conventional radiography. Delayed diagnosis can lead to a severe infection, extension of the uterus, rupturing of the bladder, and death. Emphysematous cystitis has an overall mortality rate of 7%. However, surgery is only considered in severe cases where the disease progresses involving the ureters, kidneys, or adrenal glands. When required, surgery may be extensive.
Treatment
Even when caught early, aggressive treatment is required. Antibiotics are proven to cure Emphysematous cystitis over time and reduce the amount of gas inside the bladder wall. Prognosis is poor if antibiotics are not used to treat the patient. Additional treatment consists of urinary drainage and good control of blood glucose. The treatment of underlying comorbid diseases, such as diabetes, is extremely important because they can intensify the infection. Hyperbaric oxygen is an effective treatment, and has cured some cases in as little as 48 hours. Although it is unclear as to how gas formation occurs in emphysematous cystitis, its dependent on whether or not the patient has contributing diseases. Gas formation in diabetic patients diagnosed with Emphysematous cystitis has been determined to occur due to the production of carbon dioxide as a result of the fermentation of the high concentrations of glucose. Gas formation in nondiabetic patients is most likely due to the breaking down of urinary lactulose and tissue proteins. Inflammation caused by infection increases pressure and decreases circulation, which provides the perfect environment for bacteria to produce gas.
References
Further reading
== External links == |
Gelastic seizure | A gelastic seizure, also known as "gelastic epilepsy", is a rare type of seizure that involves a sudden burst of energy, usually in the form of laughing. This syndrome usually occurs for no obvious reason and is uncontrollable. It is slightly more common in males than females.
This syndrome can go for very long periods of time without a diagnosis, as it may resemble normal laughing or crying if it occurs infrequently. It has been associated with several conditions, such as temporal and frontal lobe lesions, tumors, atrophy, tuberous sclerosis, hemangiomas, and post-infectious foci, but mainly hypothalamic hamartomas.
The term "gelastic" originates from the Greek word "gelos", which means laughter.
Signs and symptoms
The main sign of a gelastic seizure is a sudden outburst of laughter with no apparent cause. The laughter may sound unpleasant and sardonic rather than joyful. The outburst usually lasts for less than a minute. During or shortly after a seizure, an individual might display some twitching, strange eye movements, lip smacking, fidgeting or mumbling. If a person who has the seizures is hooked up to an electroencephalogram, it will reveal interictal epileptic discharges. This syndrome usually manifests itself before the individual reaches the age of three or four. The temporal lobes, and the hypothalamus are the areas of the brain with the most involvement with these seizures. This may cause learning disabilities, and faulted cognitive function as well. It is not uncommon for children to have tonic-clonic seizures, and atonic seizures directly following the seizure. Those that are associated with hypothalamic hamartomas may occur as often as several times hourly and typically begin during infancy. Seizures that occur in infancy may include bursts of cooing, respirations, giggling, and smiling. Due to early hypothalamic-pituitary-gonadal axis activation in girls who have the seizures, it is not uncommon for them to display secondary sex characteristics before the age of eight.
Causes
A gelastic seizure is classically associated with a hypothalamic hamartoma (a type of brain tumor). A hypothalamic hamartoma is defined as a benign mass of glial tissue on or near the hypothalamus. The size of the hamartoma can vary from one centimeter to larger than three centimeters. They can cause several different types of seizures including a Gelastic Seizure. These structures can be detected with different imaging modalities such as computed tomography, magnetic resonance imaging, Single Photon emission computed tomography (SPECT) and Positron Emission Tomography (PET-CT). A computed tomography scan of an individual with a hypothalamic hamartoma would reveal a suprasellar mass with the same density as brain tissue. Images of these masses are not enhanced with the use of contrast. However, although a computed tomography scan may be useful in diagnosing the cause of a seizure, in the case of a hypothalamic hamartoma, magnetic resonance imaging is the tool of choice due to the cerebrospinal fluid which defines these masses. Single Photon emission computed tomography (SPECT) may also be used which involves the use of a radiotracer that is taken up by the ictal region of the brain where, typically the tumor lies. Positron Emission Tomography (PET-CT) using F-18 fluorodeoxyglucose (FDG) show reduced metabolism at the site of seizure onset. Gelastic seizures have been observed after taking a birth control pill (Maxim (R)).
Optic nerve hypoplasia is the only reported condition with gelastic seizures without hypothalamic hamartomas, suggesting that hypothalamic disorganization alone can cause gelastic seizures.
History
Very likely gelastic seizures were already recognized at the time of Babylonian medicine. A detailed description was given by the Scottish physician Robert Whytt in 1765, and the term "gelastic seizure" was coined in 1898 by the French neurologist, neuropathologist and epileptologist Charles Féré.
Notable Cases
George William Helon (Australian author and businessman) is a Gelastic seizure patient, mentor, counsellor and advocate.
Media references
Gelastic syncope was also referred to in one paper also as "Seinfeld syncope" after an incident in which a patient repeatedly fainted while watching an episode of Seinfeld.
References
External links
Gelastic Seizures - Goran Brandberg, Orvar Eeg-Olofsson
Epilepsy Ontario - Gelastic seizures
Hypothalamic hamartomas and gelastic epilepsy
MR imaging of hypothalamic hamartoma |
Nodular lichen myxedematosus | Nodular lichen myxedematosus is a cutaneous condition characterized by multiple nodules on the limbs and trunk, with a mild or absent papular component.
See also
Papular mucinosis
List of cutaneous conditions
== References == |
Acrocephalosyndactyly | In pediatric medicine, acrocephalosyndactyly is the common presentation of craniosynostosis and syndactyly. When there is also polydactyly the classification is acrocephalopolysyndactyly.
Cause
Diagnosis
Classification
It has several different types:
type I – Apert syndrome: 577
type II – Crouzon syndrome: 577
type III – Saethre–Chotzen syndrome
type IV – Goodman Syndrome
type V – Pfeiffer syndromeA related term, acrocephalopolysyndactyly, refers to the inclusion of polydactyly to the presentation. It also has multiple types:
type I – Noack syndrome; now classified with Pfeiffer syndrome
type II – Carpenter syndrome
type III – Sakati–Nyhan–Tisdale syndrome
type IV – Goodman syndrome; now classified with Carpenter syndrome
type V – Pfeiffer syndromeIt has been suggested that the distinction between "acrocephalosyndactyly" versus "acrocephalopolysyndactyly" should be abandoned.
Treatment
See also
List of skin conditions
Oxycephaly
References
External links
Acrocephalosyndactylia at the US National Library of Medicine Medical Subject Headings (MeSH) |
Fetal warfarin syndrome | Fetal warfarin syndrome is a disorder of the embryo which occurs in a child whose mother took the medication warfarin (brand name: Coumadin) during pregnancy. Resulting abnormalities include low birth weight, slower growth, intellectual disability, deafness, small head size, and malformed bones, cartilage, and joints.Warfarin is an oral anticoagulant drug (blood thinner) used to reduce blood clots, deep vein thrombosis, and embolism in people with prosthetic heart valves, atrial fibrillation, or those who have had ischemic stroke. Warfarin blocks the action of vitamin K, causing an inhibition of blood clotting factors and the pro-bone-building hormone osteocalcin.
Warfarin is a teratogen which can cross from the mother to the developing fetus. The inhibition of clotting factors can lead to internal bleeding of the fetus while the inhibition of osteocalcin causes lower bone growth. As well as birth defects, warfarin can induce spontaneous abortion or stillbirth. Because of this, warfarin is contraindicated during pregnancy.
Signs and symptoms
The key symptoms, visible at birth, vary between individuals exposed to warfarin in utero. The severity and occurrence of symptoms is dose dependent with higher doses (>5 mg warfarin daily) more likely to cause immediately noticeable defects.The period of pregnancy in which warfarin is administered can affect the category of defects which develop. Warfarin taken in the first trimester of pregnancy is more likely to result in physical abnormalities while warfarin taken in the second and third trimester more commonly causes abnormalities of the central nervous system. The more extreme symptoms such as severe intellectual disability, blindness and deafness occur more often when warfarin is used throughout all three trimesters.
Growth
Babies born with fetal warfarin syndrome may have a below-average birth weight and do continue to grow at a reduced rate.
Facial features
Children with fetal warfarin syndrome show many otolaryngological abnormalities consistent with abnormal bone and cartilage growth. Children may present with hypoplasia of the nasal ridge and a deep groove at the midline of the nose, thinned or absent nasal septum, choanal atresia; a narrowing the airway at the posterior nasal cavity, cleft lip and laryngomalacia; large soft protrusions into the larynx. These facial defects and narrowing of the airways often lead to respiratory distress, noisy breathing and later; speech defects. Narrow airways often widen with age and allow for easier breathing. Dental problems are also seen with abnormally large dental buds and late eruption of deciduous teeth.Development of the eyes is also affected by warfarin. Microphthalmia; abnormally small eyes, telecanthus; abnormally far apart eyes and strabismus; misaligned or crossed eyes are common signs of fetal warfarin syndrome. The appearance of an ectopic lacrimal duct, where the tear duct protrudes laterally onto the eye has also been noted.
Bodily features
Whole body skeletal abnormalities are common in fetal warfarin syndrome. A generalized reduction in bone size causes rhizomelia; disproportionally short limbs, brachydactyly; short fingers and toes, a shorter neck, short trunk, scoliosis; abnormal curvature of the spine and stippled epiphyses; malformation of joints. Abnormalities of the chest: either pectus carinatum; a protruding sternum, or pectus excavatum; a sunken sternum form an immediately recognizable sign of fetal warfarin syndrome.
Congenital heart defects such as a thinned atrial septum, coarctation of the aorta, patent ductus arteriosus; a connection between the pulmonary artery and aorta occur in 8% of fetal warfarin syndrome patients. Situs inversus totalis, the complete left-right mirroring of thoracic organs, has also been observed
CNS
Defects of the central nervous system can lead to profound intellectual disabilities. Fetal warfarin syndrome can lead to microcephaly; an abnormally small head, hydrocephaly; increased ventricle size and CSF volume, and agenesis of the corpus callosum. These defects contribute to the appearance of significant intellectual disability in 31% of fetal warfarin syndrome cases. Hypotonia, whole body muscle relaxation, can appear in newborns with severe nervous deficits. Atrophy of the optic nerve can also cause blindness in fetal warfarin syndrome.
Physiological
Inhibition of coagulation and resultant internal bleeding can cause too few red blood cells to be present in the bloodstream and low blood pressure in newborns with fetal warfarin syndrome. Low hemoglobin levels can lead to partial oxygen starvation, a high level of lactic acid in the bloodstream, and acidosis. Prolonged oozing of fluid from the stump of the cut umbilical cord is common.
Cause
Fetal warfarin syndrome appears in greater than 6% of children whose mothers took warfarin during pregnancy. Warfarin has a low molecular weight so can pass from the maternal to fetal bloodstream through the tight filter-like junctions of the placental barrier.
As the teratogenic effects of warfarin are well known, the medication is rarely prescribed to pregnant women. However, for some patients, the risks associated with discontinuing warfarin use may outweigh the risk of embryopathy. Patients with prosthetic heart valves carry a particularly high risk of thrombus formation due to the inorganic surface and turbulent blood flow generated by a mechanical prosthesis. The risk of blood clotting is further increased by generalized hypercoagulability as concentrations of clotting factors rise during pregnancy. This increased chance of blood clots leads to an increased risk of potentially fatal pulmonary or systemic emboli cutting off blood flow and oxygen to critical organs. Thus, some patients may continue taking warfarin throughout the pregnancy despite the risks to the developing child.
Mechanism
Warfarins ability to cause fetal warfarin syndrome in utero stems from its ability to limit vitamin K activation. Warfarin binds to and blocks the enzyme Vitamin K epoxide reductase which is usually responsible for activating vitamin K during vitamin K recycling. Vitamin K, once activated, is able to add a carboxylic acid group to glutamate residues of certain proteins which assists in correct protein folding. Without active vitamin K, a fetus exposed to warfarin is unable to produce large quantities of clotting and bone growth factors.
Without vitamin K, clotting factors II, VII, IX and X are unable to be produced. Without these vital parts of the coagulation cascade a durable fibrin plug cannot form to block fluid escaping from damaged or permeable vasculature. Anemia is common in fetuses exposed to warfarin as blood constantly seeps into the interstitial fluid or amniotic cavity. High doses of warfarin and heavy bleeding lead to abortion and stillbirth.
Osteocalcin is another protein dependent on vitamin K for correct folding and function. Osteocalcin is normally secreted by osteoblast cells and plays a role in aiding correct bone mineralization and bone maturation. In the presence of warfarin and subsequent absence of vitamin K and active osteocalcin, bone mineralization and growth are stunted.
Prevention
Fetal warfarin syndrome is prevented by withholding prescription to pregnant women or those trying to conceive. As warfarin can remain in the mothers body for up to five days, warfarin should not be administered in the days leading up to conception. Doctors must take care to ensure women of reproductive age are aware of the risks to the baby should they get pregnant, before prescribing warfarin.
For some women, such as those with prosthetic heart valves, anticoagulation medication cannot be suspended during pregnancy as the risk of thrombus and emboli is too high. In such cases an alternate anticoagulant, which cannot pass through the placental barrier to the fetus, is proscribed in place of warfarin. Heparin is one such anticoagulant medication, although its efficacy in patients with prosthetic heart valves is not well established. New anticoagulant medications, which are efficacious and non-teratogenic such as ximelagatran continue to be developed.
Management
Medication
As well as the routine dose of vitamin K given to newborns after birth, babies born with fetal warfarin syndrome are given additional doses intramuscularly to overcome any remaining warfarin in the circulation and prevent further bleeding. Fresh frozen plasma is also administered to raise concentrations of active blood clotting factors. If the child is anemic from extensive bleeding in-utero, red blood cell concentrate is given to restore oxygen carrying capacity.
Surgical correction
Surgical interventions can be given to improve functionality and correct cosmetic abnormalities. Osteotomy (bone cutting) and zetaplasty surgeries are used to cut away abnormal tissue growths at the piriform aperture around and pharynx to reduce airway obstruction. Rhinoplasty surgery is used to restore normal appearance and function of the nose. Heart surgery may also be required to close a patent ductus arteriosus.
References
External links
Datagenno - Fetal Warfarin Syndrome |
Polyradiculoneuropathy | Polyradiculoneuropathy describes a condition in which polyneuropathy and polyradiculopathy occur together. An example is Guillain–Barré syndrome.Treatment with a single course of intravenous immunoglobulin (IVIG) infusions has been demonstrated to be a potentially effective treatment (reported to have caused prolonged remission in a case associated with systemic lupus (Systemic lupus erythematosus) ).
References
External links
Polyradiculoneuropathy at the US National Library of Medicine Medical Subject Headings (MeSH) |
Necrotizing fasciitis | Necrotizing fasciitis (NF), also known as flesh-eating disease, is a bacterial infection that results in the death of parts of the bodys soft tissue. It is a severe disease of sudden onset that spreads rapidly. Symptoms usually include red or purple skin in the affected area, severe pain, fever, and vomiting. The most commonly affected areas are the limbs and perineum.Typically, the infection enters the body through a break in the skin such as a cut or burn. Risk factors include poor immune function such as from diabetes or cancer, obesity, alcoholism, intravenous drug use, and peripheral artery disease. It does not typically spread between people. The disease is classified into four types, depending on the infecting organism. Between 55 and 80% of cases involve more than one type of bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) is involved in up to a third of cases. Medical imaging is often helpful to confirm the diagnosis.Necrotizing fasciitis may be prevented with proper wound care and handwashing. It is usually treated with surgery to remove the infected tissue, and intravenous antibiotics. Often, a combination of antibiotics is used, such as penicillin G, clindamycin, IV vancomycin, and gentamicin. Delays in surgery are associated with a much higher risk of death. Despite high-quality treatment, the risk of death is between 25 and 35%.Necrotizing fasciitis occurs in about 0.4 people per 100,000 per year in the U.S., and about 1 per 100,000 in Western Europe. Both sexes are affected equally. It becomes more common among older people and is rare in children. It has been described at least since the time of Hippocrates. The term "necrotizing fasciitis" first came into use in 1952.
Signs and symptoms
Symptoms may include fever, swelling, and complaints of excessive pain. The initial skin changes are similar to cellulitis or abscess, thus making the diagnosis at early stages difficult. Hardening of the skin and soft tissue and swelling beyond the area of skin changes are commonly present in those with early necrotizing changes. The redness and swelling usually blend into surrounding normal tissues. The overlying skin may appear shiny and tense. Other signs which are more suggestive of necrotizing changes (but present in later stages in 7 to 44% of the cases) are: formation of bullae, bleeding into the skin which is present before skin necrosis (skin turning from red to purple and black due to thrombosis of blood vessels), presence of gas in tissues, and reduced or absent sensation over the skin (due to the necrosis of the underlying nerves). Rapid progression to shock despite antibiotic therapy is another indication of necrotizing fasciitis. Necrotizing changes affecting the groin are known as Fournier gangrene.However, those who are immunocompromised (have cancer, use corticosteroid, on radiotherapy, chemotherapy, HIV/AIDS, or prior organ or bone marrow transplantation) may not show typical symptoms. Immunocompromised persons also have twice the risk of death from necrotizing infections, so higher suspicion should be maintained in this group.
Cause
Risk factors
More than 70% of cases are recorded in people with at least one of these clinical situations: immunosuppression, diabetes, alcoholism/drug abuse/smoking, malignancies, and chronic systemic diseases. For reasons that are unclear, it occasionally occurs in people with an apparently normal general condition.Necrotizing fasciitis can occur at any part of the body, but it is more commonly seen at the extremities, perineum, and genitals. Only a few of such cases arise from the chest and abdomen. Trauma is the usual cause of the infection, such as from intravenous drug injection, insulin injection, animal and insect bites, catheter insertion over the skin, or a fistula connecting skin to the internal body organs. Skin infections such as abscess and ulcers can also complicate necrotizing fasciitis. Spreading of infection through blood has been suggested for those with streptococcal pharyngitis. For infection of the perineum and genitals (Fournier gangrene), trauma, surgery, urinary tract infection, stones, and Bartholin gland abscess are the usual causes.The risk of developing necrotizing fasciitis from a wound can be reduced by good wound care and handwashing.
Bacteria
Types of soft-tissue necrotizing infection can be divided into four classes according to the types of bacteria infecting the soft tissue. This classification system was first described by Giuliano and his colleagues in 1977.Type I infection: This is the most common type of infection, and accounts for 70 to 80% of cases. It is caused by a mixture of bacterial types, usually in abdominal or groin areas. This type of infection is usually caused by various species of Gram-positive cocci, (Staphylococcus aureus, Streptococcus pyogenes, and enterococci), Gram-negative rods, (Escherichia coli, Pseudomonas aeruginosa), and anaerobes, (Bacteroides and Clostridium species). Populations of those affected are typically older with medical comorbidities such as diabetes mellitus, obesity, and immunodeficiency. Usually, trauma is not the cause of such infections. Previous history of abscess infection or gut perforation with bacterial translocation may be elicited. Clostridial infection accounts for 10% of type I infection. Clostridium species involved are Clostridium perfringens, Clostridium septicum, and Clostridium sordellii, which typically cause gas gangrene (also known as myonecrosis). Clostridium perfringens produces two deadly toxins: alpha-toxin and theta-toxin. Alpha-toxin causes excessive platelet aggregation which blocks blood vessels and deprives the vital organs of oxygen supply. This creates an acidic, oxygen-deficient environment for the proliferation of bacteria. When alpha-toxin is absorbed by soft tissues, it can inhibit the migration of white blood cells from blood vessels into the soft tissue, thus impairing phagocyte function. The two toxins together can cause destruction of red blood cells in blood vessels, damage to the integrity of the blood vessels, and suppression of heart function.Clostridium sordellii can also produce two major toxins: all known virulent strains produce the essential virulence factor lethal toxin (TcsL), and a number also produce haemorrhagic toxin (TcsH). TcsL and TcsH are both members of the large clostridial cytotoxin (LCC) family. The key Clostridium septicum virulence factor is a pore-forming toxin called alpha-toxin, though it is unrelated to the Clostridium perfringens alpha-toxin. Myonecrotic infections caused by these clostridial species commonly occur in injecting heroin users. Those with clostridial infections typically have severe pain at the wound site, where the wound typically drains foul-smelling blood mixed with serum (serosanguinous discharge). Shock can progress rapidly after initial injury or infection, and once the state of shock is established, the chance of dying exceeds 50%. Another bacterium associated with similar rapid disease progression is group A streptococcal infection (mostly Streptococcus pyogenes). Meanwhile, other bacterial infections require two or more days to become symptomatic.Type II infection: This infection accounts for 20 to 30% of cases, mainly involving the extremities. This mainly involves Streptococcus pyogenes bacteria, alone or in combination with staphylococcal infections. Both types of bacteria can progress rapidly and manifest as toxic shock syndrome. Streptococcus species produce M protein, which acts as a superantigen, stimulating a massive systemic immune response which is not effective against the bacterial antigen, precipitating shock. Type II infection more commonly affects young, healthy adults with a history of injury.Type III infection: Vibrio vulnificus, a bacterium found in saltwater, is a rare cause of this infection, which occurs through a break in the skin. Disease progression is similar to type II but sometimes with little visible skin changes.Type IV infection: Some authors have described the type IV infection as fungal in nature.
Diagnosis
Early diagnosis is difficult, as the disease often looks early on like a simple superficial skin infection. While a number of laboratory and imaging modalities can raise the suspicion for necrotizing fasciitis, none can rule it out. The gold standard for diagnosis is a surgical exploration in a setting of high suspicion. When in doubt, a small incision can be made into the affected tissue, and if a finger easily separates the tissue along the fascial plane, the diagnosis is confirmed and an extensive debridement should be performed.
Medical imaging
Imaging has a limited role in the diagnosis of necrotizing fasciitis. The time delay in performing imaging is a major concern. Plain radiography may show subcutaneous emphysema (gas in the subcutaneous tissue), which is strongly suggestive of necrotizing changes, but it is not sensitive enough to detect all the cases, because necrotizing skin infections caused by bacteria other than clostridial infections usually do not show subcutaneous emphysema. If the diagnosis is still in doubt, computed tomography (CT) scans and magnetic resonance imaging (MRI) are more sensitive modalities than plain radiography. However, both the CT scan and MRI are not sensitive enough to rule out necrotizing changes completely. CT scan may show fascial thickening, edema, subcutaneous gas, and abscess formation. In MRI, when fluid collection with deep fascia involvement occurs, thickening or enhancement with contrast injection, necrotizing fasciitis should be strongly suspected. Meanwhile, ultrasonography can show superficial abscess formation, but is not sensitive enough to diagnose necrotizing fasciitis. CT scan is able to detect about 80% of cases, while MRI may pick up slightly more.
Scoring system
A white blood cell count greater than 15,000 cells/mm3 and serum sodium level less than 135 mmol/L have a sensitivity of 90% in detecting the necrotizing soft tissue infection. It also has a 99% chance of ruling out necrotizing changes if the values have shown otherwise. Various scoring systems are being developed to determine the likelihood of getting necrotizing fasciitis, but a scoring system developed by Wong and colleagues in 2004 is the most commonly used. It is the laboratory risk indicator for necrotizing fasciitis (LRINEC) score, which can be used to stratify by risk those people having signs of severe cellulitis or abscess to determine the likelihood of necrotizing fasciitis being present. It uses six laboratory values: C-reactive protein, total white blood cell count, hemoglobin, sodium, creatinine, and blood glucose. A score of 6 or more indicates that necrotizing fasciitis should be seriously considered. The scoring criteria are:
CRP (mg/L) ≥150: 4 points
WBC count (×103/mm3)
<15: 0 points
15–25: 1 point
>25: 2 points
Hemoglobin (g/dL)
>13.5: 0 points
11–13.5: 1 point
<11: 2 points
Sodium (mmol/L) <135: 2 points
Creatinine (umol/L) >141: 2 points
Glucose (mmol/L) >10: 1 pointHowever, the scoring system has not been validated. The values would be falsely positive if any other inflammatory conditions are present. Therefore, the values derived from this scoring system should be interpreted with caution. About 10% of patients with necrotizing fasciitis in the original study still had a LRINEC score <6. A validation study showed that patients with a LRINEC score ≥6 have a higher rate of both death and amputation.
Prevention
Necrotizing fasciitis can be partly prevented by good wound care and handwashing.
Treatment
Surgical debridement (cutting away affected tissue) is the mainstay of treatment for necrotizing fasciitis. Early medical treatment is often presumptive; thus, antibiotics should be started as soon as this condition is suspected. Tissue cultures (rather than wound swabs) are taken to determine appropriate antibiotic coverage, and antibiotics may be changed in light of results. Besides blood pressure control and hydration, support should be initiated for those with unstable vital signs and low urine output.
Surgery
Aggressive wound debridement should be performed early, usually as soon as the diagnosis of necrotizing soft tissue infection (NSTI) is made. Surgical incisions often extend beyond the areas of induration (the hardened tissue) to remove the damaged blood vessels that are responsible for the induration. However, cellulitic soft tissues are sometimes spared from debridement for later skin coverage of the wound. More than one operation may be used to remove additional necrotic tissue. In some cases when an extremity is affected by a NSTI, amputation may be the surgical treatment of choice. After the wound debridement, adequate dressings should be applied to prevent exposure of bones, tendons, and cartilage so that such structures do not dry out and to promote wound healing.For necrotizing infection of the perineal area (Fourniers gangrene), wound debridement and wound care in this area can be difficult because of the excretory products that often render this area dirty and affect the wound-healing process. Therefore, regular dressing changes with a fecal management system can help to keep the wound at the perineal area clean. Sometimes, colostomy may be necessary to divert the excretory products to keep the wound at the perineal area clean.
Antibiotics
Empiric antibiotics are usually initiated as soon as the diagnosis of NSTI has been made, and then later changed to culture-guided antibiotic therapy. In the case of NSTIs, empiric antibiotics are broad-spectrum, covering gram-positive (including MRSA), gram-negative, and anaerobic bacteria.While studies have compared moxifloxacin (a fluoroquinolone) and amoxicillin-clavulanate (a penicillin) and evaluated appropriate duration of treatment (varying from 7 to 21 days), no definitive conclusions on the efficacy of treatment, ideal duration of treatment, or the adverse effects could be made due to poor-quality evidence.
Add-on therapy
Hyperbaric oxygen: While human and animal studies have shown that high oxygen tension in tissues helps to reduce edema, stimulate fibroblast growth, increase the killing ability of white blood cells, inhibit bacterial toxin release, and increase antibiotic efficacy, no high-quality trials have been shown to support or refute the use of hyperbaric oxygen therapy in patients with NSTIs.
Intravenous immunoglobulin (IVIG): No clear difference between using IVIG and placebo has been shown in the treatment of NSTIs, and one study showed serious adverse effects with IVIG use, including acute kidney injury, allergic reactions, aseptic meningitis syndrome, haemolytic anaemia, thrombi, and transmissible agents.
AB103: One study assessed the efficacy of a new type of treatment that affects the immune response, called AB103. The study showed no difference in mortality with use of this therapy, but it is difficult to draw definitive conclusions due to low-quality evidence.
Supportive therapy: Supportive therapy, often including intravenous hydration, wound care, anticoagulants to prevent thromboembolic events, pain control, etc. should always be provided to patients when appropriate.
Epidemiology
Necrotizing fasciitis affects about 0.4 in every 100,000 people per year in the United States. About 1,000 cases of necrotizing fasciitis occur per year in the United States, but the rates have been increasing. This could be due to increasing awareness of this condition, leading to increased reporting, or bacterial virulence or increasing bacterial resistance against antibiotics. In some areas of the world, it is as common as one in every 100,000 people.Higher rates of necrotizing fasciitis are seen in those with obesity or diabetes, and those who are immunocompromised or alcoholic, or have peripheral artery disease. However, the disease may also occur in young, healthy adults with no underlying illnesses. NSAIDs may increase the rates of necrotizing infections due to the modification of immune response in the body, because NSAIDs inhibit the cycloxygenase-1 and cycloxygenase-2 enzymes which are important in producing thromboxane and prostaglandin E2. Prostaglandin has been responsible for fever, inflammation, and pain. The inhibition of prostaglandin E2 production reduces inflammatory response and leukocyte adhesion, and thus reduces immune response against bacterial invasion, giving rise to soft-tissue infection.
History
In the fifth century BCE, Hippocrates described necrotizing soft tissue infection as a disease where those affected would have "erysipelas all over the body while the cause was only a trivial accident. Bones, flesh, and sinew (cord, tendon, or nerve) would fall off from the body and there were many deaths". The first English description for necrotizing soft-tissue infection was by British surgeon Leonard Gillespie and British physicians Gilbert Blaine and Thomas Trotter in the 18th century. At that time, necrotizing soft-tissue infections were known variously as "phagedaenic ulcer" (ulceration that spreads and destroys surrounding tissue), "gangrenous phagedena", "gangrenous ulcer", "malignant ulcer", "putrid ulcer", "fulminating gangrene", "necrotizing erysipelas", "gangrenous erysipelas", "crepitant cellulitis", "gangrenous cellulitis", "Meleney cellulitis", "necrotizing synergistic cellulitis", "hemolytic streptococcal gangrene", "progressive bacterial synergistic gangrene", "necrotizing abscess", "galloping gangrene", or "hospital gangrene". Later, "hospital gangrene" became more commonly used. In 1871 Confederate States Army surgeon Joseph Jones reported 2,642 cases of hospital gangrene with a mortality rate of 46%. In 1883, Dr Jean-Alfred Fournier described the necrotizing infection of the perineum and scrotum, now called Fournier gangrene. The term "necrotizing fasciitis" was first coined by Wilson in 1952. Its definition has become broader, to include not only infection of fascia, but also other soft-tissue infection. Despite being disfavored by the medical community, the term "galloping gangrene" is frequently used in sensationalistic news media to refer to outbreaks of necrotizing fasciitis.
Society and culture
Notable cases
1994 Lucien Bouchard, former premier of Québec, Canada, who was infected while leader of the federal official opposition Bloc Québécois party, lost a leg to the illness.
1994 A cluster of cases occurred in Gloucestershire, in the west of England. Of five confirmed and one probable infection, two died. The cases were believed to be connected. The first two had acquired the Streptococcus pyogenes bacteria during surgery; the remaining four were community-acquired. The cases generated much newspaper coverage, with lurid headlines such as "Flesh Eating Bug Ate My Face".
1997 Ken Kendrick, former agent and partial owner of the San Diego Padres and Arizona Diamondbacks, contracted the disease. He had seven surgeries in a little more than a week and later fully recovered.
2004 Don Rickles, American stand-up comedian, actor, and author, known especially for his insult comedy, contracted the disease in his left leg. He had six operations and later recovered. The condition confined him in his later years to performing comedy from a chair.
2004 Eric Allin Cornell, winner of the 2001 Nobel Prize in Physics, lost his left arm and shoulder to the disease.
2005 Alexandru Marin, an experimental particle physicist, professor at MIT, Boston University, and Harvard University, and researcher at CERN and JINR, died from the disease.
2006 Alan Coren, British writer and satirist, announced in his Christmas column for The Times that his long absence as a columnist had been caused by his contracting the disease while on holiday in France.
2009 R. W. Johnson, British journalist and historian, contracted the disease in March after injuring his foot while swimming. His leg was amputated above the knee.
2011 Jeff Hanneman, guitarist for the thrash metal band Slayer, contracted the disease. He died of liver failure two years later, on May 2, 2013, and it was speculated that his infection was the cause of death. However, on May 9, 2013, the official cause of death was announced as alcohol-related cirrhosis. Hanneman and his family had apparently been unaware of the extent of the condition until shortly before his death.
2011 Peter Watts, Canadian science-fiction author, contracted the disease. On his blog, Watts reported, "Im told I was a few hours away from being dead...If there was ever a disease fit for a science-fiction writer, flesh-eating disease has got to be it. This...spread across my leg as fast as a Star Trek space disease in time-lapse."
2014 Daniel Gildenlöw, Swedish singer and songwriter for the band Pain of Salvation, spent several months in a hospital after being diagnosed with necrotizing fasciitis on his back in early 2014. After recovering, he wrote the album In the Passing Light of Day, a concept album about his experience during the hospitalization.
2015 Edgar Savisaar, Estonian politician, had his right leg amputated. He got the disease during a trip to Thailand.
2018 Alex Smith, an American football quarterback for the Washington Football Team of the National Football League (NFL), contracted the disease after being injured during a game. He suffered an open compound fracture in his lower leg, which became infected. Smith narrowly avoided amputation, and eventually returned to playing professional football in October 2020. Smiths injury and recovery is the subject of the ESPN documentary "E60 Presents: Project 11".
See also
Capnocytophaga canimorsus
Gangrene
Mucormycosis, a rare fungal infection that can resemble necrotizing fasciitis (See type IV NF listing above)
Noma (disease)
Toxic shock syndrome
Vibrio vulnificus
References
External links
Necrotizing fasciitis at Curlie
LRINEC Score Online |
Suntan | Suntan may refer to:
Sun tanning
Suntan (apple), a cultivar
Lockheed CL-400 Suntan, a concept aircraft
Suntan (1976 film), a Bollywood drama film
Suntan (2016 film), a Greek drama film
Project Suntan, a NASA project involving liquid nitrogen research |
Iatrogenesis | Iatrogenesis is the causation of a disease, a harmful complication, or other ill effect by any medical activity, including diagnosis, intervention, error, or negligence. First used in this sense in 1924, the term was introduced to sociology in 1976 by Ivan Illich, alleging that industrialized societies impair quality of life by overmedicalizing life. Iatrogenesis may thus include mental suffering via medical beliefs or a practitioners statements. Some iatrogenic events are obvious, like amputation of the wrong limb, whereas others, like drug interactions, can evade recognition. In a 2013 estimate, about 20 million negative effects from treatment had occurred globally. In 2013, an estimated 142,000 persons died from adverse effects of medical treatment, up from an estimated 94,000 in 1990.
Iatrogenic avenues
Risk associated with medical interventions
Adverse effects of prescription drugs
Overuse of drugs (causing, for example, antibiotic resistance in bacteria)
Prescription drug interaction
Medical errors
Incorrect prescription, perhaps due to illegible handwriting or computer typos
Faulty procedures, techniques, information, methods, or equipment
Negligence
Hospital-acquired infections
Causes and consequences
Medical error and negligence
Iatrogenic conditions need not result from medical errors, such as mistakes made in surgery, or the prescription or dispensing of the wrong therapy, such as a drug. In fact, intrinsic and sometimes adverse effects of a medical treatment are iatrogenic. For example, radiation therapy and chemotherapy—necessarily aggressive for therapeutic effect – frequently produce such iatrogenic effects as hair loss, hemolytic anemia, diabetes insipidus, vomiting, nausea, brain damage, lymphedema, infertility, etc. The loss of function resulting from the required removal of a diseased organ is iatrogenic, as in the case of diabetes consequential to the removal of all or part of the pancreas.
The incidence of iatrogenesis may be misleading in some cases. For example, a ruptured aortic aneurysm is fatal in most cases; the survival rate for treatment of a ruptured aortic aneurysm is under 25%. Patients who die during or after an operation will still be considered iatrogenic deaths, but the procedure itself remains a better bet than the probability of death if left untreated.
Other situations may involve actual negligence or faulty procedures, such as when pharmacotherapists produce handwritten prescriptions for drugs.
Adverse effects
A very common iatrogenic effect is caused by drug interaction, i.e., when pharmacotherapists fail to check for all medications a patient is taking and prescribe new ones that interact agonistically or antagonistically (thereby potentiating or attenuating the intended therapeutic effect). Such situations can cause significant morbidity and mortality. Adverse reactions, such as allergic reactions to drugs, even when unexpected by pharmacotherapists, are also classified as iatrogenic.
The evolution of antibiotic resistance in bacteria is iatrogenic as well. Bacterial strains resistant to antibiotics have evolved in response to the over prescription of antibiotic drugs.Certain drugs are toxic in their own right in therapeutic doses because of their mechanism of action. Alkylating antineoplastic agents, for example, cause DNA damage, which is more harmful to cancer cells than regular cells. However, alkylation causes severe side-effects and is actually carcinogenic in its own right, with potential to lead to the development of secondary tumors. In a similar manner, arsenic-based medications like melarsoprol, used to treat trypanosomiasis, can cause arsenic poisoning.
Adverse effects can appear mechanically. The design of some surgical instruments may be decades old, hence certain adverse effects (such as tissue trauma) may never have been properly characterized.
Psychiatry
In psychiatry, iatrogenesis can occur due to misdiagnosis (including diagnosis with a false condition, as was the case of hystero-epilepsy). An example of a partially iatrogenic condition due to common misdiagnosis is bipolar disorder, especially in pediatric patients. Other conditions such as somatoform disorder and chronic fatigue syndrome are theorized to have significant sociocultural and iatrogenic components. Posttraumatic stress disorder is hypothesized to be prone to iatrogenic complications based on treatment modality. Even use of antipsychotic drugs leads to loss of brain mass.The psychiatric treatment of some conditions and populations, such as substance abuse are regarded as carrying risks for iatrogenesis. At the other end of the spectrum, dissociative identity disorder is considered by a minority of theorists to be a wholly iatrogenic disorder with the bulk of diagnoses arising from a tiny fraction of practitioners.The degree of association of any particular condition with iatrogenesis is unclear and in some cases controversial. The over-diagnosis of psychiatric conditions (with the assignment of mental illness terminology) may relate primarily to clinician dependence on subjective criteria. The assignment of pathological nomenclature is rarely a benign process and can easily rise to the level of emotional iatrogenesis, especially when no alternatives outside of the diagnostic naming process have been considered. Many former patients come to the conclusion that their difficulties are largely the result of the power relationships inherent in psychiatric treatment, which has led to the rise of the anti-psychiatry movement.
Iatrogenic poverty
Meessen et al. used the term "iatrogenic poverty" to describe impoverishment induced by medical care. Impoverishment is described for households exposed to catastrophic health expenditure or to hardship financing. Every year, worldwide, over 100,000 households fall into poverty due to health care expenses. A study reported that in the United States in 2001, illness and medical debt caused half of all personal bankruptcies. Especially in countries in economic transition, the willingness to pay for health care is increasing, and the supply side does not stay behind and develops very fast. But the regulatory and protective capacity in those countries is often lagging behind. Patients easily fall into a vicious cycle of illness, ineffective therapies, consumption of savings, indebtedness, sale of productive assets, and eventually poverty.
Social and cultural iatrogenesis
The 20th-century social critic Ivan Illich broadened the concept of medical iatrogenesis in his 1974 book Medical Nemesis: The Expropriation of Health by defining it at three levels.
First, clinical iatrogenesis is the injury done to patients by ineffective, unsafe, and erroneous treatments as described above. In this regard, he described the need for evidence-based medicine 20 years before the term was coined.
Second, at another level social iatrogenesis is the medicalization of life in which medical professionals, pharmaceutical companies, and medical device companies have a vested interest in sponsoring sickness by creating unrealistic health demands that require more treatments or treating non-diseases that are part of the normal human experience, such as age-related declines. In this way, aspects of medical practice and medical industries can produce social harm in which society members ultimately become less healthy or excessively dependent on institutional care. He argued that medical education of physicians contributes to medicalization of society because they are trained predominantly for diagnosing and treating illness, therefore they focus on disease rather than on health. Iatrogenic poverty (above) can be considered a specific manifestation of social iatrogenesis.
Third, cultural iatrogenesis refers to the destruction of traditional ways of dealing with, and making sense of, death, suffering, and sickness. In this way the medicalization of life leads to cultural harm as society members lose their autonomous coping skills. It is worth noting that in these critiques "Illich does not reject all benefits of modern society but rejects those that involve unwarranted dependency and exploitation."
Epidemiology
Globally it is estimated that 142,000 people died in 2013 from adverse effects of medical treatment, an increase of 51 percent from 94,000 in 1990. In the United States, estimated deaths per year include:
12,000 due to unnecessary surgery
7,000 due to medication errors in hospitals
20,000 due to other errors in hospitals
80,000 due to nosocomial infections in hospitals
106,000 due to non-error, negative effects of drugsBased on these figures, iatrogenesis may cause as many as 225,000 deaths per year in the United States (excluding recognizable error). An earlier Institute of Medicine report estimated 230,000 to 284,000 iatrogenic deaths annually.
History
The term iatrogenesis means brought forth by a healer, from the Greek ἰατρός (iatros, "healer") and γένεσις (genesis, "origin"); as such, in its earlier forms, it could refer to good or bad effects.
Since at least the time of Hippocrates, people have recognized the potentially damaging effects of medical intervention. "First do no harm" (primum non nocere) is a primary Hippocratic mandate in modern medical ethics. Iatrogenic illness or death caused purposefully or by avoidable error or negligence on the healers part became a punishable offense in many civilizations.The transfer of pathogens from the autopsy room to maternity patients, leading to shocking historical mortality rates of puerperal fever (also known as "childbed fever") at maternity institutions in the 19th century, was a major iatrogenic catastrophe of the era. The infection mechanism was first identified by Ignaz Semmelweis.With the development of scientific medicine in the 20th century, it could be expected that iatrogenic illness or death might be more easily avoided. Antiseptics, anesthesia, antibiotics, better surgical techniques, evidence-based protocols and best practices continue to be developed to decrease iatrogenic side effects and mortality.
See also
Notes
References
External links
Patient Safety Network (US) |
Cutaneous endometriosis | Cutaneous endometriosis is characterized by the appearance of papules at the umbilicus or in lower abdominal scars after gynecologic surgery in middle-aged women.: 628 The size averages to 2 cm in diameter. Its colour ranges from blue to violet, brown or skin-coloured.Rarely, endometriosis may present inside the muscles of the abdominal wall instead of the skin after caesarean section.
See also
Endometriosis
Skin lesion
== References == |
Uterine atony | Uterine atony is the failure of the uterus to contract adequately following delivery. Contraction of the uterine muscles during labor compresses the blood vessels and slows flow, which helps prevent hemorrhage and facilitates coagulation. Therefore, a lack of uterine muscle contraction can lead to an acute hemorrhage, as the vasculature is not being sufficiently compressed. Uterine atony is the most common cause of postpartum hemorrhage, which is an emergency and potential cause of fatality. Across the globe, postpartum hemorrhage is among the top five causes of maternal death. Recognition of the warning signs of uterine atony in the setting of extensive postpartum bleeding should initiate interventions aimed at regaining stable uterine contraction.
Risk factors
There are many risk factors for uterine atony and several are due to the type of labor a mother experiences such as prolonged labor, labor lasting less than 3 hours, uterine inversion, the use of magnesium sulfate infusions, and extended use of oxytocin. Uterine distention caused by things like more than one fetus present, polyhydramnios, fetal macrosomia, uterine fibroids, chorioamnionitis can also lead to decreased uterine function and atony. Retained placental tissue or placental disorders, such as an adherent placenta, placenta previa, and abruption placentae increase the mothers risk of PPH. Body mass index (BMI) above 40 and coagulopathies are known risk factors.Magnesium sulfate is used often in patients with preeclampsia and eclampsia, can inadvertently inhibit uterine contractions. In addition, preeclampsia can lead to blood disorders such as thrombocytopenia, platelet abnormalities, and disseminated intravascular coagulation. Cesarean delivery, especially after prolonged labor, may cause the muscles of the uterus to become tired and stop contracting or contraction can be inhibited at the surgical site.
Epidemiology
Uterine atony occurs during 1 in 40 births in the United States and is responsible for at least 80% of cases of postpartum hemorrhage.
Pathophysiology
The uterus is composed of an interconnected muscle fibers known as the myometrium. The blood vessels that provide the blood supply to the placenta pass through this muscle. After labor it is the contraction of these muscles that physically squeeze the blood vessels so that hemostasis can occur after the delivery of the fetus and the placenta. Local hemostatic factors like tissue factor type-1 plasminogen activator inhibitor and platelets and clotting factors aid in stopping the blood flow.This physiological contraction does not occur if the myometrium becomes atonic. Oxytocin is released continuously during labor to stimulate uterine muscle contraction so the that the fetus can be delivered and it is continued to be released after delivery to stop blood flow. If the oxytocin receptors become desensitized and no longer respond to the hormone then the uterus does not contract. The uterus can also be structurally damaged or distended to prevent contraction. Therefore, as placenta is delivered arteries are damaged and without the muscle contractions hemostasis cannot be reached.Blood loss is an expected part of labor and less than 500 mL is considered normal. Generally, primary PPH is classified as being more than 500 mL of blood lost in the first 24 hours following delivery. Those who have a caesarean section typically have more blood loss than a vaginal birth; so 1000 mL is commonly used to determine excessive blood loss. It is easy to underestimate maternal blood loss because the primary method of assessment is visual observation.
Evaluation and diagnosis
Identifying risk factors early in the pregnancy is essential in managing uterine atony and PPH. This allows for planning and organizing the necessary resources including staff, medicines, assistive devices, and the proper blood products. The delivery plan should also be cognizant of the ability of the hospital or facility to provide an appropriate level of care if any complications occur.Most diagnosis of uterine atony are made during the physical exam directly upon completion of the delivery. Diffuse uterine atony is typically diagnosed by patient observation rather than blood loss. The uterus can be directly palpated or observed indirectly using a bimanual examination post delivery. An atonic uterus can feel soft, "boggy" and/or enlarged. Bleeding from the cervical os is also common. If the atony is localized to one area of the uterus, the upper, fundal region may be still be squeezing while the lower uterine segment is non functional. This can be difficult to see with a cursory abdominal examination and easily overlooked. Therefore, a comprehensive vaginal, abdominal, and rectal examination should be performed. The physical examination may include ultrasound imaging for rapid visualization of the uterus and other causes of bleeding. Expulsion of gestational products such as the placenta and rapid identification of obstetric lacerations, helps exclude other causes of PPH. Laboratory tests can be drawn if coagulopathies are suspected.
Treatment and management
Prevention
Before delivery all patients should be screened for risk factors and then assigned a postpartum hemorrhage risk stratification based on the American College of Obstetricians and Gynecologists recommendations. If the woman is at a medium risk, blood should be typed and screened. Those assessed to be high risk should be typed and cross-matched.
Active management of the third stage of labor is routinely implemented and is considered the standard for patient care. It can be utilized to reduce the risk of PPH. Active management of the third stage includes uterine massage and a IV low dose oxytocin. Whether it is given just before or after the delivery of the placenta is subject to provider preference. It is suggested that using an uterotonic, such as oxytocin, prophylactically will help reduce blood loss and the need for a blood transfusion after delivery.A uterine massage is performed by placing a hand on the lower abdomen and using repetitive massaging or squeezing movements in attempt to stimulate the uterus. It is theorized, the massaging motion stimulates uterine contraction and may also trigger the release of local prostaglandins to help hemostasis.
Treatment
If uterine atony occurs even after all preventative measures have been taken, medical management should be implemented. Uterine fundal massage and compression should be maintained, while drugs are administered. An intravenous catheter should also be started to administer fluids, medications, and blood productsThere are several different types of uterotonic drugs that may be given, and the each has its own advantages and disadvantages. Moreover, the use of combination uterotonic therapy is a common practice and might be more effective at controlling bleeding than monotherapy. Some combinations might include oxytocin plus misoprostol, oxytocin plus ergometrine, and carbetocin.Medications used for PPH include the following:
Oxytocin (Pitocin) Stimulation of oxytocin receptors in the uterine muscle leads to contractions. The number of these receptors increases during pregnancy and with labor. There are also more in the fundus than in the lower uterine segment. Oxytocin has a quick onset of action, within a few minutes, but also loses effectiveness quickly because of a short half-life. The medicine is given in a rapid infusion and may cause hypotension. Oxytocin alone is the usually treatment of atony in the US. However, if bleeding is uncontrolled after administration of oxytocin, then a second uterotonic is given.
Carbetocin: A synthetic analog of oxytocin, works similarly to oxytocin but the half-life is much longer. It binds to smooth muscle receptors of the uterus, like oxytocin and has been reported to produce a stable uterine contraction, followed by rhythmic contractions. It is not available in the US but is available in many countries for the prevention of uterine atony and hemorrhage.
Methylergonovine: This is an ergot alkaloid and has multiple mechanisms of action to induce fast, regular uterine contractions which leads to sustained uterine contraction. It can cause peripheral vasoconstriction and is contraindicated in patients with hypertension or pregnancy related hypertension.
15-methyl-PGF2-alpha (Hemabate, Carboprost) Highly effective but it is expensive. It can cause bronchospasm and it should be avoided in asthmatics. May cause diarrhea, fevers, or tachycardia.
Misoprostol (Cytotec): A synthetic prostaglandin E1 analog oral medication that can stimulate uterine contractions. Misoprostol does not need to be refrigerated because it is heat stable. It is easy to administer compared with oxytocin and ergot alkaloids in low-resource areas where refrigeration and sterile needles are not available. May cause a low-grade fever.
Dinoprostone (Prostin E2): An alternative prostaglandin to misoprostol.After the medication is administered, the mother should be closely observed for to confirm the bleeding has stopped. If the bleeding has not stopped or physical exam does not show signs of restored uterine function within 30 minutes of medication administration, immediate invasive interventions are recommended.Tamponade techniques include uterine packing (extending into the vagina) with gauze that also has a Foley catheter in place to allow for bladder drainage. It is inexpensive and readily available. Balloon tamponade is the suggested method of tamponade in guidelines for management of PPH. A bakri balloon to tamponade (also with vaginal packing) can be used with Foley catheter insertion to facilitate bladder drainage. Vacuum-induced uterine tamponade is newer technique that uses low-level vacuum to evacuate blood from the uterine cavity and facilitate uterine contractionSurgical management techniques include:
Compression sutures such as the B-Lynch
Uterine curettage to remove retained placental products
Uterine artery ligation, with or without ligation of the tubo-ovarian vessels. Ligation of the uterine and utero-ovarian arteries can decrease uterine bleeding by reducing the pressure of arterial blood flow in the uterus. It will not completely control the bleeding but may decrease blood loss while other interventions are being attempted.
Hypogastric artery ligation. Bilateral ligation of the internal iliac arteries reduces the pulse pressure of blood flowing to the uterus similar to uterine artery ligation. However, it is not a common procedure because of the degree of difficulty and risks.
Hysterectomy
Complications
PPH can cause a multitude of complications including:
death
hypovolemic shock
disseminated intravascular coagulopathy
renal failure
hepatic failure
adult respiratory distress syndromeIn low‐income countries there are several other factors that play a role in PPH risk. Poor nutritional status, lack of healthcare access, and limited blood product supply are additional factors that increase morbidity and mortality.Postpartum anemia is common after an episode of uterine atony and postpartum hemorrhage. Severe anemia due to PPH may require red cell transfusions, depending on the severity of anemia and the degree of symptomatology attributable to anemia. A common practice is to offer a transfusion to symptomatic women with a hemoglobin value less than 7 g/dL. In most cases of uterine atony-related postpartum hemorrhage, the amount of iron lost is not fully replaced by the transfused blood. Oral iron should thus be also considered. Parenteral iron therapy is an option as it accelerated recovery. Most women with mild to moderate anemia, however, resolve the anemia sufficiently rapidly with oral iron alone and do not need parenteral iron.
Prognosis
Women with a history of PPH have a 2 to 3 times higher risk of PPH in their following pregnancies.
References
== External links == |
Gonadotropin-resistant ovary syndrome | Resistant ovary syndrome, previously known as Savage syndrome, is a cause of ovarian failure that can lead to secondary amenorrhea. Resistant ovaries result from a functional disturbance of the gonadotropin receptors in the ovarian follicles. It may be a cause of primary or secondary amenorrhea and is resistant to exogenous gonadotropin stimulation.
Diagnosis of this condition requires that the patient has a normal 46,XX karyotype, normal secondary sexual characteristics, elevated plasma follicle-stimulating hormone and luteinizing hormone – in the menopausal range – and that normal, multiple follicles are seen on ovarian biopsy.
Spontaneous reversal of the receptor resistance may occur.
== References == |
Trevor disease | Trevor disease, also known as dysplasia epiphysealis hemimelica and Trevors disease, is a congenital bone developmental disorder. There is 1 case per million population. The condition is three times more common in males than in females.
Presentation
This disorder is rare, and is characterised by an asymmetrical limb deformity due to localized overgrowth of cartilage, histologically resembling osteochondroma. It is believed to affect the limb bud in early fetal life. The condition occurs mostly in the ankle or knee region and it is always confined to a single limb. This usually involves only the lower extremities and on medial side of the epiphysis. It is named after researcher David Trevor.
Diagnosis
Differential diagnosis
Trevor disease can often mimic posttraumatic osseous fragments, synovial chondromatosis, ostechondroma, or anterior spur of ankle. It is not possible to distinguish DEH from osteochondroma on the basis of histopathology alone. Special molecular tests of the genes EXT1, EXT2 are used for the analysis of genetic expressions. These are within normal ranges in DEH, while they are lower in ostechondroma (owing to a mutation). These tests are expensive and the diagnosis is often made on clinical and radiological findings. Synovial chondromatosis occurs in a much older age group and can be ruled out on this basis.
Treatment
Most reported cases of DEH in the literature have been treated surgically, usually with excision of the mass, as well as by the correction
of any deformity, while preserving the integrity of the affected joint as much as possible.
History
Trevor disease was first described by the French surgeon Albert Mouchet and J. Belot in 1926. In 1956, the name "dysplasia epiphysealis hemimelica" was proposed by Fairbank. The usual symptoms are the appearance of an osseous protuberance, on one side of the knee, ankle or foot joint which gradually increases Radiologically, the condition shows a nonuniformity of growth and multiple unconnected ossification centers around the epiphyses.
See also
Multiple epiphyseal dysplasia
References
== External links == |
Post-vagotomy diarrhea | Post-vagotomy diarrhea is a form of diarrhea which occurs in 10% of people after a truncal vagotomy, which can range from severe to debilitating in approximately 2% to 4% of patients. However, the occurrence of post-vagotomy diarrhea is significantly reduced after proximal selective vagotomy, specifically when celiac and hepatic branches of the vagus are retained.
Diagnosis
Treatment
Surgical treatment for refractory post-vagotomy diarrhea is rarely needed and at least one year from the occurrence of symptoms should be allotted to ensure all non-surgical treatments have been appropriately explored. Under severe cases, where surgical intervention does become necessary, a 10 cm reverse jejunal interposition is usually the procedure of choice.
== References == |
Qigong | Qigong (), qi gong, chi kung, chi ung, or chi gung (simplified Chinese: 气功; traditional Chinese: 氣功; pinyin: qìgōng; Wade–Giles: ch‘i kung; lit. life-energy cultivation) is a system of coordinated body-posture and movement, breathing, and meditation used for the purposes of health, spirituality, and martial-arts training. With roots in Chinese medicine, philosophy, and martial arts, qigong is traditionally viewed by the Chinese and throughout Asia as a practice to cultivate and balance qi (pronounced approximately as "chi" or "chee"), translated as "life energy".Qigong practice typically involves moving meditation, coordinating slow-flowing movement, deep rhythmic breathing, and a calm meditative state of mind. People practice qigong throughout China and worldwide for recreation, exercise, relaxation, preventive medicine, self-healing, alternative medicine, meditation, self-cultivation, and training for martial arts.
Etymology
Qigong (Pinyin), chi kung (Wade-Giles), and chi gung (Yale) are Romanized words for two Chinese characters: qì (气／氣) and gōng (功).
Qi (or chi) primarily means air, gas or breath but is often translated as a metaphysical concept of vital energy, referring to a supposed energy circulating through the body; though a more general definition is universal energy, including heat, light, and electromagnetic energy; and definitions often involve breath, air, gas, or the relationship between matter, energy, and spirit. Qi is the central underlying principle in traditional Chinese medicine and martial arts. Gong (or kung) is often translated as cultivation or work, and definitions include practice, skill, mastery, merit, achievement, service, result, or accomplishment, and is often used to mean gongfu (kung fu) in the traditional sense of achievement through great effort. The two words are combined to describe systems to cultivate and balance life energy, especially for health and wellbeing.The term qigong as currently used was promoted in the late 1940s through the 1950s to refer to a broad range of Chinese self-cultivation exercises, and to emphasize health and scientific approaches, while de-emphasizing spiritual practices, mysticism, and elite lineages.
History and origins
With roots in ancient Chinese culture dating back more than 4,000 years, a wide variety of qigong forms have developed within different segments of Chinese society: in traditional Chinese medicine for preventive and curative functions; in Confucianism to promote longevity and improve moral character; in Daoism and Buddhism as part of meditative practice; and in Chinese martial arts to enhance self defending abilities. Contemporary qigong blends diverse and sometimes disparate traditions, in particular the Daoist meditative practice of "internal alchemy" (Neidan 內丹術), the ancient meditative practices of "circulating qi" (Xing qi 行氣) and "standing meditation" (Zhan zhuang 站桩), and the slow gymnastic breathing exercise of "guiding and pulling" (Dao yin 導引). Traditionally, qigong was taught by master to students through training and oral transmission, with an emphasis on meditative practice by scholars and gymnastic or dynamic practice by the working masses.Starting in the late 1940s and the 1950s, the mainland Chinese government tried to integrate disparate qigong approaches into one coherent system, with the intention of establishing a firm scientific basis for qigong practice. In 1949, Liu Guizhen established the name "Qigong" to refer to the system of life-preserving practices that he and his associates developed, based on Dao yin and other philosophical traditions. This attempt is considered by some sinologists as the start of the modern or scientific interpretation of qigong. During the Great Leap Forward (1958–1963) and the Cultural Revolution (1966–1976), qigong, along with other traditional Chinese medicine, was under tight control with limited access among the general public, but was encouraged in state-run rehabilitation centers and spread to universities and hospitals. After the Cultural Revolution, qigong, along with tai chi, was popularized as daily morning exercise practiced en masse throughout China.
Popularity of qigong grew rapidly during the Deng and Jiang eras after Mao Zedongs death in 1976 through the 1990s, with estimates of between 60 and 200 million practitioners throughout China. Along with popularity and state sanction came controversy and problems: claims of extraordinary abilities bordering on the supernatural, pseudoscience explanations to build credibility, a mental condition labeled qigong deviation, formation of cults, and exaggeration of claims by masters for personal benefit. In 1985, the state-run National Qigong Science and Research Organization was established to regulate the nations qigong denominations. In 1999, in response to widespread revival of old traditions of spirituality, morality, and mysticism, and perceived challenges to State control, the Chinese government took measures to enforce control of public qigong practice, including shutting down qigong clinics and hospitals, and banning groups such as Zhong Gong and Falun Gong.: 161–174
Since the 1999 crackdown, qigong research and practice have only been officially supported in the context of health and traditional Chinese medicine. The Chinese Health Qigong Association, established in 2000, strictly regulates public qigong practice, with limitation of public gatherings, requirement of state approved training and certification of instructors, and restriction of practice to state-approved forms.Through the forces of migration of the Chinese diaspora, tourism in China, and globalization, the practice of qigong spread from the Chinese community to the world. Today, millions of people around the world practice qigong and believe in the benefits of qigong to varying degrees. Similar to its historical origin, those interested in qigong come from diverse backgrounds and practice it for different reasons, including for recreation, exercise, relaxation, preventive medicine, self-healing, alternative medicine, self-cultivation, meditation, spirituality, and martial arts training.
Overview
Practices
Qigong comprises a diverse set of practices that coordinate body (調身), breath (調息), and mind (調心) based on Chinese philosophy. Practices include moving and still meditation, massage, chanting, sound meditation, and non-contact treatments, performed in a broad array of body postures. Qigong is commonly classified into two foundational categories: 1) dynamic or active qigong (dong gong), with slow flowing movement; and 2) meditative or passive qigong (jing gong), with still positions and inner movement of the breath.: 21770–21772 From a therapeutic perspective, qigong can be classified into two systems:
1) internal qigong, which focuses on self-care and self-cultivation, and;
2) external qigong, which involves treatment by a therapist who directs or transmits qi.: 21777–21781 As moving meditation, qigong practice typically coordinates slow stylized movement, deep diaphragmatic breathing, and calm mental focus, with visualization of guiding qi through the body. While implementation details vary, generally qigong forms can be characterized as a mix of four types of practice: dynamic, static, meditative, and activities requiring external aids.
Dynamic practiceinvolves fluid movement, usually carefully choreographed, coordinated with breath and awareness. Examples include the slow stylized movements of Tai chi chuan, Baguazhang, and Xing Yi Quan. Other examples include graceful movement that mimics the motion of animals in Five Animals (Wu Qin Xi qigong), White Crane, and Wild Goose (Dayan) Qigong. As a form of gentle exercise, qigong is composed of movements that are typically repeated, strengthening and stretching the body, increasing fluid movement (blood, synovial, and lymph), enhancing balance and proprioception, and improving the awareness of how the body moves through space.Static practiceinvolves holding postures for sustained periods of time. In some cases this bears resemblance to the practice of Yoga and its continuation in the Buddhist tradition. For example Yiquan, a Chinese martial art derived from xingyiquan, emphasizes static stance training. In another example, the healing form Eight Pieces of Brocade (Baduanjin qigong) is based on a series of static postures.Meditative practiceutilizes breath awareness, visualization, mantra, chanting, sound, and focus on philosophical concepts such as qi circulation, aesthetics, or moral values. In traditional Chinese medicine and Daoist practice, the meditative focus is commonly on cultivating qi in dantian energy centers and balancing qi flow in meridian and other pathways. In various Buddhist traditions, the aim is to still the mind, either through outward focus, for example on a place, or through inward focus on the breath, a mantra, a koan, emptiness, or the idea of the eternal. In the Confucius scholar tradition, meditation is focused on humanity and virtue, with the aim of self-enlightenment.Use of external agentsMany systems of qigong practice include the use of external agents such as ingestion of herbs, massage, physical manipulation, or interaction with other living organisms. For example, specialized food and drinks are used in some medical and Daoist forms, whereas massage and body manipulation are sometimes used in martial arts forms. In some medical systems a qigong master uses non-contact treatment, purportedly guiding qi through his or her own body into the body of another person.
Forms
There are numerous qigong forms. 75 ancient forms that can be found in ancient literature and also 56 common or contemporary forms have been described in a qigong compendium.: 203–433 The list is by no means exhaustive. Many contemporary forms were developed by people who had recovered from their illness after qigong practice.
Most of the qigong forms come under the following categories:
Medical qigong
Martial qigong
Spiritual qigong
Intellectual qigong
Life nourishing qigong
Development of "health qigong"
In 1995, there was Qigong Talent Bank, an organization of Science Research of Chinese Qigong, functioning as network system of the senior Chinese qigong talents in China. In order to promote qigong exercises in a standardised and effective way with a scientific approach, The Chinese Health Qigong Association (CHQA) appointed panels of Qigong experts, Chinese medicine doctors and sport science professors from different hospitals, universities and qigong lineage across China to research and develop new sets of qigong exercises. In 2003 the CHQA officially promoted a new system called "health qigong", which consisted of four newly developed health qigong forms:
Health Qigong Muscle-Tendon Change Classic (Health Qigong Yì Jīn Jīng 易筋經).
Health Qigong Five Animals Frolics (Health qigong Wu Qin Xi 五禽戲).
Health Qigong Six Healing Sounds (Health Qigong Liu Zi Jue 六字訣).
Health Qigong Eight Pieces of Brocade (Health Qigong Ba Duan Jin 八段錦).In 2010, the Chinese Health Qigong Association officially introduced five additional health qigong forms:
Health Qigong Tai Chi Yang Sheng Zhang (太極養生杖): a tai chi form from the stick tradition.
Health Qigong Shi Er Duan Jin (十二段錦): seated exercises to strengthen the neck, shoulders, waist, and legs.
Health Qigong Daoyin Yang Sheng Gong Shi Er Fa (導引養生功十二法): 12 routines from Daoyin tradition of guiding and pulling qi.
Health Qigong Mawangdui Daoyin (馬王堆導引术): guiding qi along the meridians with synchronous movement and awareness.
Health Qigong Da Wu (大舞): choreographed exercises to lubricate joints and guide qi.Other commonly practised qigong styles and forms include:
Soaring Crane Qigong
Wisdom Healing Qigong
Pan Gu Mystical Qigong
Wild Goose (Dayan) Qigong
Dragon and Tiger Qigong
Primordial Qigong (Wujigong)
Chilel Qigong
Phoenix Qigong
Yuan Qigong
Zhong Yuan Qigong
Techniques
Whether viewed from the perspective of exercise, health, philosophy, or martial arts training, several main principles emerge concerning the practice of qigong:
Intentional movement: careful, flowing balanced style
Rhythmic breathing: slow, deep, coordinated with fluid movement
Awareness: calm, focused meditative state
Visualization: of qi flow, philosophical tenets, aesthetics
Chanting/Sound: use of sound as a focal pointAdditional principles:
Softness: soft gaze, expressionless face
Solid Stance: firm footing, erect spine
Relaxation: relaxed muscles, slightly bent joints
Balance and Counterbalance: motion over the center of gravityAdvanced goals:
Equanimity: more fluid, more relaxed
Tranquility: empty mind, high awareness
Stillness: smaller and smaller movements, eventually to complete stillnessThe most advanced practice is generally considered to be with little or no motion.
Traditional and classical theory
Over time, five distinct traditions or schools of qigong developed in China, each with its own theories and characteristics: Chinese Medical Qigong, Daoist Qigong, Buddhist Qigong, Confucian Qigong, and Martial Qigong.: 30–80 All of these qigong traditions include practices intended to cultivate and balance qi.
Traditional Chinese medicine
The theories of ancient Chinese qigong include the Yin-Yang and Five Phases Theory, Essence-Qi-Spirit Theory, Zang-Xiang Theory, and Meridians and Qi-Blood Theory, which have been synthesized as part of Traditional Chinese Medicine (TCM).: 45–57 TCM focuses on tracing and correcting underlying disharmony, in terms of deficiency and excess, using the complementary and opposing forces of yin and yang (陰陽), to create a balanced flow of qi. Qi is believed to be cultivated and stored in three main dantian energy centers and to travel through the body along twelve main meridians (Jīng Luò 經絡), with numerous smaller branches and tributaries. The main meridians correspond to twelve main organs ) (Zàng fǔ 臟腑). Qi is balanced in terms of yin and yang in the context of the traditional system of Five Phases (Wu xing 五行). A person is believed to become ill or die when qi becomes diminished or unbalanced. Health is believed to be returned by rebuilding qi, eliminating qi blockages, and correcting qi imbalances. These TCM concepts do not translate readily to modern science and medicine.
Daoism
In Daoism, various practices now known as Daoist qigong are claimed to provide a way to achieve longevity and spiritual enlightenment, as well as a closer connection with the natural world.
Buddhism
In Buddhism meditative practices now known as Buddhist qigong are part of a spiritual path that leads to spiritual enlightenment or Buddhahood.
Confucianism
In Confucianism practices now known as Confucian qigong provide a means to become a Junzi (君子) through awareness of morality.
Contemporary qigong
In contemporary China, the emphasis of qigong practice has shifted away from traditional philosophy, spiritual attainment, and folklore, and increasingly to health benefits, traditional medicine and martial arts applications, and a scientific perspective. Qigong is now practiced by millions worldwide, primarily for its health benefits, though many practitioners have also adopted traditional philosophical, medical, or martial arts perspectives, and even use the long history of qigong as evidence of its effectiveness.
Contemporary Chinese medical qigong
Qigong has been recognized as a "standard medical technique" in China since 1989, and is sometimes included in the medical curriculum of major universities in China.: 34 The 2013 English translation of the official Chinese Medical Qigong textbook used in China: iv, 385 defines CMQ as "the skill of body-mind exercise that integrates body, breath, and mind adjustments into one" and emphasizes that qigong is based on "adjustment" (tiao 調, also translated as "regulation", "tuning", or "alignment") of body, breath, and mind.: 16–18 As such, qigong is viewed by practitioners as being more than common physical exercise, because qigong combines postural, breathing, and mental training in one to produce a particular psychophysiological state of being.: 15 While CMQ is still based on traditional and classical theory, modern practitioners also emphasize the importance of a strong scientific basis.: 81–89 According to the 2013 CMQ textbook, physiological effects of qigong are numerous, and include improvement of respiratory and cardiovascular function, and possibly neurophysiological function.: 89–102
Conventional medicine
Especially since the 1990s, conventional or mainstream Western medicine often strives to heed the model of evidence-based medicine, EBM, which demotes medical theory, clinical experience, and physiological data to prioritize the results of controlled, and especially randomized, clinical trials of the treatment itself. Although some clinical trials support qigongs effectiveness in treating conditions diagnosed in Western medicine, the quality of these studies is mostly low and, overall, their results are mixed.
Integrative, complementary, and alternative medicine
Integrative medicine (IM) refers to "the blending of conventional and complementary medicines and therapies with the aim of using the most appropriate of either or both modalities to care for the patient as a whole",: 455–456 whereas complementary is using a non-mainstream approach together with conventional medicine, while alternative is using a non-mainstream approach in place of conventional medicine. Qigong is used by integrative medicine practitioners to complement conventional medical treatment, based on complementary and alternative medicine interpretations of the effectiveness and safety of qigong.: 22278–22306
Scientific basis
Scientists interested in qigong have sought to describe or verify the effects of qigong, to explore mechanisms of effects, to form scientific theory with respect to qigong, and to identify appropriate research methodology for further study.: 81–89 In terms of traditional theory, the existence of qi has not been independently verified in an experimental setting. In any case, some researches have reported effects on pathophysiological parameters of biomedical interest.
Practitioners, uses and cautions
Recreation and popular use
People practice qigong for many different reasons, including for recreation, exercise and relaxation, preventive medicine and self-healing, meditation and self-cultivation, and training for martial arts. Practitioners range from athletes to people with disabilities. Because it is low impact and can be done lying, sitting, or standing, qigong is accessible for people with disabilities, seniors, and people recovering from injuries.
Therapeutic use
Therapeutic use of qigong is directed by TCM, CAM, integrative medicine, and other health practitioners. In China, where it is considered a "standard medical technique",: 34 qigong is commonly prescribed to treat a wide variety of conditions, and clinical applications include hypertension, coronary artery disease, peptic ulcers, chronic liver diseases, diabetes mellitus, obesity, menopause syndrome, chronic fatigue syndrome, insomnia, tumors and cancer, lower back and leg pain, cervical spondylosis, and myopia.: 261–391 Outside China qigong is used in integrative medicine to complement or supplement accepted medical treatments, including for relaxation, fitness, rehabilitation, and treatment of specific conditions. However, there is no high-quality evidence that qigong is actually effective for these conditions. Based on systematic reviews of clinical research, there is insufficient evidence for the effectiveness of using qigong as a therapy for any medical condition.
Safety and cost
Qigong is generally viewed as safe. No adverse effects have been observed in clinical trials, such that qigong is considered safe for use across diverse populations. Cost for self-care is minimal, and cost efficiencies are high for group delivered care. Typically the cautions associated with qigong are the same as those associated with any physical activity, including risk of muscle strains or sprains, advisability of stretching to prevent injury, general safety for use alongside conventional medical treatments, and consulting with a physician when combining with conventional treatment.
Clinical research
Overview
Although there is ongoing clinical research examining the potential health effects of qigong, there is little financial or medical incentive to support high-quality research, and still only a limited number of studies meet accepted medical and scientific standards of randomized controlled trials (RCTs). Clinical research concerning qigong has been conducted for a wide range of medical conditions, including bone density, cardiopulmonary effects, physical function, falls and related risk factors, quality of life, immune function, inflammation, hypertension, pain, and cancer treatment.
Systematic reviews
A 2009 systematic review on the effect of qigong exercises on reducing pain concluded that "the existing trial evidence is not convincing enough to suggest that internal qigong is an effective modality for pain management."A 2010 systematic review of the effect of qigong exercises on cancer treatment concluded "the effectiveness of qigong in cancer care is not yet supported by the evidence from rigorous clinical trials." A separate systematic review that looked at the effects of qigong exercises on various physiological or psychological outcomes found that the available studies were poorly designed, with a high risk of bias in the results. Therefore, the authors concluded, "Due to limited number of RCTs in the field and methodological problems and high risk of bias in the included studies, it is still too early to reach a conclusion about the efficacy and the effectiveness of qigong exercise as a form of health practice adopted by the cancer patients during their curative, palliative, and rehabilitative phases of the cancer journey."A 2011 overview of systematic reviews of controlled clinical trials, Lee et al. concluded that "the effectiveness of qigong is based mostly on poor quality research" and "therefore, it would be unwise to draw firm conclusions at this stage." Although a 2010 comprehensive literature review found 77 peer-reviewed RCTs, Lee et al.s overview of systematic reviews as to particular health conditions found problems like sample size, lack of proper control groups, with lack of blinding associated with high risk of bias.A 2015 systematic review of the effect of qigong exercises on cardiovascular diseases and hypertension found no conclusive evidence for effect. Also in 2015, a systemic review into the effects on hypertension suggested that it may be effective, but that the evidence was not conclusive because of the poor quality of the trials it included, and advised more rigorous research in the future. Another 2015 systematic review of qigong on biomarkers of cardiovascular disease concluded that some trials showed favorable effects, but concludes, "Most of the trials included in this review are likely to be at high risk of bias, so we have very low confidence in the validity of the results.
Mental health
Many claims have been made that qigong can benefit or ameliorate mental health conditions, including improved mood, decreased stress reaction, and decreased anxiety and depression. Most medical studies have only examined psychological factors as secondary goals, although various studies have shown decreases in cortisol levels, a chemical hormone produced by the body in response to stress.
China
Basic and clinical research in China during the 1980s was mostly descriptive, and few results were reported in peer-reviewed English-language journals.: 22060–22063 Qigong became known outside China in the 1990s, and clinical randomized controlled trials investigating the effectiveness of qigong on health and mental conditions began to be published worldwide, along with systematic reviews.: 21792–21798
Challenges
Most existing clinical trials have small sample sizes and many have inadequate controls. Of particular concern is the impracticality of double blinding using appropriate sham treatments, and the difficulty of placebo control, such that benefits often cannot be distinguished from the placebo effect.: 22278–22306 Also of concern is the choice of which qigong form to use and how to standardize the treatment or amount with respect to the skill of the practitioner leading or administering treatment, the tradition of individualization of treatments, and the treatment length, intensity, and frequency.: 6869–6920, 22361–22370
Meditation and self-cultivation applications
Qigong is practiced for meditation and self-cultivation as part of various philosophical and spiritual traditions. As meditation, qigong is a means to still the mind and enter a state of consciousness that brings serenity, clarity, and bliss. Many practitioners find qigong, with its gentle focused movement, to be more accessible than seated meditation.Qigong for self-cultivation can be classified in terms of traditional Chinese philosophy: Daoist, Buddhist, and Confucian.
Martial arts applications
The practice of qigong is an important component in both internal and external style Chinese martial arts. Focus on qi is considered to be a source of power as well as the foundation of the internal style of martial arts (Neijia). Tai Chi Chuan, Xing Yi Quan, and Baguazhang are representative of the types of Chinese martial arts that rely on the concept of qi as the foundation. Extraordinary feats of martial arts prowess, such as the ability to withstand heavy strikes (Iron Shirt, 鐵衫) and the ability to break hard objects (Iron Palm, 鐵掌) are abilities attributed to qigong training.
Tai Chi Chuan and qigong
Tai Chi Chuan (Taijiquan) is a widely practiced Chinese internal martial style based on the theory of taiji, closely associated with qigong, and typically involving more complex choreographed movement coordinated with breath, done slowly for health and training, or quickly for self-defense. Many scholars consider tai chi chuan to be a type of qigong, traced back to an origin in the seventeenth century. In modern practice, qigong typically focuses more on health and meditation rather than martial applications, and plays an important role in training for tai chi chuan, in particular used to build strength, develop breath control, and increase vitality ("life energy").
See also
Yoga
International Day of Yoga
Asahi Health
Hua Tuo
Wushu
Kung fu
Jing (TCM)
Physiotherapy
Mind-body problem
Neidan
Neigong
Paidagong
Silk reeling
Tao Yin
Taoist sexual practices
Therapeutic nihilism
World Tai Chi and Qigong Day
Yangsheng
Zhong Gong
Zhan Zhuang
References
External links
The dictionary definition of qigong at Wiktionary
Media related to Chi Kung at Wikimedia Commons |
Panophthalmitis | Panophthalmitis is the inflammation of all coats of the animal eye including intraocular structures. It can be caused by infection, particularly from Pseudomonas species, such as Pseudomonas aeruginosa, Clostridium species, Whipples disease, and also fungi. It can also be cause by other stress.
References
Further reading
Font, R. L. (1967). "Endogenous Mycotic Panophthalmitis Caused by Blastomyces dermatitidis". Archives of Ophthalmology. 77 (2): 217–22. doi:10.1001/archopht.1967.00980020219012. ISSN 0003-9950. PMID 6019015.
Chawla, Rohan, et al. "Case report of tuberculous panophthalmitis." Medical Science Monitor 10.10 (2004): CS57-CS59.
== External links == |
Cardiorenal syndrome | Cardiorenal syndrome (CRS) is an umbrella term used in the medical field that defines disorders of the heart and kidneys whereby "acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other". The kidney and the heart are compared to a marriage that has "bumps" in the road, some may even say it can come to an end. The heart and kidney play vital functions that contribute to the wellbeing of the body in a healthy person. When one of these organs fail, the other subsequently fails as well, like a domino affect. The heart and the kidneys are involved in maintaining hemodynamic stability and organ perfusion through an intricate network. Patients who have renal failure first may be hard to determine if Heart Failure is concurrent. These two organs communicate with one another through a variety of pathways in an interdependent relationship. In a 2004 report from National Heart, Lung and Blood Institute, CRS was defined as a condition where treatment of congestive heart failure is limited by decline in kidney function. This definition has since been challenged repeatedly but there still remains little consensus over a universally accepted definition for CRS. At a consensus conference of the Acute Dialysis Quality Initiative (ADQI), the CRS was classified into five subtypes primarily based upon the organ that initiated the insult as well as the acuity of disease.
Signs and symptoms
Risk factors
The following risk factors have been associated with increased incidence of CRS.
Older age
Comorbid conditions (diabetes mellitus, uncontrolled hypertension, anemia)
Drugs (anti-inflammatory agents, diuretics, ACE inhibitors, ARBs)
History of heart failure with impaired left ventricular ejection fraction
Prior myocardial infarction
Elevated New York Heart Association (NYHA) functional class
Elevated cardiac troponins
Chronic kidney disease (reduced eGFR, elevated BUN, creatinine, or cystatin)
Pathophysiology
The pathophysiology of CRS can be attributed to two broad categories of "hemodynamic factors" such as low cardiac output, elevation of both intra-abdominal and central venous pressures, and non-hemodynamic factors or "cardiorenal connectors" such as neurohormonal and inflammatory activation. It was previously believed that low cardiac output in heart failure patients result in decreased blood flow to the kidneys which can lead to progressive deterioration of kidney function. As a result, diuresis of these patients will result in hypovolemia and pre-renal azotemia. However, several studies did not find an association between kidney dysfunction and cardiac output or other hemodynamic parameters. In addition, CRS has been observed in patients with diastolic dysfunction who have normal left ventricular systolic function. Therefore, there must be additional mechanisms involved in the progression of CRS. Elevated intra-abdominal pressures resulting from ascites and abdominal wall edema may be associated with worsening kidney functions in heart failure patients. Several studies have shown that as a result of this increased intra-abdominal pressure there is increased central venous pressure and congestion of the kidneys veins, which can lead to worsening kidney function. In addition, many neurohormonal and inflammatory agents are implicated in the progression of CRS. These include increased formation of reactive oxygen species, endothelin, arginine vasopressin, and excessive sympathetic activity which can result in myocardial hypertrophy and necrosis. Other cardiorenal connectors include renin-angiotensin-system activation, nitric oxide/reactive oxygen species imbalance, inflammatory factors and abnormal activation of the sympathetic nervous system, which can cause structural and functional abnormalities in both heart and/or the kidney. There is a close interaction within these cardiorenal connectors as well as between these factors and the hemodynamic factors which makes the study of CRS pathophysiology complicated.
Diagnosis
It is critical to diagnose CRS at an early stage in order to achieve optimal therapeutic efficacy. However, unlike markers of heart damage or stress such as troponin, creatine kinase, natriuretic peptides, reliable markers for acute kidney injury are lacking. Recently, research has found several biomarkers that can be used for early detection of acute kidney injury before serious loss of organ function may occur. Several of these biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-B-D-glucosaminidase (NAG), Cystatin C, and kidney injury molecule-1 (KIM-1) which have been shown to be involved in tubular damage. Other biomarkers that have been shown to be useful include BNP, IL-18, and fatty acid binding protein (FABP). However, there is great variability in the measurement of these biomarkers and their use in diagnosing CRS must be assessed.
Classification
Ronco et al. first proposed a five-part classification system for CRS in 2008 which was also accepted at ADQI consensus conference in 2010. These include:
The distinction between CRS type 2 and CRS type 4 is based on the assumption that, also in advanced and chronic disease, two different pathophysiological mechanisms can be distinguished, whereas both CKD and HF often develop due to a common pathophysiological background, most notably hypertension and diabetes mellitus. Furthermore, the feasibility of the distinction between CRS type 2 and 4 in terms of diagnosis can be questioned.Braam et al. argue that classifying the CRS based on the order in which the organs are affected and the timeframe (acute vs chronic) is too simplistic and without a mechanistic classification it is difficult to study CRS. They view the cardiorenal syndrome in a more holistic, integrative manner. They defined the cardiorenal syndrome as a pathophysiological condition in which combined heart and kidney dysfunction amplifies progression of failure of the individual organ, by inducing similar pathophysiological mechanisms. Therefore, regardless of which organ fails first, the same neurohormonal systems are activated causing accelerated cardiovascular disease, and progression of damage and failure of both organs. These systems are broken down into two broad categories of "hemodynamic factors" and non-hemodynamic factors or "cardiorenal connectors".
Management
Medical management of patients with CRS is often challenging as focus on treatment of one organ may have worsening outcome on the other. It is known that many of the medications used to treat HF may worsen kidney function. "As the population ages and the burden of renal disease and cardiovascular disease continue to rise, efforts to better understand the complicated relationship between these two organ systems are greatly needed." In addition, many trials on HF excluded patients with advanced kidney dysfunction. Therefore, our understanding of CRS management is still limited to this date. One study showes how ACE inhibitors and angiotensin II receptor antagonists have been found to prevent nephropathy in patients who have diabetes. Patients with kidney failure are less likely to get all guide-lined base therapies. Patients who have moderate to sever CKD was seen to have similar care when compared to those patients who had normal kidney function. This helps show how healthcare workers can do more to increase the outcome of those suffering.
Diuretics
Used in the treatment of heart failure and CRS patients, however must be carefully dosed to prevent kidney injury. Diuretic resistance is frequently a challenge for physicians to overcome which they may tackle by changing the dosage, frequency, or adding a second drug.ACEI, ARB, renin inhibitors, aldosterone inhibitors
The use of ACE inhibitors have long term protective effect on kidney and heart tissue. However, they should be used with caution in patients with CRS and kidney failure. Although patients with kidney failure may experience slight deterioration of kidney function in the short term, the use of ACE inhibitors is shown to have prognostic benefit over the long term. Two studies have suggested that the use of ACEI alongside statins might be an effective regimen to prevent a substantial number of CRS cases in high risk patients and improve survival and quality of life in these people. There are data suggesting combined use of statin and an ACEI improves clinical outcome more than a statin alone and considerably more than ACE inhibitor alone.Natriuretic peptides
Nesiritide which is an analogue of brain natriuretic peptide (BNP) was shown to result in poorer kidney outcome or have no effect.Vasopressin antagonists
Tolvaptan showed to have no benefit. It is also a very costly drug.Adenosine antagonists
Adenosine is responsible for constriction of afferent arteriole and reduction in GFR. It was found that an adenosine A1-receptor antagonist called KW-3902 was able to improve kidney function in CRS patients.Ultrafiltration
Many case reports have shown improved kidney function with ultrafiltration.Inotropes
Their roles remain unknown.
Epidemiology
Kidney failure is very common in patients with congestive heart failure. It was shown that kidney failure complicates one-third of all admissions for heart failure, which is the leading cause of hospitalization in the United States among adults over 65 years old. Not only is this the leading cause of hospitalization, it also increases the stays in the ICU.These complications led to longer hospital stay, higher mortality, and greater chance for readmission. The impatient mortality was seen to be much higher for patients with much more sever renal dysfunction. The increase of hospital and ICU stays also increases the cost of care in the hospital. Not only are there patients suffering from their disease, they are also suffering financially due to the cost of the hospital stays. Another study found that 39% of patients in NYHA class 4 and 31% of patients in NYHA class 3 had severely impaired kidney function. Similarly, kidney failure can have deleterious effects on cardiovascular function. It was estimated that about 44% of deaths in patients with end-stage kidney failure (ESKF) are due to cardiovascular disease.
References
== External links == |
Syncope (medicine) | Syncope, commonly known as fainting, or passing out, is a loss of consciousness and muscle strength characterized by a fast onset, short duration, and spontaneous recovery. It is caused by a decrease in blood flow to the brain, typically from low blood pressure. There are sometimes symptoms before the loss of consciousness such as lightheadedness, sweating, pale skin, blurred vision, nausea, vomiting, or feeling warm. Syncope may also be associated with a short episode of muscle twitching. Psychiatric causes can also be determined when a patient experiences fear, anxiety, or panic; particularly before a stressful event usually medical in nature. When consciousness and muscle strength are not completely lost, it is called presyncope. It is recommended that presyncope be treated the same as syncope.Causes range from non-serious to potentially fatal. There are three broad categories of causes: heart or blood vessel related; reflex, also known as neurally mediated; and orthostatic hypotension. Issues with the heart and blood vessels are the cause in about 10% and typically the most serious while neurally mediated is the most common. Heart related causes may include an abnormal heart rhythm, problems with the heart valves or heart muscle and blockages of blood vessels from a pulmonary embolism or aortic dissection among others. Neurally mediated syncope occurs when blood vessels expand and heart rate decreases inappropriately. This may occur from either a triggering event such as exposure to blood, pain, strong feelings or a specific activity such as urination, vomiting, or coughing. Neurally mediated syncope may also occur when an area in the neck known as the carotid sinus is pressed. The third type of syncope is due to a drop in blood pressure when changing position such as when standing up. This is often due to medications that a person is taking but may also be related to dehydration, significant bleeding or infection. There also seems to be a genetic component to syncope.A medical history, physical examination, and electrocardiogram (ECG) are the most effective ways to determine the underlying cause. The ECG is useful to detect an abnormal heart rhythm, poor blood flow to the heart muscle and other electrical issues, such as long QT syndrome and Brugada syndrome. Heart related causes also often have little history of a prodrome. Low blood pressure and a fast heart rate after the event may indicate blood loss or dehydration, while low blood oxygen levels may be seen following the event in those with pulmonary embolism. More specific tests such as implantable loop recorders, tilt table testing or carotid sinus massage may be useful in uncertain cases. Computed tomography (CT) is generally not required unless specific concerns are present. Other causes of similar symptoms that should be considered include seizure, stroke, concussion, low blood oxygen, low blood sugar, drug intoxication and some psychiatric disorders among others. Treatment depends on the underlying cause. Those who are considered at high risk following investigation may be admitted to hospital for further monitoring of the heart.Syncope affects about three to six out of every thousand people each year. It is more common in older people and females. It is the reason for one to three percent of visits to emergency departments and admissions to hospital. Up to half of women over the age of 80 and a third of medical students describe at least one event at some point in their lives. Of those presenting with syncope to an emergency department, about 4% died in the next 30 days. The risk of a poor outcome, however, depends very much on the underlying cause.
Causes
Causes range from non-serious to potentially fatal. There are three broad categories of causes: heart or blood vessel related; reflex, also known as neurally mediated; and orthostatic hypotension. Issues with the heart and blood vessels are the cause in about 10% and typically the most serious while neurally mediated is the most common. There also seems to be a genetic component to syncope. A recent genetic study has identified first risk locus for syncope and collapse. The lead genetic variant, residing at chromosome 2q31.1, is an intergenic variant approximately 250 kb downstream of the ZNF804A gene. The variant effected the expression of ZNF804A, making this gene the strongest driver of the association.
Neurally mediated syncope
Reflex syncope or neurally mediated syncope occurs when blood vessels expand and heart rate decreases inappropriately leading to poor blood flow to the brain. This may occur from either a triggering event such as exposure to blood, pain, strong feelings, or a specific activity such as urination, vomiting, or coughing.
Vasovagal syncope
Vasovagal (situational) syncope is one of the most common types which may occur in response to any of a variety of triggers, such as scary, embarrassing or uneasy situations, during blood drawing, or moments of sudden unusually high stress. There are many different syncope syndromes which all fall under the umbrella of vasovagal syncope related by the same central mechanism. First, the person is usually predisposed to decreased blood pressure by various environmental factors. A lower than expected blood volume, for instance, from taking a low-salt diet in the absence of any salt-retaining tendency. Or heat causing vaso-dilation and worsening the effect of the relatively insufficient blood volume. The next stage is the adrenergic response. If there is underlying fear or anxiety (e.g., social circumstances), or acute fear (e.g., acute threat, needle phobia), the vaso-motor centre demands an increased pumping action by the heart (flight or fight response). This is set in motion via the adrenergic (sympathetic) outflow from the brain, but the heart is unable to meet requirements because of the low blood volume, or decreased return. A feedback response to the medulla is triggered via the afferent vagus nerve. The high (ineffective) sympathetic activity is thereby modulated by vagal (parasympathetic) outflow leading to excessive slowing of heart rate. The abnormality lies in this excessive vagal response causing loss of blood flow to the brain. The tilt-table test typically evokes the attack. Avoiding what brings on the syncope and possibly greater salt intake is often all that is needed.Associated symptoms may be felt in the minutes leading up to a vasovagal episode and are referred to as the prodrome. These consist of light-headedness, confusion, pallor, nausea, salivation, sweating, tachycardia, blurred vision, and sudden urge to defecate among other symptoms.Vasovagal syncope can be considered in two forms:
Isolated episodes of loss of consciousness, unheralded by any warning symptoms for more than a few moments. These tend to occur in the adolescent age group and may be associated with fasting, exercise, abdominal straining, or circumstances promoting vaso-dilation (e.g., heat, alcohol). The subject is invariably upright. The tilt-table test, if performed, is generally negative.
Recurrent syncope with complex associated symptoms. This is neurally mediated syncope (NMS). It is associated with any of the following: preceding or succeeding sleepiness, preceding visual disturbance ("spots before the eyes"), sweating, lightheadedness. The subject is usually but not always upright. The tilt-table test, if performed, is generally positive. It is relatively uncommon.Syncope has been linked with psychological triggers. This includes fainting in response to the sight or thought of blood, needles, pain, and other emotionally stressful situations. One theory in evolutionary psychology is that fainting at the sight of blood might have evolved as a form of playing dead which increased survival from attackers and might have slowed blood loss in a primitive environment. "Blood-injury phobia", as this is called, is experienced by about 15% of people. It is often possible to manage these symptoms with specific behavioral techniques.
Another evolutionary psychology view is that some forms of fainting are non-verbal signals that developed in response to increased inter-group aggression during the paleolithic. A non-combatant who has fainted signals that she or he is not a threat. This would explain the association between fainting and stimuli such as bloodletting and injuries seen in blood-injection-injury type phobias such as needle phobia as well as the gender differences.Much of this pathway was discovered in animal experiments by Bezold (Vienna) in the 1860s. In animals, it may represent a defence mechanism when confronted by danger ("playing possum").
Situational syncope
Syncope may be caused by specific behaviors including coughing, urination, defecation, vomiting, swallowing (deglutition), and following exercise. Manisty et al. note: "Deglutition syncope is characterised by loss of consciousness on swallowing; it has been associated not only with ingestion of solid food, but also with carbonated and ice-cold beverages, and even belching." Fainting can occur in "cough syncope" following severe fits of coughing, such as that associated with pertussis or "whooping cough." Neurally mediated syncope may also occur when an area in the neck known as the carotid sinus is pressed. A normal response to carotid sinus massage is reduction in blood pressure and slowing of the heart rate. Especially in people with hypersensitive carotid sinus syndrome this response can cause syncope or presyncope.
Cardiac
Heart-related causes may include an abnormal heart rhythm, problems with the heart valves or heart muscle, or blockages of blood vessels from a pulmonary embolism or aortic dissection, among others.
Cardiac arrhythmias
The most common cause of cardiac syncope is cardiac arrhythmia (abnormal heart rhythm) wherein the heart beats too slowly, too rapidly, or too irregularly to pump enough blood to the brain. Some arrhythmias can be life-threatening.Two major groups of arrhythmias are bradycardia and tachycardia. Bradycardia can be caused by heart blocks. Tachycardias include SVT (supraventricular tachycardia) and VT (ventricular tachycardia). SVT does not cause syncope except in Wolff-Parkinson-White syndrome. Ventricular tachycardia originate in the ventricles. VT causes syncope and can result in sudden death. Ventricular tachycardia, which describes a heart rate of over 100 beats per minute with at least three irregular heartbeats as a sequence of consecutive premature beats, can degenerate into ventricular fibrillation, which is rapidly fatal without cardiopulmonary resuscitation (CPR) and defibrillation.Long QT syndrome can cause syncope when it sets off ventricular tachycardia or torsades de pointes. The degree of QT prolongation determines the risk of syncope. Brugada syndrome also commonly presents with syncope secondary to arrhythmia.Typically, tachycardic-generated syncope is caused by a cessation of beats following a tachycardic episode. This condition, called tachycardia-bradycardia syndrome, is usually caused by sinoatrial node dysfunction or block or atrioventricular block.
Obstructive cardiac lesion
Blockages in major vessels or within the heart can also impede blood flow to the brain. Aortic stenosis and mitral stenosis are the most common examples. Major valves of the heart become stiffened and reduce the efficiency of the hearts pumping action. This may not cause symptoms at rest but with exertion, the heart is unable to keep up with increased demands leading to syncope. Aortic stenosis presents with repeated episodes of syncope. Rarely, cardiac tumors such as atrial myxomas can also lead to syncope.
Structural cardiopulmonary disease
Diseases involving the shape and strength of the heart can be a cause of reduced blood flow to the brain, which increases risk for syncope. The most common cause in this category is fainting associated with an acute myocardial infarction or ischemic event. The faint in this case is primarily caused by an abnormal nervous system reaction similar to the reflex faints. Women are significantly more likely to experience syncope as a presenting symptom of a myocardial infarction. In general, faints caused by structural disease of the heart or blood vessels are particularly important to recognize, as they are warning of potentially life-threatening conditions.Among other conditions prone to trigger syncope (by either hemodynamic compromise or by a neural reflex mechanism, or both), some of the most important are hypertrophic cardiomyopathy, acute aortic dissection, pericardial tamponade, pulmonary embolism, aortic stenosis, and pulmonary hypertension.
Other cardiac causes
Sick sinus syndrome, a sinus node dysfunction, causing alternating bradycardia and tachycardia. Often there is a long pause (asystole) between heartbeats.Adams-Stokes syndrome is a cardiac syncope that occurs with seizures caused by complete or incomplete heart block. Symptoms include deep and fast respiration, weak and slow pulse, and respiratory pauses that may last for 60 seconds.
Subclavian steal syndrome arises from retrograde (reversed) flow of blood in the vertebral artery or the internal thoracic artery, due to a proximal stenosis (narrowing) and/or occlusion of the subclavian artery. Symptoms such as syncope, lightheadedness, and paresthesias occur while exercising the arm on the affected side (most commonly the left).
Aortic dissection (a tear in the aorta) and cardiomyopathy can also result in syncope.Various medications, such as beta blockers, may cause bradycardia induced syncope.A pulmonary embolism can cause obstructed blood vessels and is the cause of syncope in less than 1% of people who present to the emergency department.
Blood pressure
Orthostatic (postural) hypotensive syncope is caused primarily by an excessive drop in blood pressure when standing up from a previous position of lying or sitting down. When the head is elevated above the feet the pull of gravity causes blood pressure in the head to drop. This is sensed by stretch receptors in the walls of vessels in the carotid sinus and aortic arch. These receptors then trigger a sympathetic nervous response to compensate and redistribute blood back into the brain. The sympathetic response causes peripheral vasoconstriction and increased heart rate. These together act to raise blood pressure back to baseline. Apparently healthy individuals may experience minor symptoms ("lightheadedness", "greying-out") as they stand up if blood pressure is slow to respond to the stress of upright posture. If the blood pressure is not adequately maintained during standing, faints may develop. However, the resulting "transient orthostatic hypotension" does not necessarily signal any serious underlying disease. It is as common or perhaps even more common than vasovagal syncope.
This may be due to medications, dehydration, significant bleeding or infection. The most susceptible individuals are elderly frail individuals, or persons who are dehydrated from hot environments or inadequate fluid intake. For example, medical students would be at risk for orthostatic hypotensive syncope while observing long surgeries in the operating room. There is also evidence that exercise training can help reduce orthostatic intolerance. More serious orthostatic hypotension is often the result of certain commonly prescribed medications such as diuretics, β-adrenergic blockers, other anti-hypertensives (including vasodilators), and nitroglycerin. In a small percentage of cases, the cause of orthostatic hypotensive faints is structural damage to the autonomic nervous system due to systemic diseases (e.g., amyloidosis or diabetes) or in neurological diseases (e.g., Parkinsons disease).Hyperadrenergic orthostatic hypotension refers to an orthostatic drop in blood pressure despite high levels of sympathetic adrenergic response. This occurs when a person with normal physiology is unable to compensate for >20% loss in intravascular volume. This may be due to blood loss, dehydration or third-spacing. On standing the person will experience reflex tachycardia (at least 20% increased over supine) and a drop in blood pressure.Hypoadrenergic orthostatic hypotension occurs when the person is unable to sustain a normal sympathetic response to blood pressure changes during movement despite adequate intravascular volume. There is little to no compensatory increase in heart rate or blood pressure when standing for up to 10 minutes. This is often due to an underlying disorder or medication use and is accompanied by other hypoadrenergic signs.
Central nervous system ischemia
The central ischemic response is triggered by an inadequate supply of oxygenated blood in the brain. Common examples include strokes and transient ischemic attacks. While these conditions often impair consciousness they rarely meet the medical definition of syncope. Vertebrobasilar transient ischemic attacks may produce true syncope as a symptom.The respiratory system may compensate for dropping oxygen levels through hyperventilation, though a sudden ischemic episode may also proceed faster than the respiratory system can respond. These processes cause the typical symptoms of fainting: pale skin, rapid breathing, nausea, and weakness of the limbs, particularly of the legs. If the ischemia is intense or prolonged, limb weakness progresses to collapse. The weakness of the legs causes most people to sit or lie down if there is time to do so. This may avert a complete collapse, but whether the patient sits down or falls down, the result of an ischaemic episode is a posture in which less blood pressure is required to achieve adequate blood flow. An individual with very little skin pigmentation may appear to have all color drained from his or her face at the onset of an episode. This effect combined with the following collapse can make a strong and dramatic impression on bystanders.
Vertebro-basilar arterial disease
Arterial disease in the upper spinal cord, or lower brain that causes syncope if there is a reduction in blood supply. This may occur with extending the neck or with use of medications to lower blood pressure.
Other causes
There are other conditions which may cause or resemble syncope.
Seizures and syncope can be difficult to differentiate. Both often present as sudden loss of consciousness and convulsive movements may be present or absent in either. Movements in syncope are typically brief and more irregular than seizures. Akinetic seizures can present with sudden loss of postural tone without associated tonic-clonic movements. Absence of a long post-ictal state is indicative of syncope rather than an akinetic seizure.
Subarachnoid hemorrhage may result in syncope. Often this is in combination with sudden, severe headache. It may occur as a result of a ruptured aneurysm or head trauma.Heat syncope occurs when heat exposure causes decreased blood volume and peripheral vasodilatation. Position changes, especially during vigorous exercise in the heat, may lead to decreased blood flow to the brain. Closely related to other causes of syncope related to hypotension (low blood pressure) such as orthostatic syncope. Lactose intolerance can cause "a release of histamine, resulting in an extreme dilatation of the bloodvessels, resulting in a drop of blood pressure so that not enough blood reaches the brains, leading to dizziness, fainting, syncope, itching, hives, tingling or swelling of the lips, tongue, or throat; chest tightness, shortness of breath, or difficulty breathing, wheezing." (More in the article on
Lactose intolerance).
Some psychological conditions (anxiety disorder, somatic symptom disorder, conversion disorder) may cause symptoms resembling syncope. A number of psychological interventions are available.Low blood sugar can be a rare cause of syncope.Narcolepsy may present with sudden loss of consciousness similar to syncope.
Diagnostic approach
A medical history, physical examination, and electrocardiogram (ECG) are the most effective ways to determine the underlying cause of syncope. Guidelines from the American College of Emergency Physicians and American Heart Association recommend a syncope workup include a thorough medical history, physical exam with orthostatic vitals, and a 12-lead ECG. The ECG is useful to detect an abnormal heart rhythm, poor blood flow to the heart muscle and other electrical issues, such as long QT syndrome and Brugada syndrome. Heart related causes also often have little history of a prodrome. Low blood pressure and a fast heart rate after the event may indicate blood loss or dehydration, while low blood oxygen levels may be seen following the event in those with pulmonary embolism. Routine broad panel laboratory testing detects abnormalities in <2–3% of results and is therefore not recommended.Based on this initial workup many physicians will tailor testing and determine whether a person qualifies as high-risk, intermediate risk or low-risk based on risk stratification tools. More specific tests such as implantable loop recorders, tilt table testing or carotid sinus massage may be useful in uncertain cases. Computed tomography (CT) is generally not required unless specific concerns are present. Other causes of similar symptoms that should be considered include seizure, stroke, concussion, low blood oxygen, low blood sugar, drug intoxication and some psychiatric disorders among others. Treatment depends on the underlying cause. Those who are considered at high risk following investigation may be admitted to hospital for further monitoring of the heart.A hemoglobin count may indicate anemia or blood loss. However, this has been useful in only about 5% of people evaluated for fainting. The tilt table test is performed to elicit orthostatic syncope secondary to autonomic dysfunction (neurogenic). A number of factors make a heart related cause more likely including age over 35, prior atrial fibrillation, and turning blue during the event.
Electrocardiogram
Electrocardiogram (ECG) finds that should be looked for include signs of heart ischemia, arrhythmias, atrioventricular blocks, a long QT, a short PR, Brugada syndrome, signs of hypertrophic obstructive cardiomyopathy (HOCM), and signs of arrhythmogenic right ventricular dysplasia (ARVD/C). Signs of HCM include large voltages in the precordial leads, repolarization abnormalities, and a wide QRS with a slurred upstroke. Signs of ARVD/C include T wave inversion and epsilon waves in lead V1 to V3.It is estimated that from 20 to 50% of people have an abnormal ECG. However, while an ECG may identify conditions such as atrial fibrillation, heart block, or a new or old heart attack, it typically does not provide a definite diagnosis for the underlying cause for fainting. Sometimes, a Holter monitor may be used. This is a portable ECG device that can record the wearers heart rhythms during daily activities over an extended period of time. Since fainting usually does not occur upon command, a Holter monitor can provide a better understanding of the hearts activity during fainting episodes. For people with more than two episodes of syncope and no diagnosis on "routine testing", an insertable cardiac monitor might be used. It lasts 28–36 months and is inserted just beneath the skin in the upper chest area.
Imaging
Echocardiography and ischemia testing may be recommended for cases where initial evaluation and ECG testing is nondiagnostic. For people with uncomplicated syncope (without seizures and a normal neurological exam) computed tomography or MRI is not generally needed. Likewise, using carotid ultrasonography on the premise of identifying carotid artery disease as a cause of syncope also is not indicated. Although sometimes investigated as a cause of syncope, carotid artery problems are unlikely to cause that condition. Additionally an electroencephalogram (EEG) is generally not recommended. A bedside ultrasound may be performed to rule out abdominal aortic aneurysm in people with concerning history or presentation.
Differential diagnosis
Other diseases which mimic syncope include seizure, low blood sugar, and certain types of stroke. While these may appear as "fainting", they do not fit the strict definition of syncope being a sudden reversible loss of consciousness due to decreased blood flow to the brain.
Management
Management of syncope focuses on treating the underlying cause. This can be challenging as the underlying cause is unclear in half of all cases. Several risk stratification tools (explained below) have been developed to combat the vague nature of this diagnosis. People with an abnormal ECG reading, history of congestive heart failure, family history of sudden cardiac death, shortness of breath, HCT<30, hypotension or evidence of bleeding should be admitted to the hospital for further evaluation and monitoring. Low-risk cases of vasovagal or orthostatic syncope in younger people with no significant cardiac history, no family history of sudden unexplained death, and a normal EKG and initial evaluation may be candidates for discharge to follow-up with their primary care provider.Recommended acute treatment of vasovagal and orthostatic (hypotension) syncope involves returning blood to the brain by positioning the person on the ground, with legs slightly elevated or sitting leaning forward and the head between the knees for at least 10–15 minutes, preferably in a cool and quiet place. For individuals who have problems with chronic fainting spells, therapy should focus on recognizing the triggers and learning techniques to keep from fainting. At the appearance of warning signs such as lightheadedness, nausea, or cold and clammy skin, counter-pressure maneuvers that involve gripping fingers into a fist, tensing the arms, and crossing the legs or squeezing the thighs together can be used to ward off a fainting spell. After the symptoms have passed, sleep is recommended. Lifestyle modifications are important for treating people experiencing repeated syncopal episodes. Avoiding triggers and situations where loss of consciousness would be seriously hazardous (operating heavy machinery, commercial pilot, etc.) has been shown to be effective.
If fainting spells occur often without a triggering event, syncope may be a sign of an underlying heart disease. In the case where syncope is caused by cardiac disease, the treatment is much more sophisticated than that of vasovagal syncope and may involve pacemakers and implantable cardioverter-defibrillators depending on the precise cardiac cause.
Risk tools
The San Francisco syncope rule was developed to isolate people who have higher risk for a serious cause of syncope. High risk is anyone who has: congestive heart failure, hematocrit <30%, electrocardiograph abnormality, shortness of breath, or systolic blood pressure <90 mmHg. The San Francisco syncope rule however was not validated by subsequent studies.The Canadian syncope risk score was developed to help select low-risk people that may be viable for discharge home. A score of <0 on the Canadian syncope risk score is associated with <2% risk of serious adverse event within 30 days. It has been shown to be more effective than older syncope risk scores even combined with cardiac biomarkers at predicting adverse events.
Epidemiology
There are 18.1–39.7 syncope episodes per 1000 people in the general population. Rates are highest between the ages of 10–30 years old. This is likely because of the high rates of vasovagal syncope in the young adult population. Older adults are more likely to have orthostatic or cardiac syncope.
Syncope affects about three to six out of every thousand people each year. It is more common in older people and females. It is the reason for 2–5% of visits to emergency departments and admissions to hospital. Up to half of women over the age of 80 and a third of medical students describe at least one event at some point in their lives.
Prognosis
Of those presenting with syncope to an emergency department, about 4% died in the next 30 days. The risk of a poor outcome, however, depends very much on the underlying cause. Situational syncope is not at increased risk of death or adverse outcomes. Cardiac syncope is associated with worse prognosis compared to noncardiac syncope. Factors associated with poor outcomes include history of heart failure, history of myocardial infarction, ECG abnormalities, palpitations, signs of hemorrhage, syncope during exertion, and advanced age.
Society and culture
Fainting in women was a commonplace trope or stereotype in Victorian England and in contemporary and modern depictions of the period.
Syncope and presyncope are common in young athletes. In 1990 the American college basketball player Hank Gathers suddenly collapsed and died during a televised intercollegiate |
Syncope (medicine) | basketball game. He had previously collapsed during a game a few months prior. He was diagnosed with exercise-induced ventricular tachycardia at the time. There was speculation that he had since stopped taking the prescribed medications on game days.Falling-out is a culture-bound syndrome primarily reported in the southern United States and the Caribbean.
Etymology
The term is derived from the Late Latin syncope, from Ancient Greek συγκοπή (sunkopē) cutting up, sudden loss of strength, from σύν (sun, "together, thoroughly") and κόπτειν (koptein, "strike, cut off").
See also
Voodoo death
References
External links
Syncope (medicine) at Curlie
2004 European Society of Cardiology Guidelines on Management (Diagnosis and Treatment) of Syncope
2017 American College of Cardiology Guideline
Tilt table test
The San Francisco syncope rule
"Fainting". MedlinePlus. U.S. National Library of Medicine. |
Granulosis rubra nasi | Granulosis rubra nasi is a rare familial disease of children, occurring on the nose, cheeks, and chin, characterized by diffuse redness, persistent excessive sweating, and small dark red papules that disappear on diascopic pressure.: 780
See also
Skin lesion
List of cutaneous conditions
References
== External links == |
Pyromania | Pyromania is an impulse control disorder in which individuals repeatedly fail to resist impulses to deliberately start fires, to relieve some tension or for instant gratification. The term pyromania comes from the Greek word πῦρ (pyr, fire). Pyromania is distinct from arson, the deliberate setting of fires for personal, monetary or political gain. Pyromaniacs start fires to release anxiety and tension, or for arousal. Other impulse disorders include kleptomania and intermittent explosive disorder.
There are specific symptoms that separate pyromaniacs from those who start fires for criminal purposes or due to emotional motivations not specifically related to fire. Someone with this disorder deliberately and purposely sets fires on more than one occasion, and before the act of lighting the fire the person usually experiences tension and an emotional buildup. When around fires, a person with pyromania gains intense interest or fascination and may also experience pleasure, gratification or relief. Another long term contributor often linked with pyromania is the buildup of stress. When studying the lifestyle of someone with pyromania, a buildup of stress and emotion is often evident and this is seen in teens attitudes towards friends and family. At times it is difficult to distinguish the difference between pyromania and experimentation in childhood because both involve pleasure from the fire.
Classification
ICD
The World Health Organizations International Classification of Diseases (11th Revision) ICD-11, regarded as the global standard, was released in June 2018 and came into full effect from January 2022. It states the following about pyromania:
Pyromania is characterised by a recurrent failure to control strong impulses to set fires, resulting in multiple acts of, or attempts at, setting fire to property or other objects, in the absence of an apparent motive (e.g., monetary gain, revenge, sabotage, political statement, attracting attention or recognition). There is an increasing sense of tension or affective arousal prior to instances of fire setting, persistent fascination or preoccupation with fire and related stimuli (e.g., watching fires, building fires, fascination with firefighting equipment), and a sense of pleasure, excitement, relief or gratification during, and immediately after the act of setting the fire, witnessing its effects, or participating in its aftermath.
It also notes that pyromania has no relation to intellectual impairment, substance abuse, or other mental and behavioral disorder. ICD-11 was produced by professionals from 55 countries out of the 90 countries involved and is one of the most widely used reference worldwide by clinicians, with the other being the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR from 2022, DSM-5 from 2013, or their predecessors)
DSM
The American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders, First Edition, released in 1952, categorized pyromania as a subset of Obsessive–compulsive disorder. In the Second Edition, the disorder was dropped. In the Third Edition, it returned under the category of impulse-control disorders.The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), released in 2022, states that the essential feature of pyromania is "the presence of multiple episodes of deliberate and purposeful fire setting." Pyromania moved from the DSM-4 chapter "Impulse-Control Disorders Not Otherwise Specified," to the chapter "Disruptive, impulse-control, and conduct disorders" in DSM-5.
Signs and symptoms
According to DSM-5, there are six signs of pyromania. Pyromania is mainly categorized by the purposeful setting of fire, tension or arousal before a fire is set, interest in or attraction to fire, and pleasure or relief after setting a fire. These fires not set for personal gain, are not meant to express anger or conceal illegal activity, are not in support of sociopolitical ideologies, are not in response to delusions, and are not signs of intellectual disability. For diagnosis, the setting of fire should not be better explained by a conduct disorder, manic episode, or a personality disorder (antisocial personality disorder). ICD-11 also adds substance abuse to this list. According to ICD-11, signs of fire setting may occur "in response to feelings of depressed mood, anxiety, boredom, loneliness, or other negative affective states." Those with pyromania exhibit problems in social environments and learning disabilities. Women pyromaniacs "often report histories of exposure to trauma, including sexual abuse, and self-harm." Episodic fire setting may become more intense and violent over time, becoming potentially chronic if untreated.
Causes
Most studied cases of pyromania occur in children and teenagers. There is a range of causes, but an understanding of the different motives and actions of fire setters can provide a platform for prevention. Common causes of pyromania can be broken down into two main groups: individual and environmental. This includes the complex understanding of factors such as individual temperament, parental psychopathology, and possible neurochemical predispositions. Many studies have shown that patients with pyromania were in households without a father figure present.Pyromania can be common in those with substance use disorders, problem gambling, mood disorders, disruptive behaviour, anti-social disorders, another impulse-control disorder.
Environmental
Environmental factors that may lead to pyromania include an event that the patient has experienced in the environment they live in. Environmental factors include neglect from parents and physical or emotional abuse in earlier life. Other causes include early experiences of watching adults or teenagers using fire inappropriately and lighting fires as a stress reliever.
Treatment and prognosis
The appropriate treatment for pyromania varies with the age of the patient and the seriousness of the condition. For children and adolescents treatment usually is cognitive behavioral therapy sessions in which the patients situation is diagnosed to find out what may have caused this impulsive behavior. Once the situation is diagnosed, repeated therapy sessions usually help continue to a recovery. Other important steps must be taken as well with the interventions and the cause of the impulse behavior. Some other treatments include parenting training, over-correction/satiation/negative practice with corrective consequences, behavior contracting/token reinforcement, special problem-solving skills training, relaxation training, covert sensitization, fire safety and prevention education, individual and family therapy, and medication. The prognosis for recovery in adolescents and children with pyromania depends on the environmental or individual factors in play, but is generally positive. Pyromania is generally harder to treat in adults, often due to lack of cooperation by the patient. Treatment usually consists of more medication to prevent stress or emotional outbursts, in addition to long-term psychotherapy. In adults, however, the recovery rate is generally poor, and if an adult does recover, it usually takes a longer period of time.
History
Pyromania was thought in the 1800s to be a concept involved with moral insanity and moral treatment, but had not been categorized under impulse control disorders. Pyromania is one of the four recognized types of arson, alongside burning for profit, to cover up an act of crime and for revenge. Pyromania is the second most common type of arson. Common synonyms for pyromaniacs in colloquial English include firebug (US) and fire raiser (UK), but these also refer to arsonists. Pyromania is a rare disorder with an incidence of less than one percent in most studies; also, pyromaniacs hold a very small proportion of psychiatric hospital admissions. Pyromania can occur in children as young as age three, though such cases are rare. Only a small percentage of children and teenagers arrested for arson are child pyromaniacs. A preponderance of the individuals are male; one source states that ninety percent of those diagnosed with pyromania are male. Based on a survey of 9,282 Americans using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, impulse-control problems such as gambling, pyromania and compulsive shopping collectively affect 9% of the population. A 1979 study by the Law Enforcement Assistance Administration found that only 14% of fires were started by pyromaniacs and others with mental illness. A 1951 study by Lewis and Yarnell, one of the largest epidemiological studies conducted, found that 39% of those who had intentionally set fires had been diagnosed with pyromania.
Popular culture
Beavis
Fire (The X-Files)
Firefly (DC Comics)
Mamimi Samejima
Trashcan Man
Deidara (Naruto)
The Pyro (Team Fortress 2)
In the videogame Lego Star Wars: The Skywalker Saga jedi master Yoda mentions that Chewbacca is a pyromaniac
See also
Child pyromaniac
Macdonald triad
Pyrophobia – the hatred or fear of fire
Pyrophilia – arousal or sexual gratification involving fire
Penhallow Hotel fire – a suspected pyromaniac attack
References
== External links == |
Hydranencephaly | Hydranencephaly is a condition in which the brains cerebral hemispheres are absent to a great degree and the remaining cranial cavity is filled with cerebrospinal fluid. "Cephalic" is the scientific term for "head" or "head end of body".
Hydranencephaly is a type of cephalic disorder. These disorders are congenital conditions that derive from damage to, or abnormal development of, the fetal nervous system in the earliest stages of development in utero. These conditions do not have any definitive identifiable cause factor. Instead, they are generally attributed to a variety of hereditary or genetic conditions, but also by environmental factors such as maternal infection, pharmaceutical intake, or even exposure to high levels of radiation.Hydranencephaly should not be confused with hydrocephalus, which is an accumulation of excess cerebrospinal fluid in the ventricles of the brain.
In hemihydranencephaly, only half of the cranial cavity is affected.
Signs and symptoms
An infant with hydranencephaly may appear normal at birth or may have some distortion of the skull and upper facial features due to fluid pressure inside the skull. The infants head size and spontaneous reflexes such as sucking, swallowing, crying, and moving the arms and legs may all seem normal, depending on the severity of the condition. However, after a few weeks the infant sometimes becomes irritable and has increased muscle tone (hypertonia). After several months of life, seizures and hydrocephalus may develop, if they did not exist at birth. Other symptoms may include visual impairment, lack of growth, deafness, blindness, spastic quadriparesis (paralysis), and intellectual deficits.Some infants may have additional abnormalities at birth including seizures, myoclonus (involuntary sudden, rapid jerks), limited thermoregulation abilities, and respiratory problems. Still other infants display no obvious symptoms at birth, going many months without a confirmed diagnosis of hydranencephaly. In some cases severe hydrocephalus, or another cephalic condition, is misdiagnosed.
Causes
Hydranencephaly is an extreme form of porencephaly, which is characterized by a cyst or cavity in the cerebral hemispheres.Although the exact cause of hydranencephaly remains undetermined in most cases, the most likely general cause is by vascular insult, such as stroke, injury, intrauterine infections, or traumatic disorders after the first trimester of pregnancy. In a number of cases where intrauterine infection was determined to be the causing factor, most involved toxoplasmosis and viral infections such as enterovirus, adenovirus, parvovirus, cytomegalovirus, herpes simplex, Epstein-Barr, and syncytial viruses. Another cause factor is monochorionic twin pregnancies, involving the death of one twin in the second trimester, which in turn causes vascular exchange to the living twin through placental circulation through twin-to-twin transfusion, causing hydranencephaly in the surviving fetus. One medical journal reports hydranencephaly as an autosomal inherited disorder with an unknown mode of transmission, causing a blockage of the carotid artery where it enters the cranium; this causes obstruction and damage to the cerebral cortex.
Genetic
Hydranencephaly is a recessive genetic condition, so both parents must carry the asymptomatic gene and pass it along to their child. There is a 25% chance that both parents will pass the gene to their child, resulting in hydranencephaly. Genetic hydranencephaly afflicts both males and females in equal numbers.
Post-natal brain injury
Though hydranencephaly is typically a congenital disorder, it can occur as a postnatal diagnosis in the aftermath of meningitis, intracerebral infarction, ischemia, or a traumatic brain injury.
Diagnosis
An accurate, confirmed diagnosis is generally impossible until after birth, though prenatal diagnosis using fetal ultrasonography (ultrasound) can identify characteristic physical abnormalities. After birth, diagnosis may be delayed for several months because the infants early behavior appears to be relatively normal. The most accurate diagnostic techniques are thorough clinical evaluation (considering physical findings and a detailed patient history); advanced imaging techniques, such as angiography, computerized tomography (CT scan), and magnetic resonance imaging (MRI); and (more rarely) transillumination. However, diagnostic literature fails to provide a clear distinction between severe obstructive hydrocephalus and hydranencephaly, leaving some children with an unsettled diagnosis.Preliminary diagnosis may be made in utero via standard ultrasound, and can be confirmed with a standard anatomy ultrasound. Hydranencephaly is sometimes misdiagnosed as bilaterally symmetric schizencephaly (a less destructive developmental process on the brain), severe hydrocephalus (cerebrospinal fluid excess within the skull), or alobar holoprosencephaly (a neurological developmental anomaly).
Once destruction of the brain is complete, the cerebellum, midbrain, thalami, basal ganglia, choroid plexus, and portions of the occipital lobes typically remain preserved to varying degrees. The cerebral cortex is absent; however, in most cases, the fetal head remains enlarged due to increased intracranial pressure, which results from inadequate reabsorption of the cerebrospinal fluid produced in the choroid plexus.
Prognosis
There is no standard treatment for hydranencephaly. Treatment is symptomatic and supportive. An accompanying diagnosis of hydrocephalus may be treated with surgical insertion of a shunt; this often improves prognosis and quality of life.The prognosis for children with hydranencephaly is generally quite poor. Death often occurs within the first year of life, though many children live several years, or even into adulthood; in one reported case, a person with hydranencephaly lived until age 19.
Occurrence
This condition affects under 1 in 10,000 births worldwide. Hydranencephaly is a rare disorder in the United States, which is defined as affecting fewer than 1 in 250,000.
See also
Microhydranencephaly
References
External links
Hydranencephaly at NINDS |
Vertebral column | The vertebral column, also known as the backbone or spine, is part of the axial skeleton. The vertebral column is the defining characteristic of a vertebrate in which the notochord (a flexible rod of uniform composition) found in all chordates has been replaced by a segmented series of bone: vertebrae separated by intervertebral discs. Individual vertebrae are named according to their region and position, and can be used as anatomical landmarks in order to guide procedures such as lumbar punctures. The vertebral column houses the spinal canal, a cavity that encloses and protects the spinal cord.
There are about 50,000 species of animals that have a vertebral column. The human vertebral column is one of the most-studied examples. Many different diseases in humans can affect the spine, with spina bifida and scoliosis being recognisable examples.
The general structure of human vertebrae is fairly typical of that found in mammals, reptiles, and birds. The shape of the vertebral body does, however, vary somewhat between different groups.
Structure
The number of vertebrae in a region can vary but overall the number remains the same. In a human vertebral column, there are normally 33 vertebrae. The upper 24 pre-sacral vertebrae are articulating and separated from each other by intervertebral discs, and the lower nine are fused in adults, five in the sacrum and four in the coccyx, or tailbone. The articulating vertebrae are named according to their region of the spine. There are 7 cervical vertebrae, 12 thoracic vertebrae and 5 lumbar vertebrae. The number of those in the cervical region, however, is only rarely changed, while that in the coccygeal region varies most. One study of 908 human adults found 43 individuals with 23 pre-sacral vertebrae (4.7%), 826 individuals with 24 pre-sacral vertebrae (91%), and 39 with 25 pre-sacral vertebrae (4.3%).There are ligaments extending the length of the column at the front and the back, and in between the vertebrae joining the spinous processes, the transverse processes and the vertebral laminae.
Vertebrae
The vertebrae in the human vertebral column is divided into different regions, which correspond to the curves of the vertebral column. The articulating vertebrae are named according to their region of the spine. Vertebrae in these regions are essentially alike, with minor variation. These regions are called the cervical spine, thoracic spine, lumbar spine, sacrum, and coccyx. There are seven cervical vertebrae, twelve thoracic vertebrae, and five lumbar vertebrae.
The number of vertebrae in a region can vary but overall the number remains the same. The number of those in the cervical region, however, is only rarely changed. The vertebrae of the cervical, thoracic, and lumbar spines are independent bones and generally quite similar. The vertebrae of the sacrum and coccyx are usually fused and unable to move independently. Two special vertebrae are the atlas and axis, on which the head rests.
A typical vertebra consists of two parts: the vertebral body and the vertebral arch. The vertebral arch is posterior, meaning it faces the back of a person. Together, these enclose the vertebral foramen, which contains the spinal cord. Because the spinal cord ends in the lumbar spine, and the sacrum and coccyx are fused, they do not contain a central foramen. The vertebral arch is formed by a pair of pedicles and a pair of laminae, and supports seven processes, four articular, two transverse, and one spinous, the latter also being known as the neural spine. Two transverse processes and one spinous process are posterior to (behind) the vertebral body. The spinous process comes out the back, one transverse process comes out the left, and one on the right. The spinous processes of the cervical and lumbar regions can be felt through the skin.
Above and below each vertebra are joints called facet joints. These restrict the range of movement possible, and are joined by a thin portion of the neural arch called the pars interarticularis. In between each pair of vertebrae are two small holes called intervertebral foramina. The spinal nerves leave the spinal cord through these holes.
Individual vertebrae are named according to their region and position. From top to bottom, the vertebrae are:
Cervical spine: 7 vertebrae (C1–C7)
Thoracic spine: 12 vertebrae (T1–T12)
Lumbar spine: 5 vertebrae (L1–L5)
Sacrum: 5 (fused) vertebrae (S1–S5)
Coccyx: 4 (3–5) (fused) vertebrae (Tailbone)The combined region of the thoracic and lumbar vertebrae is known as the thoracolumbar division, or region.
Shape
The vertebral column is curved in several places, a result of human bipedal evolution. The curves allow the human spine to better stabilize the body in the upright position.The upper cervical spine has a curve, convex forward, that begins at the axis (second cervical vertebra) at the apex of the odontoid process or dens and ends at the middle of the second thoracic vertebra; it is the least marked of all the curves. This inward curve is known as a lordotic curve.
The thoracic curve, concave forward, begins at the middle of the second and ends at the middle of the twelfth thoracic vertebra. Its most prominent point behind corresponds to the spinous process of the seventh thoracic vertebra. This curve is known as a kyphotic curve.
The lumbar curve is more marked in the female than in the male; it begins at the middle of the last thoracic vertebra, and ends at the sacrovertebral angle. It is convex anteriorly, the convexity of the lower three vertebrae being much greater than that of the upper two. This curve is described as a lordotic curve.
The sacral curve begins at the sacrovertebral articulation, and ends at the point of the coccyx; its concavity is directed downward and forward as a kyphotic curve.
The thoracic and sacral kyphotic curves are termed primary curves, because they are present in the fetus. The cervical and lumbar curves are compensatory, or secondary, and are developed after birth. The cervical curve forms when the infant is able to hold up its head (at three or four months) and sit upright (at nine months). The lumbar curve forms later from twelve to eighteen months, when the child begins to walk.
Surfaces
Anterior surfaceWhen viewed from in front, the width of the bodies of the vertebrae is seen to increase from the second cervical to the first thoracic; there is then a slight diminution in the next three vertebrae. Below this, there is again a gradual and progressive increase in width as low as the sacrovertebral angle. From this point there is a rapid diminution, to the apex of the coccyx.
Posterior surfaceFrom behind, the vertebral column presents in the median line the spinous processes. In the cervical region (with the exception of the second and seventh vertebrae), these are short, horizontal, and bifid. In the upper part of the thoracic region they are directed obliquely downward; in the middle they are almost vertical, and in the lower part they are nearly horizontal. In the lumbar region they are nearly horizontal. The spinous processes are separated by considerable intervals in the lumbar region, by narrower intervals in the neck, and are closely approximated in the middle of the thoracic region. Occasionally one of these processes deviates a little from the median line — which can sometimes be indicative of a fracture or a displacement of the spine. On either side of the spinous processes is the vertebral groove formed by the laminae in the cervical and lumbar regions, where it is shallow, and by the laminae and transverse processes in the thoracic region, where it is deep and broad; these grooves lodge the deep muscles of the back. Lateral to the spinous processes are the articular processes, and still more laterally the transverse processes. In the thoracic region, the transverse processes stand backward, on a plane considerably behind that of the same processes in the cervical and lumbar regions. In the cervical region, the transverse processes are placed in front of the articular processes, lateral to the pedicles and between the intervertebral foramina. In the thoracic region they are posterior to the pedicles, intervertebral foramina, and articular processes. In the lumbar region they are in front of the articular processes, but behind the intervertebral foramina.
Lateral surfacesThe sides of the vertebral column are separated from the posterior surface by the articular processes in the cervical and thoracic regions and by the transverse processes in the lumbar region. In the thoracic region, the sides of the bodies of the vertebrae are marked in the back by the facets for articulation with the heads of the ribs. More posteriorly are the intervertebral foramina, formed by the juxtaposition of the vertebral notches, oval in shape, smallest in the cervical and upper part of the thoracic regions and gradually increasing in size to the last lumbar. They transmit the special spinal nerves and are situated between the transverse processes in the cervical region and in front of them, in the thoracic and lumbar regions.
Ligaments
There are different ligaments involved in the holding together of the vertebrae in the column, and in the columns movement. The anterior and posterior longitudinal ligaments extend the length of the vertebral column along the front and back of the vertebral bodies. The interspinous ligaments connect the adjoining spinous processes of the vertebrae. The supraspinous ligament extends the length of the spine running along the back of the spinous processes, from the sacrum to the seventh cervical vertebra. From there it is continuous with the nuchal ligament.
Development
The striking segmented pattern of the spine is established during embryogenesis when somites are rhythmically added to the posterior of the embryo. Somite formation begins around the third week when the embryo begins gastrulation and continues until all somites are formed. Their number varies between species: there are 42 to 44 somites in the human embryo and around 52 in the chick embryo. The somites are spheres, formed from the paraxial mesoderm that lies at the sides of the neural tube and they contain the precursors of spinal bone, the vertebrae ribs and some of the skull, as well as muscle, ligaments and skin. Somitogenesis and the subsequent distribution of somites is controlled by a clock and wavefront model acting in cells of the paraxial mesoderm. Soon after their formation, sclerotomes, which give rise to some of the bone of the skull, the vertebrae and ribs, migrate, leaving the remainder of the somite now termed a dermamyotome behind. This then splits to give the myotomes which will form the muscles and dermatomes which will form the skin of the back. Sclerotomes become subdivided into an anterior and a posterior compartment. This subdivision plays a key role in the definitive patterning of vertebrae that form when the posterior part of one somite fuses to the anterior part of the consecutive somite during a process termed resegmentation. Disruption of the somitogenesis process in humans results in diseases such as congenital scoliosis. So far, the human homologues of three genes associated to the mouse segmentation clock, (MESP2, DLL3 and LFNG), have been shown to be mutated in cases of congenital scoliosis, suggesting that the mechanisms involved in vertebral segmentation are conserved across vertebrates. In humans the first four somites are incorporated in the base of the occipital bone of the skull and the next 33 somites will form the vertebrae, ribs, muscles, ligaments and skin. The remaining posterior somites degenerate. During the fourth week of embryogenesis, the sclerotomes shift their position to surround the spinal cord and the notochord. This column of tissue has a segmented appearance, with alternating areas of dense and less dense areas.
As the sclerotome develops, it condenses further eventually developing into the vertebral body. Development of the appropriate shapes of the vertebral bodies is regulated by HOX genes.
The less dense tissue that separates the sclerotome segments develop into the intervertebral discs.
The notochord disappears in the sclerotome (vertebral body) segments but persists in the region of the intervertebral discs as the nucleus pulposus. The nucleus pulposus and the fibers of the anulus fibrosus make up the intervertebral disc.
The primary curves (thoracic and sacral curvatures) form during fetal development. The secondary curves develop after birth. The cervical curvature forms as a result of lifting the head and the lumbar curvature forms as a result of walking.
Function
Spinal cord
The vertebral column surrounds the spinal cord which travels within the spinal canal, formed from a central hole within each vertebra. The spinal cord is part of the central nervous system that supplies nerves and receives information from the peripheral nervous system within the body. The spinal cord consists of grey and white matter and a central cavity, the central canal. Adjacent to each vertebra emerge spinal nerves. The spinal nerves provide sympathetic nervous supply to the body, with nerves emerging forming the sympathetic trunk and the splanchnic nerves.
The spinal canal follows the different curves of the column; it is large and triangular in those parts of the column that enjoy the greatest freedom of movement, such as the cervical and lumbar regions, and is small and rounded in the thoracic region, where motion is more limited. The spinal cord terminates in the conus medullaris and cauda equina.
Clinical significance
Disease
Spina bifida is a congenital disorder in which there is a defective closure of the vertebral arch. Sometimes the spinal meninges and also the spinal cord can protrude through this, and this is called spina bifida cystica. Where the condition does not involve this protrusion it is known as spina bifida occulta. Sometimes all of the vertebral arches may remain incomplete.Another, though rare, congenital disease is Klippel–Feil syndrome, which is the fusion of any two of the cervical vertebrae.
Spondylolisthesis is the forward displacement of a vertebra and retrolisthesis is a posterior displacement of one vertebral body with respect to the adjacent vertebra to a degree less than a dislocation.
Spondylolysis, also known as a pars defect, is a defect or fracture at the pars interarticularis of the vertebral arch.
Spinal disc herniation, more commonly called a "slipped disc", is the result of a tear in the outer ring (anulus fibrosus) of the intervertebral disc, which lets some of the soft gel-like material, the nucleus pulposus, bulge out in a hernia.
Spinal stenosis is a narrowing of the spinal canal which can occur in any region of the spine though less commonly in the thoracic region. The stenosis can constrict the spinal canal giving rise to a neurological deficit.
Pain at the coccyx (tailbone) is known as coccydynia.Spinal cord injury is damage to the spinal cord that causes changes in its function, either temporary or permanent. Spinal cord injuries can be divided into categories: complete transection, hemisection, central spinal cord lesions, posterior spinal cord lesions, and anterior spinal cord lesions.
Scalloping vertebrae is the increase in the concavity of the posterior vertebral body. It can be seen on lateral X-ray and sagittal views of CT and MRI scans. Its concavity is due to the increased pressure exerting on the vertebrae due to a mass. Internal spinal mass such as spinal astrocytoma, ependymoma, schwannoma, neurofibroma, and achondroplasia causes vertebrae scalloping.
Curvature
Excessive or abnormal spinal curvature is classed as a spinal disease or dorsopathy and includes the following abnormal curvatures:
Kyphosis is an exaggerated kyphotic (convex) curvature of the thoracic region in the sagittal plane, also called hyperkyphosis. This produces the so-called "humpback" or "dowagers hump", a condition commonly resulting from osteoporosis.
Lordosis is an exaggerated lordotic (concave) curvature of the lumbar region in the sagittal plane, is known as lumbar hyperlordosis and also as "swayback". Temporary lordosis is common during pregnancy.
Scoliosis, lateral curvature, is the most common abnormal curvature, occurring in 0.5% of the population. It is more common among females and may result from unequal growth of the two sides of one or more vertebrae, so that they do not fuse properly. It can also be caused by pulmonary atelectasis (partial or complete deflation of one or more lobes of the lungs) as observed in asthma or pneumothorax.
Kyphoscoliosis, a combination of kyphosis and scoliosis.
Anatomical landmarks
Individual vertebrae of the human vertebral column can be felt and used as surface anatomy, with reference points are taken from the middle of the vertebral body. This provides anatomical landmarks that can be used to guide procedures such as a lumbar puncture and also as vertical reference points to describe the locations of other parts of human anatomy, such as the positions of organs.
Other animals
Variations in vertebrae
The general structure of vertebrae in other animals is largely the same as in humans. Individual vertebrae are composed of a centrum (body), arches protruding from the top and bottom of the centrum, and various processes projecting from the centrum and/or arches. An arch extending from the top of the centrum is called a neural arch, while the haemal arch or chevron is found underneath the centrum in the caudal (tail) vertebrae of fish, most reptiles, some birds, some dinosaurs and some mammals with long tails. The vertebral processes can either give the structure rigidity, help them articulate with ribs, or serve as muscle attachment points. Common types are transverse process, diapophyses, parapophyses, and zygapophyses (both the cranial zygapophyses and the caudal zygapophyses). The centrum of the vertebra can be classified based on the fusion of its elements. In temnospondyls, bones such as the spinous process, the pleurocentrum and the intercentrum are separate ossifications. Fused elements, however, classify a vertebra as having holospondyly.
A vertebra can also be described in terms of the shape of the ends of the centrum. Centra with flat ends are acoelous, like those in mammals. These flat ends of the centra are especially good at supporting and distributing compressive forces. Amphicoelous vertebra have centra with both ends concave. This shape is common in fish, where most motion is limited. Amphicoelous centra often are integrated with a full notochord. Procoelous vertebrae are anteriorly concave and posteriorly convex. They are found in frogs and modern reptiles. Opisthocoelous vertebrae are the opposite, possessing anterior convexity and posterior concavity. They are found in salamanders, and in some non-avian dinosaurs. Heterocoelous vertebrae have saddle-shaped articular surfaces. This type of configuration is seen in turtles that retract their necks, and birds, because it permits extensive lateral and vertical flexion motion without stretching the nerve cord too extensively or wringing it about its long axis.
In horses, the Arabian (breed) can have one less vertebrae and pair of ribs. This anomaly disappears in foals that are the product of an Arabian and another breed of horse.
Regional vertebrae
Vertebrae are defined by the regions of the vertebral column that they occur in, as in humans. Cervical vertebrae are those in the neck area. With the exception of the two sloth genera (Choloepus and Bradypus) and the manatee genus, (Trichechus), all mammals have seven cervical vertebrae. In other vertebrates, the number of cervical vertebrae can range from a single vertebra in amphibians to as many as 25 in swans or 76 in the extinct plesiosaur Elasmosaurus. The dorsal vertebrae range from the bottom of the neck to the top of the pelvis. Dorsal vertebrae attached to the ribs are called thoracic vertebrae, while those without ribs are called lumbar vertebrae. The sacral vertebrae are those in the pelvic region, and range from one in amphibians, to two in most birds and modern reptiles, or up to three to five in mammals. When multiple sacral vertebrae are fused into a single structure, it is called the sacrum. The synsacrum is a similar fused structure found in birds that is composed of the sacral, lumbar, and some of the thoracic and caudal vertebra, as well as the pelvic girdle. Caudal vertebrae compose the tail, and the final few can be fused into the pygostyle in birds, or into the coccygeal or tail bone in chimpanzees (and humans).
Fish and amphibians
The vertebrae of lobe-finned fishes consist of three discrete bony elements. The vertebral arch surrounds the spinal cord, and is of broadly similar form to that found in most other vertebrates. Just beneath the arch lies a small plate-like pleurocentrum, which protects the upper surface of the notochord, and below that, a larger arch-shaped intercentrum to protect the lower border. Both of these structures are embedded within a single cylindrical mass of cartilage. A similar arrangement was found in the primitive Labyrinthodonts, but in the evolutionary line that led to reptiles (and hence, also to mammals and birds), the intercentrum became partially or wholly replaced by an enlarged pleurocentrum, which in turn became the bony vertebral body.
In most ray-finned fishes, including all teleosts, these two structures are fused with, and embedded within, a solid piece of bone superficially resembling the vertebral body of mammals. In living amphibians, there is simply a cylindrical piece of bone below the vertebral arch, with no trace of the separate elements present in the early tetrapods.In cartilaginous fish, such as sharks, the vertebrae consist of two cartilaginous tubes. The upper tube is formed from the vertebral arches, but also includes additional cartilaginous structures filling in the gaps between the vertebrae, and so enclosing the spinal cord in an essentially continuous sheath. The lower tube surrounds the notochord, and has a complex structure, often including multiple layers of calcification.Lampreys have vertebral arches, but nothing resembling the vertebral bodies found in all higher vertebrates. Even the arches are discontinuous, consisting of separate pieces of arch-shaped cartilage around the spinal cord in most parts of the body, changing to long strips of cartilage above and below in the tail region. Hagfishes lack a true vertebral column, and are therefore not properly considered vertebrates, but a few tiny neural arches are present in the tail.
Other vertebrates
The general structure of human vertebrae is fairly typical of that found in mammals, reptiles, and birds. The shape of the vertebral body does, however, vary somewhat between different groups. In mammals, such as humans, it typically has flat upper and lower surfaces, while in reptiles the anterior surface commonly has a concave socket into which the expanded convex face of the next vertebral body fits. Even these patterns are only generalisations, however, and there may be variation in form of the vertebrae along the length of the spine even within a single species. Some unusual variations include the saddle-shaped sockets between the cervical vertebrae of birds and the presence of a narrow hollow canal running down the centre of the vertebral bodies of geckos and tuataras, containing a remnant of the notochord.Reptiles often retain the primitive intercentra, which are present as small crescent-shaped bony elements lying between the bodies of adjacent vertebrae; similar structures are often found in the caudal vertebrae of mammals. In the tail, these are attached to chevron-shaped bones called haemal arches, which attach below the base of the spine, and help to support the musculature. These latter bones are probably homologous with the ventral ribs of fish. The number of vertebrae in the spines of reptiles is highly variable, and may be several hundred in some species of snake.In birds, there is a variable number of cervical vertebrae, which often form the only truly flexible part of the spine. The thoracic vertebrae are partially fused, providing a solid brace for the wings during flight. The sacral vertebrae are fused with the lumbar vertebrae, and some thoracic and caudal vertebrae, to form a single structure, the synsacrum, which is thus of greater relative length than the sacrum of mammals. In living birds, the remaining caudal vertebrae are fused into a further bone, the pygostyle, for attachment of the tail feathers.Aside from the tail, the number of vertebrae in mammals is generally fairly constant. There are almost always seven cervical vertebrae (sloths and manatees are among the few exceptions), followed by around twenty or so further vertebrae, divided between the thoracic and lumbar forms, depending on the number of ribs. There are generally three to five vertebrae with the sacrum, and anything up to fifty caudal vertebrae.
Dinosaurs
The vertebral column in dinosaurs consists of the cervical (neck), dorsal (back), sacral (hips), and caudal (tail) vertebrae. Saurischian dinosaur vertebrae sometimes possess features known as pleurocoels, which are hollow depressions on the lateral portions of the vertebrae, perforated to create an entrance into the air chambers within the vertebrae, which served to decrease the weight of these bones without sacrificing strength. These pleurocoels were filled with air sacs, which would have further decreased weight. In sauropod dinosaurs, the largest known land vertebrates, pleurocoels and air sacs may have reduced the animals weight by over a ton in some instances, a handy evolutionary adaption in animals that grew to over 30 metres in length. In many hadrosaur and theropod dinosaurs, the caudal vertebrae were reinforced by ossified tendons. The presence of three or more sacral vertebrae, in association with the hip bones, is one of the defining characteristics of dinosaurs. The occipital condyle is a structure on the posterior part of a dinosaurs skull that articulates with the first cervical vertebra.
See also
Low back pain
Neuromechanics of idiopathic scoliosis
Neutral spine
References
External links
Spinal Term Glossary
VIRTUAL Spine - online learning resource |
Café au lait spot | Café au lait spots, or café au lait macules, are flat, hyperpigmented birthmarks. The name café au lait is French for "coffee with milk" and refers to their light-brown color. Café au lait lesions with rough borders ("coast of Maine") may be seen in McCune-Albright syndrome. In contrast, Café au lait lesions of neurofibromatosis have smooth borders ("coast of California").They are caused by a collection of pigment-producing melanocytes in the epidermis of the skin.These spots are typically permanent and may grow or increase in number over time.Café au lait spots are often harmless but may be associated with syndromes such as neurofibromatosis type 1 and McCune–Albright syndrome.
Cause
Café au lait spots can arise from diverse and unrelated causes:
Ataxia–telangiectasia
Basal cell nevus syndrome
Benign congenital skin lesion
Bloom syndrome
Chédiak–Higashi syndrome
Congenital melanocytic naevus
Fanconi anemia
Gaucher disease
Hunter syndrome
Jaffe–Campanacci syndrome
Legius syndrome
Maffucci syndrome
They can be caused by vitiligo in the rare McCune–Albright syndrome.
Multiple mucosal neuroma syndrome
Having six or more café au lait spots greater than 5 mm in diameter before puberty, or greater than 15 mm in diameter after puberty, is a diagnostic feature of neurofibromatosis type I (NF-1), but other features are required to diagnose NF-1. Familial multiple cafe-au-lait spots have been observed without an NF-1 diagnosis.
Noonan syndrome
Silver–Russell syndrome
Tuberous sclerosis
Watson syndrome
Wiskott–Aldrich syndrome
Diagnosis
Diagnosis is visual with measurement of spot size. The number of spots can have clinical significance for diagnosis of associated disorders such as Neurofibromatosis type I. Six or more spots of at least 5mm in diameter in pre-pubertal children and at least 15mm in post-pubertal individuals is one of the major diagnostic criteria for NF1.
Prognosis
Café au lait spots are usually present at birth, permanent, and may grow in size or increase in number over time.Cafe au lait spots are themselves benign and do not cause any illness or problems. However, they may be associated with syndromes such as Neurofibromatosis Type 1 and McCune-Albright syndrome.The size and shape of the spots can vary in terms of description. In Neurofibromatosis Type 1, the spots tend to be described as ovoid, with smooth borders. In other disorders, the spots can be less ovoid, with jagged borders. In Neurofibromatosis Type 1, the spots tend to resemble the "coast of California," rather than the "coast of Maine," meaning the edges are smoother and more linear.
Treatment
Café au lait spots can be removed with lasers. Results are variable as the spots are often not completely removed or can come back after treatment. Often, a test spot is treated first to help predict the likelihood of treatment success.
See also
Birthmark
Nevus
List of cutaneous conditions
List of conditions associated with café au lait macules
References
External links
eMedicine |
Triangular alopecia | Triangular alopecia is hair loss that may be congenital but usually appears in childhood as a focal patch of loss that may be complete or leaving fine vellus hairs behind.: 643 Affected individuals are typically entirely healthy. Hair restoration surgery using follicular unit transplantation has been a successful treatment modality for TTA
Presentation
Association with Other Conditions
TTA has been associated with several disorders, such as Phakomatosis pigmentovascularis. And a rare syndrome Setleis syndrome. It is inherited by the autosomal dominant trait and is characterized by cutis aplasia or atrophic skin at the temples, which is said to resemble forceps marks. There may also be a coarse facial appearance, anomalies of the eyelashes and eyebrows, and periorbital puffiness.
Frequency
The suggested frequency for this condition in the general population is around 0.11%. The hair loss is non-progressive and does not expand beyond these areas. It is a non-inflammatory, non-scarring form of hair loss easily confused with alopecia areata. In one report, the condition was incorrectly believed by the parents to be induced by doctors inserting intravenous cannulas into scalp vessels during the neonatal period. The condition is permanent and the affected skin does not change later in life.Of the 53 reported cases of TTA, more than half (55.8%) were detected in childhood between the ages of 2 and 9 years, while 36.5% were detected at birth and only 3.8% (only two cases) in adulthood.
See also
Alopecia
Skin lesion
List of cutaneous conditions
== References == |
Stenosis of pulmonary artery | Stenosis of the pulmonary artery is a condition where the pulmonary artery is subject to an abnormal constriction (or stenosis). Peripheral pulmonary artery stenosis may occur as an isolated event or in association with Alagille syndrome, Berardinelli-Seip congenital lipodystrophy type 1, Costello syndrome, Keutel syndrome, nasodigitoacoustic syndrome (Keipert syndrome), Noonan syndrome or Williams syndrome.It should not be confused with a pulmonary valve stenosis, which is in the heart, but can have similar hemodynamic effects. Both stenosis of the pulmonary artery and pulmonary valve stenosis are causes of pulmonic stenosis.In some cases it is treated with surgery.
References
== External links == |
Myospherulosis | Myospherulosis, also known as spherulocytosis, is a foreign body-type granulomatous reaction to lipid-containing material and blood.It may be seen in various settings including:
Fat necrosis.
Malignancy, e.g. renal cell carcinoma.
Placement of topical tetracycline in a petrolatum base into a surgical site.The resultant histopathologic pattern is most unusual and initially was mistakenly thought to represent a previously undescribed endosporulating fungus.
See also
Fat necrosis
== References == |
Infantile esotropia | Infantile esotropia is an ocular condition of early onset in which one or either eye turns inward. It is a specific sub-type of esotropia and has been a subject of much debate amongst ophthalmologists with regard to its naming, diagnostic features, and treatment.
Presentation
Historically the term congenital strabismus was used to describe constant esotropias with onset between birth and six months of age. However, this term was felt to be an inadequate classification as it covered a variety of esotropias with different causes, features and prognoses.
In 1988, American ophthalmologist Gunter K. Von Noorden discussed what he described as Essential Infantile Esotropia. He described the condition as:
"early acquired, not... congenital ..., although congenital factors may favor its development between the ages of 3 and 6 months"
and identified this squint sub-type as having the following features:
Onset between birth and six months of age.
Large size (greater than 30 dioptres)
Stable size
Not associated with abnormalities of the central nervous system.
Often associated with defective abduction (outward movement) and excessive adduction (inward movement) of the eyes.
Also associated with oblique muscle dysfunction and Dissociated Vertical Deviation.
Initial alternation of the squint present with crossed fixation, i.e. the affected individual uses the left eye to look right and the right eye to look left.
Limited potential for binocular vision.The same condition had also previously been described by other ophthalmologists, notably Cianca (1962) who named it Ciancas Syndrome and noted the presence of manifest latent nystagmus, and Lang (1968) who called it Congenital Esotropia Syndrome and noted the presence of abnormal head postures. In both cases, however, the essential characteristics were the same, but with emphasis placed on different elements of the condition.
Helveston (1993) further clarified and expanded upon von Noordens work, and incorporated the work of both Lang and Cianca into his summary of the characteristics of the condition:
Esotropia between 10 and 90 dioptres in size
Either alternation or fixation preference may be present (if the latter then amblyopia may result).
Neurologically normal.
Hyperopic correction does not eliminate or significantly reduce the squint size.
Frequent nystagmus (latent or manifest latent).
The patient may or may not have any or all of the following associated conditions: Oblique muscle dysfunction, vertical incomitance, dissociated vertical deviation, asymmetric optokinetic nystagmus, torticollis.
Presence will be confirmed by six months.
Best treatment results in subnormal binocular vision.The expressions congenital esotropia, infantile esoptropia, idiopathic infantile esotropia and essential infantile esotropia are often used interchangeably.
Cross-fixation
Cross-fixation congenital esotropia, also called Ciancis syndrome is a particular type of large-angle infantile esotropia associated with tight medius rectus muscles. With the tight muscles, which hinder adduction, there is a constant inward eye turn. The patient cross-fixates, that is, to fixate objects on the left, the patient looks across the nose with the right eye, and vice versa. The patient tends to adopt a head turn, turning the head to the right to better see objects in the left visual field and turning the head to the left to see those in the right visual field. Binasal occlusion can be used to discourage cross-fixation. However, the management of cross-fixation congenital esotropia usually involves surgery.
Cause
This remains undetermined at the present time. A recent study by Major et al. reports that:
Prematurity, family history or secondary ocular history, perinatal or gestational complications, systemic disorders, use of supplemental oxygen as a neonate, use of systemic medications, and male sex were found to be significant risk factors for infantile esotropia.
Further recent evidence indicates that a cause for infantile strabismus may lie with the input that is provided to the visual cortex. In particular, neonates who suffer injuries that, directly or indirectly, perturb binocular inputs into the primary visual cortex (V1) have a far higher risk of developing strabismus than other infants.
Diagnosis
Differential Diagnosis
Clinically Infantile esotropia must be distinguished from:
VIth Cranial nerve or abducens palsy
Nystagmus Blockage Syndrome
Esotropia arising secondary to central nervous system abnormalities (in cerebral palsy for example)
Primary Constant esotropia
Duanes Syndrome
Treatment
According to a Cochrane review of 2012, controversies remain regarding type of surgery, non-surgical intervention and age of intervention.The aims of treatment are as follows:
The elimination of any amblyopia
A cosmetically acceptable ocular alignment
Long-term stability of eye position
Binocular cooperation
Initially
It is essential that a child with strabismus is presented to the ophthalmologist as early as possible for diagnosis and treatment in order to allow best possible monocular and binocular vision to develop. Initially, the patient will have a full eye examination to identify any associated pathology, and any glasses required to optimise acuity will be prescribed – although infantile esotropia is not typically associated with refractive error. Studies have found that approximately 15% of infantile esotropia patients have accommodative esotropia. For these patients, antiaccommodative therapy (with spectacles) is indicated before any surgery as antiaccommodative therapy fully corrects their esotropia in many cases and significantly decreases their deviation angle in others.Amblyopia will be treated via occlusion treatment (using patching or atropine drops) of the non-squinting eye with the aim of achieving full alternation of fixation. Management thereafter will be surgical. As alternative to surgery, also botulinum toxin therapy has been used in children with infantile esotropia. Furthermore, as accompaniment to ophthalmologic treatment, craniosacral therapy may be performed in order to relieve tension (see also: Management of strabismus).
Surgery
Controversy has arisen regarding the selection and planning of surgical procedures, the timing of surgery and about what constitutes a favourable outcome.
1. Selection and planning
Some ophthalmologists, notably Ing and Helveston, favour a prescribed approach often involving multiple surgical episodes whereas others prefer to aim for full alignment of the eyes in one procedure and let the number of muscles operated upon during this procedure be determined by the size of the squint.
2. Timing and outcome
This debate relates to the technical anatomical difficulties of operating on the very young versus the possibility of an increased potential for binocularity associated with early surgery. Infants are often operated upon at the age of six to nine months of age and in some cases even earlier at three or four months of age. Some emphasize the importance of intervening early such as to keep the duration of the patients abnormal visual experience to a minimum. Advocates of early surgery believe that those who have their surgery before the age of one are more likely to be able to use both eyes together post-operatively.
A Dutch study (ELISSS) compared early with late surgery in a prospective, controlled, non-randomized, multicenter trial and reported that:
Children operated early had better gross stereopsis at age six as compared to children operated late. They had been operated more frequently, however, and a substantial number of children in both [originally-recruited] groups had not been operated at all.
Other studies also report better results with early surgery, notably Birch and Stager and Murray et al. but do not comment on the number of operations undertaken. A recent study on 38 children concluded that surgery for infantile esotropia is most likely to result in measureable stereopsis if patient age at alignment is not more than 16 months.
Another study found that for children with infantile esotropia early surgery decreases the risk of dissociated vertical deviation developing after surgery.Aside the strabismus itself, there are other aspects or conditions that appear to improve after surgery or botulinum toxin eye alignment. Study outcomes have indicated that after surgery the child catches up in development of fine-motor skills (such as grasping a toy and handling a bottle) and of large-muscle skills (such as sitting, standing, and walking) in case a developmental delay was present before. Evidence also indicates that as of the age of six, strabismic children become less accepted by their peers, leaving them potentially exposed to social exclusion starting at this age unless their eye positioning is corrected by this time (see also: Psychosocial effects of strabismus).
References
External links
Infantile esotropia, Medscape, updated 30 May 2012 |
Boutonniere deformity | Boutonniere deformity is a deformed position of the fingers or toes, in which the joint nearest the knuckle (the proximal interphalangeal joint, or PIP) is permanently bent toward the palm while the farthest joint (the distal interphalangeal joint, or DIP) is bent back away (PIP flexion with DIP hyperextension). Causes include injury, inflammatory conditions like rheumatoid arthritis, and genetic conditions like Ehlers-Danlos syndrome.
Pathophysiology
This flexion deformity of the proximal interphalangeal joint is due to interruption of the central slip of the extensor tendon such that the lateral slips separate and the head of the proximal phalanx pops through the gap like a finger through a button hole (thus the name, from French boutonnière "button hole"). The distal joint is subsequently drawn into hyperextension because the two peripheral slips of the extensor tendon are stretched by the head of the proximal phalanx (note that the two peripheral slips are inserted into the distal phalanx, while the proximal slip is inserted into the middle phalanx). This deformity makes it difficult or impossible to extend the proximal interphalangeal joint.
Diagnosis
Stages
Mild extension lag, passively correctable
Moderate extension lag, passively correctable
Mild flexion contracture
Advanced flexion contractureHigher numbers indicate a more severe problem and greater likelihood of a poor outcome.
Treatment
Usually treated with a splint placing the proximal interphalangeal joint in extension for 4–6 weeks. Occasionally surgery is needed when splinting is unsuccessful.
See also
Swan neck deformity
Z-deformity
References
Further reading
Coons, Matthew S.; Green, Steven M. (August 1995). "Boutonniere deformity". Hand Clinics. 11 (3): 387–402. doi:10.1016/S0749-0712(21)00060-3. PMID 7559817.
Souter, William A. (October 1974). "The Problem of Boutonniere Deformity". Clinical Orthopaedics and Related Research. 104 (104): 116–133. doi:10.1097/00003086-197410000-00012. PMID 4607222.
Nalebuff, Edward A.; Millender, Lewis H. (July 1975). "Surgical Treatment of the Boutonniere Deformity in Rheumatoid Arthritis". Orthopedic Clinics of North America. 6 (3): 753–763. doi:10.1016/S0030-5898(20)30987-1. PMID 1099508.
Littler, J. William; Eaton, Richard G. (October 1967). "Redistribution of Forces in the Correction of the Boutonnière Deformity". JBJS. 49 (7): 1267–1274. doi:10.2106/00004623-196749070-00002. PMID 5622971.
To, Philip; Watson, Jeffry T. (January 2011). "Boutonniere Deformity". The Journal of Hand Surgery. 36 (1): 139–142. doi:10.1016/j.jhsa.2010.10.032. PMID 21193133.
Massengill, James B. (November 1992). "The boutonniere deformity". Hand Clinics. 8 (4): 787–801. doi:10.1016/S0749-0712(21)00744-7. PMID 1460075.
Aiache, Adrien; Barsky, Arthur J.; Weiner, Daniel L. (August 1970). "Prevention of the boutonniere deformity". Plastic and Reconstructive Surgery. 46 (2): 164–167. doi:10.1097/00006534-197008000-00010. PMID 5423482. S2CID 39268503.
Curtis, Raymond M.; Reid, Robert L.; Provost, John M. (March 1983). "A staged technique for the repair of the traumatic boutonniere deformity". The Journal of Hand Surgery. 8 (2): 167–171. doi:10.1016/s0363-5023(83)80009-4. PMID 6833725.
Urbaniak, James R.; Hayes, Michael G. (July 1981). "Chronic boutonniere deformity—An anatomic reconstruction". The Journal of Hand Surgery. 6 (4): 379–383. doi:10.1016/s0363-5023(81)80048-2. PMID 7252114.
Dolphin, James A. (January 1965). "Extensor Tenotomy for Chronic Boutonnière Deformity of the Finger: REPORT OF TWO CASES". JBJS. 47 (1): 161–164. doi:10.2106/00004623-196547010-00011. PMID 14256963.
External links
Boutonniere Deformity at eMedicine |
Incidental imaging finding | In medical or research imaging, an incidental imaging finding (also called an incidentaloma) is an unanticipated finding which is not related to the original diagnostic inquiry. As with other types of incidental medical findings, they may represent a diagnostic, ethical, and philosophical dilemma because their significance is unclear. While some coincidental findings may lead to beneficial diagnoses, others may lead to overdiagnosis that results in unnecessary testing and treatment, sometimes called the "cascade effect".Incidental findings are common in imaging. For instance, around 1 in every 3 cardiac MRIs result in an incidental finding. Incidence is similar for chest CT scans (~30%).As the use of medical imaging increases, the number of incidental findings also increases.
Adrenal
Incidental adrenal masses on imaging are common (0.6 to 1.3% of all abdominal CT). Differential diagnosis include adenoma, myelolipoma, cyst, lipoma, pheochromocytoma, adrenal cancer, metastatic cancer, hyperplasia, and tuberculosis. Some of these lesions are easily identified by radiographic appearance; however, it is often adenoma vs. cancer/metastasis that is most difficult to distinguish. Thus, clinical guidelines have been developed to aid in diagnosis and decision-making. Although adrenal incidentalomas are common, they are not commonly cancerous - less than 1% of all adrenal incidentalomas are malignant.The first considerations are size and radiographic appearance of the mass. Suspicious adrenal masses or those ≥4 cm are recommended for complete removal by adrenalectomy. Masses <4 cm may also be recommended for removal if they are found to be hormonally active, but are otherwise recommended for observation. All adrenal masses should receive hormonal evaluation. Hormonal evaluation includes:
1-mg overnight dexamethasone suppression test
24-hour urinary specimen for measurement of fractionated metanephrines and catecholamines
Blood plasma aldosterone concentration and plasma renin activity, if hypertension is presentOn CT scan, benign adenomas typically are of low radiodensity (due to fat content). A radiodensity equal to or below 10 Hounsfield units (HU) is considered diagnostic of an adenoma. An adenoma also shows rapid radiocontrast washout (50% or more of the contrast medium washes out at 10 minutes). If the hormonal evaluation is negative and imaging suggests benign lesion, follow up may be considered. Imaging at 6, 12, and 24 months and repeat hormonal evaluation yearly for 4 years is often recommended, but there exists controversy about harm/benefit of such screening as there is a high subsequent false-positive rate (about 50:1) and overall low incidence of adrenal carcinoma.
Brain
Autopsy series have suggested that pituitary incidentalomas may be quite common. It has been estimated that perhaps 10% of the adult population may harbor such endocrinologically inert lesions. Most of these lesions, especially those which are small, will not grow. However, some form of long-term surveillance has been recommended based on the size and presentation of the lesion. With pituitary adenomas larger than 1cm, a baseline pituitary hormonal function test should be done, including measurements of serum levels of TSH, prolactin, IGF-1 (as a test of growth hormone activity), adrenal function (i.e. 24 hour urine cortisol, dexamethasone suppression test), testosterone in men, and estradiol in amenorrheic women.
Thyroid and parathyroid
Incidental thyroid masses may be found in 9% of patients undergoing bilateral carotid duplex ultrasonography.Some experts recommend that nodules > 1 cm (unless the TSH is suppressed) or those with ultrasonographic features of malignancy should be biopsied by fine needle aspiration. Computed tomography is inferior to ultrasound for evaluating thyroid nodules. Ultrasonographic markers of malignancy are:
solid hypoechoic appearance
irregular or blurred margins
intranodular vascular spots or pattern
microcalcificationsIncidental parathyroid masses may be found in 0.1% of patients undergoing bilateral carotid duplex ultrasonography.The American College of Radiology recommends the following workup for thyroid nodules as incidental imaging findings on CT, MRI or PET-CT:
Pulmonary
Studies of whole body screening computed tomography find abnormalities in the lungs of 14% of patients. Clinical practice guidelines by the American College of Chest Physicians advise on the evaluation of the solitary pulmonary nodule.
Kidney
Most renal cell carcinomas are now found incidentally. Tumors less than 3 cm in diameter less frequently have aggressive histology.A CT scan is the first choice modality for workup of solid masses in the kidneys. Nevertheless, hemorrhagic cysts can resemble renal cell carcinomas on CT, but they are easily distinguished with Doppler ultrasonography (Doppler US). In renal cell carcinomas, Doppler US often shows vessels with high velocities caused by neovascularization and arteriovenous shunting. Some renal cell carcinomas are hypovascular and not distinguishable with Doppler US. Therefore, renal tumors without a Doppler signal, which are not obvious simple cysts on US and CT, should be further investigated with contrast-enhanced ultrasound, as this is more sensitive than both Doppler US and CT for the detection of hypovascular tumors.
Spinal
The increasing use of MRI, often during diagnostic work-up for back or lower extremity pain, has led to a significant increase in the number of incidental findings that are most often clinically inconsequential. The most common include:
vertebral hemangioma
fibrolipoma (a lipoma with fibrous areas)
Tarlov cystSometimes normally asymptomatic findings can present with symptoms and these cases when identified cannot then be considered as incidentalomas.
Criticism
The concept of the "incidentaloma" has been criticized, as such lesions do not have much in common other than the history of an incidental identification and the assumption that they are clinically inert. It has been proposed just to say that such lesions have been "incidentally found." The underlying pathology shows no unifying histological concept.
== References == |
Periorbital hyperpigmentation | Periorbital hyperpigmentation, also known as hereditary dark circles, is characterized by darker skin around the eyes caused by the presence of additional melanin. It is an extremely common hereditary human characteristic and is frequently found on individuals with dark skin. Periorbital hyperpigmentation is most prevalent within the 16–25 age group.
See also
Eye shadow
Kohl (cosmetics)
Freckles
References
== External links == |
Verrucous carcinoma | Verrucous carcinoma (VC) is an uncommon variant of squamous cell carcinoma. This form of cancer is often seen in those who chew tobacco or use snuff orally, so much so that it is sometimes referred to as "Snuff dippers cancer".
Signs and symptoms
Age – usually over 60 years old
Sex – males are more prone
Site – gingiva, buccal mucosa, alveolar mucosa, hard palate, floor of the mouth, larynx, oesophagus, penis, vagina, scrotum.
Clinical presentation:
It is a slow growing, diffuse, exophytic lesion usually covered by leukoplakic patches.
Invasive lesions quickly invade bones.
It can rapidly become fixed with underlying periosteum and cause gradual destruction of jaw bone.
Enlarged regional lymph nodes.
Lesion shows painful multiple rugae-like folds and deep clefts between them.
Regional lymph nodes tender and enlarged.
Pain and difficulty in mastication.
Cause
This form of cancer is often seen in those who chew tobacco or use snuff orally, so much so that it is sometimes referred to as "Snuff dippers cancer". Chewing betel nuts is an additional risk factor commonly seen in Taiwan.
Risk factors
The major risk factors are cigarette smoking and alcohol consumption, while betel nut is an additional factor in Taiwan. Different gene mutation sites in head and neck cancer between western countries and Taiwan have been reported.The presentation of VC originated from exposure to different carcinogens may not be the same.
Locations
Verrucous carcinoma may occur in various head and neck locations, as well as in the genitalia or sole of the foot. The oral cavity is the most common site of this tumor. The ages range from 50 to 80 years with a male predominance and a median age of 67 years. VC may grow large in size, resulting in the destruction of adjacent tissue, such as bone and cartilage.
Diagnosis
Surgeons must provide adequate specimens including the full thickness of the tumors and adjacent uninvolved mucosa for correct histopathology diagnosis.
Subtypes
Epithelioma cuniculatum (also known as Carcinoma cuniculatum,: 654 and Ackerman tumor) is a subtype of verrucous carcinoma, characterized by well-differentiated epithelial cells which lack cytological atypia, but display a blunt papillary/pebbly surface and keratin-filled crypts extending deep into the connective tissue. These keratin-filled resemble rabbit burrows. It is located almost exclusively on the foot, but at least oral location has also been described.
Treatment
Surgery is considered the treatment of choice, but the extent of surgical margin and the adjuvant radiotherapy are still controversial.
Surgical excision alone is effective for controlling VC, but elective neck dissection is not necessary even in patients in the advanced stages.
Prognosis
Most patients with verrucous carcinoma have a good prognosis. Local recurrence is not uncommon, but metastasis to distant parts of the body is rare. Patients with oral verrucous carcinoma may be at greater risk of a second oral squamous cell carcinoma, for which the prognosis is worse.
See also
List of cutaneous conditions
List of verrucous carcinoma subtypes
References
External links
eMedicine.com article |
Choreoathetosis | Choreoathetosis is the occurrence of involuntary movements in a combination of chorea (irregular migrating contractions) and athetosis (twisting and writhing).
It is caused by many different diseases and agents. It is a symptom of several diseases, including Lesch–Nyhan syndrome, phenylketonuria, and Huntington disease and can be a feature of kernicterus (rapidly increasing unconjugated bilirubin that cross the blood-brain-barrier in infants).
Choreoathetosis is also a common presentation of dyskinesia as a side effect of levodopa-carbidopa in the treatment of Parkinson disease.The use of crack cocaine or amphetamines can result in conditions nicknamed crack dancing, or tweaking respectively, described as choreathetoid.
See also
Ulegyria
References
== External links == |
Warm antibody autoimmune hemolytic anemia | Warm antibody autoimmune hemolytic anemia (WAIHA) is the most common form of autoimmune haemolytic anemia. About half of the cases are of unknown cause, with the other half attributable to a predisposing condition or medications being taken. Contrary to cold autoimmune hemolytic anemia (e.g., cold agglutinin disease and paroxysmal cold hemoglobinuria) which happens in cold temperature (28–31 °C), WAIHA happens at body temperature.
Causes
AIHA may be:
Idiopathic, that is, without any known cause
Secondary to another disease, such as an antecedent upper respiratory tract infection, systemic lupus erythematosus or a malignancy, such as chronic lymphocytic leukemia (CLL)
Medications
Several medications have been associated with the development of warm AIHA. These medications include quinidine, nonsteroidal anti-inflammatory drugs (NSAIDs), alpha methyldopa, and antibiotics such as penicillins, cephalosporins (such as ceftriaxone and cefotetan), and ciprofloxacin.
Pathophysiology
The most common antibody isotype involved in warm antibody AIHA is IgG, though sometimes IgA is found. The IgG antibodies attach to a red blood cell, leaving their FC portion exposed with maximal reactivity at 37 °C (versus cold antibody induced hemolytic anemia whose antibodies only bind red blood cells at low body temperatures, typically 28-31 °C). The FC region is recognized and grabbed onto by FC receptors found on monocytes and macrophages in the spleen. These cells will pick off portions of the red cell membrane, almost as if they are taking a bite. The loss of membrane causes the red blood cells to become spherocytes. Spherocytes are not as flexible as normal RBCs and will be singled-out for destruction in the red pulp of the spleen as well as other portions of the reticuloendothelial system. The red blood cells trapped in the spleen cause the spleen to enlarge, leading to the splenomegaly often seen in these patients.There are two models for this: the hapten model and the autoantibody model. The hapten model proposes that certain drugs, especially penicillin and cephalosporins, will bind to certain proteins on the red cell membrane and act as haptens (small molecules that can elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself). Antibodies are created against the protein-drug complex, leading to the destructive sequence described above. The autoantibody model proposes that, through a mechanism not yet understood, certain drugs will cause antibodies to be made against red blood cells which again leads to the same destructive sequence.
It is possible for it to occur in an immunocompromised patient.
Diagnosis
Diagnosis is made by a positive direct Coombs test, other lab tests, and clinical examination and history. The direct Coombs test looks for antibodies attached to the surface of red blood cells.
Clinical findings
Laboratory findings include severe anemia, normal MCV (mean corpuscular volume), and hyperbilirubinemia (from increased red cell destruction) that can be of the conjugated or unconjugated type.
Treatment
Corticosteroids and immunoglobulins are two commonly used treatments for warm antibody AIHA. Initial medical treatment consists of prednisone. If ineffective, splenectomy should be considered.If refractory to both these therapies, other options include rituximab, danazol, cyclosphosphamide, azathioprine, or ciclosporin. High-dose intravenous immune globulin may be effective in controlling hemolysis, but the benefit is short lived (1–4 weeks), and the therapy is very expensive.
See also
List of circulatory system conditions
References
External links
Case report of warm-antibody autoimmune hemolytic anemia with typical laboratory findings. Clinical Cases and Images
The wAIHA Warriors is a 501(c)3 support and advocacy group for caregivers and patients of warm autoimmune hemolytic anemia. www.waihawarriors.org |
Systemic vasculitis | Necrotizing vasculitis, also called systemic necrotizing vasculitus, is a category of vasculitis, comprising vasculitides that present with necrosis.Examples include giant cell arteritis, microscopic polyangiitis, and granulomatosis with polyangiitis.
ICD-10 uses the variant "necrotizing vasculopathy". ICD-9, while classifying these conditions together, does not use a dedicated phrase, instead calling them "polyarteritis nodosa and allied conditions".
When using the influential classification known as the "Chapel Hill Consensus Conference", the terms "systemic vasculitis" or "primary systemic vasculitides" are commonly used. Although the word necrotizing is omitted, the conditions described are largely the same.
Classification
Large vessel vasculitis
Giant-cell arteritis and Takayasus arteritis have much in common, but usually affect patients of different ages, with Takayasus arteritis affecting younger people, and giant-cell arteritis having a later age of onset.
Aortitis can also be considered a large-vessel disease.Takayasu arteritis. Primarily affects the aorta and its main branches. At least three out of six criteria yields sensitivity and specificity of 90.5 and 97.8%:
Onset < 40 years affects young and middle -aged women (ages 15–45)
Claudication of extremities
Decreased pulsation of one or both brachial arteries
At least 10 mmHg systolic difference in both arms
Bruit over one or both carotid arteries or abdominal aorta
Arteriographic narrowing of aorta, its primary branches, or large arteries in upper or lower extremities
Ocular manifestation
Visual loss or field defects
Retinal hemorrhages
Neurological abnormalities
Treatment: steroidsGiant cell (temporal) arteritis. Chronic vasculitis of both large and medium vessels, primarily affecting cranial branches of the arteries arising from the aortic arch. At least three out of five criteria yields sensitivity and specificity of 95 and 91%:
Age at onset ≥ 50 years
New onset headache with localized tenderness
Temporal artery tenderness or decreased pulsation
Elevated ESR ≥ 50 mm/hour Westergren
Temporal artery biopsy showing vasculitis with mononuclear cell infiltrate or granulomatous inflammation, usually with multinucleated giant cells
Medium vessel vasculitis
These conditions are sometimes considered together with the small vessel vasculitides.Polyarteritis nodosa (PAN). Systemic necrotizing vasculitis and aneurysm formation affecting both medium and small arteries. If only small vessels are affected, it is called microscopic polyangiitis, although it is more associated with granulomatosis with polyangiitis than to classic PAN. At least 3 out of 10 criteria yields sensitivity and specificity of 82 and 87%:
Unexplained weight loss > 4 kg
Livedo reticularis
Testicular pain
Myalgias, weakness
Abdominal pain, diarrhea, and GI bleeding
Mononeuropathy or polyneuropathy
New onset diastolic blood pressure > 90 mmHg
Elevated serum blood urea nitrogen (> 40 mg/dL) or serum creatinine (> 1.5 mg/dL)
Hepatitis B infection
Arteriographic abnormalities
Arterial biopsy showing polymorphonuclear cellsKawasaki disease. Usually in children (age<4), it affects large, medium, and small vessels, prominently the coronary arteries. Associated with a mucocutaneous lymph node syndrome. Diagnosis requires fever lasting five days or more with at least four out of five criteria:
Bilateral conjunctival injection
Injected or fissured lips, injected pharynx, or strawberry tongue
Erythema of palms/soles, edema of hands/feet, periungual desquamation
Polymorphous rash
Cervical lymphadenopathy (at least one node > 1.5 cm)Isolated cerebral vasculitis. Affects medium and small arteries over a diffuse CNS area, without symptomatic extracranial vessel involvement. Patients have CNS symptoms as well as cerebral vasculitis by angiography and leptomeningeal biopsy.
Small vessel vasculitis
There are several vasculitides that affect small vessels.
Pauci-immune
Granulomatosis with polyangiitis. Systemic vasculitis of medium and small arteries, including venules and arterioles. Produces granulomatous inflammation of the respiratory tracts and necrotizing, pauci-immune glomerulonephritis. Most common cause of saddle nose deformity in USA (nose flattened due to destruction of nasal septum by granulomatous inflammation). Almost all patients with granulomatosis with polyangiitis have c-antineutrophil cytoplasmic antibody, but not vice versa. Current treatment of choice is cyclophosphamide. At least two out of four criteria yields sensitivity and specificity of 88 and 92%.
Nasal or oral inflammation (oral ulcers or purulent/bloody nasal discharge, may be painful)
Abnormal chest X-ray with showing nodules, infiltrates, or cavities
Microscopic hematuria or red blood cell casts
Vessel biopsy shows granulomatous inflammation
Peak incidence: ages 40–60, males > femalesEosinophilic granulomatosis with polyangiitis (formerly known as Churg–Strauss syndrome). Affects medium and small vessels with vascular and extravascular granulomatosis. Classically involves arteries of lungs and skin, but may be generalized. At least four criteria yields sensitivity and specificity of 85 and 99.7%.
Asthma (history of wheezing or presently wheezing)
Eosinophilia > 10% on complete blood count
Mononeuropathy or polyneuropathy
Migratory or transient pulmonary opacities on chest x-ray
Paranasal sinus abnormalities
Vessel biopsy showing eosinophils in extravascular areasMicroscopic polyarteritis/polyangiitis. Affects capillaries, venules, or arterioles. Thought to be part of a group that includes granulomatosis with polyangiitis since both are associated with antineutrophil cytoplasmic antibody and similar extrapulmonary manifestations. Patients do not usually have symptomatic or histologic respiratory involvement.
Immune complex
Hypersensitivity vasculitis (allergic vasculitis). Usually due to a hypersensitivity reaction to a known drug. Drugs most commonly implicated are penicillin, sulphonamides and thiazide diuretics. Methamphetamine and other sympathomimetics can cause a cerebral vasculitis alongside polyarteritis nodosa like systemic features. With other drugs,there is presence of skin vasculitis with palpable petechiae or purpura. Biopsy of these lesions reveal inflammation of the small vessels, termed leukocytoclastic vasculitis, which is most prominent in postcapillary venules. At least three out of five criteria yields sensitivity and specificity of 71 and 84%:
Age > 16
Use of possible triggering drug in relation to symptoms
Palpable purpura
Maculopapular rash
Skin biopsy showing neutrophils around vesselIgA vasculitis (formerly known as Henoch–Schonlein purpura). Systemic vasculitis due to tissue deposition of IgA-containing immune complexes. Biopsy of lesions shows inflammation of small vessels. It is considered a form of hypersensitivity vasculitis but is distinguished by prominent deposits of IgA. This is the most common vasculitis in children. Presence of three or more criteria yielded sensitivity of 87% while less than two criteria yielded hypersensitivity vasculitis in 74%:
Palpable purpura (usually of buttocks and legs)
Bowel angina
GI bleed
Hematuria
Onset < 20 years
No new medicationsEssential cryoglobulinemic vasculitis. Most often due to hepatitis C infection, immune complexes of cryoglobulins – proteins that consists of immunoglobulins and complement and precipitate in the cold while dissolving upon rewarming – are deposited in walls of capillaries, venules, or arterioles. Therefore, complement will be low with histology showing vessel inflammation with immune deposits.
Other/ungrouped
Vasculitis secondary to connective tissue disorders. Usually secondary to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), relapsing polychondritis, Behçets disease, and other connective tissue disorders.
Vasculitis secondary to viral infection. Usually due to hepatitis B and C, human immunodeficiency virus, cytomegalovirus, Epstein–Barr virus, and parvovirus B19.
Signs and symptoms
Patients usually present with systemic symptoms with single or multiorgan dysfunction. Common (and nonspecific) complaints include fatigue, weakness, fever, joint pains, abdominal pain, hypertension, chronic kidney disease, and neurologic dysfunction. The following symptoms should raise a strong suspicion of a vasculitis:
Mononeuritis multiplex. Also known as asymmetric polyneuropathy, in a non-diabetic this is suggestive of vasculitis.
Palpable purpura. If patients have this in isolation, it is most likely due to cutaneous leukocytoclastic vasculitis. If the purpura is in combination with systemic organ involvement, it is most likely to be Henoch–Schönlein purpura or microscopic polyangiitis.
Pulmonary-renal syndrome. Individuals who are coughing up blood and have kidney involvement are likely to have granulomatosis with polyangiitis, microscopic polyangiitis, or anti-GBM disease (Goodpasture syndrome).
Diagnosis
A detailed history is important to elicit any recent medications, any risk of hepatitis infection, or any recent diagnosis with a connective tissue disorder such as systemic lupus erythematosus (SLE). A thorough physical exam is needed as usual.
Lab tests. Basic lab tests may include a complete blood count, chemiestries (look for creatinine), creatine phosphokinase level, liver function tests, erythrocyte sedimentation rate, hepatitis serologies, urinalysis, chest X-ray, and an electrocardiogram. Additional, more specific tests include:
Antinuclear antibody test can detect an underlying connective tissue disorder, especially lupus erythematosus
Complement levels that are low can suggest mixed cryoglobulinemia, hepatitis C infection, and lupus erythematosus], but not most other vasculitides.
Antineutrophil cytoplasmic antibody may suggest granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, or drug-induced vasculitis, but is not diagnostic.
Electromyography. It is useful if a systemic vasculitis is suspected and neuromuscular symptoms are present.
Arteriography. Arteriograms are helpful in vasculitis affecting the large and medium vessels but not helpful in small vessel vasculitis. Angiograms of mesenteric or renal arteries in polyarteritis nodosa may show aneurysms, occlusions, and vascular wall abnormalities. Arteriography are not diagnostic in itself if other accessible areas for biopsy are present. However, in Takayasus arteritis, where the aorta may be involved, it is unlikely a biopsy will be successful and angiography can be diagnostic.
Tissue biopsy. This is the gold standard of diagnosis when it is taken from the most involved area.
Treatment
Treatment is targeted to the underlying cause. However, most vasculitis in general are treated with steroids (e.g., methylprednisolone) because the underlying cause of the vasculitis is due to hyperactive immunological damage. Immunosuppressants such as cyclophosphamide and azathioprine may also be given.
A systematic review of antineutrophil cytoplasmic antibody-positive vasculitis identified best treatments depending on whether the goal is to induce remission or maintenance and depending on severity of the vasculitis.
References
== External links == |
Atypical chronic myeloid leukemia | Atypical chronic myeloid leukemia (aCML) is a type of leukemia. It is a heterogeneous disorder belonging to the group of myelodysplastic/myeloproliferative (MDS/MPN) syndromes.
In aCML many clinical features (splenomegaly, myeloid predominance in the bone marrow with some dysplastic features but without a differentiation block) and laboratory abnormalities (myeloid proliferation, low leukocyte alkaline phosphatase values) suggest the diagnosis of chronic myelogenous leukemia (CML). However the lack of the pathognomonic Philadelphia chromosome and of the resulting BCR-ABL1 fusion point to a different pathogenetic process. Since no specific recurrent genomic or karyotypic abnormalities have been identified in aCML, the molecular pathogenesis of this disease has remained elusive and the outcome dismal (median survival 37 months) with no improvement over the last 20 years. This sharply contrasts with the outcome for CML, for which the prognosis was dramatically improved by the development of imatinib as a specific inhibitor of the BCR-ABL protein and in particular for CML.In 2012 SETBP1 was identified as a novel oncogene in aCML; specific somatic mutations of this gene were discovered in people with aCML and related diseases. These mutations, which are identical to the ones present in SGS as germline mutations, impair the degradation of SETBP1 and therefore cause increased cellular levels of the protein.
== References == |
Abdominal migraine | Abdominal migraine is a variant type of migraine. It primarily affects children, and is rare in adults. It mainly causes episodes of abdominal pain without an accompanying headache. It is poorly understood. It is difficult to confirm the diagnosis, as periumbilical abdominal pain has an extensive differential diagnosis. It may be treated with analgesia in some patients, and other medications. Avoiding triggers can prevent an episode of abdominal migraine.
Signs and Symptoms
Symptoms of abdominal migraine may include:
Abdominal pain
Nausea
Vomiting
Headache
Photosensitivity
Loss of appetite
PallorThese occur in distinct episodes. This can have a significant effect on day-to-day life. It usually does not occur with a headache. Body mass index is usually unaffected, and physical development is normal.
Causes
Common migraine triggers may trigger abdominal migraines. Psychological stress (such as from school), a change in location (such as travel), changes to sleep, and exercise when this is not wanted, may all cause abdominal migraine.
Pathophysiology
Abdominal migraine is poorly understood.
Diagnosis
As with other types of migraines, there is no diagnostic test to identify abdominal migraines. Diagnosis is based on symptoms, a family history of migraines, and eliminations of other possible causes. It can take time before a diagnosis is made, as symptoms are not specific to abdominal migraine.Diagnostic criteria from the International Classification of Headache Disorders are:
A. At least 5 attacks fulfilling criteria B-D.
B. Attacks of abdominal pain lasting 1–72 hours (untreated or unsuccessfully treated)
C. Abdominal pain has all of the following characteristics:
1. midline location, periumbilical or poorly localized
2. dull or "just sore" quality
3. moderate or severe intensity
D. During abdominal pain at least 2 of the following:
1. loss of appetite
2. nausea
3. vomiting
4. pallor
E. Not attributed to another disorder
Differential diagnosis
Abdominal migraine must be distinguished from other causes of chronic or recurrent abdominal pain. These include irritable bowel syndrome, peptic ulcer disease, gastroesophageal reflux disease, mast cell activation syndrome, and celiac artery compression syndrome. It must also be distinguished from causes of acute abdominal pain, such as appendicitis, as wrong diagnosis may lead to unnecessary appendectomy.
Treatment
Short term
Analgesia may be effective against abdominal migraine in some patients. Avoidance of intense light tends to have a short-term beneficial effect.
Long term
Avoidance of triggers can be very helpful. Medications such as pizotifen, propanolol, and cyproheptadine may be used in rare circumstances.
Prognosis
Abdominal migraine can have a significant impact on day-to-day life. Children may miss school or other activities. It resolves in many patients. Prognosis is generally good in children, but variable in adults.
Epidemiology
Abdominal migraine primarily affects children, for whom it is a common cause of chronic abdominal pain. It may be as high as 9% or as low as 1% among children. It is rare in adults. However, children diagnosed with abdominal migraines may have migraine headaches as adults. The mean age of diagnosis is 7 years. It appears to be slightly more common in women.
History
This condition was first described in 1921 by Buchanan. It was once considered a controversial diagnosis. However, it is now accepted as a common cause of chronic abdominal pain in children.
== References == |
Lathosterolosis | Lathosterolosis is a defect in cholesterol biosynthesis.
See also
SC5DL
Lathosterol
References
== External links == |
Miller syndrome | Miller syndrome, also known as Genée–Wiedemann syndrome, Wildervanck–Smith syndrome or postaxial acrofacial dystosis, is an extremely rare genetic condition that manifests as craniofacial, limb and eye deformities. It is caused by a mutation in the DHODH gene. The incidence of the condition is not known, and nothing is known of its pathogenesis.
Presentation
The syndrome consists of severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the postaxial elements of the limbs, coloboma of the eyelids and supernumerary nipples. Additional features of the syndrome include downward-slanting palpebral fissures, malar hypoplasia, malformed ears, and a broad nasal ridge. Other features include supernumerary vertebrae and other vertebral segmentation and rib defects, heart defects (patent ductus arteriosus, ventricular septal defect and ostium primum atrial septal defect), lung disease from chronic infection, single umbilical artery, absence of the hemidiaphragm, hypoplasia of the femora, ossification defects of the ischium and pubis, bilobed tongue, lung hypoplasia, and renal reflux.
Cause
The gene responsible for this disorder is DHODH located at chromosome 16q22. This gene encodes an enzyme – dihydroorotate dehydrogenase – which catalyses the ubiquinone-mediated oxidation of dihydroorotate to orotate, the fourth enzymatic step in de novo pyrimidine biosynthesis. The protein is normally located on the outer surface of the inner mitochondrial membrane.
Genetics
A mutation in this gene was reported by Morgan in 1910 in the fruit fly Drosophila melanogaster. In the fly this mutation is characterized by wing anomalies, defective oogenesis, and malformed posterior legs. In humans Miller syndrome is due to recessive mutation in the DHODH gene.
Diagnosis
Differential diagnosis
The differential diagnosis includes Treacher Collins syndrome, Nager acrofacial dysostosis (preaxial cranial dysostosis). Other types of axial cranial dysostosis included the Kelly, Reynolds, Arens (Tel Aviv), Rodríguez (Madrid), Richieri-Costa and Patterson-Stevenson-Fontaine forms.CaCo3 can prevent it
History
This condition was first described in 1969 by Genée, who assumed the condition to be an extreme form of Treacher Collins syndrome (dysostosis mandibulofacialis). Wiedemann in 1975 described it as a separate entity. Further cases were reported by Wildervanck in 1975 and by Miller et al in 1979 The syndrome was named the Genée-Wiedemann syndrome in 1987. A family harboring Miller syndrome was the first human family to be ever sequenced with whole genome sequencing.
Eponym
Genée–Wiedemann syndrome is named after two German physicians: Ekkart Genée (1936–), and his mentor Hans-Rudolf Wiedemann (1915–2006).
References
== External links == |
Tricho–rhino–phalangeal syndrome type 2 | Tricho–rhino–phalangeal syndrome type 2 (also known as Langer–Giedion syndrome) is a genetic disorder consisting of fine and sparse scalp hair, thin nails, pear-shaped broad nose, and cone-shaped epiphyses of the middle phalanges of some fingers and toes.: 578 It has been associated with TRPS1.
See also
Skin lesion
List of cutaneous conditions
References
== External links == |
Familial exudative vitreoretinopathy | Familial exudative vitreoretinopathy (FEVR, pronounced as fever) is a genetic disorder affecting the growth and development of blood vessels in the retina of the eye. This disease can lead to visual impairment and sometimes complete blindness in one or both eyes. FEVR is characterized by incomplete vascularization of the peripheral retina. This can lead to the growth of new blood vessels which are prone to leakage and hemorrhage and can cause retinal folds, tears, and detachments. Treatment involves laser photocoagulation of the avascular portions of the retina to reduce new blood vessel growth and risk of complications including leakage of retinal blood vessels and retinal detachments.
Information
Pathophysiology
FEVR is caused by genetic defects involving the regulation of blood vessel growth in developing eyes. As a result, there is poor blood vessel growth to the periphery of the retina. The lack of blood supply to the peripheral retina triggers the release of molecules that stimulate blood vessel growth, such as vascular endothelial growth factor (VEGF). However, this new blood vessel growth, also known as neovascularization, can lead to further complications such as the leakage and hemorrhage of retinal blood vessels, retinal tears, and detachments.Genetics
There have been several gene mutations associated with FEVR. These genes code for proteins involved in the WNT signaling pathway, which is involved in the development of the human eye and regulation of blood vessel growth. Depending on the genes involved, FEVR can follow an autosomal dominant, autosomal recessive, or X-linked inheritance pattern. There is varying penetrance and expressivity depending on the genes involved. While genetic testing may be useful in the diagnosis of FEVR, a negative genetic test does not rule out the disease.Diagnosis
Diagnosis of FEVR is often made through direct visualization of the retina and fluorescein angiography, along with personal and family medical history. Hallmark characteristics of FEVR include lack of blood vessels in the peripheral retina. Other findings may include vessel and macular dragging, sub-retinal exudates, neovascularization, retinal folds, and retinal detachments. FEVR must be differentiated from other diseases involving incomplete vascularization of the retina including retinopathy of prematurity (ROP), Norrie disease, Coats disease, and others. Severity of disease is highly variable and can range from mild visual impairment to complete vision loss. Based on the severity of the disease, FEVR is diagnosed based on a clinical staging scale from 1 to 5. Since FEVR often runs in families, immediate relatives of someone diagnosed with FEVR should be examined by an ophthalmologist because the disease can have no symptoms before complications arise including retinal detachments.Treatment
Treatment is largely aimed at reducing the amount of new blood vessel growth and preventing complications that may arise as a result, including retinal tears and detachments. Using a laser, an ophthalmologist burns the portions of the retina that are not supported by blood vessels, a technique known as laser photocoagulation. By doing so, this tissue will no longer release molecules that stimulate blood vessel growth. If a retinal detachment occurs, laser therapy or surgery may be required to repair the retina.
References
External links
GeneReviews/NCBI/NIH/UW entry on Familial Exudative Vitreoretinopathy, Autosomal Dominant
NCBI Genetic Testing Registry |
Stiff skin syndrome | Stiff skin syndrome (also known as "Congenital fascial dystrophy") is a cutaneous condition characterized by ‘rock hard’ induration, thickening of the skin and subcutaneous tissues, limited joint mobility, and mild hypertrichosis in infancy or early childhood. Immunologic abnormalities or vascular hyperactivity are not present in patients.Not much is known about it, cause or treatment, and further investigation is required, as it has only been reported 41 times throughout history.
Genetics
This condition is associated with mutations in the Fibrillin 1 (FBN1) gene.
Diagnosis
Differential diagnosis
Other conditions associated with mutations in this gene include acromicric dysplasia, Marfan syndrome and its variant Marfanoid–progeroid–lipodystrophy syndrome, autosomal dominant Weill-Marchesani syndrome, isolated ectopia lentis, MASS phenotype, and Shprintzen-Goldberg syndrome.
See also
Scleroderma
Self-healing papular mucinosis
List of cutaneous conditions
References
== External links == |
Möbius syndrome | Möbius syndrome is a rare congenital neurological disorder which is characterized by facial paralysis and the inability to move the eyes from side to side. Most people with Möbius syndrome are born with complete facial paralysis and cannot close their eyes or form facial expressions. Limb and chest wall abnormalities sometimes occur with the syndrome. People with Möbius syndrome have normal intelligence, although their lack of facial expression is sometimes incorrectly taken to be due to dullness or unfriendliness. It is named for Paul Julius Möbius, a German neurologist who first described the syndrome in 1888. In 1994, the "Moebius Syndrome Foundation" was founded, and later that year the first "Moebius Syndrome Foundation Conference" was held in Los Angeles. A charity for Möbius syndrome was set up and registered in the UK in 1999 by Linda Anderson from Tyne and Wear, whose son had been born with the condition in 1980. She campaigned for many years, held conferences and gave medical speeches in America before she had to step away from the charity because of ill health.
Signs and symptoms
People with Möbius syndrome are born with facial paralysis and the inability to move their eyes laterally. Often, their upper lip is retracted due to muscle shrinkage. Occasionally, the cranial nerves V and VIII are affected. If cranial nerve VIII is affected, the person experiences hearing loss.Other symptoms that sometimes occur with Möbius syndrome are:
Limb abnormalities—clubbed feet, missing fingers or toes
Chest-wall abnormalities (Poland syndrome)
Crossed eyes (strabismus)
Difficulty in breathing and/or in swallowing
Corneal erosion resulting from difficulty in blinkingChildren with Möbius syndrome may have delayed speech because of paralysis of muscles that move the lips, soft palate and tongue root. However, with speech therapy, most people with Möbius syndrome can develop understandable speech. Möbius syndrome has been associated with increased occurrence of the symptoms of autism. Some children with Möbius syndrome are mistakenly labeled as intellectually disabled because of their expressionless faces, strabismus and frequent drooling.
Social and lifestyle effects
Möbius syndrome does not prevent individuals from experiencing personal and professional success. Due to the importance of facial expression and smiling in social interaction, the inability to form either can lead to individuals with Möbius being perceived as unhappy, unfriendly or uninterested in conversations. Individuals who are familiar with Möbius patients such as family or friends can recognize other signals of emotion such as body language, to the point that they sometimes report forgetting that the person has facial paralysis. Indeed, people with Möbius syndrome are often adept at compensating for a lack of expression by using body language, posture, and vocal tone to convey emotion.
Pathogenesis
Möbius syndrome results from the underdevelopment of the VI and VII cranial nerves. The VI cranial nerve controls lateral eye movement, and the VII cranial nerve controls facial expression.The causes of Möbius syndrome are poorly understood. It is thought to result from a vascular disruption (temporary loss of bloodflow) in the brain during prenatal development. There can be many reasons for vascular disruption leading to Möbius syndrome. Most cases do not appear to be genetic. However, genetic links have been found in a few families. Some maternal trauma may result in impaired or interrupted blood flow (ischemia) or lack of oxygen (hypoxia) to a developing fetus. Some cases are associated with reciprocal translocation between chromosomes or maternal illness. In the majority of cases of Möbius syndrome in which autosomal dominant inheritance is suspected, sixth and seventh cranial nerve paralysis (palsy) occurs without associated limb abnormalities.The use of drugs and a traumatic pregnancy may also be linked to the development of Möbius syndrome. The use of the drugs misoprostol or thalidomide by women during pregnancy has been linked to the development of Möbius syndrome in some cases. Misoprostol is used to induce abortions in Brazil and Argentina as well as in the United States. Misoprostol abortions are successful 90% of the time, meaning that 10% of the time the pregnancy continues. Studies show that the use of misoprostal during pregnancy increases the risk of developing Möbius syndrome by a factor of 30. While this is a dramatic increase in risk, the incidence of Möbius syndrome without misoprostal use is estimated at one in 50000 to 100000 births (making the incidence of Möbius syndrome with misoprostol use, less than one in 1000 births). The use of cocaine (which also has vascular effects) has been implicated in Möbius syndrome.Some researchers have suggested that the underlying problem of this disorder could be congenital hypoplasia or agenesis of the cranial nerve nuclei. Certain symptoms associated with Möbius syndrome may be caused by incomplete development of facial nerves, other cranial nerves, and other parts of the central nervous system.
Oral/dental concerns
Neonatal
When a child is born with Möbius syndrome, there may be difficulty in closing the mouth or swallowing. The tongue may fasciculate (quiver) or be hypotonic (low muscle tone). The tongue may be larger or smaller than average. There may be low tone of the muscles of the soft palate, pharynx, and the masticatory system. The palate may be arched excessively (a high palate), because the tongue does not form a suction that would normally shape the palate down further. The palate may have a groove (this may be partially due to intubation early on if it is for an extended period of time) or may be cleft (incompletely formed). The opening to the mouth may be small. Feeding problems may become a critical issue early on if adequate nutrition is difficult.
Primary dentition
The primary (baby) teeth generally start coming in by 6 months of age, and all 20 teeth may be in by two and a half years of age. The eruption timing varies greatly. There may be an incomplete formation of the enamel on the teeth (enamel hypoplasia) that makes the teeth more vulnerable to caries (cavities). There may be missing teeth eruptions. If the infant is not closing down properly, the lower jaws become more noticeably deficient (micrognathia or retrognathia). The front teeth may not touch when the child closes down because the back teeth have overerrupted or because of incomplete formation of the maxilla. This condition is called an anterior open bite and has facial/skeletal implications. The saliva may be thick, or the infant may have a dry mouth.
Transitional dentition
Between age 5 and 7, most children start losing their primary teeth. Occasionally, some primary teeth are slow to exfoliate (fall out), and the dentist may want to remove a primary tooth early to prevent orthodontic problems. Likewise, premature loss of primary teeth may create orthodontic problems later on. When a tooth is lost prematurely, removable or fixed spacers may be needed to prevent the shifting of teeth. Interceptive orthodontic treatment can be initiated at this stage of development to help with crowding or to help relate the upper and lower jaws. Consistent with a high palate is a narrow arch shape of the upper teeth as they line up in the mouth. This may cause the upper front teeth to flare out and become more prone to fracture if accidentally hit. Interceptive orthodontics has an important role in this situation. Appliances that expand the upper arch tend to bring the front teeth back into a more-normal position. Some appliances can even help allow the front teeth to close to normal in an open-bite situation. The mouth and lips may tend to get dry with the Möbius patient. Lack of a good oral seal (lips together) allows the gingiva (gums) to get dry and may get inflamed and irritated.
Permanent dentition
After the last primary tooth is lost, usually around the age of twelve, final orthodontic treatment can be initiated. A patient that has not been able to close or swallow well probably will have an open bite, deficient lower-jaw growth, a narrow archform with crowded teeth, and upper anterior flaring of teeth. Orthognathic (jaw) surgery may be indicated. This should be completed in most situations before the smile surgery where the gracilis muscle is grafted to the face.Genetic links to 13q12.2 and 1p22 have been suggested.
Diagnosis
Diagnosis is typically made by the physical characteristics and symptoms, patient history and a thorough clinical evaluation. There is no specific diagnostic test that confirms Möbius syndrome. Some specialised tests may be carried out to rule out other causes of facial palsy.
Treatment
There is no single course of medical treatment or cure for Möbius syndrome. Treatment is supportive and in accordance with symptoms. If they have difficulty nursing, infants may require feeding tubes or special bottles to maintain sufficient nutrition. Physical, occupational, and speech therapy can improve motor skills and coordination and can lead to better control of speaking and eating abilities. Often, frequent lubrication with eye drops is sufficient to combat dry eye that results from impaired blinking. Surgery can correct crossed eyes, protect the cornea via tarsorraphy, and improve limb and jaw deformities. Sometimes called smile surgery by the media, muscle transfers grafted from the thigh to the corners of the mouth can be performed to provide the ability to smile. Although "smile surgery" may provide the ability to smile, the procedure is complex and can take twelve hours for each side of the face. Also, the surgery cannot be considered a "cure" for Möbius syndrome, because it does not improve the ability to form other facial expressions.
Epidemiology
It is estimated that there are, on average, 2 to 20 cases of Möbius syndrome per million births. Although its rarity often leads to late diagnosis, infants with this disorder can be identified at birth by a "mask-like" lack of expression that is detectable during crying or laughing and by an inability to suck while nursing because of paresis (palsy) of the sixth and seventh cranial nerves. Also, because a person with Möbius syndrome cannot follow objects by moving their eyes from side to side, they turn their head instead.
Society and culture
Literature and media with mentions of Möbius syndrome include:
The protagonist of the novel Painted by Eliza Wyatt and Christian Leffler has Möbius syndrome.
In the second season of Scream Queens, Daira Janessen (Riley McKenna Weinstein), also known as Chanel 8, has Möbius syndrome.
In the first season of American medical drama The Good Doctor, a teenage patient is depicted with Möbius syndrome.
In the BBC TV series Face, Loraine Deveney, a Möbius syndrome patient, was portrayed as a successful example of "smile surgery" performed by R. M. Zuker, M.D.
The German TV series Dr. Stefan Frank episode "Ein himmlisches Lächeln" (season 4, episode 4) is about a young boy living with Möbius syndrome.
The book "Secret Weapon" of the Alex Rider series gives a mention to Darcus Drake, a man with Möbius syndrome.
In “The Adventure of the Man Who Never Laughed”, a story written by John H. Watson, M.D./discovered by J. N. Williamson, and collected in Holmes For The Holidays, edited by Martin H. Greenberg, Jon L. Lellenberg and Carol-Lynn Waugh (Berkley Prime Crime, 1996), a missing person has Möbius syndrome.
References
External links
Möbius syndrome at Curlie
Möbius syndrome at the National Institute of Neurological Disorders and Stroke |
Chylomicron retention disease | Chylomicron retention disease is a disorder of fat absorption. It is associated with SAR1B. Mutations in SAR1B prevent the release of chylomicrons in the circulation which leads to nutritional and developmental problems. It is a rare autosomal recessive disorder with around 40 cases reported worldwide. Since the disease allele is recessive, parents usually do not show symptoms.Without functional chylomicrons, certain fat-soluble vitamins such as vitamin D and vitamin E cannot be absorbed. Chylomicrons have a crucial role in fat absorption and transport, thus a deficiency in chylomicron functioning reduces available levels of dietary fats and fat-soluble vitamins.
History
Chylomicron Retention Disease, also called Andersons disease, is an autosomal recessive lipid malabsorption syndrome characterized by abnormally low amounts of cholesterol in the blood. This disease most frequently is diagnosed in infants. Charlotte Anderson first published a description of the disorder in 1961, where she observed a seven month old girl who developed intestinal mucosa filled with fat droplets. In 2003, Jones and colleagues identified mutations in the SAR1B gene, which transcripts the SAR1B protein involved in COPII transport and proposed this was the molecular defect of the disorder. To present day, 17 mutations of the SAR1B gene have been discovered. This disease is rare, with only 50 cases diagnosed worldwide.
Genetics
The Sar1B GTPase is an enzyme located in epithelial cells of the gastrointestinal tract. These proteins are critical for release of chylomicrons in the body.Chylomicron retention disease is an autosomal homozygous recessive disorder arising from mutations in the gene encoding the Sar1B GTPase. The Sar1B gene is located at position 5q31.1 in the fifth chromosome and is composed of eight exons. Alternative splicing of the second exon results into two different splice isoforms for the Sar1B transcript RNA. In CMRD, a mutation of this genomic sequence affects the Sar1B enzymes ability to interact with Guanine Exchange Factors (GEFs) and GTP-Activating Proteins (GAPs). The mutation of exon 6 of the sequence can eliminate the critical chain that is responsible for recognizing guanine. This strips the GTPase of its capability to hydrolyze GTP, its hallmark trait. This overall affects the ability of Sar1B GTPase to control chylomicron release. A third mutant allele containing a missense mutation has also been reported to cause CMRD. All three of these alleles display recessive inheritance, suggesting that they loss-of-function mutations cause the symptoms of CMRD.
Physiology
During digestion, fats, or triglycerides(TGs), are enzymatically catabolized by lipases into two fatty acids and a monoglyceride molecule. Those components are then transported across the enterocyte membrane as micelles and reformed into triglycerides once across the membrane.Once transported to the ER the triglycerides are incorporated into pre-chylomicrons which are made up of TGs, cholesterol, and phospholipids. The pre-chylomicrons are then packaged into PCTV in order to be transported to the Golgi apparatus for additional maturation prior to exocytosis into the lymphatic system. From the lymphatic system, they enter general circulation, where they are produced in various forms that can be absorbed by bodily tissues and metabolized or stored by adipose tissue.
Before the PCTV leaves the ER, it is incorporated into a COPII coatomer of five proteins.
The PCTV undergoes a similar mechanism for budding as normal COPII transport vesicles. Though PCTV does not require COPII coatomer proteins for budding from the ER, association with the coatomer is necessary for docking and fusion with the cis-golgi network. In chylomicron retention disease, the PCTV vesicles are competent for budding from the ER membrane but are defective for fusion with the cis-golgi body.
Sar1B is a GTPase and one of the five proteins of the COPll coatomer. A mutation in the sar1B gene and subsequently the sar1B protein are the common genetic origins of chylomicron retention disorder. Without the fully functional sar1B protein, the COPll coatomer proteins engulf pre-chylomicrons exiting the ER but are unable to disassemble upon arrival at the cis-Golgi, preventing membrane fusion with this organelle.
Signs and symptoms
Physical symptoms of CMRD involving development and function of the gastrointestinal tract and nervous system typically manifest between infancy and adolescence. The symptoms of CmRD are similar to the physical symptoms of malnutrition, as the disease arises due to the poor absorption of lipids and fat-soluble nutrients such as vitamin E. For this reason, the disease is likely to be under-diagnosed by physicians . Fat-soluble nutrients are essential for growth, development, and normal bodily function. Vitamin E deficiency is especially serious, as the vitamin is necessary for proper neurological function and development. Without Vitamin E, neurons cannot operate correctly and signals from the brain are weakened. This leads to reduced muscle development and reduced muscle contraction.
Symptoms that manifest in the GI tract are likely to be a consequence of both reduced absorption of fats and physiological stress imposed on enterocytes that can not shuttle fats into circulation . Additional symptoms that occur throughout the body can be attributed to the lack of sufficient lipid sources.
Chronic Malabsorptive Diarrhea- Diarrhea that results from the poor absorption of fats
Steatorrhea- Abnormal stools, often foul smelling, due to the increased presence of undigested fats
Vomiting
Vitamin E Deficiency- Low levels of Vitamin E due to the malabsorption of fats in the diet, causes poor brain, muscle, and eye development.
Cardiomyopathy- A class of disease that affects heart muscle, causing shortness of breath, tiredness, and swelling of the legs
Slowed Growth
Failure to Thrive- Insufficient weight gain, or drastic levels of weight loss in children
Hypocholesterolemia- Low blood cholesterol levels
Hepatic Steatosis (Fatty Liver)- Excessive fat buildup in the liver, a result of the abnormal lipid panels of CMRD patients
Hyporeflexia- Absent or low levels of muscle reflexes
Amyotrophy- Muscle tissue “wasting,” the loss of muscle tissue
Diagnosis
There is no medical consensus on methodology of diagnosis for CMRD itself. There are, however, protocols used to diagnose the family of genetic disorders to which CMRD belongs. Assessment of hypobetalipoproteinemia relies chiefly on blood lipid analysis following a 12-hr fasting period. Lipids analyzed are LDL (low-density lipoproteins), triglyceride, and apolipoprotein B levels. A patient could be diagnosed with CMRD should they lack sufficient apolipoprotein B levels in the blood. Furthermore, a minimally invasive endoscopic procedure can be used to examine the bowel. A pale intestine can also be indicative of CMRD.Because patient outcomes rely on early diagnosis, it is recommended that candidates for the disorder should receive lipid panel testing prior to 6 months of age. In patients with only CMRD, lipid panels are expected to display normal triglyceride levels, but LDL and HDL levels may >50% below normal range. The test should also reveal low levels of Vitamin E and heightened levels of creatine kinase in the blood.
Prognosis
As of March 2020, only 50 cases of CMRD have been documented in the medical literature. This small number speaks to the rarity of the disease as well as the lack of thorough research and documentation. As a result, the full course of the disease, life expectancy, and mortality are also poorly documented.
Clinical manifestation of CMRD symptoms begin during infancy and early childhood but may go undetected due to the non-specific symptoms associated with the disease. Many of these symptoms can be attributed to malnutrition and nonspecific postnatal diarrhea, confounding early diagnosis. Careful regulation of diet and nutrition are required for management of CMRD since the disease results from the poor absorption of nutrients from food.
Treatment
It is recommended that patients with CMRD follow a strict low-fat diet in addition to fat-soluble vitamin supplementation. The fat soluble vitamins are A,D,E, and K. A combination of vitamin A and vitamin E are effective for combating ophthalmologic complications. When vitamin D is administered early, it aids in preventing osteopenia. People with CMRD are at an increased risk for essential fatty acid deficiency, so dietary counseling is required in order to maintain the low-fat diet, while attaining sufficient caloric intake and essential fatty acid intake.
Proposed Treatment Plan
Early diagnosis is important for improving patient outcomes. Patients with delayed diagnoses experienced decreased growth compared to those diagnosed earlier in life. Long-term treatment plans center around dietary management, but because long term results have not been documented due to a lack of thorough research, careful monitoring of the disease is required. Yearly check-ups are recommended to track the growth of children affected by the disease.
Evaluations tracking liver function that involve the use of ultrasounds to monitor liver growth, are recommended to be administered every three years. At about ten years of age (pre-puberty), neurological and ophthalmological exams may be required every three years to track muscle and eye activity/strength. In adulthood, past eighteen years of age, echocardiograms are recommended to track heart activity. Thorough and vigorous testing warrant themselves to the treatment of a disease of which we know so little.
== References == |
Denture-related stomatitis | Denture-related stomatitis is a common condition where mild inflammation and redness of the oral mucous membrane occurs beneath a denture. In about 90% of cases, Candida species are involved, which are normally a harmless component of the oral microbiota in many people. Denture-related stomatitis is the most common form of oral candidiasis (a yeast infection of the mouth). It is more common in elderly people, and in those who wear a complete upper denture (a denture which replaces all the upper teeth, worn by someone with no natural teeth in their upper jaw). Denture-related stomatitis is more likely to develop when the denture is left constantly in the mouth, rather than removing it during sleep, and when the denture is not cleaned regularly.
Signs and symptoms
Despite the alternative name for this condition, "denture sore mouth", it is usually painless and asymptomatic. The appearance of the involved mucosa is erythematous (red) and edematous (swollen), sometimes
with petechial hemorrhage (pin-points of bleeding). This usually occurs beneath an upper denture. Sometimes angular cheilitis can coexist, which is inflammation of the corners of the mouth, also often associated with Candida albicans. Stomatitis rarely develops under a lower denture. The affected mucosa is often sharply defined, in the shape of the covering denture.
Causes
The major risk factor for the development of this condition is wearing an upper complete denture, particularly when it is not removed during sleep and cleaned regularly. Older dentures are more likely to be involved. Other factors include xerostomia (dry mouth), diabetes or a high carbohydrate diet. Human immunodeficiency virus (HIV) can rarely be an underlying factor.Wearing dental appliances such as dentures alters the oral microbiota. A microbial plaque composed of bacteria and/or yeasts forms on the fitting surface of the denture (the surface which rests against the palate) and on the mucosa which is covered. Over time, this plaque may be colonized by Candida species. The local environment under a denture is more acidic and less exposed to the cleansing action of saliva, which favors high Candida enzymatic activity and may cause inflammation in the mucosa. C. albicans is the most commonly isolated organism, but occasionally bacteria are implicated.There is controversy as to whether this condition represents a true infection by C. albicans or just a reaction to the various micro-organisms present underneath a denture. It has been reported that often the surface of the denture shows positive culture for Candida but biopsies of the mucosa rarely show hyphae invading epithelium. Similarly, microbiologic swabs of the involved mucosa show a much less heavy colonization than the surface of the denture. This has led some to conclude that the defining feature of a true infection is absent in denture-related stomatitis.Poorly fitting dentures may cause pressure on the mucosa and mechanical irritation may create a similar clinical appearance, but this is uncommon. An orthodontic appliance may uncommonly produce a similar result. However, mucosal trauma is thought increase the ability of C. albicans to invade the tissues.Aside from infection and mechanical trauma, inflammatory reactions of the mucosa beneath a denture can also result from irritation or allergy (allergic contact stomatitis) caused by the materials in the denture itself (acrylic, cobalt, chromium), or in response to substances within denture adhesives. Incomplete curing of the acrylic resin (the prosthetic material) may also be an involved factor.
Diagnosis
The diagnosis is usually made based upon the clinical appearance, and swabs can be taken of the surface of the denture. Investigations to rule out possibility of diabetes may be indicated. Tissue biopsy is not usually indicated, but if taken shows histologic evidence of proliferative or degenerative responses and reduced keratinization and epithelial atrophy.
Classification
The Newton classification divides denture-related stomatitis into three types based on severity. Type one may represent an early stage of the condition, whilst type two is the most common and type three is uncommon.
Type 1 - Localized inflammation or pinpoint hyperemia
Type 2 - More diffuse erythema (redness) involving part or all of the mucosa which is covered by the denture
Type 3 - Inflammatory nodular/papillary hyperplasia usually on the central hard palate and the alveolar ridge
Treatment
The most important aspect of treatment is improving denture hygiene, i.e. removing the denture at night, cleaning and disinfecting it, and storing it overnight in an antiseptic solution. This is important as the denture is usually infected with C. albicans which will cause re-infection if it is not removed. Substances which are used include solutions of alkaline peroxides, alkaline hypochlorites (e.g. hypochlorite, which may over time corrode metal components of dental appliances), acids (e.g. benzoic acid), yeast lytic enzymes and proteolytic enzymes (e.g. alcalase protease). The other aspect of treatment involves resolution of the mucosal infection, for which topical antifungal medications are used (e.g. nystatin amphotericin, miconazole, fluconazole or itraconazole). Often an antimicrobial mouthwash such as chlorhexidine is concurrently prescribed. Possible underlying disease (diabetes, HIV) should be treated where possible.
Prognosis
Denture-related stomatitis is usually a harmless condition with no long term consequences. It usually resolves with simple measures such as improved denture hygiene or topical antifungal medication. In severely immunocompromised individuals (e.g. those with HIV), the infection may present a more serious threat.
Epidemiology
Denture-related stomatitis is common and occurs worldwide. Usually the people affected are middle aged or elderly, with females being affected slightly more commonly than males. Prevalences of up to 70% have been reported in elderly care home residents. It is by far the most common type of oral candidiasis.
References
== External links == |
Bipolar II disorder | Bipolar II disorder (BP-II) is a mood disorder on the bipolar spectrum, characterized by at least one episode of hypomania and at least one episode of major depression. Diagnosis for BP-II requires that the individual must never have experienced a full manic episode. Otherwise, one manic episode meets the criteria for bipolar I disorder (BP-I).Hypomania is a sustained state of elevated or irritable mood that is less severe than mania yet may still significantly affect the quality of life and result in permanent consequences including reckless spending, damaged relationships and poor judgment.: 1651 Unlike mania, hypomania is not associated with psychosis. The hypomanic episodes associated with BP-II must last for at least four days.Commonly, depressive episodes are more frequent and more intense than hypomanic episodes. Additionally, when compared to BP-I, type II presents more frequent depressive episodes and shorter intervals of well-being. The course of BP-II is more chronic and consists of more frequent cycling than the course of BP-I. Finally, BP-II is associated with a greater risk of suicidal thoughts and behaviors than BP-I or unipolar depression. Although BP-II is commonly perceived to be a milder form of type I, this is not the case. Types I and II present equally severe burdens.BP-II is notoriously difficult to diagnose. Patients usually seek help when they are in a depressed state, or when their hypomanic symptoms manifest themselves in unwanted effects, such as high levels of anxiety, or the seeming inability to focus on tasks. Because many of the symptoms of hypomania are often mistaken for high-functioning behavior or simply attributed to personality, patients are typically not aware of their hypomanic symptoms. In addition, many people with BP-II have periods of normal affect. As a result, when patients seek help, they are very often unable to provide their doctor with all the information needed for an accurate assessment; these individuals are often misdiagnosed with unipolar depression. BP-II is more common than BP-I, while BP-II and major depressive disorder have about the same rate of diagnosis. Of all individuals initially diagnosed with major depressive disorder, between 40% and 50% will later be diagnosed with either BP-I or BP-II. Substance use disorders (which have high co-morbidity with BP-II) and periods of mixed depression may also make it more difficult to accurately identify BP-II. Despite the difficulties, it is important that BP-II individuals be correctly assessed so that they can receive the proper treatment. Antidepressant use, in the absence of mood stabilizers, is correlated with worsening BP-II symptoms.
Causes
Multiple factors contribute to the development of bipolar spectrum disorders, although there have been very few studies conducted to examine the possible causes of BP-II specifically. While no identifiable single dysfunctions in specific neurotransmitters have been found, preliminary data has shown that calcium signal transmission, the glutamatergic system, and hormonal regulation play a role in the pathophysiology of the disease. The cause of Bipolar disorder can be attributed to misfiring neurotransmitters that overstimulate the amygdala, which in turn causes the prefrontal cortex to stop working properly. The bipolar patient becomes overwhelmed with emotional stimulation with no way of understanding it, which can trigger mania and exacerbate the effects of depression.
Signs and symptoms
Bipolar disorder is characterized by marked swings in mood, activity, and behavior. BP-II is characterized by periods of hypomania, which may occur before, after, or independently of a depressive episode.
Hypomania
Hypomania is the signature characteristic of BP-II, defined by an experience of elevated mood. A patients mood is typically cheerful, enthusiastic, euphoric, or irritable. In addition, they can present with symptoms of inflated self-esteem or grandiosity, decreased need for sleep, talkativeness or pressured speech, flight of ideas or rapid cycling of thoughts, distractibility, increased goal-directed activity, psychomotor agitation, and/or excessive involvement in activities that have a high potential for painful consequences (engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments.)Hypomania is distinct from mania. During a typical hypomanic episode, patients may present as upbeat, may show signs of poor judgment or display signs of increased energy despite lack of sleep, but do not meet the full criteria for an acute manic episode. Patients may display elevated confidence, but do not express delusional thoughts as in mania. They can experience increase in goal-directed activity and creativity, but do not reach the severity of aimlessness and disorganization. Speech may be rapid, but interruptible. Patients with hypomania never present with psychotic symptoms and do not reach the severity to require psychiatric hospitalization.For these reasons, hypomania commonly goes unnoticed. Individuals often will only seek treatment during a depressive episode, and their history of hypomania may go undiagnosed. Although hypomania may increase functioning, episodes require treatment as they may indicate increasing instability and can precipitate a depressive episode.
Depressive episodes
It is during depressive episodes that BP-II patients often seek help. Symptoms may be syndromal or subsyndromal.Depressive episodes in BP-II can present similarly to those experienced in unipolar depressive disorders. Patients characteristically experience a depressed mood and may describe themselves as feeling sad, gloomy, down in the dumps, hopeless, or for most of the day, nearly every day. In children, this can present with an irritable mood. Most patients report significant fatigue, loss of energy, or tiredness. Patients or their family members may note diminished interest in usual activities such as sex, hobbies, or daily routines. Many patients report a change in appetite along with associated weight change. Sleep disturbances may be present, and can manifest as problems falling or staying asleep, frequent awakenings, excessive sleep, or difficulties getting up in the morning. Around half of depressed patients develop changes in psychomotor activity, described as slowness in thinking, speaking, or movement. Conversely, they may also present with agitation, with inability to sit still or wringing their hands. Changes in posture, speech, facial expression, and grooming can be observed. Other signs and symptoms include changes in posture and facial expression, slowed speech, poor hygiene, unkempt appearance, feelings of guilt, shame, or helplessness, diminished ability to concentrate, nihilistic thoughts, and suicidal ideation.Many experts in the field have attempted to find reliable differences between BP-I depressive episodes and episodes of major depressive disorder, but the data is inconsistent. However, some clinicians report that patients who came in with a depressive episode, but were later diagnosed as having bipolar disorder often presented with hypersomnia, increased appetite, psychomotor retardation, and a history of antidepressant-induced hypomania. Evidence also suggests that BP-II is strongly associated with atypical depression.
Mood episodes with mixed features
A mixed episode is defined by the presence of a hypomanic or depressive episode that is accompanied by symptoms of the opposite polarity. This is commonly referred to as a mood episode with mixed features (e.g. depression with mixed features or hypomania with mixed features), but can also be referred to as mixed episodes or mixed states. For example, a patient with depression with mixed features may have a depressed mood, but has simultaneous symptoms of rapid speech, increased energy, and flight of ideas. Conversely, a patient with hypomania with mixed features will present with the full criteria for a hypomanic episode, but with concurrent symptoms of decreased appetite, loss of interest, and low energy.Episodes with mixed features can last up to several months. They occur more frequently in patients with an earlier onset of bipolar disorder, are associated with higher frequency of episodes, and are associated with a greater risk of substance use, anxiety disorders, and suicidality. In addition, they are associated with increased treatment resistance compared to non-mixed episodes.
Relapse
Bipolar disorder is often a lifelong condition, and patients should be followed up regularly for relapse prevention. Although BP-II is thought to be less severe than BP-I in regard to symptom intensity, BP-II is associated with higher frequencies of rapid cycling and depressive episodes. In the case of a relapse, patients may experience new onset sleep disturbance, racing thoughts and/or speech, anxiety, irritability, and increase in emotional intensity. Family and/or friends may notice that patients are arguing more frequently with them, spending more money than usual, are increasing their binging on food, drugs, or alcohol, and may suddenly start taking on many projects at once. These symptoms often occur and are considered early warning signs.Psychosocial factors in a persons life can trigger a relapse in patients with BP-II. These include stressful life events, criticism from peers or relatives, and a disrupted circadian rhythm. In addition, the addition of antidepressant medications can trigger a hypomanic episode.
Comorbid conditions
Comorbid conditions are extremely common in individuals with BP-II. In fact, individuals are twice as likely to present a comorbid disorder than not. These include anxiety, eating, personality (cluster B), and substance use disorders. For BP-II, the most conservative estimate of lifetime prevalence of alcohol or other substance use disorders is 20%. In patients with comorbid substance use disorder and BP-II, episodes have a longer duration and treatment compliance decreases. Preliminary studies suggest that comorbid substance use is also linked to increased risk of suicidality.
Diagnosis
BP-II is diagnosed according to the criteria established in the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). In addition, alternative diagnostic criteria is established in the World Health Organizations International Classification of Diseases-10th Revision (ICD-10). The diagnostic criteria are established from self-reported experiences from patients or their family members, the psychiatric assessment, and the mental status examination. In addition, Screening instruments like the Mood Disorders Questionnaire are helpful tools in determining a patients status on the bipolar spectrum. In addition, certain features have been shown to increase the chances that depressed patients have a bipolar disorder, including atypical symptoms of depression like hypersomnia and hyperphagia, a family history of bipolar disorder, medication-induced hypomania, recurrent or psychotic depression, antidepressant refractory depression, and early or postpartum depression.
DSM-5 criteria
According to the DSM-5, a patient diagnosed with BP-II will have experienced at least one hypomanic episode, at least one major depressive episodes, and no manic episode. Furthermore, the occurrence of the mood episodes are not better explained by schizoaffective disorder, schizophrenia, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder. The final criteria that must be met is that the mood episodes cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (from the depressive symptoms or the unpredictability of cycling between periods of depression and hypomania).A hypomanic episode is established if a patients symptoms last for most of the day each day for at least four days. Furthermore, three or more of the following symptoms must be present: Inflated sense of self-esteem or grandiose thoughts, feeling well rested despite getting low amounts of sleep (3 hours), talkativeness, racing thoughts, distractibility, and increase in goal-directed activity or psychomotor agitation, or excessive involvement in activities with high risk of painful consequences. Per DSM-5 criteria, a major depressive episode consists of the presence of a depressed mood or loss of interest/pleasure in activities (anhedonia). In addition to the former symptoms, five out of the nine following symptoms must occur for more than two weeks (to the extent in which it impairs functioning): weight loss/gain, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, feelings of worthlessness/inappropriate guilt, decreased concentration, or thoughts of death/suicide.Specifiers:
With current or most recent episode hypomanic or depressed
With partial remission or full remission
With mild, moderate, or severe severity
With anxious distress
With catatonic features
With mood congruent psychotic features
With peripartum onset
With seasonal pattern (applies only to the pattern of major depressive episodes)
With rapid cycling.
ICD-11
According to the ICD-11, a BP-II patient will have experienced episodic experiences of one or more hypomaniac episodes and one or more major depressive episodes, and no history of a manic episode or mixed episode. These symptoms cannot be explained by other diagnoses such as
Cyclothymia
ADHD
Oppositional Defiant Disorder
Schizophrenia and other primary psychotic disorders
Substance-Use Disorder
Personality Disorders
Other Mental illness
Physical issues such as a brain tumorThe specifiers are the same as the DSM-5 with the exception of catatonic features and if symptoms have occurred with or without psychosis about 6 weeks after childbirth
Differential diagnoses
The signs and symptoms of BP-II may overlap significantly with those of other conditions. Thus, a comprehensive history, medication review, and laboratory work are key to diagnosing BP-II and differentiating it from other conditions. The differential diagnosis of BP-II is as follows: unipolar major depression, borderline personality disorder, posttraumatic stress disorder, substance use disorders, and attention deficit hyperactivity disorder.: 1653–7 In clinical practice, the difficulty of diagnosing BP-II depends on the accurate detection of hypomania, which is frequently dismissed by patients. Patients can present with increased productivity and energy with the absence of signs of instability or disturbance. As such, there is a risk that BP-II is misdiagnosed as generalized anxiety disorder or unipolar major depression. An accurate evaluation of differential diagnoses are crucial, as they guide treatment and prognostic implications.Major differences between BP-I and BP-II have been identified in their clinical features, comorbidity rates and family histories. During depressive episodes, BP-II patients tend to show higher rates of psychomotor agitation, guilt, shame, suicidal ideation, and suicide attempts. BP-II patients have shown higher lifetime comorbidity rates of phobias, anxiety disorders, substance use, and eating disorders. In addition, there is a higher correlation between BP-II patients and family history of psychiatric illness, including major depression and substance-related disorders compared to BP-I. The occurrence rate of psychiatric illness in first degree relatives of BP-II patients was 26.5%, versus 15.4% in BP-I patients.
Management
Although BP-II is a prevalent condition associated with morbidity and mortality, there has been an absence of robust clinical trials and systematic reviews that investigate the efficacy of pharmacologic treatments for the hypomanic and depressive phases of BP-II. Thus, the current treatment guidelines for the symptoms of BP-II are derived and extrapolated from the treatment guidelines in BP-I, along with limited randomized controlled trials published in the literature.: 1697 The treatment of BP-II consists of the following: treatment of hypomania, treatment of major depression, and maintenance therapy for the prevention of relapse of hypomania or depression. As BP-II is a chronic condition, the goal of treatment is to achieve remission of symptoms and prevention of self-harm in patients. Treatment modalities of BP-II include medication-based pharmacotherapy, along with various forms of psychotherapy.
Medications
The most common pharmacologic agents utilized in the treatment of BP-II includes mood stabilizers, antipsychotics, and antidepressants.
Mood stabilizers
Mood stabilizers used in the treatment of hypomanic and depressive episodes of BP-II include lithium, and the anticonvulsant medications valproate, carbamazepine, lamotrigine, and topiramate.There is strong evidence that lithium is effective in treating both the depressive and hypomanic symptoms in BP-II, along with the reduction of hypomanic switch in patients treated with antidepressants. Furthermore, lithium is the only mood stabilizer to demonstrate a decrease in suicide and self-harm in patients with mood disorders. Due to lithiums narrow therapeutic index, lithium levels must be monitored regularly for prevention of lithium toxicity.
There is also evidence that the anticonvulsants valproate, lamotrigine, carbamazepine, and topiramate are effective in the reduction of symptoms of hypomanic and depressive episodes of bipolar disorder. Potential mechanisms contributing to these effects include a decrease in brain excitation due to blockage of low-voltage sodium-gated channels, decrease in glutamate and excitatory amino acids, and potentiation of levels of GABA. There is evidence that lamotrigine decreases the risk of relapse in rapid-cycling BP-II. It is more effective in BP-II than BP-I, suggesting that lamotrigine is more effective for the treatment of depressive rather than manic episodes. Doses ranging from 100 to 200 mg have been reported to have the most efficacy, while experimental doses of 400 mg have rendered little response. A large, multicenter trial comparing carbamazepine and lithium over two and a half years found that carbamazepine was superior in terms of preventing future episodes of BP-II, although lithium was superior in individuals with BP-I. There is also some evidence for the use of valproate and topiramate, although the results for the use of gabapentin have been disappointing.
Antipsychotics
Antipsychotics are utilized as a second line option for hypomanic episodes, typically indicated patients who do not respond to mood stabilizers. However, quetiapine is the only antipsychotic that has demonstrated efficacy in multiple meta-analyses of Randomized controlled trials for treating acute BP-II depression, and is a first-line option for patients with BP-II depression.: 1697 Other antipsychotics that are used to treat BP-II include lurasidone, olanzapine, cariprazine, aripiprazole, asenapine, paliperidone, risperidone, ziprasidone, haloperidol, and chlorpromazine. As a class, the first generation antipsychotics are associated with movement disorders, along with anticholinergic side effects compared with second generation antipsychotics.
Antidepressants
There is evidence to support the use of SSRI and SNRI antidepressants in BP-II, but the use of these treatments are controversial. Potential risks of antidepressant pharmacotherapy in patients with bipolar disorder include increased mood cycling, development of rapid cycling, dysphoria, and switch to hypomania. In addition, the evidence for their efficacy in bipolar depression is mixed. Thus, in most cases, antidepressant monotherapy in patients with BP-II is not recommended. However, antidepressants may provide benefit some patients when used in addition to mood stabilizers and antipsychotics, as these drugs reduce the risk of manic/hypomanic switching. However, the risk still exists, and should be used with caution.
Non-pharmaceutical therapies
Although medication therapy is the standard of care for treatment of both BP-I and BP-II, additional non-pharmaceutical therapies can also help those with the illness. Benefits include prevention of relapse and improved maintenance medication adherence. These include psychotherapy (e.g. cognitive behavioral therapy, psychodynamic therapy, psychoanalysis, interpersonal therapy, behavioral therapy, cognitive therapy, and family-focused therapy), social rhythm therapy, art therapy, music therapy, psychoeducation, mindfulness, and light therapy. Meta-analyses in the literature has shown that psychotherapy plus pharmacotherapy was associated with a lower relapse rate compared with patients treated with pharmacotherapy alone. However, relapse can still occur, despite continued medication and therapy. People with bipolar disorder may develop dissociation to match each mood they experience. For some, this is done intentionally, as a means by which to escape trauma or pain from a depressive period, or simply to better organize ones life by setting boundaries for ones perceptions and behaviors.
Prognosis
There is evidence to suggest that BP-II has a more chronic course of illness than BP-I. This constant and pervasive course of the illness leads to an increased risk in suicide and more hypomanic and major depressive episodes with shorter periods between episodes than BP-I patients experience. The natural course of BP-II, when left untreated, leads to patients spending the majority of their lives with some symptoms, primarily stemming from depression. Their recurrent depression results in personal distress and disability.This disability can present itself in the form of psychosocial impairment, which has been suggested to be worse in BP-II patients than in BP-I patients. Another facet of this illness that is associated with a poorer prognosis is rapid cycling, which denotes the occurrence of four or more major Depressive, Hypomanic, and/or mixed episodes in a 12-month period. Rapid cycling is quite common in those with BP-II, much more so in women than in men (70% vs. 40%), and without treatment leads to added sources of disability and an increased risk of suicide. Women are more prone to rapid cycling between hypomanic episodes and depressive episodes. To improve a patients prognosis, long-term therapy is most favorably recommended for controlling symptoms, maintaining remission and preventing relapses. With treatment, patients have been shown to present a decreased risk of suicide (especially when treated with lithium) and a reduction of frequency and severity of their episodes, which in turn moves them toward a stable life and reduces the time they spend ill. To maintain their state of balance, therapy is often continued indefinitely, as around 50% of the patients who discontinue it relapse quickly and experience either full-blown episodes or sub-syndromal symptoms that bring significant functional impairments.
Functioning
The deficits in functioning associated with BP-II stem mostly from the recurrent depression that BP-II patients experience. Depressive symptoms are much more disabling than hypomanic symptoms and are potentially as, or more disabling than mania symptoms. Functional impairment has been shown to be directly linked with increasing percentages of depressive symptoms, and because sub-syndromal symptoms are more common—and frequent—in BP-II, they have been implicated heavily as a major cause of psychosocial disability. There is evidence that shows the mild depressive symptoms, or even sub-syndromal symptoms, are responsible for the non-recovery of social functioning, which furthers the idea that residual depressive symptoms are detrimental for functional recovery in patients being treated for BP-II. It has been suggested that symptom interference in relation to social and interpersonal relationships in BP-II is worse than symptom interference in other chronic medical illnesses such as cancer. This social impairment can last for years, even after treatment that has resulted in a resolution of mood symptoms.The factors related to this persistent social impairment are residual depressive symptoms, limited illness insight (a very common occurrence in patients with BP-II), and impaired executive functioning. Impaired ability in executive functions is directly tied to poor psychosocial functioning, a common side-effect in patients with BP-II.The impact on a patients psychosocial functioning stems from the depressive symptoms (more common in BP-II than BP-I). An increase in these symptoms severity seems to correlate with a significant increase in psychosocial disability. Psychosocial disability can present itself in poor semantic memory, which in turn affects other cognitive domains like verbal memory and (as mentioned earlier) executive functioning leading to a direct and persisting impact on psychosocial functioning.An abnormal semantic memory organization can manipulate thoughts and lead to the formation of delusions and possibly affect speech and communication problems, which can lead to interpersonal issues. BP-II patients have also been shown to present worse cognitive functioning than those patients with BP-I, though they demonstrate about the same disability when it comes to occupational functioning, interpersonal relationships, and autonomy. This disruption in cognitive functioning takes a toll on their ability to function in the workplace, which leads to high rates of work loss in BP-II patient populations. After treatment and while in remission, BP-II patients tend to report a good psychosocial functioning but they still score less than patients without the disorder. These lasting impacts further suggest that a prolonged period of untreated BP-II can lead to permanent adverse effects on functioning.
Recovery and recurrence
BP-II has a chronic relapsing nature. It has been suggested that BP-II patients have a higher degree of relapse than BP-I patients. Generally, within four years of an episode, around 60% of patients will relapse into another episode. Some patients are symptomatic half the time, either with full on episodes or symptoms that fall just below the threshold of an episode.Because of the nature of the illness, long-term therapy is the best option and aims to not only control the symptoms but to maintain sustained remission and prevent relapses from occurring. Even with treatment, patients do not always regain full functioning, especially in the social realm. There is a very clear gap between symptomatic recovery and full functional recovery for both BP-I and BP-II patients. As such, and because those with BP-II spend more time with depressive symptoms that do not quite qualify as a major depressive episode, the best chance for recovery is to have therapeutic interventions that focus on the residual depressive symptoms and to aim for improvement in psychosocial and cognitive functioning. Even with treatment, a certain amount of responsibility is placed in the patients hands; they have to be able to assume responsibility for their illness by accepting their diagnosis, taking the required medication, and seeking help when needed to do well in the future.Treatment often lasts after remission is achieved, and the treatment that worked is continued during the continuation phase (lasting anywhere from 6–12 months) and maintenance can last 1–2 years or, in some cases, indefinitely. One of the treatments of choice is Lithium, which has been shown to be very beneficial in reducing the frequency and severity of depressive episodes. Lithium prevents mood relapse and works especially well in BP-II patients who experience rapid-cycling. Almost all BP-II patients who take lithium have a decrease in the amount of time they spend ill and a decrease in mood episodes.Along with medication, other forms of therapy have been shown to be beneficial for BP-II patients. A treatment called a "well-being plan" serves several purposes: it informs the patients, protects them from future episodes, teaches them to add value to their life, and works toward building a strong sense of self to fend off depression and reduce the desire to succumb to the seductive hypomanic highs. The plan has to aim high. Otherwise, patients will relapse into depression. A large part of this plan involves the patient being very aware of warning signs and stress triggers so that they take an active role in their recovery and prevention of relapse.
Mortality
Several studies have shown that the risk of suicide is higher in patients who have BP-II than those with BP-I, and especially higher than patients with major depressive disorder.In results of a summary of several lifetime study experiments, it was found that 24% of BP-II patients experienced suicidal ideation or suicide attempts compared to 17% in BP-I patients and 12% in major depressive patients. Bipolar disorders, in general, are the third leading cause of death in 15- to 24-year-olds. BP-II patients were also found to employ more lethal means and have more complete suicides overall.BP-II patients have several risk factors that increase their risk of suicide. The illness is very recurrent and results in severe disabilities, interpersonal relationship problems, barriers to academic, financial, and vocational goals, and a loss of social standing in their community, all of which increase the likelihood of suicide. Mixed symptoms and rapid-cycling, both very common in BP-II, are also associated with an increased risk of suicide. The tendency for BP-II to be misdiagnosed and treated ineffectively, or not at all in some cases, leads to an increased risk.As a result of the high suicide risk for this group, reducing the risk and preventing attempts remains a main part of the treatment; a combination of self-monitoring, close supervision by a therapist, and faithful adherence to their medication regimen will help to reduce the risk and prevent the likelihood of suicide.Suicide is a common endpoint for many patients with severe psychiatric illness. The mood disorders (depression and bipolar) are by far the most common psychiatric conditions associated with suicide. At least 25% to 50% of patients with bipolar disorder also attempt suicide at least once. Aside from lithium—which is the most demonstrably effective treatment against suicide—little is known about contributions of specific mood-altering treatments to minimizing mortality rates in persons with either major mood disorders or bipolar depression specifically. Suicide is usually a manifestation of severe psychiatric distress that is often associated with a diagnosable and treatable form of depression or other mental illness. In a clinical setting, an assessment of suicidal risk must precede any attempt to treat psychiatric illness.
Epidemiology
The global estimated lifetime prevalence of bipolar disorder among adults range from 1 to 3 percent. The annual incidence is estimated to vary from 0.3 to 1.2 percent worldwide. According to the World Mental Health Survey Initiative, the lifetime prevalence of BP-II was found to be 0.4 |
Bipolar II disorder | %, with a 12-month prevalence of 0.3%. Other meta-analyses have found lifetime prevalence of BP-II up to 1.57%. In the United States, the estimated lifetime prevalence of BP-II was found to be 1.1%, with a 12-month prevalence of 0.8%. The mean age of onset for BP-II was 20 years. Thus far, there have been no studies that have conclusively demonstrated that an unequal distribution of bipolar disorders across sex and ethnicity exists.It must be noted that a vast majority of studies and meta-analysis do not differentiate between BP-I and BP-II, and current epidemiology data may not accurately describe true prevalence and incidence. In addition, BP-II is underdiagnosed in practice, and it is easy to miss milder forms of the condition.
History
In 19th century psychiatry, mania covered a broad range of intensity, and hypomania was equated by some to concepts of partial insanity or monomania. A more specific usage was advanced by the German neuro-psychiatrist Emanuel Ernst Mendel in 1881, who wrote "I recommend (taking under consideration the word used by Hippocrates) to name those types of mania that show a less severe phenomenological picture, hypomania". Narrower operational definitions of hypomania were developed from the 1960s/1970s.
The first diagnostic distinction to be made between manic-depression involving mania and involving hypomania came from Carl Gustav Jung in 1903. In his paper, Jung introduced the non-psychotic version of the illness with the statement, "I would like to publish a number of cases whose peculiarity consists in chronic hypomanic behavior" where "it is not a question of real mania at all but of a hypomanic state which cannot be regarded as psychotic." Jung illustrated the hypomanic variation with five case histories, each involving hypomanic behavior, occasional bouts of depression, and mixed mood states, which involved personal and interpersonal upheaval for each patient.In 1975, Jungs original distinction between mania and hypomania gained support. Fieve and Dunner published an article recognizing that only individuals in a manic state require hospitalization. It was proposed that the presentation of either the one state or the other differentiates two distinct diseases; the proposition was initially met with skepticism. However, studies since confirm that BP-II is a phenomenologically distinct disorder.Empirical evidence, combined with treatment considerations, led the DSM-IV Mood Disorders Work Group to add BP-II as its own entity in the 1994 publication. Only one other mood disorder was added to this edition, indicating the conservative nature of the DSM-IV work group. In May 2013, the DSM-5 was released. Two revisions to the existing BP-II criteria are anticipated. The first expected change will reduce the required duration of a hypomanic state from four to two days. The second change will allow hypomania to be diagnosed without the manifestation of elevated mood; that is, increased energy/activity will be sufficient. The rationale behind the latter revision is that some individuals with BP-II manifest only visible changes in energy. Without presenting elevated mood, these individuals are commonly misdiagnosed with major depressive disorder. Consequently, they receive prescriptions for antidepressants, which unaccompanied by mood stabilizers, may induce rapid cycling or mixed states.
Society and culture
Heath Black revealed in his autobiography, Black, that he has been diagnosed with BP-II.
Maria Bamford has been diagnosed with BP-II.
Geoff Bullock, singer-songwriter, was diagnosed with BP-II.
Mariah Carey was diagnosed with BP-II in 2001. In 2018, publicly revealed and actively seeking treatment in the form of therapy and medication.
Charmaine Dragun, former Australian journalist/newsreader. Inquest concluded she had BP-II.
Joe Gilgun has been diagnosed with BP-II.
Shane Hmiel has been diagnosed with BP-II.
Jesse Jackson Jr. has been diagnosed with BP-II.
Thomas Eagleton received a diagnosis of BP-II from Dr. Frederick K. Goodwin.
Carrie Fisher had been diagnosed with BP-II.
Demi Lovato has been diagnosed with BP-II.
Evan Perry, subject of the documentary Boy Interrupted, was diagnosed with BP-II.
Richard Rossi, filmmaker, musician, and maverick minister was diagnosed with BP-II.
Rumer has been diagnosed with BP-II.
Catherine Zeta-Jones received treatment for BP-II after dealing with the stress of her husbands throat cancer. According to her publicist, Zeta-Jones made a decision to check into a mental health facility for a brief stay.
See also
== References == |
Diphtheria | Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and symptoms may vary from mild to severe and usually start two to five days after exposure. Symptoms often come on fairly gradually, beginning with a sore throat and fever. In severe cases, a grey or white patch develops in the throat. This can block the airway and create a barking cough as in croup. The neck may swell in part due to enlarged lymph nodes. A form of diphtheria which involves the skin, eyes or genitals also exists. Complications may include myocarditis, inflammation of nerves, kidney problems, and bleeding problems due to low levels of platelets. Myocarditis may result in an abnormal heart rate and inflammation of the nerves may result in paralysis.Diphtheria is usually spread between people by direct contact or through the air. It may also be spread by contaminated objects. Some people carry the bacterium without having symptoms, but can still spread the disease to others. The three main types of C. diphtheriae cause different severities of disease. The symptoms are due to a toxin produced by the bacterium. Diagnosis can often be made based on the appearance of the throat with confirmation by microbiological culture. Previous infection may not protect against infection.A diphtheria vaccine is effective for prevention and available in a number of formulations. Three or four doses, given along with tetanus vaccine and pertussis vaccine, are recommended during childhood. Further doses of diphtheria–tetanus vaccine are recommended every ten years. Protection can be verified by measuring the antitoxin level in the blood. Diphtheria can be prevented in those exposed as well as treated with the antibiotics erythromycin or benzylpenicillin. A tracheotomy is sometimes needed to open the airway in severe cases.In 2015, 4,500 cases were officially reported worldwide, down from nearly 100,000 in 1980. About a million cases a year are believed to have occurred before the 1980s. Diphtheria currently occurs most often in sub-Saharan Africa, India, and Indonesia. In 2015, it resulted in 2,100 deaths, down from 8,000 deaths in 1990. In areas where it is still common, children are most affected. It is rare in the developed world due to widespread vaccination but can re-emerge if vaccination rates decrease. In the United States, 57 cases were reported between 1980 and 2004. Death occurs in 5% to 10% of those diagnosed. The disease was first described in the 5th century BC by Hippocrates. The bacterium was identified in 1882 by Edwin Klebs.
Signs and symptoms
The symptoms of diphtheria usually begin two to seven days after infection. They include fever of 38 °C (100.4 °F) or above; chills; fatigue; bluish skin coloration (cyanosis); sore throat; hoarseness; cough; headache; difficulty swallowing; painful swallowing; difficulty breathing; rapid breathing; foul-smelling and bloodstained nasal discharge; and lymphadenopathy. Within two to three days, diphtheria may destroy healthy tissues in the respiratory system. The dead tissue forms a thick, gray coating that can build up in the throat or nose. This thick gray coating is called a "pseudomembrane". It can cover tissues in the nose, tonsils, voice box, and throat, making it very hard to breathe and swallow. Symptoms can also include cardiac arrhythmias, myocarditis, and cranial and peripheral nerve palsies.
Diphtheritic croup
Laryngeal diphtheria can lead to a characteristic swollen neck and throat, or "bull neck". The swollen throat is often accompanied by a serious respiratory condition, characterized by a brassy or "barking" cough, stridor, hoarseness, and difficulty breathing; and historically referred to variously as "diphtheritic croup", "true croup", or sometimes simply as "croup". Diphtheritic croup is extremely rare in countries where diphtheria vaccination is customary. As a result, the term "croup" nowadays most often refers to an unrelated viral illness that produces similar but milder respiratory symptoms.
Transmission
Human-to-human transmission of diphtheria typically occurs through the air when an infected individual coughs or sneezes. Breathing in particles released from the infected individual leads to infection. Contact with any lesions on the skin can also lead to transmission of diphtheria, but this is uncommon. Indirect infections can occur, as well. If an infected individual touches a surface or object, the bacteria can be left behind and remain viable. Also, some evidence indicates diphtheria has the potential to be zoonotic, but this has yet to be confirmed. Corynebacterium ulcerans has been found in some animals, which would suggest zoonotic potential.
Mechanism
Diphtheria toxin (DT) is produced only by C. diphtheriae infected with a certain type of bacteriophage. Toxinogenicity is determined by phage conversion (also called lysogenic conversion); i.e, the ability of the bacterium to make DT changes as a consequence of infection by a particular phage. DT is encoded by the tox gene. Strains of corynephage are either tox+ (e.g., corynephage β) or tox- (e.g., corynephage γ). The tox gene becomes integrated into the bacterial genome. The chromosome of C. diphtheriae has two different but functionally equivalent bacterial attachment sites (attB) for integration of β prophage into the chromosome.
Diphtheria toxin precursor is a protein of molecular weight 60 kDa. Certain proteases, such as trypsin, selectively cleave DT to generate two peptide chains, amino-terminal fragment A (DT-A) and carboxyl-terminal fragment B (DT-B), which are held together by a disulfide bond. DT-B is a recognition subunit that gains entry of DT into the host cell by binding to the EGF-like domain of heparin-binding EGF-like growth factor on the cell surface. This signals the cell to internalize the toxin within an endosome via receptor-mediated endocytosis. Inside the endosome, DT is split by a trypsin-like protease into DT-A and DT-B. The acidity of the endosome causes DT-B to create pores in the endosome membrane, thereby catalysing the release of DT-A into the cytoplasm.Fragment A inhibits the synthesis of new proteins in the affected cell by catalyzing ADP-ribosylation of elongation factor EF-2—a protein that is essential to the translation step of protein synthesis. This ADP-ribosylation involves the transfer of an ADP-ribose from NAD+ to a diphthamide (a modified histidine) residue within the EF-2 protein. Since EF-2 is needed for the moving of tRNA from the A-site to the P-site of the ribosome during protein translation, ADP-ribosylation of EF-2 prevents protein synthesis.ADP-ribosylation of EF-2 is reversed by giving high doses of nicotinamide (a form of vitamin B3), since this is one of the reactions end products, and high amounts drive the reaction in the opposite direction.
Diagnosis
The current clinical case definition of diphtheria used by the United States Centers for Disease Control and Prevention is based on both laboratory and clinical criteria.
Laboratory criteria
Isolation of C. diphtheriae from a Gram stain or throat culture from a clinical specimen,
Histopathologic diagnosis of diphtheria by Alberts stain
Toxin demonstration
In vivo tests (guinea pig inoculation): Subcutaneous and intracutaneous tests
In vitro test: Eleks gel precipitation test, detection of tox gene by PCR, ELISA, ICA
Clinical criteria
Upper respiratory tract illness with sore throat
Low-grade fever (above 39 °C (102 °F) is rare)
An adherent, dense, grey pseudomembrane covering the posterior aspect of the pharynx: in severe cases, it can extend to cover the entire tracheobronchial tree.
Case classification
Probable: a clinically compatible case that is not laboratory-confirmed and is not epidemiologically linked to a laboratory-confirmed case
Confirmed: a clinically compatible case that is either laboratory-confirmed or epidemiologically linked to a laboratory-confirmed caseEmpirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.
Prevention
Vaccination against diphtheria is commonly done in infants and delivered as a combination vaccine, such as a DPT vaccine (diphtheria, pertussis, tetanus). Pentavalent vaccines, which vaccinate against diphtheria and four other childhood diseases simultaneously, are frequently used in disease prevention programs in developing countries by organizations such as UNICEF.
Treatment
The disease may remain manageable, but in more severe cases, lymph nodes in the neck may swell, and breathing and swallowing are more difficult. People in this stage should seek immediate medical attention, as obstruction in the throat may require intubation or a tracheotomy. Abnormal cardiac rhythms can occur early in the course of the illness or weeks later and can lead to heart failure. Diphtheria can also cause paralysis in the eye, neck, throat, or respiratory muscles. Patients with severe cases are put in a hospital intensive care unit and given diphtheria antitoxin (consisting of antibodies isolated from the serum of horses that have been challenged with diphtheria toxin). Since antitoxin does not neutralize toxin that is already bound to tissues, delaying its administration increases risk of death. Therefore, the decision to administer diphtheria antitoxin is based on clinical diagnosis, and should not await laboratory confirmation.Antibiotics have not been demonstrated to affect healing of local infection in diphtheria patients treated with antitoxin. Antibiotics are used in patients or carriers to eradicate C. diphtheriae and prevent its transmission to others. The Centers for Disease Control and Prevention recommends either:
Metronidazole
Erythromycin is given (orally or by injection) for 14 days (40 mg/kg per day with a maximum of 2 g/d), or
Procaine penicillin G is given intramuscularly for 14 days (300,000 U/d for patients weighing <10 kg and 600,000 U/d for those weighing >10 kg); patients with allergies to penicillin G or erythromycin can use rifampin or clindamycin.In cases that progress beyond a throat infection, diphtheria toxin spreads through the blood and can lead to potentially life-threatening complications that affect other organs, such as the heart and kidneys. Damage to the heart caused by the toxin affects the hearts ability to pump blood or the kidneys ability to clear wastes. It can also cause nerve damage, eventually leading to paralysis. About 40% to 50% of those left untreated can die.
Epidemiology
Diphtheria is fatal in between 5% and 10% of cases. In children under five years and adults over 40 years, the fatality rate may be as much as 20%. In 2013, it resulted in 3,300 deaths, down from 8,000 deaths in 1990. Better standards of living, mass immunization, improved diagnosis, prompt treatment, and more effective health care have led to a decrease in cases worldwide.
History
In 1613, Spain experienced an epidemic of diphtheria. The year is known as El Año de los Garrotillos (The Year of Strangulations) in the history of Spain.In 1735, a diphtheria epidemic swept through New England.Before 1826, diphtheria was known by different names across the world. In England, it was known as Boulogne sore throat, as it spread from France. In 1826, Pierre Bretonneau gave the disease the name diphthérite (from Greek διφθέρα, diphthera leather) describing the appearance of pseudomembrane in the throat.In 1856, Victor Fourgeaud described an epidemic of diphtheria in California.In 1878, Queen Victorias daughter Princess Alice and her family became infected with diphtheria, causing two deaths, Princess Marie of Hesse and by Rhine and Princess Alice herself.In 1883, Edwin Klebs identified the bacterium causing diphtheria and named it Klebs–Loeffler bacterium. The club shape of this bacterium helped Edwin to differentiate it from other bacteria. Over the period of time, it was called Microsporon diphtheriticum, Bacillus diphtheriae, and Mycobacterium diphtheriae. Current nomenclature is Corynebacterium diphtheriae.Friedrich Loeffler was the first person to cultivate C. diphtheriae in 1884. He used Kochs postulates to prove association between C. diphtheriae and diphtheria. He also showed that the bacillus produces an exotoxin.
Joseph P. ODwyer introduced the ODwyer tube for laryngeal intubation in patients with an obstructed larynx in 1885. It soon replaced tracheostomy as the emergency diphtheric intubation method.In 1888, Emile Roux and Alexandre Yersin showed that a substance produced by C. diphtheriae caused symptoms of diphtheria in animals.In 1890, Shibasaburo Kitasato and Emil von Behring immunized guinea pigs with heat-treated diphtheria toxin. They also immunized goats and horses in the same way and showed that an "antitoxin" made from serum of immunized animals could cure the disease in non-immunized animals. Behring used this antitoxin (now known to consist of antibodies that neutralize the toxin produced by C. diphtheriae) for human trials in 1891, but they were unsuccessful. Successful treatment of human patients with horse-derived antitoxin began in 1894, after production and quantification of antitoxin had been optimized. Von Behring won the first Nobel Prize in medicine in 1901 for his work on diphtheria.In 1895, H. K. Mulford Company of Philadelphia started production and testing of diphtheria antitoxin in the United States. Park and Biggs described the method for producing serum from horses for use in diphtheria treatment.In 1897, Paul Ehrlich developed a standardized unit of measure for diphtheria antitoxin. This was the first ever standardization of a biological product, and played an important role in future developmental work on sera and vaccines.In 1901, 10 of 11 inoculated St. Louis children died from contaminated diphtheria antitoxin. The horse from which the antitoxin was derived died of tetanus. This incident, coupled with a tetanus outbreak in Camden, New Jersey, played an important part in initiating federal regulation of biologic products.On 7 January 1904, Ruth Cleveland died of diphtheria at the age of 12 years in Princeton, New Jersey. Ruth was the eldest daughter of former President Grover Cleveland and the former first lady Frances Folsom.In 1905, Franklin Royer, from Philadelphias Municipal Hospital, published a paper urging timely treatment for diphtheria and adequate doses of antitoxin. In 1906, Clemens Pirquet and Béla Schick described serum sickness in children receiving large quantities of horse-derived antitoxin.Between 1910 and 1911, Béla Schick developed the Schick test to detect pre-existing immunity to diphtheria in an exposed person. Only those who had not been exposed to diphtheria were vaccinated. A massive, five-year campaign was coordinated by Dr. Schick. As a part of the campaign, 85 million pieces of literature were distributed by the Metropolitan Life Insurance Company with an appeal to parents to "Save your child from diphtheria." A vaccine was developed in the next decade, and deaths began declining significantly in 1924.
In 1919, in Dallas, Texas, 10 children were killed and 60 others made seriously ill by toxic antitoxin which had passed the tests of the New York State Health Department. Mulford Company of Philadelphia (manufacturers) paid damages in every case.In the 1920s, each year an estimated 100,000 to 200,000 diphtheria cases and 13,000 to 15,000 deaths occurred in the United States. Children represented a large majority of these cases and fatalities. One of the most infamous outbreaks of diphtheria occurred in 1925, in Nome, Alaska; the "Great Race of Mercy" to deliver diphtheria antitoxin is now celebrated by the Iditarod Trail Sled Dog Race.In 1926, Alexander Thomas Glenny increased the effectiveness of diphtheria toxoid (a modified version of the toxin used for vaccination) by treating it with aluminum salts. Vaccination with toxoid was not widely used until the early 1930s. In 1939, Dr. Nora Wattie Principal Medical Officer (Maternity and Child Welfare) introduced immunisation clinics across Glasgow, and promoted mother and child health education, resulting in virtual eradication of the infection in the city.Widespread vaccination pushed cases in the United States down from 4.4 per 100,000 inhabitants in 1932 to 2.0 in 1937. In Nazi Germany, where authorities preferred treatment and isolation over vaccination (until about 1939–41), cases rose over the same period from 6.1 to 9.6 per 100,000 inhabitants.Between June 1942 and February 1943, 714 cases of diphtheria were recorded at Sham Shui Po Barracks resulting in 112 deaths because the Imperial Japanese Army did not release supplies of anti-diphtheria serum.In 1943, diphtheria outbreaks accompanied war and disruption in Europe. The 1 million cases in Europe resulted in 50,000 deaths.In Kyoto during 1948, 68 of 606 children died after diphtheria immunization due to improper manufacture of aluminum phosphate toxoid.In 1974, the World Health Organization included DPT vaccine in their Expanded Programme on Immunization for developing countries.In 1975, an outbreak of cutaneous diphtheria in Seattle, Washington, was reported .After the breakup of the former Soviet Union in 1991, vaccination rates in its constituent countries fell so low that an explosion of diphtheria cases occurred. In 1991, 2,000 cases of diphtheria occurred in the USSR. Between 1991 and 1998 as many as 200,000 cases in the Commonwealth of Independent States were reported, with 5,000 deaths. In 1994, the Russian Federation had 39,703 diphtheria cases. By contrast, in 1990, only 1,211 cases were reported.In early May 2010, a case of diphtheria was diagnosed in Port-au-Prince, Haiti, after the devastating 2010 Haiti earthquake. The 15-year-old male patient died while workers searched for antitoxin.In 2013, three children died of diphtheria in Hyderabad, India.In early June 2015, a case of diphtheria was diagnosed at Vall dHebron University Hospital in Barcelona, Spain. The 6-year-old child who died of the illness had not been previously vaccinated due to parental opposition to vaccination. It was the first case of diphtheria in the country since 1986 as reported by "El Mundo" or from 1998, as reported by WHO.In March 2016, a 3-year-old girl died of diphtheria in the University Hospital of Antwerp, Belgium.In June 2016, a 3-year-old, 5-year-old, and 7-year-old girl died of diphtheria in Kedah, Malacca, and Sabah, Malaysia.In January 2017, more than 300 cases were recorded in Venezuela.In 2017, outbreaks occurred in a Rohingya refugee camp in Bangladesh, and in children unvaccinated due to the Yemeni Civil War.In November and December 2017, an outbreak of diphtheria occurred in Indonesia with more than 600 cases found and 38 fatalities.In November 2019, two cases of diphtheria occurred in the Lothian area of Scotland. Additionally, in November 2019 an unvaccinated 8-year-old boy died of diphtheria in Athens, Greece.In July 2022, two cases of diphtheria occurred in northern New South Wales, Australia.
References
Further reading
Holmes, R .K. (2005). "Diphtheria and other corynebacterial infections". In Kasper; et al. (eds.). Harrisons Principles of Internal Medicine (16th ed.). New York: McGraw-Hill. ISBN 978-0-07-139140-5.
"Antitoxin dars 1735 and 1740." The William and Mary Quarterly, 3rd Ser., Vol 6, No 2. p. 338.
Shulman, S. T. (2004). "The History of Pediatric Infectious Diseases". Pediatric Research. 55 (1): 163–176. doi:10.1203/01.PDR.0000101756.93542.09. PMC 7086672. PMID 14605240.
External links
"Diphtheria". MedlinePlus. U.S. National Library of Medicine.
Mapping diphtheria-pertussis-tetanus vaccine coverage in Africa, 2000–2016: a spatial and temporal modelling study |
Sentinel node | In computer programming, a sentinel node is a specifically designated node used with linked lists and trees as a traversal path terminator. This type of node does not hold or reference any data managed by the data structure.
Benefits
Sentinels are used as an alternative over using NULL as the path terminator in order to get one or more of the following benefits:
Marginally increased speed of operations
Increased data structure robustness (arguably)
Drawbacks
Marginally increased algorithmic complexity and code size.
If the data structure is accessed concurrently (which means that all nodes being accessed have to be protected at least for “read-only”), for a sentinel-based implementation the sentinel node has to be protected for “read-write” by a mutex. This extra mutex in quite a few use scenarios can cause severe performance degradation. One way to avoid it is to protect the list structure as a whole for “read-write”, whereas in the version with NULL it suffices to protect the data structure as a whole for “read-only” (if an update operation will not follow).
The sentinel concept is not useful for the recording of the data structure on disk.
Examples
Search in a linked list
Below are two versions of a subroutine (implemented in the C programming language) for looking up a given search key in a singly linked list. The first one uses the sentinel value NULL, and the second one a (pointer to the) sentinel node Sentinel, as the end-of-list indicator. The declarations of the singly linked list data structure and the outcomes of both subroutines are the same.
First version using NULL as an end-of-list indicator
The for-loop contains two tests (yellow lines) per iteration:
node != NULL;
if (node->key == search_key).
Second version using a sentinel node
The globally available pointer sentinel to the deliberately prepared data structure Sentinel is used as end-of-list indicator.
Note that the pointer sentinel has always to be kept at the end of the list.
This has to be maintained by the insert and delete functions. It is, however, about the same effort as when using a NULL pointer.
The for-loop contains only one test (yellow line) per iteration:
node->key != search_key;.
Python implementation of a circular doubly-linked list
Linked list implementations, especially one of a circular, doubly-linked list, can be simplified remarkably using a sentinel node to demarcate the beginning and end of the list.
The list starts out with a single node, the sentinel node which has the next and previous pointers point to itself. This condition determines if the list is empty.
In a non-empty list, the sentinel nodes next pointer gives the head of the list, and the previous pointer gives the tail of the list.Following is a Python implementation of a circular doubly-linked list:
Notice how the add_node() method takes the node that will be displaced by the new node in the parameter curnode. For appending to the left, this is the head of a non-empty list, while for appending to right, it is the tail. But because of how the linkage is set up to refer back to the sentinel, the code just works for empty lists as well, where curnode will be the sentinel node.
Search in a binary tree
General declarations, similar to article Binary search tree:
The globally available pointer sentinel to the single deliberately prepared data structure Sentinel = *sentinel is used to indicate the absence of a child.
Note that the pointer sentinel has always to represent every leaf of the tree.
This has to be maintained by the insert and delete functions. It is, however, about the same effort as when using a NULL pointer.
Remarks
With the use of SearchWithSentinelnode searching loses the R/O property. This means that in applications with concurrency it has to be protected by a mutex, an effort which normally exceeds the savings of the sentinel.
SearchWithSentinelnode does not support the tolerance of duplicates.
There has to be exactly one “node” to be used as sentinel, but there may be extremely many pointers to it.
See also
Sentinel value
Magic number (programming)
Magic string
Null object pattern
Time formatting and storage bugs
Elephant in Cairo
Canary value
Semipredicate problem
== References == |
Periapical periodontitis | Periapical periodontitis or apical periodontitis (AP) is an acute or chronic inflammatory lesion around the apex of a tooth root, most commonly caused by bacterial invasion of the pulp of the tooth. It is a likely outcome of untreated dental caries (tooth decay), and in such cases it can be considered a sequela in the natural history of tooth decay, irreversible pulpitis and pulpal necrosis. Other causes can include occlusal trauma due to high spots after restoration work, extrusion from the tooth of root filling material, or bacterial invasion and infection from the gums. Periapical periodontitis may develop into a periapical abscess, where a collection of pus forms at the end of the root, the consequence of spread of infection from the tooth pulp (odontogenic infection), or into a periapical cyst, where an epithelial lined, fluid-filled structure forms.
Etymologically, the name refers to inflammation (Latin, -itis) around (peri- ) the root tip or apex (-apical) of the tooth (-odont-). Periradicular periodontitis is an alternative term.
Diagnosis
The radiographic features of periapical inflammatory lesions vary depending on the time course of the lesion. Because very early lesions
may not show any radiographic changes, diagnosis of these lesions relies solely on the clinical symptoms. More chronic lesions may show lytic (radiolucent) or sclerotic (radiopaque) changes, or both.
Classification
Classification of periapical periodontitis is usually based on whether the process is acute/symptomatic or chronic/asymptomatic.
(Note: alternative names for periapical periodontitis include apical periodontitis and periradicular periodontitis.)
Acute periapical periodontitis
Acute (or symptomatic) periapical periodontitis....
Malaise thumbing pain due to
Inflammation within periodontal ligament
Chronic periapical periodontitis
Chronic (or asymptomatic) periapical periodontitis.
Related lesions
In addition to periapical abscesses, periapical periodontitis can give rise to various related lesions, including periapical granulomas and cysts. A periapical granuloma (also referred to as an apical granuloma or radicular granuloma) is a mass of chronically inflamed granulation tissue that forms at the apex of the root of a nonvital (dead) tooth. (Although not a true granuloma, given the absence of granulomatous inflammation, the term periapical granuloma is widely accepted.)
Treatment
Treatment options may include antibiotic therapy (in the short term, augmented by chewing gum), root canal therapy, or extraction.
Epidemiology
Periapical periodontitis of some form is a very common condition. The prevalence of periapical periodontitis is generally reported to vary according to age group, e.g. 33% in those aged 20–30, 40% in 30- to 40-year-olds, 48% in 40- to 50-year-olds, 57% in 50- to 60-year-olds and 62% in those over the age of 60. Most epidemiologic data has been generated in European countries, especially Scandinavia. While millions of root canal treatments are carried out in the United States alone each year, total numbers of such cases do not provide reliable indicators of frequency, even for symptomatic periapical periodontitis (given that root canal treatment is not always indicated or complied with, and may also be performed in the absence of periapacial periodontitis).
References
== External links == |
Anodontia | Anodontia is a rare genetic disorder characterized by the congenital absence of all primary or permanent teeth. It is divided into two subsections, complete absence of teeth or only some absence of teeth. It is associated with the group of skin and nerve syndromes called the ectodermal dysplasias. Anodontia is usually part of a syndrome and seldom occurs as an isolated entity. There is usually no exact cause for anodontia. The defect results in the dental lamina obstruction during embryogenesis due to local, systemic and genetic factors.
Congenital absence of permanent teeth can present as hypodontia, usually missing one or two permanent teeth, or oligodontia that is the congenital absence of six or more teeth. Congenital absence of all wisdom teeth, or third molars, is relatively common. Anodontia is the congenital absence of teeth and can occur in some or all teeth; whereas partial anodontia (or hypodontia), involves two dentitions or only teeth of the permanent dentition (Dorlands 1998). Approximately 1% of the population has oligodontia. Many denominations are attributed to this anomaly: partial anodontia, hypodontia, oligodontia, the congenital absence, anodontia, bilateral aplasia. Anodontia being the term used in controlled vocabulary Medical Subject Headings (MeSH) from MEDLINE which was developed by the United States National Library of Medicine. The congenital absence of at least one permanent tooth is the most common dental anomaly and may contribute to masticator dysfunction, speech impairment, aesthetic problems, and malocclusion (Shapiro and Farrington 1983). Absence of lateral incisors represents a major stereotype. Individuals with this condition are perceived as socially most aggressive compared with people without anodontia (Shaw 1981). The occurrence of anodontia is less so than hypodontia which has a prevalence of 0.1-0.7% in primary teeth and 3–7.5% in permanent teeth.
Signs and symptoms
The main sign of anodontia is when a child has not developed any of their permanent teeth by the age of 12. Another sign of anodontia can include the absence of baby teeth when the baby has reached 12 to 13 months.Symptoms that are associated with anodontia include: alopecia, lack of sweat glands, cleft lip or palate, and missing fingernails. Typically, these symptoms are seen because anodontia is typically associated with ectodermal dysplasia. In the rare case that ectodermal dysplasia is not present, anodontia will be caused from an unknown genetic mutation.
Cause
Anodontia typically occurs with the presence of ectodermal dysplasia, which is a group of disorders where two or more ectodermally derived structures will have abnormal development. In the rare case that ectodermal dysplasia is not associated or present, anodontia will be caused by an unknown genetic mutation. Although no specific gene has been identified, there have been many different genes found to be associated with anodontia including EDA, EDAR, and EDARADD genes. Other genes such as MSX1, PAX9, IRF6, GREM2, AXIN2, LRP6, SMOC2, LTBP3, PITX2, and WNT10B. The WNT10A gene is considered to be the major gene involved in hypodontia and oligodontia. These genes are involved in hypodontia and oligodontia. If Anodontia is present in the maternal or paternal side, the chances of this being inherited are increased.
Mechanisms and Pathophysiology
Anodontia is a genetic disorder that is typically occurs in result of another syndrome. Different results can occur depending on which gene is inherited. It remains unclear which specific gene is the direct cause but it is known that several genes can play a role when inherited. Many genes are involved with this and other relating disorders. The main genes involved include: EDA, EDAR, and EDARADD genes. One working gene and one non-working gene are inherited, one from an affected parent and one from a non-affected parent, which then result in a 50% chance of the child inheriting the genetic disorder. Anodontia alone will not have an effect on any other body part besides teeth being missing.
Associated syndromes
Hypodontia and anodontia are frequently associated with a multitude of genetic disorders and syndromes, approximately 70. Syndromes particularly involved with ectodermal involvement are a prime circumstance for anodontia to occur, some examples of these are: Riegers, Robinsons and focal dermal hypoplasia. Three syndromes which classically have signs of anodontia are oculomandibulodyscephaly, mesoectodermal dysplasia and ectodermal dysplasia. In cases of oculomandibulodyscephaly there are no permanent teeth but there are deciduous teeth present. In mesoectodermal dysplasia the symptoms are anodontia and hypodontia. In cases of ectodermal dysplasia oligodontia is also present.
Other symptoms associated with anodontia include: Alopecia, loss of sweat glands, cleft lip or palate, or missing finger nails.
Diagnosis
Anodontia can be diagnosed when a baby does not begin to develop teeth around the age of 12 to 13 months or when a child does not develop their permanent teeth by the age of 10. The dentist can use a special X-ray, such as a panoramic image, to check if there are any teeth developing. There is also a higher risk for a child to develop anodontia if their parent has this disorder as well. In the absence of all permanent teeth, anodontia will be diagnosed. If between one to five teeth are missing, this will be diagnosed as hypodontia. In the absence of six or more teeth, this will be diagnosed as oligodontia.
Complications
The complications associated with anodontia can vary but the majority results in problems with aesthetic appearance, speaking, and masticatory function. Complications may occur with the placement of the dental implant. Although it is rare, some complications may include the screw of the implant becoming loose or sore spots.
Prevention and Treatment
Anodontia cannot be prevented due to it being a genetic disorder. Prosthetic replacement of missing teeth is possible using dental implant technology or dentures. This treatment can be successful in giving patients with anodontia a more aesthetically pleasing appearance. The use of an implant prosthesis in the lower jaw could be recommended for younger patients as it is shown to significantly improve the craniofacial growth, social development and self-image. The study associated with this evidence worked with individuals who had ectodermal dysplasia of varying age groups of up to 11, 11 to 18 and more than 18 years. It was noted that the risk of implant failure was significantly higher in patients younger than 18 years, but there is significant reason to use this methodology of treatment in those older. Overall the use of an implant-prosthesis has a considerable functional, aesthetic and psychological advantage when compared to a conventional denture, in the patients.
Prognosis
Patients diagnosed with anodontia are expected to have a normal life expectancy. Once anodontia is diagnosed, dental implants or dentures will need to worn in order to treat this disorder. There is an 88.5% to 100% chance for dental implants in patients with ectodermal dysplasia or tooth agenesis to be successful when placed after the age of 18.
Epidemiology
The prevalence of anodontia is unknown but it is a very rare disorder. Anodontia occurs in less than 2-8% of the general population in regards to permanent teeth and 0.1-0.7% in primary teeth. Gender and ethnicity do not play a role in anodontia.
Research
A recent study in 2019 by R. Constance Wiener and Christopher water looked at anodontia, hypodontia, and oligodontia in children West Virginia. There is a high prevalence of children with missing permanent teeth in West Virginia compared to the rest of the nation. During this study, 500 panoramic images were taken of children between the ages of 6 to 11. Out of the 500 images taken, 60 children had at least one or more missing permanent teeth. The results showed that more females had one or more missing permanent teeth than males. From the 60 children who had missing permanent teeth, 15.5% were female and 8.8% were males.A case study conducted in 2016 of a 6 year old boy presented with anodontia. There was no family history of anodontia and the patient did not present any other symptoms for ectodermal dysplasia. It was observed the hypodontia was present in the maxillary arch and the only teeth present were the left primary first molar and the bilateral primary second molars. It was also observed that the buccal mucosa, palate, and floor of the mouth were considered normal. The patient proceeded with oral rehabilitation and give removable denture to wear. The patient struggled in the beginning to keep wearing the denture until gradually learning to adjust to it. The family reported no problems with retention and began a monthly recall visit in order to monitor any eruptions of teeth or adjustments that needed to be made. Improvements in speech skills, communication, and self esteem were also observed after placement of the denture.Another case study in 2013 of an eight year old boy who reported missing teeth, difficulty chewing, and difficulty speaking was seen to have other symptoms of ectodermal dysplasia. The father confirmed there is a family history of missing teeth. The patient also had sensitivity to heat, absence of sweating, dry skin, absent eyebrows and eyelashes, hyper pigmentation, and many other ectodermal dysplasia symptoms. After a full examination, the patient was diagnosed with complete anodontia. The patient was treated with a complete set of removable dentures. After the dentures were given, the patients facial presentation and expressions improved. The patient was also set up for recall follow ups every six months. Drastic improvement was seen with improvements with chewing and speech.
See also
Hypodontia, the condition at which the patient has missing teeth
Hyperdontia, meaning more than the usual number of teeth.
References
== External links == |
Cancer | Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans.Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as Helicobacter pylori, hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV). These factors act, at least partly, by changing the genes of a cell. Typically, many genetic changes are required before cancer develops. Approximately 5–10% of cancers are due to inherited genetic defects. Cancer can be detected by certain signs and symptoms or screening tests. It is then typically further investigated by medical imaging and confirmed by biopsy.The risk of developing certain cancers can be reduced by not smoking, maintaining a healthy weight, limiting alcohol intake, eating plenty of vegetables, fruits, and whole grains, eating resistant starch, vaccination against certain infectious diseases, limiting consumption of processed meat and red meat, and limiting exposure to direct sunlight. Early detection through screening is useful for cervical and colorectal cancer. The benefits of screening for breast cancer are controversial. Cancer is often treated with some combination of radiation therapy, surgery, chemotherapy and targeted therapy. Pain and symptom management are an important part of care. Palliative care is particularly important in people with advanced disease. The chance of survival depends on the type of cancer and extent of disease at the start of treatment. In children under 15 at diagnosis, the five-year survival rate in the developed world is on average 80%. For cancer in the United States, the average five-year survival rate is 66%.In 2015, about 90.5 million people worldwide had cancer. In 2019, annual cancer cases grew by 23.6 million people and there were 10 million deaths worldwide, representing over the previous decade increases of 26% and 21%, respectively.The most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer, and stomach cancer. In females, the most common types are breast cancer, colorectal cancer, lung cancer, and cervical cancer. If skin cancer other than melanoma were included in total new cancer cases each year, it would account for around 40% of cases. In children, acute lymphoblastic leukemia and brain tumors are most common, except in Africa, where non-Hodgkin lymphoma occurs more often. In 2012, about 165,000 children under 15 years of age were diagnosed with cancer. The risk of cancer increases significantly with age, and many cancers occur more commonly in developed countries. Rates are increasing as more people live to an old age and as lifestyle changes occur in the developing world. The global total economic costs of cancer were estimated at US$1.16 trillion per year as of 2010.
Etymology and definitions
The word comes from the ancient Greek καρκίνος, meaning crab and tumor. Greek physicians Hippocrates and Galen, among others, noted the similarity of crabs to some tumors with swollen veins. The word was introduced in English in the modern medical sense around 1600.Cancers comprise a large family of diseases that involve abnormal cell growth with the potential to invade or spread to other parts of the body. They form a subset of neoplasms. A neoplasm or tumor is a group of cells that have undergone unregulated growth and will often form a mass or lump, but may be distributed diffusely.All tumor cells show the six hallmarks of cancer. These characteristics are required to produce a malignant tumor. They include:
Cell growth and division absent the proper signals
Continuous growth and division even given contrary signals
Avoidance of programmed cell death
Limitless number of cell divisions
Promoting blood vessel construction
Invasion of tissue and formation of metastasesThe progression from normal cells to cells that can form a detectable mass to outright cancer involves multiple steps known as malignant progression.
Signs and symptoms
When cancer begins, it produces no symptoms. Signs and symptoms appear as the mass grows or ulcerates. The findings that result depend on the cancers type and location. Few symptoms are specific. Many frequently occur in individuals who have other conditions. Cancer can be difficult to diagnose and can be considered a "great imitator."People may become anxious or depressed post-diagnosis. The risk of suicide in people with cancer is approximately double.
Local symptoms
Local symptoms may occur due to the mass of the tumor or its ulceration. For example, mass effects from lung cancer can block the bronchus resulting in cough or pneumonia; esophageal cancer can cause narrowing of the esophagus, making it difficult or painful to swallow; and colorectal cancer may lead to narrowing or blockages in the bowel, affecting bowel habits. Masses in breasts or testicles may produce observable lumps. Ulceration can cause bleeding that can lead to symptoms such as coughing up blood (lung cancer), anemia or rectal bleeding (colon cancer), blood in the urine (bladder cancer), or abnormal vaginal bleeding (endometrial or cervical cancer). Although localized pain may occur in advanced cancer, the initial tumor is usually painless. Some cancers can cause a buildup of fluid within the chest or abdomen.
Systemic symptoms
Systemic symptoms may occur due to the bodys response to the cancer. This may include fatigue, unintentional weight loss, or skin changes. Some cancers can cause a systemic inflammatory state that leads to ongoing muscle loss and weakness, known as cachexia.Some cancers, such as Hodgkins disease, leukemias, and liver or kidney cancers, can cause a persistent fever.Some systemic symptoms of cancer are caused by hormones or other molecules produced by the tumor, known as paraneoplastic syndromes. Common paraneoplastic syndromes include hypercalcemia, which can cause altered mental state, constipation and dehydration, or hyponatremia, which can also cause altered mental status, vomiting, headaches, or seizures.
Metastasis
Metastasis is the spread of cancer to other locations in the body. The dispersed tumors are called metastatic tumors, while the original is called the primary tumor. Almost all cancers can metastasize. Most cancer deaths are due to cancer that has metastasized.Metastasis is common in the late stages of cancer and it can occur via the blood or the lymphatic system or both. The typical steps in metastasis are local invasion, intravasation into the blood or lymph, circulation through the body, extravasation into the new tissue, proliferation and angiogenesis. Different types of cancers tend to metastasize to particular organs, but overall the most common places for metastases to occur are the lungs, liver, brain and the bones.
Causes
The majority of cancers, some 90–95% of cases, are due to genetic mutations from environmental and lifestyle factors. The remaining 5–10% are due to inherited genetics. Environmental refers to any cause that is not inherited, such as lifestyle, economic, and behavioral factors and not merely pollution. Common environmental factors that contribute to cancer death include tobacco use (25–30%), diet and obesity (30–35%), infections (15–20%), radiation (both ionizing and non-ionizing, up to 10%), lack of physical activity, and pollution. Psychological stress does not appear to be a risk factor for the onset of cancer, though it may worsen outcomes in those who already have cancer.It is not generally possible to prove what caused a particular cancer because the various causes do not have specific fingerprints. For example, if a person who uses tobacco heavily develops lung cancer, then it was probably caused by the tobacco use, but since everyone has a small chance of developing lung cancer as a result of air pollution or radiation, the cancer may have developed for one of those reasons. Excepting the rare transmissions that occur with pregnancies and occasional organ donors, cancer is generally not a transmissible disease, however factors that may have contributed to the development of cancer can be transmissible; such as oncoviruses like hepatitis B, Epstein-Barr virus and HIV.
Chemicals
Exposure to particular substances have been linked to specific types of cancer. These substances are called carcinogens.
Tobacco smoke, for example, causes 90% of lung cancer. It also causes cancer in the larynx, head, neck, stomach, bladder, kidney, esophagus and pancreas. Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons.Tobacco is responsible for about one in five cancer deaths worldwide and about one in three in the developed world. Lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990.In Western Europe, 10% of cancers in males and 3% of cancers in females are attributed to alcohol exposure, especially liver and digestive tract cancers. Cancer from work-related substance exposures may cause between 2 and 20% of cases, causing at least 200,000 deaths. Cancers such as lung cancer and mesothelioma can come from inhaling tobacco smoke or asbestos fibers, or leukemia from exposure to benzene.Exposure to perfluorooctanoic acid (PFOA), which is predominantly used in the production of Teflon, is known to cause two kinds of cancer.
Diet and exercise
Diet, physical inactivity and obesity are related to up to 30–35% of cancer deaths. In the United States, excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of cancer deaths. A UK study including data on over 5 million people showed higher body mass index to be related to at least 10 types of cancer and responsible for around 12,000 cases each year in that country. Physical inactivity is believed to contribute to cancer risk, not only through its effect on body weight but also through negative effects on the immune system and endocrine system. More than half of the effect from diet is due to overnutrition (eating too much), rather than from eating too few vegetables or other healthful foods.
Some specific foods are linked to specific cancers. A high-salt diet is linked to gastric cancer. Aflatoxin B1, a frequent food contaminant, causes liver cancer. Betel nut chewing can cause oral cancer. National differences in dietary practices may partly explain differences in cancer incidence. For example, gastric cancer is more common in Japan due to its high-salt diet while colon cancer is more common in the United States. Immigrant cancer profiles mirror those of their new country, often within one generation.
Infection
Worldwide approximately 18% of cancer deaths are related to infectious diseases. This proportion ranges from a high of 25% in Africa to less than 10% in the developed world. Viruses are the usual infectious agents that cause cancer but cancer bacteria and parasites may also play a role.
Oncoviruses (viruses that can cause cancer) include human papillomavirus (cervical cancer), Epstein–Barr virus (B-cell lymphoproliferative disease and nasopharyngeal carcinoma), Kaposis sarcoma herpesvirus (Kaposis sarcoma and primary effusion lymphomas), hepatitis B and hepatitis C viruses (hepatocellular carcinoma) and human T-cell leukemia virus-1 (T-cell leukemias). Bacterial infection may also increase the risk of cancer, as seen in Helicobacter pylori-induced gastric carcinoma. Parasitic infections associated with cancer include Schistosoma haematobium (squamous cell carcinoma of the bladder) and the liver flukes, Opisthorchis viverrini and Clonorchis sinensis (cholangiocarcinoma).
Radiation
Radiation exposure such as ultraviolet radiation and radioactive material is a risk factor for cancer. Many non-melanoma skin cancers are due to ultraviolet radiation, mostly from sunlight. Sources of ionizing radiation include medical imaging and radon gas.Ionizing radiation is not a particularly strong mutagen. Residential exposure to radon gas, for example, has similar cancer risks as passive smoking. Radiation is a more potent source of cancer when combined with other cancer-causing agents, such as radon plus tobacco smoke. Radiation can cause cancer in most parts of the body, in all animals and at any age. Children are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.Medical use of ionizing radiation is a small but growing source of radiation-induced cancers. Ionizing radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer. It is also used in some kinds of medical imaging.Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.Non-ionizing radio frequency radiation from mobile phones, electric power transmission and other similar sources has been described as a possible carcinogen by the World Health Organizations International Agency for Research on Cancer. Evidence, however, has not supported a concern. This includes that studies have not found a consistent link between mobile phone radiation and cancer risk.
Heredity
The vast majority of cancers are non-hereditary (sporadic). Hereditary cancers are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation that has a large effect on cancer risk and these cause less than 3–10% of cancer. Some of these syndromes include: certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer, and hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome), which is present in about 3% of people with colorectal cancer, among others.
Statistically for cancers causing most mortality, the relative risk of developing colorectal cancer when a first-degree relative (parent, sibling or child) has been diagnosed with it is about 2. The corresponding relative risk is 1.5 for lung cancer, and 1.9 for prostate cancer. For breast cancer, the relative risk is 1.8 with a first-degree relative having developed it at 50 years of age or older, and 3.3 when the relative developed it when being younger than 50 years of age.Taller people have an increased risk of cancer because they have more cells than shorter people. Since height is genetically determined to a large extent, taller people have a heritable increase of cancer risk.
Physical agents
Some substances cause cancer primarily through their physical, rather than chemical, effects. A prominent example of this is prolonged exposure to asbestos, naturally occurring mineral fibers that are a major cause of mesothelioma (cancer of the serous membrane) usually the serous membrane surrounding the lungs. Other substances in this category, including both naturally occurring and synthetic asbestos-like fibers, such as wollastonite, attapulgite, glass wool and rock wool, are believed to have similar effects. Non-fibrous particulate materials that cause cancer include powdered metallic cobalt and nickel and crystalline silica (quartz, cristobalite and tridymite). Usually, physical carcinogens must get inside the body (such as through inhalation) and require years of exposure to produce cancer.Physical trauma resulting in cancer is relatively rare. Claims that breaking bones resulted in bone cancer, for example, have not been proven. Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer or brain cancer. One accepted source is frequent, long-term application of hot objects to the body. It is possible that repeated burns on the same part of the body, such as those produced by kanger and kairo heaters (charcoal hand warmers), may produce skin cancer, especially if carcinogenic chemicals are also present. Frequent consumption of scalding hot tea may produce esophageal cancer. Generally, it is believed that cancer arises, or a pre-existing cancer is encouraged, during the process of healing, rather than directly by the trauma. However, repeated injuries to the same tissues might promote excessive cell proliferation, which could then increase the odds of a cancerous mutation.
Chronic inflammation has been hypothesized to directly cause mutation. Inflammation can contribute to proliferation, survival, angiogenesis and migration of cancer cells by influencing the tumor microenvironment. Oncogenes build up an inflammatory pro-tumorigenic microenvironment.
Hormones
Some hormones play a role in the development of cancer by promoting cell proliferation. Insulin-like growth factors and their binding proteins play a key role in cancer cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis.Hormones are important agents in sex-related cancers, such as cancer of the breast, endometrium, prostate, ovary and testis and also of thyroid cancer and bone cancer. For example, the daughters of women who have breast cancer have significantly higher levels of estrogen and progesterone than the daughters of women without breast cancer. These higher hormone levels may explain their higher risk of breast cancer, even in the absence of a breast-cancer gene. Similarly, men of African ancestry have significantly higher levels of testosterone than men of European ancestry and have a correspondingly higher level of prostate cancer. Men of Asian ancestry, with the lowest levels of testosterone-activating androstanediol glucuronide, have the lowest levels of prostate cancer.Other factors are relevant: obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers. Women who take hormone replacement therapy have a higher risk of developing cancers associated with those hormones. On the other hand, people who exercise far more than average have lower levels of these hormones and lower risk of cancer. Osteosarcoma may be promoted by growth hormones. Some treatments and prevention approaches leverage this cause by artificially reducing hormone levels and thus discouraging hormone-sensitive cancers.
Autoimmune diseases
There is an association between celiac disease and an increased risk of all cancers. People with untreated celiac disease have a higher risk, but this risk decreases with time after diagnosis and strict treatment, probably due to the adoption of a gluten-free diet, which seems to have a protective role against development of malignancy in people with celiac disease. However, the delay in diagnosis and initiation of a gluten-free diet seems to increase the risk of malignancies. Rates of gastrointestinal cancers are increased in people with Crohns disease and ulcerative colitis, due to chronic inflammation. Also, immunomodulators and biologic agents used to treat these diseases may promote developing extra-intestinal malignancies.
Pathophysiology
Genetics
Cancer is fundamentally a disease of tissue growth regulation. For a normal cell to transform into a cancer cell, the genes that regulate cell growth and differentiation must be altered.The affected genes are divided into two broad categories. Oncogenes are genes that promote cell growth and reproduction. Tumor suppressor genes are genes that inhibit cell division and survival. Malignant transformation can occur through the formation of novel oncogenes, the inappropriate over-expression of normal oncogenes, or by the under-expression or disabling of tumor suppressor genes. Typically, changes in multiple genes are required to transform a normal cell into a cancer cell.Genetic changes can occur at different levels and by different mechanisms. The gain or loss of an entire chromosome can occur through errors in mitosis. More common are mutations, which are changes in the nucleotide sequence of genomic DNA.
Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material. Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukemia and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase.
Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter region of a gene and affect its expression, or may occur in the genes coding sequence and alter the function or stability of its protein product. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, leading to the expression of viral oncogenes in the affected cell and its descendants.
Replication of the data contained within the DNA of living cells will probabilistically result in some errors (mutations). Complex error correction and prevention is built into the process and safeguards the cell against cancer. If a significant error occurs, the damaged cell can self-destruct through programmed cell death, termed apoptosis. If the error control processes fail, then the mutations will survive and be passed along to daughter cells.
Some environments make errors more likely to arise and propagate. Such environments can include the presence of disruptive substances called carcinogens, repeated physical injury, heat, ionising radiation or hypoxia.The errors that cause cancer are self-amplifying and compounding, for example:
A mutation in the error-correcting machinery of a cell might cause that cell and its children to accumulate errors more rapidly.
A further mutation in an oncogene might cause the cell to reproduce more rapidly and more frequently than its normal counterparts.
A further mutation may cause loss of a tumor suppressor gene, disrupting the apoptosis signaling pathway and immortalizing the cell.
A further mutation in the signaling machinery of the cell might send error-causing signals to nearby cells.The transformation of a normal cell into cancer is akin to a chain reaction caused by initial errors, which compound into more severe errors, each progressively allowing the cell to escape more controls that limit normal tissue growth. This rebellion-like scenario is an undesirable survival of the fittest, where the driving forces of evolution work against the bodys design and enforcement of order. Once cancer has begun to develop, this ongoing process, termed clonal evolution, drives progression towards more invasive stages. Clonal evolution leads to intra-tumour heterogeneity (cancer cells with heterogeneous mutations) that complicates designing effective treatment strategies and requires an evolutionary approach to designing treatment.
Characteristic abilities developed by cancers are divided into categories, specifically evasion of apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signals, sustained angiogenesis, limitless replicative potential, metastasis, reprogramming of energy metabolism and evasion of immune destruction.
Epigenetics
The classical view of cancer is a set of diseases driven by progressive genetic abnormalities that include mutations in tumor-suppressor genes and oncogenes, and in chromosomal abnormalities. A role for epigenetic alterations was identified in the early 21st century.Epigenetic alterations are functionally relevant modifications to the genome that do not change the nucleotide sequence. Examples of such modifications are changes in DNA methylation (hypermethylation and hypomethylation), histone modification and changes in chromosomal architecture (caused by inappropriate expression of proteins such as HMGA2 or HMGA1). Each of these alterations regulates gene expression without altering the underlying DNA sequence. These changes may remain through cell divisions, endure for multiple generations, and can be considered as equivalent to mutations.
Epigenetic alterations occur frequently in cancers. As an example, one study listed protein coding genes that were frequently altered in their methylation in association with colon cancer. These included 147 hypermethylated and 27 hypomethylated genes. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers and many others were hypermethylated in more than 50% of colon cancers.While epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, may be of particular importance. Such alterations may occur early in progression to cancer and are a possible cause of the genetic instability characteristic of cancers.Reduced expression of DNA repair genes disrupts DNA repair. This is shown in the figure at the 4th level from the top. (In the figure, red wording indicates the central role of DNA damage and defects in DNA repair in progression to cancer.) When DNA repair is deficient DNA damage remains in cells at a higher than usual level (5th level) and cause increased frequencies of mutation and/or epimutation (6th level). Mutation rates increase substantially in cells defective in DNA mismatch repair or in homologous recombinational repair (HRR). Chromosomal rearrangements and aneuploidy also increase in HRR defective cells.Higher levels of DNA damage cause increased mutation (right side of figure) and increased epimutation. During repair of DNA double strand breaks, or repair of other DNA damage, incompletely cleared repair sites can cause epigenetic gene silencing.Deficient expression of DNA repair proteins due to an inherited mutation can increase cancer risks. Individuals with an inherited impairment in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) have increased cancer risk, with some defects ensuring a 100% lifetime chance of cancer (e.g. p53 mutations). Germ line DNA repair mutations are noted on the figures left side. However, such germline mutations (which cause highly penetrant cancer syndromes) are the cause of only about 1 percent of cancers.In sporadic cancers, deficiencies in DNA repair are occasionally caused by a mutation in a DNA repair gene but are much more frequently caused by epigenetic alterations that reduce or silence expression of DNA repair genes. This is indicated in the figure at the 3rd level. Many studies of heavy metal-induced carcinogenesis show that such heavy metals cause a reduction in expression of DNA repair enzymes, some through epigenetic mechanisms. DNA repair inhibition is proposed to be a predominant mechanism in heavy metal-induced carcinogenicity. In addition, frequent epigenetic alterations of the DNA sequences code for small RNAs called microRNAs (or miRNAs). miRNAs do not code for proteins, but can "target" protein-coding genes and reduce their expression.
Cancers usually arise from an assemblage of mutations and epimutations that confer a selective advantage leading to clonal expansion (see Field defects in progression to cancer). Mutations, however, may not be as frequent in cancers as epigenetic alterations. An average cancer of the breast or colon can have about 60 to 70 protein-altering mutations, of which about three or four may be "driver" mutations and the remaining ones may be "passenger" mutations.
Metastasis
Metastasis is the spread of cancer to other locations in the body. The dispersed tumors are called metastatic tumors, while the original is called the primary tumor. Almost all cancers can metastasize. Most cancer deaths are due to cancer that has metastasized.Metastasis is common in the late stages of cancer and it can occur via the blood or the lymphatic system or both. The typical steps in metastasis are local invasion, intravasation into the blood or lymph, circulation through the body, extravasation into the new tissue, proliferation and angiogenesis. Different types of cancers tend to metastasize to particular organs, but overall the most common places for metastases to occur are the lungs, liver, brain and the bones.
Metabolism
Normal cells typically generate only about 30% of energy from glycolysis, whereas most cancers rely on glycolysis for energy production (Warburg effect). But a minority of cancer types rely on oxidative phosphorylation as the primary energy source, including lymphoma, leukemia, and endometrial cancer. Even in these cases, however, the use of glycolysis as an energy source rarely exceeds 60%. A few cancers use glutamine as the major energy source, partly because it provides nitrogen required for nucleotide (DNA, RNA) synthesis. Cancer stem cells often use oxidative phosphorylation or glutamine as a primary energy source.Several studies have indicated that the enzyme sirtuin 6 is selectively inactivated during oncogenesis in a variety of tumor types by inducing glycolysis. Another sirtuin, sirtuin 3 inhibits cancers that depend upon glycolysis, but promotes cancers that depend upon oxidative phosphorylation.A low-carbohydr |
Cancer | ate diet (ketogenic diet) has sometimes been recommended as a supportive therapy for cancer treatment.
Diagnosis
Most cancers are initially recognized either because of the appearance of signs or symptoms or through screening. Neither of these leads to a definitive diagnosis, which requires the examination of a tissue sample by a pathologist. People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, (contrast) CT scans and endoscopy.
The tissue diagnosis from the biopsy indicates the type of cell that is proliferating, its histological grade, genetic abnormalities and other features. Together, this information is useful to evaluate the prognosis and to choose the best treatment.
Cytogenetics and immunohistochemistry are other types of tissue tests. These tests provide information about molecular changes (such as mutations, fusion genes and numerical chromosome changes) and may thus also indicate the prognosis and best treatment.
Cancer diagnosis can cause psychological distress and psychosocial interventions, such as talking therapy, may help people with this.
Classification
Cancers are classified by the type of cell that the tumor cells resemble and is therefore presumed to be the origin of the tumor. These types include:
Carcinoma: Cancers derived from epithelial cells. This group includes many of the most common cancers and include nearly all those in the breast, prostate, lung, pancreas and colon.
Sarcoma: Cancers arising from connective tissue (i.e. bone, cartilage, fat, nerve), each of which develops from cells originating in mesenchymal cells outside the bone marrow.
Lymphoma and leukemia: These two classes arise from hematopoietic (blood-forming) cells that leave the marrow and tend to mature in the lymph nodes and blood, respectively.
Germ cell tumor: Cancers derived from pluripotent cells, most often presenting in the testicle or the ovary (seminoma and dysgerminoma, respectively).
Blastoma: Cancers derived from immature "precursor" cells or embryonic tissue.Cancers are usually named using -carcinoma, -sarcoma or -blastoma as a suffix, with the Latin or Greek word for the organ or tissue of origin as the root. For example, cancers of the liver parenchyma arising from malignant epithelial cells is called hepatocarcinoma, while a malignancy arising from primitive liver precursor cells is called a hepatoblastoma and a cancer arising from fat cells is called a liposarcoma. For some common cancers, the English organ name is used. For example, the most common type of breast cancer is called ductal carcinoma of the breast. Here, the adjective ductal refers to the appearance of cancer under the microscope, which suggests that it has originated in the milk ducts.
Benign tumors (which are not cancers) are named using -oma as a suffix with the organ name as the root. For example, a benign tumor of smooth muscle cells is called a leiomyoma (the common name of this frequently occurring benign tumor in the uterus is fibroid). Confusingly, some types of cancer use the -noma suffix, examples including melanoma and seminoma.
Some types of cancer are named for the size and shape of the cells under a microscope, such as giant cell carcinoma, spindle cell carcinoma and small-cell carcinoma.
Prevention
Cancer prevention is defined as active measures to decrease cancer risk. The vast majority of cancer cases are due to environmental risk factors. Many of these environmental factors are controllable lifestyle choices. Thus, cancer is generally preventable. Between 70% and 90% of common cancers are due to environmental factors and therefore potentially preventable.Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: tobacco, excess weight/obesity, poor diet, physical inactivity, alcohol, sexually transmitted infections and air pollution. Further, poverty could be considered as an indirect risk factor in human cancers. Not all environmental causes are controllable, such as naturally occurring background radiation and cancers caused through hereditary genetic disorders and thus are not preventable via personal behavior.
Dietary
While many dietary recommendations have been proposed to reduce cancer risks, the evidence to support them is not definitive. The primary dietary factors that increase risk are obesity and alcohol consumption. Diets low in fruits and vegetables and high in red meat have been implicated but reviews and meta-analyses do not come to a consistent conclusion. A 2014 meta-analysis found no relationship between fruits and vegetables and cancer. Coffee is associated with a reduced risk of liver cancer. Studies have linked excessive consumption of red or processed meat to an increased risk of breast cancer, colon cancer and pancreatic cancer, a phenomenon that could be due to the presence of carcinogens in meats cooked at high temperatures. In 2015 the IARC reported that eating processed meat (e.g., bacon, ham, hot dogs, sausages) and, to a lesser degree, red meat was linked to some cancers.Dietary recommendations for cancer prevention typically include an emphasis on vegetables, fruit, whole grains and fish and an avoidance of processed and red meat (beef, pork, lamb), animal fats, pickled foods and refined carbohydrates.
Medication
Medications can be used to prevent cancer in a few circumstances. In the general population, NSAIDs reduce the risk of colorectal cancer; however, due to cardiovascular and gastrointestinal side effects, they cause overall harm when used for prevention. Aspirin has been found to reduce the risk of death from cancer by about 7%. COX-2 inhibitors may decrease the rate of polyp formation in people with familial adenomatous polyposis; however, it is associated with the same adverse effects as NSAIDs. Daily use of tamoxifen or raloxifene reduce the risk of breast cancer in high-risk women. The benefit versus harm for 5-alpha-reductase inhibitor such as finasteride is not clear.Vitamin supplementation does not appear to be effective at preventing cancer. While low blood levels of vitamin D are correlated with increased cancer risk, whether this relationship is causal and vitamin D supplementation is protective is not determined. One 2014 review found that supplements had no significant effect on cancer risk. Another 2014 review concluded that vitamin D3 may decrease the risk of death from cancer (one fewer death in 150 people treated over 5 years), but concerns with the quality of the data were noted.Beta-Carotene supplementation increases lung cancer rates in those who are high risk. Folic acid supplementation is not effective in preventing colon cancer and may increase colon polyps. Selenium supplementation has not been shown to reduce the risk of cancer.
Vaccination
Vaccines have been developed that prevent infection by some carcinogenic viruses. Human papillomavirus vaccine (Gardasil and Cervarix) decrease the risk of developing cervical cancer. The hepatitis B vaccine prevents infection with hepatitis B virus and thus decreases the risk of liver cancer. The administration of human papillomavirus and hepatitis B vaccinations is recommended where resources allow.
Screening
Unlike diagnostic efforts prompted by symptoms and medical signs, cancer screening involves efforts to detect cancer after it has formed, but before any noticeable symptoms appear. This may involve physical examination, blood or urine tests or medical imaging.Cancer screening is not available for many types of cancers. Even when tests are available, they may not be recommended for everyone. Universal screening or mass screening involves screening everyone. Selective screening identifies people who are at higher risk, such as people with a family history. Several factors are considered to determine whether the benefits of screening outweigh the risks and the costs of screening. These factors include:
Possible harms from the screening test: for example, X-ray images involve exposure to potentially harmful ionizing radiation
The likelihood of the test correctly identifying cancer
The likelihood that cancer is present: Screening is not normally useful for rare cancers.
Possible harms from follow-up procedures
Whether suitable treatment is available
Whether early detection improves treatment outcomes
Whether the cancer will ever need treatment
Whether the test is acceptable to the people: If a screening test is too burdensome (for example, extremely painful), then people will refuse to participate.
Cost
Recommendations
U.S. Preventive Services Task Force
The U.S. Preventive Services Task Force (USPSTF) issues recommendations for various cancers:
Strongly recommends cervical cancer screening in women who are sexually active and have a cervix at least until the age of 65.
Recommend that Americans be screened for colorectal cancer via fecal occult blood testing, sigmoidoscopy, or colonoscopy starting at age 50 until age 75.
Evidence is insufficient to recommend for or against screening for skin cancer, oral cancer, lung cancer, or prostate cancer in men under 75.
Routine screening is not recommended for bladder cancer, testicular cancer, ovarian cancer, pancreatic cancer, or prostate cancer.
Recommends mammography for breast cancer screening every two years from ages 50–74, but does not recommend either breast self-examination or clinical breast examination. A 2013 Cochrane review concluded that breast cancer screening by mammography had no effect in reducing mortality because of overdiagnosis and overtreatment.
Japan
Screens for gastric cancer using photofluorography due to the high incidence there.
Genetic testing
Genetic testing for individuals at high-risk of certain cancers is recommended by unofficial groups. Carriers of these mutations may then undergo enhanced surveillance, chemoprevention, or preventative surgery to reduce their subsequent risk.
Management
Many treatment options for cancer exist. The primary ones include surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy and palliative care. Which treatments are used depends on the type, location and grade of the cancer as well as the patients health and preferences. The treatment intent may or may not be curative.
Chemotherapy
Chemotherapy is the treatment of cancer with one or more cytotoxic anti-neoplastic drugs (chemotherapeutic agents) as part of a standardized regimen. The term encompasses a variety of drugs, which are divided into broad categories such as alkylating agents and antimetabolites. Traditional chemotherapeutic agents act by killing cells that divide rapidly, a critical property of most cancer cells.
It was found that providing combined cytotoxic drugs is better than a single drug, a process called the combination therapy, which has an advantage in the statistics of survival and response to the tumor and in the progress of the disease. A Cochrane review concluded that combined therapy was more effective to treat metastasized breast cancer. However, generally it is not certain whether combination chemotherapy leads to better health outcomes, when both survival and toxicity are considered.Targeted therapy is a form of chemotherapy that targets specific molecular differences between cancer and normal cells. The first targeted therapies blocked the estrogen receptor molecule, inhibiting the growth of breast cancer. Another common example is the class of Bcr-Abl inhibitors, which are used to treat chronic myelogenous leukemia (CML). Currently, targeted therapies exist for many of the most common cancer types, including bladder cancer, breast cancer, colorectal cancer, kidney cancer, leukemia, liver cancer, lung cancer, lymphoma, pancreatic cancer, prostate cancer, skin cancer, and thyroid cancer as well as other cancer types.The efficacy of chemotherapy depends on the type of cancer and the stage. In combination with surgery, chemotherapy has proven useful in cancer types including breast cancer, colorectal cancer, pancreatic cancer, osteogenic sarcoma, testicular cancer, ovarian cancer and certain lung cancers. Chemotherapy is curative for some cancers, such as some leukemias, ineffective in some brain tumors, and needless in others, such as most non-melanoma skin cancers. The effectiveness of chemotherapy is often limited by its toxicity to other tissues in the body. Even when chemotherapy does not provide a permanent cure, it may be useful to reduce symptoms such as pain or to reduce the size of an inoperable tumor in the hope that surgery will become possible in the future.
Radiation
Radiation therapy involves the use of ionizing radiation in an attempt to either cure or improve symptoms. It works by damaging the DNA of cancerous tissue, thereby killing it. To spare normal tissues (such as skin or organs, which radiation must pass through to treat the tumor), shaped radiation beams are aimed from multiple exposure angles to intersect at the tumor, providing a much larger dose there than in the surrounding, healthy tissue. As with chemotherapy, cancers vary in their response to radiation therapy.Radiation therapy is used in about half of cases. The radiation can be either from internal sources (brachytherapy) or external sources. The radiation is most commonly low energy X-rays for treating skin cancers, while higher energy X-rays are used for cancers within the body. Radiation is typically used in addition to surgery and or chemotherapy. For certain types of cancer, such as early head and neck cancer, it may be used alone. For painful bone metastasis, it has been found to be effective in about 70% of patients.
Surgery
Surgery is the primary method of treatment for most isolated, solid cancers and may play a role in palliation and prolongation of survival. It is typically an important part of definitive diagnosis and staging of tumors, as biopsies are usually required. In localized cancer, surgery typically attempts to remove the entire mass along with, in certain cases, the lymph nodes in the area. For some types of cancer this is sufficient to eliminate the cancer.
Palliative care
Palliative care is treatment that attempts to help the patient feel better and may be combined with an attempt to treat the cancer. Palliative care includes action to reduce physical, emotional, spiritual and psycho-social distress. Unlike treatment that is aimed at directly killing cancer cells, the primary goal of palliative care is to improve quality of life.
People at all stages of cancer treatment typically receive some kind of palliative care. In some cases, medical specialty professional organizations recommend that patients and physicians respond to cancer only with palliative care. This applies to patients who:
display low performance status, implying limited ability to care for themselves
received no benefit from prior evidence-based treatments
are not eligible to participate in any appropriate clinical trial
no strong evidence implies that treatment would be effectivePalliative care may be confused with hospice and therefore only indicated when people approach end of life. Like hospice care, palliative care attempts to help the patient cope with their immediate needs and to increase comfort. Unlike hospice care, palliative care does not require people to stop treatment aimed at the cancer.
Multiple national medical guidelines recommend early palliative care for patients whose cancer has produced distressing symptoms or who need help coping with their illness. In patients first diagnosed with metastatic disease, palliative care may be immediately indicated. Palliative care is indicated for patients with a prognosis of less than 12 months of life even given aggressive treatment.
Immunotherapy
A variety of therapies using immunotherapy, stimulating or helping the immune system to fight cancer, have come into use since 1997. Approaches include antibodies, checkpoint therapy, and adoptive cell transfer.
Laser therapy
Laser therapy uses high-intensity light to treat cancer by shrinking or destroying tumors or precancerous growths. Lasers are most commonly used to treat superficial cancers that are on the surface of the body or the lining of internal organs. It is used to treat basal cell skin cancer and the very early stages of others like cervical, penile, vaginal, vulvar, and non-small cell lung cancer. It is often combined with other treatments, such as surgery, chemotherapy, or radiation therapy. Laser-induced interstitial thermotherapy (LITT), or interstitial laser photocoagulation, uses lasers to treat some cancers using hyperthermia, which uses heat to shrink tumors by damaging or killing cancer cells. Laser are more precise than surgery and cause less damage, pain, bleeding, swelling, and scarring. A disadvantage is surgeons must have specialized training. It may be more expensive than other treatments.
Alternative medicine
Complementary and alternative cancer treatments are a diverse group of therapies, practices and products that are not part of conventional medicine. "Complementary medicine" refers to methods and substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine. Most complementary and alternative medicines for cancer have not been studied or tested using conventional techniques such as clinical trials. Some alternative treatments have been investigated and shown to be ineffective but still continue to be marketed and promoted. Cancer researcher Andrew J. Vickers stated, "The label unproven is inappropriate for such therapies; it is time to assert that many alternative cancer therapies have been disproven."
Prognosis
Survival rates vary by cancer type and by the stage at which it is diagnosed, ranging from majority survival to complete mortality five years after diagnosis. Once a cancer has metastasized, prognosis normally becomes much worse. About half of patients receiving treatment for invasive cancer (excluding carcinoma in situ and non-melanoma skin cancers) die from that cancer or its treatment. A majority of cancer deaths are due to metastases of the primary tumor.Survival is worse in the developing world, partly because the types of cancer that are most common there are harder to treat than those associated with developed countries.Those who survive cancer develop a second primary cancer at about twice the rate of those never diagnosed. The increased risk is believed to be due to the random chance of developing any cancer, the likelihood of surviving the first cancer, the same risk factors that produced the first cancer, unwanted side effects of treating the first cancer (particularly radiation therapy), and better compliance with screening.Predicting short- or long-term survival depends on many factors. The most important are the cancer type and the patients age and overall health. Those who are frail with other health problems have lower survival rates than otherwise healthy people. Centenarians are unlikely to survive for five years even if treatment is successful. People who report a higher quality of life tend to survive longer. People with lower quality of life may be affected by depression and other complications and/or disease progression that both impairs quality and quantity of life. Additionally, patients with worse prognoses may be depressed or report poorer quality of life because they perceive that their condition is likely to be fatal.
People with cancer have an increased risk of blood clots in their veins which can be life-threatening. The use of blood thinners such as heparin decrease the risk of blood clots but have not been shown to increase survival in people with cancer. People who take blood thinners also have an increased risk of bleeding.Although extremely rare, some forms of cancer, even from an advanced stage, can heal spontaneously. This phenomenon is known as the spontaneous remission.
Epidemiology
Estimates are that in 2018, 18.1 million new cases of cancer and 9.6 million deaths occur globally. About 20% of males and 17% of females will get cancer at some point in time while 13% of males and 9% of females will die from it.In 2008, approximately 12.7 million cancers were diagnosed (excluding non-melanoma skin cancers and other non-invasive cancers) and in 2010 nearly 7.98 million people died. Cancers account for approximately 16% of deaths. The most common as of 2018 are lung cancer (1.76 million deaths), colorectal cancer (860,000) stomach cancer (780,000), liver cancer (780,000), and breast cancer (620,000). This makes invasive cancer the leading cause of death in the developed world and the second leading in the developing world. Over half of cases occur in the developing world.Deaths from cancer were 5.8 million in 1990. Deaths have been increasing primarily due to longer lifespans and lifestyle changes in the developing world. The most significant risk factor for developing cancer is age. Although it is possible for cancer to strike at any age, most patients with invasive cancer are over 65. According to cancer researcher Robert A. Weinberg, "If we lived long enough, sooner or later we all would get cancer." Some of the association between aging and cancer is attributed to immunosenescence, errors accumulated in DNA over a lifetime and age-related changes in the endocrine system. Agings effect on cancer is complicated by factors such as DNA damage and inflammation promoting it and factors such as vascular aging and endocrine changes inhibiting it.Some slow-growing cancers are particularly common, but often are not fatal. Autopsy studies in Europe and Asia showed that up to 36% of people have undiagnosed and apparently harmless thyroid cancer at the time of their deaths and that 80% of men develop prostate cancer by age 80. As these cancers do not cause the patients death, identifying them would have represented overdiagnosis rather than useful medical care.
The three most common childhood cancers are leukemia (34%), brain tumors (23%) and lymphomas (12%). In the United States cancer affects about 1 in 285 children. Rates of childhood cancer increased by 0.6% per year between 1975 and 2002 in the United States and by 1.1% per year between 1978 and 1997 in Europe. Death from childhood cancer decreased by half between 1975 and 2010 in the United States.
History
Cancer has existed for all of human history. The earliest written record regarding cancer is from circa 1600 BC in the Egyptian Edwin Smith Papyrus and describes breast cancer. Hippocrates (c. 460 BC – c. 370 BC) described several kinds of cancer, referring to them with the Greek word καρκίνος karkinos (crab or crayfish). This name comes from the appearance of the cut surface of a solid malignant tumor, with "the veins stretched on all sides as the animal the crab has its feet, whence it derives its name". Galen stated that "cancer of the breast is so called because of the fancied resemblance to a crab given by the lateral prolongations of the tumor and the adjacent distended veins".: 738 Celsus (c. 25 BC – 50 AD) translated karkinos into the Latin cancer, also meaning crab and recommended surgery as treatment. Galen (2nd century AD) disagreed with the use of surgery and recommended purgatives instead. These recommendations largely stood for 1000 years.In the 15th, 16th and 17th centuries, it became acceptable for doctors to dissect bodies to discover the cause of death. The German professor Wilhelm Fabry believed that breast cancer was caused by a milk clot in a mammary duct. The Dutch professor Francois de la Boe Sylvius, a follower of Descartes, believed that all disease was the outcome of chemical processes and that acidic lymph fluid was the cause of cancer. His contemporary Nicolaes Tulp believed that cancer was a poison that slowly spreads and concluded that it was contagious.The physician John Hill described tobacco snuff as the cause of nose cancer in 1761. This was followed by the report in 1775 by British surgeon Percivall Pott that chimney sweeps carcinoma, a cancer of the scrotum, was a common disease among chimney sweeps. With the widespread use of the microscope in the 18th century, it was discovered that the cancer poison spread from the primary tumor through the lymph nodes to other sites ("metastasis"). This view of the disease was first formulated by the English surgeon Campbell De Morgan between 1871 and 1874.
Society and culture
Although many diseases (such as heart failure) may have a worse prognosis than most cases of cancer, cancer is the subject of widespread fear and taboos. The euphemism of "a long illness" to describe cancers leading to death is still commonly used in obituaries, rather than naming the disease explicitly, reflecting an apparent stigma. Cancer is also euphemised as "the C-word"; Macmillan Cancer Support uses the term to try to lessen the fear around the disease. In Nigeria, one local name for cancer translates into English as "the disease that cannot be cured". This deep belief that cancer is necessarily a difficult and usually deadly disease is reflected in the systems chosen by society to compile cancer statistics: the most common form of cancer—non-melanoma skin cancers, accounting for about one-third of cancer cases worldwide, but very few deaths—are excluded from cancer statistics specifically because they are easily treated and almost always cured, often in a single, short, outpatient procedure.Western conceptions of patients rights for people with cancer include a duty to fully disclose the medical situation to the person, and the right to engage in shared decision-making in a way that respects the persons own values. In other cultures, other rights and values are preferred. For example, most African cultures value whole families rather than individualism. In parts of Africa, a diagnosis is commonly made so late that cure is not possible, and treatment, if available at all, would quickly bankrupt the family. As a result of these factors, African healthcare providers tend to let family members decide whether, when and how to disclose the diagnosis, and they tend to do so slowly and circuitously, as the person shows interest and an ability to cope with the grim news. People from Asian and South American countries also tend to prefer a slower, less candid approach to disclosure than is idealized in the United States and Western Europe, and they believe that sometimes it would be preferable not to be told about a cancer diagnosis. In general, disclosure of the diagnosis is more common than it was in the 20th century, but full disclosure of the prognosis is not offered to many patients around the world.In the United States and some other cultures, cancer is regarded as a disease that must be "fought" to end the "civil insurrection"; a War on Cancer was declared in the US. Military metaphors are particularly common in descriptions of cancers human effects, and they emphasize both the state of the patients health and the need to take immediate, decisive actions himself rather than to delay, to ignore or to rely entirely on others. The military metaphors also help rationalize radical, destructive treatments.In the 1970s, a relatively popular alternative cancer treatment in the US was a specialized form of talk therapy, based on the idea that cancer was caused by a bad attitude. People with a "cancer personality"—depressed, repressed, self-loathing and afraid to express their emotions—were believed to have manifested cancer through subconscious desire. Some psychotherapists said that treatment to change the patients outlook on life would cure the cancer. Among other effects, this belief allowed society to blame the victim for having caused the cancer (by "wanting" it) or having prevented its cure (by not becoming a sufficiently happy, fearless and loving person). It also increased patients anxiety, as they incorrectly believed that natural emotions of sadness, anger or fear shorten their lives. The idea was ridiculed by Susan Sontag, who published Illness as Metaphor while recovering from treatment for breast cancer in 1978. Although the original idea is now generally regarded as nonsense, the idea partly persists in a reduced form with a widespread, but incorrect, belief that deliberately cultivating a habit of positive thinking will increase survival. This notion is particularly strong in breast cancer culture.One idea about why people with cancer are blamed or stigmatized, called the just-world hypothesis, is that blaming cancer on the patients actions or attitudes allows the blamers to regain a sense of control. This is based upon the blamers belief that the world is fundamentally just and so any dangerous illness, like cancer, must be a type of punishment for bad choices, because in a just world, bad things would not happen to good people.
Economic effect
The total health care expenditure on cancer in the US was estimated to be $80.2 billion in 2015. Even though cancer-related health care expenditure have increased in absolute terms during recent decades, the share of health expenditure devoted to cancer treatment has remained close to 5% between the 1960s and 2004. A similar pattern has been observed in Europe where about 6% of all health care expenditure are spent on cancer treatment. In addition to health care expenditure and financial toxicity, cancer causes indirect costs in the form of productivity losses due to sick days, permanent incapacity and disability as well as premature death during working age. Cancer causes also costs for informal care. Indirect costs and informal care costs are typically estimated to exceed or equal the health care costs of cancer.
Workplace
In the United States, cancer is included as a protected condition by the Equal Employment Opportunity Commission (EEOC), mainly due to the potential for cancer having discriminating effects on workers. Discrimination in the workplace could occur if an employer holds a false belief that a person with cancer is not capable of doing a job properly, and may ask for more sick leave than other employees. Employers may also make hiring or firing decisions based on misconceptions about cancer disabilities, if present. The EEOC provides interview guidelines for employers, as well as lists of possible solutions for assessing and accommodating employees with cancer.
Research
Because cancer is a class of diseases, it is unlikely that there will ever be a single |
Cancer | "cure for cancer" any more than there will be a single treatment for all infectious diseases. Angiogenesis inhibitors were once incorrectly thought to have potential as a "silver bullet" treatment applicable to many types of cancer. Angiogenesis inhibitors and other cancer therapeutics are used in combination to reduce cancer morbidity and mortality.Experimental cancer treatments are studied in clinical trials to compare the proposed treatment to the best existing treatment. Treatments that succeeded in one cancer type can be tested against other types. Diagnostic tests are under development to better target the right therapies to the right patients, based on their individual biology.Cancer research focuses on the following issues:
Agents (e.g. viruses) and events (e.g. mutations) that cause or facilitate genetic changes in cells destined to become cancer.
The precise nature of the genetic damage and the genes that are affected by it.
The consequences of those genetic changes on the biology of the cell, both in generating the defining properties of a cancer cell and in facilitating additional genetic events that lead to further progression of the cancer.The improved understanding of molecular biology and cellular biology due to cancer research has led to new treatments for cancer since US President Richard Nixon declared the "War on Cancer" in 1971. Since then, the country has spent over $200 billion on cancer research, including resources from public and private sectors. The cancer death rate (adjusting for size and age of the population) declined by five percent between 1950 and 2005.Competition for financial resources appears to have suppressed the creativity, cooperation, risk-taking and original thinking required to make fundamental discoveries, unduly favoring low-risk research into small incremental advancements over riskier, more innovative research. Other consequences of competition appear to be many studies with dramatic claims whose results cannot be replicated and perverse incentives that encourage grantee institutions to grow without making sufficient investments in their own faculty and facilities.Virotherapy, which uses convert viruses, is being studied.
In the wake of the COVID-19 pandemic, there has been a worry that cancer research and treatment are slowing down.
Pregnancy
Cancer affects approximately 1 in 1,000 pregnant women. The most common cancers found during pregnancy are the same as the most common cancers found in non-pregnant women during childbearing ages: breast cancer, cervical cancer, leukemia, lymphoma, melanoma, ovarian cancer and colorectal cancer.Diagnosing a new cancer in a pregnant woman is difficult, in part because any symptoms are commonly assumed to be a normal discomfort associated with pregnancy. As a result, cancer is typically discovered at a somewhat later stage than average. Some imaging procedures, such as MRIs (magnetic resonance imaging), CT scans, ultrasounds and mammograms with fetal shielding are considered safe during pregnancy; some others, such as PET scans, are not.Treatment is generally the same as for non-pregnant women. However, radiation and radioactive drugs are normally avoided during pregnancy, especially if the fetal dose might exceed 100 cGy. In some cases, some or all treatments are postponed until after birth if the cancer is diagnosed late in the pregnancy. Early deliveries are often used to advance the start of treatment. Surgery is generally safe, but pelvic surgeries during the first trimester may cause miscarriage. Some treatments, especially certain chemotherapy drugs given during the first trimester, increase the risk of birth defects and pregnancy loss (spontaneous abortions and stillbirths).Elective abortions are not required and, for the most common forms and stages of cancer, do not improve the mothers survival. In a few instances, such as advanced uterine cancer, the pregnancy cannot be continued and in others, the patient may end the pregnancy so that she can begin aggressive chemotherapy.Some treatments can interfere with the mothers ability to give birth vaginally or to breastfeed. Cervical cancer may require birth by Caesarean section. Radiation to the breast reduces the ability of that breast to produce milk and increases the risk of mastitis. Also, when chemotherapy is given after birth, many of the drugs appear in breast milk, which could harm the baby.
Other animals
Veterinary oncology, concentrating mainly on cats and dogs, is a growing specialty in wealthy countries and the major forms of human treatment such as surgery and radiotherapy may be offered. The most common types of cancer differ, but the cancer burden seems at least as high in pets as in humans. Animals, typically rodents, are often used in cancer research and studies of natural cancers in larger animals may benefit research into human cancer.Across wild animals, there is still limited data on cancer. Nonetheless, a study published in 2022, explored cancer risk in (non-domesticated) zoo mammals, belonging to 191 species, 110,148 individual, demonstrated that cancer is a ubiquitous disease of mammals and it can emerge anywhere along the mammalian phylogeny. This research also highlighted that cancer risk is not uniformly distributed along mammals. For instance, species in the order Carnivora are particularly prone to be affected by cancer (e.g. over 25% of clouded leopards, bat-eared foxes and red wolves die of cancer), while ungulates (especially even-toed ungulates) appear to face consistently low cancer risks.
In non-humans, a few types of transmissible cancer have also been described, wherein the cancer spreads between animals by transmission of the tumor cells themselves. This phenomenon is seen in dogs with Stickers sarcoma (also known as canine transmissible venereal tumor), and in Tasmanian devils with devil facial tumour disease (DFTD).
References
Further reading
External links
Cancer at Curlie
"On telling cancer patients to have a positive attitude" at The Atlantic |
Reactive gastropathy | Reactive gastropathy, chemical gastropathy also called gastritis of « C type » or "chemical gastritis" is an abnormality in the stomach caused by chemicals, e.g. bile, alcohol, and characteristically has minimal inflammation.
Cause
Reactive gastropathy has a large number of causes, including:
Alcohol use disorder.
Bile reflux, such as may be seen post-Billroth II.
NSAIDs.
Diagnosis
The diagnosis is by examination of tissue, e.g. a stomach biopsy.
Relation to gastritis
Reactive gastropathy is morphologically distinct entity that can be separated from gastritis, which by definition has a significant inflammatory component.
As a reactive gastropathy may mimic a (true) gastritis symptomatically and visually in an endoscopic examination, it may incorrectly be referred to as a gastritis. Even aware of the underlying etiology of the pathologic process, e.g. NSAID use, the label "chemical gastritis" is applied to a chemical gastropathy.
See also
Gastritis
References
External links
Reactive gastropathy - surgical pathology criteria (stanford.edu). |
Hangmans fracture | Hangmans fracture is the colloquial name given to a fracture of both pedicles, or partes interarticulares, of the axis vertebra (C2).
Causes
The injury mainly occurs from falls, usually in elderly adults, and motor accidents mainly due to impacts of high force causing extension of the neck and great axial load onto the C2 vertebra.
In a study based in Norway, 60% of reported cervical fractures came from falls and 21% from motor-related accidents.
According to the Agency for Healthcare Research and Quality (AHRQ), the group under the highest risk of C2 fractures are elderly people within the age group of 65-84 (39.02%) at risks of falls (61%) or motor accidents (21%) in metropolitan areas (94%). There were 203 discharges from the age group 1-17; 1,843 from 18- to 44-year-olds; 2,147 from 45- to 64-year-olds, 4,890 from 65- to 84-year-olds, and 3440 from 85+-year-olds. Females accounted for 54.45% of occurrences while males accounted for the other 45.38%.
Mechanisms
The mechanism of the injury is forcible hyperextension of the head, usually with distraction of the neck. Traditionally this would occur during judicial hanging, when the noose was placed below the condemned subjects chin. When the subject was dropped, the head would be forced into hyperextension by the full weight of the body, a sufficient force to cause the fracture. However, despite its long association with judicial hangings, one study of a series of such hangings showed that only a small minority of hangings produced a hangmans fracture.Apart from hangings, the mechanism of injury—a sudden forceful hyperextension centered just under the chin—occurs mainly with deceleration injuries in which the victims face or chin strike an unyielding object with the neck in extension. The most common scenario is a frontal motor vehicle accident with an unrestrained passenger or driver, with the person striking the dashboard or windshield with their face or chin. Other scenarios include falls, diving injuries, and collisions between players in contact sports.Although a hangmans fracture is unstable, survival from this fracture is relatively common, as the fracture itself tends to expand the spinal canal at the C2 level. It is not unusual for patients to walk in for treatment and have such a fracture discovered on X-rays. Only if the force of the injury is severe enough that the vertebral body of C2 is severely subluxed from C3 does the spinal cord become crushed, usually between the vertebral body of C3 and the posterior elements of C1 and C2.
Prevention
Car crashes
Most commonly this can occur during a car accident. A person involved in a car crash, especially with no seat belt, can slam their chin against the steering wheel, dashboard, or windshield, causing the hyperextension to occur.
Contact sports
Falling and colliding with other people in a contact sport can also cause this fracture. Falling causes the weight of the body to force hyperextension. In full-contact sports such as American football and Rugby, diving for the ball can lead a player to land on his head, forcing the neck into hyperextension. The further piling of players on top of an injured player adds more weight and can lead to further occurrences of this fracture.
Treatment
Non-surgical or surgical
Hangmans fractures treatments are both non-surgical and surgical.
Benefits of surgical hangmans fracture treatment
Sasso also observed that people who underwent surgical treatment will not be affected by pin site infections, brain abscesses, facet joint stiffness, loss of spinal alignment, and skin breakdown. Another study concerns the surgical treatment of the ring of axis conducted by Barsa et al. (2006) based on 30 cases within 41 patients treated by using anterior cervical fixation and fusion and 11 cases treated by a posterior CT.
Result of the surgical treatment
As a result, Barsa et al. showed that the result of fracture fusion reduced after one year but only one patient died of other disease during the follow-up. Hakalo and Wronski (2008) showed the benefits of operative treatment such as using transoral C2-C3 discectomy with plate-cage stabilization or posterior direct pars screw repair for the reducing and healing process. In deliberate or suicidal hanging, asphyxia is much more likely to be the cause of death due to associated prevertebral swelling. A common sign is a constricted pupil (Horners syndrome) on the ipsilateral side due to loss of sympathetic innervation to the eye, caused by damage to the sympathetic trunk in the neck.
Epidemiology
The C2 fracture accounts for nearly 19% of spinal fractures and 55% of cervical fractures (in patients with head injury). Within C2 fractures, the hangmans fracture accounts for 23% of occurrences while the odontoid or dens fracture accounts for 55% of them.
Society
Statistics from the AHRQ show that there were 12,532 hospital discharges from C2 fractures in the US during 2010. The mean healthcare costs were $17,015 and the "national bill" or the aggregate charges were $749,553,403. Only 460 in-hospital deaths related to the C2 fracture occurred. From 2000 to 2010, the number of discharges has increased from 4,875 to 12,532, almost a 250 percent increase. Mean health care costs went from $24,771 to $59,939.
See also
Cervical fracture
Cervical vertebrae
References
== External links == |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.