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Curlings ulcer | Curlings ulcer is an acute gastric erosion resulting as a complication from severe burns when reduced plasma volume leads to ischemia and cell necrosis (sloughing) of the gastric mucosa. The condition was first described in 1823 and named for a doctor, Thomas Blizard Curling, who observed ten such patients in 1842.These stress ulcers (actually shallow multiple erosions) were once a common complication of serious burns, presenting in over 10% of cases, and especially common in child burn victims. They result in perforation and hemorrhage more often than other forms of intestinal ulceration and had correspondingly high mortality rates (at least 80%).A similar condition involving elevated intracranial pressure is known as Cushings ulcer.
Treatment
While emergency surgery was once the only treatment, combination therapies including enteral feeding with powerful antacids such as H2-receptor antagonists or, more recently, proton pump inhibitors such as omeprazole have made Curlings ulcer a rare complication.
See also
Cushing ulcer
References
== External links == |
Encephalopathy | Encephalopathy (; from Ancient Greek: ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome has many possible organic and inorganic causes.
Signs and symptoms
The hallmark of encephalopathy is an altered mental state or delirium. Characteristic of the altered mental state is impairment of the cognition, attention, orientation, sleep–wake cycle and consciousness. An altered state of consciousness may range from failure of selective attention to drowsiness. Hypervigilance may be present; with or without: cognitive deficits, headache, epileptic seizures, myoclonus (involuntary twitching of a muscle or group of muscles) or asterixis ("flapping tremor" of the hand when wrist is extended).Depending on the type and severity of encephalopathy, common neurological symptoms are loss of cognitive function, subtle personality changes, and an inability to concentrate. Other neurological signs may include dysarthria, hypomimia, problems with movements (they can be clumsy or slow), ataxia, tremor. Other neurological signs may include involuntary grasping and sucking motions, nystagmus (rapid, involuntary eye movement), jactitation (restlessness while in bed), and respiratory abnormalities such as Cheyne-Stokes respiration (cyclic waxing and waning of tidal volume), apneustic respirations and post-hypercapnic apnea. Focal neurological deficits are less common.Wernicke encephalopathy can co-occur with Korsakoff alcoholic syndrome, characterized by amnestic-confabulatory syndrome: retrograde amnesia, anterograde amnesia, confabulations (invented memories), poor recall and disorientation.Anti-NMDA receptor encephalitis is the most common autoimmune encephalitis. It can cause paranoid and grandiose delusions, agitation, hallucinations (visual and auditory), bizarre behavior, fear, short-term memory loss, and confusion.HIV encephalopathy can lead to dementia.
Types
There are many types of encephalopathy. Some examples include:
Mitochondrial encephalopathy: Metabolic disorder caused by dysfunction of mitochondrial DNA. Can affect many body systems, particularly the brain and nervous system.
Glycine encephalopathy: A genetic metabolic disorder involving excess production of glycine.
Hepatic encephalopathy: Arising from advanced cirrhosis of the liver.
Hypoxic ischemic encephalopathy: Permanent or transitory encephalopathy arising from severely reduced oxygen delivery to the brain.
Static encephalopathy: Unchanging, or permanent, brain damage, usually caused by prenatal exposure to ethanol.
Uremic encephalopathy: Arising from high levels of toxins normally cleared by the kidneys—rare where dialysis is readily available.
Wernickes encephalopathy: Arising from thiamine (B1) deficiency, usually in the setting of alcoholism.
Hashimotos encephalopathy: Arising from an auto-immune disorder.
Anti-NMDA receptor encephalitis: An auto-immune encephalitis.
Hyperammonemia: a condition caused by high levels of ammonia, which is due to inborn errors of metabolism (including urea cycle disorder or multiple carboxylase deficiency), a diet with excessive levels of protein, deficiencies of specific nutrients such as arginine or biotin, or organ failure.
Hypertensive encephalopathy: Arising from acutely increased blood pressure.
Chronic traumatic encephalopathy: a progressive degenerative disease associated with multiple concussions and other forms of brain injury
Lyme encephalopathy: Arising from Lyme disease bacteria, including Borrelia burgdorferi.
Toxic encephalopathy: A form of encephalopathy caused by chemicals and prescription drugs, often resulting in permanent brain damage.
Toxic-metabolic encephalopathy: A catch-all for brain dysfunction caused by infection, organ failure, or intoxication.
Transmissible spongiform encephalopathy: A collection of diseases all caused by prions, and characterized by "spongy" brain tissue (riddled with holes), impaired locomotion or coordination, and a 100% mortality rate. Includes bovine spongiform encephalopathy (mad cow disease), scrapie, and kuru among others.
Neonatal encephalopathy (hypoxic-ischemic encephalopathy): An obstetric form, often occurring due to lack of oxygen in bloodflow to brain-tissue of the fetus during labour or delivery.
Salmonella encephalopathy: A form of encephalopathy caused by food poisoning (especially out of peanuts and rotten meat) often resulting in permanent brain damage and nervous system disorders.
Encephalomyopathy: A combination of encephalopathy and myopathy. Causes may include mitochondrial disease (particularly MELAS) or chronic hypophosphatemia, as may occur in cystinosis.
Creutzfeldt–Jakob disease (CJD; transmissible spongiform encephalopathy).
HIV encephalopathy (encephalopathy associated with HIV infection and AIDS, characterized by atrophy and ill-defined white matter hyperintensity).
Sepsis-associated encephalopathy (this type can occur in the setting of apparent sepsis, trauma, severe burns, or trauma, even without clear identification of an infection).
Epileptic encephalopathies:
Early infantile epileptic encephalopathy (acquired or congenital abnormal cortical development).
Early myoclonic epileptic encephalopathy (possibly due to metabolic disorders).
Gluten encephalopathy: Focal abnormalities of the white matter (generally area of low perfusion) are appreciated through magnetic resonance. Migraine is the most common symptom reported.
Toxicity from chemotherapy
Chemotherapy medication, for example, fludarabine can cause a
permanent severe global encephalopathy. Ifosfamide can cause
a severe encephalopathy (but it can be reversible with stopping use of the drug and starting the use of methylene blue). Bevacizumab and other anti–vascular endothelial growth factor medication can cause posterior reversible encephalopathy syndrome.
Toxicity from psychotropic medications
All therapeutic interventions are double-edged swords with benefits and adverse effects, and pharmacotherapy is not an exception. Shortly after the introduction of conventional antipsychotic drugs into clinical practice, relatively rare but serious complications with hyperthermia, muscle rigidity, autonomic instability, and disturbed mental status were recognized to develop in some patients treated with antipsychotics. This type of encephalopathy induced by the use of antipsychotics was referred to as neuroleptic malignant syndrome (NMS), and almost all physicians prescribing antipsychotics are nowadays aware of this adverse phenomenon. Another well-known type of encephalopathy associated with psychotropic drug therapy is serotonin toxicity (ST) or serotonin syndrome (SS), which is characterized by autonomic and neuromuscular symptoms and altered mental status. In contrast with the idiosyncratic nature of NMS, ST is a spectrum pathophysiological state assumed to derive from excess serotonergic neural transmission caused by serotonin-related psychotropic agents. In these two decades, pharmacotherapy with psychotropic drugs for mentally ill patients has been dramatically changed, and classical prototypal antipsychotics and antidepressants have been replaced with atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs), respectively. These newly developed psychotropic drugs are generally safer and more tolerable than older drugs. However, atypical antipsychotics are not free of the risk of development of NMS, and the explosive prevalence of SSRIs prescribed not only for depression but also for a number of psychiatric diagnoses such as anxiety, eating, impulse-control, and personality disorders may increase the incidence of ST. Therefore, these two pathological states still remain as major adverse effects of psychotropic drugs involving altered functioning of the central nervous system (CNS), to which all clinicians prescribing psychoactive drugs should pay attention. The popularity of SSRIs also increased the case reports of patients experiencing discontinuation syndrome, which sometimes includes CNS symptoms like anxiety and irritability. In this chapter, the author provides a comprehensive overview of the above- mentioned adverse effects affecting the CNS function associated with psychotropic pharmacotherapy. In addition, several other pathological conditions potentially causing encephalopathic symptoms in psychiatric patients treated with psychotropic drugs, e.g., hyponatremia, valproate-induced hyperammonemia, transient splenial lesion of the corpus callosum, and so on, are also described.
Diagnosis
Blood tests, cerebrospinal fluid examination by lumbar puncture (also known as spinal tap), brain imaging studies, electroencephalography (EEG), neuropsychological testing and similar diagnostic studies may be used to differentiate the various causes of encephalopathy.
Diagnosis is frequently clinical. That is, no set of tests give the diagnosis, but the entire presentation of the illness with nonspecific test results informs the experienced clinician of the diagnosis.
Treatment
Treatment varies according to the type and severity of the encephalopathy. Anticonvulsants may be prescribed to reduce or halt any seizures. Changes to diet and nutritional supplements may help some people. In severe cases, dialysis or organ replacement surgery may be needed.
Sympathomimetic drugs can increase motivation, cognition, motor performance and alertness in persons with encephalopathy caused by brain injury, chronic infections, strokes, brain tumors.When the encephalopathy is caused by untreated celiac disease or non-celiac gluten sensitivity, the gluten-free diet stops the progression of brain damage and improves the headaches.
Prognosis
Treating the underlying cause of the disorder may improve or reverse symptoms. However, in some cases, the encephalopathy may cause permanent structural changes and irreversible damage to the brain. These permanent deficits can be considered a form of stable dementia. Some encephalopathies can be fatal.
Terminology
Encephalopathy is a difficult term because it can be used to denote either a disease or finding (i.e., an observable sign in a person).
When referring to a finding, encephalopathy refers to permanent (or degenerative) brain injury, or a reversible one. It can be due to direct injury to the brain, or illness remote from the brain. The individual findings that cause a clinician to refer to a person as having encephalopathy include intellectual disability, irritability, agitation, delirium, confusion, somnolence, stupor, coma and psychosis. As such, describing a person as having a clinical picture of encephalopathy is not a very specific description.
When referring to a disease, encephalopathy refers to a wide variety of brain disorders with very different etiologies, prognoses and implications. For example, prion diseases, all of which cause transmissible spongiform encephalopathies, are invariably fatal, but other encephalopathies are reversible and can have a number of causes including nutritional deficiencies and toxins.
See also
Brain damage
Neuroscience
Neurological disorder
Psychoorganic syndrome
References
Adapted from: Office of Communications and Public Liaison (9 November 2010). "NINDS Encephalopathy Information Page". National Institute of Neurological Disorders and Stroke, National Institutes of Health. Archived from the original on 2009-03-23. Retrieved 2005-09-01.
Further reading
The Diagnosis of Stupor and Coma by Plum and Posner, ISBN 0-19-513898-8, remains one of the best detailed observational references to the condition. |
Tubercle (bone) | In the skeleton of humans and other animals, a tubercle, tuberosity or apophysis is a protrusion or eminence that serves as an attachment for skeletal muscles. The muscles attach by tendons, where the enthesis is the connective tissue between the tendon and bone. A tuberosity is generally a larger tubercle.
Main tubercles
Humerus
The humerus has two tubercles, the greater tubercle and the lesser tubercle. These are situated at the proximal end of the bone, that is the end that connects with the scapula. The greater/lesser tubercule is located from the top of the acromion laterally and inferiorly. The radius has two, the radial tuberosity and Listers tubercle.
Ribs
On a rib, tubercle is an eminence on the back surface, at the junction between the neck and the body of the rib. It consists of an articular and a non-articular area. The lower and more medial articular area is a small oval surface for articulation with the transverse process of the lower of the two vertebrae which gives attachment to the head. The higher, non-articular area is a rough elevation which gives attachment to the ligament of the tubercle. The tubercle is much more prominent in the upper ribs than in the lower ribs.
Tibia
The most prominent tubercle of the tibia, a leg bone which is more commonly known as the shinbone or shankbone, is the tibial tuberosity. The tibial tuberosity is located on the tibias anterior surface, distal to the medial condyle. It creates a bony prominence just below the patella, and can be easily located with the fingers. It creates an attachment point for the ligamentum patellae, or patellar ligament. Other tubercles of the tibia include the medial intercondylar tubercle, the lateral intercondylar tubercle, and Gerdys tubercle.
Femur
A trochanter is one of up to three tubercles of the femur:
Greater trochanter
Lesser trochanter
Third trochanter, which is occasionally present
Fifth metatarsal
In the fifth metatarsal bone, the most proximal part of the bone is termed the "tuberosity", and the secondary ossification center that is normally present thereon in children is termed the "apophysis".
Related diseases and conditions
Fractures
The main type of fracture affecting tubercles is avulsion fracture, by pulling the attached tendon.
Apophysitis
Apophysitis is an inflammation of a tubercle. It mainly affects growing children, with overuse of the affected tubercle. Examples include:
Osgood–Schlatter disease (apophysitis of the tibial tubercle)
Severs disease (apophysitis of the posterior tubercle of the heel)
Sinding-Larsen and Johansson syndrome (apophysitis of the inferior pole of the patella)
Enthesitis
Enthesitis is an anatomically close but separate condition, wherein there is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is associated with HLA B27 arthropathies such as ankylosing spondylitis, psoriatic arthritis, and reactive arthritis.
== References == |
Phoria | Phoria are an English art rock band based in Brighton, consisting of Trewin Howard, Ed Sanderson, Jeb Hardwick, James "Cheese" Cheeseman, and Seryn Burden.
Phoria released their debut EP, Yourself Still, in 2010, followed by Bloodworks (2013) and Display (2014). The records earned the band international critical and popular acclaim.
The bands first full-length album, Volition, was released on 3 June 2016.
Their second album, Caught a Black Rabbit, came out on 13 November 2020.
Biography
Phoria members Trewin, Jeb and Ed went to primary as school together in Salisbury, where they learned cello, classical guitar, and violin respectively.
As friends, they spent their youth making music together before leaving for university in 2005.
Jeb and Ed both attended the University of Southampton. Ed continued to study music, specialising in violin and piano. Jeb studied for a sociology degree, though spent much of his time experimenting with music and visual arts.
Trewin attended the Dartington College of Arts in Devon. He had initially enrolled on as fine arts course but was soon drawn back to music.
Having completed their studies, Trewin, Ed, and Jeb returned to Salisbury and took full time jobs. Jebs included a brief spell as an insurance agent. Ed, with a passion for acting, took large but unfulfilling parts in a series of niche-market films.
It was not long before the three of them realised that their future lay elsewhere, and moved to Brighton to start their musical careers.
While studying at Southampton, Jeb and Ed had met Tim Douglas through a mutual friend. Following successful spells playing guitar in bands across the South West, Tim moved to Brighton to play bass, and complete the Phoria line-up along with then drummer, Ross Crick.
Seryn Burden joined the band in August 2011, twelve months after the release of Yourself Still, following Rosss departure.
In 2016, following the release of Volition, and a string of successful EPs and UK and international tours, Jeb Hardwick left Phoria to pursue a career in filmmaking. He was replaced by James Cheeseman.
Jeb returned for the recording of the second album Caught A Black Rabbit (2020).
Yourself Still EP (2010)
The bands first EP Yourself Still was released in 2010 and earned positive reviews from various music blogs. The blog The Sirens Sound reviewed the EP, stating that [Yourself Still]...carries various musical vibes from cinematic orchestra to post-rock and indie-rock to a stunning pop environment leading the overall outcome of this record to blazed emotion. Describing Phoria as A band you definitely want to keep an eye on.
Bloodworks EP (2013)
Bloodworks was released through Akira Records in Spring 2013.
Lead single "Red" hit number 2 in The Hype Machine blog aggregator charts within only a few days, cementing the track as one of the standout singles of 2013 from a relatively unknown band. With the single released just days before the EP, ThisIsFakeDIY said of the track [It gives] the impression that this here EPs going to be a game-changer. Glossy production is met midway by a startling, intimate style of songwriting, half Youth Lagoon, half something grander and more orchestral.Several tracks from the EP have been licensed to festival-featured European cinema, and Canadian television series Saving Hope.
Display EP (2014)
Display was released in June 2014. The lead single Emanate received 250,000 plays across YouTube and Soundcloud in the first two weeks.
Volition (2016)
Volition was released in June 2016 following several delays. It received positive reviews across the critical sphere, with The 405 describing the album as gigantic...[yet] effortlessly intimate, praising the cohesion in sound and vision. Ben Yung of therevue.ca gave a glowing review, stating: Volition is stunning, an absolute emotional roller coaster from start to finish. It is easy to understand why it took two years for the Brighton-based five-piece to complete their debut, as every single detail has been given the utmost attention and the production is refined and masterful. Every note, every vocal component, every lyric, every instrumental texture has been attended to and nothing feels out of place. With the precision of a surgeon and the steely aim of an assassin, Phoria hits every mark, including piercing a hole through our hearts with their visceral and emotional electronica.
The album was supported by festival appearances throughout 2016 and a UK and European tour.
In 2018, the song "Evolve" was featured in an episode of the Syfy original show, The Magicians.
Tim Douglas left the band in 2019 citing personal reasons.
Saving Us A Riot was used in Season 3 of Killing Eve. It was announced Jeb Hardwick had rejoined the band in August 2019
Caught A Black Rabbit (2020)
In August 2019, photos were shared of the band recording at Abbey Road Studios. On the 23rd June the band shared the first track from the upcoming album, Intro. Their second album Caught A Black Rabbit was announced on Facebook, and is due for release on the 13th November 2020. It has been described by the band as contemporary classical. The first single from the album, Current was premiered on Clash on the 23rd of July. Trewin Howard said about the song, "We all have hidden depths, through which our vulnerable excitement flows... sometimes a storm will brew and the glassy surface that hides it all is disturbed," Circuit Sweet wrote ‘It’s a harrowing orchestration, a feeling of courage shines deep within this elegant track. This is such a beautiful and powerful release.’
Style
Phoria draw on a range of musical genres to create their sound. In the days of Yourself Still, chordal guitar figures and often dense instrumentation drew comparisons to such bands as Radiohead, Sigur Rós, and Mew. The music blog therecommender.net, when reviewing preview material from the bands then forthcoming Bloodworks EP, wrote This...isnt just reminiscent of Radiohead, this is reminiscent of Radiohead at their best. Martin Grech, Cinematic Orchestra, and Elbow are also major influences. The band have more recently been compared favourably to Aphex Twin, Autechre, and James Blake.
Discography
Yourself Still (EP) (2010)
Bloodworks (EP) (2013)
Display (EP) (2014)
Volition (2016)
Caught A Black Rabbit (2020)
References
External links
Phoriamusic.com
Youtube.com
Phoria.bandcamp.com/ |
Vestibular papillomatosis | Vestibular papillomatosis (VP) are normal small bumps in the genital area of females. They appear in multiple numbers, are rounded and are not painful, itchy or uncomfortable. They are analogous to pearly penile papules, which occur in males.They are not infectious and are not due to HPV. Diagnosis is by visualization. The bumps are less yellow and more pinkish when compared to Fordyce spots. They should not be mistaken for genital warts. No treatment is required.They are common in pregnancy. Historically they were sometimes incorrectly called "microwarts".
== References == |
Chalicosis | Chalicosis is a form of pneumoconiosis affecting the lungs or bronchioles, found chiefly among stonecutters.
The disease is caused by the inhalation of fine particles of stone. The term is from Greek, χάλιξ, gravel.
References
== External links == |
Beckwith–Wiedemann syndrome | Beckwith–Wiedemann syndrome (; abbreviated BWS) is an overgrowth disorder usually present at birth, characterized by an increased risk of childhood cancer and certain congenital features. A minority (<15%) cases of BWS are familial, meaning that a close relative may also have BWS, and parents of an affected child may be at increased risk of having other children with BWS. While children with BWS are at increased risk of childhood cancer, most children with BWS do not develop cancer and the vast majority of children who do develop cancer can be treated successfully.
Presentation
No consensus clinical diagnostic criteria for Beckwith–Wiedemann syndrome (BWS) exist. Beckwith–Wiedemann syndrome (BWS) should be suspected in individuals who have one or more of the following major and/or minor findings.Major findings associated with BWS
Macrosomia (traditionally defined as weight and length/height >97th centile)
Macroglossia
Hemihyperplasia (asymmetric overgrowth of one or more regions of the body)
Omphalocele (also called exomphalos) or umbilical hernia
Embryonal tumor (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, rhabdomyosarcoma) in childhood
Visceromegaly involving one or more intra-abdominal organs including liver, spleen, kidneys, adrenal glands, and/or pancreas
Cytomegaly of the fetal adrenal cortex (pathognomonic)
Renal abnormalities including structural abnormalities, nephromegaly, nephrocalcinosis, and/or later development of medullary sponge kidney
Anterior linear ear lobe creases and/or posterior helical ear pits
Placental mesenchymal dysplasia
Cleft palate (rare in BWS)
Cardiomyopathy (rare in BWS)
Positive family history (≥1 family members with a clinical diagnosis of BWS or a history or features suggestive of BWS)Minor findings associated with BWS
Pregnancy-related findings including polyhydramnios and prematurity in fetuses with the condition.
Neonatal hypoglycemia
Vascular lesions including nevus simplex (typically appearing on the forehead, glabella, and/or back of the neck) or hemangiomas (cutaneous or extracutaneous)
Characteristic facies including midface retrusion and infraorbital creases
Structural cardiac anomalies or cardiomegaly
Diastasis recti
Advanced bone age (common in overgrowth/endocrine disorders)The diagnosis of BWS is established in a proband with either of the following:
Three major or two major plus at least one minor criteria Note: BWS should be considered a clinical spectrum, with some affected individuals having only one or two suggestive clinical findings. Therefore, the generally accepted clinical criteria proposed here should not be viewed as absolute but rather as guidelines. In other words, they cannot be used to rule out a diagnosis of BWS and cannot substitute for clinical judgment.
An epigenetic or genomic alteration leading to abnormal methylation at 11p15.5 or a heterozygous BWS-causing pathogenic variant in CDKN1C in the presence of one or more clinical findingsMost children with BWS do not have all of these features. In addition, some children with BWS have other findings including: nevus flammeus, prominent occiput, midface hypoplasia, hemihypertrophy, genitourinary anomalies (enlarged kidneys), cardiac anomalies, musculoskeletal abnormalities, and hearing loss. Also, some premature newborns with BWS do not have macroglossia until closer to their anticipated delivery date.Given the variation among individuals with BWS and the lack of a simple diagnostic test, identifying BWS can be difficult. In an attempt to standardize the classification of BWS, DeBaun et al. have defined a child as having BWS if the child has been diagnosed by a physician as having BWS and if the child has at least two of the five common features associated with BWS (macroglossia, macrosomia, midline abdominal wall defects, ear creases, neonatal hypoglycemia). Another definition presented by Elliot et al. includes the presence of either three major features (anterior abdominal wall defect, macroglossia, or prepostnatal overgrowth) or two major plus three minor findings (ear creases, nevus flammeus, neonatal hypoglycemia, nephromegaly, or hemihyperplasia).In general, children with BWS do very well and grow up to become adults of normal size and intelligence, usually without the syndromic features of their childhood.
Neoplasms
Most children (>80%) with BWS do not develop cancer; however, children with BWS are much more likely (~600 times more) than other children to develop certain childhood cancers, particularly Wilms tumor (nephroblastoma), pancreatoblastoma and hepatoblastoma. Individuals with BWS appear to only be at increased risk for cancer during childhood (especially before age four) and do not have an increased risk of developing cancer in adulthood. If 100 children with BWS were followed from birth until age ten, about 10 cases of cancer would be expected in the group before age four, and about 1 case of cancer in the group would be expected between age four and ten.
In addition to Wilms tumor and hepatoblastoma, children with BWS have been shown in individual case reports to develop ganglioneuroma, adrenocortical carcinoma, acute lymphoid leukemia, liver sarcoma, thyroid carcinoma, melanoma, rhabdomyosarcoma, and mesoblastic nephroma.Wilms tumor, hepatoblastoma, and mesoblastic nephroma can usually be cured if diagnosed early. Early diagnosis allows physicians to treat the cancer when it is at an early stage. In addition, there is less toxic treatment. Given the importance of early diagnosis, all children with BWS should receive cancer screening.An abdominal ultrasound every 3 months until at least eight years of age is recommended and a blood test to measure alpha-fetoprotein (AFP) every 6 weeks until at least four years of age. Families and physicians should determine screening schedules for specific patients, especially the age at which to discontinue screening, based upon their own evaluation of the risk-benefit ratio.
Genetics
Most (>85%) cases of BWS are sporadic, meaning that, typically, no one else in that family has BWS, and parents of an affected child are not at increased risk of having other children with BWS. However, some (<15%) cases of BWS are familial, meaning that a close relative may also have BWS, and parents of an affected child may be at increased risk of having other children with BWS. BWS has been shown to specifically involve mutations in a defined region on the short arm of chromosome 11 referred to as 11p15.5, that leads to overactivity of the IGF-2 gene (growth factor) and/or no active copy of CDKN1C (inhibitor of cell proliferation gene).BWS can be caused by a range of different genetic defects. Over five distinct errors involving 11p15.5 have been identified in different BWS patients. Some patients have maternal chromosomal rearrangements of 11p15.5. Other patients have paternal uniparental disomy (UPD) of chromosome 11, meaning that the maternal copy of this chromosome is replaced with an extra paternal copy. Many other patients have abnormal DNA methylation in different areas of 11p15.5, meaning that normal epigenetic marks that regulate imprinted genes in this region are altered. A few other patients have a single gene copy located within 11p15, instead of two copies.The absence of a mutation in a child with clinical findings suggestive of BWS should not preclude a diagnosis of BWS. Even after extensive molecular testing, the specific defect causing BWS in an affected individual may remain unknown. BWS remains a clinical, rather than genetic, diagnosis, since physicians cannot identify and test for all the genetic causes of BWS. The clinical definition used for BWS is limited, because no standard diagnostic criteria exist that have been independently verified with patients who have either genetic or epigenetic mutations. When molecular analyses were completed in 10 children who met a research criterion for BWS, only 7 of the 10 children had genetic or epigenetic mutations.Given that the genetics of BWS are complex, a child with BWS should be under the medical care of a geneticist or an expert in the management of BWS.
Genes involved are IGF-2, CDKN1C, H19, and KCNQ1OT1.
Association with CDKN1C
CDKN1C is a protein coding gene that encodes a cyclin-dependent kinase inhibitor that acts as a negative regulator of cell proliferation, effectively making CDKN1C a tumor suppressor gene. CDKN1C also works during fetal development, preventing the fetus from becoming too large. It is located on the short arm of the human chromosome 11 in the ICR2 region, along with many other imprinted genes. Since CDKN1C is preferentially maternally expressed, hypomethylation in the ICR2 region of the maternal allele can result in pathologies such as cancer or a defect known as Beckwith-Weidemann Syndrome. Beckwith-Weidemann Syndrome (BWS) may also be brought about by CDKN1C 11p15 epimutations. It may also be a result of deletions of small amounts of DNA that cause chromosomal abnormalities, rendering the gene inactive. This leaves only the paternally expressed IGF2 to promote cell proliferation. The reduction of growth restriction results in the overgrowth of many tissues, leading to the common symptoms of BWS. These symptoms may include macroglossia, organomegaly, periorbital fullness, and hernias. Knockout models for CDKN1C in mice do exist; in fact, many of the affected offspring exhibit fetal and neonatal lethality and have most of the features related to Beckwith-Weidemann Syndrome.
Diagnosis
Management
Abdominal wall defects are common in newborns with BWS and may require surgical treatment. These defects can range in severity from omphalocele (most serious) to umbilical hernia and diastasis recti (least serious). An omphalocele is a congenital malformation in which a newborns intestines, and sometimes other abdominal organs, protrude out of the abdomen through the umbilicus. Newborns with an omphalocele typically require surgery to place the abdominal contents back into the abdomen in order to prevent serious infection or shock. An umbilical hernia is also a defect in which abdominal contents come through weak abdominal wall muscle at the umbilicus. In general, newborns with umbilical hernias do not require treatment because often these hernias spontaneously close by age four. If, after this time, a hernia is still present, surgery may be recommended. Diastasis recti is a separation of the left and right sides of the rectus abdominis muscle that are normally joined. Children with diastasis recti usually require no treatment because the condition resolves as the child grows.Neonatal hypoglycemia, low blood glucose in the first month of life, occurs in about half of children with BWS. Most of these hypoglycemic newborns are asymptomatic and have a normal blood glucose level within days. However, untreated persistent hypoglycemia can lead to permanent brain damage. Hypoglycemia in newborns with BWS should be managed according to standard protocols for treating neonatal hypoglycemia. Usually this hypoglycemia can easily be treated with more frequent feedings or medical doses of glucose. Rarely (<5%) children with BWS will continue to have hypoglycemia after the neonatal period and require more intensive treatment. Such children may require tube feedings, oral hyperglycemic medicines, or a partial pancreatectomy.Macroglossia, a large tongue, is a very common (>90%) and prominent feature of BWS. Infants with BWS and macroglossia typically cannot fully close their mouth in front of their large tongue, causing it to protrude out. Macroglossia in BWS becomes less noticeable with age and often requires no treatment; but it does cause problems for some children with BWS. In severe cases, macroglossia can cause respiratory, feeding, and speech difficulties. Children with BWS and significant macroglossia should be evaluated by a craniofacial team.The best time to perform surgery for a large tongue is not known. Some surgeons recommend performing the surgery between 3 and 6 months of age. Surgery for macroglossia involves removing a small part of the tongue so that it fits within the mouth to allow for proper jaw and tooth development.These children are often managed by a multidisciplinary craniofacial team. These teams include speech and language therapists, Craniofacial and Paediatric Plastic Surgeons and Orthodontists who decide the appropriateness and timing of tongue reduction surgery. Some countries have designated centres for the management of macroglossia. For example, in the United Kingdom, children who have macroglossia associated with Beckwith Wiedemann Syndrome are managed in a national specialised service. The service is commissioned as highly specialised service by NHS England and is located at Great Ormond Street Hospital.Nevus flammeus (port-wine stain) is a flat, red birthmark caused by a capillary (small blood vessel) malformation. Children with BWS often have nevus flammeus on their forehead or the back of their neck. Nevus flammeus is benign and commonly does not require any treatment.
Hemihypertrophy (hemihyperplasia) is an abnormal asymmetry between the left and right sides of the body occurring when one part of the body grows faster than normal. Children with BWS and hemihypertrophy can have an isolated asymmetry of one body part, or they can have a difference affecting the entire one side of the body. Individuals who do not have BWS can also have hemihypertrophy. Isolated hemihypertrophy is associated with a higher risk for cancer. The types of cancer and age of the cancers are similar to children with BWS. As a result, children with hemihypertrophy should follow the general cancer screening protocol for BWS.
Hemihypertrophy can also cause various orthopedic problems, so children with significant limb hemihyperplasia should be evaluated and followed by an orthopedic surgeon.
Hemihyperplasia affecting the face can sometimes cause significant cosmetic concerns that may be addressed by a cranial facial team.
Prognosis
In general, the prognosis is very good. Children with BWS usually do very well and grow up to become the heights expected based on their parents heights. While they are at increased risk of childhood cancer, most of them do not develop the disease, and the vast majority of the children who do can be treated successfully.Children with BWS for the most part had no significant delays when compared to their siblings. However, some of them do have speech problems that could be related to macroglossia or hearing loss.Advances in treating neonatal complications and premature infants in the last twenty years have significantly improved the true infant mortality rate associated with BWS. In a review of pregnancies that resulted in 304 children with BWS, no neonatal deaths were reported. This is compared to a previously reported mortality rate of 20%. The data from the former study was derived from a BWS registry, a database that may be slightly biased towards involving living children; however, death was not an exclusion criterion to join the registry. This suggests that while infants with BWS are likely to have a higher than normal infant mortality risk, it may not be as high as 20%.
Assisted reproductive technology
Assisted reproductive technology (ART) is a general term referring to methods used to achieve pregnancy by artificial or partially artificial means. According to the CDC, in general, ART procedures involve surgically removing eggs from a womans ovaries, combining them with sperm in the laboratory, and returning them to the womans body or donating them to another woman. ART has been associated with epigenetic syndromes, specifically BWS and Angelman syndrome. Three groups have shown an increased rate of ART conception in children with BWS. A retrospective case control study from Australia found a 1 in 4000 risk of BWS in their in-vitro population, several times higher than the general population. Another study found that children conceived by in vitro fertilisation (IVF) are three to four times more likely to develop the condition. No specific type of ART has been more closely associated with BWS. The mechanism by which ART produces this effect is still under investigation.
Epidemiology
Beckwith–Wiedemann syndrome has an estimated incidence of one in 13,700; about 300 children with BWS are born each year in the United States. The exact incidence of BWS is unknown because of the marked variability in the syndromes presentation and difficulties with diagnosis. The number of reported infants born with BWS is most likely low because many are born with BWS, but have clinical features that are less prominent and therefore missed. BWS has been documented in a variety of ethnic groups and occurs equally in males and females.Children conceived through In vitro fertilization have a three to fourfold increased chance of developing Beckwith–Wiedemann syndrome. It is thought that this is due to genes being turned on or off by the IVF procedures.
History
In the 1960s, Dr. John Bruce Beckwith, an American pathologist and Dr. Hans-Rudolf Wiedemann, a German pediatrician, independently reported cases of a proposed new syndrome. Originally termed EMG syndrome (for exomphalos, macroglossia, and gigantism), this syndrome over time became known as Beckwith–Wiedemann syndrome or Wiedemann Beckwith syndrome.
Originally, Dr. Hans-Rudolf Wiedemann (born 16 February 1915, Bremen, Germany, died 4 August 2006, Kiel) coined the term exomphalos-macroglossia-gigantism (EMG) syndrome to describe the combination of congenital abdominal wall defects as hernia (exomphalos), large tongues (macroglossia), and large bodies and/or long limbs (gigantism). Over time, this constellation was renamed Beckwith–Wiedemann syndrome following the autoptical observations of Prof. John Bruce Beckwith (born 18 September 1933, Spokane, Washington), who also observed a severe increase in the size of the adrenal glands in some of these patients.
See also
Perlman syndrome
References
Further reading
GeneReview/UW/NIH entry on Beckwith-Wiedemann syndrome
== External links == |
Dissociative disorder | Dissociative disorders (DD) are conditions that involve disruptions or breakdowns of memory, awareness, identity, or perception. People with dissociative disorders use dissociation as a defense mechanism, pathologically and involuntarily. The individual experiences these dissociations to protect themselves. Some dissociative disorders are triggered by psychological trauma, but depersonalization-derealization disorder may be preceded only by stress, psychoactive substances, or no identifiable trigger at all.The dissociative disorders listed in the American Psychiatric Associations DSM-5 are as follows:
Dissociative identity disorder (formerly multiple personality disorder): the alternation of two or more distinct personality states with impaired recall among personality states. In extreme cases, the host personality is unaware of the other, alternating personalities; however, the alternate personalities can be aware of all the existing personalities.
Dissociative amnesia (formerly psychogenic amnesia): the temporary loss of recall memory, specifically episodic memory, due to a traumatic or stressful event. It is considered the most common dissociative disorder amongst those documented. This disorder can occur abruptly or gradually and may last minutes to years depending on the severity of the trauma and the patient. Dissociative fugue was previously a separate category but is now treated as a specifier for dissociative amnesia.
Depersonalization-derealization disorder: periods of detachment from self or surrounding which may be experienced as "unreal" (lacking in control of or "outside" self) while retaining awareness that this is only a feeling and not a reality.
The old category of dissociative disorder not otherwise specified is now split into two: other specified dissociative disorder, and unspecified dissociative disorder. These categories are used for forms of pathological dissociation that do not fully meet the criteria of the other specified dissociative disorders; or if the correct category has not been determined; or the disorder is transient.The ICD11 lists dissociative disorders as:
Dissociative neurological symptom disorder
Dissociative amnesia
Dissociative amnesia with dissociative fugue
Trance disorder
Possession trance disorder
Dissociative identity disorder
Partial dissociative identity disorder
Depersonalization-derealization disorder
Cause and treatment
Dissociative identity disorder
Cause: Dissociative identity disorder is caused by ongoing childhood trauma that occurs before the ages of six to nine. People with dissociative identity disorder usually have close relatives who have also had similar experiences.Treatment: Long-term psychotherapy to improve the patients quality of life.
Dissociative amnesia
Cause: A way to cope with trauma.
Treatment: Psychotherapy (e.g. talk therapy) counseling or psychosocial therapy which involves talking about your disorder and related issues with a mental health provider. Psychotherapy often involves hypnosis (help you remember and work through the trauma); creative art therapy (using creative process to help a person who cannot express his or her thoughts); cognitive therapy (talk therapy to identify unhealthy and negative beliefs/behaviors); and medications (antidepressants, anti-anxiety medications, or sedatives). These medications help control the symptoms associated with the dissociative disorders, but there are no medications yet that specifically treat dissociative disorders. However, the medication pentothal can sometimes help to restore the memories. The length of an event of dissociative amnesia may be a few minutes or several years. If an episode is associated with a traumatic event, the amnesia may clear up when the person is removed from the traumatic situation. Dissociative fugue was a separate category but is now listed as a specifier for dissociative amnesia.
Depersonalization-derealization disorder
Cause: Dissociative disorders usually develop as a way to cope with trauma. The disorders most often form in children subjected to chronic physical, sexual or emotional abuse or, less frequently, a home environment that is otherwise frightening or highly unpredictable; however, this disorder can also acutely form due to severe traumas such as war or the death of a loved one.
Treatment: Same treatment as dissociative amnesia. An episode of depersonalization-derealization disorder can be as brief as a few seconds or continue for several years.Dissociative disorders, especially dissociative identity disorder (DID), while being the result of extraordinary abuse and trauma in childhood, it should not be attributed exotic status. DID would be better examined through a more holistic lens, taking into considering the social, cognitive, and neural components, and how they interact with one another.
Medications
There are no medications to treat dissociative disorders, however, drugs to treat anxiety and depression that may accompany the disorders can be given.
Diagnosis and prevalence
The lifetime prevalence of dissociative disorders varies from 10% in the general population to 46% in psychiatric inpatients. Diagnosis can be made with the help of structured clinical interviews such as the Dissociative Disorders Interview Schedule (DDIS) and the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D-R), and behavioral observation of dissociative signs during the interview. Additional information can be helpful in diagnosis, including the Dissociative Experiences Scale or other questionnaires, performance-based measures, records from doctors or academic records, and information from partners, parents, or friends. A dissociative disorder cannot be ruled out in a single session and it is common for patients diagnosed with a dissociative disorder to not have a previous dissociative disorder diagnosis due to a lack of clinician training. Some diagnostic tests have also been adapted or developed for use with children and adolescents such as the Adolescent Dissociative Experiences Scale, Childrens Version of the Response Evaluation Measure (REM-Y-71), Child Interview for Subjective Dissociative Experiences, Child Dissociative Checklist (CDC), Child Behavior Checklist (CBCL) Dissociation Subscale, and the Trauma Symptom Checklist for Children Dissociation Subscale.Dissociative disorders have been found to be quite prevalent in outpatient populations, as well as within low-income communities. One study found that in a population of poor inner-city outpatients, there was a 29% prevalence of dissociative disorders.There are problems with classification, diagnosis and therapeutic strategies of dissociative and conversion disorders which can be understood by the historic context of hysteria. Even current systems used to diagnose DD such as the DSM-IV and ICD-10 differ in the way the classification is determined. In most cases mental health professionals are still hesitant to diagnose patients with Dissociative Disorder, because before they are considered to be diagnosed with Dissociative Disorder these patients have more than likely been diagnosed with major depressive disorder, anxiety disorder, and most often post-traumatic stress disorder. It has been found from interviews with those who may be afflicted with dissociative disorders may be more effective at getting an accurate diagnosis than self-scoring assessments and scales.The prevalence of dissociative disorders is not completely understood due to the many difficulties in diagnosing dissociative disorders. Many of these difficulties stem from a misunderstanding of dissociative disorders, from an unfamiliarity diagnosis or symptoms to disbelief in some dissociative disorders entirely. Due to this it has been found that only 28% to 48% of people diagnosed with a dissociative disorder receive treatment for their mental health. Patients who are misdiagnosed are often those more likely to be hospitalised repeatedly, and lack of treatment can result in intensive outpatient treatment and higher rates of disability.An important concern in the diagnosis of dissociative disorders in forensic interviews is the possibility that the patient may be feigning symptoms in order to escape negative consequences. Young criminal offenders report much higher levels of dissociative disorders, such as amnesia. In one study it was found that 1% of young offenders reported complete amnesia for a violent crime, while 19% claimed partial amnesia. There have also been cases in which people with dissociative identity disorder provide conflicting testimonies in court, depending on the personality that is present.
The world-wide prevalence of dissociative disorders is not well understood due to different cultural beliefs surrounding human emotions and the human brain.
Children and adolescents
Dissociative disorders (DD) are widely believed to have roots in adverse childhood experiences including abuse and loss, but the symptoms often go unrecognized or are misdiagnosed in children and adolescents. However, a recent western Chinese study showed a increase in awareness of dissociative disorders present in children These studies show that DDs have an intricate relationship with the patients mental, physical and socio-cultural environments. This study suggested that dissociative disorders are more common in Western, or developing countries, however, some cases have been seen in both clinical and non-clinical Chinese populations. There are several reasons why recognizing symptoms of dissociation in children is challenging: it may be difficult for children to describe their internal experiences; caregivers may miss signals or attempt to conceal their own abusive or neglectful behaviors; symptoms can be subtle or fleeting; disturbances of memory, mood, or concentration associated with dissociation may be misinterpreted as symptoms of other disorders.Another resource, Beacon House, informs us of dissociative disorder in children, suggesting that it is a survival mechanism that often goes unnoticed in children that have been traumatised. Dr. Shoshanah Lyons suggests that traumatised children often continue to dissociate even though they might not be in any danger, and that they are often unaware that they are dissociating. In addition to developing diagnostic tests for children and adolescents (see above), a number of approaches have been developed to improve recognition and understanding of dissociation in children. Recent research has focused on clarifying the neurological basis of symptoms associated with dissociation by studying neurochemical, functional and structural brain abnormalities that can result from childhood trauma. Others in the field have argued that recognizing disorganized attachment (DA) in children can help alert clinicians to the possibility of dissociative disorders. In their 2008 article, Rebecca Seligman and Laurence Kirmayer suggest the existence of evidence of linkages between trauma experienced in childhood and the capacity for dissociation or depersonalisation. They also suggest that individuals who are able to utilise dissociative techniques are able to keep this as an extended strategy to cope with stressful situations.Clinicians and researchers stress the importance of using a developmental model to understand both symptoms and the future course of DDs. In other words, symptoms of dissociation may manifest differently at different stages of child and adolescent development and individuals may be more or less susceptible to developing dissociative symptoms at different ages. Further research into the manifestation of dissociative symptoms and vulnerability throughout development is needed. Related to this developmental approach, more research is required to establish whether a young patients recovery will remain stable over time.
Current debates and the DSM-5
A number of controversies surround DD in adults as well as children. First, there is ongoing debate surrounding the etiology of dissociative identity disorder (DID). The crux of this debate is if DID is the result of childhood trauma and disorganized attachment. A proposed view is that dissociation has a physiological basis, in that it involves automatically triggered mechanisms such as increased blood pressure and alertness, that would, as Lynn contends, imply its existence as a cross-species disorder. A second area of controversy surrounds the question of whether or not dissociation as a defense versus pathological dissociation are qualitatively or quantitatively different. Experiences and symptoms of dissociation can range from the more mundane to those associated with posttraumatic stress disorder (PTSD) or acute stress disorder (ASD) to dissociative disorders. Mirroring this complexity, the DSM-5 workgroup considered grouping dissociative disorders with other trauma/stress disorders, but instead decided to put them in the following chapter to emphasize the close relationship. The DSM-5 also introduced a dissociative subtype of PTSD.A 2012 review article supports the hypothesis that current or recent trauma may affect an individuals assessment of the more distant past, changing the experience of the past and resulting in dissociative states. However, experimental research in cognitive science continues to challenge claims concerning the validity of the dissociation construct, which is still based on Janetian notions of structural dissociation. Even the claimed etiological link between trauma/abuse and dissociation has been questioned. Links observed between trauma/abuse and DD are largely only present from a Western cultural context. For non-Western cultures dissociation "may constitute a "normal" psychological capacity". An alternative model proposes a perspective on dissociation based on a recently established link between a labile sleep–wake cycle and memory errors, cognitive failures, problems in attentional control, and difficulties in distinguishing fantasy from reality."Debates around DD also stem from Western versus non-Western lenses of viewing the disorder, and associated views of causes of DD. DID was initially believed to be specific to the West, until cross-cultural studies indicated its occurrence worldwide. Conversely, anthropologists have largely done little work on DD in the West relating to its perceptions of possession syndromes that would be present in non-Western societies. While dissociation has been viewed and catalogued by anthropologists differently in the West and non-Western societies, there are aspects of each that show DD has universal characteristics. For example, while shamanic and rituals of non-Western societies may hold dissociative aspects, this is not exclusive as many Christian sects, such as "possession by the Holy Ghost" share similar qualities to those of non-Western trances.
See also
Complex post-traumatic stress disorder
References
External links
Dissociative disorders—Mayo Clinic
Depersonalization Disorder—Cleveland Clinic
International Society for the Study of Trauma and Dissociation |
Contact dermatitis | Contact dermatitis is a type of acute or chronic inflammation of the skin caused by exposure to chemical or physical agents. Symptoms of contact dermatitis can include itchy or dry skin, a red rash, bumps, blisters, or swelling. These rashes are not contagious or life-threatening, but can be very uncomfortable.
Contact dermatitis results from either exposure to allergens (allergic contact dermatitis), or irritants (irritant contact dermatitis). Allergic contact dermatitis involves a delayed type of hypersensitivity and previous exposure to an allergen to produce a reaction. Irritant contact dermatitis is the most common type and represents 80% of all cases. It is caused by prolonged exposure to irritants, leading to direct injury of the epidermal cells of the skin, which activates an immune response, resulting in an inflammatory cutaneous reaction. Phototoxic dermatitis occurs when the allergen or irritant is activated by sunlight. Diagnosis of allergic contact dermatitis can often be supported by patch testing.
Epidemiology
Contact dermatitis constitutes 95% of all occupational skin disorders. There are few accurate statistics on the incidence and prevalence of contact dermatitis. The results of the few studies that have been undertaken cannot be compared because of methodological differences.
Signs and symptoms
Contact dermatitis is a localized rash or irritation of the skin caused by contact with a foreign substance. Only the superficial regions of the skin are affected in contact dermatitis. Inflammation of the affected tissue is present in the epidermis (the outermost layer of skin) and the outer dermis (the layer beneath the epidermis).Contact dermatitis results in large, burning, and itchy rashes. These can take anywhere from several days to weeks to heal. This differentiates it from contact urticaria (hives), in which a rash appears within minutes of exposure and then fades away within minutes to hours. Even after days, contact dermatitis fades only if the skin no longer comes in contact with the allergen or irritant. Chronic contact dermatitis can develop when the removal of the offending agent no longer provides expected relief.
Irritant dermatitis is usually confined to the area where the trigger actually touched the skin, whereas allergic dermatitis may be more widespread on the skin. Irritant dermatitis usually found on hands whereas exposed areas of skin. Symptoms of both forms include the following:
Red rash. This is the usual reaction. The rash appears immediately in irritant contact dermatitis; in allergic contact dermatitis, the rash sometimes does not appear until 24–72 hours after exposure to the allergen.
Blisters or wheals. Blisters, wheals (welts), and urticaria (hives) often form in a pattern where skin was directly exposed to the allergen or irritant.
Itchy, burning skin. Irritant contact dermatitis tends to be more painful than itchy, while allergic contact dermatitis often itches.
The surface appearance of skin is dry and fissured in the irritant contact dermatitis whereas vesicles and bullae are seen in allergic contact dermatitis.
lichenified lesions.While either form of contact dermatitis can affect any part of the body, irritant contact dermatitis often affects the hands, which have been exposed by resting in or dipping into a container (sink, pail, tub, swimming pools with high chlorine) containing the irritant.
Causes
The percentage of cases attributable to occupational contact dermatitis varies substantially depending on the industries that predominate, the employment that people have, the risks to which they are exposed, the centers that record cases, and variances in defining and confirming diagnoses.Common causes of allergic contact dermatitis include: nickel allergy, 14K or 18K gold, Balsam of Peru (Myroxylon pereirae), and chromium. In the Americas they include the oily coating from plants of the genus Toxicodendron: poison ivy, poison oak, and poison sumac. Millions of cases occur each year in North America alone. The alkyl resorcinols in Grevillea banksii and Grevillea Robyn Gordon are responsible for contact dermatitis. Bilobol, another alkyl resorcinol found in Ginkgo biloba fruits, is also a strong skin irritant.Common causes of irritant contact dermatitis include solvents, metalworking fluids, latex, kerosene, ethylene oxide, paper, especially papers coated with chemicals and printing inks, certain foods and drink, food flavorings and spices, perfume, surfactants in topical medications and cosmetics, alkalis, low humidity from air conditioning, and many plants. Other common causes of irritant contact dermatitis are harsh alkaline soaps, detergents, and cleaning products.There are three types of contact dermatitis: irritant contact dermatitis; allergic contact dermatitis; and photocontact dermatitis. Photocontact dermatitis is divided into two categories: phototoxic and photoallergic.
Irritant contact dermatitis
The irritants direct cytotoxic impact on epidermal keratinocytes causes Irritant contact dermatitis. This disrupts the skin barrier and activates the innate immune system. Keratinocytes in the epidermis can be actually affected by irritants. It is a complicated reaction that is influenced by genetic and environmental elements, both of which have a role in the pathogenesis of the disease. It can be seen in both occupational and non-occupational environments but its more common in the occupations dealing in low humidity conditions.
Irritant contact dermatitis (ICD) can be divided into forms caused by chemical irritants, and those caused by physical irritants. Common chemical irritants implicated include: solvents (alcohol, xylene, turpentine, esters, acetone, ketones, and others); metalworking fluids (neat oils, water-based metalworking fluids with surfactants); latex; kerosene; ethylene oxide; surfactants in topical medications and cosmetics (sodium lauryl sulfate); and alkalis (drain cleaners, strong soap with lye residues).
Physical irritant contact dermatitis may most commonly be caused by low humidity from air conditioning. Also, many plants directly irritate the skin.
Allergic contact dermatitis
Allergic contact dermatitis (ACD) is accepted to be the most prevalent form of immunotoxicity found in humans, and is a common occupational and environmental health problem. By its allergic nature, this form of contact dermatitis is a hypersensitive reaction that is atypical within the population. The development of the disease occurs in two phases, which are induction and elicitation. The process of skin sensitization begins when a susceptible subject is exposed to the allergen in sufficient concentration to elicit the required cutaneous immune response. This causes sensitization and when exposure to the same allergen at a later time at the same or different skin site leads to a secondary immune response at the point of contact. The mechanisms by which this reaction occurs are complex, with many levels of fine control. Their immunology centres on the interaction of immunoregulatory cytokines and discrete subpopulations of T lymphocytes.
Allergens include nickel, gold, Balsam of Peru (Myroxylon pereirae), chromium, and the oily coating from plants of the genus Toxicodendron, such as poison ivy, poison oak, and poison sumac. Acrylates, rubber chemicals, emulsifiers and dyes, epoxy resin chemicals are just several of the substances that might induce Allergic Contact Dermatitis. Much of the allergic contact dermatitis that arises is caused by occupational exposure. Non-occupational exposure to allergens in medicaments, clothing, cosmetics, and plants are also a significant cause of allergic contact dermatitis.
Photocontact dermatitis
Sometimes termed "photoaggravated", and divided into two categories, phototoxic and photoallergic, PCD is the eczematous condition which is triggered by an interaction between an otherwise unharmful or less harmful substance on the skin and ultraviolet light (320–400 nm UVA) (ESCD 2006), therefore manifesting itself only in regions where the affected person has been exposed to such rays.
Without the presence of these rays, the photosensitiser is not harmful. For this reason, this form of contact dermatitis is usually associated only with areas of skin that are left uncovered by clothing, and it can be soundly defeated by avoiding exposure to sunlight. The mechanism of action varies from toxin to toxin, but is usually due to the production of a photoproduct. Toxins which are associated with PCD include the psoralens. Psoralens are in fact used therapeutically for the treatment of psoriasis, eczema, and vitiligo.
Photocontact dermatitis is another condition in which the distinction between forms of contact dermatitis is not clear-cut. Immunological mechanisms can also play a part, causing a response similar to ACD.
Diagnosis
Since contact dermatitis relies on an irritant or an allergen to initiate the reaction, it is important for the patient to identify the responsible agent and avoid it. This can be accomplished by having patch tests, one of various methods commonly known as allergy testing. The patch tests were based on the concept of a type IV hypersensitivity reaction where there is exposure of allergens to skin and checking for the development of contact dermatitis in that area. This test involves the application of suspected irritant to a part of the skin and cover it with impermeable material and attached to the skin with the help of adhesive plaster. The top three allergens found in patch tests from 2005 to 2006 were: nickel sulfate (19.0%), Myroxylon pereirae (Balsam of Peru, 11.9%), and fragrance mix I (11.5%).The patient must know where the irritant or allergen is found to be able to avoid it. It is important to also note that chemicals sometimes have several different names, and do not always appear on labels.The distinction between the various types of contact dermatitis is based on a number of factors. The morphology of the tissues, the histology, and immunologic findings are all used in diagnosis of the form of the condition. However, as suggested previously, there is some confusion in the distinction of the different forms of contact dermatitis. Using histology on its own is insufficient, as these findings have been acknowledged not to distinguish, and even positive patch testing does not rule out the existence of an irritant form of dermatitis as well as an immunological one.
Prevention
In an industrial setting the employer has a duty of care to its worker to provide the correct level of safety equipment to mitigate exposure to harmful irritants. This can take the form of protective clothing, gloves, or barrier cream, depending on the working environment. It is impossible to eliminate the complete exposure to harmful irritants but can be avoided using the multidimensional approach. The multidimensional approach includes eight basic elements to follow. They are:
Identification of possible cutaneous irritants and allergens
To avoid skin exposure, use appropriate control measures or chemical substitutes.
Personal protection can be achieved by the use of protective clothes or barrier creams.
Maintenance of personal and environmental hygiene
Use of harmful irritants in the workplace should be regulated
Efforts to raise knowledge of potential allergies and irritants through education
promoting safe working conditions and practices
health screenings before and after employment and on a regular basis Topical antibiotics should not be used to prevent infection in wounds after surgery. When they are used, it is inappropriate, and the person recovering from surgery is at significantly increased risk of developing contact dermatitis.
Treatment
Self-care
If blistering develops, cold moist compresses applied for 30 minutes, 3 times a day can offer relief.
Calamine lotion may relieve itching.
Oral antihistamines such as diphenhydramine (Benadryl, Ben-Allergin) can relieve itching.
Avoid scratching.
Immediately after exposure to a known allergen or irritant, wash with soap and cool water to remove or inactivate most of the offending substance.
For mild cases that cover a relatively small area, hydrocortisone cream in nonprescription strength may be sufficient.
Weak acid solutions (lemon juice, vinegar) can be used to counteract the effects of dermatitis contracted by exposure to basic irritants.
A barrier cream, such as those containing zinc oxide (e.g., Desitin, etc.), may help protect the skin and retain moisture.
Medical care
If the rash does not improve or continues to spread after 2–3 of days of self-care, or if the itching and/or pain is severe, the patient should contact a dermatologist or other physician. Medical treatment usually consists of lotions, creams, or oral medications.
Corticosteroids. A corticosteroid medication like hydrocortisone may be prescribed to combat inflammation in a localized area. It may be applied to the skin as a cream or ointment. If the reaction covers a relatively large portion of the skin or is severe, a corticosteroid in pill or injection form may be prescribed.In severe cases, a stronger medicine like halobetasol may be prescribed by a dermatologist.
Antihistamines. Prescription antihistamines may be given if non-prescription strengths are inadequate.
See also
Urushiol-induced contact dermatitis
Nickel allergy
Eczema
References
External links
eMedicine Health article on contact dermatitis |
Normal tension glaucoma | Normal tension glaucoma (NTG) is an eye disease, a neuropathy of the optic nerve, that shows all the characteristics of primary open angle glaucoma except one: the elevated intraocular pressure (IOP) - the classic hallmark of glaucoma - is missing. Normal tension glaucoma is in many cases closely associated with general issues of blood circulation and of organ perfusion like arterial hypotension, metabolic syndrome, and Flammer syndrome.
Clinical relevance
Over many years, glaucoma has been defined by an intraocular pressure of more than 20 mm Hg. Incompatible with this (now obsolete) definition of glaucoma was the ever larger number of cases that have been reported in medical literature in the 1980s and 1990s who had the typical signs of glaucomatous damage, like optic nerve head excavation and thinning of the retinal nerve fiber layer, while these patients had an IOP that would generally have been regarded as "normal". It is now widely estimated that a larger percentage of patients with primary open-angle glaucoma (POAG) are suffering from normal tension glaucoma. Among Americans of Japanese descent, for instance, the prevalence of NTG is about four times as high as the prevalence of the "classical glaucoma" with an IOP of 22 mm Hg and higher. The pillar of the current understanding of normal tension glaucoma is a reduced IOP tolerance of the retinal ganglion cells and the cells in the optic nerve head - an IOP of, for example, 17 or 19 mm Hg that would not affect a healthy eye leads to damage in the eye of an NTG patient.
Risk factors
In many patients, normal tension glaucoma is common in individuals with a generalized reduced perfusion of organs and certain body tissues. A low blood pressure - whether consistently low or with sudden pressure drops - is associated with NTG as are conditions like Flammer syndrome and obstructive sleep apnea. Flammer syndrome has been attributed to increase the likelihood of ganglion cell damage in normal tension glaucoma patients with disc hemorrhages as a characteristic clinical sign. Besides race (Japanese) and low blood pressure, the female gender is also a risk factor.
Diagnosis
While tonometry, the measuring of IOP and thus a classical instrument in the diagnosis of glaucoma, is not helpful, ophthalmoscopy leads to the diagnosis by showing typical glaucomatous damage, primarily at the optic nerve head, in the absence of elevated IOP. While the excavation of the optic nerve head and the thinning of its rim appear in all kinds of glaucoma (with high tension and with normal tension, in Primary open angle glaucoma (POAG) and in secondary glaucoma), small hemorrhages close to the optic disc have been identified as a characteristic clinical sign of normal tension glaucoma. Visual field is very important to detect NTG. It shows a defect that typically appears deeper, steeper and closer to fixation comparing to patients with POAG.
Since NTG is closely linked to vascular irregularities, a medical check-up by a general practitioner or a specialist in internal medicine is widely recommended in cases of newly diagnosed normal tension glaucoma. An examination that is considered to be of particular importance is a 24-hour monitoring of the blood pressure. NTG patients tend to suffer "dips", sudden and unnoticed drops in blood pressure during sleep.
Treatment
Without treatment, NTG leads to progressive visual field loss and in the last consequence to blindness. The mainstay of conventional glaucoma therapy, reducing IOP by pressure-lowering eye drops or by surgery, is applied in cases of NTG as well. The rationale: the lower the IOP, the less the risk of ganglion cell loss and thus in the long run of visual function. The appearance of disc hemorrhages is always a warning sign that therapeutic approaches are not successful - the small bleedings, usually described as flame-shaped, almost always indicate a progression of the disease.
Besides this classical glaucoma therapy, the vascular component that exists in the majority of NTG patients has to be managed as well. Dips in blood pressure or a generally low blood pressure have to be prevented - which is a rather uncommon approach in modern medicine where high blood pressure is always seen as an immense clinical challenge, affecting large segments of the population. In patients with systemic hypertension under therapy, the blood pressure should not be lowered too rigorously. NTG might be the only severe (= sight-threatening) disease caused in numerous cases by a too low blood pressure. Both magnesium and low dose calcium channel blockers have been employed in the treatment of some NTG patients. There are therapeutic approaches to underlying conditions like Flammer syndrome. A change in nutrition like the intake of sodium-rich foods has been tried as has the oral administration of low-dosed steroids. Lifestyle interventions are recommended in patients with Flammer syndrome like avoidance of fasting and certain stimuli like a cold environment and stress.
== References == |
Angiostrongylus cantonensis | Angiostrongylus cantonensis is a parasitic nematode (roundworm) that causes angiostrongyliasis, the most common cause of eosinophilic meningitis in Southeast Asia and the Pacific Basin. The nematode commonly resides in the pulmonary arteries of rats, giving it the common name rat lungworm. Snails are the primary intermediate hosts, where larvae develop until they are infectious.
Humans are incidental hosts of this roundworm, and may become infected through ingestion of larvae in raw or undercooked snails or other vectors, or from contaminated water and vegetables. The larvae are then transported via the blood to the central nervous system, where they are the most common cause of eosinophilic meningitis, a serious condition that can lead to death or permanent brain and nerve damage. Angiostrongyliasis is an infection of increasing public health importance, as globalization contributes to the geographic spread of the disease.
History
First described by the renowned Chinese parasitologist Hsin-Tao Chen (1904–1977) in 1935, after examining Cantonese rat specimens, the nematode Angiostrongylus cantonensis was identified in the cerebrospinal fluid of a patient with eosinophilic meningitis by Nomura and Lim in Taiwan in 1944. They noted that raw food eaten by the patient may have been contaminated by rats. In 1955, Mackerass and Sanders identified the lifecycle of the worm in rats, defining snails and slugs as the intermediate hosts, and noting the path of transmission through the blood, brain, and lungs in rats.
Infectious agent
A. cantonensis is a helminth of the phylum Nematoda, order Strongylida, and superfamily Metastrongyloidea. Nematodes are roundworms characterized by a tough outer cuticle, unsegmented bodies, and a fully developed gastrointestinal tract. The order Strongylida includes hookworms and lungworms. Metastrongyloidea are characterized as 2-cm-long, slender, threadlike worms that reside in the lungs of the definitive host. Angiostrongylus costaricensis is a closely related worm that causes intestinal angiostrongyliasis in Central and South America.
Epidemiology and pathogenesis
Following World War II, A. cantonensis spread throughout Southeast Asia and Western Pacific Islands, including Australia, Melanesia, Micronesia, and Polynesia. Cases were soon reported in New Caledonia, the Philippines, Rarotonga, Saipan, Sumatra, Taiwan, and Tahiti. In the 1960s, even more cases were reported from the region from locations such as Cambodia, Guam, Hawaii, Java, Thailand, Sarawak, Vietnam, and Vanuatu.In 1961, an epidemiological study of eosinophilic meningitis in humans was conducted by Rosen, Laigret, and Bories, who hypothesized that the parasite causing these infections was carried by fish. However, Alicata noted that raw fish was consumed by large numbers of people in Hawaii without apparent consequences, and patients presenting with meningitis symptoms had a history of eating raw snails or prawns in the weeks before presenting with symptoms. This observation, along with epidemiology and autopsy of infected brains, confirmed A. cantonensis infection in humans as the cause of the majority of eosinophilic meningitis cases in Southeast Asia and the Pacific Islands.Since then, cases of A. cantonensis infestations have appeared in American Samoa, Australia, Hong Kong, Bombay, Fiji, Hawaii, Honshu, India, Kyushu, New Britain, Okinawa, Ryukyu Islands, Western Samoa, and most recently mainland China. Other sporadic occurrences of the parasite in its rat hosts have been reported in Cuba, Egypt, Louisiana, Madagascar, Nigeria, and Puerto Rico.In 2013, A. cantonensis was confirmed present in Florida, USA, where its range and prevalence are expanding. In 2018, a case was found in a New Yorker who had visited Hawaii.In recent years, the parasite has been shown to be proliferating at an alarming rate due to modern food-consumption trends and global transportation of food products. Scientists are calling for a more thorough study of the epidemiology of A. cantonensis, stricter food-safety policies, and the increase of knowledge on how to properly consume products commonly infested by the parasite, such as snails and slugs that act as intermediate hosts or those that act as paratenic hosts, such as fish, frogs, or freshwater prawns. Ingestion of food items that can be contaminated by the mucus excretions of intermediate or paratenic hosts, such as snails and slugs, or by the feces of rats that act as definitive hosts, can lead to infection of A. cantonensis. The most common route of infection of A. cantonesis in humans is by ingestion of either intermediate or paratenic hosts of the larvae. Unwashed fruits and vegetables, especially romaine lettuce, can be contaminated with snail and slug mucus or can result in accidental ingestion of these intermediate and paratenic hosts. These items need to be properly washed and handled to prevent accidental ingestion of A. cantonensis larvae or the larvae-containing hosts. The best mechanism of prevention of A. cantonesis outbreak is to institute an aggressive control of snail and slug population, proper cooking of intermediate and paratenic hosts such as fish, freshwater prawn, frogs, molluscs, and snails along with proper food-handling techniques. The common prevention techniques for diarrheal illness are very effective in preventing A. cantonensis infection. Not much is known about why it targets the brain in humans, but a chemically induced chemotaxis has been implicated recently. Acetylcholine has been previously reported to enhance motility of this worm via nicotinic acetylcholine receptors. Experimental assays in animal models are needed to validate a chemically induced chemotaxis by use of anticholinergic drugs to prevent cerebral infection following infections by A. cantonesis.
Hosts
Intermediate hosts of larvae of for A. cantonensis include:
Land snails: Thelidomus aspera from Jamaica, Pleurodonte sp. from Jamaica, Sagda sp. from Jamaica, Poteria sp. from Jamaica, Achatina fulica, Satsuma mercatoria, Acusta despecta, Bradybaena brevispira, Bradybaena circulus Bradybaena ravida, Bradybaena similaris, Plectotropis appanata and Parmarion martensi from Okinawa and Hawaii, Camaena cicatricosa, Trichochloritis rufopila, Trichochloritis hungerfordianus and Cyclophorus spp.
Freshwater snails: Pila spp., Pomacea canaliculata, Cipangopaludina chinensis, Bellamya aeruginosa and Bellamya quadrata
Slugs: Limax maximus, Limax flavus Deroceras laeve, Deroceras reticulatum, Laevicaulis alte, Sarasinula plebeia, Vaginulus yuxjsjs, Lehmannia valentiana, Phiolomycus bilineatus, Macrochlamys loana, Meghimatium bilineatum and probably other species of slugs.Definitive hosts of A. cantonensis include wild rodents, especially the brown rat (Rattus norvegicus) and the black rat (Rattus rattus).Paratenic hosts of A. cantonensis include the predatory land flatworm Platydemus manokwari and the amphibians, Bufo asiaticus, Rana catesbeiana, Rhacophorus leucomystax and Rana limnocharis.In 2004, a captive yellow-tailed black cockatoo (Calyptorhynchus funereus) and two free-living tawny frogmouths (Podargus strigoides) suffering neurological symptoms were shown to have the parasite. They were the first avian hosts discovered for the organism. In 2018, in Mallorca two North African hedgehogs with signs of acute neurological disease were found to have A. cantonensis in their brains, one of them with a gravid female. It was the first report of hedgehogs as hosts of Angiostrongylus.The Hawaiʻi Dept. of Health states that fresh water opihi can carry the parasite, as well as other aquatic organisms such as prawns, frogs, and water monitor lizards. House pets may interact with A. cantonensis-carrying animals yet not well studied. Cats are known to carry and spread feline lungworm in rat and snail interactions.
Pathogenesis of human angiostrongylosis
The presence of parasitic worms burrowed in the neural tissue of the human central nervous system (CNS) causes complications. All of the following result in damage to the CNS:
Direct mechanical damage to neural tissue from the worms motion
Toxic byproducts such as nitrogenous waste
Antigens released by dead and living parasites
Eosinophilic meningitis
Although the clinical disease caused by Angiostrongylus invasion into the CNS is commonly referred to as "eosinophilic meningitis", the actual pathophysiology is of a meningoencephalitis with invasion not just of the meninges, or superficial lining of the brain, but also deeper brain tissue. Initial invasion through the lining of the brain, the meninges, may cause a typical inflammation of the meninges and a classic meningitis picture of headache, stiff neck, and often fever. The parasites subsequently invade deeper into the brain tissue, causing specific localizing neurological symptoms depending on where in the brain parenchyma they migrate. Neurologic findings and symptoms wax and wane as initial damage is done by the physical in-migration of the worms and secondary damage is done by the inflammatory response to the presence of dead and dying worms. This inflammation can lead in the short term to paralysis, bladder dysfunction, visual disturbance, and coma and in the long term to permanent nerve damage, mental retardation, nerve damage, permanent brain damage, or death.Eosinophilic meningitis is commonly defined by the increased number of eosinophils in the cerebrospinal fluid (CSF). In most cases, eosinophil levels rise to 10 or more eosinophils per μl in the CSF, accounting for at least 10% of the total CSF leukocyte (white blood cell) count. The chemical analysis of the CSF typically resembles the findings in "aseptic meningitis" with slightly elevated protein levels, normal glucose levels, and negative bacterial cultures. Presence of a significantly decreased glucose on CSF analysis is an indicator of severe meningoencephalitis and may indicate a poor medical outcome. Initial CSF analysis early in the disease process may occasionally show no increase of eosinophils, only to have classical increases in eosinophils in subsequent CSF analysis. Caution should be advised in using eosinophilic meningitis as the only criterion for diagnosing angiostrongylus infestation in someone with classic symptoms, as the disease evolves with the migration of the worms into the CNS.Eosinophils are specialized white blood cells of the granulocytic cell line, which contain granules in their cytoplasm. These granules contain proteins that are toxic to parasites. When these granules degranulate, or break down, chemicals are released that combat parasites such as A. cantonensis. Eosinophils, which are located throughout the body, are guided to sites of inflammation by chemokines when the body is infested with parasites such as A. cantonensis. Once at the site of inflammation, type 2 cytokines are released from helper T cells, which communicate with the eosinophils, signaling them to activate. Once activated, eosinophils can begin the process of degranulation, releasing their toxic proteins in the fight against the foreign parasite.
Clinical signs and symptoms
According to a group case study, the most common symptoms in mild eosinophilic meningitis tend to be headache (with 100% of people in the study suffering from this symptom), photophobia or visual disturbance (92%), neck stiffness (83%), fatigue (83%), hyperesthesias (75%), vomiting (67%), and paresthesias (50%). Incubation period is often 3 weeks, but can be 3–36 days and even 80 days.Possible clinical signs and symptoms of mild and severe eosinophilic meningitis are:
Fever is often minor or absent, but the presence of high fever suggests severe disease.
Headaches are progressive and severe, a bitemporal character in the frontal or occipital lobe.
Meningismus - neck stiffness
Photophobia - sensitivity to light
Muscle weakness and fatigue
Nausea with or without vomiting
Paresthesias - tingling, prickling, or numbing of skin, may last for several weeks or months
Hyperesthesia - severe sensitivity to touch; may last for several weeks or months
Radiculitis - pain irradiated along certain areas of skin
Bladder dysfunction with urinary retention
Constipation
Brudzińskis sign
Vertigo
Blindness
Paralysis localized to one area; e.g. paralysis of extraocular muscles and facial palsy
General paralysis (flaccid) often ascending in nature starting with the feet and progressing upwards to involve the entire body
Coma
Death
Treatment
The severity and clinical course of Angiostrongylus disease depends significantly on the ingested load of third-stage larvae, creating great variability from case to case, making clinical trials difficult to design, and effectiveness of treatments difficult to discern. Typical conservative medical management including analgesics and sedatives provide minimal relief for the headaches and hyperesthesias. Removing cerebrospinal fluid at regular 3- to 7-day intervals is the only proven method of significantly reducing intracranial pressure and can be used for symptomatic treatment of headaches. This process may be repeated until improvement is shown. There is growing evidence of moderate quality that suggests corticosteroid therapy using prednisolone or dexamethasone has beneficial effect in treating the CNS symptoms related to A. cantonensis infections. Although early research did not show treatment with antihelminthic agents (parasite-killing drugs) such as thiobendazole or albendazole effective in improving the clinical course of the illness, a number of recent studies from Thailand and China show that the combination of glucocorticoids and antihelminthics is safe and decreases the duration of headaches and the number of patients who had significant headache. Although the addition of antihelminthic agents for management of A. cantonensis infection has a theoretic risk of precipitating a neurologic crisis by releasing an overwhelming load of antigens through simultaneous death of the larvae, no study has shown this to exist in the clinical setting. Additionally, the failure to kill parasites before they attempt to migrate out of the CNS increases the risk of mechanical damage by migrating larvae. Although combination therapy using albendazole and prednisolone has no significant advantage compared to treatment using prednisolone alone in mild cases, the treatment with antihelminthics is demonstrably safe and may have significant benefit for patients with high parasite loads at risk for permanent disability or death.
Diagnosis
The diagnosis of disease caused by A. cantonensis infestation is often difficult and relies heavily on the history of a likely ingestion of a commonly infested host and the presence of typical features of the disease. The presumptive diagnosis is particularly strong when eosinophilic meningoencephalitis can be confirmed. The diagnosis of eosinophilic meningitis can be arrived at through detection of elevated cranial pressure and increased numbers of eosinophils. The diagnosis of the cause of eosinophilic meningitis and the presence of A. cantonensis is remarkably more difficult. A spinal tap, or a sample of CSF, must be taken to search for A. cantonensis worms or larvae. A. cantonensis is undetectable in the CSF of more than half of the infected individuals. Current methods of detecting specific antigens associated with A. cantonensis are also unreliable. Consequently, alternative approaches to detect antigen-antibody reactions are being explored, such as immuno-PCR. A rapid dot-blot ELISA test is also available for quick, effective, and economical on-site diagnosis of A. cantonensis.
References
External links
"Angiostrongylus". CDC.gov. Centers for Disease Control and Prevention. 2015-12-28. Retrieved 2017-04-04.
"DPDx - Angiostrongyliasis". CDC. 2016-10-17. Retrieved 2017-04-04. Tabs for Parasite Biology, Image Gallery, Laboratory Diagnosis, and Treatment Information.
Angiostrongylus+cantonensis at the US National Library of Medicine Medical Subject Headings (MeSH)
Sydney Morning Herald story of human infection, Example of Angiostrongylus cantonensis human infection: Hard to swallow: slug-eating dare causes rare disease
Angiostronglyus cantonensis on the UF / IFAS Featured Creatures website. |
Radial tunnel syndrome | Radial tunnel syndrome (RTS) is caused by increased pressure on the radial nerve as it travels from the upper arm (the brachial plexus) to the hand and wrist.
Symptoms and signs
Radial tunnel syndrome causes posterolateral elbow pain that is similar to tennis elbow and may sometimes occur in conjunction with that condition. Patients may typically have weakness of extension at the wrist and third digit. The pain is often reproduced upon resisted supination of the forearm, and pain at the radial tunnel on resisted hyperextension of the wrist.
Cause
The theory is that the radial nerve becomes irritated and/or inflamed from friction caused by compression by muscles in the forearm.Some speculate that radial tunnel syndrome is a type of repetitive strain injury (RSI), but there is no detectable pathophysiology and even the existence of this disorder is questioned.The term "radial tunnel syndrome" is used for compression of the posterior interosseous nerve, a division of the radial nerve, at the lateral intermuscular septum of arm, while "supinator syndrome" is used for compression at the arcade of Frohse.The "radial tunnel" is the region from the humeroradial joint past the proximal origin of the supinator muscle. Some scientists believe the radial tunnel extends as far as the distal border of the supinator. The radial nerve is commonly compressed within a 5 cm region near the elbow, but it can be compressed anywhere along the forearm if the syndrome is caused by injury (e.g. a fracture that puts pressure on the radial nerve). The radial nerve provides sensation to the skin of posterior arm, posterior and lateral forearm and wrist, and the joints of the elbow, wrist and hand. The nerve also provides sensory branches that travel to the periosteum of the lateral epicondyle, the anterior radiohumeral joint, and the annular ligament. It provides motor function through innervation to most extensor muscles of the posterior arm and forearm. Therefore, it is extremely important in upper body extremity movement and can cause significant pain to patients presenting with radial tunnel syndrome. Unlike carpal tunnel syndrome, radial tunnel syndrome does not present tingling or numbness, since the posterior interosseous nerve mainly affects motor function.This problem is often caused by: bone tumors, injury (specifically fractures of the forearm), noncancerous fatty tumors (lipomas), and inflammation of surrounding tissue.
Diagnosis
The diagnosis is based on symptoms and signs alone and objective testing is expected to be normal. This syndrome may be clinically tested by flexing the patients long finger while the patient extends the wrist and fingers. Pain is a positive finding.
The chief complaint of this disease is usually pain in the dorsal aspect of the upper forearm, and any weakness described is secondary to the pain. Tenderness to palpation occurs over the area of the radial neck. Also, the disease can be diagnosed by a positive "middle finger test", where resisted middle finger extension produces pain. Radiographic evaluation of the elbow should be performed to rule out other diagnoses.
Treatment
Non-surgical treatment of radial tunnel syndrome includes rest, NSAID, therapy with modalities, work modification, ergonomic modification, injection if associated with lateral epicondylitis.Patients whose conditions are more adapted to surgical intervention are those who do not respond to prolonged conservative treatment. The patient must have pain with resisted supination, positive middle finger test, positive electrodiagnostic findings, and pain relief after anesthetic injection into the radial tunnel. Based on 2002 data, surgical decompression leads to 60–70% good or excellent results.
See also
Golfers elbow
Repetitive strain injury
Tennis elbow
References
Further reading
Books
Rind, Libi; Pobre, Thomas; Weiss, Frederick; Magyar, Yasha; Ruotolo, Charles; Aldad, Tamir; Mahboubian, Shahab; Knijnikov, Alexander; Asheld, Wilbur J. (2010). "Radial tunnel syndrome and supinator syndrome". In Weiss, Lyn D.; Weiss, Jay M.; Pobre, Thomas (eds.). Oxford American Handbook of Physical Medicine & Rehabilitation. Oxford University Press. pp. 96–7. ISBN 978-0-19-536777-5.
Wertsch, Jacqueline J.; Hoch, Anne Zeni (2009). "Radial Tunnel Syndrome". In Akuthota, Venu; Herring, Stanley A. (eds.). Nerve and Vascular Injuries in Sports Medicine. Berlin: Springer. pp. 79–80. ISBN 978-0-387-76599-0.
Russell, Stephen M. (2006). "Radial Tunnel Syndrome". Examination of peripheral nerve injuries: an anatomical approach. Stuttgart: Thieme. p. 62. ISBN 978-3-13-143071-7.
Saladin, Kenneth S. (2012). Anatomy & Physiology: The Unity of Form and Function. McGraw Hill. p. 496. ISBN 978-0-07-337825-1.
Journals
Dickerman, Rob D.; Stevens, Qualls E. J.; Cohen, Anders J.; Jaikumar, S. (2002). "Radial tunnel syndrome in an elite power athlete: a case of direct compressive neuropathy". Journal of the Peripheral Nervous System. 7 (4): 229–32. doi:10.1046/j.1529-8027.2002.02030.x. PMID 12477169.
Huisstede, Bionka; Miedema, Harald S.; van Opstal, Twan; de Ronde, Manon T.; Verhaar, Jan A.; Koes, Bart W. (2008). "Interventions for Treating the Radial Tunnel Syndrome: A Systematic Review of Observational Studies". The Journal of Hand Surgery. 33 (1): 72–8. doi:10.1016/j.jhsa.2007.10.001. PMID 18261668.
Henry, Mark; Stutz, Christopher (2006). "A Unified Approach to Radial Tunnel Syndrome and Lateral Tendinosis". Techniques in Hand and Upper Extremity Surgery. 10 (4): 200–5. doi:10.1097/01.bth.0000231580.32406.71. PMID 17159475. S2CID 9709553.
Cleary, C (2006). "Management of Radial Tunnel Syndrome: A Therapists Clinical Perspective". Journal of Hand Therapy. 19 (2): 186–91. doi:10.1197/j.jht.2006.02.020. PMID 16713866.
Sarris, Ioannis K.; Papadimitriou, Nikolaos G.; Sotereanos, Dean G. (2002). "Radial Tunnel Syndrome". Techniques in Hand and Upper Extremity Surgery. 6 (4): 209–12. doi:10.1097/00130911-200212000-00010. PMID 16520604.
Smola, C. (2004). "Zur Problematik des algetischen Supinatorsyndroms oder Wo hört der Tennisarm auf und wo fängt das Supinatorsyndrom an?" [About the problem of radial tunnel syndrome or where does the tennis elbow end and where does the radial tunnel syndrome begin?]. Handchirurgie, Mikrochirurgie, Plastische Chirurgie (in German). 36 (4): 241–5. doi:10.1055/s-2004-817947. PMID 15368151.
Loh, YC; Lam, WL; Stanley, JK; Soames, RW (2004). "A new clinical test for radial tunnel syndrome—the Rule-of-Nine test: A cadaveric study" (PDF). Journal of Orthopaedic Surgery. 12 (1): 83–6. doi:10.1177/230949900401200115. PMID 15237127. S2CID 14049155.
Rosenbaum, Richard (1999). "Disputed radial tunnel syndrome". Muscle & Nerve. 22 (7): 960–7. doi:10.1002/(SICI)1097-4598(199907)22:7<960::AID-MUS26>3.0.CO;2-C. PMID 10398221.
Portilla Molina, A. E.; Bour, C.; Oberlin, C.; Nzeusseu, A.; Vanwijck, R. (1998). "The posterior interosseous nerve and the radial tunnel syndrome: an anatomical study". International Orthopaedics. 22 (2): 102–6. doi:10.1007/s002640050218. PMC 3619716. PMID 9651775.
Jebson, Peter J. L.; Engber, William D. (1997). "Radial tunnel syndrome: Long-term results of surgical decompression". The Journal of Hand Surgery. 22 (5): 889–96. doi:10.1016/S0363-5023(97)80086-X. PMID 9330150.
Sarris, Ioannis K.; Papadimitriou, Nikolaos G.; Sotereanos, Dean G. (2002). "Radial Tunnel Syndrome". Techniques in Hand and Upper Extremity Surgery. 6 (4): 209–212. doi:10.1097/00130911-200212000-00010. PMID 16520604.
== External links == |
Perifolliculitis | Perifolliculitis is the presence of inflammatory cells in the skin around the hair follicles. It is often found accompanying folliculitis, or inflammation of the hair follicle itself. It can have infectious or non-infectious causes.
== References == |
Selenium | Selenium is a chemical element with the symbol Se and atomic number 34. It is a nonmetal (more rarely considered a metalloid) with properties that are intermediate between the elements above and below in the periodic table, sulfur and tellurium, and also has similarities to arsenic. It seldom occurs in its elemental state or as pure ore compounds in the Earths crust. Selenium – from Greek selḗnē (σελήνη Moon) – was discovered in 1817 by Jöns Jacob Berzelius, who noted the similarity of the new element to the previously discovered tellurium (named for the Earth).
Selenium is found in metal sulfide ores, where it partially replaces the sulfur. Commercially, selenium is produced as a byproduct in the refining of these ores, most often during production. Minerals that are pure selenide or selenate compounds are known but rare. The chief commercial uses for selenium today are glassmaking and pigments. Selenium is a semiconductor and is used in photocells. Applications in electronics, once important, have been mostly replaced with silicon semiconductor devices. Selenium is still used in a few types of DC power surge protectors and one type of fluorescent quantum dot.
Although trace amounts of selenium are necessary for cellular function in many animals, including humans, both elemental selenium and (especially) selenium salts are toxic in even small doses, causing selenosis. Selenium is listed as an ingredient in many multivitamins and other dietary supplements, as well as in infant formula, and is a component of the antioxidant enzymes glutathione peroxidase and thioredoxin reductase (which indirectly reduce certain oxidized molecules in animals and some plants) as well as in 3 deiodinase enzymes. Selenium requirements in plants differ by species, with some plants requiring relatively large amounts and others apparently not requiring any.
Characteristics
Physical properties
Selenium forms several allotropes that interconvert with temperature changes, depending somewhat on the rate of temperature change. When prepared in chemical reactions, selenium is usually an amorphous, brick-red powder. When rapidly melted, it forms the black, vitreous form, usually sold commercially as beads. The structure of black selenium is irregular and complex and consists of polymeric rings with up to 1000 atoms per ring. Black Se is a brittle, lustrous solid that is slightly soluble in CS2. Upon heating, it softens at 50 °C and converts to gray selenium at 180 °C; the transformation temperature is reduced by presence of halogens and amines.The red α, β, and γ forms are produced from solutions of black selenium by varying the evaporation rate of the solvent (usually CS2). They all have a relatively low, monoclinic crystal symmetry (space group 14) and contain nearly identical puckered Se8 rings with different arrangements, as in sulfur. The eight atoms of a ring are not equivalent (i.e. they are not mapped one onto another by any symmetry operation), and in fact in the γ-monoclinic form, half the rings are in one configuration (and its mirror image) and half in another. The packing is most dense in the α form. In the Se8 rings, the Se-Se distance varies depending on where the pair of atoms is in the ring, but the average is 233.5 pm, and the Se-Se-Se angle is on average 105.7°. Other selenium allotropes may contain Se6 or Se7 rings.The most stable and dense form of selenium is gray and has a chiral hexagonal crystal lattice (space group 152 or 154 depending on the chirality) consisting of helical polymeric chains, where the Se-Se distance is 237.3 pm and Se-Se-Se angle is 103.1°. The minimum distance between chains is 343.6 pm. Gray Se is formed by mild heating of other allotropes, by slow cooling of molten Se, or by condensing Se vapor just below the melting point. Whereas other Se forms are insulators, gray Se is a semiconductor showing appreciable photoconductivity. Unlike the other allotropes, it is insoluble in CS2. It resists oxidation by air and is not attacked by nonoxidizing acids. With strong reducing agents, it forms polyselenides. Selenium does not exhibit the changes in viscosity that sulfur undergoes when gradually heated.
Optical properties
Owing to its use as a photoconductor in flat-panel x-ray detectors (see below), the optical properties of amorphous selenium (α-Se) thin films have been the subject of intense research.
Isotopes
Selenium has seven naturally occurring isotopes. Five of these, 74Se, 76Se, 77Se, 78Se, 80Se, are stable, with 80Se being the most abundant (49.6% natural abundance). Also naturally occurring is the long-lived primordial radionuclide 82Se, with a half-life of 9.2×1019 years. The non-primordial radioisotope 79Se also occurs in minute quantities in uranium ores as a product of nuclear fission. Selenium also has numerous unstable synthetic isotopes ranging from 64Se to 95Se; the most stable are 75Se with a half-life of 119.78 days and 72Se with a half-life of 8.4 days. Isotopes lighter than the stable isotopes primarily undergo beta plus decay to isotopes of arsenic, and isotopes heavier than the stable isotopes undergo beta minus decay to isotopes of bromine, with some minor neutron emission branches in the heaviest known isotopes.
Chemical compounds
Selenium compounds commonly exist in the oxidation states −2, +2, +4, and +6.
Chalcogen compounds
Selenium forms two oxides: selenium dioxide (SeO2) and selenium trioxide (SeO3). Selenium dioxide is formed by the reaction of elemental selenium with oxygen:
Se
8
+
8
O
2
⟶
8
SeO
2
{\displaystyle {\ce {Se8 + 8 O2 -> 8 SeO2}}}
It is a polymeric solid that forms monomeric SeO2 molecules in the gas phase. It dissolves in water to form selenous acid, H2SeO3. Selenous acid can also be made directly by oxidizing elemental selenium with nitric acid:
3
Se
+
4
HNO
3
+
H
2
O
⟶
3
H
2
SeO
3
+
4
NO
{\displaystyle {\ce {3 Se + 4 HNO3 + H2O -> 3 H2SeO3 + 4 NO}}}
Unlike sulfur, which forms a stable trioxide, selenium trioxide is thermodynamically unstable and decomposes to the dioxide above 185 °C:
2
SeO
3
⟶
2
SeO
2
+
O
2
{\displaystyle {\ce {2 SeO3 -> 2 SeO2 + O2}}}
(ΔH = −54 kJ/mol)Selenium trioxide is produced in the laboratory by the reaction of anhydrous potassium selenate (K2SeO4) and sulfur trioxide (SO3).Salts of selenous acid are called selenites. These include silver selenite (Ag2SeO3) and sodium selenite (Na2SeO3).
Hydrogen sulfide reacts with aqueous selenous acid to produce selenium disulfide:
H
2
SeO
3
+
2
H
2
S
⟶
SeS
2
+
3
H
2
O
{\displaystyle {\ce {H2SeO3 + 2 H2S -> SeS2 + 3 H2O}}}
Selenium disulfide consists of 8-membered rings. It has an approximate composition of SeS2, with individual rings varying in composition, such as Se4S4 and Se2S6. Selenium disulfide has been used in shampoo as an antidandruff agent, an inhibitor in polymer chemistry, a glass dye, and a reducing agent in fireworks.Selenium trioxide may be synthesized by dehydrating selenic acid, H2SeO4, which is itself produced by the oxidation of selenium dioxide with hydrogen peroxide:
SeO
2
+
H
2
O
2
⟶
H
2
SeO
4
{\displaystyle {\ce {SeO2 + H2O2 -> H2SeO4}}}
Hot, concentrated selenic acid can react with gold to form gold(III) selenate.
Halogen compounds
Iodides of selenium are not well known. The only stable chloride is selenium monochloride (Se2Cl2), which might be better known as selenium(I) chloride; the corresponding bromide is also known. These species are structurally analogous to the corresponding disulfur dichloride. Selenium dichloride is an important reagent in the preparation of selenium compounds (e.g. the preparation of Se7). It is prepared by treating selenium with sulfuryl chloride (SO2Cl2). Selenium reacts with fluorine to form selenium hexafluoride:
Se
8
+
24
F
2
⟶
8
SeF
6
{\displaystyle {\ce {Se8 + 24 F2 -> 8 SeF6}}}
In comparison with its sulfur counterpart (sulfur hexafluoride), selenium hexafluoride (SeF6) is more reactive and is a toxic pulmonary irritant.
Some of the selenium oxyhalides, such as selenium oxyfluoride (SeOF2) and selenium oxychloride (SeOCl2) have been used as specialty solvents.
Selenides
Analogous to the behavior of other chalcogens, selenium forms hydrogen selenide, H2Se. It is a strongly odiferous, toxic, and colorless gas. It is more acidic than H2S. In solution it ionizes to HSe−. The selenide dianion Se2− forms a variety of compounds, including the minerals from which selenium is obtained commercially. Illustrative selenides include mercury selenide (HgSe), lead selenide (PbSe), zinc selenide (ZnSe), and copper indium gallium diselenide (Cu(Ga,In)Se2). These materials are semiconductors. With highly electropositive metals, such as aluminium, these selenides are prone to hydrolysis:
Al
2
Se
3
+
3
H
2
O
⟶
Al
2
O
3
+
3
H
2
Se
{\displaystyle {\ce {Al2Se3 + 3 H2O -> Al2O3 + 3 H2Se}}}
Alkali metal selenides react with selenium to form polyselenides, Se2−n, which exist as chains.
Other compounds
Tetraselenium tetranitride, Se4N4, is an explosive orange compound analogous to tetrasulfur tetranitride (S4N4). It can be synthesized by the reaction of selenium tetrachloride (SeCl4) with [((CH3)3Si)2N]2Se.Selenium reacts with cyanides to yield selenocyanates:
8
KCN
+
Se
8
⟶
8
KSeCN
{\displaystyle {\ce {8 KCN + Se8 -> 8 KSeCN}}}
Organoselenium compounds
Selenium, especially in the II oxidation state, forms stable bonds to carbon, which are structurally analogous to the corresponding organosulfur compounds. Especially common are selenides (R2Se, analogues of thioethers), diselenides (R2Se2, analogues of disulfides), and selenols (RSeH, analogues of thiols). Representatives of selenides, diselenides, and selenols include respectively selenomethionine, diphenyldiselenide, and benzeneselenol. The sulfoxide in sulfur chemistry is represented in selenium chemistry by the selenoxides (formula RSe(O)R), which are intermediates in organic synthesis, as illustrated by the selenoxide elimination reaction. Consistent with trends indicated by the double bond rule, selenoketones, R(C=Se)R, and selenaldehydes, R(C=Se)H, are rarely observed.
History
Selenium (Greek σελήνη selene meaning "Moon") was discovered in 1817 by Jöns Jacob Berzelius and Johan Gottlieb Gahn. Both chemists owned a chemistry plant near Gripsholm, Sweden, producing sulfuric acid by the lead chamber process. The pyrite from the Falun Mine created a red precipitate in the lead chambers which was presumed to be an arsenic compound, so the pyrites use to make acid was discontinued. Berzelius and Gahn wanted to use the pyrite and they also observed that the red precipitate gave off a smell like horseradish when burned. This smell was not typical of arsenic, but a similar odor was known from tellurium compounds. Hence, Berzeliuss first letter to Alexander Marcet stated that this was a tellurium compound. However, the lack of tellurium compounds in the Falun Mine minerals eventually led Berzelius to reanalyze the red precipitate, and in 1818 he wrote a second letter to Marcet describing a newly found element similar to sulfur and tellurium. Because of its similarity to tellurium, named for the Earth, Berzelius named the new element after the Moon.In 1873, Willoughby Smith found that the electrical resistance of grey selenium was dependent on the ambient light. This led to its use as a cell for sensing light. The first commercial products using selenium were developed by Werner Siemens in the mid-1870s. The selenium cell was used in the photophone developed by Alexander Graham Bell in 1879. Selenium transmits an electric current proportional to the amount of light falling on its surface. This phenomenon was used in the design of light meters and similar devices. Seleniums semiconductor properties found numerous other applications in electronics. The development of selenium rectifiers began during the early 1930s, and these replaced copper oxide rectifiers because they were more efficient. These lasted in commercial applications until the 1970s, following which they were replaced with less expensive and even more efficient silicon rectifiers.
Selenium came to medical notice later because of its toxicity to industrial workers. Selenium was also recognized as an important veterinary toxin, which is seen in animals that have eaten high-selenium plants. In 1954, the first hints of specific biological functions of selenium were discovered in microorganisms by biochemist, Jane Pinsent. It was discovered to be essential for mammalian life in 1957. In the 1970s, it was shown to be present in two independent sets of enzymes. This was followed by the discovery of selenocysteine in proteins. During the 1980s, selenocysteine was shown to be encoded by the codon UGA. The recoding mechanism was worked out first in bacteria and then in mammals (see SECIS element).
Occurrence
Native (i.e., elemental) selenium is a rare mineral, which does not usually form good crystals, but, when it does, they are steep rhombohedra or tiny acicular (hair-like) crystals. Isolation of selenium is often complicated by the presence of other compounds and elements.
Selenium occurs naturally in a number of inorganic forms, including selenide, selenate, and selenite, but these minerals are rare. The common mineral selenite is not a selenium mineral, and contains no selenite ion, but is rather a type of gypsum (calcium sulfate hydrate) named like selenium for the moon well before the discovery of selenium. Selenium is most commonly found as an impurity, replacing a small part of the sulfur in sulfide ores of many metals.In living systems, selenium is found in the amino acids selenomethionine, selenocysteine, and methylselenocysteine. In these compounds, selenium plays a role analogous to that of sulfur. Another naturally occurring organoselenium compound is dimethyl selenide.Certain soils are selenium-rich, and selenium can be bioconcentrated by some plants. In soils, selenium most often occurs in soluble forms such as selenate (analogous to sulfate), which are leached into rivers very easily by runoff. Ocean water contains significant amounts of selenium.Typical background concentrations of selenium do not exceed 1 ng/m3 in the atmosphere; 1 mg/kg in soil and vegetation and 0.5 μg/L in freshwater and seawater.Anthropogenic sources of selenium include coal burning, and the mining and smelting of sulfide ores.
Production
Selenium is most commonly produced from selenide in many sulfide ores, such as those of copper, nickel, or lead. Electrolytic metal refining is particularly productive of selenium as a byproduct, obtained from the anode mud of copper refineries. Another source was the mud from the lead chambers of sulfuric acid plants, a process that is no longer used. Selenium can be refined from these muds by a number of methods. However, most elemental selenium comes as a byproduct of refining copper or producing sulfuric acid. Since its invention, solvent extraction and electrowinning (SX/EW) production of copper produces an increasing share of the worldwide copper supply. This changes the availability of selenium because only a comparably small part of the selenium in the ore is leached with the copper.Industrial production of selenium usually involves the extraction of selenium dioxide from residues obtained during the purification of copper. Common production from the residue then begins by oxidation with sodium carbonate to produce selenium dioxide, which is mixed with water and acidified to form selenous acid (oxidation step). Selenous acid is bubbled with sulfur dioxide (reduction step) to give elemental selenium.About 2,000 tonnes of selenium were produced in 2011 worldwide, mostly in Germany (650 t), Japan (630 t), Belgium (200 t), and Russia (140 t), and the total reserves were estimated at 93,000 tonnes. These data exclude two major producers: the United States and China. A previous sharp increase was observed in 2004 from $4–$5 to $27/lb. The price was relatively stable during 2004–2010 at about US$30 per pound (in 100 pound lots) but increased to $65/lb in 2011. The consumption in 2010 was divided as follows: metallurgy – 30%, glass manufacturing – 30%, agriculture – 10%, chemicals and pigments – 10%, and electronics – 10%. China is the dominant consumer of selenium at 1,500–2,000 tonnes/year.
Applications
Fertilizers
Researchers found that application of selenium fertilizer to lettuce crops decreased the accumulation of lead and cadmium. Peaches and pears given a foliar selenium spray contained higher levels of selenium and also stayed firm and ripe longer when in storage. In low doses, selenium has shown a beneficial effect on plant resistance to various environmental stress factors including drought, UV-B, soil salinity, and cold or hot temperatures. However, it can damage plants at higher doses.
Manganese electrolysis
During the electrowinning of manganese, the addition of selenium dioxide decreases the power necessary to operate the electrolysis cells. China is the largest consumer of selenium dioxide for this purpose. For every tonne of manganese, an average 2 kg selenium oxide is used.
Glass production
The largest commercial use of Se, accounting for about 50% of consumption, is for the production of glass. Se compounds confer a red color to glass. This color cancels out the green or yellow tints that arise from iron impurities typical for most glass. For this purpose, various selenite and selenate salts are added. For other applications, a red color may be desired, produced by mixtures of CdSe and CdS.
Alloys
Selenium is used with bismuth in brasses to replace more toxic lead. The regulation of lead in drinking water applications such as in the US with the Safe Drinking Water Act of 1974, made a reduction of lead in brass necessary. The new brass is marketed under the name EnviroBrass. Like lead and sulfur, selenium improves the machinability of steel at concentrations around 0.15%. Selenium produces the same machinability improvement in copper alloys.
Lithium–selenium batteries
The lithium–selenium (Li–Se) battery is one of the most promising systems for energy storage in the family of lithium batteries. The Li–Se battery is an alternative to the lithium–sulfur battery, with an advantage of high electrical conductivity.
Solar cells
Selenium was the basis of the very first solar cells, with the first example of rooftop solar being a selenium cell from 1884. Such cells were later used in battery-free light meters for photography. Copper indium gallium selenide is a material used in solar cells.
Photoconductors
Amorphous selenium (α-Se) thin films have found application as photoconductors in flat panel x-ray detectors. These detectors use amorphous selenium to capture and convert incident x-ray photons directly into electric charge.
Rectifiers
Selenium rectifiers were first used in 1933. Their use continued into the 1990s.
Other uses
Small amounts of organoselenium compounds have been used to modify the catalysts used for the vulcanization for the production of rubber.The demand for selenium by the electronics industry is declining. Its photovoltaic and photoconductive properties are still useful in photocopying, photocells, light meters and solar cells. Its use as a photoconductor in plain-paper copiers once was a leading application, but in the 1980s, the photoconductor application declined (although it was still a large end-use) as more and more copiers switched to organic photoconductors. Though once widely used, selenium rectifiers have mostly been replaced (or are being replaced) by silicon-based devices. The most notable exception is in power DC surge protection, where the superior energy capabilities of selenium suppressors make them more desirable than metal-oxide varistors.
Zinc selenide was the first material for blue LEDs, but gallium nitride dominates that market. Cadmium selenide was an important component in quantum dots. Sheets of amorphous selenium convert X-ray images to patterns of charge in xeroradiography and in solid-state, flat-panel X-ray cameras. Ionized selenium (Se+24) is one of the active mediums used in X-ray lasers.Selenium is a catalyst in some chemical reactions, but it is not widely used because of issues with toxicity. In X-ray crystallography, incorporation of one or more selenium atoms in place of sulfur helps with multiple-wavelength anomalous dispersion and single wavelength anomalous dispersion phasing.Selenium is used in the toning of photographic prints, and it is sold as a toner by numerous photographic manufacturers. Selenium intensifies and extends the tonal range of black-and-white photographic images and improves the permanence of prints.75Se is used as a gamma source in industrial radiography.
Pollution
In high concentrations, selenium acts as an environmental contaminant. Sources of pollution include waste materials from certain mining, agricultural, petrochemical, and industrial manufacturing operations. In Belews Lake North Carolina, 19 species of fish were eliminated from the lake due to 150–200 μg Se/L wastewater discharged from 1974 to 1986 from a Duke Energy coal-fired power plant. At the Kesterson National Wildlife Refuge in California, thousands of fish and waterbirds were poisoned by selenium in agricultural irrigation drainage.
Substantial physiological changes may occur in fish with high tissue concentrations of selenium. Fish affected by selenium may experience swelling of the gill lamellae, which impedes oxygen diffusion across the gills and blood flow within the gills. Respiratory capacity is further reduced due to selenium binding to hemoglobin. Other problems include degeneration of liver tissue, swelling around the heart, damaged egg follicles in ovaries, cataracts, and accumulation of fluid in the body cavity and head. Selenium often causes a malformed fish fetus which may have problems feeding or respiring; distortion of the fins or spine is also common. Adult fish may appear healthy despite their inability to produce viable offspring.
Selenium is bioaccumulated in aquatic habitats, which results in higher concentrations in organisms than the surrounding water. Organoselenium compounds can be concentrated over 200,000 times by zooplankton when water concentrations are in the 0.5 to 0.8 μg Se/L range. Inorganic selenium bioaccumulates more readily in phytoplankton than zooplankton. Phytoplankton can concentrate inorganic selenium by a factor of 3000. Further concentration through bioaccumulation occurs along the food chain, as predators consume selenium rich prey. It is recommended that a water concentration of 2 μg Se/L be considered highly hazardous to sensitive fish and aquatic birds. Selenium poisoning can be passed from parents to offspring through the egg, and selenium poisoning may persist for many generations. Reproduction of mallard ducks is impaired at dietary concentrations of 7 μg Se/L. Many benthic invertebrates can tolerate selenium concentrations up to 300 μg/L of Se in their diet.Selenium pollution might impact some aquatic systems and may be caused by anthropogenic factors such as farming runoff and industrial processes. Fish are a major source of protein for humans, people who eat more fish are generally healthier than those who eat less, indicating selenium pollution does not appear to be a problem, although it might be useful to be aware that selenium has a potential effect on humans.Bioaccumulation of selenium in aquatic environments causes fish kills depending on the species in the affected area. There are, however, a few species that have been seen to survive these events and tolerate the increased selenium. It has also been suggested that season could have an impact on the harmful effects of selenium on fish.Selenium poisoning of water systems may result whenever new agricultural run-off courses through dry lands. This process leaches natural soluble selenium compounds (such as selenates) into the water, which may then be concentrated in wetlands as the water evaporates. Selenium pollution of waterways also occurs when selenium is leached from coal flue ash, mining and metal smelting, crude oil processing, and landfill. High selenium levels in waterways were found to cause congen |
Selenium | ital disorders in oviparous species, including wetland birds and fish. Elevated dietary methylmercury levels can amplify the harm of selenium toxicity in oviparous species.
Biological role
Although it is toxic in large doses, selenium is an essential micronutrient for animals. In plants, it occurs as a bystander mineral, sometimes in toxic proportions in forage (some plants may accumulate selenium as a defense against being eaten by animals, but other plants, such as locoweed, require selenium, and their growth indicates the presence of selenium in soil).Selenium is a component of the unusual amino acids selenocysteine and selenomethionine. In humans, selenium is a trace element nutrient that functions as cofactor for reduction of antioxidant enzymes, such as glutathione peroxidases and certain forms of thioredoxin reductase found in animals and some plants (this enzyme occurs in all living organisms, but not all forms of it in plants require selenium).
The glutathione peroxidase family of enzymes (GSH-Px) catalyze certain reactions that remove reactive oxygen species such as hydrogen peroxide and organic hydroperoxides:
2 GSH + H2O2----GSH-Px → GSSG + 2 H2OThe thyroid gland and every cell that uses thyroid hormone use selenium, which is a cofactor for the three of the four known types of thyroid hormone deiodinases, which activate and then deactivate various thyroid hormones and their metabolites; the iodothyronine deiodinases are the subfamily of deiodinase enzymes that use selenium as the otherwise rare amino acid selenocysteine. (Only the deiodinase iodotyrosine deiodinase, which works on the last breakdown products of thyroid hormone, does not use selenium.)Selenium may inhibit Hashimotos disease, in which the bodys own thyroid cells are attacked as foreign. A reduction of 21% on TPO antibodies is reported with the dietary intake of 0.2 mg of selenium.Increased dietary selenium reduces the effects of mercury toxicity, although it is effective only at low to modest doses of mercury. Evidence suggests that the molecular mechanisms of mercury toxicity includes the irreversible inhibition of selenoenzymes that are required to prevent and reverse oxidative damage in brain and endocrine tissues. An antioxidant, selenoneine, which is derived from selenium and has been found to be present in the blood of bluefin tuna, is the subject of scientific research regarding its possible roles in inflammatory and chronic diseases, methylmercury detoxification, and oxidative damages. It seems as though when mercury levels in a marine fish rise, so do the selenium levels. To the knowledge of researchers, there are no reports of mercury levels exceeding that of selenium levels in ocean fish.
Evolution in biology
From about three billion years ago, prokaryotic selenoprotein families drive the evolution of selenocysteine, an amino acid. Selenium is incorporated into several prokaryotic selenoprotein families in bacteria, archaea, and eukaryotes as selenocysteine, where selenoprotein peroxiredoxins protect bacterial and eukaryotic cells against oxidative damage. Selenoprotein families of GSH-Px and the deiodinases of eukaryotic cells seem to have a bacterial phylogenetic origin. The selenocysteine-containing form occurs in species as diverse as green algae, diatoms, sea urchins, fish, and chickens. Selenium enzymes are involved in the small reducing molecules glutathione and thioredoxin. One family of selenium-bearing molecules (the glutathione peroxidases) destroys peroxide and repairs damaged peroxidized cell membranes, using glutathione. Another selenium-bearing enzyme in some plants and in animals (thioredoxin reductase) generates reduced thioredoxin, a dithiol that serves as an electron source for peroxidases and also the important reducing enzyme ribonucleotide reductase that makes DNA precursors from RNA precursors.Trace elements involved in GSH-Px and superoxide dismutase enzymes activities, i.e. selenium, vanadium, magnesium, copper, and zinc, may have been lacking in some terrestrial mineral-deficient areas. Marine organisms retained and sometimes expanded their selenoproteomes, whereas the selenoproteomes of some terrestrial organisms were reduced or completely lost. These findings suggest that, with the exception of vertebrates, aquatic life supports selenium use, whereas terrestrial habitats lead to reduced use of this trace element. Marine fishes and vertebrate thyroid glands have the highest concentration of selenium and iodine. From about 500 million years ago, freshwater and terrestrial plants slowly optimized the production of "new" endogenous antioxidants such as ascorbic acid (vitamin C), polyphenols (including flavonoids), tocopherols, etc. A few of these appeared more recently, in the last 50–200 million years, in fruits and flowers of angiosperm plants. In fact, the angiosperms (the dominant type of plant today) and most of their antioxidant pigments evolved during the late Jurassic period.The deiodinase isoenzymes constitute another family of eukaryotic selenoproteins with identified enzyme function. Deiodinases are able to extract electrons from iodides, and iodides from iodothyronines. They are, thus, involved in thyroid-hormone regulation, participating in the protection of thyrocytes from damage by H2O2 produced for thyroid-hormone biosynthesis. About 200 million years ago, new selenoproteins were developed as mammalian GSH-Px enzymes.
Nutritional sources of selenium
Dietary selenium comes from meat, nuts, cereals and mushrooms. Brazil nuts are the richest dietary source (though this is soil-dependent, since the Brazil nut does not require high levels of the element for its own needs).The US Recommended Dietary Allowance (RDA) of selenium for teenagers and adults is 55 µg/day. Selenium as a dietary supplement is available in many forms, including multi-vitamins/mineral supplements, which typically contain 55 or 70 µg/serving. Selenium-specific supplements typically contain either 100 or 200 µg/serving.
In June 2015, the US Food and Drug Administration (FDA) published its final rule establishing the requirement of minimum and maximum levels of selenium in infant formula.The selenium content in the human body is believed to be in the 13–20 mg range.
Indicator plant species
Certain species of plants are considered indicators of high selenium content of the soil because they require high levels of selenium to thrive. The main selenium indicator plants are Astragalus species (including some locoweeds), princes plume (Stanleya sp.), woody asters (Xylorhiza sp.), and false goldenweed (Oonopsis sp.)
Detection in biological fluids
Selenium may be measured in blood, plasma, serum, or urine to monitor excessive environmental or occupational exposure, to confirm a diagnosis of poisoning in hospitalized victims, or investigate a suspected case of fatal overdose. Some analytical techniques are capable of distinguishing organic from inorganic forms of the element. Both organic and inorganic forms of selenium are largely converted to monosaccharide conjugates (selenosugars) in the body prior to elimination in the urine. Cancer patients receiving daily oral doses of selenothionine may achieve very high plasma and urine selenium concentrations.
Toxicity
Although selenium is an essential trace element, it is toxic if taken in excess. Exceeding the Tolerable Upper Intake Level of 400 micrograms per day can lead to selenosis. This 400 µg Tolerable Upper Intake Level is based primarily on a 1986 study of five Chinese patients who exhibited overt signs of selenosis and a follow up study on the same five people in 1992. The 1992 study actually found the maximum safe dietary Se intake to be approximately 800 micrograms per day (15 micrograms per kilogram body weight), but suggested 400 micrograms per day to avoid creating an imbalance of nutrients in the diet and to accord with data from other countries. In China, people who ingested corn grown in extremely selenium-rich stony coal (carbonaceous shale) have suffered from selenium toxicity. This coal was shown to have selenium content as high as 9.1%, the highest concentration in coal ever recorded.Signs and symptoms of selenosis include a garlic odor on the breath, gastrointestinal disorders, hair loss, sloughing of nails, fatigue, irritability, and neurological damage. Extreme cases of selenosis can exhibit cirrhosis of the liver, pulmonary edema, or death. Elemental selenium and most metallic selenides have relatively low toxicities because of low bioavailability. By contrast, selenates and selenites have an oxidant mode of action similar to that of arsenic trioxide and are very toxic. The chronic toxic dose of selenite for humans is about 2400 to 3000 micrograms of selenium per day. Hydrogen selenide is an extremely toxic, corrosive gas. Selenium also occurs in organic compounds, such as dimethyl selenide, selenomethionine, selenocysteine and methylselenocysteine, all of which have high bioavailability and are toxic in large doses.
On 19 April 2009, 21 polo ponies died shortly before a match in the United States Polo Open. Three days later, a pharmacy released a statement explaining that the horses had received an incorrect dose of one of the ingredients used in a vitamin/mineral supplement compound that had been incorrectly prepared by a compounding pharmacy. Analysis of blood levels of inorganic compounds in the supplement indicated the selenium concentrations were 10 to 15 times higher than normal in the blood samples, and 15 to 20 times higher than normal in the liver samples. Selenium was later confirmed to be the toxic factor.
In fish and other wildlife, selenium is necessary for life, but toxic in high doses. For salmon, the optimal concentration of selenium is about 1 microgram selenium per gram of whole body weight. Much below that level, young salmon die from deficiency; much above, they die from toxic excess.The Occupational Safety and Health Administration (OSHA) has set the legal limit (permissible exposure limit) for selenium in the workplace at 0.2 mg/m3 over an 8-hour workday. The National Institute for Occupational Safety and Health (NIOSH) has set a Recommended exposure limit (REL) of 0.2 mg/m3 over an 8-hour workday. At levels of 1 mg/m3, selenium is immediately dangerous to life and health.
Deficiency
Selenium deficiency can occur in patients with severely compromised intestinal function, those undergoing total parenteral nutrition, and in those of advanced age (over 90). Also, people dependent on food grown from selenium-deficient soil are at risk. Although New Zealand soil has low levels of selenium, adverse health effects have not been detected in the residents.Selenium deficiency, defined by low (<60% of normal) selenoenzyme activity levels in brain and endocrine tissues, occurs only when a low selenium level is linked with an additional stress, such as high exposures to mercury or increased oxidant stress from vitamin E deficiency.Selenium interacts with other nutrients, such as iodine and vitamin E. The effect of selenium deficiency on health remains uncertain, particularly in relation to Kashin-Beck disease. Also, selenium interacts with other minerals, such as zinc and copper. High doses of Se supplements in pregnant animals might disturb the Zn:Cu ratio and lead to Zn reduction; in such treatment cases, Zn levels should be monitored. Further studies are needed to confirm these interactions.In the regions (e.g. various regions within North America) where low selenium soil levels lead to low concentrations in the plants, some animal species may be deficient unless selenium is supplemented with diet or injection. Ruminants are particularly susceptible. In general, absorption of dietary selenium is lower in ruminants than other animals, and is lower from forages than from grain. Ruminants grazing certain forages, e.g., some white clover varieties containing cyanogenic glycosides, may have higher selenium requirements, presumably because cyanide is released from the aglycone by glucosidase activity in the rumen and glutathione peroxidases is deactivated by the cyanide acting on the glutathione moiety. Neonate ruminants at risk of white muscle disease may be administered both selenium and vitamin E by injection; some of the WMD myopathies respond only to selenium, some only to vitamin E, and some to either.
Health effects
The effects of selenium intake on cancer have been studied in several clinical trials and epidemiologic studies in humans. Selenium may have a chemo-preventive role in cancer risk as an anti-oxidant, and it might trigger the immune response. At low levels, it is used in the body to create anti-oxidant selenoproteins, at higher doses than normal it causes cell death.Selenium (in close interrelation with iodine) plays a role in thyroid health. Selenium is a cofactor for the three thyroid hormone deiodinases, helping activate and then deactivate various thyroid hormones and their metabolites. Isolated selenium deficiency is now being investigated for its role in induction autoimmune reactions in thyroid gland in Hashimotos disease. However, in a case of combined iodine and selenium deficiency, selenium deficiency was shown to play a thyroid-protecting role.
See also
Abundance of elements in Earths crust
ACES (nutritional supplement)
Selenium yeast
Notes
References
External links
Selenium at The Periodic Table of Videos (University of Nottingham)
National Institutes of Health page on Selenium
Assay Archived 2012-02-26 at the Wayback Machine
ATSDR – Toxicological Profile: Selenium
CDC – NIOSH Pocket Guide to Chemical Hazards
Peter van der Krogt elements site |
Parry–Romberg syndrome | Parry–Romberg syndrome (PRS) is a rare disease characterized by progressive shrinkage and degeneration of the tissues beneath the skin, usually on only one side of the face (hemifacial atrophy) but occasionally extending to other parts of the body. An autoimmune mechanism is suspected, and the syndrome may be a variant of localized scleroderma, but the precise cause and pathogenesis of this acquired disorder remains unknown. It has been reported in the literature as a possible consequence of sympathectomy. The syndrome has a higher prevalence in females and typically appears between 5 and 15 years of age.
In addition to the connective tissue disease, the condition is sometimes accompanied by neurological, ocular and oral symptoms. The range and severity of associated symptoms and findings are highly variable.
Signs and symptoms
Skin and connective tissues
Initial facial changes usually involve the area of the face covered by the temporal or buccinator muscles. The disease progressively spreads from the initial location, resulting in atrophy of the skin and its adnexa, as well as underlying subcutaneous structures such as connective tissue, (fat, fascia, cartilage, bones) and/or muscles of one side of the face. The mouth and nose are typically deviated towards the affected side of the face.The process may eventually extend to involve tissues between the nose and the upper corner of the lip, the upper jaw, the angle of the mouth, the area around the eye and brow, the ear, and/or the neck. The syndrome often begins with a circumscribed patch of scleroderma in the frontal region of the scalp which is associated with a loss of hair and the appearance of a depressed linear scar extending down through the midface on the affected side. This scar is referred to as a "coup de sabre" lesion because it resembles the scar of a wound made by a sabre, and is indistinguishable from the scar observed in frontal linear scleroderma.In 20% of cases, the hair and skin overlying affected areas may become hyperpigmented or hypopigmented with patches of unpigmented skin. In up to 20% of cases the disease may involve the ipsilateral (on the same side) or contralateral (on the opposite side) neck, trunk, arm, or leg. The cartilage of the nose, ear and larynx can be involved. The disease has been reported to affect both sides of the face in 5 to 10% of cases.Symptoms and physical findings usually become apparent during the first or early during the second decade of life. The average age of onset is nine years of age, and the majority of individuals experience symptoms before 20 years of age. The disease may progress for several years before eventually going into remission (abruptly ceasing).
Neurological
Neurological abnormalities are common. Roughly 45% of people with Parry–Romberg syndrome also have trigeminal neuralgia (severe pain in the tissues supplied by the ipsilateral trigeminal nerve, including the forehead, eye, cheek, nose, mouth and jaw) and/or migraine (severe headaches that may be accompanied by visual abnormalities, nausea and vomiting).10% of affected individuals develop a seizure disorder as part of the disease. The seizures are typically Jacksonian in nature (characterized by rapid spasms of a muscle group that subsequently spread to adjacent muscles) and occur on the side contralateral to the affected side of the face. Half of these cases are associated with abnormalities in both the gray and white matter of the brain—usually ipsilateral but sometimes contralateral—that are detectable on magnetic resonance imaging (MRI) scan.
Ocular
Enophthalmos (recession of the eyeball within the orbit) is the most common eye abnormality observed in Parry–Romberg syndrome. It is caused by a loss of subcutaneous tissue around the orbit. Other common findings include drooping of the eyelid (ptosis), constriction of the pupil (miosis), redness of the conjunctiva, and decreased sweating (anhidrosis) of the affected side of the face. Collectively, these signs are referred to as Horners syndrome. Other ocular abnormalities include ophthalmoplegia (paralysis of one or more of the extraocular muscles) and other types of strabismus, uveitis, and heterochromia of the iris.
Oral
The tissues of the mouth, including the tongue, gingiva, teeth and soft palate are commonly involved in Parry–Romberg syndrome. 50% of affected individuals develop dental abnormalities such as delayed eruption, dental root exposure, or resorption of the dental roots on the affected side. 35% have difficulty or inability to normally open the mouth or other jaw symptoms, including temporomandibular joint disorder and spasm of the muscles of mastication on the affected side. 25% experience atrophy of one side of the upper lip and tongue.
Causes
The fact that some people affected with this disease have circulating antinuclear antibodies in their serum supports the theory that Parry–Romberg syndrome may be an autoimmune disease, specifically a variant of localized scleroderma. Several instances have been reported where more than one member of a family has been affected, prompting speculation of an autosomal dominant inheritance pattern. However, there has also been at least one report of monozygotic twins in which only one of the twins was affected, casting doubt on this theory. Further, the National Organization for Rare Disorders has stated there is currently no evidence that Parry–Romberg syndrome is genetic or that it can be passed on to children. Various other theories about the cause and pathogenesis have been suggested, including alterations in the peripheral sympathetic nervous system (perhaps as a result of trauma or infection involving the cervical plexus or the sympathetic trunk), as the literature reported it following sympathectomy, disorders in migration of cranial neural crest cells, or chronic cell-mediated inflammatory process of the blood vessels. It is likely that the disease results from different mechanisms in different people, with all of these factors potentially being involved.
Diagnosis
Diagnosis can be made solely on the basis of history and physical examination in people who present with only facial asymmetry. For those who report neurological symptoms such as migraine or seizures, MRI scan of the brain is the imaging modality of choice. A diagnostic lumbar puncture and serum test for autoantibodies may also be indicated in people who present with a seizure disorder of recent onset. Oligoclonal bands and an elevated IgG index may be found in 50% of the patients.
Management
Medical
Medical management may involve immunosuppressive drugs such as methotrexate, corticosteroids, cyclophosphamide, and azathioprine. No randomized controlled trials have yet been conducted to evaluate such treatments, so the benefits have not been clearly established.
Surgical
Affected individuals may benefit from autologous fat transfer or fat grafts to restore a more normal contour to the face. However, greater volume defects may require microsurgical reconstructive surgery which may involve the transfer of an island parascapular fasciocutaneous flap or a free flap from the groin, rectus abdominis muscle (Transverse Rectus Abdominis Myocutaneous or "TRAM" flap) or latissimus dorsi muscle to the face. Severe deformities may require additional procedures, such as pedicled temporal fascia flaps, cartilage grafts, bone grafts, orthognathic surgery, and bone distraction. The timing of surgical intervention is controversial; some surgeons prefer to wait until the disease has run its course while others recommend early intervention.
Epidemiology
Parry–Romberg syndrome appears to occur randomly and for unknown reasons. Prevalence is higher in females than males, with a ratio of roughly 3:2. The condition is observed on the left side of the face about as often as on the right side.
History
The disease was first described in 1825 by Caleb Hillier Parry (1755–1822), in a collection of his medical writings which were published posthumously by his son Charles Henry Parry (1779–1860). It was described a second time in 1846 by Moritz Heinrich Romberg (1795–1873) and Eduard Heinrich Henoch (1820–1910). German neurologist Albert Eulenburg (1840–1917) was the first to use the descriptive title "progressive hemifacial atrophy" in 1871.
See also
Hemifacial microsomia
List of cutaneous conditions
Trigeminal trophic lesion
References
Further reading
Karim A, Laghmari M, Ibrahimy W, Essakali HN, Mohcine Z (October 2005). "[Neuroretinitis, Parry-Romberg syndrome, and scleroderma]". Journal Français dOphtalmologie (in French). 28 (8): 866–70. doi:10.1016/S0181-5512(05)81008-3. PMID 16249769.
Lakhani PK, David TJ (February 1984). "Progressive hemifacial atrophy with scleroderma and ipsilateral limb wasting (Parry-Romberg syndrome)". Journal of the Royal Society of Medicine. 77 (2): 138–9. doi:10.1177/014107688407700215. PMC 1439690. PMID 6737396.
Larner AJ, Bennison DP (September 1993). "Some observations on the aetiology of progressive hemifacial atrophy ("Parry-Romberg syndrome")". Journal of Neurology, Neurosurgery, and Psychiatry. 56 (9): 1035–6. doi:10.1136/jnnp.56.9.1035-a. PMC 489747. PMID 8410030.
Miller MT, Spencer MA (1995). "Progressive hemifacial atrophy. A natural history study". Transactions of the American Ophthalmological Society. 93: 203–15, discussion 215–7. PMC 1312058. PMID 8719679.
Pinheiro TP, Silva CC, Silveira CS, Botelho PC, Pinheiro MD, Pinheiro JJ (March 2006). "Progressive Hemifacial Atrophy--case report". Medicina Oral, Patologia Oral y Cirugia Bucal. 11 (2): E112-4. PMID 16505785.
Zafarulla MY (July 1985). "Progressive hemifacial atrophy: a case report". The British Journal of Ophthalmology. 69 (7): 545–7. doi:10.1136/bjo.69.7.545. PMC 1040666. PMID 4016051.
External links
Progressive hemifacial atrophy; Parry-Romberg syndrome at NIHs Office of Rare Diseases |
Trichosporonosis | Trichosporonosis is a systemic disease associated with fungi in the genus Trichosporon.
It can appear in patients who are immunosuppressed.
References
== External links == |
Granulocytosis | In medicine, granulocytosis is the presence of an increased number of granulocytes in the peripheral blood. Often, the word refers to an increased neutrophil granulocyte count (neutrophilia), but granulocytosis formally refers to the combination of neutrophilia, eosinophilia, and basophilia. Leukocytosis refers to an increase in the number of all white blood cells.
Causes
Granulocytosis can be a feature of a number of diseases, including:
Infection, especially bacterial
Malignancy, most notably leukemia (it is the main feature of chronic myelogenous leukemia, CML)
Autoimmune disease
Diagnosis
Diagnosis of granulocytosis is usually done by obtaining a complete blood count.
Prognostic
In cardiovascular disease, increased white blood cell counts have been shown to indicate a worse prognosis.
See also
Agranulocytosis
Bandemia
Complete blood count
References
== External links == |
Saddle nose | Saddle nose is a condition associated with nasal trauma, congenital syphilis, relapsing polychondritis, granulomatosis with polyangiitis, cocaine abuse, and leprosy, among other conditions. The most common cause is nasal trauma. It is characterized by a loss of height of the nose, because of the collapse of the bridge. The depressed nasal dorsum may involve bony, cartilaginous or both bony and cartilaginous components of the nasal dorsum.
It can usually be corrected with augmentation rhinoplasty by filling the dorsum of nose with cartilage, bone or synthetic implant. If the depression is only cartilaginous, cartilage is taken from the nasal septum or auricle and laid in single or multiple layers. If deformity involves both cartilage and bone, cancellous bone from iliac crest is the best replacement. Autografts are preferred over allografts. Saddle deformity can also be corrected by synthetic implants of teflon or silicon, but they are likely to be extruded.
See also
Saber shin
List of cutaneous conditions
References
== External links == |
Millipede burn | Millipede burns are a cutaneous condition caused by some millipedes that secrete a toxic liquid that causes a brownish pigmentation or burn when it comes into contact with the skin. Some millipedes produce quinones in their defensive secretions, which have been reported to cause brown staining of the skin.
See also
Centipede bite
Skin lesion
References
== External links == |
Hernia | A hernia is the abnormal exit of tissue or an organ, such as the bowel, through the wall of the cavity in which it normally resides. Various types of hernias can occur, most commonly involving the abdomen, and specifically the groin. Groin hernias are most commonly of the inguinal type but may also be femoral. Other types of hernias include hiatus, incisional, and umbilical hernias. Symptoms are present in about 66% of people with groin hernias. This may include pain or discomfort in the lower abdomen, especially with coughing, exercise, or urinating or defecating. Often, it gets worse throughout the day and improves when lying down. A bulge may appear at the site of hernia, that becomes larger when bending down. Groin hernias occur more often on the right than left side. The main concern is bowel strangulation, where the blood supply to part of the bowel is blocked. This usually produces severe pain and tenderness in the area. Hiatus, or hiatal hernias often result in heartburn but may also cause chest pain or pain while eating.Risk factors for the development of a hernia include smoking, chronic obstructive pulmonary disease, obesity, pregnancy, peritoneal dialysis, collagen vascular disease and previous open appendectomy, among others. Predisposition to hernias is genetic and occur more often in certain families. Deleterious mutations causing predisposition to hernias seem to have dominant inheritance (especially for men). It is unclear if groin hernias are associated with heavy lifting. Hernias can often be diagnosed based on signs and symptoms. Occasionally, medical imaging is used to confirm the diagnosis or rule out other possible causes. The diagnosis of hiatus hernias is often by endoscopy.Groin hernias that do not cause symptoms in males do not need to be repaired. Repair, however, is generally recommended in women due to the higher rate of femoral hernias, which have more complications. If strangulation occurs, immediate surgery is required. Repair may be done by open surgery or laparoscopic surgery. Open surgery has the benefit of possibly being done under local anesthesia rather than general anesthesia. Laparoscopic surgery generally has less pain following the procedure. A hiatus hernia may be treated with lifestyle changes such as raising the head of the bed, weight loss and adjusting eating habits. The medications H2 blockers or proton pump inhibitors may help. If the symptoms do not improve with medications, a surgery known as laparoscopic Nissen fundoplication may be an option.About 27% of males and 3% of females develop a groin hernia at some point in their lives. Inguinal, femoral and abdominal hernias were present in 18.5 million people and resulted in 59,800 deaths in 2015. Groin hernias occur most often before the age of 1 and after the age of 50. It is not known how commonly hiatus hernias occur, with estimates in North America varying from 10% to 80%. The first known description of a hernia dates back to at least 1550 BC, in the Ebers Papyrus from Egypt.
Signs and symptoms
By far the most common hernias develop in the abdomen when a weakness in the abdominal wall evolves into a localized hole, or "defect", through which adipose tissue, or abdominal organs covered with peritoneum, may protrude. Another common hernia involves the spinal discs and causes sciatica. A hiatus hernia occurs when the stomach protrudes into the mediastinum through the esophageal opening in the diaphragm.
Hernias may or may not present with either pain at the site, a visible or palpable lump, or in some cases more vague symptoms resulting from pressure on an organ that has become "stuck" in the hernia, sometimes leading to organ dysfunction. Fatty tissue usually enters a hernia first, but it may be followed or accompanied by an organ.
Hernias are caused by a disruption or opening in the fascia, or fibrous tissue, which forms the abdominal wall. It is possible for the bulge associated with a hernia to come and go, but the defect in the tissue will persist.
Symptoms and signs vary depending on the type of hernia. Symptoms may or may not be present in some inguinal hernias. In the case of reducible hernias, a bulge in the groin or in another abdominal area can often be seen and felt. When standing, such a bulge becomes more obvious. Besides the bulge, other symptoms include pain in the groin that may also include a heavy or dragging sensation, and in men, there is sometimes pain and swelling in the scrotum around the testicular area.Irreducible abdominal hernias or incarcerated hernias may be painful, but their most relevant symptom is that they cannot return to the abdominal cavity when pushed in. They may be chronic, although painless, and can lead to strangulation (loss of blood supply), obstruction (kinking of intestine), or both. Strangulated hernias are always painful and pain is followed by tenderness. Nausea, vomiting, or fever may occur in these cases due to bowel obstruction. Also, the hernia bulge, in this case, may turn red, purple or dark and pink.
In the diagnosis of abdominal hernias, imaging is the principal means of detecting internal diaphragmatic and other nonpalpable or unsuspected hernias. Multidetector CT (MDCT) can show with precision the anatomic site of the hernia sac, the contents of the sac, and any complications. MDCT also offers clear detail of the abdominal wall allowing wall hernias to be identified accurately.
Complications
Complications may arise post-operation, including rejection of the mesh that is used to repair the hernia. In the event of a mesh rejection, the mesh will very likely need to be removed. Mesh rejection can be detected by obvious, sometimes localized swelling and pain around the mesh area. Continuous discharge from the scar is likely for a while after the mesh has been removed.
A surgically treated hernia can lead to complications such as inguinodynia, while an untreated hernia may be complicated by:
Inflammation
Obstruction of any lumen, such as bowel obstruction in intestinal hernias
Strangulation
Hydrocele of the hernial sac
Hemorrhage
Autoimmune problems
Irreducibility or incarceration, in which it cannot be reduced, or pushed back into place, at least not without very much external effort. In intestinal hernias, this also substantially increases the risk of bowel obstruction and strangulation.
Causes
Causes of hiatus hernia vary depending on each individual. Among the multiple causes, however, are the mechanical causes which include: improper heavy weight lifting, hard coughing bouts, sharp blows to the abdomen, and incorrect posture.Furthermore, conditions that increase the pressure of the abdominal cavity may also cause hernias or worsen the existing ones. Some examples would be: obesity, straining during a bowel movement or urination (constipation, enlarged prostate), chronic lung disease, and also, fluid in the abdominal cavity (ascites).Also, if muscles are weakened due to poor nutrition, smoking, and overexertion, hernias are more likely to occur.
The physiological school of thought contends that in the case of inguinal hernia, the above-mentioned are only an anatomical symptom of the underlying physiological cause. They contend that the risk of hernia is due to a physiological difference between patients who have hernia and those who do not, namely the presence of aponeurotic extensions from the transversus abdominis aponeurotic arch.Abdominal wall hernia may occur due to trauma. If this type of hernia is due to blunt trauma it is an emergency condition and could be associated with various solid organs and hollow viscus injuries.
Diagnosis
Inguinal
By far the most common hernias (up to 75% of all abdominal hernias) are inguinal hernias, which are further divided into the more common indirect inguinal hernia (2/3, depicted here), in which the inguinal canal is entered via a congenital weakness at its entrance (the internal inguinal ring), and the direct inguinal hernia type (1/3), where the hernia contents push through a weak spot in the back wall of the inguinal canal. Inguinal hernias are the most common type of hernia in both men and women. In some selected cases, they may require surgery.
There are special cases where a direct and indirect hernia appear together. A pantaloon hernia (or saddlebag hernia) is a combined direct and indirect hernia when the hernial sac protrudes on either side of the inferior epigastric vessels.
Additionally, though very rare, two or more indirect hernias may appear together such as in a double indirect hernia.
Femoral
Femoral hernias occur just below the inguinal ligament, when abdominal contents pass into the weak area at the posterior wall of the femoral canal. They can be hard to distinguish from the inguinal type (especially when ascending cephalad): however, they generally appear more rounded, and, in contrast to inguinal hernias, there is a strong female preponderance in femoral hernias. The incidence of strangulation in femoral hernias is high. Repair techniques are similar for femoral and inguinal hernia.
A Coopers hernia is a femoral hernia with two sacs, the first being in the femoral canal, and the second passing through a defect in the superficial fascia and appearing almost immediately beneath the skin.
Umbilical
They involve protrusion of intra-abdominal contents through a weakness at the site of passage of the umbilical cord through the abdominal wall.
Umbilical hernias in adults are largely acquired, and are more frequent in obese or pregnant women. Abnormal decussation of fibers at the linea alba may be a contributing factor.
Incisional
An incisional hernia occurs when the defect is the result of an incompletely healed surgical wound. When these occur in median laparotomy incisions in the linea alba, they are termed ventral hernias. These can be the most frustrating and difficult to treat, as the repair utilizes already attenuated tissue. These occur in about 13% of people at 2 years following surgery.
Diaphragmatic
Higher in the abdomen, an (internal) "diaphragmatic hernia" results when part of the stomach or intestine protrudes into the chest cavity through a defect in the diaphragm.
A hiatus hernia is a particular variant of this type, in which the normal passageway through which the esophagus meets the stomach (esophageal hiatus) serves as a functional "defect", allowing part of the stomach to (periodically) "herniate" into the chest. Hiatus hernias may be either "sliding", in which the gastroesophageal junction itself slides through the defect into the chest, or non-sliding (also known as para-esophageal), in which case the junction remains fixed while another portion of the stomach moves up through the defect. Non-sliding or para-esophageal hernias can be dangerous as they may allow the stomach to rotate and obstruct. Repair is usually advised.
A congenital diaphragmatic hernia is a distinct problem, occurring in up to 1 in 2000 births, and requiring pediatric surgery. Intestinal organs may herniate through several parts of the diaphragm, posterolateral (in Bochdaleks triangle (lumbocostal triangle), resulting in a Bochdalek hernia), or anteromedial-retrosternal (in the cleft of foramina of Morgagni (sternocostal triangle), resulting in a Morgagnis hernia).
Other hernias
Since many organs or parts of organs can herniate through many orifices, it is very difficult to give an exhaustive list of hernias, with all synonyms and eponyms. The above article deals mostly with "visceral hernias", where the herniating tissue arises within the abdominal cavity. Other hernia types and unusual types of visceral hernias are listed below, in alphabetical order:
Abdominal wall hernias:
Umbilical hernia
Epigastric hernia: a hernia through the linea alba above the umbilicus.
Spigelian hernia, also known as spontaneous lateral ventral hernia
Amyands hernia: containing the appendix vermiformis within the hernia sac
Brain herniation, sometimes referred to as brain hernia, is a potentially deadly side effect of very high intracranial pressure that occurs when a part of the brain is squeezed across structures within the skull.
Broad ligament hernia, of the uterus.
Double indirect hernia: an indirect inguinal hernia with two hernia sacs, without a concomitant direct hernia component (as seen in a pantaloon hernia).
Hiatus hernia: a hernia due to "short oesophagus" — insufficient elongation — stomach is displaced into the thorax
Littres hernia: a hernia involving a Meckels diverticulum. It is named after the French anatomist Alexis Littré (1658–1726).
Lumbar hernia: a hernia in the lumbar region (not to be confused with a lumbar disc hernia), contains the following entities:
Petits hernia: a hernia through Petits triangle (inferior lumbar triangle). It is named after French surgeon Jean Louis Petit (1674–1750).
Grynfeltts hernia: a hernia through Grynfeltt-Lesshaft triangle (superior lumbar triangle). It is named after physician Joseph Grynfeltt (1840–1913).
Maydls hernia: two adjacent loops of small intestine are within a hernial sac with a tight neck. The intervening portion of bowel within the abdomen is deprived of its blood supply and eventually becomes necrotic.
Obturator hernia: hernia through obturator canal
Parastomal hernias, which is when tissue protrudes adjacent to a stoma tract.
Paraumbilical hernia: a type of umbilical hernia occurring in adults
Perineal hernia: a perineal hernia protrudes through the muscles and fascia of the perineal floor. It may be primary but usually is acquired following perineal prostatectomy, abdominoperineal resection of the rectum, or pelvic exenteration.
Properitoneal hernia: rare hernia located directly above the peritoneum, for example, when part of inguinal hernia projects from the deep inguinal ring to the preperitoneal space.
Richters hernia: a hernia involving only one sidewall of the bowel, which can result in bowel strangulation leading to perforation through ischaemia without causing bowel obstruction or any of its warning signs. It is named after German surgeon August Gottlieb Richter (1742–1812).
Sliding hernia: occurs when an organ drags along part of the peritoneum, or, in other words, the organ is part of the hernia sac. The colon and the urinary bladder are often involved. The term also frequently refers to sliding hernias of the stomach.
Sciatic hernia: this hernia in the greater sciatic foramen most commonly presents as an uncomfortable mass in the gluteal area. Bowel obstruction may also occur. This type of hernia is only a rare cause of sciatic neuralgia.
Sports hernia: a hernia characterized by chronic groin pain in athletes and a dilated superficial inguinal ring.
Tibialis anterior hernia: can present as a bulge in the shins. Pain on rest, walking, or during exercise may occur. The bulge can typically not be present unless pressure or flexing of the leg occurs.
Velpeau hernia: a hernia in the groin in front of the femoral blood vessels
Treatment
Truss
The benefits of the use of an external device to maintain reduction of the hernia without repairing the underlying defect (such as hernia trusses, trunks, belts, etc.) are unclear.
Surgery
Surgery is recommended for some types of hernias to prevent complications such as obstruction of the bowel or strangulation of the tissue, although umbilical hernias and hiatus hernias may be watched, or are treated with medication. Most abdominal hernias can be surgically repaired, but surgery has complications. Time needed for recovery after treatment is reduced if hernias are operated on laparoscopically. However, open surgery can be done sometimes without general anesthesia. Robot-assisted hernia surgery has also recently gained popularity as safe alternatives to open surgery.
Uncomplicated hernias are principally repaired by pushing back, or "reducing", the herniated tissue, and then mending the weakness in muscle tissue (an operation called herniorrhaphy). If complications have occurred, the surgeon will check the viability of the herniated organ and remove part of it if necessary.
Muscle reinforcement techniques often involve synthetic materials (a mesh prosthesis). The mesh is placed either over the defect (anterior repair) or under the defect (posterior repair). At times staples are used to keep the mesh in place. These mesh repair methods are often called "tension free" repairs because, unlike some suture methods (e.g., Shouldice), muscle is not pulled together under tension. However, this widely used terminology is misleading, as there are many tension-free suture methods that do not use mesh (e.g., Desarda, Guarnieri, Lipton-Estrin, etc.).
Evidence suggests that tension-free methods (with or without mesh) often have lower percentage of recurrences and the fastest recovery period compared to tension suture methods. However, among other possible complications, prosthetic mesh usage seems to have a higher incidence of chronic pain and can also cause infections.The frequency of surgical correction ranges from 10 per 100,000 (U.K.) to 28 per 100,000 (U.S.).
Recovery
Many patients are managed through day surgery centers and are able to return to work within a week or two, though intense activities are prohibited for a longer period. People who have their hernias repaired with mesh often recover within a month, but pain can last longer. Surgical complications may include pain that lasts more than three months, surgical site infections, nerve and blood vessel injuries, injury to nearby organs, and hernia recurrence. Pain that lasts more than three months occurs in about 10% of people following hernia repair.
Epidemiology
About 27% of males and 3% of females develop a groin hernia at some time in their lives. In 2013 about 25 million people had a hernia. Inguinal, femoral and abdominal hernias resulted in 32,500 deaths globally in 2013 and 50,500 in 1990.
References
External links
Hernia at Curlie
"hernia". MedlinePlus. U.S. National Library of Medicine. |
Enamel-renal syndrome | Enamel-renal syndrome is a rare autosomal recessive condition. This condition is also known as idiopathic multicentric osteolysis with nephropathy. It is characterised by dental abnormalities and nephrocalcinosis.
Presentation
The dental abnormalities include
hypoplastic amelogenesis imperfecta
microdontia
intra-pulpal calcification
impacted posterior teeth with hyperplastic pericoronal follicles
gingival fibromatosis
ectopic calcifications on gingival and pericoronal tissues
Genetics
This condition is caused by mutations in the FAM20A gene. This gene encodes a protein – the Golgi apparatus associated secretory pathway pseudokinase. The gene is located on the long arm of chromosome 17 (17q24.2).
Pathogensis
The protein is an allosteric activator of the Golgi serine/threonine protein kinase and is involved in biomineralization of teeth.
Diagnosis
The diagnosis may be suspected on the basis of the constellation of clinical features. It is made by sequencing the FAM20A gene.
This condition is usually diagnosed in childhood but may not be recognised until early adulthood. The diagnosis is suspected on the combination of nephrocalcinosis and dental abnormalities.
Differential diagnosis
Epidermolysis bullosa
Jalili syndrome
Raine syndrome
Tricho-dento-osseous syndrome
Treatment
There is no specific treatment for this condition currently known and management of its various features is the norm.
History
This condition was first described in 1972.
== References == |
Congenital nephrotic syndrome | Congenital nephrotic syndrome is a rare kidney disease which manifests in infants during the first 3 months of life, and is characterized by high levels of protein in the urine (proteinuria), low levels of protein in the blood, and swelling. This disease is primarily caused by genetic mutations which result in damage to components of the glomerular filtration barrier and allow for leakage of plasma proteins into the urinary space.
Signs and symptoms
Urine protein loss leads to total body swelling (generalized edema) and abdominal distension in the first several weeks to months of life. Fluid retention may lead to cough (from pulmonary edema), ascites, and widened cranial sutures and fontanelles. High urine protein loss can lead to foamy appearance of urine. Infants may be born prematurely with low birth weight, and have meconium stained amniotic fluid or a large placenta.
Complications
Frequent, severe infections: urinary loss of immunoglobulins
Malnutrition and poor growth
Blood clots (hypercoagulability): imbalance of plasma coagulation factors from urine protein loss
Hypothyroidism: urinary loss of thyroid-binding protein
Poor bone health associated with vitamin D deficiency: urinary loss of vitamin D binding protein
Acute kidney injury
Chronic kidney disease and ultimately end-stage kidney disease
Causes
Primary (genetic) causes
Mutations in the following five genes account for greater than 80% of the genetic causes of congenital nephrotic syndrome:
NPHS1 (Finnish Type): The gene NPHS1 encodes for the protein nephrin. This genetic variant is characterized by severe protein loss in the first several days to weeks of life. Fin-major and Fin-minor were the first two main genetic mutations identified in Finnish newborns, however, numerous mutations have now been identified in patients all over the world from various ethnic groups. NPHS1 mutations are the most common cause of primary congenital nephrotic syndrome, accounting for 40-80% of cases.
NPHS2: This gene encodes for the protein podocin. Patients with this genetic mutation develop nephrotic syndrome in the first few weeks of infancy, but can also manifest symptoms later in life. Urinary protein loss is less severe when compared with the Finnish type. Both nephrin and podocin play important roles in the structure and function of the podocyte filtration slit diaphragm and disease involvement is typically limited to the kidneys
WT1: The Wilms tumor suppressor gene regulates the expression of many genes involved in kidney and urogenital development. Mutations lead to several types of developmental syndromes, including Denys-Drash syndrome, Frasier syndrome, WAGR syndrome (Wilms tumor, aniridia, genitourinary abnormalities, and intellectual disability), and isolated nephrotic syndrome in infants. Depending on the specific syndrome, patients are at risk for Wilms and other tumors, genital abnormalities, and nephrotic syndrome.
LAMβ2 (Pierson syndrome): This gene encodes for the protein laminin β2, which helps attach podocytes to the glomerular basement membrane. Patients with Pierson syndrome have eye abnormalities, including nonreactive narrowing of the pupils (microcoria), and neurologic deficits.
PLCε1: Codes for the enzyme Phospholipase Cε1, which is expressed in podocytes.
Secondary Causes
Congenital infections: syphilis, cytomegalovirus, toxoplasmosis, rubella, human immunodeficiency virus (HIV), malaria, hepatitis B
Immunologic: maternal systemic lupus erythematosus
Diagnosis
An examination reveals massive fluid retention and generalized swelling. Abnormal sounds are heard when listening to the heart and lungs with a stethoscope. Blood pressure may be high. The patient may have signs of malnutrition.A urinalysis reveals large amounts of protein and sometimes small amounts of blood in the urine. Kidney function may be normal in the first weeks or months of life. Laboratory studies show low serum levels of protein (albumin) and immunoglobulins, and elevated levels of triglycerides and cholesterol. Blood work may also show thyroid and vitamin D deficiency. Kidneys on ultrasound imaging may appear enlarged and brighter (hyperechoic). The disorder can be screened during pregnancy by finding elevated levels of alpha-fetoprotein on a routine sampling of amniotic fluid.Indication for kidney biopsy remains unclear as histologic findings do no reveal the cause of congenital nephrotic syndrome, but findings may help in developing treatment strategies. Findings on light microscopy can vary from minimal change nephropathy to focal segmental glomerulosclerosis or diffuse mesanigial sclerosis. Electron microscopy shows podocyte disruption (loss of foot processes or slit diaphragm).Genetic analysis and infectious workup are needed to determine the precise cause of congenital nephrotic syndrome. Understanding the underlying cause can assist in disease management, prognosis, and genetic counseling.
Treatment
Genetic forms of nephrotic syndrome are typically resistant to steroid and other immunosuppressive treatment. Goals of therapy are to control urinary protein loss and swelling, provide good nutrition to allow the child to grow, and prevent complications. Early and aggressive treatment is required to control the disorder.
Patients with severe urine protein loss require albumin infusions help replace protein loss and diuretic medications help rid the body of excess fluid. For patients with mild to moderate urine protein losses, ACE inhibitor medications (like Captopril and others) and non-steroidal anti-inflammatory drugs (like indomethacin) are used to slow the spilling of protein (albumin) in the urine. Removal of the kidneys (one at the time or both) can decrease protein loss and limit the number of albumin infusions needed. Infants with WT1 mutations will undergo bilateral kidney removal to prevent development of Wilms tumor.Antibiotics may be needed to control infections. Immunizations are recommended after kidney removal but prior to transplantation. Patients may also take iron supplements, potassium chloride, thyroxine and other vitamins to replenish what minerals the kidneys have leaked out. Anticoagulants (such as aspirin, dipyridamole, and warfarin) are used to prevent clot formation.Dietary modifications may include the restriction of sodium and use of dietary supplements as appropriate for the nature and extent of malnutrition. Fluids may be restricted to help control swelling. Children with this disease require diets high in calories and protein, and many patients require a feeding tube (nasogastric tube or gastrostomy tube (g-tube)) for medication and/or feeds. Some patients develop oral aversions and will use the tube for all feeds. Other patients eat well and only use the tube for medicine or supplemental feeds. The tube is also useful for patients needing to drink large amounts of fluids around the time of transplant.While infants with infectious causes of congenital nephrotic syndrome may improve with antibiotics or antiviral medications, those with genetic causes progress to end-stage renal disease and require dialysis, and ultimately a kidney transplant.
Prognosis
Congenital nephrotic syndrome can be successfully controlled with early diagnosis and aggressive treatment including albumin infusions, nephrectomy, and medications. Affected children have rapid decline in kidney function resulting in end-stage renal disease within the first years of life, and require treatment with dialysis and kidney transplantation. Most children live fairly normal life post-transplant but will spend significant time hospitalised pre-transplant and have numerous surgeries to facilitate treatment. Kidney transplantation outcomes for children with congenital nephrotic syndrome are similar to those of other patient groups. Nephrotic syndrome typically does not reoccur following kidney transplantation, however recurrences have been seen in children with NPHS1 mutations who develop anti-nephrin antibodies.Due to the protein (albumin) losses many patients have reduced muscle tone and may experience delays in certain physical milestones such as sitting, crawling and walking. Similarly many patients experience growth delays due to protein loss. Delays vary from mild to significant but most patients experience growth spurts once they receive their transplanted kidney. Physical therapy may be useful for the child to strengthen muscle tone. Children who have a history of stroke from thrombotic complications can have neurologic delays.Undiagnosed cases are often fatal in the first year due to blood clots, infections or other complications.
References
External links
OMIM: 256300 Congenital nephrotic syndrome, Finnish type; Congenital nephrotic syndrome 1 at NIHs Office of Rare Diseases
OMIM: 609049 Pierson syndrome; Microcoria and congenital nephrotic syndrome at NIHs Office of Rare Diseases |
Ichthyosis hystrix | Ichthyosis hystrix is a group of rare skin disorders in the ichthyosis family of skin disorders characterized by massive hyperkeratosis with an appearance like spiny scales. This term is also used to refer to a type of epidermal nevi with extensive bilateral distribution.
Types
Ichthyosis hystrix, Curth-Macklin type
The symptoms of ichthyosis hystrix Curth-Macklin are similar to epidermolytic hyperkeratosis (NPS-2 type) but there is no blistering and the hyperkeratosis is verrucous or spine-like. The hyperkeratosis is brown-grey in colour and is most obvious on the arms and legs. It is an autosomal dominant condition and can be caused by errors to the KRT1 gene. It is named after Helen Ollendorff Curth (1899-1982), a German-Jewish dermatologist, and Madge Thurlow Macklin (1893–1962), an American medical geneticist, and is one of the first syndromes named after two women.
Ichthyosis hystrix, Lambert type
Also known as ichthyosis hystrix gravior or porcupine man. This disease is characterised by spiny scales which cover the entire body except the face, genitals, palms and soles. The only known cases were in Edward Lambert (known as the porcupine man) who was exhibited in front of the Royal Society in London in 1731 and three generations of his descendants. No cases of this disease are now known though some experts believe that it may have been a type of epidermolytic hyperkeratosis. From the history of the Lambert family the disease appears to have been an autosomal dominant condition.
Hystrix-like ichthyosis with deafness syndrome
HID syndrome is also known as ichthyosis hystrix, Rheydt type after the German city of Rheydt near Düsseldorf where it was first discovered. Symptoms are bilateral hearing loss and spiky hyperkeratotic masses which cover the whole body though the palms and soles are less badly affected. It can be differentiated from KID syndrome which also has symptoms of deafness and ichthyosis by the different distribution of hyperkeratosis. It is an autosomal dominant condition caused by a mutation to the GJB2 gene (the same gene affected by KID syndrome).
Ichthyosis hystrix, Baefvertstedt type
An extremely rare disease of which only a few isolated cases are known.
See also
List of cutaneous conditions
List of cutaneous conditions caused by mutations in keratins
List of radiographic findings associated with cutaneous conditions
References
== External links == |
Klatskin tumor | A Klatskin tumor (or hilar cholangiocarcinoma) is a cholangiocarcinoma (cancer of the biliary tree) occurring at the confluence of the right and left hepatic bile ducts. The disease was named after Gerald Klatskin, who in 1965 described 15 cases and found some characteristics for this type of cholangiocarcinoma
Cause
The cause of cholangiocarcinoma has not been defined. A number of pathologic conditions, however, resulting in either acute or chronic biliary tract epithelial injury may predispose to malignant change. Primary sclerosing cholangitis, an idiopathic inflammatory condition of the biliary tree, has been associated with the development of cholangiocarcinoma in up to 40% of patients. Congenital biliary cystic disease, such as choledochal cysts or Carolis disease, has also been associated with malignant transformation in up to 25% of cases. These conditions appear to be related to an anomalous pancreatico-biliary duct junction and, perhaps, are related to the reflux of pancreatic secretions into the bile duct. Chronic biliary tract parasitic infection, seen commonly in Southeast Asia due to Clonorchis sinensis and Opisthorchis viverrini, has also been identified as a risk factor. Although gallstones and cholecystectomy are not thought to be associated with an increased incidence of cholangiocarcinoma, hepatolithiasis and choledocholithiasis may predispose to malignant change. Further, industrial exposure to asbestos and nitrosamines, and the use of the radiologic contrast agent, Thorotrast (thorium dioxide), are considered to be risk factors for the development of cholangiocarcinoma.
Diagnosis
Levels of the tumor markers carbohydrate antigen 19-9 (CA 19–9), carcinoembryonic antigen (CEA) and CA 125 are abnormally high in the bloodstreams of patients with intrahepatic cholangiocarcinoma and Klatskin tumor. The serum CA 19–9 in particular may be very high. The ultrasonography (and the use of Doppler modes) permit definitive diagnosis of a large number of lesions and the involvement of hepatic hilum, but it is less sensitive than CT or MRI in detecting focal lesions. Ultrasonography always detects dilatation of the bile ducts, but more rarely the tumor itself.Magnetic resonance cholangiopancreatography (MRCP) is a good non-invasive alternative to these other procedure. This technique demonstrates hepatic parenchyma and its accurate for detecting nodular carcinomas and infiltrating lesions.
Treatment
Because of their location, these tumors tend to become symptomatic late in their development and therefore are not usually resectable at the time of presentation. Complete resection of the tumor, especially in early-stage disease, offers hope of long-term survival. However, patients that are candidates for resectability are few and moreover many of these patients will have a relapse despite apparent removal of the tumor. The type of surgery and the extent of the resection depend on the location of the tumor and the degree of extension. In some cases, the obstruction, jaundice may present early and compel the patient to seek help. More often, liver resection is not a viable option because many patients are of advanced age, have multiple co-pathologies and are therefore at high risk.
Of late there has been renewed interest in liver transplantation from deceased donors along with add on therapy. Prognosis remains poor.
Epidemiology
Approximately 15,000 new cases of liver and biliary tract carcinoma are diagnosed annually in the United States, with roughly 10% of these cases being Klatskin tumors. Cholangiocarcinoma accounts for approximately 2% of all cancer diagnoses, with an overall incidence of 1.2/100,000 individuals. Two-thirds of cases occur in patients over the age of 65, with a nearly ten-fold increase in patients over 80 years of age. The incidence is similar in both men and women.
References
== External links == |
Speech delay | Speech delay, also known as alalia, refers to a delay in the development or use of the mechanisms that produce speech. Speech – as distinct from language – is the actual process of making sounds, using such organs and structures as the lungs, vocal cords, mouth, tongue, teeth, etc. Language delay refers to a delay in the development or use of the knowledge of language.
Because language and speech are two independent stages, they may be individually delayed. For example, a child may be delayed in speech (i.e., unable to produce intelligible speech sounds), but not delayed in language. In this case, the child would be attempting to produce an age appropriate amount of language, but that language would be difficult or impossible to understand. Conversely, since a child with a language delay typically has not yet had the opportunity to produce speech sounds, it is likely to have a delay in speech as well.
Signs and symptoms
The warning signs of early speech delay are categorized into age-related milestones, beginning at the age of 12 months and continuing through early adolescence.At the age of 12 months, there is cause for concern if the child is not able to do the following:
Using gestures such as waving good-bye and pointing at objects
Practicing the use of several different consonant sounds
Vocalizing or communicating needsBetween the ages of 15 and 18 months children are at a higher risk for speech delay if they are displaying the following:
Not saying "momma" and "dada"
Not reciprocating when told "no", "hello", and "bye"
Does not have a one to three word vocabulary at 12 months and up to 15 words by 18 months
Is unable to identify body parts
Displaying difficulties imitating sounds and actions
Shows preference to gestures over verbalizationAdditional signs of speech delay after the age of 2 years and up to the age of 4 include the following:
Inability to spontaneously produce words and phrases
Inability to follow simple directions and commands
Cannot make two word connections
Lacks consonant sounds at the beginning or end of words
Is difficult to understand by close family members
Is not able to display the tasks of common household objects
Is unable to form simple 2 to 3 word sentences
Effects
Studies show that children diagnosed with speech delay are more likely to present with behavioral and social emotional problems both in childhood and as adults. Decreased receptive language, reading, and learning skills are common side effects for children that have a speech delay and do not receive adequate intervention. Similar studies suggest that children with speech delays are more likely to have a difficult time communicating and bonding with peers, which could have negative effects on their psychosocial health later in life.
Causes
At times, speech delay and impairment is caused by a physical disruption in the mouth such as a deformed frenulum, lips, or palate. If the motion or ability to form words and appropriate sounds is disrupted, the child may be slow to pick up words and lack the ability to shape their mouth and tongue in the formation of words.Other more serious concerns are those that can be caused by oral-motor issues. Oral-motor dysfunction refers to a lack or delay in the area of the brain that speech is formed and created and communicated to the mouth and tongue. While speech may be the only concern, this disorder can be highlighted with feeding issues as well.Children that are having speech delay disorders could have the following characteristics (Shriberg 1982):
Speech mechanism in which speech is associated with hearing, motor speech and craniofacial malfunction
Cognitive-linguistic aspects in which the impairment is associated with the childs intellectual, receptive, expressive and linguistic ability.
Psychosocial issues in which the impairment is associated with caregiver, school environment, and the childs self behaviors such as aggression and maturityThe many other causes of speech delay include bilingual children with phonological disorders, autism spectrum conditions, childhood apraxia, auditory processing disorder, prematurity, cognitive impairment and hearing loss. In addition, when children are addicted to screens, they arent stimulated to be involved in conversations, causing speech delays. Broomfield and Dodds (2004a) found out after survey that 6.4% of children who are perfectly normal showed speech difficulty while they lacked these disorders will often show early signs and are at times identified as "at risk" when the speech delay is diagnosed.
In the case of speech delay in a child with autism, there may not be a physiological cause such as an oral-motor issue or hearing loss. The child may prefer to communicate using non-spoken language or use a nonverbal communication method. Studies show that early interventions may help a child with cerebral palsy, autism spectrum disorder or Down syndrome acquire language skills necessary for social communication to a certain degree.
Therapies and treatments
After the initial diagnosis of speech delay, a hearing test will be administered to ensure that hearing loss or deafness is not an underlying cause of the delay. If a child has successfully completed the hearing test, the therapy or therapies used will be determined. There are many therapies available for children that have been diagnosed with a speech delay, and for every child, the treatment and therapies needed vary with the degree, severity, and cause of the delay. While speech therapy is the most common form of intervention, many children may benefit from additional help from occupational and physical therapies as well. Physical and occupational therapies can be used for a child that has a speech delay due to physical malformations and children that have also been diagnosed with a developmental delay such as autism or a language processing delay. Music therapy has effective results in the fundamentals of speech development, including phonological memory, sentence understanding, sentence memory, and morphological rule generation. Children that have been identified with hearing loss can be taught simple sign language to build and improve their vocabulary in addition to attending speech therapy.
The parents of a delayed child are the first and most important tool in helping overcome the speech delay. The parent or caregiver of the child can provide the following activities at home, in addition to the techniques suggested by a speech therapist, to positively influence the growth of speech and vocabulary:
Reading to the child regularly
Use of questions and simple, clear language
Positive reinforcement in addition to patienceFor children that have a physical disorder that is causing difficulty forming and pronouncing words, parents and caregivers suggest using and introducing different food textures to exercise and build jaw muscles while promoting new movements of the jaw while chewing. Another less studied technique used to combat and treat speech delay is a form of therapy using music to promote and facilitate speech and language development. It is important to understand that music therapy is a newer therapy and has yet to be thoroughly studied and practiced on children with speech delays and impediments.
See also
References
Further reading
Kennison, S. M. (2013). Introduction to Language Development. Los Angeles, CA: Sage.
External links
American Speech-Language-Hearing Association (ASHA): Different Issues in Speech and Language Development.
KidsHealth:Delay in Speech and Language
Early Identification of Speech-Language Delays and Disorders
The Listen Up Web-Language Development
YourChild: Speech and Language Delays and Disorders University of Michigan Health System |
Sialidosis | Mucolipidosis type I (ML I) is an inherited lysosomal storage disease that results from a deficiency of the enzyme alpha-N -acetyl neuraminidase (sialidase). The lack of this enzyme results in an abnormal accumulation of complex carbohydrates known as mucopolysaccharides, and of fatty substances known as mucolipids. Both of these substances accumulate in bodily tissues.
Presentation
Symptoms of ML I are either present at birth or develop within the first year of life. In many infants with ML I, excessive swelling throughout the body is noted at birth. These infants are often born with coarse facial features, such as a flat nasal bridge, puffy eyelids, enlargement of the gums, and excessive tongue size (macroglossia). Many infants with ML I are also born with skeletal malformations such as hip dislocation. Infants often develop sudden involuntary muscle contractions (called myoclonus) and have red spots in their eyes (cherry red spots). They are often unable to coordinate voluntary movement (called ataxia). Tremors, impaired vision, and seizures also occur in children with ML I. Tests reveal abnormal enlargement of the liver (hepatomegaly) and spleen (splenomegaly) and extreme abdominal swelling. Infants with ML I generally lack muscle tone (hypotonia) and have mental retardation that is either initially or progressively severe. Many patients suffer from failure to thrive and from recurrent respiratory infections. Most infants with ML I die before the age of 1 year.
Related conditions
Other diseases that result from a deficiency in the sialidase enzyme are categorized in a broader group known as sialidoses. Because ML I is classified as a sialidosis, it is sometimes referred to as sialidosis type II.
A rarer form of sialidosis – sialidosis type 1– occurs in children and adolescents and is often referred to as the juvenile form of the disorder. Children usually begin to show symptoms during the second decade of life, and myoclonus and cherry-red macules are often the initial symptoms. Patients usually develop seizures and progressive deterioration of coordinated muscular and mental activities.
Pathophysiology
The role of sialidase is to remove a particular form of sialic acid (a sugar molecule) from sugar-protein complexes (referred to as glycoproteins), which allows the cell to function properly. Because the enzyme is deficient, small chains containing the sugar-like material accumulate in neurons, bone marrow, and various cells that defend the body against infection.
Diagnosis
The detection of high urinary sialyl oligosaccharides and the confirmation of lysosomal enzyme deficiency in leukocytes or cultured fibroblasts make the diagnosis.
Management
Treatment of sialidosis is similar to the other progressive myoclonic epilepsy disorders, which consists of managing seizures and myoclonus along with palliative, supportive, and rehabilitative care.
See also
Fucosidosis
Sialic acid
Neuraminidase
Mucolipidosis
Lysosomal storage disease
Notes
References
mucolipidoses at NINDS - article derived from detail sheet available here
External links
Sialidosis type 1 and 3 at NIHs Office of Rare Diseases
Sialidosis at NIHs Office of Rare Diseases |
Neonatal jaundice | Neonatal jaundice is a yellowish discoloration of the white part of the eyes and skin in a newborn baby due to high bilirubin levels. Other symptoms may include excess sleepiness or poor feeding. Complications may include seizures, cerebral palsy, or kernicterus.In most of cases there is no specific underlying disorder (physiologic). In other cases it results from red blood cell breakdown, liver disease, infection, hypothyroidism, or metabolic disorders (pathologic). A bilirubin level more than 34 μmol/L (2 mg/dL) may be visible. Concerns, in otherwise healthy babies, occur when levels are greater than 308 μmol/L (18 mg/dL), jaundice is noticed in the first day of life, there is a rapid rise in levels, jaundice lasts more than two weeks, or the baby appears unwell. In those with concerning findings further investigations to determine the underlying cause are recommended.The need for treatment depends on bilirubin levels, the age of the child, and the underlying cause. Treatments may include more frequent feeding, phototherapy, or exchange transfusions. In those who are born early more aggressive treatment tends to be required. Physiologic jaundice generally lasts less than seven days. The condition affects over half of babies in the first week of life. Of babies that are born early about 80% are affected. Globally over 100,000 late-preterm and term babies die each year as a result of jaundice.
Sign and symptoms
Bronze baby syndrome (dark pigmentation of skin).
The primary symptom is yellowish discoloration of the white part of the eyes and skin in a newborn baby. Other symptoms may include excess sleepiness or poor feeding.A bilirubin level more than 34 μmol/L (2 mg/dL) may be visible. For the feet to be affected level generally must be over 255 μmol/L (15 mg/dL).
Complications
Prolonged hyperbilirubinemia (severe jaundice) can result in chronic bilirubin encephalopathy (kernicterus). Quick and accurate treatment of neonatal jaundice helps to reduce the risk of neonates developing kernicterus.Infants with kernicterus may have a fever or seizures. High pitched crying is an effect of kernicterus.Exchange transfusions performed to lower high bilirubin levels are an aggressive treatment.
Causes
In newborns, jaundice tends to develop because of two factors—the breakdown of fetal hemoglobin as it is replaced with adult hemoglobin and the relatively immature metabolic pathways of the liver, which are unable to conjugate and so excrete bilirubin as quickly as an adult. This causes an accumulation of bilirubin in the blood (hyperbilirubinemia), leading to the symptoms of jaundice.If the neonatal jaundice is not resolved with simple phototherapy, other causes such as biliary atresia, Progressive familial intrahepatic cholestasis, bile duct paucity, Alagille syndrome, alpha 1-antitrypsin deficiency, and other pediatric liver diseases should be considered. The evaluation for these will include blood work and a variety of diagnostic tests. Prolonged neonatal jaundice is serious and should be followed up promptly.Severe neonatal jaundice may indicate the presence of other conditions contributing to the elevated bilirubin levels, of which there are a large variety of possibilities (see below). These should be detected or excluded as part of the differential diagnosis to prevent the development of complications. They can be grouped into the following categories:
Unconjugated
Hemolytic
Intrinsic causes of hemolysis
Membrane conditions
Spherocytosis
Hereditary elliptocytosis
Enzyme conditions
Glucose-6-phosphate dehydrogenase deficiency (also called G6PD deficiency)
Pyruvate kinase deficiency
Globin synthesis defect
sickle cell disease
Alpha-thalassemia, e.g. HbH disease
Extrinsic causes of hemolysis
Systemic conditions
Sepsis
Arteriovenous malformation
Alloimmunity (The neonatal or cord blood gives a positive direct Coombs test and the maternal blood gives a positive indirect Coombs test)
Hemolytic disease of the newborn (ABO)
Rh disease
Hemolytic disease of the newborn (anti-Kell)
Hemolytic disease of the newborn (anti-Rhc)
Other blood type mismatches causing hemolytic disease of the newborn
Non-hemolytic causes
Breastfeeding jaundice
Breast milk jaundice
Cephalohematoma
Polycythemia
Urinary tract infection
Sepsis
Hypothyroidism
Gilberts syndrome
Crigler–Najjar syndrome
High GI obstruction (Pyloric stenosis, Bowel obstruction)
Conjugated (Direct)
Liver causes
Infections
Sepsis
Hepatitis A
Hepatitis B
TORCH infections
Metabolic
Galactosemia
Alpha 1-antitrypsin deficiency, which is commonly missed, and must be considered in DDx
Cystic fibrosis
Dubin–Johnson syndrome
Rotor syndrome
Drugs
Total parenteral nutrition
Idiopathic
Post-liver
Biliary atresia or bile duct obstruction
Alagille syndrome
Choledochal cyst
Non-organic causes
Breastfeeding jaundice
"Breastfeeding jaundice" (or "lack of breastfeeding jaundice") is caused by insufficient breast milk intake, resulting in inadequate quantities of bowel movements to remove bilirubin from the body. This leads to increased enterohepatic circulation, resulting in increased reabsorption of bilirubin from the intestines. Usually occurring in the first week of life, most cases can be ameliorated by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk production.
Breast milk jaundice
Whereas breastfeeding jaundice is a mechanical problem, breast milk jaundice is a biochemical occurrence and the higher bilirubin possibly acts as an antioxidant. Breast milk jaundice occurs later in the newborn period, with the bilirubin level usually peaking in the sixth to 14th days of life. This late-onset jaundice may develop in up to one third of healthy breastfed infants.
The gut is sterile at birth and normal gut flora takes time to establish. The bacteria in the adult gut convert conjugated bilirubin to stercobilinogen which is then oxidized to stercobilin and excreted in the stool. In the absence of sufficient bacteria, the bilirubin is de-conjugated by brush border β-glucuronidase and reabsorbed. This process of re-absorption is called enterohepatic circulation. It has been suggested that bilirubin uptake in the gut (enterohepatic circulation) is increased in breast fed babies, possibly as the result of increased levels of epidermal growth factor (EGF) in breast milk. Breast milk also contains glucoronidase which will increase deconjugation and enterohepatic recirculation of bilirubin.
The breast-milk of some women contains a metabolite of progesterone called 3-alpha-20-beta pregnanediol. This substance inhibits the action of the enzyme uridine diphosphoglucuronic acid (UDPGA) glucuronyl transferase responsible for conjugation and subsequent excretion of bilirubin. In the newborn liver, activity of glucuronyl transferase is only at 0.1-1% of adult levels, so conjugation of bilirubin is already reduced. Further inhibition of bilirubin conjugation leads to increased levels of bilirubin in the blood. However, these results have not been supported by subsequent studies.
An enzyme in breast milk called lipoprotein lipase produces increased concentration of nonesterified free fatty acids that inhibit hepatic glucuronyl transferase, which again leads to decreased conjugation and subsequent excretion of bilirubin.
Physiological jaundice
Most infants develop visible jaundice due to elevation of unconjugated bilirubin concentration during their first week. This is called physiological jaundice. This pattern of hyperbilirubinemia has been classified into two functionally distinct periods.
Phase oneTerm infants - jaundice lasts for about 10 days with a rapid rise of serum bilirubin up to 204 μmol/L (12 mg/dL).
Preterm infants - jaundice lasts for about two weeks, with a rapid rise of serum bilirubin up to 255 μmol/L (15 mg/dL).Phase two - bilirubin levels decline to about 34 μmol/L (2 mg/dL) for two weeks, eventually mimicking adult values.Preterm infants - phase two can last more than one month.
Exclusively breastfed infants - phase two can last more than one month.Mechanisms involved in physiological jaundice include:
Relatively low activity of the enzyme glucuronosyltransferase which normally converts unconjugated bilirubin to conjugated bilirubin that can be excreted into the gastrointestinal tract. Before birth, this enzyme is actively down-regulated, since bilirubin needs to remain unconjugated in order to cross the placenta to avoid being accumulated in the fetus. After birth, it takes some time for this enzyme to gain function.
Shorter life span of fetal red blood cells, being approximately 80 to 90 days in a full term infant, compared to 100 to 120 days in adults.
Relatively low conversion of bilirubin to urobilinogen by the intestinal flora, resulting in relatively high absorption of bilirubin back into the circulation.
Diagnosis
Diagnosis is often by measuring the serum bilirubin level in the blood. In those who are born after 35 weeks and are more than a day old transcutaneous bilirubinometer may also be used. The use of an icterometer, a piece of transparent plastic painted in five transverse strips of graded yellow lines, is not recommended.
Transcutaneous bilirubinometer
This is hand held, portable and rechargeable but expensive. When pressure is applied to the photoprobe, a xenon tube generates a strobe light, and this light passes through the subcutaneous tissue. The reflected light returns through the second fiber optic bundle to the spectrophotometric module. The intensity of the yellow color in this light, after correcting for the hemoglobin, is measured and instantly displayed in arbitrary units.
Pathological jaundice
Any of the following features suggests pathological jaundice:
Clinical jaundice appearing in the first 24 hours or greater than 14 days of life.
Increases in the level of total bilirubin by more than 8.5 μmol/L (0.5 mg/dL) per hour or (85 μmol/L) 5 mg/dL per 24 hours.
Total bilirubin more than 331.5 μmol/L (19.5 mg/dL) (hyperbilirubinemia).
Direct bilirubin more than 34 μmol/L (2.0 mg/dL).The signs which help detect pathological jaundice are the presence of intrauterine growth restriction, stigma of intrauterine infections (e.g. cataracts, small head, and enlargement of the liver and spleen), cephalohematoma, bruising, signs of bleeding in the brains ventricles. History of illness is noteworthy. Family history of jaundice and anemia, family history of neonatal or early infant death due to liver disease, maternal illness suggestive of viral infection (fever, rash or lymphadenopathy), maternal drugs (e.g. sulphonamides, anti-malarials causing red blood cell destruction in G6PD deficiency) are suggestive of pathological jaundice in neonates.
Treatment
The bilirubin levels for initiative of phototherapy varies depends on the age and health status of the newborn. However, any newborn with a total serum bilirubin greater than 359 μmol/L ( 21 mg/dL) should receive phototherapy.
Phototherapy
Babies with neonatal jaundice may be treated with colored light called phototherapy, which works by changing trans-bilirubin into the water-soluble cis-bilirubin isomer.: 2533 The phototherapy involved is not ultraviolet light therapy but rather a specific frequency of blue light. The light can be applied with overhead lamps, which means that the babys eyes need to be covered, or with a device called a biliblanket, which sits under the babys clothing close to its skin.The use of phototherapy was first discovered, accidentally, at Rochford Hospital in Essex, England, when a nurse, Sister Jean Ward, noticed that babies exposed to sunlight had reduced jaundice, and a pathologist, Dr. Perryman, who noticed that a vial of blood left in the sun had turned green. Drs Cremer, Richards and Dobbs put together these observations, leading to a landmark randomized clinical trial which was published in Pediatrics in 1968; it took another ten years for the practice to become established.
Massage therapy could be useful in addition to phototherapy in order to reduce the phototherapy duration. However, it does not appear to reduce the requirement for phototherapy in the treatment of neonatal jaundice.Recent studies from several countries show that phototherapy can safely and effectively be performed in the families home and since 2022 home phototherapy is recommended as an option to readmission to hospital in the american national guidelines.
Exchange transfusions
Much like with phototherapy the level at which exchange transfusion should occur depends on the health status and age of the newborn. It should however be used for any newborn with a total serum bilirubin of greater than 428 μmol/L ( 25 mg/dL ).: 2533
Research
Penicillamine was studied in the 1970s in hyperbilirubinemia due to ABO hemolytic disease. While tin mesoporphyrin IX may decrease bilirubin such use is not recommended in babies. Preclinical studies have looked at minocycline to help prevent neurotoxicity. Clofibrate may decrease the duration of phototherapy. Evidence as of 2012 however is insufficient to recommend its use.
References
External links
American Academy of Pediatrics has issued guidelines for managing this disease, which can be obtained for free.
National Institute for Health and Care Excellence (NICE) has issued guidelines for the recognition and treatment of neonatal jaundice in the United Kingdom. |
Sprue | A sprue may refer to:
Sprue (manufacturing), a feature in molding and casting molds
Coeliac disease, also known as sprue, a disease of the small intestine
Tropical sprue, disease
Sprue Asparagus, first pickings of asparagus |
Occupational acne | Occupational acne is caused by several different groups of industrial compounds, including coal tar derivatives, insoluble cutting oils, and chlorinated hydrocarbons (chlornaphthalenes, chlordiphenyls, and chlordiphenyloxides).: 499
See also
List of cutaneous conditions
References
== External links == |
Sheehans syndrome | Sheehans syndrome, also known as postpartum pituitary gland necrosis, is hypopituitarism (decreased functioning of the pituitary gland), caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth.
Signs and symptoms
The various signs and symptoms in Sheehans syndrome are caused by damage to the pituitary, thereby causing a decrease in one or more of the hormones it normally secretes. Because the pituitary controls many glands in the endocrine system, partial or complete loss of a variety of functions may result.The most common initial symptoms of Sheehans syndrome are agalactorrhea (absence of lactation) and/or difficulties with lactation. Many women also report amenorrhea or oligomenorrhea after delivery. In some cases, a woman with Sheehan syndrome is relatively asymptomatic; therefore, the diagnosis would not be made until years later, with features of hypopituitarism. Such features include secondary hypothyroidism (hypothyroidism due to pituitary dysfunction) with tiredness, intolerance to cold, constipation, weight gain, hair loss and slowed thinking, as well as a slowed heart rate and low blood pressure. Another such feature is secondary adrenal insufficiency (lack of ACTH secretion from the anterior pituitary). In a more chronic case, it is similar to Addisons disease with symptoms including fatigue, weight loss, hypoglycemia (low blood sugar levels), anemia and hyponatremia (low sodium levels). Such a patient may become acutely exacerbated when her body is stressed by a severe infection or surgery years after her delivery: a condition equivalent with an Addisonian crisis. The symptoms of adrenal crisis should be treated immediately and can be life-threatening. Gonadotropin deficiency will often cause amenorrhea, oligomenorrhea, hot flashes, or decreased libido. Cessation of menses is an important indicator of Gonadotropin deficiency as a result of Sheehan’s syndrome. Growth hormone deficiency causes many vague symptoms including fatigue and decreased muscle mass.Growth-hormone deficiency is the most common symptom of hypopituitarism seen in Sheehan’s syndrome with a 90–100% occurrence seen in the Netherlands, Costa Rica, and Saudi Arabia. In these populations the occurrence of Cortisol, TSH, and gonadotropin deficiencies ranges from 50 to 100%. Hematological changes may occur due to a decrease in erythropoietin synthesis as a result of these cortisol and thyroid hormone decreases.Uncommonly, Sheehan syndrome may also appear acutely after delivery, mainly by hyponatremia. Electrolytic imbalances might result from the increased secretion of ADH, which may be caused by a decrease in blood pressure due to glucocorticoid deficiency. There are several possible mechanisms by which hypopituitarism can result in hyponatremia, including decreased free-water clearance by hypothyroidism, direct syndrome of inappropriate antidiuretic hormone (ADH) hypersecretion, decreased free-water clearance by glucocorticoid deficiency (independent of ADH). Serum potassium levels, however, will not change due to Sheehan’s syndrome. This is because potassium levels are primarily regulated independently from the pituitary gland (the renin-angiotensin-aldosterone system begins in the kidney).
Causes
In the developed world Sheehan’s Syndrome is a rare complication of pregnancy, usually manifesting after excessive blood loss after delivery. The presence of disseminated intravascular coagulation (i.e., in amniotic fluid embolism or HELLP syndrome) also appears to be a factor in its development. A retrospective study in Turkey found that the prevalence of Sheehan’s syndrome was directly proportional to the amount of at-home deliveries each decade. This may be due to previously limited obstetric techniques present in a home environment. For example, an area of improvement in preventing the condition could be an increase in the efficacy of treatment to hypovolemic shock through blood transfusion.Pituitary necrosis may directly result from a lack of blood flow in the hypophyseal artery as a result of pituitary gland enlargement during pregnancy. One cause of pituitary growth associated with the risk of Sheehan’s syndrome is the hyperplasia of lactotrophs (responsible for prolactin production). Ischemia may occur as a result of vasospasm, thrombosis, or vascular compression sometimes as a result of an increase in the amount of lactotroph cells throughout gestation (contributing to the enlargement of the pituitary gland). Necrosis may occur as a result of severe hypotension or shock due to excessive uterine bleeding following childbirth. Sheehan’s syndrome may occur as a result of the arterial constriction and abnormal hypotension in conjunction with an insufficiency to meet the increased demand in blood supply of the pituitary gland seen during pregnancy. This increased blood-flow and metabolic demand is associated with the previously mentioned hyperplasia of lactotrophs.Some possible predisposing factors to Sheehan’s syndrome may include: inherited or acquired disseminated blood coagulation (DIC), restriction pituitary blood supply, small sella size, vasospasm, or thrombosis. Post-Partum Hemorrhaging (PPH) is believed to be a predictor of Sheehan’s syndrome, so the symptoms of anaemia, obesity, and advanced maternal age may increase the risk of Sheehan Syndrome. Atony of the uterus may be related to PPH that could induce Sheehan’s syndrome. This results in the abnormally prolonged flow of blood to the placenta after delivery.
Pathophysiology
Sheehans syndrome is caused by damage to the pituitary, thereby causing a decrease in one or more of the hormones it normally secretes. The anterior pituitary is supplied by a low pressure portal venous system. A 1995 study found that 56.2% of patients with diagnosed Sheehan’s syndrome experienced a loss of all pituitary hormones (with the remaining 43.8% having selective pituitary insufficiency). Since the growth hormone-secreting cells are located at the periphery of the pituitary (and are therefore most likely to be affected by ischemia), all of the patients experienced growth hormone deficiency.
Diagnosis
Hormonal assays are conducted to determine a patient has low levels of T4, TSH, estrogen, gonadotropin, cortisol, and ACTH depending on the extent of necrosis. It might be difficult to detect damage to these hormone pathways if hormone levels are at the borderline of the abnormal range. In this case, stimulation tests will be done to determine if the pituitary is responsive to hypothalamic hormones. For example, to determine deficiencies in cortisol release, synthetic ACTH might be administered, and hormonal assays will be conducted to determine the strength of the response. Additionally, MRI of the pituitary and hypothalamus: this helps to exclude tumor or other pathologies.
Treatment
Lifelong hormone replacement therapy for the hormones that are missing. This may involve treatment with glucocorticoids. After hormone profiling, treatment with cortisol, ACTH, thyroid hormones, gonadotropins, and prolactin as seen in cases of hypopituitarism may occur.
Epidemiology
In a study of 1,034 symptomatic adults, Sheehan’s syndrome was found to be the sixth-most frequent etiology of growth hormone deficiency, being responsible for 3.1% of cases (versus 53.9% due to a pituitary tumor).Sheehan syndrome is more prevalent in developing countries than developed countries. Additionally, it was found that the majority of women who experienced Sheehan syndrome gave birth at home rather than in a hospital.
History
The specific association with postpartum shock or hemorrhage was described in 1937 by the British pathologist Harold Leeming Sheehan (1900–1988). The initial distinction was made in the research article “Post-Partum Necrosis of the Anterior Pituitary”. In his research, Dr. Sheehan reviewed (through autopsy) the effects of pituitary necrosis on 12 cases of patient’s that experienced postpartum necrosis. He observed cases where lesions and death occurred during or after pregnancy, as well as cases where death occurred in the late stage of necrosis (years later). This started the initial distinction of Sheehan’s syndrome from Simmonds’ disease (also known as hypopituitarism). Dr. Sheehan noted that significant features of these patient cases was hemorrhaging, which in his experience was most commonly caused by either: placenta Previa (low placenta), uterine rupture, cervical or uterine tears, post-partum atony, or retained placenta. Simmonds disease, however, occurs in either sex due to causes unrelated to pregnancy.However, in his 1939 publication: “Simmonds’ Disease due to Post-partum Necrosis of the Anterior Pituitary”, Dr. Sheehan displays post-partum necrosis as a cause of Simmonds’ disease, thus establishing the relationship between the two conditions. According to Sheehan in 1939 approximately 41% of survivors of severe postpartum hemorrhage (PPH) and/or hypovolemic shock experienced severe or partial hypopituitarism.
References
== External links == |
Arterial insufficiency ulcer | Arterial insufficiency ulcers (also known as ischemic ulcers, or ischemic wounds) are mostly located on the lateral surface of the ankle or the distal digits. They are commonly caused by peripheral artery disease (PAD).
Characteristics
The ulcer has punched-out appearance. It is intensely painful. It has gray or yellow fibrotic base and undermining skin margins. Pulses are not palpable. Associated skin changes may be observed, such as thin shiny skin and absence of hair. They are most common on distal ends of limbs. A special type of ischemic ulcer developing in duodenum after severe burns is called Curlings ulcer.
Cause
The ulcers are caused by lack of blood flow to the capillary beds of the lower extremities. Most often endothelial dysfunction is causative factor in diabetic microangiopathy and macroangiopathy. In microangiopathy, neuropathy and autoregulation of capillaries leads to poor perfusion of tissues, especially wound base. When pressure is placed on the skin, the skin is damaged and is unable to be repaired due to the lack of blood perfusing the tissue. The wound has a characteristic deep, punched out look, often extending down to the tendons. The wounds are very painful.
Diagnosis
The lesion can be easily identified clinically. Arterial doppler and pulse volume recordings are performed for baseline assessment of blood flow. Radiographs may be necessary to rule out osteomyelitis.
Differential diagnoses
Neuropathic ulcer
Gangrene
Infected wound
Management
The prevalence of arterial insufficiency ulcers among people with Diabetes is high due to decreased blood flow caused by the thinning of arteries and the lack of sensation due to diabetic neuropathy. Prevention is the first step in avoiding the development of an arterial insufficiency ulcer. These steps could include annual podiatry check ups that include, "assessment of skin, checking of pedal pulses (assessing for blood flow) and assessing physical sensation".
The management of arterial insufficiency ulcers depends on the severity of the underlying arterial insufficiency. The affected region can sometimes be revascularized via vascular bypass or angioplasty. If infection is present, appropriate antibiotics are prescribed. When proper blood flow is established, debridement is performed. If the wound is plantar (on walking surface of foot), patient is advised to give rest to foot to avoid enlargement of the ulcer. Proper glycemic control in diabetics is important. Smoking should be avoided to aid wound healing.
Epidemiology
These ulcers are difficult to heal by basic wound care and require advanced therapy, such as hyperbaric oxygen therapy or bioengineered skin substitutes. If not taken care of in time, there are very high chances that these may become infected and eventually may have to be amputated. Individuals with history of previous ulcerations are 36 times more likely to develop another ulcer.
See also
Peripheral artery disease
Venous insufficiency ulceration
List of cutaneous conditions
== References == |
Primary inoculation tuberculosis | Primary inoculation tuberculosis is a skin condition that develops at the site of inoculation of tubercle bacilli into a tuberculosis-free individual.: 334
See also
Tuberculosis verrucosa cutis
Skin lesion
List of cutaneous conditions
== References == |
Ebola | Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after becoming infected with the virus. The first symptoms are usually fever, sore throat, muscle pain, and headaches. These are usually followed by vomiting, diarrhoea, rash and decreased liver and kidney function, at which point, some people begin to bleed both internally and externally. The disease kills between 25% and 90% of those infected – about 50% on average. Death is often due to shock from fluid loss, and typically occurs between six and 16 days after the first symptoms appear.The virus spreads through direct contact with body fluids, such as blood from infected humans or other animals, or from contact with items that have recently been contaminated with infected body fluids. There have been no documented cases, either in nature or under laboratory conditions, of the disease spreading through the air between humans or other primates. After a person recovers from Ebola, their semen or breast milk may continue to carry the virus for anywhere between several weeks to several months. Fruit bats are believed to be the normal carrier in nature; they are able to spread the virus without being affected by it. The symptoms of Ebola may resemble those of several other diseases, including malaria, cholera, typhoid fever, meningitis and other viral hemorrhagic fevers. Diagnosis is confirmed by testing blood samples for the presence of viral RNA, viral antibodies or the virus itself.Control of outbreaks requires coordinated medical services and community engagement, including rapid detection, contact tracing of those exposed, quick access to laboratory services, care for those infected, and proper disposal of the dead through cremation or burial. Samples of body fluids and tissues from people with the disease should be handled with extreme caution. Prevention measures include wearing proper protective clothing and washing hands when around a person with the disease, and limiting the spread of the disease from infected animals to humans – by wearing protective clothing while handling potentially infected bushmeat, and by cooking bushmeat thoroughly before eating it. An Ebola vaccine was approved in the United States in December 2019. While there is no approved treatment for Ebola as of 2019, two treatments (atoltivimab/maftivimab/odesivimab and ansuvimab) are associated with improved outcomes. Supportive efforts also improve outcomes. These include oral rehydration therapy (drinking slightly sweetened and salty water) or giving intravenous fluids, and treating symptoms. In October 2020, Atoltivimab/maftivimab/odesivimab (Inmazeb) was approved for medical use in the United States to treat the disease caused by Zaire ebolavirus.The disease was first identified in 1976, in two simultaneous outbreaks: one in Nzara (a town in South Sudan) and the other in Yambuku (the Democratic Republic of the Congo), a village near the Ebola River, from which the disease takes its name. Ebola outbreaks occur intermittently in tropical regions of sub-Saharan Africa. Between 1976 and 2012, according to the World Health Organization, there were 24 outbreaks of Ebola resulting in a total of 2,387 cases, and 1,590 deaths. The largest Ebola outbreak to date was an epidemic in West Africa from December 2013 to January 2016, with 28,646 cases and 11,323 deaths. On 29 March 2016, it was declared to no longer be an emergency. Other outbreaks in Africa began in the Democratic Republic of the Congo in May 2017, and 2018. In July 2019, the World Health Organization declared the Congo Ebola outbreak a world health emergency.
Signs and symptoms
Onset
The length of time between exposure to the virus and the development of symptoms (incubation period) is between 2 and 21 days, and usually between 4 and 10 days. However, recent estimates based on mathematical models predict that around 5% of cases may take longer than 21 days to develop.Symptoms usually begin with a sudden influenza-like stage characterised by fatigue, fever, weakness, decreased appetite, muscular pain, joint pain, headache, and sore throat. The fever is usually higher than 38.3 °C (101 °F). This is often followed by nausea, vomiting, diarrhoea, abdominal pain, and sometimes hiccups. The combination of severe vomiting and diarrhoea often leads to severe dehydration. Next, shortness of breath and chest pain may occur, along with swelling, headaches, and confusion. In about half of the cases, the skin may develop a maculopapular rash, a flat red area covered with small bumps, five to seven days after symptoms begin.
Bleeding
In some cases, internal and external bleeding may occur. This typically begins five to seven days after the first symptoms. All infected people show some decreased blood clotting. Bleeding from mucous membranes or from sites of needle punctures has been reported in 40–50% of cases. This may cause vomiting blood, coughing up of blood, or blood in stool. Bleeding into the skin may create petechiae, purpura, ecchymoses or haematomas (especially around needle injection sites). Bleeding into the whites of the eyes may also occur. Heavy bleeding is uncommon; if it occurs, it is usually in the gastrointestinal tract. The incidence of bleeding into the gastrointestinal tract was reported to be ~58% in the 2001 outbreak in Gabon, but in the 2014–15 outbreak in the US it was ~18%, possibly due to improved prevention of disseminated intravascular coagulation.
Recovery or death
Recovery may begin between seven and 14 days after first symptoms. Death, if it occurs, follows typically six to sixteen days from first symptoms and is often due to shock from fluid loss. In general, bleeding often indicates a worse outcome, and blood loss may result in death. People are often in a coma near the end of life.Those who survive often have ongoing muscular and joint pain, liver inflammation, and decreased hearing, and may have continued tiredness, continued weakness, decreased appetite, and difficulty returning to pre-illness weight. Problems with vision may develop. It is recommended that survivors of EVD wear condoms for at least twelve months after initial infection or until the semen of a male survivor tests negative for Ebola virus on two separate occasions.Survivors develop antibodies against Ebola that last at least 10 years, but it is unclear whether they are immune to additional infections.
Cause
EVD in humans is caused by four of six viruses of the genus Ebolavirus. The four are Bundibugyo virus (BDBV), Sudan virus (SUDV), Taï Forest virus (TAFV) and one simply called Ebola virus (EBOV, formerly Zaire Ebola virus). EBOV, species Zaire ebolavirus, is the most dangerous of the known EVD-causing viruses, and is responsible for the largest number of outbreaks. The fifth and sixth viruses, Reston virus (RESTV) and Bombali virus (BOMV), are not thought to cause disease in humans, but have caused disease in other primates. All five viruses are closely related to marburgviruses.
Virology
Ebolaviruses contain single-stranded, non-infectious RNA genomes. Ebolavirus genomes contain seven genes including 3-UTR-NP-VP35-VP40-GP-VP30-VP24-L-5-UTR. The genomes of the five different ebolaviruses (BDBV, EBOV, RESTV, SUDV and TAFV) differ in sequence and the number and location of gene overlaps. As with all filoviruses, ebolavirus virions are filamentous particles that may appear in the shape of a shepherds crook, of a "U" or of a "6," and they may be coiled, toroid or branched. In general, ebolavirions are 80 nanometers (nm) in width and may be as long as 14,000 nm.Their life cycle is thought to begin with a virion attaching to specific cell-surface receptors such as C-type lectins, DC-SIGN, or integrins, which is followed by fusion of the viral envelope with cellular membranes. The virions taken up by the cell then travel to acidic endosomes and lysosomes where the viral envelope glycoprotein GP is cleaved. This processing appears to allow the virus to bind to cellular proteins enabling it to fuse with internal cellular membranes and release the viral nucleocapsid. The Ebolavirus structural glycoprotein (known as GP1,2) is responsible for the virus ability to bind to and infect targeted cells. The viral RNA polymerase, encoded by the L gene, partially uncoats the nucleocapsid and transcribes the genes into positive-strand mRNAs, which are then translated into structural and nonstructural proteins. The most abundant protein produced is the nucleoprotein, whose concentration in the host cell determines when L switches from gene transcription to genome replication. Replication of the viral genome results in full-length, positive-strand antigenomes that are, in turn, transcribed into genome copies of negative-strand virus progeny. Newly synthesised structural proteins and genomes self-assemble and accumulate near the inside of the cell membrane. Virions bud off from the cell, gaining their envelopes from the cellular membrane from which they bud. The mature progeny particles then infect other cells to repeat the cycle. The genetics of the Ebola virus are difficult to study because of EBOVs virulent characteristics.
Transmission
It is believed that between people, Ebola disease spreads only by direct contact with the blood or other body fluids of a person who has developed symptoms of the disease. Body fluids that may contain Ebola viruses include saliva, mucus, vomit, feces, sweat, tears, breast milk, urine and semen. The WHO states that only people who are very sick are able to spread Ebola disease in saliva, and the virus has not been reported to be transmitted through sweat. Most people spread the virus through blood, feces and vomit. Entry points for the virus include the nose, mouth, eyes, open wounds, cuts and abrasions. Ebola may be spread through large droplets; however, this is believed to occur only when a person is very sick. This contamination can happen if a person is splashed with droplets. Contact with surfaces or objects contaminated by the virus, particularly needles and syringes, may also transmit the infection. The virus is able to survive on objects for a few hours in a dried state, and can survive for a few days within body fluids outside of a person.The Ebola virus may be able to persist for more than three months in the semen after recovery, which could lead to infections via sexual intercourse. Virus persistence in semen for over a year has been recorded in a national screening programme. Ebola may also occur in the breast milk of women after recovery, and it is not known when it is safe to breastfeed again. The virus was also found in the eye of one patient in 2014, two months after it was cleared from his blood. Otherwise, people who have recovered are not infectious.The potential for widespread infections in countries with medical systems capable of observing correct medical isolation procedures is considered low. Usually when someone has symptoms of the disease, they are unable to travel without assistance.Dead bodies remain infectious; thus, people handling human remains in practices such as traditional burial rituals or more modern processes such as embalming are at risk. 69% of the cases of Ebola infections in Guinea during the 2014 outbreak are believed to have been contracted via unprotected (or unsuitably protected) contact with infected corpses during certain Guinean burial rituals.Health-care workers treating people with Ebola are at greatest risk of infection. The risk increases when they do not have appropriate protective clothing such as masks, gowns, gloves and eye protection; do not wear it properly; or handle contaminated clothing incorrectly. This risk is particularly common in parts of Africa where the disease mostly occurs and health systems function poorly. There has been transmission in hospitals in some African countries that reuse hypodermic needles. Some health-care centres caring for people with the disease do not have running water. In the United States the spread to two medical workers treating infected patients prompted criticism of inadequate training and procedures.Human-to-human transmission of EBOV through the air has not been reported to occur during EVD outbreaks, and airborne transmission has only been demonstrated in very strict laboratory conditions, and then only from pigs to primates, but not from primates to primates. Spread of EBOV by water, or food other than bushmeat, has not been observed. No spread by mosquitos or other insects has been reported. Other possible methods of transmission are being studied.Airborne transmission among humans is theoretically possible due to the presence of Ebola virus particles in saliva, which can be discharged into the air with a cough or sneeze, but observational data from previous epidemics suggests the actual risk of airborne transmission is low. A number of studies examining airborne transmission broadly concluded that transmission from pigs to primates could happen without direct contact because, unlike humans and primates, pigs with EVD get very high ebolavirus concentrations in their lungs, and not their bloodstream. Therefore, pigs with EVD can spread the disease through droplets in the air or on the ground when they sneeze or cough. By contrast, humans and other primates accumulate the virus throughout their body and specifically in their blood, but not very much in their lungs. It is believed that this is the reason researchers have observed pig to primate transmission without physical contact, but no evidence has been found of primates being infected without actual contact, even in experiments where infected and uninfected primates shared the same air.
Initial case
Although it is not entirely clear how Ebola initially spreads from animals to humans, the spread is believed to involve direct contact with an infected wild animal or fruit bat. Besides bats, other wild animals sometimes infected with EBOV include several species of monkeys such as baboons, great apes (chimpanzees and gorillas), and duikers (a species of antelope).Animals may become infected when they eat fruit partially eaten by bats carrying the virus. Fruit production, animal behavior and other factors may trigger outbreaks among animal populations.Evidence indicates that both domestic dogs and pigs can also be infected with EBOV. Dogs do not appear to develop symptoms when they carry the virus, and pigs appear to be able to transmit the virus to at least some primates. Although some dogs in an area in which a human outbreak occurred had antibodies to EBOV, it is unclear whether they played a role in spreading the disease to people.
Reservoir
The natural reservoir for Ebola has yet to be confirmed; however, bats are considered to be the most likely candidate. Three types of fruit bats (Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata) were found to possibly carry the virus without getting sick. As of 2013, whether other animals are involved in its spread is not known. Plants, arthropods, rodents, and birds have also been considered possible viral reservoirs.Bats were known to roost in the cotton factory in which the first cases of the 1976 and 1979 outbreaks were observed, and they have also been implicated in Marburg virus infections in 1975 and 1980. Of 24 plant and 19 vertebrate species experimentally inoculated with EBOV, only bats became infected. The bats displayed no clinical signs of disease, which is considered evidence that these bats are a reservoir species of EBOV. In a 2002–2003 survey of 1,030 animals including 679 bats from Gabon and the Republic of the Congo, immunoglobulin G (IgG) immune defense molecules indicative of Ebola infection were found in three bat species; at various periods of study, between 2.2 and 22.6% of bats were found to contain both RNA sequences and IgG molecules indicating Ebola infection. Antibodies against Zaire and Reston viruses have been found in fruit bats in Bangladesh, suggesting that these bats are also potential hosts of the virus and that the filoviruses are present in Asia.Between 1976 and 1998, in 30,000 mammals, birds, reptiles, amphibians and arthropods sampled from regions of EBOV outbreaks, no Ebola virus was detected apart from some genetic traces found in six rodents (belonging to the species Mus setulosus and Praomys) and one shrew (Sylvisorex ollula) collected from the Central African Republic. However, further research efforts have not confirmed rodents as a reservoir. Traces of EBOV were detected in the carcasses of gorillas and chimpanzees during outbreaks in 2001 and 2003, which later became the source of human infections. However, the high rates of death in these species resulting from EBOV infection make it unlikely that these species represent a natural reservoir for the virus.Deforestation has been mentioned as a possible contributor to recent outbreaks, including the West African Ebola virus epidemic. Index cases of EVD have often been close to recently deforested lands.
Pathophysiology
Like other filoviruses, EBOV replicates very efficiently in many cells, producing large amounts of virus in monocytes, macrophages, dendritic cells and other cells including liver cells, fibroblasts, and adrenal gland cells. Viral replication triggers high levels of inflammatory chemical signals and leads to a septic state.EBOV is thought to infect humans through contact with mucous membranes or skin breaks. After infection, endothelial cells (cells lining the inside of blood vessels), liver cells, and several types of immune cells such as macrophages, monocytes, and dendritic cells are the main targets of attack. Following infection, immune cells carry the virus to nearby lymph nodes where further reproduction of the virus takes place. From there the virus can enter the bloodstream and lymphatic system and spread throughout the body. Macrophages are the first cells infected with the virus, and this infection results in programmed cell death. Other types of white blood cells, such as lymphocytes, also undergo programmed cell death leading to an abnormally low concentration of lymphocytes in the blood. This contributes to the weakened immune response seen in those infected with EBOV.Endothelial cells may be infected within three days after exposure to the virus. The breakdown of endothelial cells leading to blood vessel injury can be attributed to EBOV glycoproteins. This damage occurs due to the synthesis of Ebola virus glycoprotein (GP), which reduces the availability of specific integrins responsible for cell adhesion to the intercellular structure and causes liver damage, leading to improper clotting. The widespread bleeding that occurs in affected people causes swelling and shock due to loss of blood volume. The dysfunctional bleeding and clotting commonly seen in EVD has been attributed to increased activation of the extrinsic pathway of the coagulation cascade due to excessive tissue factor production by macrophages and monocytes.After infection, a secreted glycoprotein, small soluble glycoprotein (sGP or GP) is synthesised. EBOV replication overwhelms protein synthesis of infected cells and the host immune defences. The GP forms a trimeric complex, which tethers the virus to the endothelial cells. The sGP forms a dimeric protein that interferes with the signalling of neutrophils, another type of white blood cell. This enables the virus to evade the immune system by inhibiting early steps of neutrophil activation.
Immune system evasion
Filoviral infection also interferes with proper functioning of the innate immune system. EBOV proteins blunt the human immune systems response to viral infections by interfering with the cells ability to produce and respond to interferon proteins such as interferon-alpha, interferon-beta, and interferon gamma.The VP24 and VP35 structural proteins of EBOV play a key role in this interference. When a cell is infected with EBOV, receptors located in the cells cytosol (such as RIG-I and MDA5) or outside of the cytosol (such as Toll-like receptor 3 (TLR3), TLR7, TLR8 and TLR9) recognise infectious molecules associated with the virus. On TLR activation, proteins including interferon regulatory factor 3 and interferon regulatory factor 7 trigger a signalling cascade that leads to the expression of type 1 interferons. The type 1 interferons are then released and bind to the IFNAR1 and IFNAR2 receptors expressed on the surface of a neighbouring cell. Once interferon has bound to its receptors on the neighbouring cell, the signalling proteins STAT1 and STAT2 are activated and move to the cells nucleus. This triggers the expression of interferon-stimulated genes, which code for proteins with antiviral properties. EBOVs V24 protein blocks the production of these antiviral proteins by preventing the STAT1 signalling protein in the neighbouring cell from entering the nucleus. The VP35 protein directly inhibits the production of interferon-beta. By inhibiting these immune responses, EBOV may quickly spread throughout the body.
Diagnosis
When EVD is suspected, travel, work history, and exposure to wildlife are important factors with respect to further diagnostic efforts.
Laboratory testing
Possible non-specific laboratory indicators of EVD include a low platelet count; an initially decreased white blood cell count followed by an increased white blood cell count; elevated levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and abnormalities in blood clotting often consistent with disseminated intravascular coagulation (DIC) such as a prolonged prothrombin time, partial thromboplastin time, and bleeding time. Filovirions such as EBOV may be identified by their unique filamentous shapes in cell cultures examined with electron microscopy.The specific diagnosis of EVD is confirmed by isolating the virus, detecting its RNA or proteins, or detecting antibodies against the virus in a persons blood. Isolating the virus by cell culture, detecting the viral RNA by polymerase chain reaction (PCR) and detecting proteins by enzyme-linked immunosorbent assay (ELISA) are methods best used in the early stages of the disease and also for detecting the virus in human remains. Detecting antibodies against the virus is most reliable in the later stages of the disease and in those who recover. IgM antibodies are detectable two days after symptom onset and IgG antibodies can be detected six to 18 days after symptom onset. During an outbreak, isolation of the virus with cell culture methods is often not feasible. In field or mobile hospitals, the most common and sensitive diagnostic methods are real-time PCR and ELISA. In 2014, with new mobile testing facilities deployed in parts of Liberia, test results were obtained 3–5 hours after sample submission. In 2015, a rapid antigen test which gives results in 15 minutes was approved for use by WHO. It is able to confirm Ebola in 92% of those affected and rule it out in 85% of those not affected.
Differential diagnosis
Early symptoms of EVD may be similar to those of other diseases common in Africa, including malaria and dengue fever. The symptoms are also similar to those of other viral haemorrhagic fevers such as Marburg virus disease, Crimean–Congo haemorrhagic fever, and Lassa fever.The complete differential diagnosis is extensive and requires consideration of many other infectious diseases such as typhoid fever, shigellosis, rickettsial diseases, cholera, sepsis, borreliosis, EHEC enteritis, leptospirosis, scrub typhus, plague, Q fever, candidiasis, histoplasmosis, trypanosomiasis, visceral leishmaniasis, measles, and viral hepatitis among others.Non-infectious diseases that may result in symptoms similar to those of EVD include acute promyelocytic leukaemia, haemolytic uraemic syndrome, snake envenomation, clotting factor deficiencies/platelet disorders, thrombotic thrombocytopenic purpura, hereditary haemorrhagic telangiectasia, Kawasaki disease, and warfarin poisoning.
Prevention
Vaccines
An Ebola vaccine, rVSV-ZEBOV, was approved in the United States in December 2019. It appears to be fully effective ten days after being given. It was studied in Guinea between 2014 and 2016. More than 100,000 people have been vaccinated against Ebola as of 2019.
Infection control
Caregivers
People who care for those infected with Ebola should wear protective clothing including masks, gloves, gowns and goggles. The U.S. Centers for Disease Control (CDC) recommend that the protective gear leaves no skin exposed. These measures are also recommended for those who may handle objects contaminated by an infected persons body fluids. In 2014, the CDC began recommending that medical personnel receive training on the proper suit-up and removal of personal protective equipment (PPE); in addition, a designated person, appropriately trained in biosafety, should be watching each step of these procedures to ensure they are done correctly. In Sierra Leone, the typical training period for the use of such safety equipment lasts approximately 12 days.
Patients and household members
The infected person should be in barrier-isolation from other people. All equipment, medical waste, patient waste and surfaces that may have come into contact with body fluids need to be disinfected. During the 2014 outbreak, kits were put together to help families treat Ebola disease in their homes, which included protective clothing as well as chlorine powder and other cleaning supplies. Education of caregivers in these techniques, and providing such barrier-separation supplies has been a priority of Doctors Without Borders.
Disinfection
Ebolaviruses can be eliminated with heat (heating for 30 to 60 minutes at 60 °C or boiling for five minutes). To disinfect surfaces, some lipid solvents such as some alcohol-based products, detergents, sodium hypochlorite (bleach) or calcium hypochlorite (bleaching powder), and other suitable disinfectants may be used at appropriate concentrations.
General population
Education of the general public about the risk factors for Ebola infection and of the protective measures individuals may take to prevent infection is recommended by the World Health Organization. These measures include avoiding direct contact with infected people and regular hand washing using soap and water.
Bushmeat
Bushmeat, an important source of protein in the diet of some Africans, should be handled and prepared with appropriate protective clothing and thoroughly cooked before consumption. Some research suggests that an outbreak of Ebola disease in the wild animals used for consumption may result in a corresponding human outbreak. Since 2003, such animal outbreaks have been monitored to predict and prevent Ebola outbreaks in humans.
Corpses, burial
If a person with Ebola disease dies, direct contact with the body should be avoided. Certain burial rituals, which may have included making various direct contacts with a dead body, require reformulation so that they consistently maintain a proper protective barrier between the dead body and the living. Social anthropologists may help find alternatives to traditional rules for burials.
Transport, travel, contact
Transportation crews are instructed to follow a certain isolation procedure, should anyone exhibit symptoms resembling EVD. As of August 2014, the WHO does not consider travel bans to be useful in decreasing spread of the disease. In October 2014, the CDC defined four risk levels used to determine the level of 21-day monitoring for symptoms and restrictions on public activities. In the United States, the CDC recommends that restrictions on public activity, including travel restrictions, are not required for the following defined risk levels:
having been in a country with widespread Ebola disease transmission and having no known exposure (low risk); or having been in that country more than 21 days ago (no risk)
encounter with a person showing symptoms; but not within three feet of the person with Ebola without wearing PPE; and no direct contact with body fluids
having had brief skin contact with a person showing symptoms of Ebola disease when the person was believed to be not very contagious (low risk)
in countries without widespread Ebola disease transmission: direct contact with a person showing symptoms of the disease while wearing PPE (low risk)
contact with a person with Ebola disease before the person was showing symptoms (no risk).The CDC recommends monitoring for the symptoms of Ebola disease for those both at "low risk" and at higher risk |
Ebola | .
Laboratory
In laboratories where diagnostic testing is carried out, biosafety level 4-equivalent containment is required. Laboratory researchers must be properly trained in BSL-4 practices and wear proper PPE.
Isolation
Isolation refers to separating those who are sick from those who are not. Quarantine refers to separating those who may have been exposed to a disease until they either show signs of the disease or are no longer at risk. Quarantine, also known as enforced isolation, is usually effective in decreasing spread. Governments often quarantine areas where the disease is occurring or individuals who may transmit the disease outside of an initial area. In the United States, the law allows quarantine of those infected with ebolaviruses.
Contact tracing
Contact tracing is considered important to contain an outbreak. It involves finding everyone who had close contact with infected individuals and monitoring them for signs of illness for 21 days. If any of these contacts comes down with the disease, they should be isolated, tested and treated. Then the process is repeated, tracing the contacts contacts.
Management
While there is no approved treatment for Ebola as of 2019, two treatments (atoltivimab/maftivimab/odesivimab and ansuvimab) are associated with improved outcomes. The U.S. Food and Drug Administration (FDA) advises people to be careful of advertisements making unverified or fraudulent claims of benefits supposedly gained from various anti-Ebola products.In October 2020, the U.S. Food and Drug Administration (FDA) approved atoltivimab/maftivimab/odesivimab with an indication for the treatment of infection caused by Zaire ebolavirus.
Standard support
Treatment is primarily supportive in nature. Early supportive care with rehydration and symptomatic treatment improves survival. Rehydration may be via the oral or intravenous route. These measures may include pain management, and treatment for nausea, fever, and anxiety. The World Health Organization (WHO) recommends avoiding aspirin or ibuprofen for pain management, due to the risk of bleeding associated with these medications.Blood products such as packed red blood cells, platelets, or fresh frozen plasma may also be used. Other regulators of coagulation have also been tried including heparin in an effort to prevent disseminated intravascular coagulation and clotting factors to decrease bleeding. Antimalarial medications and antibiotics are often used before the diagnosis is confirmed, though there is no evidence to suggest such treatment helps. Several experimental treatments are being studied.Where hospital care is not possible, the WHOs guidelines for home care have been relatively successful. Recommendations include using towels soaked in a bleach solution when moving infected people or bodies and also applying bleach on stains. It is also recommended that the caregivers wash hands with bleach solutions and cover their mouth and nose with a cloth.
Intensive care
Intensive care is often used in the developed world. This may include maintaining blood volume and electrolytes (salts) balance as well as treating any bacterial infections that may develop. Dialysis may be needed for kidney failure, and extracorporeal membrane oxygenation may be used for lung dysfunction.
Prognosis
EVD has a risk of death in those infected of between 25% and 90%. As of September 2014, the average risk of death among those infected is 50%. The highest risk of death was 90% in the 2002–2003 Republic of the Congo outbreak.Death, if it occurs, follows typically six to sixteen days after symptoms appear and is often due to low blood pressure from fluid loss. Early supportive care to prevent dehydration may reduce the risk of death.If an infected person survives, recovery may be quick and complete. Prolonged cases are often complicated by the occurrence of long-term problems, such as inflammation of the testicles, joint pains, fatigue, hearing loss, mood and sleep disturbances, muscular pain, abdominal pain, menstrual abnormalities, miscarriages, skin peeling, or hair loss. Inflammation and swelling of the uveal layer of the eye is the most common eye complication in survivors of Ebola virus disease. Eye symptoms, such as light sensitivity, excess tearing, and vision loss have been described.Ebola can stay in some body parts like the eyes, breasts, and testicles after infection. Sexual transmission after recovery has been suspected. If sexual transmission occurs following recovery it is believed to be a rare event. One case of a condition similar to meningitis has been reported many months after recovery, as of October 2015.A study of 44 survivors of the Ebola virus in Sierra Leone reported musculoskeletal pain in 70%, headache in 48%, and eye problems in 14%.
Epidemiology
The disease typically occurs in outbreaks in tropical regions of Sub-Saharan Africa. From 1976 (when it was first identified) through 2013, the WHO reported 2,387 confirmed cases with 1,590 overall fatalities. The largest outbreak to date was the Ebola virus epidemic in West Africa, which caused a large number of deaths in Guinea, Sierra Leone, and Liberia.
1976
Sudan
The first known outbreak of EVD was identified only after the fact. It occurred between June and November 1976, in Nzara, South Sudan (then part of Sudan), and was caused by Sudan virus (SUDV). The Sudan outbreak infected 284 people and killed 151. The first identifiable case in Sudan occurred on 27 June in a storekeeper in a cotton factory in Nzara, who was hospitalised on 30 June and died on 6 July. Although the WHO medical staff involved in the Sudan outbreak knew that they were dealing with a heretofore unknown disease, the actual "positive identification" process and the naming of the virus did not occur until some months later in Zaire.
Zaire
On 26 August 1976, the second outbreak of EVD began in Yambuku, a small rural village in Mongala District in northern Zaire (now known as the Democratic Republic of the Congo). This outbreak was caused by EBOV, formerly designated Zaire ebolavirus, a different member of the genus Ebolavirus than in the first Sudan outbreak. The first person infected with the disease was the village schools headmaster Mabalo Lokela, who began displaying symptoms on 26 August 1976. Lokela had returned from a trip to Northern Zaire near the border of the Central African Republic, after visiting the Ebola River between 12 and 22 August. He was originally believed to have malaria and was given quinine. However, his symptoms continued to worsen, and he was admitted to Yambuku Mission Hospital on 5 September. Lokela died on 8 September 14 days after he began displaying symptoms.Soon after Lokelas death, others who had been in contact with him also died, and people in Yambuku began to panic. The countrys Minister of Health and Zaire President Mobutu Sese Seko declared the entire region, including Yambuku and the countrys capital, Kinshasa, a quarantine zone. No-one was permitted to enter or leave the area, and roads, waterways, and airfields were placed under martial law. Schools, businesses and social organisations were closed. The initial response was led by Congolese doctors, including Jean-Jacques Muyembe-Tamfum, one of the discoverers of Ebola. Muyembe took a blood sample from a Belgian nun; this sample would eventually be used by Peter Piot to identify the previously unknown Ebola virus. Muyembe was also the first scientist to come into direct contact with the disease and survive. Researchers from the Centers for Disease Control and Prevention (CDC), including Piot, co-discoverer of Ebola, later arrived to assess the effects of the outbreak, observing that "the whole region was in panic."Piot concluded that Belgian nuns had inadvertently started the epidemic by giving unnecessary vitamin injections to pregnant women without sterilizing the syringes and needles. The outbreak lasted 26 days and the quarantine lasted two weeks. Researchers speculated that the disease disappeared due to the precautions taken by locals, the quarantine of the area, and discontinuing of the injections.During this outbreak, Ngoy Mushola recorded the first clinical description of EVD in Yambuku, where he wrote the following in his daily log: "The illness is characterised with a high temperature of about 39 °C (102 °F), haematemesis, diarrhoea with blood, retrosternal abdominal pain, prostration with heavy articulations, and rapid evolution death after a mean of three days."The virus responsible for the initial outbreak, first thought to be the Marburg virus, was later identified as a new type of virus related to the genus Marburgvirus. Virus strain samples isolated from both outbreaks were named "Ebola virus" after the Ebola River, near the first-identified viral outbreak site in Zaire. Reports conflict about who initially coined the name: either Karl Johnson of the American CDC team or Belgian researchers. Subsequently, a number of other cases were reported, almost all centred on the Yambuku mission hospital or close contacts of another case. In all, 318 cases and 280 deaths (an 88% fatality rate) occurred in Zaire. Although the two outbreaks were at first believed connected, scientists later realised that they were caused by two distinct ebolaviruses, SUDV and EBOV.
1995–2014
The second major outbreak occurred in Zaire (now the Democratic Republic of the Congo, DRC), in 1995, affecting 315 and killing 254.In 2000, Uganda had an outbreak infecting 425 and killing 224; in this case, the Sudan virus was found to be the Ebola species responsible for the outbreak.In 2003, an outbreak in the DRC infected 143 and killed 128, a 90% death rate, the highest of a genus Ebolavirus outbreak to date.In 2004, a Russian scientist died from Ebola after sticking herself with an infected needle.Between April and August 2007, a fever epidemic in a four-village region of the DRC was confirmed in September to have been cases of Ebola. Many people who attended the recent funeral of a local village chief died. The 2007 outbreak eventually infected 264 individuals and killed 187.On 30 November 2007, the Uganda Ministry of Health confirmed an outbreak of Ebola in the Bundibugyo District in Western Uganda. After confirming samples tested by the United States National Reference Laboratories and the Centers for Disease Control, the World Health Organization (WHO) confirmed the presence of a new species of genus Ebolavirus, which was tentatively named Bundibugyo. The WHO reported 149 cases of this new strain and 37 of those led to deaths.The WHO confirmed two small outbreaks in Uganda in 2012, both caused by the Sudan variant. The first outbreak affected seven people, killing four, and the second affected 24, killing 17.On 17 August 2012, the Ministry of Health of the DRC reported an outbreak of the Ebola-Bundibugyo variant in the eastern region. Other than its discovery in 2007, this was the only time that this variant has been identified as responsible for an outbreak. The WHO revealed that the virus had sickened 57 people and killed 29. The probable cause of the outbreak was tainted bush meat hunted by local villagers around the towns of Isiro and Viadana.In 2014, an outbreak occurred in the DRC. Genome-sequencing showed that this outbreak was not related to the 2014–15 West Africa Ebola virus outbreak, but was the same EBOV species, the Zaire species. It began in August 2014, and was declared over in November with 66 cases and 49 deaths. This was the 7th outbreak in the DRC, three of which occurred during the period when the country was known as Zaire.
2013–2016 West Africa
In March 2014, the World Health Organization (WHO) reported a major Ebola outbreak in Guinea, a West African nation. Researchers traced the outbreak to a one-year-old child who died in December 2013. The disease rapidly spread to the neighbouring countries of Liberia and Sierra Leone. It was the largest Ebola outbreak ever documented, and the first recorded in the region. On 8 August 2014, the WHO declared the epidemic an international public health emergency. Urging the world to offer aid to the affected regions, its Director-General said, "Countries affected to date simply do not have the capacity to manage an outbreak of this size and complexity on their own. I urge the international community to provide this support on the most urgent basis possible." By mid-August 2014, Doctors Without Borders reported the situation in Liberias capital, Monrovia, was "catastrophic" and "deteriorating daily". They reported that fears of Ebola among staff members and patients had shut down much of the citys health system, leaving many people without medical treatment for other conditions. In a 26 September statement, WHO said, "The Ebola epidemic ravaging parts of West Africa is the most severe acute public health emergency seen in modern times. Never before in recorded history has a biosafety level four pathogen infected so many people so quickly, over such a broad geographical area, for so long."Intense contact tracing and strict isolation largely prevented further spread of the disease in the countries that had imported cases.
It caused significant mortality, with a considerable case fatality rate. By the end of the epidemic, 28,616 people had been infected; of these, 11,310 had died, for a case-fatality rate of 40%. As of 8 May 2016, 28,646 suspected cases and 11,323 deaths were reported; however, the WHO said that these numbers may be underestimated. Because they work closely with the body fluids of infected patients, healthcare workers were especially vulnerable to infection; in August 2014, the WHO reported that 10% of the dead were healthcare workers.
In September 2014, it was estimated that the countries capacity for treating Ebola patients was insufficient by the equivalent of 2,122 beds; by December there were a sufficient number of beds to treat and isolate all reported Ebola cases, although the uneven distribution of cases was causing serious shortfalls in some areas. On 28 January 2015, the WHO reported that for the first time since the week ending 29 June 2014, there had been fewer than 100 new confirmed cases reported in a week in the three most-affected countries. The response to the epidemic then moved to a second phase, as the focus shifted from slowing transmission to ending the epidemic. On 8 April 2015, the WHO reported only 30 confirmed cases, the lowest weekly total since the third week of May 2014.On 29 December 2015, 42 days after the last person tested negative for a second time, Guinea was declared free of Ebola transmission. At that time, a 90-day period of heightened surveillance was announced by that agency. "This is the first time that all three countries – Guinea, Liberia and Sierra Leone – have stopped the original chains of transmission...", the organisation stated in a news release. A new case was detected in Sierra Leone on 14 January 2016. However, the outbreak was declared no longer an emergency on 29 March 2016.
2014 spread outside West Africa
On 19 September, Eric Duncan flew from his native Liberia to Texas; five days later he began showing symptoms and visited a hospital but was sent home. His condition worsened and he returned to the hospital on 28 September, where he died on 8 October. Health officials confirmed a diagnosis of Ebola on 30 September – the first case in the United States.In early October, Teresa Romero, a 44-year-old Spanish nurse, contracted Ebola after caring for a priest who had been repatriated from West Africa. This was the first transmission of the virus to occur outside Africa. Romero tested negative for the disease on 20 October, suggesting that she may have recovered from Ebola infection.On 12 October, the Centers for Disease Control and Prevention (CDC) confirmed that a nurse in Texas, Nina Pham, who had treated Duncan tested positive for the Ebola virus, the first known case of transmission in the United States. On 15 October, a second Texas health-care worker who had treated Duncan was confirmed to have the virus. Both of these people recovered. An unrelated case involved a doctor in New York City, who returned to the United States from Guinea after working with Médecins Sans Frontières and tested positive for Ebola on 23 October. The person recovered and was discharged from Bellevue Hospital on 11 November. On 24 December 2014, a laboratory in Atlanta, Georgia reported that a technician had been exposed to Ebola.On 29 December 2014, Pauline Cafferkey, a British nurse who had just returned to Glasgow from Sierra Leone, was diagnosed with Ebola at Glasgows Gartnavel General Hospital. After initial treatment in Glasgow, she was transferred by air to RAF Northolt, then to the specialist high-level isolation unit at the Royal Free Hospital in London for longer-term treatment.
2017 Democratic Republic of the Congo
On 11 May 2017, the DRC Ministry of Public Health notified the WHO about an outbreak of Ebola. Four people died, and four people survived; five of these eight cases were laboratory-confirmed. A total of 583 contacts were monitored. On 2 July 2017, the WHO declared the end of the outbreak.
2018 Équateur province
On 14 May 2018, the World Health Organization reported that "the Democratic Republic of Congo reported 39 suspected, probable or confirmed cases of Ebola between 4 April and 13 May, including 19 deaths." Some 393 people identified as contacts of Ebola patients were being followed up. The outbreak centred on the Bikoro, Iboko, and Wangata areas in Equateur province, including in the large city of Mbandaka. The DRC Ministry of Public Health approved the use of an experimental vaccine. On 13 May 2018, WHO Director-General Tedros Adhanom Ghebreyesus visited Bikoro. Reports emerged that maps of the area were inaccurate, not so much hampering medical providers as epidemiologists and officials trying to assess the outbreak and containment efforts. The 2018 outbreak in the DRC was declared over on 24 July 2018.
2018–2020 Kivu
On 1 August 2018, the worlds 10th Ebola outbreak was declared in North Kivu province of the Democratic Republic of the Congo. It was the first Ebola outbreak in a military conflict zone, with thousands of refugees in the area. By November 2018, nearly 200 Congolese had died of Ebola, about half of them from the city of Beni, where armed groups are fighting over the regions mineral wealth, impeding medical relief efforts.By March 2019, this became the second largest Ebola outbreak ever recorded, with more than 1,000 cases and insecurity continuing to be the major resistance to providing an adequate response. As of 4 June 2019, the WHO reported 2025 confirmed and probable cases with 1357 deaths. In June 2019, two people died of Ebola in neighbouring Uganda.In July 2019, an infected man travelled to Goma, home to more than two million people. One week later, on 17 July 2019, the WHO declared the Ebola outbreak a global health emergency, the fifth time such a declaration has been made by the organisation. A government spokesman said that half of the Ebola cases are unidentified, and he added that the current outbreak could last up to three years.On 25 June 2020, the second biggest EVD outbreak ever was declared over.
2020 Équateur province
On 1 June 2020, the Congolese health ministry announced a new DRC outbreak of Ebola in Mbandaka, Équateur Province, a region along the Congo River. Genome sequencing suggests that this outbreak, the 11th outbreak since the virus was first discovered in the country in 1976, is unrelated to the one in North Kivu Province or the previous outbreak in the same area in 2018. It was reported that six cases had been identified; four of the people had died. It is expected that more people will be identified as surveillance activities increase. By 15 June the case count had increased to 17 with 11 deaths, with more than 2,500 people having been vaccinated. The 11th EVD outbreak was officially declared over on 19 November 2020. By the time the Équateur outbreak ended, it had 130 confirmed cases with 75 recoveries and 55 deaths.
2021
North Kivu
On 7 February 2021, the Congolese health ministry announced a new case of Ebola near Butembo, North Kivu detected a day before. The case was a 42-year-old woman who had symptoms of Ebola in Biena on 1 February 2021. A few days after, she died in a hospital in Butembo. The WHO said that more than 70 people with contact with the woman had been tracked.On 11 February 2021, another woman who had contact with the previous woman died in the same town, and the number of traced contacts increased to 100. A day after, a third case was detected in Butembo.On 3 May 2021, the 12th EVD outbreak was declared over, resulting in 12 cases and six deaths. Heightened surveillance will continue for 90 days after the declaration, in case of resurgence.
Guinea
In February 2021, Dr Sakoba Keita, head of Guineas national health agency confirmed that three people had died of Ebola in the south-eastern region near the city of Nzérékoré. A further five people also tested positive. Keita also confirmed more testing was underway, and attempts to trace and isolate further cases had begun. On 14 February, the Guinean government declared an Ebola epidemic. The outbreak may have started following reactivation of a latent case in a survivor of an earlier outbreak. As of 4 May 2021, 23 cases were reported, with no new cases or deaths since 3 April 2021. A 42-day countdown period was started on 8 May 2021, and on 19 June, the outbreak was declared over.
Ivory Coast
On 14 August 2021, The Ministry of Health of Cote d’Ivoire confirmed the countrys first case of Ebola since 1994. This came after the Institut Pasteur in Cote dIvoire confirmed the Ebola Virus Disease in samples collected from a patient, who was hospitalized in the commercial capital of Abidjan, after arriving from Guinea.However, on 31 August 2021, the WHO found that, after further tests in a laboratory in Lyon, the patient did not have Ebola. The cause of her disease is still being analyzed.
2022
On 23 April 2022, a case of Ebola was confirmed in the DRC in the Equateur province. The case was a 31-year-old man whose symptoms began on 5 April, but did not seek treatment for over a week. On 21 April, he was admitted to an Ebola treatment centre and died later that day. By 24 May 2022, there were 5 recorded deaths in the DRC. On 15 August, the fifth case was buried, and the outbreak was declared over, 42 days after, on 4 July 2022. In September 2022, Uganda reported 7 cases infected with the Ebola Sudan strain.
Society and culture
Weaponisation
Ebolavirus is classified as a biosafety level 4 agent, as well as a Category A bioterrorism agent by the Centers for Disease Control and Prevention. It has the potential to be weaponised for use in biological warfare, and was investigated by Biopreparat for such use, but might be difficult to prepare as a weapon of mass destruction because the virus becomes ineffective quickly in open air. Fake emails pretending to be Ebola information from the WHO or the Mexican government have, in 2014, been misused to spread computer malware. The BBC reported in 2015 that "North Korean state media has suggested the disease was created by the U.S. military as a biological weapon."
Literature
Richard Prestons 1995 best-selling book, The Hot Zone, dramatised the Ebola outbreak in Reston, Virginia.William Closes 1995 Ebola: A Documentary Novel of Its First Explosion and 2002 Ebola: Through the Eyes of the People focused on individuals reactions to the 1976 Ebola outbreak in Zaire.Tom Clancys 1996 novel, Executive Orders, involves a Middle Eastern terrorist attack on the United States using an airborne form of a deadly Ebola virus strain named "Ebola Mayinga" (see Mayinga NSeka).As the Ebola virus epidemic in West Africa developed in 2014, a number of popular self-published and well-reviewed books containing sensational and misleading information about the disease appeared in electronic and printed formats. The authors of some such books admitted that they lacked medical credentials and were not technically qualified to give medical advice. The World Health Organization and the United Nations stated that such misinformation had contributed to the spread of the disease.
Other animals
Wild animals
Ebola has a high mortality rate among primates. Frequent outbreaks of Ebola may have resulted in the deaths of 5,000 gorillas. Outbreaks of Ebola may have been responsible for an 88% decline in tracking indices of observed chimpanzee populations in the 420 km2 Lossi Sanctuary between 2002 and 2003. Transmission among chimpanzees through meat consumption constitutes a significant risk factor, whereas contact between the animals, such as touching dead bodies and grooming, is not.Recovered gorilla carcasses have contained multiple Ebola virus strains, suggesting multiple introductions of the virus. Bodies decompose quickly and carcasses are not infectious after three to four days. Contact between gorilla groups is rare, suggesting that transmission among gorilla groups is unlikely, and that outbreaks result from transmission between viral reservoirs and animal populations.
Domestic animals
In 2012, it was demonstrated that the virus can travel without contact from pigs to nonhuman primates, although the same study failed to achieve transmission in that manner between primates.Dogs may become infected with EBOV but not develop symptoms. Dogs in some parts of Africa scavenge for food, and they sometimes eat EBOV-infected animals and also the corpses of humans. A 2005 survey of dogs during an EBOV outbreak found that although they remain asymptomatic, about 32 percent of dogs closest to an outbreak showed a seroprevalence for EBOV versus nine percent of those farther away. The authors concluded that there were "potential implications for preventing and controlling human outbreaks."
Reston virus
In late 1989, Hazelton Research Products Reston Quarantine Unit in Reston, Virginia, had an outbreak of fatal illness amongst certain lab monkeys. This lab outbreak was initially diagnosed as simian haemorrhagic fever virus (SHFV) and occurred amongst a shipment of crab-eating macaque monkeys imported from the Philippines. Hazeltons veterinary pathologist in Reston sent tissue samples from dead animals to the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick, Maryland, where an ELISA test indicated the antibodies present in the tissue were a response to Ebola virus and not SHFV. An electron microscopist from USAMRIID discovered filoviruses similar in appearance, in crystalloid aggregates and as single filaments with a shepherds hook, to Ebola in the tissue samples sent from Hazelton Research Products Reston Quarantine Unit.A US Army team headquartered at USAMRIID euthanised the surviving monkeys, and brought all the dead monkeys to Fort Detrick for study by the Armys veterinary pathologists and virologists, and eventual disposal under safe conditions. Blood samples were taken from 178 animal handlers during the incident. Of those, six animal handlers eventually seroconverted, including one who had cut himself with a bloody scalpel. Despite its status as a Level‑4 organism and its apparent pathogenicity in monkeys, when the handlers did not become ill, the CDC concluded that the virus had a very low pathogenicity to humans.The Philippines and the United States had no previous cases of Ebola infection, and upon further isolation, researchers concluded it was another strain of Ebola, or a new filovirus of Asian origin, which they named Reston ebolavirus (RESTV) after the location of the incident. Reston virus ( |
Ebola | RESTV) can be transmitted to pigs. Since the initial outbreak it has since been found in nonhuman primates in Pennsylvania, Texas, and Italy, where the virus had infected pigs. According to the WHO, routine cleaning and disinfection of pig (or monkey) farms with sodium hypochlorite or detergents should be effective in inactivating the Reston ebolavirus. Pigs that have been infected with RESTV tend to show symptoms of the disease.
Research
Treatments
As of July 2015, no medication has been proven safe and effective for treating Ebola. By the time the Ebola virus epidemic in West Africa began in 2013, there were at least nine different candidate treatments. Several trials were conducted in late 2014, and early 2015, but some were abandoned due to lack of efficacy or lack of people to study.As of August 2019, two experimental treatments known as atoltivimab/maftivimab/odesivimab and ansuvimab were found to be 90% effective.
Diagnostic tests
The diagnostic tests currently available require specialised equipment and highly trained personnel. Since there are few suitable testing centres in West Africa, this leads to delay in diagnosis.On 29 November 2014, a new 15-minute Ebola test was reported that if successful, "not only gives patients a better chance of survival, but it prevents transmission of the virus to other people." The new equipment, about the size of a laptop and solar-powered, allows testing to be done in remote areas.On 29 December 2014, the U.S. Food and Drug Administration (FDA) approved the LightMix Ebola Zaire rRT-PCR test for patients with symptoms of Ebola.
Disease models
Animal models and in particular non-human primates are being used to study different aspects of Ebola virus disease. Developments in organ-on-a-chip technology have led to a chip-based model for Ebola haemorrhagic syndrome.
See also
Bibliography of Ebola
Notes
References
The article uses public domain text from the CDC as cited.
Bibliography
External links
Ebola (Ebola Virus Disease) – Centers for Disease Control and Prevention, Viral Special Pathogens Branch.
Health topics: Ebola virus disease – World Health Organization.
Videos: Ebola outbreak response – World Health Organization.
"Ebola Preparedness and Response". U.S. Food and Drug Administration (FDA). 13 January 2021.
Ebola: What You Need to Know – Scientific American articles related to Ebola; note these are general reading articles, they are not scientific peer-reviewed research articles. |
Alopecia mucinosa | Alopecia mucinosa (also known as "Follicular mucinosis," "Mucinosis follicularis", "Pinkus follicular mucinosis," and "Pinkus follicular mucinosis–benign primary form") is a skin disorder that generally presents, but not exclusively, as erythematous plaques or flat patches without hair primarily on the scalp, neck and face.: 649 : 188 This can also be present on the body as a follicular mucinosis and may represent a systemic disease.Alopecia mucinosa occurs when mucinous material accumulates in the hair follicles and sebaceous glands. This triggers an inflammatory response, and affects the follicles ability to produce hair. This hair loss is reversible in the early stages, but once the disease advances, the hair follicles are destroyed, and Scarring alopecia occurs.
See also
List of cutaneous conditions
References
== External links == |
Southern tick-associated rash illness | Southern tick-associated rash illness (STARI) is an emerging infectious disease related to Lyme disease that occurs in southeastern and south-central United States. It is spread by tick bites and it was hypothesized that the illness was caused by the bacteria Borrelia lonestari. However, there is insufficient evidence to declare this Borrelia strain as a causative agent.
Symptoms
Diagnosis is based on a circular "bulls-eye" rash at the site of infection called erythema chronicum migrans, which is very similar to that seen in Lyme disease. However, the symptoms of STARI are mild, and resemble influenza, with fatigue, muscle pains, and headache. Fever is sometimes seen, but is not characteristic.
Causes
This illness is a tick-borne disease carried by the lone star tick Amblyomma americanum. This tick was first proposed as a possible vector of disease in 1984, and the illnesses associated with the tick called "Lyme-like disease", but it was not recognized to be distinct from Lyme disease until the late 1990s.Several studies have failed to detect Borrelia burgdorferi, which is the causative agent of Lyme disease, in patients from the southern United States. This disease may be caused by the related bacterium Borrelia lonestari, which is a spirochete first isolated in culture in 2004. However, this conclusion is controversial since the spirochete is not detected in all cases of the syndrome, which has led some authors to argue that the illness is not caused by a bacterial pathogen.
Treatment
Infections are treated with antibiotics, particularly doxycycline, and the acute symptoms appear to respond to these drugs.
Prognosis
No serious long-term effects are known for this disease, but preliminary evidence suggests, if such symptoms do occur, they are less severe than those associated with Lyme disease.
See also
Borrelia
Zoonosis
References
External links
Southern Tick-Associated Rash Illness (STARI) Home Page Centers for Disease Control
STARI Fact Sheet Florida Department of Health
Southern Tick-Associated Rash Illness (STARI) SCWDS Briefs, January 2003, Vol.18, No.4 |
High-grade prostatic intraepithelial neoplasia | High-grade prostatic intraepithelial neoplasia (HGPIN) is an abnormality of prostatic glands and believed to precede the development of prostate adenocarcinoma (the most common form of prostate cancer).It may be referred to simply as prostatic intraepithelial neoplasia (PIN). It is considered to be a pre-malignancy, or carcinoma in situ, of the prostatic glands.
Signs and symptoms
HGPIN in isolation is asymptomatic. It is typically discovered in prostate biopsies taken to rule-out prostate cancer and very frequently seen in prostates removed for prostate cancer.
Relation to prostate cancer
There are several reasons why PIN is the most likely prostate cancer precursor. PIN is more common in men with prostate cancer. High grade PIN can be found in 85 to 100% of radical prostatectomy specimens, nearby or even in connection with prostate cancer. It tends to occur in the peripheral zone of the prostate. With age, it becomes increasingly multifocal, like prostate cancer. Molecular analysis has shown that high grade PIN and prostate cancer share many genetic abnormalities.The risk for men with high grade PIN of being diagnosed with prostate cancer after repeat biopsy has decreased since the introduction of biopsies at more than six locations (traditional sextant biopsies).
Histology
HGPIN typically has one of four different histologic patterns:
tufted,
micropapillary,
cribriform and,
flat.Its cytologic features are that of prostatic adenocarcinoma:
presence of nucleoli,
increased nuclear-to-cytoplasmic ratio and,
increased nuclear size.Microscopically, PIN is a collection of irregular, atypical epithelial cells. The architecture of the glands and ducts remains normal. The epithelial cells proliferate and crowding results in a pseudo-multilayer appearance. They remain fully contained within a prostate acinus (the berry-shaped termination of a gland, where the secretion is produced) or duct. The latter can be demonstrated with special staining techniques (immunohistochemistry for cytokeratins) to identify the basal cells forming the supporting layer of the acinus. In prostate cancer, the abnormal cells spread beyond the boundaries of the acinus and form clusters without basal cells. In HGPIN, the basal cell layer is disrupted but present. PIN is primarily found in the peripheral zone of the prostate (75-80%), rarely in the transition zone (10-15%) and very rarely in the central zone (5%), a distribution that parallels the zonal distribution for prostate carcinoma.Because it is thought to be a premalignant state, PIN is often considered the prostate equivalent of what is called carcinoma in situ (localized cancer) in other organs. However, PIN differs from carcinoma in situ in that it may remain unchanged or even spontaneously regress.Several architectural variants of PIN have been described, and many cases have multiple patterns. The main ones are tufting, micropapillary, cribriform, and flat. Although these different appearances may cause confusion with other conditions, they have not been found to be of clinical importance. Rarer types are signet-ring-cell, small-cell-neuroendocrine, mucinous, foamy, inverted, and with squamous differentiation.
Diagnosis
HGPIN is diagnosed from tissue by a pathologist, which may come from:
a needle biopsy taken via the rectum and,
surgical removal of prostate tissue:
transurethral resection of the prostate - removal of extra prostate tissue to improve urination (a treatment for benign prostatic hyperplasia),
radical prostatectomy - complete removal of prostate and seminal vesicles (a treatment for prostate cancer).Blood tests for prostate specific antigen (PSA), digital rectal examination, ultrasound scanning of the prostate via the rectum, fine needle aspiration or medical imaging studies (such as magnetic resonance imaging) are not useful for diagnosing HGPIN.
Treatment
HGPIN in isolation does not require treatment. In prostate biopsies it is not predictive of prostate cancer in one year if the prostate was well-sampled, i.e. if there were 8 or more cores.The exact timing of repeat biopsies remains an area of controversy, as the time required for, and probability of HGPIN transformations to prostate cancer are not well understood.
Prognosis
On a subsequent biopsy, given a history of a HGPIN diagnosis, the chance of finding prostatic adenocarcinoma is approximately 30%.
History
PIN was historically subdivided into different stages, based on the level of cell atypia. PIN was formerly classified as PIN 1, 2 or 3, in order of increasing cell irregularities. Nowadays, PIN 1 is referred to as low grade PIN, and PIN 2 and PIN 3 are grouped together as high grade PIN. Only high grade PIN has been shown to be a risk factor for prostate cancer. Because low grade PIN has no significance and does not require repeat biopsies or treatment, it is not mentioned in pathology reports. As such, PIN has become synonymous with high grade PIN.
See also
Atypical small acinar proliferation
References
== External links == |
Ventilator-associated lung injury | Ventilator-associated lung injury (VALI) is an acute lung injury that develops during mechanical ventilation and is termed ventilator-induced lung injury (VILI) if it can be proven that the mechanical ventilation caused the acute lung injury. In contrast, ventilator-associated lung injury (VALI) exists if the cause cannot be proven. VALI is the appropriate term in most situations because it is virtually impossible to prove what actually caused the lung injury in the hospital.
Cause
It is generally regarded, based on animal models and human studies, that volutrauma is the most harmful aspect of mechanical ventilation. This may be regarded as the over-stretching of the airways and alveoli.During mechanical ventilation, the flow of gas into the lung will take the path of least resistance. Areas of the lung that are collapsed (atelectasis) or filled with secretions will be underinflated, while those areas that are relatively normal will be overinflated. These areas will become overdistended and injured. This may be reduced by using smaller tidal volumes.During positive pressure ventilation, atelectatic regions will inflate, however, the alveoli will be unstable and will collapse during the expiratory phase of the breath (atelectotrauma). This repeated alveolar collapse and expansion (RACE) is thought to cause VALI. By opening the lung and keeping the lung open RACE (and VALI) is reduced.Another possible ventilator-associated lung injury is known as biotrauma. Biotrauma involves the lung suffering injury from any mediators of the inflammatory response or from bacteremia.
Finally oxygen toxicity contributes to ventilator-associated lung injury through several mechanisms including oxidative stress.
Possible reasons for predisposition to VALI include:
An injured lung may be at risk for further injury
Cyclic atelectasis is particularly common in an injured lung
Pathogenesis
Overdistension of alveoli and cyclic atelectasis (atelectotrauma) are the primary causes for alveolar injury during positive pressure mechanical ventilation. Severe injury to alveoli causes swelling of the tissues (edema) in the lungs, bleeding of the alveoli, loss of surfactant (decrease in lung compliance) and complete alveoli collapse (biotrauma). High flow rates are associated with rheotrauma, high volumes with volutrauma and pressures with barotrauma. Collectively these may be converted into a single unit of mechanical power.
Diagnosis
VALI does not need to be distinguished from progressive ALI/ARDS because management is the same in both. Additionally, definitive diagnosis of VALI may not be possible because of lack of sign or symptoms.
Prevention
Preventing alveolar overdistension
Alveolar overdistension is mitigated by using small tidal volumes, maintaining a low plateau pressure, and most effectively by using volume-limited ventilation. A 2018 systematic review by The Cochrane Collaboration provided evidence that low tidal volume ventilation reduced post operative pneumonia and reduced the requirement for both invasive and non invasive ventilation after surgery
Preventing cyclic atelectasis (atelectotrauma)
Applied positive end-expiratory pressure (PEEP) is the principal method used to keep the alveoli open and lessen cyclic atelectasis.
Open lung ventilation
Open lung ventilation is a ventilatory strategy that combines small tidal volumes (to lessen alveolar overdistension) and an applied PEEP above the low inflection point on the pressure-volume curve (to lessen cyclic atelectasis).
High frequency ventilation is thought to reduce ventilator-associated lung injury, especially in the context of ARDS and acute lung injury.Permissive hypercapnia and hypoxaemia allow the patient to be ventilated at less aggressive settings and can, therefore, mitigate all forms of ventilator-associated lung injury
Epidemiology
VALI is most common in people receiving mechanical ventilation for acute lung injury or acute respiratory distress syndrome (ALI/ARDS).24 percent of people mechanically ventilated will develop VALI for reasons other than ALI or ARDS. The incidence is probably higher among people who already have ALI/ARDS, but estimates vary widely. The variable estimates reflect the difficulty in distinguishing VALI from progressive ALI/ARDS.
References
External links
Ventilators and COVID-19: What You Need to Know, Yale Medicine |
Lentigo maligna melanoma | Lentigo maligna melanoma is a melanoma that has evolved from a lentigo maligna,: 695 as seen as a lentigo maligna with melanoma cells invading below the boundaries of the epidermis. They are usually found on chronically sun damaged skin such as the face and the forearms of the elderly.
Lentigo maligna is the non-invasive skin growth that some pathologists consider to be a melanoma-in-situ. A few pathologists do not consider lentigo maligna to be a melanoma at all, but a precursor to melanomas. Once a lentigo maligna becomes a lentigo maligna melanoma, it is treated as if it were an invasive melanoma.
Presentation
An invasive tumor arising from a classical lentigo maligna. Usually a darkly pigmented raised papule or nodule, arising from a patch of irregularly pigmented flat brown to dark brown lesion of sun exposed skin of the face or arms in an elderly patient.
Diagnosis
The first problem is difficulty. As lentigo malignas often present on severely sun damaged skin, it is frequently found amongst numerous pigmented lesions – thin seborrheic keratoses, lentigo senilis, lentigines. It is difficult to distinguish these lesions with the naked eye alone, and even with some difficulty using dermatoscopy. As the lentigo maligna is often very large, it often merges with, or encompasses other skin tumors – such as lentigines, melanocytic nevi, and seborrheic keratosis.
The second difficulty is the biopsy technique. Even though excisional biopsy (removing the entire lesion) is ideal, and advocated by pathologists, practical considerations may indicate that this should not be done. These tumors are often large and presenting on the facial area. Excision of such large tumor would be absolutely contraindicated if the lesions identity is uncertain. The preferred method of diagnosis is by using a shave biopsy because punch biopsies give up to an 80% false negative rate. While one section of the tumor might show benign melanocytic nevus, another section might show features concerning of severe cellular atypia. When cellular atypia is noted, a pathologist might indicate that the entire lesion should be removed. It is at this point that one can comfortably remove the entire lesion, thus confirming the final diagnosis of lentigo maligna. Despite the high false negative rate, punch biopsies are often used and the size of the punch biopsy can vary from 1 mm to 2 mm, but it is preferred to use a punch 1.5 mm or larger. Representative samples of the most atypical part of the nevus should be biopsy, often by the aid of dermatoscopy.
Treatment
Treatment depends on the thickness of the invasive component of the lentigo maligna. Treatment is essentially identical to other melanomas of the same thickness and stage.
See also
Melanoma
References
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Chronic actinic dermatitis | Chronic actinic dermatitis is a condition where a subjects skin becomes inflamed due to a reaction to sunlight or artificial light. Patients often have other related conditions of the skin that cause dermatitis in response to a variety of stimuli (e.g., flowers, sunscreens, cosmetics, etc.).
Symptoms
Once affected, the symptoms may not show for several days. The symptoms can be severe burning, itching, swelling and pain in the affected areas. The areas exposed to sunlight may have the appearance of a sunburn - where clothing is worn the skin is protected. There is no known reaction to moonlight, but reflections from windows and mirrors of sunlight can still cause damage.
Diagnosis
Diagnosis can occur at any age, ranging from soon after birth to adulthood. A GP may refer a patient to a dermatologist if the condition is not showing clear symptoms, and a variety of tests - usually completed at a hospital - can then determine the exact nature and cause of the patients condition.
Reactions, which vary depending on the severity of the case, include rashes, flared bumpy patches, affected areas being extremely hot to touch, and outbreaks shortly (or within 24 hours) after direct or indirect exposure to UVA and/or UVB light. The skin most likely reacts on the upper chest, hands and face, however it is not unlikely for reactions to happen all over the body. The patient may feel burning, stinging or throbbing sensations in these areas, which causes mild, yet uncomfortable pain in some patients. Others liken the pain and sensation to a chemical burn that doesnt go away. It is a mistake to think that the reaction is like a sunburn, it is far deeper in the skin and often requires the use of ingestible steroids as well as topical steroids in order to alleviate the condition to a degree. The best protection is to be fully covered from sunlight, even when cloudy or hazy. The use of UV-rated clothing is suggested as well as a UV-rated umbrella for outdoors.
See also
List of cutaneous conditions
Photosensitivity with HIV infection
Skin lesion
References
== External links == |
Terson syndrome | Terson syndrome or Tersons syndrome is the occurrence of a vitreous hemorrhage of the human eye in association with subarachnoid hemorrhage. Vitreous hemorrhage of the eye can also occur in association with intracranial hemorrhage and elevated intracranial pressure (ICP). Intraocular hemorrhage can be a subretinal, retinal, preretinal, subhyaloidal, or intra-vitreal hemorrhage. Its likely cause is a rapid increase in ICP. The classic presentation is in the subhyaloidal space, which is beneath the posterior vitreous face and in front of the retina.In subarachnoid hemorrhage, 13% of patients have Tersons syndrome, which is associated with more severe SAH (higher Hunt-Hess score, a marker of severity), and risk of death is significantly increased.The first known report of the association was by the German ophthalmologist Moritz Litten in 1881. Still, French ophthalmologist Albert Tersons name is more commonly associated with the condition after a report by his hand from 1900.
References
External links
eMedicine topic |
Acute abdomen | An acute abdomen refers to a sudden, severe abdominal pain. It is in many cases a medical emergency, requiring urgent and specific diagnosis. Several causes need immediate surgical treatment.
Differential diagnosis
The differential diagnosis of acute abdomen includes:
Acute appendicitis
Acute peptic ulcer and its complications
Acute cholecystitis
Acute pancreatitis
Acute intestinal ischemia (see section below)
Acute diverticulitis
Ectopic pregnancy with tubal rupture
Ovarian torsion
Acute peritonitis (including hollow viscus perforation)
Acute ureteric colic
Bowel volvulus
Bowel obstruction
Acute pyelonephritis
Adrenal crisis
Biliary colic
Abdominal aortic aneurysm
Familial Mediterranean fever
Hemoperitoneum
Ruptured spleen
Kidney stone
Sickle cell anaemia
Carcinoid
Peritonitis
Acute abdomen is occasionally used synonymously with peritonitis. While this is not entirely incorrect, peritonitis is the more specific term, referring to inflammation of the peritoneum. It manifests on physical examination as rebound tenderness, or pain upon removal of pressure more than on application of pressure to the abdomen. Peritonitis may result from several of the above diseases, notably appendicitis and pancreatitis. While rebound tenderness is commonly associated with peritonitis, the most specific finding is rigidity.
Ischemic acute abdomen
Vascular disorders are more likely to affect the small bowel than the large bowel. Arterial supply to the intestines is provided by the superior and inferior mesenteric arteries (SMA and IMA respectively), both of which are direct branches of the aorta.The superior mesenteric artery supplies:
Small bowel
Ascending and proximal two-thirds of the transverse colonThe inferior mesenteric artery supplies:
Distal one-third of the transverse colon
Descending colon
Sigmoid colonOf note, the splenic flexure, or the junction between the transverse and descending colon, is supplied by the most distal portions of both the inferior mesenteric artery and superior mesenteric artery, and is thus referred to medically as a watershed area, or an area especially vulnerable to ischemia during periods of systemic hypoperfusion, such as in shock.Acute abdomen of the ischemic variety is usually due to:
A thromboembolism from the left side of the heart, such as may be generated during atrial fibrillation, occluding the SMA.
Nonocclusive ischemia, such as that seen in hypotension secondary to heart failure, may also contribute, but usually results in a mucosal or mural infarct, as contrasted with the typically transmural infarct seen in thromboembolus of the SMA.
Primary mesenteric vein thromboses may also cause ischemic acute abdomen, usually precipitated by hypercoagulable states such as polycythemia vera.Clinically, patients present with diffuse abdominal pain, bowel distention, and bloody diarrhea. On physical exam, bowel sounds will be absent. Laboratory tests reveal a neutrophilic leukocytosis, sometimes with a left shift, and increased serum amylase. Abdominal radiography will show many air-fluid levels, as well as widespread edema. Acute ischemic abdomen is a surgical emergency. Typically, treatment involves removal of the region of the bowel that has undergone infarction, and subsequent anastomosis of the remaining healthy tissue.
Workup
Stable patients presenting to A&E (accident and emergency department) or ER (emergency room) with severe abdominal pain will almost always have an abdominal x-ray and/or a CT scan. These tests can provide a differential diagnosis between simple and complex pathologies. However, in the unstable patient, fluid resuscitation and a FAST-ultrasound are done first, and if the latter is positive for free fluid, straight to surgery. They may also provide evidence to the doctor whether surgical intervention is necessary.Patients will also most likely receive a complete blood count (or full blood count in the U.K.), looking for characteristic findings such as neutrophilia in appendicitis.Traditionally, the use of opiates or other painkillers in patients with an acute abdomen has been discouraged before the clinical examination, because these would alter the examination. However, the scientific literature does not reveal any negative results from these alterations.
References
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Pityriasis amiantacea | Pityriasis amiantacea is an eczematous condition of the scalp in which thick tenaciously adherent scale infiltrates and surrounds the base of a group of scalp hairs. It does not result in scarring or alopecia.: 647 Pityriasis amiantacea was first described by Alibert in 1832. Pityriasis amiantacea affects the scalp as shiny asbestos-like (amiantaceus) thick scales attached in layers to the hair shaft. The scales surround and bind down tufts of hair. The condition can be localised or covering over the entire scalp. Temporary alopecia and scarring alopecia may occur due to repeated removal of hairs attached to the scale. It is a rare disease with a female predilection.
Diagnosis
Pityriasis amiantacea can easily be misdiagnosed due to its close resemblance to other scalp diseases such as psoriasis, seborrhoeic dermatitis or lichen planus. However, in pityriasis amiantacea the scales are attached to both the hair shaft and the scalp. Pityriasis amiantacea may be present with other inflammatory conditions such as atopic dermatitis or seborrhoeic dermatitis and sebaceous scales and alopecia can occur. According to Bolognias textbook "Dermatology," this rare condition is most often combined with psoriasis, but it may also develop as secondarily infected atopic dermatitis, seborrheic dermatitis, and/or tinea capitis.
Treatment
The bacteria staphylococci are present in the majority of cases. Treatment with systemic antibiotics and coal tar shampoo can completely clear the condition when Staphylococcus aureus bacteria are found. Fungal infections such as tinea capitis are known to mimic the symptoms of the condition and can be cleared with antifungal treatment.
See also
List of cutaneous conditions
References
== External links == |
Vaginal yeast infection | Vaginal yeast infection, also known as candidal vulvovaginitis and vaginal thrush, is excessive growth of yeast in the vagina that results in irritation. The most common symptom is vaginal itching, which may be severe. Other symptoms include burning with urination, a thick, white vaginal discharge that typically does not smell bad, pain during sex, and redness around the vagina. Symptoms often worsen just before a womans period.
Vaginal yeast infections are due to excessive growth of Candida. These yeast are normally present in the vagina in small numbers. Vaginal yeast infections are typically caused by the yeast species Candida albicans. Candida albicans is a common fungus often harbored in the mouth, digestive tract, or vagina without causing adverse symptoms. The causes of excessive Candida growth are not well understood, but some predisposing factors have been identified.
It is not classified as a sexually transmitted infection; however, it may occur more often in those who are frequently sexually active. Risk factors include taking antibiotics, pregnancy, diabetes, and HIV/AIDS. Tight clothing, type of underwear, and personal hygiene do not appear to be factors. Diagnosis is by testing a sample of vaginal discharge. As symptoms are similar to that of the sexually transmitted infections, chlamydia and gonorrhea, testing may be recommended.
Treatment is with an antifungal medication. This may be either as a cream such as clotrimazole or with oral medications such as fluconazole. Despite the lack of evidence, wearing cotton underwear and loose fitting clothing is often recommended as a preventive measure. Avoiding douching and scented hygiene products is also recommended. Probiotics have not been found to be useful for active infections.
Around 75% of women have at least one vaginal yeast infection at some point in their lives, while nearly half have at least two. Around 5% have more than three infections in a single year. It is the second most common cause of vaginal inflammation after bacterial vaginosis.
Signs and symptoms
The symptoms of vaginal thrush include vulval itching, vulval soreness and irritation, pain or discomfort during sexual intercourse (superficial dyspareunia), pain or discomfort during urination (dysuria) and vaginal discharge, which is usually odourless. Although the vaginal discharge associated with yeast infection is often described as thick and lumpy, like paper paste or cottage cheese, it can also be thin and watery, or thick and of uniform texture. In one study, women with vaginal yeast infection were no more likely to describe their discharge as cottage-cheese like than women without.As well as the above symptoms of thrush, vulvovaginal inflammation can also be present. The signs of vulvovaginal inflammation include erythema (redness) of the vagina and vulva, vaginal fissuring (cracked skin), edema (swelling from a build-up of fluid), also in severe cases, satellite lesions (sores in the surrounding area). This is rare, but may indicate the presence of another fungal condition, or the herpes simplex virus (the virus that causes genital herpes).Vaginal candidiasis can very rarely cause congenital candidiasis in newborns.
Causes
Medications
Infection occurs in about 30% of women who are taking a course of antibiotics by mouth. Broad-spectrum antibiotics kill healthy bacteria in the vagina, such as Lactobacillus. These bacteria normally help to limit yeast colonization.Oral contraceptive use is also associated with increased risk of vaginal thrush.
Pregnancy
In pregnancy, higher levels of estrogen make a woman more likely to develop a yeast infection. During pregnancy, the Candida fungus is more common, and recurrent infection is also more likely. There is tentative evidence that treatment of asymptomatic candidal vulvovaginitis in pregnancy reduces the risk of preterm birth.
Lifestyle
While infections may occur without sex, a high frequency of intercourse increases the risk. Personal hygiene methods or tight-fitting clothing, such as tights and thong underwear, do not appear to increase the risk.
Diseases
Those with poorly controlled diabetes have increased rates of infection while those with well controlled diabetes do not. The risk of developing thrush is also increased when there is poor immune function, as with HIV/AIDS, or in those receiving chemotherapy.
Diet
A diet high in sugar may increase the risk of vaginal thrush; in some women, reducing sugar intake seems to reduce the risk of reoccurring vaginal thrush.
Species of yeast responsible
While Candida albicans is the most common yeast species associated with vaginal thrush, infection by other types of yeast can produce similar symptoms. A Hungarian study of 370 patients with confirmed vaginal yeast infections identified the following types of infection:
Candida albicans: 85.7%
Non-albicans Candida (8 species): 13.2%
Saccharomyces cerevisiae: 0.8%
Candida albicans and Candida glabrata: 0.3%Non-albicans Candida are often found in complicated cases of vaginal thrush in which the first line of treatment is ineffective. These cases are more likely in those who are immunocompromised.
Diagnosis
Vulvovaginal candidosis is the presence of Candida in addition to vaginal inflammation. The presence of yeast is typically diagnosed in one of three ways: vaginal wet mount microscopy, microbial culture, and antigen tests. The results may be described as being either uncomplicated or complicated.
Uncomplicated
Uncomplicated thrush is when there are less than four episodes in a year, the symptoms are mild or moderate, it is likely caused by Candida albicans, and there are no significant host factors such as poor immune function.
Complicated
Complicated thrush is four or more episodes of thrush in a year or when severe symptoms of vulvovaginal inflammation are experienced. It is also complicated if coupled with pregnancy, poorly controlled diabetes, poor immune function, or the thrush is not caused by Candida albicans.
Recurrent
About 5-8% of the reproductive age female population will have four or more episodes of symptomatic Candida infection per year; this condition is called recurrent vulvovaginal candidiasis (RVVC). Because vaginal and gut colonization with Candida is commonly seen in people with no recurrent symptoms, recurrent symptomatic infections are not simply due to the presence of Candida organisms. There is some support for the theory that RVVC results from an especially intense inflammatory reaction to colonization. Candida antigens can be presented to antigen-presenting cells, which may trigger cytokine production and activate lymphocytes and neutrophils that then cause inflammation and edema.
Treatment
The following treatments are typically recommended:
Intravaginal (vaginal suppository): butoconazole, clotrimazole, miconazole, nystatin, tioconazole, terconazole. Candidal vulvovaginitis in pregnancy should be treated with intravaginal clotrimazole or nystatin for at least 7 days. All are more or less equally effective.
By mouth: ibrexafungerp, fluconazole as a single dose. For severe disease another dose after 3 days may be used.Short-course topical formulations (i.e., single dose and regimens of 1–3 days) effectively treat uncomplicated candidal vulvovaginitis. The topically applied azole drugs are more effective than nystatin. Treatment with azoles results in relief of symptoms and negative cultures in 80–90% of patients who complete therapy.The creams and suppositories in this regimen are oil-based and might weaken latex condoms and diaphragms. Treatment for vagina thrush using antifungal medication is ineffective in up to 20% of cases. Treatment for thrush is considered to have failed if the symptoms do not clear within 7–14 days. There are a number of reasons for treatment failure. For example, if the infection is a different kind, such as bacterial vaginosis (the most common cause of abnormal vaginal discharge), rather than thrush.
Recurrent
For infrequent recurrences, the simplest and most cost-effective management is self-diagnosis and early initiation of topical therapy. However, women whose condition has previously been diagnosed with candidal vulvovaginitis are not necessarily more likely to be able to diagnose themselves; therefore, any woman whose symptoms persist after using an over the counter preparation, or who has a recurrence of symptoms within two months, should be evaluated with office-based testing. Unnecessary or inappropriate use of topical preparations is common and can lead to a delay in the treatment of other causes of vulvovaginitis, which can result in worse outcomes.When there are more than four recurrent episodes of candidal vulvovaginitis per year, a longer initial treatment course is recommended, such as orally administered fluconazole followed by a second and third dose 3 and 6 days later, respectively.Other treatments after more than four episodes per year, may include ten days of either oral or topical treatment followed by fluconazole orally once per week for six months. About 10-15% of recurrent candidal vulvovaginitis cases are due to non-Candida albicans species. Non-albicans species tend to have higher levels of resistance to fluconazole. Therefore, recurrence or persistence of symptoms while on treatment indicates speciation and antifungal resistance tests to tailor antifungal treatment.
Alternative medicine
Up to 40% of women seek alternatives to treat vaginal yeast infection. Example products are herbal preparations, probiotics and vaginal acidifying agents. Other alternative treatment approaches include switching contraceptive, treatment of the sexual partner and gentian violet. However, the effectiveness of such treatments has not received much study.Probiotics (either as pills or as yogurt) do not appear to decrease the rate of occurrence of vaginal yeast infections. No benefit has been found for active infections. Example probiotics purported to treat and prevent candida infections are Lactobacillus fermentum RC-14, Lactobacillus fermentum B-54, Lactobacillus rhamnosus GR-1, Lactobacillus rhamnosus GG and Lactobacillus acidophilus.There is no evidence to support the use of special cleansing diets and colonic hydrotherapy for prevention.
Epidemiology
The number of cases of vaginal yeast infection is not entirely clear because it is not a reportable disease and it is commonly diagnosed clinically without laboratory confirmation.Candidiasis is one of the three most common vaginal infections along with bacterial vaginosis and trichomonas. About 75% of women have at least one infection in their lifetime, 40%–45% will have two or more episodes, and approximately 20% of women get an infection yearly.
Research
Vaccines that target C. albicans are under active development since several years. Phase 2 results published in June 2018 showed a safe and high immunogenicity of the NDV-3A vaccine candidate.
== References == |
Genodermatosis | Genodermatosis is a hereditary skin disease with three inherited modes including single gene inheritance, multiple gene inheritance and chromosome inheritance. There are many different types of genodermatosis, the prevalence of genodermatosis ranges from 1 per 6000 people to 1 per 500,000 people. Genodermatosis has influence on the texture, color and structure of skin cuticle and connective tissue, specific lesion site and clinical manifestations on the body vary depending on the type. In the spite of the variety and complexity of genodermatosis, there are still some common methods that can help people diagnose. After diagnosis, different types of genodermatosis require different levels of therapy including interventions, nursing interventions and treatments. Among that, research of therapy for some new, complex and rare types are still in the developing stage. The impact of genodermatosis not only can be seen in body but also can be seen in all aspects of patients life, including but not limited to psychological, family life, economic conditions and social activities. Accordingly, the patients need treatment, support and help in these areas.
Hereditary modes
Genodermatosis is inherited in three modes: single gene inheritance, multiple gene inheritance and chromosome inheritance.
Single gene (monogenic)
Single-gene inheritance of genodermatosis refers to the inheritance of a skin disease caused by one genetic abnormality and single gene heredity is divided into four kinds mainly.
Autosomal dominant inheritance
The first kind is autosomal dominant inheritance, in this kind of inheritance, patients can be of any sex and their genodermatosis are often inherited from one of the parents. Cases of skin disease that may be inherited in this kind of mode include epidermolysis bullosa simplex (EBS), acute intermittent porphyria, white sponge nevus, ichthyosis, epidermolytic palmoplantar keratoderma, hereditary benign intraepithelial dyskeratosis and so on.
Autosomal recessive inheritance
The second kind is autosomal recessive inheritance, in this kind of inheritance, patients can be of any sex and inbreeding tends to lead to this inheritance. Cases of skin disease that may be inherited in this kind of mode include epidermolysis bullosa, xeroderma pigmentosum, acrodermatitis enteropathica, ichthyosis and so on.
X-linked dominant inheritance
The third kind is X-linked dominant inheritance, in this kind of inheritance, patients can be of any sex. Male patients can pass the disease on to their sons and the chances of female patients passing it to their daughters or sons are almost equal. Cases of skin disease that may be inherited in this kind of mode include incontinentia pigmenti, focal dermal hypoplasia and so on.
X-linked recessive inheritance
The last kind is X-linked recessive inheritance, in this kind of inheritance, patients can be of any sex and the prevalence in men is higher than that in women. Male patients cannot pass the disease on to their sons. Cases of skin disease that may be inherited in this kind of mode include fabry disease, anhidrotic ectodermal dysplasia, dyskeratosis congenita and so on.
Multiple gene (polygenic)
Multiple-gene inheritance of genodermatosis refers to the inheritance of a skin disease caused by multiple genetic abnormalities. Cases of skin disease that may be inherited in this mode include vitiligo, psoriasis, pemphigus vulgaris, systemic lupus erythematosus and so on.
Chromosome
Chromosome inheritance of genodermatosis refers to the inheritance of a skin disease caused by chromosome abnormality.
The same disease can be inherited in different modes. For instance, epidermolysis bullosa can be inherited in the mode of autosomal dominant or in the mode of autosomal recessive.
Types
Genodermatosis has many types, many of which are rare.
Common types
Ichthyosis
Ichthyosis refers mainly to ichthyosis vulgaris, a common genodermatosis, people with this disease have a fishy, dry skin, which usually appears in early childhood and may disappear in adulthood. The prevalence of ichthyosis vulgaris is high, affecting almost 1 per 250 people. There are also rare types of ichthyosis, such as epidermolytic hyperkeratosis, harlequin ichthyosis and so on.
Rare types
Michelin tyre baby syndrome
Michelin tyre baby syndrome is a rare genodermatosis that occurs at birth, the skin of the patients is stacked symmetrically in layers like the image of the Michelin tyres mascot, which is also how this disease got its name.
Epidermolysis bullosa
Epidermolysis bullosa is a rare type of genodermatosis, people with this disease have blisters on their skin and this disease is never completely cured for a lifetime. Epidermolysis bullosa is mainly subdivided into four types: dystrophic epidermolysis bullosa, epidermolysis bullosa simplex, junctional epidermolysis bullosa and kindler syndrome. Almost 1 in 50,000 people has epidermolysis bullosa.
Pachyonychia congenita
Pachyonychia congenita is a rare type of genodermatosis, its clinical manifestations are abnormal enlargement of fingernails or toenails, excessive or poor palmoplantar keratinization, excessive sweating in the palmar or the plantar. Between 5000 and 10000 people in the world have pachyonychia congenita.
Epidermolytic palmoplantar keratoderma
Epidermolytic palmoplantar keratoderma often appears at birth and it is almost impossible to be cured completely. The clinical manifestations of this disease include excessive palmoplantar keratinization, the palmar or plantar become yellow divergently with around the edges or abnormally excessive sweating and clinical manifestation appear in a symmetrical form on the body.
Hereditary benign intraepithelial dyskeratosis
Hereditary benign intraepithelial dyskeratosis is a rare type of genodermatosis that may occur in infancy and early childhood, its symptoms often appear in the patients eyes and mouths. The patients eyes appear red due to the dilatation of superficial vessels and appearance of conjunctival plaques in their eyes, patients may have variable-size, thick, soft and white plaques in their mouth. Spring is an acute episode of symptoms, such as itching, erythema, photophobia and so on.
Epidermolytic hyperkeratosis
Epidermolytic hyperkeratosis is a rare genodermatosis which is also referred to as disorder of cornification type 3 and bullous congenital ichthyosiform erthroderma, affecting almost 1 per 200,000 - 300,000 people. They also stated that its clinical manifestations often begin at birth with large rashes all over the body, and the patients skin will be so sensitive that even mild wounds can cause blisters and peeling. Potential complications of this disease include electrolyte disturbances, sepsis and so on.
Hidrotic ectodermal dysplasia
Hidrotic ectodermal dysplasia is a rare genodermatosis which is also known as Clouston syndrome. The patients nails may be too thick, too brittle, too bent or have different colors, their hair also appear mottled, sparse and other abnormalities. These symptoms often begin when the patient is an infant.
Diagnostic methods
Genodermatosis is often rare and varied, but diagnostic methods have some commonalities, the diagnosis of rare genodermatosis is basically divided into six steps: 1. Each genodermatosis has different clinical manifestations. People can observe the special features and changes of the skin to judge whether they are sick or not. Features will be different in different age groups, so it is necessary to observe and record the special features of the skin in each age group; 2. Genodermatosis is a hereditary disease, knowing as much as possible about a detailed and complete family history helps in screening and diagnosis; 3. People can do a detailed physical examination to observe the special features and manifestations of other organs besides skin. It can help to narrow down the disease and make a definitive diagnosis; 4. People can carry out laboratory tests such as skin biopsies with high-tech and precise scientific instruments to have further results; 5. Different genodermatosis and their clinical manifestations may be caused by abnormalities in the same gene, and abnormalities in different genes may also lead to the same clinical manifestations. In order to have a definitive diagnosis or identify complex and specific types of genodermatosis, genotype–phenotype correlation needs attention; 6. If the above five steps fails to help people who suspected of having a genodermatosis to obtain the diagnosis result, they should keep all their information such as the diagnosis record and the clinical manifestations at different stages, and continue to record the changes of the body, waiting with a positive attitude, the future medicine may give the answer.
Therapy
The therapy of genodermatosis not only needs to take care of patients skin, reduce their pain and prevent complications, but also needs to carry out mental support for patients and their families.
Prevention and care
Different types of genodermatosis require different kinds of prevention and care.
Ichthyosis
There is no radical therapeutic method for ichthyosis, but some care can ease the symptoms. To prevent skin thickening and hydrate skin, patients can apply a cream containing alpha hydroxy acids and patients can also be treated with antibiotics for subsequent infections.
Epidermolysis bullosa
For epidermolysis bullosa, daily care is important. When treating a wound, keep it clean and reduce friction, the bandages and dressing used must be non-sticky and gentle, and the patient should wear loose clothing to avoid damaging the wound.
Epidermolytic hyperkeratosis
The treatment of Epidermolytic hyperkeratosis is mainly control and alleviate symptoms, and good nursing can reduce the incidence of complications like electrolyte disturbances and sepsis. To improve the look and feeling of the skin, patients can apply a cream containing alpha hydroxy acids, glycerol and urea, and if necessary, patients can use antibiotics to control secondary infections.
Pachyonychia congenita
There is no radical therapeutic method for pachyonychia congenita, but some care can ease the symptoms. Patients can polish and trim thickened nails, some of them can use retinoids to relieve symptoms but it may increase pain.
Neurofibromatosis type I
Selumetinib and trametinib have been shown to reduce and control tumor growth in people with neurofibromatosis type I, reducing the likelihood of malignant lesions.
Therapeutic methods
There are some new and developing genetic therapies available in genodermatosis.In the case of X-linked hypohidrotic ectodermal dysplasia, unborn babies diagnosed with this disease can be treated in their mothers womb. Providing regulatory proteins in the womb during a critical period of infant growth may help correct the development of babies sweat glands.Ustekinumab is a biologic therapy that can be used in a variety of genodermatosis such as congenital ichthyosis, psoriasis, deficiency of interleukin-36 receptor antagonist (DITRA) and so on.A new topical method could treat skin abnormalities in rare inherited lipid metabolic diseases. This method obstructs abnormal mevalonate by topical application of lovastatin so that the production and cumulation of poisonous metabolic intermediates can be inhibited as much as possible and takes the place of the lacking lipid in the skin by topical application of cholesterol. The idea that similar treatments could be developed for other genodermatosis was also pointed out at the annual conference of the European Society of Dermatology and Venereology.For epidermolysis bullosa, a method called CRISPR can be used to treat this disease by gene analysis, modification and substitution, but the method is ethically controversial because it consents to editing genes highly.Treatments for some rare diseases are still being studied. The therapy of genodermatosis requires the updating of technology, and the development of technology depends on the continuous understanding of the mechanism of the disease. Research on the treatment of genodermatosis is at a positive stage of development.
Effects
Genodermatosis affects patients in many ways. Genodermatosis is a kind of skin disease, it affects the texture, color and structure of the cuticle and connective tissue of the skin, some of which can cause abnormalities in other organs. On the social side, because the genodermatosis makes the patients skin and appearance different from the ordinary people and makes them have limitations in some activities, they more or less encounter obstacles in the process of making friends, seeking a mate, going to school and entering the workplace. Difficulties in communicating with others as well as worldly prejudice may affect their mental health. Patients are also affected by genodermatosis in terms of family life. Because of the behavioral disorders and treatment of certain genodermatosis, families need to spend more time caring for the patient, and the patient may have more concerns and considerations about procreating children due to the disease. In terms of economy, the treatment of genodermatosis is not a simple and short process, which will generate additional family expenses and increase economic pressure on patients and their families.
See also
List of cutaneous conditions
References
== External links == |
Athetosis | Athetosis is a symptom characterized by slow, involuntary, convoluted, writhing movements of the fingers, hands, toes, and feet and in some cases, arms, legs, neck and tongue. Movements typical of athetosis are sometimes called athetoid movements. Lesions to the brain are most often the direct cause of the symptoms, particularly to the
corpus striatum. This symptom does not occur alone and is often accompanied by the symptoms of cerebral palsy, as it is often a result of this physical disability. Treatments for athetosis are not very effective, and in most cases are simply aimed at managing the uncontrollable movement, rather than the cause itself.
Signs and symptoms
Athetosis can vary from mild to severe motor dysfunction; it is generally characterized by unbalanced, involuntary movements of muscle and a difficulty maintaining a symmetrical posture. The associated motor dysfunction can be restricted to a part of the body or present throughout the body, depending on the individual and the severity of the symptom. One of the pronounced signs can be observed in the extremities in particular, as the writhing, convoluted movement of the digits. Athetosis can appear as early as 18 months from birth with first signs including difficulty feeding, hypotonia, spasm, and involuntary writhing movements of the hands, feet, and face, which progressively worsen through adolescence and at times of emotional distress. Athetosis is caused by lesions in several brain areas such as the hippocampus and the motor thalamus, as well as the corpus striatum; therefore children during the developmental age could possibly suffer from severe communication deficits such as speech impairment, hearing loss, and failed or delayed acquirement of sitting balance, although most people with athetosis have normal or near-normal intelligence.
Causes
Athetosis is a symptom primarily caused by the marbling, or degeneration of the basal ganglia. This degeneration is most commonly caused by complications at birth or by Huntingtons disease, in addition to rare cases in which the damage may also arise later in life due to stroke or trauma. The two complications of particular interest are intranatal asphyxia and neonatal jaundice.
Asphyxia
Asphyxia directly causes basal ganglia damage due to lack of oxygen and therefore, insufficient nutrient supply. The lesions caused by asphyxia are most prominent on the caudate nucleus and the putamen. However, a less-studied consequence of the resulting hypoxia is its effect on the concentrations of the neurotransmitter dopamine within the synapses of neurons in the basal ganglia. Hypoxia leads to an increase in the extracellular dopamine levels and therefore, an increase in the activity of the dopaminergic neurons. Furthermore, this increase in extracellular concentration is not caused by an increase in the neurotransmitter synthesis, but instead on inhibiting its reuptake back into the neurons and glial cells. Therefore, there is an increased dopaminergic effect as dopamine remains in the synapse at higher concentrations leading to additional post-synaptic response. As a result, the uncontrollable writhing motions witnessed with athetosis deal with the over-activity of synapses within the basal ganglia.
Neonatal jaundice
Neonatal jaundice is the other chief complication that leads to the basal ganglia damage associated with this condition. Jaundice is caused by hyperbilirubinemia, or abnormally high levels of bilirubin in the blood. Bilirubin is usually bound to albumin immediately and sent to the liver. However, in neonatal jaundice, the concentration of bilirubin overwhelms that of albumin and some of the bilirubin remains unconjugated and can enter the brain through the blood–brain barrier. Normally bilirubin would not be able to diffuse across the blood–brain barrier, but in infants, the barrier is immature and has higher permeability. Bilirubin is toxic as it prevents the phosphorylation of many proteins, including synapsin I which binds vesicles in the presynaptic terminal. Therefore, it directly inhibits the exocytosis of neurotransmitters and severely hinders the synapses it affects. In autopsies of children who suffered from neonatal jaundice, chronic changes of neuronal loss, gliosis and demyelination were observed in the basal ganglia and more specifically within the globus pallidus.
Thalamic stroke
Another study was done where the onset of athetoid movement followed a thalamic stroke. The thalamus is part of a pathway that is involved with the cortical feedback loop in which signals from the cortex are relayed through the striatum, pallidus and thalamus before making it back to the cortex. The striatum receives excitatory inputs from the cortex and inhibits the pallidum. By doing so it frees the thalamus from pallidal inhibition allowing the thalamus to send excitatory outputs to the cortex. Therefore, the lesions to the thalamus or any other part of this feedback loop can result in movement disorders as they can alter the reactivity of one towards the other. Also, in a case of people with thalamic stroke, a majority suffered severe sensory deficits and ataxia. It is proposed that this loss of proprioception and the ensuing loss of synergic stabilization may also lead to abnormal movements, such as those dealt with in athetosis.
Fahrs syndrome
Treatments
There are several different treatment approaches to dealing with athetosis. The most common methods are the use of drugs, surgical intervention, and retraining movements of the afflicted person. It is suggested that training a person to relearn movements can be helpful in select situations. Though, generally, this type of treatment will not work, in certain cases it can be found to be very helpful in treating the symptom of athetosis.Drugs can also be used in the treatment of athetosis, however their collective effectiveness is not very convincing. There is not a single drug that is a standard among treatment. Many different medicines can be used, including:
Artane
Cogentin
Curare, though not practical due to respiratory paralysis
Tetrabenazine
Haloperidol
Thiopropazate
DiazepamMost instances of drug use where the symptoms seem to be lessened tend to be in more mild cases of athetosis.Treatment by surgical intervention can obviously have the most immediate impact, again however, it is not a cure-all. In patients that have cerebral palsy as the cause of their athetosis, it has been demonstrated that a subthalamotomy tends to help relieve the extent of athetosis in approximately half of patients. Additionally, late 19th and early 20th century surgical accounts state that athetosis can be relieved by the removal of a part of the cerebral motor cortex or by cutting a part of the posterior spinal roots. Patients who undergo surgical treatment to relieve the athetosis often see significant improvement in the control of their limbs and digits. While surgery is often very beneficial in the short term and can produce near immediate results, in the long term it has been seen that its effects are not incredibly long lasting.
Related disorders
Choreoathetosis
Chorea is another condition which results from damage to the basal ganglia. Similar to athetosis, it results from mutations affecting the pallidum inhibition of the thalamus as well as increased dopaminergic activity at the level of the striatum. Considering the etiology of both disorders are fairly similar, it comes as no surprise that chorea and athetosis can and usually do occur together in a condition called choreoathetosis.
Cerebral palsy
Athetosis is a commonly occurring symptom in the disease cerebral palsy. Of all people with the disease, between 16% and 25% of them actually exhibit the symptom of athetosis. A component of this is the finding that most often the symptoms that involve athetosis occur as a part of choreoathetosis as opposed to athetosis alone.It is also noteworthy that the presence of athetosis in cerebral palsy (as well as other conditions) causes a significant increase in a persons basal resting metabolic rate. It has been observed that those who have cerebral palsy with athetosis require approximately 500 more Calories per day than their non-cerebral palsy non-athetoid counterpart.
Pseudoathetosis
Pseudoathetosis is a movement disorder, very similar to athetosis, in which the symptoms are not differentiable from those of actual athetosis, however the underlying cause is different. While actual athetosis is caused by damage to the brain, specifically in the basal ganglia, pseudoathetosis is caused by the loss of proprioception. The loss in proprioception is caused by damage to the area between the primary somatosensory cortex and the muscle spindles and joint receptors. Additionally, when observing an MRI, it can be seen that in the brain of a pseudoathetoid patient, lesions on the brain are not seen in the basal ganglia, the area that is oftentimes the cause of athetosis.
Social implications
Athetosis is characterized as a symptom that is present in many forms of central nervous system disorders that affect the body movement coordination, such as cerebral palsy. Children may struggle to engage in social communication, since the poor coordination of the tongue and mouth muscles can reduce their speech ability and hinder their social interaction to a greater degree. The caregivers of the affected children are encouraged to closely monitor their nutrition and growth and to provide them with hearing aids in order to relieve their symptoms as well as support their academic plans. A growing number of patients is shown to benefit from communication devices such as shorthand typing programs and computer speech devices, as well as simple picture boards.Patients living with the disorder into their adulthood often have trouble being involved in daily activities such as eating, walking, dressing, as well as performing everyday tasks. They are consistently faced with challenges that limit their ability to live on their own. They are more reluctant to be involved in social activities and romantic relationships and more likely to develop poor self-esteem and self-image related to their physical limitations as well as cognitive disabilities, though such habitual thinking is shown to decline when they feel they are accepted and supported by their peers. Patients are also inclined to associate themselves with people who tend not to be engaged in physical activities, according to the September 2008 issue of “Journal of Physical Activity and Health.”
History
The first noted case of athetosis was discovered by W. A. Hammond and described in his book Diseases of the Nervous System in 1871. Hammond was also the person who created the term "athetosis", Greek for "without position". In his initial description of athetosis, the extent of the uncontrolled movement was limited to the fingers and toes. In association with this, he noted that the patients calves and forearms were oftentimes flexed and that movements were generally slow. Over the period of time leading into the late 20th century, the definition of athetosis was expanded to include movements of the neck, tongue, face, and even the trunk. Along with the expansion of the symptoms came the recognition that it was a part of many medical conditions, including cerebral palsy and stroke.
Research directions
As athetosis is relatively difficult to treat, efforts are being made to help those with the condition live and perform tasks more effectively and more efficiently. One such example of work that has been recently undertaken is a project to help those affected with athetosis to use a computer with more ease. Software for the control of the computer uses joysticks that perform linear filtering to aid in control.An additional possible treatment option for those afflicted with the symptom is neurostimulation. Studies have begun, and in cerebral palsy patients affected with dystonia-choreoathetosis, it has been demonstrated that neurostimulation has been an effective treatment in lessening symptoms in patients. There has not been a tremendous amount of experimentation, though, in this as a possible treatment option.
See also
Chorea
Dyskinesia
Dystonia
Pupillary athetosis
References
== External links == |
Spinal cord injury | A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. Symptoms may include loss of muscle function, sensation, or autonomic function in the parts of the body served by the spinal cord below the level of the injury. Injury can occur at any level of the spinal cord and can be complete, with a total loss of sensation and muscle function at lower sacral segments, or incomplete, meaning some nervous signals are able to travel past the injured area of the cord up to the Sacral S4-5 spinal cord segments. Depending on the location and severity of damage, the symptoms vary, from numbness to paralysis, including bowel or bladder incontinence. Long term outcomes also range widely, from full recovery to permanent tetraplegia (also called quadriplegia) or paraplegia. Complications can include muscle atrophy, loss of voluntary motor control, spasticity, pressure sores, infections, and breathing problems.
In the majority of cases the damage results from physical trauma such as car accidents, gunshot wounds, falls, or sports injuries, but it can also result from nontraumatic causes such as infection, insufficient blood flow, and tumors. Just over half of injuries affect the cervical spine, while 15% occur in each of the thoracic spine, border between the thoracic and lumbar spine, and lumbar spine alone. Diagnosis is typically based on symptoms and medical imaging.Efforts to prevent SCI include individual measures such as using safety equipment, societal measures such as safety regulations in sports and traffic, and improvements to equipment. Treatment starts with restricting further motion of the spine and maintaining adequate blood pressure. Corticosteroids have not been found to be useful. Other interventions vary depending on the location and extent of the injury, from bed rest to surgery. In many cases, spinal cord injuries require long-term physical and occupational therapy, especially if it interferes with activities of daily living.
In the United States, about 12,000 people a year survive a spinal cord injury. The most commonly affected group are young adult males. SCI has seen great improvements in its care since the middle of the 20th century. Research into potential treatments includes stem cell implantation, hypothermia, engineered materials for tissue support, epidural spinal stimulation, and wearable robotic exoskeletons.
Classification
Spinal cord injury can be traumatic or nontraumatic, and can be classified into three types based on cause: mechanical forces, toxic, and ischemic (from lack of blood flow). The damage can also be divided into primary and secondary injury: the cell death that occurs immediately in the original injury, and biochemical cascades that are initiated by the original insult and cause further tissue damage. These secondary injury pathways include the ischemic cascade, inflammation, swelling, cell suicide, and neurotransmitter imbalances. They can take place for minutes or weeks following the injury.At each level of the spinal column, spinal nerves branch off from either side of the spinal cord and exit between a pair of vertebrae, to innervate a specific part of the body. The area of skin innervated by a specific spinal nerve is called a dermatome, and the group of muscles innervated by a single spinal nerve is called a myotome. The part of the spinal cord that was damaged corresponds to the spinal nerves at that level and below. Injuries can be cervical 1–8 (C1–C8), thoracic 1–12 (T1–T12), lumbar 1–5 (L1–L5), or sacral (S1–S5). A persons level of injury is defined as the lowest level of full sensation and function. Paraplegia occurs when the legs are affected by the spinal cord damage (in thoracic, lumbar, or sacral injuries), and tetraplegia occurs when all four limbs are affected (cervical damage).SCI is also classified by the degree of impairment. The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), published by the American Spinal Injury Association (ASIA), is widely used to document sensory and motor impairments following SCI. It is based on neurological responses, touch and pinprick sensations tested in each dermatome, and strength of the muscles that control key motions on both sides of the body. Muscle strength is scored on a scale of 0–5 according to the table on the right, and sensation is graded on a scale of 0–2: 0 is no sensation, 1 is altered or decreased sensation, and 2 is full sensation. Each side of the body is graded independently.
Complete and incomplete injuries
In a "complete" spinal injury, all functions below the injured area are lost, whether or not the spinal cord is severed. An "incomplete" spinal cord injury involves preservation of motor or sensory function below the level of injury in the spinal cord. To be classed as incomplete, there must be some preservation of sensation or motion in the areas innervated by S4 to S5, e.g. voluntary external anal sphincter contraction. The nerves in this area are connected to the very lowest region of the spinal cord, and retaining sensation and function in these parts of the body indicates that the spinal cord is only partially damaged. Incomplete injury by definition includes a phenomenon known as sacral sparing: some degree of sensation is preserved in the sacral dermatomes, even though sensation may be more impaired in other, higher dermatomes below the level of the lesion. Sacral sparing has been attributed to the fact that the sacral spinal pathways are not as likely as the other spinal pathways to become compressed after injury due to the lamination of fibers within the spinal cord.
Spinal cord injury without radiographic abnormality
Spinal cord injury without radiographic abnormality exists when SCI is present but there is no evidence of spinal column injury on radiographs. Spinal column injury is trauma that causes fracture of the bone or instability of the ligaments in the spine; this can coexist with or cause injury to the spinal cord, but each injury can occur without the other. Abnormalities might show up on magnetic resonance imaging (MRI), but the term was coined before MRI was in common use.
Central cord syndrome
Central cord syndrome, almost always resulting from damage to the cervical spinal cord, is characterized by weakness in the arms with relative sparing of the legs, and spared sensation in regions served by the sacral segments. There is loss of sensation of pain, temperature, light touch, and pressure below the level of injury. The spinal tracts that serve the arms are more affected due to their central location in the spinal cord, while the corticospinal fibers destined for the legs are spared due to their more external location. The most common of the incomplete SCI syndromes, central cord syndrome usually results from neck hyperextension in older people with spinal stenosis. In younger people, it most commonly results from neck flexion. The most common causes are falls and vehicle accidents; however other possible causes include spinal stenosis and impingement on the spinal cord by a tumor or vertebral disk.
Anterior cord syndrome
Anterior cord syndrome, due to damage to the front portion of the spinal cord or reduction in the blood supply from the anterior spinal artery, can be caused by fractures or dislocations of vertebrae or herniated disks. Below the level of injury, motor function, pain sensation, and temperature sensation are lost, while sense of touch and proprioception (sense of position in space) remain intact. These differences are due to the relative locations of the spinal tracts responsible for each type of function.
Brown-Séquard syndrome
Brown-Séquard syndrome occurs when the spinal cord is injured on one side much more than the other. It is rare for the spinal cord to be truly hemisected (severed on one side), but partial lesions due to penetrating wounds (such as gunshot or knife wounds) or fractured vertebrae or tumors are common. On the ipsilateral side of the injury (same side), the body loses motor function, proprioception, and senses of vibration and touch. On the contralateral (opposite side) of the injury, there is a loss of pain and temperature sensations.
Posterior cord syndrome
Posterior cord syndrome, in which just the dorsal columns of the spinal cord are affected, is usually seen in cases of chronic myelopathy but can also occur with infarction of the posterior spinal artery. This rare syndrome causes the loss of proprioception and sense of vibration below the level of injury while motor function and sensation of pain, temperature, and touch remain intact. Usually posterior cord injuries result from insults like disease or vitamin deficiency rather than trauma. Tabes dorsalis, due to injury to the posterior part of the spinal cord caused by syphilis, results in loss of touch and proprioceptive sensation.
Conus medullaris and cauda equina syndromes
Conus medullaris syndrome is an injury to the end of the spinal cord, located at about the T12–L2 vertebrae in adults. This region contains the S4–S5 spinal segments, responsible for bowel, bladder, and some sexual functions, so these can be disrupted in this type of injury. In addition, sensation and the Achilles reflex can be disrupted. Causes include tumors, physical trauma, and ischemia. The Cauda equina syndrome may also be caused by central disc prolapse or slipped disc, infections such as epidural abscess, spinal haemorrhages, secondary to medical procedures and birth abnormalities.Cauda equina syndrome (CES) results from a lesion below the level at which the spinal cord splits into the cauda equina, at levels L2–S5 below the conus medullaris. Thus it is not a true spinal cord syndrome since it is nerve roots that are damaged and not the cord itself; however, it is common for several of these nerves to be damaged at the same time due to their proximity. CES can occur by itself or alongside conus medullaris syndrome. It can cause low back pain, weakness or paralysis in the lower limbs, loss of sensation, bowel and bladder dysfunction, and loss of reflexes. Patient may present with bilateral sciatica with central disc prolapse and altered gait. Unlike in conus medullaris syndrome, symptoms often occur on only one side of the body. The cause is often compression, e.g. by a ruptured intervertebral disk or tumor. Since the nerves damaged in CES are actually peripheral nerves because they have already branched off from the spinal cord, the injury has better prognosis for recovery of function: the peripheral nervous system has a greater capacity for healing than the central nervous system.
Signs and symptoms
Signs (observed by a clinician) and symptoms (experienced by a patient) vary depending on where the spine is injured and the extent of the injury.
A section of skin innervated through a specific part of the spine is called a dermatome, and injury to that part of the spine can cause pain, numbness, or a loss of sensation in the related areas. Paraesthesia, a tingling or burning sensation in affected areas of the skin, is another symptom. A person with a lowered level of consciousness may show a response to a painful stimulus above a certain point but not below it.
A group of muscles innervated through a specific part of the spine is called a myotome, and injury to that part of the spinal cord can cause problems with movements that involve those muscles. The muscles may contract uncontrollably (spasticity), become weak, or be completely paralysed. Spinal shock, loss of neural activity including reflexes below the level of injury, occurs shortly after the injury and usually goes away within a day. Priapism, an erection of the penis may be a sign of acute spinal cord injury.The specific parts of the body affected by loss of function are determined by the level of injury. Some signs, such as bowel and bladder dysfunction can occur at any level. Neurogenic bladder involves a compromised ability to empty the bladder and is a common symptom of spinal cord injury. This can lead to high pressures in the bladder that can damage the kidneys.
Lumbosacral
The effects of injuries at or above the lumbar or sacral regions of the spinal cord (lower back and pelvis) include decreased control of the legs and hips, genitourinary system, and anus. People injured below level L2 may still have use of their hip flexor and knee extensor muscles. Bowel and bladder function are regulated by the sacral region. It is common to experience sexual dysfunction after injury, as well as dysfunction of the bowel and bladder, including fecal and urinary incontinence.
Thoracic
In addition to the problems found in lower-level injuries, thoracic (chest height) spinal lesions can affect the muscles in the trunk. Injuries at the level of T1 to T8 result in inability to control the abdominal muscles. Trunk stability may be affected; even more so in higher level injuries. The lower the level of injury, the less extensive its effects. Injuries from T9 to T12 result in partial loss of trunk and abdominal muscle control. Thoracic spinal injuries result in paraplegia, but function of the hands, arms, and neck are not affected.One condition that occurs typically in lesions above the T6 level is autonomic dysreflexia (AD), in which the blood pressure increases to dangerous levels, high enough to cause potentially deadly stroke. It results from an overreaction of the system to a stimulus such as pain below the level of injury, because inhibitory signals from the brain cannot pass the lesion to dampen the excitatory sympathetic nervous system response. Signs and symptoms of AD include anxiety, headache, nausea, ringing in the ears, blurred vision, flushed skin, and nasal congestion. It can occur shortly after the injury or not until years later.Other autonomic functions may also be disrupted. For example, problems with body temperature regulation mostly occur in injuries at T8 and above.
Another serious complication that can result from lesions above T6 is neurogenic shock, which results from an interruption in output from the sympathetic nervous system responsible for maintaining muscle tone in the blood vessels. Without the sympathetic input, the vessels relax and dilate. Neurogenic shock presents with dangerously low blood pressure, low heart rate, and blood pooling in the limbs—which results in insufficient blood flow to the spinal cord and potentially further damage to it.
Cervical
Spinal cord injuries at the cervical (neck) level result in full or partial tetraplegia (also called quadriplegia). Depending on the specific location and severity of trauma, limited function may be retained. Additional symptoms of cervical injuries include low heart rate, low blood pressure, problems regulating body temperature, and breathing dysfunction. If the injury is high enough in the neck to impair the muscles involved in breathing, the person may not be able to breathe without the help of an endotracheal tube and mechanical ventilator.
Complications
Complications of spinal cord injuries include pulmonary edema, respiratory failure, neurogenic shock, and paralysis below the injury site.
In the long term, the loss of muscle function can have additional effects from disuse, including atrophy of the muscle. Immobility can lead to pressure sores, particularly in bony areas, requiring precautions such as extra cushioning and turning in bed every two hours (in the acute setting) to relieve pressure. In the long term, people in wheelchairs must shift periodically to relieve pressure. Another complication is pain, including nociceptive pain (indication of potential or actual tissue damage) and neuropathic pain, when nerves affected by damage convey erroneous pain signals in the absence of noxious stimuli. Spasticity, the uncontrollable tensing of muscles below the level of injury, occurs in 65–78% of chronic SCI. It results from lack of input from the brain that quells muscle responses to stretch reflexes. It can be treated with drugs and physical therapy. Spasticity increases the risk of contractures (shortening of muscles, tendons, or ligaments that result from lack of use of a limb); this problem can be prevented by moving the limb through its full range of motion multiple times a day. Another problem lack of mobility can cause is loss of bone density and changes in bone structure. Loss of bone density (bone demineralization), thought to be due to lack of input from weakened or paralysed muscles, can increase the risk of fractures. Conversely, a poorly understood phenomenon is the overgrowth of bone tissue in soft tissue areas, called heterotopic ossification. It occurs below the level of injury, possibly as a result of inflammation, and happens to a clinically significant extent in 27% of people.
People with SCI are at especially high risk for respiratory and cardiovascular problems, so hospital staff must be watchful to avoid them. Respiratory problems (especially pneumonia) are the leading cause of death in people with SCI, followed by infections, usually of pressure sores, urinary tract infections and respiratory infections. Pneumonia can be accompanied by shortness of breath, fever, and anxiety.Another potentially deadly threat to respiration is deep venous thrombosis (DVT), in which blood forms a clot in immobile limbs; the clot can break off and form a pulmonary embolism, lodging in the lung and cutting off blood supply to it. DVT is an especially high risk in SCI, particularly within 10 days of injury, occurring in over 13% in the acute care setting. Preventative measures include anticoagulants, pressure hose, and moving the patients limbs. The usual signs and symptoms of DVT and pulmonary embolism may be masked in SCI cases due to effects such as alterations in pain perception and nervous system functioning.Urinary tract infection (UTI) is another risk that may not display the usual symptoms (pain, urgency, and frequency); it may instead be associated with worsened spasticity. The risk of UTI, likely the most common complication in the long term, is heightened by use of indwelling urinary catheters. Catheterization may be necessary because SCI interferes with the bladders ability to empty when it gets too full, which could trigger autonomic dysreflexia or damage the bladder permanently. The use of intermittent catheterization to empty the bladder at regular intervals throughout the day has decreased the mortality due to kidney failure from UTI in the first world, but it is still a serious problem in developing countries.An estimated 24–45% of people with SCI have disorders of depression, and the suicide rate is as much as six times that of the rest of the population. The risk of suicide is worst in the first five years after injury. In young people with SCI, suicide is the leading cause of death. Depression is associated with an increased risk of other complications such as UTI and pressure ulcers that occur more when self-care is neglected.
Causes
Spinal cord injuries are most often caused by physical trauma. Forces involved can be hyperflexion (forward movement of the head); hyperextension (backward movement); lateral stress (sideways movement); rotation (twisting of the head); compression (force along the axis of the spine downward from the head or upward from the pelvis); or distraction (pulling apart of the vertebrae). Traumatic SCI can result in contusion, compression, or stretch injury. It is a major risk of many types of vertebral fracture. Pre-existing asymptomatic congenital anomalies can cause major neurological deficits, such as hemiparesis, to result from otherwise minor trauma.In the US, Motor vehicle accidents are the most common cause of SCIs; second are falls, then violence such as gunshot wounds, then sports injuries. Another study from Asia, found that the most common cause of the SCI is fall (31.70%) from various sites such as fall from roof-tops (9.75%), electric pole (7.31%), fall from tree (7.31%) etc. Whereas road traffic accidents count for 19.51%, firearm injuries (12.19%), slipped foot (7.31%) and sports injuries (4.87%). As a result of injury, 26.82% In some countries falls are more common, even surpassing vehicle crashes as the leading cause of SCI. The rates of violence-related SCI depend heavily on place and time. Of all sports-related SCIs, shallow water dives are the most common cause; winter sports and water sports have been increasing as causes while association football and trampoline injuries have been declining. Hanging can cause injury to the cervical spine, as may occur in attempted suicide. Military conflicts are another cause, and when they occur they are associated with increased rates of SCI. Another potential cause of SCI is iatrogenic injury, caused by an improperly done medical procedure such as an injection into the spinal column.SCI can also be of a nontraumatic origin. Nontraumatic lesions cause anywhere from 30 to 80% of all SCI; the percentage varies by locale, influenced by efforts to prevent trauma. Developed countries have higher percentages of SCI due to degenerative conditions and tumors than developing countries. In developed countries, the most common cause of nontraumatic SCI is degenerative diseases, followed by tumors; in many developing countries the leading cause is infection such as HIV and tuberculosis. SCI may occur in intervertebral disc disease, and spinal cord vascular disease. Spontaneous bleeding can occur within or outside of the protective membranes that line the cord, and intervertebral disks can herniate. Damage can result from dysfunction of the blood vessels, as in arteriovenous malformation, or when a blood clot becomes lodged in a blood vessel and cuts off blood supply to the cord. When systemic blood pressure drops, blood flow to the spinal cord may be reduced, potentially causing a loss of sensation and voluntary movement in the areas supplied by the affected level of the spinal cord. Congenital conditions and tumors that compress the cord can also cause SCI, as can vertebral spondylosis and ischemia. Multiple sclerosis is a disease that can damage the spinal cord, as can infectious or inflammatory conditions such as tuberculosis, herpes zoster or herpes simplex, meningitis, myelitis, and syphilis.
Prevention
Vehicle-related SCI is prevented with measures including societal and individual efforts to reduce driving under the influence of drugs or alcohol, distracted driving, and drowsy driving. Other efforts include increasing road safety (such as marking hazards and adding lighting) and vehicle safety, both to prevent accidents (such as routine maintenance and antilock brakes) and to mitigate the damage of crashes (such as head restraints, air bags, seat belts, and child safety seats). Falls can be prevented by making changes to the environment, such as nonslip materials and grab bars in bathtubs and showers, railings for stairs, child and safety gates for windows. Gun-related injuries can be prevented with conflict resolution training, gun safety education campaigns, and changes to the technology of guns (such as trigger locks) to improve their safety. Sports injuries can be prevented with changes to sports rules and equipment to increase safety, and education campaigns to reduce risky practices such as diving into water of unknown depth or head-first tackling in association football.
Diagnosis
A persons presentation in context of trauma or non-traumatic background determines suspicion for a spinal cord injury. The features are namely paralysis, sensory loss, or both at any level. Other symptoms may include incontinence.A radiographic evaluation using an X-ray, CT scan, or MRI can determine if there is damage to the spinal column and where it is located. X-rays are commonly available and can detect instability or misalignment of the spinal column, but do not give very detailed images and can miss injuries to the spinal cord or displacement of ligaments or disks that do not have accompanying spinal column damage. Thus when X-ray findings are normal but SCI is still suspected due to pain or SCI symptoms, CT or MRI scans are used. CT gives greater detail than X-rays, but exposes the patient to more radiation, and it still does not give images of the spinal cord or ligaments; MRI shows body structures in the greatest detail. Thus it is the standard for anyone who has neurological deficits found in SCI or is thought to have an unstable spinal column injury.Neurological evaluations to help determine the degree of impairment are performed initially and repeatedly in the early stages of treatment; this determines the rate of improvement or deterioration and informs treatment and prognosis. The ASIA Impairment Scale outlined above is used to determine the level and severity of injury.
Management
Prehospital treatment
The first stage in the management of a suspected spinal cord injury is geared toward basic life support and preventing further injury: maintaining airway, breathing, and circulation and restricting further motion of the spine.
In the emergency setting, most people who has been subjected to forces strong enough to cause SCI are treated as though they have instability in the spinal column and have spinal motion restricted to prevent damage to the spinal cord. Injuries or fractures in the head, neck, or pelvis as well as penetrating trauma near the spine and falls from heights are assumed to be associated with an unstable spinal column until it is ruled out in the hospital. High-speed vehicle crashes, sports injuries involving the head or neck, and diving injuries are other mechanisms that indicate a high SCI risk. Since head and spinal trauma frequently coexist, anyone who is unconscious or has a lowered level of consciousness as a result of a head injury is spinal motion restricted.A rigid cervical collar is applied to the neck, and the head is held with blocks on either side and the person is strapped to a backboard. Extrication devices are used to move people without excessively moving the spine if they are still inside a vehicle or other confined space. The use of a cervical collar has been shown to increase mortality in people with penetrating trauma and is thus not routinely recommended in this group.Modern trauma care includes a step called clearing the cervical spine, ruling out spinal cord injury if the patient is fully conscious and not under the influence of drugs or alcohol, displays no neurological deficits, has no pain in the middle of the neck and no other painful injuries that could distract from neck pain. If these are all absent, no spinal motion restriction is necessary.If an unstable spinal column injury is moved, damage may occur to the spinal cord. Between 3 and 25% of SCIs occur not at the time of the initial trauma but later during treatment or transport. While some of this is due to the nature of the injury itself, particularly in the case of multiple or massive trauma, some of it reflects the failure to adequately restrict motion of the spine. SCI can impair the bodys ability to keep warm, so warming blankets may be needed.
Early hospital treatment
Initial care in the hospital, as in the prehospital setting, aims to ensure adequate airway, breathing, cardiovascular function, and spinal motion restriction. Imaging of the spine to determine the presence of a SCI may need to wait if emergency surgery is needed to stabilize other life-threatening injuries. Acute SCI merits treatment in an intensive care unit, especially injuries to the cervical spinal cord. People with SCI need repeated neurological assessments and treatment by neurosurgeons. People should be removed from the spine board as rapidly as possible to prevent complications from its use.If the systolic blood pressure falls below 90 mmHg within days of the injury, blood supply to the spinal cord may be reduced, resulting in further damage. Thus it is important to maintain the blood pressure which may be done using intravenous fluids and vasopressors. Vasopressors used include phenylephrine, dopamine, or norepinephrine. Mean arterial blood pressure is measured and kept at 85 to 90 mmHg for seven days after injury.The CAMPER Trial led by Dr Kwon and subsequent studies by the UCSF TRACK-SCI group (Dhall) have shown that spinal cord perfusion pressure (SCPP) goals are more closely associated with better neurologic recovery than MAP goals. Some institutions have adopted these SCPP goals and lumbar CSF drain placement as a standard of care. The treatment for shock from blood loss is different from that for neurogenic shock, and could harm people with the latter type, so it is necessary to determine why someone is in shock. However it is also possible for both causes to exist at the same time. Another important aspect of care is prevention of insufficient oxygen in the bloodstream, which could deprive the spinal cord of oxygen. People with cervical or high thoracic injuries may experience a dangerously slowed heart rate; treatment to speed it may include atropine.The corticosteroid medication methylprednisolone has been studied for use in SCI with the hope of limiting swelling and secondary injury. As there does not appear to be long term benefits and the medication is associated with risks such as gastrointestinal bleeding and infection its use is not recommended as of |
Spinal cord injury | 2018. Its use in traumatic brain injury is also not recommended.Surgery may be necessary, e.g. to relieve excess pressure on the cord, to stabilize the spine, or to put vertebrae back in their proper place. In cases involving instability or compression, failing to operate can lead to worsening of the condition. Surgery is also necessary when something is pressing on the cord, such as bone fragments, blood, material from ligaments or intervertebral discs, or a lodged object from a penetrating injury. Although the ideal timing of surgery is still debated, studies have found that earlier surgical intervention (within 12 hours of injury) is associated with better outcomes. This type of surgery is often referred to as "Ultra-Early", coined by Burke et al. at UCSF. Sometimes a patient has too many other injuries to be a surgical candidate this early. Surgery is controversial because it has potential complications (such as infection), so in cases where it is not clearly needed (e.g. the cord is being compressed), doctors must decide whether to perform surgery based on aspects of the patients condition and their own beliefs about its risks and benefits. Recent large-scale studies have shown that patients who do undergo earlier surgery (within 12–24 hours) experience significantly lower rates of life-threatening complications and spend less time in hospital and critical care.
However, in cases where a more conservative approach is chosen, bed rest, cervical collars, motion restriction devices, and optionally traction are used. Surgeons may opt to put traction on the spine to remove pressure from the spinal cord by putting dislocated vertebrae back into alignment, but herniation of intervertebral disks may prevent this technique from relieving pressure. Gardner-Wells tongs are one tool used to exert spinal traction to reduce a fracture or dislocation and to reduce motion to the affected areas.
Rehabilitation
SCI patients often require extended treatment in specialized spinal unit or an intensive care unit. The rehabilitation process typically begins in the acute care setting. Usually, the inpatient phase lasts 8–12 weeks and then the outpatient rehabilitation phase lasts 3–12 months after that, followed by yearly medical and functional evaluation. Physical therapists, occupational therapists, recreational therapists, nurses, social workers, psychologists, and other health care professionals work as a team under the coordination of a physiatrist to decide on goals with the patient and develop a plan of discharge that is appropriate for the persons condition.
In the acute phase physical therapists focus on the patients respiratory status, prevention of indirect complications (such as pressure ulcers), maintaining range of motion, and keeping available musculature active.For people whose injuries are high enough to interfere with breathing, there is great emphasis on airway clearance during this stage of recovery. Weakness of respiratory muscles impairs the ability to cough effectively, allowing secretions to accumulate within the lungs. As SCI patients have reduced total lung capacity and tidal volume, physical therapists teach them accessory breathing techniques (e.g. apical breathing, glossopharyngeal breathing) that typically are not taught to healthy individuals. Physical therapy treatment for airway clearance may include manual percussions and vibrations, postural drainage, respiratory muscle training, and assisted cough techniques. Patients are taught to increase their intra-abdominal pressure by leaning forward to induce cough and clear mild secretions. The quad cough technique is done lying on the back with the therapist applying pressure on the abdomen in the rhythm of the cough to maximize expiratory flow and mobilize secretions. Manual abdominal compression is another technique used to increase expiratory flow which later improves coughing. Other techniques used to manage respiratory dysfunction include respiratory muscle pacing, use of a constricting abdominal binder, ventilator-assisted speech, and mechanical ventilation.The amount of functional recovery and independence achieved in terms of activities of daily living, recreational activities, and employment is affected by the level and severity of injury. The Functional Independence Measure (FIM) is an assessment tool that aims to evaluate the function of patients throughout the rehabilitation process following a spinal cord injury or other serious illness or injury. It can track a patients progress and degree of independence during rehabilitation. People with SCI may need to use specialized devices and to make modifications to their environment in order to handle activities of daily living and to function independently. Weak joints can be stabilized with devices such as ankle-foot orthoses (AFOs) or knee-ankle-foot orthoses (KAFOs), but walking may still require a lot of effort. Increasing activity will increase chances of recovery.
For treatment of paralysis levels in the lower thoracic spine or lower, starting therapy with an orthosis is promising from the intermediate phase (2–26 weeks after the incident). In patients with complete paraplegia (ASIA A), this applies to lesion heights between T12 and S5. In patients with incomplete paraplegia (ASIA B-D), orthoses are even suitable for lesion heights above T12. In both cases, however, a detailed muscle function test must be carried out to precisely plan the construction with an orthosis.
Prognosis
Spinal cord injuries generally result in at least some incurable impairment even with the best possible treatment. The best predictor of prognosis is the level and completeness of injury, as measured by the ASIA impairment scale. The neurological score at the initial evaluation done 72 hours after injury is the best predictor of how much function will return. Most people with ASIA scores of A (complete injuries) do not have functional motor recovery, but improvement can occur. Most patients with incomplete injuries recover at least some function. Chances of recovering the ability to walk improve with each AIS grade found at the initial examination; e.g. an ASIA D score confers a better chance of walking than a score of C. The symptoms of incomplete injuries can vary and it is difficult to make an accurate prediction of the outcome. A person with a mild, incomplete injury at the T5 vertebra will have a much better chance of using his or her legs than a person with a severe, complete injury at exactly the same place. Of the incomplete SCI syndromes, Brown-Séquard and central cord syndromes have the best prognosis for recovery and anterior cord syndrome has the worst.People with nontraumatic causes of SCI have been found to be less likely to develop complete injuries and some complications such as pressure sores and deep vein thrombosis, and to have shorter hospital stays. Their scores on functional tests were better than those of people with traumatic SCI upon hospital admission, but when they were tested upon discharge, those with traumatic SCI had improved such that both groups results were the same. In addition to the completeness and level of the injury, age and concurrent health problems affect the extent to which a person with SCI will be able to live independently and to walk. However, in general people with injuries to L3 or below will likely be able to walk functionally, T10 and below to walk around the house with bracing, and C7 and below to live independently. New therapies are beginning to provide hope for better outcomes in patients with SCI, but most are in the experimental/translational stage.One important predictor of motor recovery in an area is presence of sensation there, particularly pain perception. Most motor recovery occurs in the first year post-injury, but modest improvements can continue for years; sensory recovery is more limited. Recovery is typically quickest during the first six months. Spinal shock, in which reflexes are suppressed, occurs immediately after the injury and resolves largely within three months but continues resolving gradually for another 15.Sexual dysfunction after spinal injury is common. Problems that can occur include erectile dysfunction, loss of ability to ejaculate, insufficient lubrication of the vagina, and reduced sensation and impaired ability to orgasm. Despite this, many people learn ways to adapt their sexual practices so they can lead satisfying sex lives.Although life expectancy has improved with better care options, it is still not as good as the uninjured population. The higher the level of injury, and the more complete the injury, the greater the reduction in life expectancy. Mortality is very elevated within a year of injury.
Epidemiology
Worldwide, the number of new cases since 1995 of SCI ranges from 10.4 to 83 people per million per year. This wide range of numbers is probably partly due to differences among regions in whether and how injuries are reported. In North America, about 39 people per every million incur SCI traumatically each year, and in Western Europe, the incidence is 16 per million. In the United States, the incidence of spinal cord injury has been estimated to be about 40 cases per 1 million people per year or around 12,000 cases per year. In China, the incidence is approximately 60,000 per year.
The estimated number of people living with SCI in the world ranges from 236 to 4187 per million. Estimates vary widely due to differences in how data are collected and what techniques are used to extrapolate the figures. Little information is available from Asia, and even less from Africa and South America. In Western Europe the estimated prevalence is 300 per million people and in North America it is 853 per million. It is estimated at 440 per million in Iran, 526 per million in Iceland, and 681 per million in Australia. In the United States there are between 225,000 and 296,000 individuals living with spinal cord injuries, and different studies have estimated prevalences from 525 to 906 per million.SCI is present in about 2% of all cases of blunt force trauma. Anyone who has undergone force sufficient to cause a thoracic spinal injury is at high risk for other injuries also. In 44% of SCI cases, other serious injuries are sustained at the same time; 14% of SCI patients also have head trauma or facial trauma. Other commonly associated injuries include chest trauma, abdominal trauma, pelvic fractures, and long bone fractures.Males account for four out of five traumatic spinal cord injuries. Most of these injuries occur in men under 30 years of age. The average age at the time of injury has slowly increased from about 29 years in the 1970s to 41. In Pakistan, spinal cord injury is more common in males (92.68%) as compared to females in the 20-30 years of age group with a median age of 40 years, although people from 12-70 years of age suffered from spinal cord injury Rates of injury are at their lowest in children, at their highest in the late teens to early twenties, then get progressively lower in older age groups; however rates may rise in the elderly. In Sweden between 50 and 70% of all cases of SCI occur in people under 30, and 25% occur in those over 50. While SCI rates are highest among people age 15–20, fewer than 3% of SCIs occur in people under 15. Neonatal SCI occurs in one in 60,000 births, e.g. from breech births or injuries by forceps. The difference in rates between the sexes diminishes in injuries at age 3 and younger; the same number of girls are injured as boys, or possibly more. Another cause of pediatric injury is child abuse such as shaken baby syndrome. For children, the most common cause of SCI (56%) is vehicle crashes. High numbers of adolescent injuries are attributable in a large part to traffic accidents and sports injuries. For people over 65, falls are the most common cause of traumatic SCI. The elderly and people with severe arthritis are at high risk for SCI because of defects in the spinal column. In nontraumatic SCI, the gender difference is smaller, the average age of occurrence is greater, and incomplete lesions are more common.
History
SCI has been known to be devastating for millennia; the ancient Egyptian Edwin Smith Papyrus from 2500 BC, the first known description of the injury, says it is "not to be treated". Hindu texts dating back to 1800 BC also mention SCI and describe traction techniques to straighten the spine. The Greek physician Hippocrates, born in the fifth century BC, described SCI in his Hippocratic Corpus and invented traction devices to straighten dislocated vertebrae. But it was not until Aulus Cornelius Celsus, born 30 BC, noted that a cervical injury resulted in rapid death that the spinal cord itself was implicated in the condition. In the second century AD the Greek physician Galen experimented on monkeys and reported that a horizontal cut through the spinal cord caused them to lose all sensation and motion below the level of the cut. The seventh-century Greek physician Paul of Aegina described surgical techniques for treatment of broken vertebrae by removing bone fragments, as well as surgery to relieve pressure on the spine. Little medical progress was made during the Middle Ages in Europe; it was not until the Renaissance that the spine and nerves were accurately depicted in human anatomy drawings by Leonardo da Vinci and Andreas Vesalius.In 1762 a surgeon named Andre Louis removed a bullet from the lumbar spine of a patient, who regained motion in the legs. In 1829 the surgeon Gilpin Smith performed a successful laminectomy that improved the patients sensation. However, the idea that SCI was untreatable remained predominant until the early 20th century. In 1934, the mortality rate in the first two years after injury was over 80%, mostly due to infections of the urinary tract and pressure sores, the latter of which were believed to be intrinsic to SCI rather than a result of continuous bedrest. It was not until the second half of the century that breakthroughs in imaging, surgery, medical care, and rehabilitation medicine contributed to a substantial improvement in SCI care. The relative incidence of incomplete compared to complete injuries has improved since the mid-20th century, due mainly to the emphasis on faster and better initial care and stabilization of spinal cord injury patients. The creation of emergency medical services to professionally transport people to the hospital is given partial credit for an improvement in outcomes since the 1970s. Improvements in care have been accompanied by increased life expectancy of people with SCI; survival times have improved by about 2000% since 1940. In 2015/2016 23% of people in nine spinal injury centres in England had their discharge delayed because of disputes about who should pay for the equipment they needed.
Research directions
Scientists are investigating various avenues for treatment of spinal cord injury. Therapeutic research is focused on two main areas: neuroprotection and neuroregeneration. The former seeks to prevent the harm that occurs from secondary injury in the minutes to weeks following the insult, and the latter aims to reconnect the broken circuits in the spinal cord to allow function to return. Neuroprotective drugs target secondary injury effects including inflammation, damage by free radicals, excitotoxicity (neuronal damage by excessive glutamate signaling), and apoptosis (cell suicide). Several potentially neuroprotective agents that target pathways like these are under investigation in human clinical trials.
Stem cell transplantation is an important avenue for SCI research: the goal is to replace lost spinal cord cells, allow reconnection in broken neural circuits by regrowing axons, and to create an environment in the tissues that is favorable to growth. A key avenue of SCI research is research on stem cells, which can differentiate into other types of cells—including those lost after SCI. Types of cells being researched for use in SCI include embryonic stem cells, neural stem cells, mesenchymal stem cells, olfactory ensheathing cells, Schwann cells, activated macrophages, and induced pluripotent stem cells. Hundreds of stem cell studies have been done in humans, with promising but inconclusive results. An ongoing Phase 2 trial in 2016 presented data showing that after 90 days, 2 out of 4 subjects had already improved two motor levels and had thus already achieved its endpoint of 2/5 patients improving two levels within 6–12 months. Six-month data is expected in January 2017.Another type of approach is tissue engineering, using biomaterials to help scaffold and rebuild damaged tissues. Biomaterials being investigated include natural substances such as collagen or agarose and synthetic ones like polymers and nitrocellulose. They fall into two categories: hydrogels and nanofibers. These materials can also be used as a vehicle for delivering gene therapy to tissues.One avenue being explored to allow paralyzed people to walk and to aid in rehabilitation of those with some walking ability is the use of wearable powered robotic exoskeletons. The devices, which have motorized joints, are put on over the legs and supply a source of power to move and walk. Several such devices are already available for sale, but investigation is still underway as to how they can be made more useful.Preliminary studies of epidural spinal cord stimulators for motor complete injuries have demonstrated some improvement and in some cases to enable walking to some degree bypassing the injuryIn 2014 Darek Fidyka underwent pioneering spinal surgery that used nerve grafts, from his ankle, to bridge the gap in his severed spinal cord and olfactory ensheathing cells (OECs) to stimulate the spinal cord cells. The surgery was performed in Poland in collaboration with Prof. Geoff Raisman, chair of neural regeneration at University College Londons Institute of Neurology, and his research team. The OECs were taken from the patients olfactory bulbs in his brain and then grown in the lab, these cells were then injected above and below the impaired spinal tissue.
See also
Paralyzed Veterans of America
References
Bibliography
External links
Spinal cord injury at Curlie |
Conjoined twins | Conjoined twins – sometimes popularly referred to as Siamese twins – are twins joined in utero. A very rare phenomenon, the occurrence is estimated to range from 1 in 49,000 births to 1 in 189,000 births, with a somewhat higher incidence in Southwest Asia and Africa. Approximately half are stillborn, and an additional one-third die within 24 hours. Most live births are female, with a ratio of 3:1.Two theories exist to explain the origins of conjoined twins. The more generally accepted theory is fission, in which the fertilized egg splits partially. The other theory, no longer believed to be the basis of conjoined twinning, is fusion, in which a fertilized egg completely separates, but stem cells (which search for similar cells) find similar stem cells on the other twin and fuse the twins together. Conjoined twins share a single common chorion, placenta, and amniotic sac, although these characteristics are not exclusive to conjoined twins, as there are some monozygotic but non-conjoined twins who also share these structures in utero.Chang and Eng Bunker (1811–1874) were brothers born in Siam (now Thailand) who traveled widely for many years and were labeled as The Siamese Twins. Chang and Eng were joined at the torso by a band of flesh, cartilage, and their fused livers. In modern times, they could have been easily separated. Due to the brothers fame and the rarity of the condition, the term "Siamese twins" came to be associated with conjoined twins.
Causes
There are two theories about the development of conjoined twins. The first is that a single fertilized egg does not fully split during the process of forming identical twins. If the zygote division occurs after two weeks of the development of the embryonic disc, it results in the formation of conjoined twins. The second theory is that a fusion of two fertilized eggs occurs earlier in development.
Partial splitting of the primitive node and streak may result in the formation of conjoined twins. These twins are classified according to the nature and degree of their union. Occasionally, monozygotic twins are connected only by a common skin bridge or by a common liver bridge. The type of twins formed depends on when and to what extent abnormalities of the node and streak occurred. Misexpression of genes, such as Goosecoid, may also result in conjoined twins. Goosecoid activates inhibitors of BMP4 and contributes to regulation of head development. Over- or underexpression of this gene in laboratory animals results in severe malformations of the head region, including duplications, similar to some types of conjoined twins.
Types
Conjoined twins are typically classified by the point at which their bodies are joined. The most common types of conjoined twins are:
Thoraco-omphalopagus (28% of cases): Two bodies fused from the upper chest to the lower chest. These twins usually share a heart and may also share the liver or part of the digestive system.
Thoracopagus (18.5%): Two bodies fused from the upper chest to lower belly. The heart is always involved in these cases. As of 2015, separation of a genuinely shared heart has not offered survival to two twins; a designated twin may survive if allotted the heart, sacrificing the other twin.
Omphalopagus (10%): Two bodies fused at the lower abdomen. Unlike thoracopagus, the heart is never involved in these cases; however, the twins often share a liver, digestive system, diaphragm and other organs.
Parasitic twins (10%): Twins that are asymmetrically conjoined, resulting in one twin that is small, less formed, and dependent on the larger twin for survival.
Craniopagus (6%): Fused skulls, but separate bodies. These twins can be conjoined at the back of the head, the front of the head, or the side of the head, but not on the face or the base of the skull.Other, less common types of conjoined twins include:
Cephalopagus: Two faces on opposite sides of a single, conjoined head; the upper portion of the body is fused while the bottom portions are separate. These twins generally cannot survive due to severe malformations of the brain. Also known as janiceps (after the two-faced Roman deity Janus).
Syncephalus: One head with a single face but four ears, and two bodies.
Cephalothoracopagus: Bodies fused in the head and thorax. In this type of twins, there are two faces facing in opposite directions, or sometimes a single face and an enlarged skull.
Xiphopagus: Two bodies fused in the xiphoid cartilage, which is approximately from the navel to the lower breastbone. These twins almost never share any vital organs, with the exception of the liver. A famous example is Chang and Eng Bunker.
Ischiopagus: Fused lower half of the two bodies, with spines conjoined end-to-end at a 180° angle. These twins have four arms; one, two, three or four legs; and typically one external set of genitalia and anus.
Omphalo-Ischiopagus: Fused in a similar fashion to ischiopagus twins, but facing each other with a joined abdomen akin to omphalopagus. These twins have four arms, and two, three, or four legs.
Parapagus: Fused side by side with a shared pelvis. Twins that are dithoracic parapagus are fused at the abdomen and pelvis, but not the thorax. Twins that are diprosopic parapagus have one trunk and two faces. Twins that are dicephalic parapagus have one trunk and two heads, and have two (dibrachius), three (tribrachius), or four (tetrabrachius) arms.
Craniopagus parasiticus: Like craniopagus, but with a second bodiless head attached to the dominant head.
Pygopagus or Iliopagus: Two bodies joined at the pelvis.
Rachipagus: Twins joined along the back of their bodies, with fusion of the vertebral arches and the soft tissue from the head to the buttocks
Tricephalus (conjoined triplets): Extremely rare conjoining of 3 fetuses. Very few confirmed cases, both human and animal, are known.
Management
Separation
Surgery to separate conjoined twins may range from very easy to very difficult depending on the point of attachment and the internal parts that are shared. Most cases of separation are extremely risky and life-threatening. In many cases, the surgery results in the death of one or both of the twins, particularly if they are joined at the head or share a vital organ. This makes the ethics of surgical separation, where the twins can survive if not separated, contentious. Alice Dreger of Northwestern University found the quality of life of twins who remain conjoined to be higher than is commonly supposed. Lori and George Schappell and Abby and Brittany Hensel are notable examples.
The first record of separating conjoined twins took place in the Byzantine Empire in the 900s. One of the conjoined twins had already died, so the doctors of the town attempted to separate the dead twin from the surviving twin. The result was partly successful as the remaining twin lived for three days after separation. The next case of separating conjoined twins was recorded in 1689 in Germany several centuries later. The first recorded successful separation of conjoined twins was performed in 1689 by Johannes Fatio. In 1955, neurosurgeon Harold Voris (1902-1980) and his team at Mercy Hospital in Chicago performed the first successful operation to separate craniopagus twins (conjoined at the head), which resulted in long-term survival for both. The larger girl was reported in 1963 as developing normally, but the smaller girl was permanently impaired.In 1957, Bertram Katz and his surgical team made international medical history performing the worlds first successful separation of conjoined twins sharing a vital organ. Omphalopagus twins John Nelson and James Edward Freeman (Johnny and Jimmy) were born in Youngstown, Ohio, on April 27, 1956. The boys shared a liver but had separate hearts and were successfully separated at North Side Hospital in Youngstown, Ohio, by Bertram Katz. The operation was funded by the Ohio Crippled Childrens Service Society.Recent successful separations of conjoined twins include that of the separation of Ganga and Jamuna Shreshta in 2001, who were born in Kathmandu, Nepal, in 2000. The 97-hour surgery on the pair of craniopagus twins was a landmark one which took place in Singapore; the team was led by neurosurgeons Chumpon Chan and Keith Goh. The surgery left Ganga with brain damage and Jamuna unable to walk. Seven years later, Ganga Shrestha died at the Model Hospital in Kathmandu in July 2009, at the age of eight, three days after being admitted for treatment of a severe chest infection.Infants Rose and Grace Attard, conjoined twins from Malta, were separated in the United Kingdom by court order Re A over the religious objections of their parents, Michaelangelo and Rina Attard. The twins were attached at the lower abdomen and spine. The surgery took place in November 2000, at St Marys Hospital in Manchester. The operation was controversial because Rose, the weaker twin, would die as a result of the procedure as her heart and lungs were dependent upon Graces. However, if the operation had not taken place, it was certain that both twins would die. Grace survived to enjoy a normal childhood.In 2003, two 29-year-old women from Iran, Ladan and Laleh Bijani, who were joined at the head but had separate brains (craniopagus) were surgically separated in Singapore, despite surgeons warnings that the operation could be fatal to one or both. Their complex case was accepted only because technologically advanced graphical imagery and modeling would allow the medical team to plan the risky surgery. However, an undetected major vein hidden from the scans was discovered during the operation. The separation was completed but both women died while still in surgery.
In 2019 Safa and Marwa Ullah were separated at Great Ormond Street Hospital in London, England. The twins, born January 2017 were joined at the top of the head with separate brains and a cylindrical shared skull with the twins each facing in opposite directions to one another. The surgery was jointly led by neurosurgeon Owase Jeelani and plastic surgeon Professor David Dunaway. The surgery presented particular difficulties due to a number of shared veins and a distortion in the shape of the girls brains, causing them to overlap. The distortion would need to be corrected in order for the separation to go ahead. The surgery utilized a team of more than 100 including bio engineers, 3D modelers and a virtual reality designer. The separation was completed in February 2019 following a total of 52 hours of surgery over three separate operations. As of July 2019, both girls remain healthy and the family planned to return to their home in Pakistan in 2020.
History
The Moche culture of ancient Peru depicted conjoined twins in their ceramics dating back to 300 CE. Writing around 415 CE, St. Augustine of Hippo, in his book, City of God, refers to a man "double in his upper, but single in his lower half—having two heads, two chests, four hands, but one body and two feet like an ordinary man."According to Theophanes the Confessor, a Byzantine historian of the 9th century, around 385/386 CE, "in the village of Emmaus in Palestine, a child was born perfectly normal below the navel but divided above it, so that it had two chests and two heads, each possessing the senses. One would eat and drink but the other did not eat; one would sleep but the other stayed awake. There were times when they played with each other, when both cried and hit each other. They lived for a little over two years. One died while the other lived for another four days and it, too, died."In Arabia, the twin brothers Hashim ibn Abd Manaf and Abd Shams were born with Hashims leg attached to his twin brothers head. Legend says that their father, Abd Manaf ibn Qusai, separated his conjoined sons with a sword and that some priests believed that the blood that had flowed between them signified wars between their progeny (confrontations did occur between Banu alAbbas and Banu Ummaya ibn Abd Shams in the year 750 AH). The Muslim polymath Abū al-Rayhān al-Bīrūnī described conjoined twins in his book Kitab-al-Saidana.The English twin sisters Mary and Eliza Chulkhurst, who were conjoined at the back (pygopagus), lived from 1100 to 1134 (or 1500 to 1534) and were perhaps the best-known early historical example of conjoined twins. Other early conjoined twins to attain notice were the "Scottish brothers", allegedly of the dicephalus type, essentially two heads sharing the same body (1460–1488, although the dates vary); the pygopagus Helen and Judith of Szőny, Hungary (1701–1723), who enjoyed a brief career in music before being sent to live in a convent; and Rita and Cristina of Parodi of Sardinia, born in 1829. Rita and Cristina were dicephalus tetrabrachius (one body with four arms) twins and although they died at only eight months of age, they gained much attention as a curiosity when their parents exhibited them in Paris.
Several sets of conjoined twins lived during the nineteenth century and made careers for themselves in the performing arts, though none achieved quite the same level of fame and fortune as Chang and Eng. Most notably, Millie and Christine McCoy (or McKoy), pygopagus twins, were born into slavery in North Carolina in 1851. They were sold to a showman, J.P. Smith, at birth, but were soon kidnapped by a rival showman. The kidnapper fled to England but was thwarted because England had already banned slavery. Smith traveled to England to collect the girls and brought with him their mother, Monimia, from whom they had been separated. He and his wife provided the twins with an education and taught them to speak five languages, play music, and sing. For the rest of the century, the twins enjoyed a successful career as "The Two-Headed Nightingale" and appeared with the Barnum Circus. In 1912, they died of tuberculosis, 17 hours apart.
Giovanni and Giacomo Tocci, from Locana, Italy, were immortalized in Mark Twains short story "Those Extraordinary Twins" as fictitious twins Angelo and Luigi. The Toccis, born in 1877, were dicephalus tetrabrachius twins, having one body with two legs, two heads, and four arms. From birth they were forced by their parents to perform and never learned to walk, as each twin controlled one leg (in modern times, physical therapy allows twins like the Toccis to learn to walk on their own). They are said to have disliked show business. In 1886, after touring the United States, the twins returned to Europe with their family. They are believed to have died around this time, though some sources claim they survived until 1940, living in seclusion in Italy.
Notable people
Born 19th century and earlier
Mary and Eliza Chulkhurst, alleged names of the Biddenden Maids (per tradition, born in the 12th century) of Kent, England. They are the earliest set of conjoined twins whose names are (purportedly) known.
Lazarus and Joannes Baptista Colloredo (1617 — after 1646), autosite-and-parasite pair
Helen and Judith of Szony (Hungary, 1701 — 1723), pygopagus.
Chang and Eng Bunker (1811–1874). The Bunker twins were born of Chinese origin in Siam (now Thailand), and the expression Siamese twins is derived from their case. They were joined by the areas around their xiphoid cartilages, but over time, the connective tissue stretched.
In 1834, a set of conjoined triplets were born in Cattania. Two of the heads shared a neck while the other head had its own. The infant, a male, was described by Galvagni.
Millie and Christine McCoy (July 11, 1851 – October 8, 1912), (oblique pygopagus). The McCoy twins were born into slavery in Columbus County, North Carolina, United States. They went by the stage names "The Two-Headed Nightingale" and "The Eighth Wonder of the World" and had an extensive career before retiring to the farm on which they were born.
Giacomo and Giovanni Battista Tocci (1875? — 1912?), (dicephalus tetrabrachius dipus)
Josefa and Rosa Blazek (January 20, 1878 — March 30, 1922), pygopagus. The Blazek twins were born in Skrejšov, Bohemia (now the Czech Republic). They began performing in public exhibitions at the age of 13, and their act later included Rosas son Franz. The sisters died in Chicago, Illinois.
Born 20th century
Daisy and Violet Hilton of Brighton, England (1908–1969), pygopagus. The Hilton twins were performers who played musical instruments, sang, and danced. At the height of their career, they had the highest paid act in vaudeville. They also appeared in the movies Freaks and Chained for Life.
Lucio and Simplicio Godina of Samar, Philippines (1908–1936)
Masha and Dasha Krivoshlyapova of Moscow, Russia (1950–2003), the rarest form of conjoined twins, one of few cases of dicephalus tetrabrachius tripus (two heads, four arms, three legs)
Ronnie and Donnie Galyon of Ohio (1951–2020), omphalopagus; longest-lived conjoined twins in the world at 68 years and 250 days.
Tjitske and Folkje de Vries of Mûnein, Netherlands (b. 1953)
Wariboko and Tamunotonye Davies, born July 25, 1953, in Kano, Nigeria. Separated in London by a team led by Ian Aird. Tamunotonye died postoperatively. Wariboko became a nurse.
Lori and George Schappell, born September 18, 1961, in Reading, Pennsylvania, American entertainers, craniopagus. As of 2022, they are the worlds oldest living conjoined twins.
Ganga and Jamuna Mondal of India, born 1969 or 1970, known professionally as The Spider Girls and The Spider Sisters. Ischiopagus.
Anna and Barbara Rozycki (born 1970), the first conjoined twins successfully separated.
Ma Nan Soe and Ma Nan San (born 1971 in Myanmar), separated in July 1971 at Yangon Pediatric Hospital. They were joined from chest to belly button. Ma Nan San died after one month and seven days after operation.
Elisa and Lisa Hansen, Ogden, Utah (1977–2020). Born by Caesarean section on October 18, 1977, were conjoined at the top of their head (craniopagus). They were separated 1979 after 16-hour surgery, were first to both survive surgery.
Ladan and Laleh Bijani of Shiraz, Iran (1974–2003); died during separation surgery in Singapore. Craniopagus.
Baby Girl A and Baby Girl B (born 1977 in New Jersey) shared a single six-chambered heart. Separation surgery, led by C. Everett Koop, involved the instant death of Baby Girl A; the difficult ethical and religious concerns generated significant local newspaper coverage. Baby Girl B survived for 3 months.
Viet and Duc Nguyen, born on February 25, 1981, in Kon Tum Province, Vietnam, and separated in 1988 in Ho Chi Minh City. Viet died on October 6, 2007. Ischiopagus.
Maria and Consolata Mwakikuti of Tanzania (1986?–2018); conjoined by the abdomen; died of respiratory problems resulting from an abnormal, inoperable chest deformity.
Patrick and Benjamin Binder, separated in 1987 by team of doctors led by Ben Carson. Craniopagus.
Andrew and Alex Olson, born in 1987, separated in April 1988 at the University of Nebraska Medical Center. Omphalopagus. Alex died in 2018.
Katie and Eilish Holton, born August 1988 in Ireland; Katie died after separation due to cardiac arrest at the age of 3,5 years.
Abigail and Brittany Hensel are dicephalic parapagus twins born on March 7, 1990, in Carver County, Minnesota. Both graduated in 2012 from Bethel University, St. Paul, hired as teachers.
Tiesha and Iesha Turner (born 1991 in Texas), separated in 1992 at Texas Childrens Hospital in Houston, Texas. Omphalopagus.
Ashley and Ashil Fokeer, born on November 2, 1992, in Mauritius
Joseph and Luka Banda (born January 23, 1997, in Zambia), separated in 1997 in South Africa by Ben Carson (with a later intervention in 2001 to artificially close their skulls). Craniopagus.
José Armando and José Luis Cevallos Herrera were born in September 1999 in Milagro, Ecuador. They were accepted in 2021 to the State University of Milagro.
Maria del Carmen Andrade Solis and Maria Guadalupe Andrade Solis (better known as Carmen and Lupita) were born in June 2000 in Veracruz, Mexico. They later moved to the United States for healthcare with their parents.
Born 21st century
Carl and Clarence Aguirre, born with vertical craniopagus in Silay City, Negros Occidental, on April 21, 2002. They were successfully separated on August 4, 2004.
Tabea and Lea Block, from Lemgo, Germany, were born as craniopagus twins joined on the tops of their heads on August 9, 2003. The girls shared some major veins, but their brains were separate. They were separated on September 16, 2004, although Tabea died about 90 minutes later.
Sohna and Mohna from Amritsar, India. Born in New Delhi on June 14, 2003. They have two hearts, arms, kidneys and spinal cords while share liver, gall bladder and legs.
Anastasia and Tatiana Dogaru, born outside Rome in Lazio, Italy, on January 13, 2004. As craniopagus twins, the top of Tatianas head is attached to the back of Anastasias head.
Lakshmi Tatma (born 2005) was an ischiopagus conjoined twin born in Araria district in the state of Bihar, India. She had four arms and four legs, resulting from a joining at the pelvis with a headless undeveloped parasitic twin.
In 2005 a set of conjoined triplets was detected, characterized as tricephalus, tetrabrachius, and tetrapus parapagothoracopagus, and the pregnancy interrupted at 22 weeks.
Kendra and Maliyah Herrin, ischiopagus twins separated in 2006 at age 4
Krista and Tatiana Hogan, Canadian twins conjoined at the head. Born October 25, 2006. Share part of their brain and can pass sensory information and thoughts between each other.
Trishna and Krishna from Bangladesh were born in December 2006. They are craniopagus twins, joined on the tops of their skulls and sharing a small amount of brain tissue. In 2009, they were separated in Melbourne, Australia.
Maria and Teresa Tapia, born in the Dominican Republic on April 8, 2010. Conjoined by the liver, pancreas, and a small portion of their small intestine. Separation occurred on November 7, 2011, at Childrens Hospital of Richmond at VCU.
Aung Myat Kyaw and Aung Khant Kyaw (born in May 2011, Mandalay, Myanmar), connected at pelvis.
Jesus and Emanuel de Nazaré are dicephalic parapagus twins born in Pará, Brazil on December 19, 2011.
Zheng Han Wei and Zheng Han Jing, born in China on August 11, 2013. Conjoined by their sternum, pericardium, and liver. In 2014, they were separated in Shanghai, China, at the Shanghai Childrens Medical Center.
Asa and Eli Hamby were born in 2014 in Georgia but died less than two days after birth due to heart failure. The twins were dicephalic parapagus having two heads but being conjoined at the torso, arms and legs. They had separate spinal columns but one heart making postnatal operations impossible.
Jadon and Anias McDonald, born in September 2015. Conjoined by the head. Successfully separated at Childrens Hospital of Montefiore Medical Center by James T. Goodrich in October 2016.
Erin and Abby Delaney, born in Philadelphia, Pennsylvania on July 24, 2016. Conjoined by the head. They were successfully separated at Childrens Hospital of Philadelphia on June 16, 2017.
Marieme and Ndeye Ndiaye, twin girls born in Senegal in 2017, living in Cardiff, UK in 2019.
Safa and Marwa Bibi, twin girls born in Hayatabad, Pakistan on January 17, 2017, conjoined by the head. Successfully separated at Great Ormond Street Hospital in February 2019.
Callie and Carter Torres, born January 30, 2017, in Houston Texas, from Blackfoot Idaho. They are Omphalo-Ischiopagus conjoined twins, attached by their pelvic area and sharing all organs from the belly button down with just one leg each.
Yiğit and Derman Evrensel, twin boys born on June 21, 2018, Antalya, Turkey. They are craniopagus twins and were separated at Great Ormond Street Hospital in 2019 by the same surgeons that separated Safa and Marwa Bibi.
Ervina and Prefina, born June 29, 2018, in the Central African Republic. They were separated on June 5, 2020, at the Bambino Gesù Pediatric Hospital in Rome, Italy.
Mercy and Goodness Ede, born August 13, 2019, conjoined by the chest and abdomen. Successfully separated at the National Hospital in Abuja, Nigeria in November 2019.
Marie-Cléa and Marie-Cléanne Papillon, born in Mauritius in 2019. Conjoined from neck to abdomen, but also from heart which had seven rooms, instead of four. Marie-Cléa did not survive the surgery to separate the two.
Susannah and Elizabeth Castle, born April 22, 2021, and separated December 10, 2021 in Philadelphia, Pennsylvania.
In fiction
Conjoined twins have been the focus of several noteworthy works of entertainment, including:
Stuck on You (2003 film), a 2003 American comedy film screen written and directed by the Farrelly brothers and starring Matt Damon and Greg Kinnear as conjoined twin brothers, whose conflicting aspirations provide both conflict and humorous situations, in particular when one of them wishes to move to Hollywood to |
Conjoined twins | pursue a career as an actor.
Alone, a Thai horror film following Pim after the death of her sister Ploy and their subsequent separation.
Blood Sisters focuses on a French Canadian model who has a separated conjoined twin.
Irish author Sarah Crossan won the Carnegie Medal for her verse novel, One. The story follows the life and survival of conjoined twin sisters. The book also won The Booksellers 2016 prize for young adult fiction and the Irish Childrens Book of the Year.
Tarot: Witch of the Black Rose graphic novel debut the ghost twin, She/they are constant companion(s) of Skeleton Man, her protector.
The Broadway musical Side Show depicts the lives of real-life conjoined twins Daisy and Violet Hilton, portrayed in the original Broadway production by Alice Ripley and Emily Skinner.
Reiko the Zombie Shop, 1990s womens horror manga, bonus chapters focus on unexpectedly life of Noriko and her "sister". Summoners Dr. Zero can resurrect and control fuse zombies called medicinal death.
MA GI & CA L., a conjoined magical alternative android, from psychology horror manga Magical Girl Apocalypse.
In the TV series The Addams Family, there are extended family members of the Addams Family who are mentioned to have two heads. In "Mother Lurch Visits the Addams Family," Morticia Addams mentions that she has a Cousin Slimy who has two good heads on his shoulder. In "Progress and the Addams Family," Morticia was making a knitted hat for Cousin Plato where Gomez Addams has stated that his left head is size 6 and his right head is size 8 3/4. In "Lurchs Little Helper," Morticia made a portrait of Cousin Crimp who has a male head and a female head.
Tamil actor Suriya portrays Vimalan and Akilan, conjoined twins in the 2012 film, Maattrraan.
The book The Girls, by Canadian novelist Lori Lansens, published in 2005, is the fictional autobiography of Canadian craniopagus twins Rose and Ruby Darlen with Slovakian background.
Irish author Sarah Crossan won the Carnegie Medal for her verse novel, One. The story follows the life and survival of conjoined twin sisters. The book also won The Booksellers 2016 prize for young adult fiction and the Irish Childrens Book of the Year.
In Lilo & Stitch: The Series, Swapper are Ischiopagus twin green stubby limbed lizard-like experiment with black eyes, purple markings on his back and three purple-tipped tendrils on each head that can emit a green ray from each heads eyes. The ray will swap the minds and voices of the targets, and the only means of returning to normal is through Swapper choosing to do so. Because Swapper is two heads on the same body, Swapper is two beings cooperating as one, though their personalities mirror each other: they can be indecisive at times but usually work well together.
In Big-Top Pee-wee, the Cabrini Circus has some conjoined twins named Ruth and Dot (portrayed by Helen Infield Siff and Carol Infield Sender).
In The Addams Family and Addams Family Values, there are conjoined twins named Flora and Fauna Amor (portrayed by Darlene and Maureen Sue Levin) who were once dates to Gomez Addams and Uncle Fester. Both films also featured a two-headed relative named Dexter and Donald Addams (portrayed by Douglas Brian Martin and Steven M. Martin).
In The Addams Family cartoon in 1992, the episode "N.J. Addams" featured Aunt Noggin who was a two-headed person who wears a Victorian dress. One head is black and speaks in a Jamaican accent and the other head is Caucasian and speaks in a Brooklyn accent.
The Farrelly brothers film Stuck on You depicts Bob and Walt Tenor, conjoined twins portrayed by Matt Damon and Greg Kinnear. 2003.
In Midnighter issue #13, Shock & Awe is a superheroine working for Los Angeles Strike Force.
Delilah and Jezebel in video games Bully.
CatDog depicts Cat and Dog, a hybrid of a dog and cat who are brothers.
On a LeapFrog Enterprises commercial advertising the Leapster from 2007, a boy is constantly playing video games from the console itself. The more he praises the Leapster, the more he grows extra heads.
Zaphod Beeblebrox is a character from Douglas Adams Hitchhikers Guide to the Galaxy, who has a second head along with a third arm.
Vaka-Waka and Nurp-Naut in Cartoon Network and The Lego Groups Mixels.
Fender and Bender (also known individually as HeadBanger) are characters in the 90s television series Toxic Crusaders, based on The Toxic Avenger films by Troma Entertainment. Fender is supposed to be a Mad Scientist while Bender is a Surfer.
Dragon Tales, a childrens show, depicts Zak and Wheezie (voiced by Jason Michas and Kathleen Barr) as a two-headed dragon that are brother and sister making them dicephalic parapagus twins.
In the Canadian mobile game My Singing Monsters, a bird-like species known as the Quibble is made up of elements Air and Water. The two-headed species plays a piano and has different colored feathers on both heads.
The Simpsons features Hugo in "Treehouse of Horror VII", who is Bart Simpsons conjoined twin. They were separated at birth by Dr. Hibbert and Hugo was imprisoned in the Simpsons attic.
The Oblongs, depicts Biff Oblong (Randy Sklar) and Chip Oblong (Jason Sklar)—17-year-old conjoined twins who are attached at the waist and share a middle leg due to their valleys pollution and radiation.
In the DC Comics series Hitman, villain Moe and Joe Dubelz is a conjoined twin gangster. Moe was alive at the time of introduction, but Joe had already died and is, in fact, undergoing putrefaction.
In the episode "Humbug" of The X-Files, Vincent Schiavelli portrayed a circus performer named Lanny, with an underdeveloped conjoined twin named Leonard. The episode also includes a reference to Chang and Eng.
The Prophet of Yonwood has a reference to Chang and Eng when the main character, Nickie, finds a picture of them in her great-grandfathers old house in Siam.
In the anime Naruto, Sakon (左近) and his conjoined twin brother Ukon (右近) are the strongest of the Sound Four and count as one member due to their abilities to merge bodies and kill an opponent at a cellular level. They both serve as antagonists.
The Broadway musical Side Show depicts the lives of real-life conjoined twins Daisy and Violet Hilton, portrayed in the original Broadway production by Alice Ripley and Emily Skinner.
The American medical drama Greys Anatomy featured several cases of conjoined twins.
The 2001 movie Not Another Teen Movie depicts Kara and Sara Fratelli, conjoined twins portrayed by Samaire Armstrong and Nectar Rose.
The musical group Evelyn, Evelyn depicts a pair of conjoined twin sisters—often referred to as "The Evelyn Sisters"—in many of their songs and music videos. The fictional sisters are shown to be child prostitutes in the music video for "Sandy Fishnets", and the song "Evelyn, Evelyn" describes their longing for privacy and to be separated from one another.
The Bride with White Hair, a 1993 Hong Kong movie, features conjoined twin villains.
The animated series Duckman featured Eric T. Duckmans sons Charles (voiced by Dana Hill in 1994–1996, Pat Musick in 1997) and Mambo (voiced by E. G. Daily) who are dicephalic parapagus twins where their heads share a body.
Fran Bow, a 2015 indie psychological horror game, includes Clara and Mia Buhalmet, a set of mentally ill conjoined twins, as characters. They were surgically sewn together, much like an experiment performed by Josef Mengele, also known as the Angel of Death, in which a pair of twins were sewn together back to back by blood vessels and organs, in an attempt to create conjoined twins.
The Peach Tree, a Korean novel and film, portrays conjoined twin brothers falling in love with the same woman.
The 1999 movie Twin Falls Idaho portrays conjoined twin brothers who are played by two non-conjoined identical twin brothers, one of whom directed the film, and both of whom co-wrote the screenplay.
In the fourth season of the American television series American Horror Story titled American Horror Story: Freak Show, the main character Bette and Dot Tattler (Sarah Paulson in a dual role) are a dicephalic parapagus twin where their two heads are side by side on one torso. This performance is done with the help of CGI.
In season two, episode eight of Rick and Morty, Michael and Pichael Thompson (voiced by Justin Roiland) are depicted as conjoined twins hosting separate TV shows at the same time.
In the Cirque Du Soleil show Kurios: Cabinetes des Curiosities, a pair of conjoined twins are among the Seekers collection. They later split during an aerial straps duo and reunite for the rest of the show.
The bilingual film Chaarulatha stars Priyamani as a conjoined twin.
In the Disney-distributed movie Jagga Jasoos, starring Ranbir Kapoor and Katrina Kaif, Basheer Alexander is shown with two heads.
On the television series Ruby Gloom, the characters Frank and Len are conjoined twins who comprise a rock group called RIP.
In the film Monsters University, two of the members of the fictitious fraternity Oozma Kappa are named Terri and Terry Perry (voiced by Sean Hayes and Dave Foley). They are dicephalic parapagus twins where they have four arms and share the same tentacles that are in place of their legs.
In the childrens cartoon Steven Universe, the Rutile twins are conjoined.
Fire and Water are conjoined twins in Chris Abanis 2014 novel The Secret History of Las Vegas.
The Knick portrays conjoined twins Zoya and Nika, who share a liver. They are successfully separated by the doctors.
Brian Aldisss 1977 novel Brothers of the Head depicts conjoined twins who become rock stars. In the 2005 film version, they are played by non-conjoined identical twins Harry Treadaway and Luke Treadaway.
The 2006 remake of The Hills Have Eyes briefly shows a photo of a set of twins, who have Cephalothoracopagus/Janiceps. This particular case, was caused by Agent Orange.
Admirals Watson and Crick are presumably conjoined twins joined at the torso in the 2015 childrens show Miles from Tomorrowland.
In the Ultimate Marvel reality of Marvel Comics, Syndicate is two conjoined twins in Ultimate X-Men. They were created by Brian K. Vaughn and Steve Dillon, and first appeared in Ultimate X-Men #58. They were killed during the crossover event Ultimatum.
In the horror video game Dead by Daylight, the playable characters “The Twins” are a brother and sister who are conjoined twins. However, the brother is able to detach from the sister.
See also
Medical law
Monoamniotic twins
Polycephaly
Notes
References
External links
Types and social history of conjoined twins
The site of the medical Saudi team responsible for numerous successful separation surgeries
Eng and Chang – The Original Siamese Twins; The University of North Carolina at Chapel Hill, The North Carolina Collection Gallery
The Human Marvels: A Historical Reference Site run by J. Tithonus Pednaud, Teratological Historian
Cases of conjoined and incomplete twins Archived 2006-06-10 at the Wayback Machine
Clara and Alta Rodriguez, joined at the pelvis and successfully separated in 1974 at Childrens Hospital of Philadelphia by surgeons including C. Everett Koop
National Library of Medicine: Selected Moments in the History of Conjoined Twins
Conjoined Twins Fast Facts (also lists additional twins)
Emedicine article (this article includes post-mortem images)
Facts About Multiples: Conjoined Records and stats
"The St. Benoit Twins", Scientific American, July 13, 1878, p. 24 |
Reticular erythematous mucinosis | Reticular erythematous mucinosis (REM) is a skin condition caused by fibroblasts producing abnormally large amounts of mucopolysaccharides. It is a disease that tends to affect women in the third and fourth decades of life.: 187
See also
Mucinosis
List of cutaneous conditions
References
== External links == |
Aneurysmal bone cyst | Aneurysmal bone cyst (ABC) is a non-cancerous bone tumor composed of multiple varying sizes of spaces in a bone which are filled with blood. The term is a misnomer, as the lesion is neither an aneurysm nor a cyst. It generally presents with pain and swelling in the affected bone. Pressure on neighbouring tissues may cause compression effects such as neurological symptoms.The cause is unknown. Diagnosis involves medical imaging. CT scan and X-ray show lytic expansion lesions with clear borders. MRI reveals fluid levels.Treatment is usually by curettage, bone grafting or surgically removing the part of bone. 20–30% may recur, usually in the first couple of years after treatment, particularly in children.It is rare. The incidence is around 0.15 cases per one million per year. Aneurysmal bone cyst was first described by Jaffe and Lichtenstein in 1942.
Signs and symptoms
The afflicted may have relatively small amounts of pain that will quickly increase in severity over a time period of 6–12 weeks. The skin temperature around the bone may increase, a bony swelling may be evident, and movement may be restricted in adjacent joints.Spinal lesions may cause quadriplegia and patients with skull lesions may have headaches.
Sites
Commonly affected sites are metaphyses of vertebra, flat bones, femur and tibia. Approximate percentages by sites are as shown:
Skull and mandible (4%)
Spine (16%)
Clavicle and ribs (5%)
Upper extremity (21%)
Pelvis and sacrum (12%)
Femur (13%)
Lower leg (24%)
Foot (3%)
Causes
Aneurysmal bone cyst has been widely regarded a reactive process of uncertain cause since its initial description by Jaffe and Lichtenstein in 1942. Many hypotheses have been proposed to explain the cause and pathogenesis of aneurysmal bone cyst, and until very recently the most commonly accepted idea was that aneurysmal bone cyst was the consequence of an increased venous pressure and resultant dilation and rupture of the local vascular network. However, studies by Panoutsakopoulus et al. and Oliveira et al. uncovered the clonal neoplastic nature of aneurysmal bone cyst. Primary cause has been regarded arteriovenous fistula within bone.The lesion may arise de novo or may arise secondarily within a pre-existing bone tumor, because the abnormal bone causes changes in hemodynamics. An aneurysmal bone cyst can arise from a pre-existing chondroblastoma, a chondromyxoid fibroma, an osteoblastoma, a giant cell tumor, or fibrous dysplasia. A giant cell tumor is the most common cause, occurring in 19–39% of cases. Less frequently, it results from some malignant tumors, such as osteosarcoma, chondrosarcoma, and hemangioendothelioma.
Pathology
Histologically, they are classified in two variants.
The classic (or standard) form (95%) has blood filled clefts among bony trabeculae. Osteoid tissue is found in stromal matrix.
The solid form (5%) shows fibroblastic proliferation, osteoid production and degenerated calcifying fibromyxoid elements.According to Buraczewski and Dabska, the development of the aneurysmal bone cyst follows three stages.
They can also be associated with a TRE17/USP6 translocation.Aneurysmal bone cysts may be intraosseous, staying inside of the bone marrow. Or they may be extraosseous, developing on the surface of the bone, and extending into the marrow. A radiograph will reveal a soap bubble appearance.
Diagnosis
X-ray and CT scan show lytic expansion lesions with clear borders. Expansion of cortex gives the lesion a balloon-like appearance. Larger lesions may appear septated. MRI reveals fluid levels. Bone scan shows outer radiotracer uptake, with a central dark area.
Differential diagnosis
Following conditions are excluded before diagnosis can be confirmed:
Unicameral bone cyst
Giant cell tumor
Telangiectatic osteosarcoma
Secondary aneurysmal bone cyst
Treatment
Curettage is performed on some people, and is sufficient for inactive lesions. The recurrence rate with curettage is significant in active lesions, and marginal resection has been advised. Liquid nitrogen, phenol, methyl methacrylate are considered for use to kill cells at margins of resected cyst.
Prognosis
20–70% recur after curettage.
Epidemiology
It is rare. The incidence is around 0.15 cases per one million per year. 80% occur in people age less than 20 years. It is second most common tumor of spine and most common benign tumor of pelvis in pediatric population. Males are affected as equally as females.
Additional images
See also
Simple bone cyst (SBC)
Giant cell tumor of bone
Traumatic bone cyst
References
== External links == |
Junctional ectopic tachycardia | Junctional ectopic tachycardia (JET) is a rare syndrome of the heart that manifests in patients recovering from heart surgery. It is characterized by cardiac arrhythmia, or irregular beating of the heart, caused by abnormal conduction from or through the atrioventricular node (AV node). In newborns and infants up to 6 weeks old, the disease may also be referred to as His bundle tachycardia or congenital JET.
Pathophysiology
In normal individuals, electrical activity in the heart is initiated in the sinoatrial (SA) node (located in the right atrium), propagates to the atrioventricular (AV) node, and then through the bundle of His to the ventricles of the heart.
The AV node acts as a gatekeeper, limiting the electrical activity that reaches the ventricles of the heart. This function of the AV node is important, because if the signals generated in the atria of the heart were to increase in rate (as they do during atrial fibrillation or atrial flutter), the AV node will limit the electrical activity that conducts to the ventricles. For instance, if the atria are electrically activated at 300 beats per minute, half those electrical impulses are blocked by the AV node, so that the ventricles are activated at 150 beats per minute (giving a pulse of 150 beats per minute). Another important property of the AV node is that it slows down individual electrical impulses. This is manifest on the ECG as the PR interval, which is about less than 200 milliseconds, the time from activation of the atria (manifest as the P wave) and activation of the ventricles (manifest as the QRS complex).Individuals with JET have a "short-circuit" in their heart, where the electricity bypasses the AV node, causing the heart to beat faster than normal. The cause of the arrhythmia, the ectopic focus, is usually near the AV node in the triangle of Koch (a rough triangle with points at the coronary sinus, the tendon of Todaro, and the tricuspid valve).Patients of heart surgery may experience an accelerated narrow complex tachycardia, usually within the first 24–48 hours (but occasionally longer) after surgery. There may be atrio-ventricular disassociation with more ventricular signals than atrial signals. The cause of JET is felt to be due to manipulation of the tissue surrounding the AV node during surgery, however debate exists regarding the exact cause, as it is seen after procedures even without significant manipulation of this area.JET-like symptoms can also manifest congenitally and in the first six months of life. This syndrome, which may also referred to as His bundle tachycardia, is resistant to therapy and can be difficult to treat.
Diagnosis
JET is most commonly diagnosed using a 12-lead ECG. The appearance is usually of a tachycardia with rapid, regular ventricular rates of 170-260 beats per minute. The QRS complexes are usually narrow, but may be broad if a bundle branch block is present. There may a 1:1 relationship between atria and ventricular activity with a short RP interval, or atrioventricular dissociation with slower atrial than ventricular rates if the AV node is unable to conduct from the ventricles to the atria.The differential diagnosis of JET includes other forms of supraventricular tachycardia, most commonly atrioventricular nodal reentrant tachycardia (AVNRT). These can be distinguished using adenosine. The response to adenosine in JET is a temporary loss of conduction to the atria leading to continuation of the tachycardia but with atrioventricular dissociation. In contrast, administration of adenosine in AVNRT will usually terminate the arrhythmia. The diagnosis can be conclusively proven by performing an invasive electrophysiological study.
Treatment
Treatment is aimed at slowing the rate by correcting acidosis, correcting electrolytes (especially magnesium and calcium), cooling the patient, and antiarrhythmic medications. Occasionally pacing of the atrium at a rate higher than the JET may allow improved cardiac function by allowing atrial and ventricular synchrony.Medications used to treat JET include beta-adrenoceptor blockers such as propranolol, calcium channel antagonists such as verapamil, and antiarrhythmics such as flecainide, amiodarone, and propafenone. Amiodarone is frequently used in the short term in children experiencing JET following heart surgery, although propanolol, flecainide and propafenone are more commonly recommended for long term use due to the frequency of side effects associated with amiodarone.In those who experience recurrent episodes of JET, an alternative to long term medical therapy is catheter ablation. In this procedure, the small area in which the cells initiating JET are found can be destroyed by heating or freezing the tissue. This is accomplished using wires passed to the heart via the femoral vein through a small puncture in the groin. The main risk of this procedure is accidental damage to the AV node. This occurs more frequently when treating JET than other forms of supraventricular tachycardia, requiring treatment with a pacemaker in 5-10% of ablations for JET. The risk is lower if the tissue is frozen rather than heated.For those at risk of developing JET such as children undergoing heart surgery, treatment can also be given prophylactically. A meta-analysis of 9 studies found that sedation with dexmedetomidine reduced the risk of JET occurring post-operatively.
Epidemiology
JET is most commonly seen in children following cardiac surgery. The arrhythmia affects 2-22% of children depending on the type of surgery performed, with higher rates seen following repair of Tetralogy of Fallot, and lower rates following the repair of ventricular septal defects and arterial switch operations.
Etymology
Junctional ectopic tachycardia derives its name from the problem it causes. "Junctional" is used as the abnormal tissue driving the ventricular rate is located close junction between the atria and ventricles, known as the AV node. Ectopic (from the Greek ektopos, meaning "out of place") refers to the fact that the ventricles are being triggered by tissue that is not the normal pacemaker tissue within the heart. Tachycardia (from the Greek takhys, meaning "swift", and kardia, meaning heart) means a swift heart rate.By this definition, junctional ectopic tachycardia is an abnormally swift heart rhythm due to cells firing within the heart near the AV node.
References
== External links == |
Primary cutaneous amyloidosis | Primary cutaneous amyloidosis is a form of amyloidosis associated with oncostatin M receptor.
This type of amyloidosis has been divided into the following types:: 520
Macular amyloidosis is a cutaneous condition characterized by itchy, brown, rippled macules usually located on the interscapular region of the back.: 521 Combined cases of lichen and macular amyloidosis are termed biphasic amyloidosis, and provide support to the theory that these two variants of amyloidosis exist on the same disease spectrum.
Lichen amyloidosis is a cutaneous condition characterized by the appearance of occasionally itchy lichenoid papules, typically appearing bilaterally on the shins.: 521
Nodular amyloidosis is a rare cutaneous condition characterized by nodules that involve the acral areas.: 521
See also
Amyloidosis
List of cutaneous conditions
References
== External links == |
Erythema induratum | Erythema induratum is a panniculitis on the calves. It occurs mainly in women, but it is very rare now. Historically, when it has occurred, it has often been concomitant with cutaneous tuberculosis, and it was formerly thought to be always a reaction to the TB bacteria. It is now considered a panniculitis that is not associated with just a single defined pathogen. The medical eponym Bazin disease was historically synonymous, but it applies only to the tuberculous form and is dated.
Pathophysiology
Predisposing factors include abnormal amount of subcutaneous fat, thick ankles and abnormally poor arterial supply. Abnormal arterial supply causes low-grade ischemia of ankle region. The ankle skin becomes sensitive to temperature changes. When weather is cold, ankle is cold, blue and often tender. In hot weather, ankle becomes hot, edematous, swollen and painful. Chilblains may be present. On palpation, small superficial and painful nodules are felt. They break down to form small and multiple ulcers. Fresh crops of nodules appear in periphery of ulcer and ultimately break down. In nodular stage, pain is present; while it subsides in ulcerative stage.
Diagnosis
Mainly clinical.
Eponym
The name Bazin disease honors Pierre-Antoine-Ernest Bazin.
Additional images
References
External links
Media related to Erythema induratum at Wikimedia Commons
PatientPlus |
Peeling skin syndrome | Peeling skin syndrome (also known as "acral peeling skin syndrome", "continual peeling skin syndrome", "familial continual skin peeling", "idiopathic deciduous skin", and "keratolysis exfoliativa congenita") is an autosomal recessive disorder characterized by lifelong peeling of the stratum corneum, and may be associated with pruritus, short stature, and easily removed anagen hair.: 502 "Acral" refers to the fact that the peeling of the skin is most noticeable on the hands and feet of this state. Peeling happens sometimes on the arms and legs, too. The peeling is typically apparent from birth, although it may start in childhood or later on in life as well. Skin peeling is caused by sun, humidity, moisture, and friction.The acral form can be associated with TGM5.
Syndromes
Peeling skin syndrome is also associated with 6 syndromes that are each caused by a different genetic defect. The various syndromes include peeling skin syndrome 1, 2, 3, 4, 5, and 6.
Peeling skin syndrome 1
Peeling skin syndrome 1 is caused by a genetic defect in the corneodesmosin (CDSN) gene. This gene localizes to the human epidermis and other epithelia. The protein experiences a chain of cleavages during corneocyte maturation. Its symptoms include short stature, abnormality of metabolism/homeostasis, scaling skin, pruritus, erythema, asthma, brittle hair, and abnormality of hair texture.
Peeling skin syndrome 2
Peeling Skin Syndrome 2 is caused by a genetic defect in the TGM5 gene. Transglutaminase 5 is best for catalyzing the cross-linking of proteins and the conjugation of polyamines to proteins. It also adds to the development of the cornified cell envelope of keratinocytes. Its symptoms include excessive wrinkling of palmar skin, skin erosion, hyperpigmentation of the skin, ichthyosis, and allergy.
Peeling skin syndrome 3
Peeling skin syndrome 3 is caused by a genetic defect in the carbohydrate sulfotransferase (CHST8) gene. This gene is characterized by a way of asymptomatic lifelong and non-stop dropping of the stratum corneum of the dermis. Its symptoms begin for the duration of the second half of the primary decade of existence and encompass generalized white scaling taking place over the upper and lower extremities.
Peeling skin syndrome 4
Peeling skin syndrome 4 is caused by a genetic defect in the cystatin A (CSTA) gene. This gene is an intracellular thiol proteinase inhibitor. It has an essential role in desmosome-mediated cell-cellular adhesion inside the lower levels of the dermis. Its symptoms include well-circumcised peeling of skin on the extremities and neck, generalized dry skin with fine scaling and sparing of face, hyperkeratosis, and palmoplantar keratoderma
Peeling skin syndrome 5
Peeling skin syndrome 5 is caused by a genetic defect in the serpin (serpin family member 8) gene. This gene is produced by platelets and can bind to and inhibit the function of furin, which is a serine protease involved in platelet functions. It is also characterized by superficial peeling of the dorsal and palmar pores and skin of the hands and feet; the pores and skin of the forearms and legs may also be involved. Its symptoms include superficial peeling of small areas of the skin that involve the dorsal and palmar surfaces of the hands and feet, superficial scaling of forearms and legs, and acanthosis.
Peeling skin syndrome 6
Peeling skin syndrome 6 is caused by a genetic defect in the filaggrin (filaggrin family member 2) gene. The function for this gene is vital for normal cellular-cell adhesion within the cornified cell layers. It is also critical for the integrity and mechanical strength of the stratum corneum of the epidermis. Its symptom include dryness of the skin, peeling of the skin. erythema at lesion sites, bullae, and hyper-pigmentation.
Symptoms and signs
Abnormal blistering of the skin
Abnormality of hair texture
Dry skin
Aminoaciduria
Hyperhidrosis
Ichthyosis
Treatment
There is no remedy for peeling skin syndrome. Treatment focuses on avoiding skin damage and treating symptoms as they occur. Ointments are also used to minimize skin peeling and when the blister grows, sterile needles may be activated. The condition can be exacerbated by hot temperatures, humidity, and friction. Individuals should be informed to avoid exacerbating triggers such as trauma, humidity, heat, perspiration, and water.
Frequency
Only several dozen cases have been reported in the literature, making it rare, but because its symptoms are mild and similar to other disorders it could very well be under-diagnosed.
See also
Idiopathic calcified nodules of the scrotum
Keratolysis exfoliativa
List of cutaneous conditions
Corneodesmosin
TGM5
Carbohydrate sulfotransferase
Cystatin A
Serpin
Filaggrin
References
== External links == |
Rubinstein–Taybi syndrome | Rubinstein–Taybi syndrome (RTS) is a rare genetic condition characterized by short stature, moderate to severe learning difficulties, distinctive facial features, and broad thumbs and first toes. Other features of the disorder vary among affected individuals. These characteristics are caused by a mutation or deletion in the CREBBP and/or EP300 gene located on chromosome 16.
People with this condition have an increased risk of developing noncancerous and cancerous tumors, leukemia, and lymphoma. This condition is sometimes inherited as an autosomal dominant pattern and is uncommon. Many times it occurs as a de novo (not inherited) occurrence. It occurs in an estimated 1 in 125,000-300,000 births.
Presentation
Rubinstein–Taybi syndrome presents itself from birth, and is usually hallmarked by delayed physical and cognitive growth.Typical features of the disorder include:
Broad thumbs and broad first toes and clinodactyly of the 5th finger
Mental disability
Small height, low bone growth, small head
Cryptorchidism in males
Unusual facies involving the eyes, nose, and palate
Anesthesia may be dangerous in these patients: "According to the medical literature, in some cases, individuals with Rubinstein–Taybi syndrome may have complications (e.g., respiratory distress and/or irregular heart beats [cardiac arrythmias]) associated with a certain muscle relaxant (succinylcholine) and certain anesthesia. Any situations requiring the administration of anesthesia or succinylcholine (e.g., surgical procedures) should be closely monitored by skilled professionals (Anesthesiologists)." Primary literature suggests the children may have a higher rate of cardiac physical and conduction abnormalities which may cause unexpected results with cardioactive medications. A further editorial reply in the British Journal of Anaesthesia discusses changes in the face and airway structure making it more difficult to secure the airway under anaesthesia, however, complications appeared in a minority of cases, and routine methods of airway control in the operating room appears to be successful. They recommended close individual evaluation of Rubinstein–Taybi patients for anaesthetic plans.A 2009 study found that children with RTS were more likely to be overweight and to have a short attention span, motor stereotypies, and poor coordination. The study hypothesized that the identified CREBBP gene impaired motor skills learning. Other research has shown a link with long-term memory (LTM) deficit.It is diagnosed when a heterozygous pathogenic variant of the CREBBP gene is identified in the individual. It exhibits an autosomal dominant inheritance pattern, but some documented cases show heterozygous individuals exhibiting germline mosaicism. This condition affects men and women equally, and is often misdiagnosed with other diseases or disabilities that result in delayed mental development.
Genetics
Rubinstein–Taybi syndrome is a microdeletion syndrome involving chromosomal segment 16p13.3 and is characterized by mutations in the CREBBP gene. Varying amounts of material are deleted from this section of the chromosome and accounts for the spectrum of physiological symptoms.The CREBBP gene makes a protein that helps control the activity of many other genes. The protein, called CREB-binding protein, plays an important role in regulating cell growth and division and is essential for normal fetal development. If one copy of the CREBBP gene is deleted or mutated, cells make only half of the normal amount of CREB binding protein. A reduction in the amount of this protein disrupts normal development before and after birth, leading to the signs and symptoms of Rubinstein–Taybi syndrome.Mutations in the EP300 gene are responsible for a small percentage of cases of Rubinstein–Taybi syndrome. These mutations result in the loss of one copy of the gene in each cell, which reduces the amount of p300 protein by half. Some mutations lead to the production of a very short, nonfunctional version of the p300 protein, while others prevent one copy of the gene from making any protein at all. Although researchers do not know how a reduction in the amount of p300 protein leads to the specific features of Rubinstein–Taybi syndrome, it is clear that the loss of one copy of the EP300 gene disrupts normal development.A mouse model has been identified in order to perform experimental research procedures. The model has exhibited the same clinical symptoms seen in humans and has become a foundation for future research.Unfortunately, in nearly 40% of cases, neither gene, CREBBP or EP300, can be implicated in the cause of the disease. In these cases, there is no mutation on the 16th chromosome leaving many more questions yet to be answered. However, new research shows that around 55% of cases involve a mutation in the CBP gene, further suggesting that this disease has its origins in mutation of the regulatory mechanisms of transcription (Izumi, 2016).
Treatment
There is no existing treatment that reverses or cures RTS. There are, however, ways to manage and reduce symptoms for patients. Patients with RTS suffer from a diverse breadth of symptoms. These include cognitive-developmental impairment, heart abnormalities, delayed bone growth and skeletal abnormalities, auditory impairment, urinary tract abnormalities, including kidney problems, and dental and speech problems. Not every patient will suffer from all or multiple symptoms, and not every patient will experience the same symptoms, meaning they differ from patient to patient. Due to there being a wide range of symptoms, RTS patients are referred to specialists that focus on each specific symptom. There is not a specialist for RTS. For example, patients will go to an orthopedic surgeon and physical therapy for skeletal and growth abnormalities, like scoliosis but will go to a cardiologist if they suffer from heart abnormalities or a dentist if they suffer from dental abnormalities. Individuals suffering from cognitive developments usually are part of special education programs and speech therapy. The specialists the individuals go to match the symptoms the individuals have. Regular check-ups and monitoring are needed for cardiac, dental, auditory, and renal abnormalities. Genetic counseling is also recommended for affected individuals and their families.
History
Rubinstein–Taybi syndrome was first unofficially mentioned in a French orthopedic medical journal in 1957 by Greek physicians doctors: Michail, Matsoukas, and Theodorou. The medical journal reported a case concerning a seven-year-old boy with radically deviated/arched thumbs, long nose, muscular hypotonia, along with physical and mental underdevelopment. At this point in time the case study mentioned by the Greek physicians was considered to be an anomaly due to the fact that there hadnt been any other reported cases of children with these specific physical and mental characteristics. The doctors accredited with discovering the syndrome and therefore bear its name-sake were unaware of this journal at the time of their discovery. However, it is acknowledged that the 1957 case reported in the French journal of orthopedic medicine is most likely the first reported case of RTS.Dr. Jack Herbert Rubinstein, an American pediatrician reported assessing a three-year-old girl with unusual facial and digital findings in 1958. Similarly, that same year Rubinstein had evaluated another child with similar characteristics, this time a seven-year-old boy. Having sensed a striking similarity between these two unrelated cases Rubinstein tried distributing photos and information concerning these two cases to other clinics in the U.S. from 1959 to 1960. Rubinstein graduated from Harvard Medical School and worked as the director of the Hamilton County Diagnostic Clinic for the Mentally Retarded. He has worked in behavioral and developmental pediatrics for many years prior to the discovery of this new syndrome.In 1961, Dr. Hooshang Taybi, an Iranian-American pediatric radiologist, reported having assessed a three-year-old boy that appeared to have the same syndrome as described by Rubinstein. During the summer of 1963 Dr. Taybi reported having evaluated seven children with characteristics such as broad thumbs and great toes, "unusual" facial features, and intellectual disabilities – these findings went on to appear in the American Journal of Diseases of Children documenting these characteristics as a syndrome. Dr. Hooshang Taybi graduated from Tehran University School of Medicine and worked for the Ministry of Health. Later in his career he taught and practiced pediatric radiology in Oklahoma and Indiana. He had identified three new syndromes with his colleagues, among them is Rubinstein–Taybi syndrome.In 1992 the first genetic abnormalities that act as markers for Rubinstein-Taybi syndrome were identified. These abnormalities are said to affect either chromosome 16 or chromosome 22. The specific chromosome impacted by a mutation determines the type of Rubinstein–Taybi syndrome that may occur. A mutation of the CREBP gene on chromosome 16 gives rise to the first form of RTS (most common). While a mutation of the EP300 gene on chromosome 22 is characteristic of the second form of RTS.
See also
Nasodigitoacoustic syndrome
List of cutaneous conditions
References
External links
GeneReview/UW/NIH entry on Rubinstein-Taybi syndrome
Rubinstein-Taybi syndrome due to 16p13.3 microdeletion on ORPHAnet |
Amok | Amok may refer to:
Running amok, the act of behaving disruptively or uncontrollably.
Film
Amok (1934 film), a French film
Amok (1944 film), a Mexican romantic drama
Amok (1983 film), a Moroccan drama
Literature
Amok (comics), an Italian comic book series
Amok (novella), by Stefan Zweig, 1922
Amok, a 1974 novel by Harry Thürk
Amok, a 2003 novel by Krystian Bala
Music
Amok (The Late B.P. Helium album), 2004
Amok (Sentenced album), 1995
Amok (Atoms for Peace album), 2013
Other uses
Steamed curry (Khmer: អាម៉ុក, amŏk), name in Cambodia for a curry steam-cooked in banana leaves
Fish amok, a Cambodian steamed fish curry
Amok (video game), a 1996 video game for the Sega Saturn
Mok language, also known as Amok
Amok (publisher), now Frémok, a Franco-Belgian comics publishing house
Amok Press, a defunct American book imprint
See also
All pages with titles beginning with Amok
All pages with titles containing Amok
"Amok Time", a 1967 episode of Star Trek: The Original Series
Amuck!, a 1972 Italian giallo film
AMOC (disambiguation) |
Ophiasis | Ophiasis is a form of alopecia areata characterized by the loss of hair in the shape of a wave at the circumference of the head.It gets its name from Greek ὄφις ophis snake because of the apparent similarity to a snake-shape and the pattern of hair loss.The term "sisaipho" is used to characterize the inverse pattern. Sisaipho is, almost, the reverse spelling of ophiasis. It is also called "ophiasis inversus".This form of hair loss "...targets the bodys own hair follicles, resulting in hair loss..." and although the immune system could be attacking hair follicle melanocytes, dermal papilla cells, and keratinocytes,” the foundational cause of this disease is yet to be confirmed.
Pattern of hair loss
This is one among many types of patterns of hair loss, “in which they have band-link hair loss across the occiput.” Hair loss can take the form of patches of hair being removed and there can also be spontaneous regrowth as well.
Duration of hair loss
Ophiasis hair loss is one form in which the hair loss can further deteriorate and can extend “for more than a year.”
References
External links
Cheng Tan, MD; Wen-Wuan Zhu, MD. "Mosaic Hair Regrowth Pattern of Ophiasis and Androgenic Alopecia in a Patient With Alopecia Areata Totalis". Medscape.{{cite web}}: CS1 maint: uses authors parameter (link) |
Sulfite oxidase | Sulfite oxidase (EC 1.8.3.1) is an enzyme in the mitochondria of all eukaryotes, with exception of the yeasts. It oxidizes sulfite to sulfate and, via cytochrome c, transfers the electrons produced to the electron transport chain, allowing generation of ATP in oxidative phosphorylation. This is the last step in the metabolism of sulfur-containing compounds and the sulfate is excreted.
Sulfite oxidase is a metallo-enzyme that utilizes a molybdopterin cofactor and a heme group (in a case of animals). It is one of the cytochromes b5 and belongs to the enzyme super-family of molybdenum oxotransferases that also includes DMSO reductase, xanthine oxidase, and nitrite reductase.
In mammals, the expression levels of sulfite oxidase is high in the liver, kidney, and heart, and very low in spleen, brain, skeletal muscle, and blood.
Structure
As a homodimer, sulfite oxidase contains two identical subunits with an N-terminal domain and a C-terminal domain. These two domains are connected by ten amino acids forming a loop. The N-terminal domain has a heme cofactor with three adjacent antiparallel beta sheets and five alpha helices. The C-terminal domain hosts a molybdopterin cofactor that is surrounded by thirteen beta sheets and three alpha helices. The molybdopterin cofactor has a Mo(VI) center, which is bonded to a sulfur from cysteine, an ene-dithiolate from pyranopterin, and two terminal oxygens. It is at this molybdenum center that the catalytic oxidation of sulfite takes place.
The pyranopterin ligand which coordinates the molybdenum centre via the enedithiolate. The molybdenum centre has a square pyramidal geometry and is distinguished from the xanthine oxidase family by the orientation of the oxo group facing downwards rather than up.
Active site and mechanism
The active site of sulfite oxidase contains the molybdopterin cofactor and supports molybdenum in its highest oxidation state, +6 (MoVI). In the enzymes oxidized state, molybdenum is coordinated by a cysteine thiolate, the dithiolene group of molybdopterin, and two terminal oxygen atoms (oxos). Upon reacting with sulfite, one oxygen atom is transferred to sulfite to produce sulfate, and the molybdenum center is reduced by two electrons to MoIV. Water then displaces sulfate, and the removal of two protons (H+) and two electrons (e−) returns the active site to its original state. A key feature of this oxygen atom transfer enzyme is that the oxygen atom being transferred arises from water, not from dioxygen (O2).
Electrons are passed one at a time from the molybdenum to the heme group which reacts with cytochrome c to reoxidize the enzyme. The electrons from this reaction enter the electron transport chain (ETC).
This reaction is generally the rate limiting reaction. Upon reaction of the enzyme with sulfite, it is reduced by 2 electrons. The negative potential seen with re-reduction of the enzyme shows the oxidized state is favoured.
Among the Mo enzyme classes, sulfite oxidase is the most easily oxidized. Although under low pH conditions the oxidative reaction become partially rate limiting.
Deficiency
Sulfite oxidase is required to metabolize the sulfur-containing amino acids cysteine and methionine in foods. Lack of functional sulfite oxidase causes a disease known as sulfite oxidase deficiency. This rare but fatal disease causes neurological disorders, mental retardation, physical deformities, the degradation of the brain, and death. Reasons for the lack of functional sulfite oxidase include a genetic defect that leads to the absence of a molybdopterin cofactor and point mutations in the enzyme. A G473D mutation impairs dimerization and catalysis in human sulfite oxidase.
See also
Sulfur metabolism
Bioinorganic chemistry
References
Further reading
External links
Sulfite+oxidase at the US National Library of Medicine Medical Subject Headings (MeSH)
Research Activity of Sarkar Group
PDBe-KB provides an overview of all the structure information available in the PDB for Human Sulfite oxidase, mitochondrial |
Rhizomelic chondrodysplasia punctata | Rhizomelic chondrodysplasia punctata is a rare developmental brain disorder characterized by systemic shortening of the proximal bones (i.e. rhizomelia), seizures, recurrent respiratory tract infections and congenital cataracts. The affected individuals have low levels of plasmalogens.
Signs and symptoms
Rhizomelic chondrodysplasia punctata has the following symptoms:
Bilateral shortening of the femur
Post-natal growth problems (deficiency)
Cataracts
Intellectual disability
Possible seizures
Possible infections of respiratory tract
Genetics
This condition is a consequence of mutations in the PEX7 gene, the GNPAT gene (which is located on chromosome 1) or the AGPS gene. The condition is acquired in an autosomal recessive manner.
Pathophysiology
The mechanism of rhizomelic chondrodysplasia punctata in the case of type 1 of this condition one finds that peroxisome objective is PEX7, in peroxisome assembly. There are 3 pathways that count on PEX7 and are:
AGPS (catalyzes plasmalogen biosynthesis)
PhYH (catalyzes catabolism of phytanic acid)
ACAA1 (catalyzes beta-oxidation of VLCFA - straight)
Diagnosis
The diagnosis of rhizomelic chondrodysplasia punctata can be based on genetic testing as well as radiography results, plus a physical examination of the individual.
Types
Type 1 (RCDP1) is associated with PEX7 mutations; these are peroxisome biogenesis disorders where proper assembly of peroxisomes is impaired.
Type 2 (RCDP2) is associated with DHAPAT mutations
Type 3 (RCDP3) is associated with AGPS mutations
Treatment
Management of rhizomelic chondrodysplasia punctata can include physical therapy; additionally orthopedic procedures improved function sometimes in affected people. However, the prognosis is poor in this condition.
See also
Plasmalogen
Peroxisomal disorder
References
Further reading
== External links == |
Impaired fasting glucose | Impaired fasting glucose is a type of prediabetes, in which a persons blood sugar levels during fasting are consistently above the normal range, but below the diagnostic cut-off for a formal diagnosis of diabetes mellitus. Together with impaired glucose tolerance, it is a sign of insulin resistance. In this manner, it is also one of the conditions associated with metabolic syndrome.
Those with impaired fasting glucose are at an increased risk of vascular complications of diabetes, though to a lesser extent. The risks are cumulative, with both higher blood glucose levels, and the total amount of time it spends elevated, increasing the overall complication rate.
IFG can eventually progress to type 2 diabetes mellitus without intervention, which typically involves lifestyle modification. Those with impaired fasting glucose have a 1.5 fold increased risk of developing clinical diabetes within 10 years, when compared to the general population. Some studies suggest that without lifestyle changes, IFG will progress to clinically diagnosable diabetes in just under 3 years, on average.Impaired fasting glucose is often, though not always, associated with impaired glucose tolerance, though it may occur in isolation, with such persons having a normal response to a glucose tolerance test.
Signs and symptoms
Impaired fasting glucose is often without any signs or symptoms, other than higher than normal glucose levels being detected in an individuals fasting blood sample. There may be signs and symptoms associated with elevated blood glucose, though these are likely to be minor, with significant symptoms suggestive of complete progression to type 2 diabetes. Such symptoms include:
Increased thirst
Increased urination, especially waking up in the night to urinate
Tiredness and fatigue
Blurred vision
Slow healing of wounds
Altered sensation, such as numbness or tingling, particularly of the hands and feet
Recurrent, and difficult to clear infections, particularly of the urinary tract
Risk factors
As impaired fasting glucose is considered a precursor condition for type 2 diabetes, it shares the same environmental and genetic risk factors.
Diagnosis
Different organisations use slightly differing levels before classifying a persons fasting blood glucose as "impaired", with the American Diabetes Association using a lower cutoff in its criteria than the World Health Organization. The upper limits remain the same, as fasting levels above this are almost universally accepted as indicative of full diabetes:
WHO criteria: fasting plasma glucose level from 6.1 mmol/L (110 mg/dL) to 6.9 mmol/L (125 mg/dL).
ADA criteria: fasting plasma glucose level from 5.6 mmol/L (100 mg/dL) to 6.9 mmol/L (125 mg/dL).
Prevention
The guidelines for preventing impaired fasting glucose are the same as those given for preventing type 2 diabetes in general. If these are adhered to, the progression to clinical diabetes can be slowed or halted. In some cases, a complete reversal of IFG can be achieved. Certain risk factors, such as being of Afro-Caribbean or South Asian ethnicity, as well as increasing age, are unavoidable, and such individuals may be advised to follow these guidelines, as well as monitor their blood glucose levels, more closely.
Management
References
== External links == |
Alcoholic polyneuropathy | Alcoholic polyneuropathy is a neurological disorder in which peripheral nerves throughout the body malfunction simultaneously. It is defined by axonal degeneration in neurons of both the sensory and motor systems and initially occurs at the distal ends of the longest axons in the body. This nerve damage causes an individual to experience pain and motor weakness, first in the feet and hands and then progressing centrally. Alcoholic polyneuropathy is caused primarily by chronic alcoholism; however, vitamin deficiencies are also known to contribute to its development. This disease typically occurs in chronic alcoholics who have some sort of nutritional deficiency. Treatment may involve nutritional supplementation, pain management, and abstaining from alcohol.
Signs and symptoms
An early warning sign (prodrome) of the possibility of developing alcoholic polyneuropathy, especially in a chronic alcoholic, would be weight loss because this usually signifies a nutritional deficiency that can lead to the development of the disease.Alcoholic polyneuropathy usually has a gradual onset over months or even years, although axonal degeneration often begins before an individual experiences any symptoms.The disease typically involves sensory issues and motor loss, as well as painful physical perceptions, though all sensory modalities may be involved.
Symptoms that affect the sensory and motor systems seem to develop symmetrically. For example, if the right foot is affected, the left foot is affected simultaneously or soon becomes affected.
In most cases, the legs are affected first, followed by the arms. The hands usually become involved when the symptoms reach above the ankle. This is called a stocking-and-glove pattern of sensory disturbances.
Sensory
Common manifestations of sensory issues include numbness or painful sensations in the arms and legs, abnormal sensations like "pins and needles," and heat intolerance. Pain experienced by individuals depends on the severity of the polyneuropathy. It may be dull and constant in some individuals while being sharp and lancinating in others. In many subjects, tenderness is seen upon the palpitation of muscles in the feet and legs. Certain people may also feel cramping sensations in the muscles affected and others say there is a burning sensation in their feet and calves.
Motor
Sensory symptoms are gradually followed by motor symptoms. Motor symptoms may include muscle cramps and weakness, erectile dysfunction in men, problems urinating, constipation, and diarrhea. Individuals also may experience muscle wasting and decreased or absent deep tendon reflexes. Some people may experience frequent falls and gait unsteadiness due to ataxia. This ataxia may be caused by cerebellar degeneration, sensory ataxia, or distal muscle weakness. Over time, alcoholic polyneuropathy may also cause difficulty swallowing (dysphagia), speech impairment (disarthria), muscle spasms, and muscle atrophy.In addition to alcoholic polyneuropathy, the individual may also show other related disorders such as Wernicke–Korsakoff syndrome and cerebellar degeneration that result from alcoholism-related nutritional disorders.
Severity
Polyneuropathy spans a large range of severity. Some cases are seemingly asymptomatic and may only be recognized on careful examination. The most severe cases may cause profound physical disability.
Causes
The general cause of this disease appears to be prolonged and heavy consumption of alcohol accompanied by a nutritional deficiency. However, there is ongoing debate over the active mechanisms, including whether the main cause is the direct toxic effect of alcohol itself or whether the disease is a result of alcoholism-related malnutrition. A 2019 metastudy found that the relationship between ethanol toxicity and neuropathy remained unproven.
Effects due to nutritional deficiency
Frequently alcoholics have disrupted social links in their lives and have an irregular lifestyle. This may cause an alcoholic to change their eating habits including more missed meals and a poor dietary balance. Alcoholism may also result in loss of appetite, alcoholic gastritis, and vomiting, which decrease food intake. Alcohol abuse damages the lining of the gastrointestinal system and reduces absorption of nutrients that are taken in. The combination of all of them may result in a nutritional deficiency that is linked to the development of alcoholic polyneuropathy.There is evidence that providing individuals with adequate vitamins improves symptoms despite continued alcohol intake, indicating that vitamin deficiency may be a major factor in the development and progression of alcoholic polyneuropathy. In experimental models of alcoholic polyneuropathy utilizing rats and monkeys no convincing evidence was found that proper nutritional intake along with alcohol results in polyneuropathy.
In most cases, individuals with alcoholic polyneuropathy have some degree of nutritional deficiency. Alcohol, a carbohydrate, increases the metabolic demand for thiamine (vitamin B1) because of its role in the metabolism of glucose. Thiamine levels are usually low in alcoholics due to their decreased nutritional intake. In addition, alcohol interferes with intestinal absorption of thiamine, thereby further decreasing thiamine levels in the body. Thiamine is important in three reactions in the metabolism of glucose: the decarboxylation of pyruvic acid, d-ketoglutaric acid, and transketolase. A lack of thiamine in the cells may therefore prevent neurons from maintaining necessary adenosine triphosphate (ATP) levels as a result of impaired glycolysis. Thiamine deficiency alone could explain the impaired nerve conduction in those with alcoholic polyneuropathy, but other factors likely play a part.The malnutrition many alcoholics experience deprives them of important cofactors for the oxidative metabolism of glucose. Neural tissues depend on this process for energy, and disruption of the cycle would impair cell growth and function. Schwann cells produce myelin that wraps around the sensory and motor nerve axons to enhance action potential conduction in the periphery. An energy deficiency in Schwann cells would account for the disappearance of myelin on peripheral nerves, which may result in damage to axons or loss of nerve function altogether. In peripheral nerves, oxidative enzyme activity is most concentrated around the nodes of Ranvier, making these locations most vulnerable to cofactor deprivation. Lacking essential cofactors reduces myelin impedance, increases current leakage, and slows signal transmission. Disruptions in conductance first affect the peripheral ends of the longest and largest peripheral nerve fibers because they suffer most from decreased action potential propagation. Thus, neural deterioration occurs in an accelerating cycle: myelin damage reduces conductance, and reduced conductance contributes to myelin degradation. The slowed conduction of action potentials in axons causes segmental demyelination extending proximally; this is also known as retrograde degeneration.Many of the studies conducted that observe alcoholic polyneuropathy in patients are often criticized for their criteria used to assess nutritional deficiency in the subjects because they may not have completely ruled out the possibility of a nutritional deficiency in the genesis of the polyneuropathy. Many researchers favor the nutritional origin of this disease, but the possibility of alcohol having a toxic effect on the peripheral nerves has not been completely ruled out.
Effects due to alcohol ingestion
The consumption of alcohol may lead to the buildup of certain toxins in the body. For example, in the process of breaking down alcohol, the body produces acetaldehyde, which can accumulate to toxic levels in alcoholics. This suggests that there is a possibility ethanol (or its metabolites) may cause alcoholic polyneuropathy. There is evidence that polyneuropathy is also prevalent in well nourished alcoholics, supporting the idea that there is a direct toxic effect of alcohol.The metabolic effects of liver damage associated with alcoholism may also contribute to the development of alcoholic polyneuropathy. Normal products of the liver, such as lipoic acid, may be deficient in alcoholics. This deficiency would also disrupt glycolysis and alter metabolism, transport, storage, and activation of essential nutrients.Acetaldehyde is toxic to peripheral nerves. There are increased levels of acetaldehyde produced during ethanol metabolism. If the acetaldehyde is not metabolized quickly the nerves may be affected by the accumulation of acetaldehyde to toxic levels.
Pathophysiology
The pathophysiology of alcoholic polyneuropathy is unclear.
Diagnosis
Alcoholic polyneuropathy is very similar to other axonal degenerative polyneuropathies and therefore can be difficult to diagnose. When alcoholics have sensorimotor polyneuropathy as well as a nutritional deficiency, a diagnosis of alcoholic polyneuropathy is often reached.To confirm the diagnosis, a physician must rule out other causes of similar clinical syndromes. Other neuropathies can be differentiated on the basis of typical clinical or laboratory features. Differential diagnoses to alcoholic polyneuropathy include amyotrophic lateral sclerosis, beriberi, Charcot-Marie-Tooth disease, diabetic lumbosacral plexopathy, Guillain Barre Syndrome, diabetic neuropathy, mononeuritis multiplex and post-polio syndrome.To clarify the diagnosis, medical workup most commonly involves laboratory tests, though, in some cases, imaging, nerve conduction studies, electromyography, and vibrometer testing may also be used.A number of tests may be used to rule out other causes of peripheral neuropathy. One of the first presenting symptoms of diabetes mellitus may be peripheral neuropathy, and hemoglobin A1C can be used to estimate average blood glucose levels. Elevated blood creatinine levels may indicate chronic kidney disease and may also be a cause of peripheral neuropathy. A heavy metal toxicity screen should also be used to exclude lead toxicity as a cause of neuropathy.Alcoholism is normally associated with nutritional deficiencies, which may contribute to the development of alcoholic polyneuropathy. Thiamine, vitamin B-12, and folic acid are vitamins that play an essential role in the peripheral and central nervous system and should be among the first analyzed in laboratory tests. It has been difficult to assess thiamine status in individuals due to difficulties in developing a method to directly assay thiamine in the blood and urine. A liver function test may also be ordered, as alcoholic consumption may cause an increase in liver enzyme levels.
Management
Although there is no known cure for alcoholic polyneuropathy, there are a number of treatments that can control symptoms and promote independence. Physical therapy is beneficial for strength training of weakened muscles, as well as for gait and balance training.
Nutrition
To best manage symptoms, refraining from consuming alcohol is essential. Abstinence from alcohol encourages proper diet and helps prevent progression or recurrence of the neuropathy. Once an individual stops consuming alcohol it is important to make sure they understand that substantial recovery usually isnt seen for a few months. Some subjective improvement may appear right away, but this is usually due to the overall benefits of alcohol detoxification. If alcohol consumption continues, vitamin supplementation alone is not enough to improve the symptoms of most individuals.Nutritional therapy with parenteral multivitamins is beneficial to implement until the person can maintain adequate nutritional intake. Treatments also include vitamin supplementation (especially thiamine). In more severe cases of nutritional deficiency 320 mg/day of benfotiamine for 4 weeks followed by 120 mg/day for 4 more weeks may be prescribed in an effort to return thiamine levels to normal.
Pain
Painful dysesthesias caused by alcoholic polyneuropathy can be treated by using gabapentin or amitriptyline in combination with over-the-counter pain medications, such as aspirin, ibuprofen, or acetaminophen. Tricyclic antidepressants such as amitriptyline, or carbamazepine may help stabbing pains and have central and peripheral anticholinergic and sedative effects. These agents have central effects on pain transmission and block the active reuptake of norepinephrine and serotonin.Anticonvulsant drugs like gabapentin or pregabalin block the active reuptake of norepinephrine and serotonin and have properties that relieve neuropathic pain. However, these medications take a few weeks to become effective and are rarely used in the treatment of acute pain.Topical analgesics like capsaicin may also relieve minor aches and pains of muscles and joints.
Prognosis
Alcoholic polyneuropathy is not life-threatening but may significantly affect ones quality of life. Effects of the disease range from mild discomfort to severe disability.It is difficult to assess the prognosis of a patient because it is hard to convince chronic alcoholics to abstain from drinking alcohol completely. It has been shown that a good prognosis may be given for mild neuropathy if the alcoholic has abstained from drinking for 3–5 years.
Early stage
During the early stages of the disease the damage appears reversible when people take adequate amounts of vitamins, such as thiamine. If the polyneuropathy is mild, the individual normally experiences a significant improvement and symptoms may be eliminated within weeks to months after proper nutrition is established. When those people diagnosed with alcohol polyneuropathy experience a recovery, it is presumed to result from regeneration and collateral sprouting of the damaged axons.
Progressed disease
As the disease progresses, the damage may become permanent. In severe cases of thiamine deficiency, a few of the positive symptoms (including neuropathic pain) may persist indefinitely. Even after the restoration of a balanced nutritional intake, those patients with severe or chronic polyneuropathy may experience lifelong residual symptoms.
Epidemiology
In 2020 the NIH quoted an estimate that in the United States 25% to 66% of chronic alcohol users experience some form of neuropathy. The rate of incidence of alcoholic polyneuropathy involving sensory and motor polyneuropathy has been stated as from 10% to 50% of alcoholics depending on the subject selection and diagnostic criteria. If electrodiagnostic criteria are used, alcoholic polyneuropathy may be found in up to 90% of individuals being assessed.The distribution and severity of the disease depends on regional dietary habits, individual drinking habits, as well as an individuals genetics. Large studies have been conducted and show that alcoholic polyneuropathy severity and incidence correlates best with the total lifetime consumption of alcohol. Factors such as nutritional intake, age, or other medical conditions are correlate in lesser degrees. For unknown reasons, alcoholic polyneuropathy has a high incidence in women.Certain alcoholic beverages can also contain congeners that may also be bioactive; therefore, the consumption of varying alcohol beverages may result in different health consequences. An individuals nutritional intake also plays a role in the development of this disease. Depending on the specific dietary habits, they may have a deficiency of one or more of the following: thiamine (vitamin B1), pyridoxine (vitamin B6), pantothenic acid and biotin, vitamin B12, folic acid, niacin (vitamin B3), and vitamin A.
Acetaldehyde
It is also thought there is perhaps a genetic predisposition for some alcoholics that results in increased frequency of alcoholic polyneuropathy in certain ethnic groups. During the bodys processing of alcohol, ethanol is oxidized to acetaldehyde mainly by alcohol dehydrogenase; acetaldehyde is then oxidized to acetate mainly by aldehyde dehydrogenase (ALDH). ALDH2 is an isozyme of ALDH and ALDH2 has a polymorphism (ALDH2*2, Glu487Lys) that makes ADLH2 inactive; this allele is more prevalent among Southeast and East Asians and results in a failure to quickly metabolize acetaldehyde. The neurotoxicity resulting from the accumulation of acetaldehyde may play a role in the pathogenesis of alcoholic polyneuropathy.
History
The first description of symptoms associated with alcoholic polyneuropathy were recorded by John C. Lettsome in 1787 when he noted hyperesthesia and paralysis in legs more than arms of patients. Jackson has also been credited with describing polyneuropathy in chronic alcoholics in 1822. The clinical title of alcoholic polyneuropathy was widely recognized by the late nineteenth century. It was thought that the polyneuropathy was a direct result of the toxic effect alcohol had on peripheral nerves when used excessively. In 1928, George C. Shattuck argued that the polyneuropathy resulted from a vitamin B deficiency commonly found in alcoholics and he claimed that alcoholic polyneuropathy should be related to beriberi. This debate continues today over what exactly causes this disease, some argue it is just the alcohol toxicity, others claim the vitamin deficiencies are to blame and still others say it is some combination of the two.
Research directions
In 2001 research directions included the effect that an alcoholics consumption and choice of alcoholic beverage might have on their development of alcoholic polyneuropathy. Some beverages may include more nutrients than others (such as thiamine), but the effects of this with regards to helping with a nutritional deficiency in alcoholics is yet unknown.Research also continued on reasons for the development of alcoholic polyneuropathy. Some argue it is a direct result of alcohols toxic effect on the nerves, but others say factors such as a nutritional deficiency or chronic liver disease may play a role in the development as well. Multiple mechanisms may be present.
References
== External links == |
Rectovaginal fistula | A rectovaginal fistula is a medical condition where there is a fistula or abnormal connection between the rectum and the vagina.Rectovaginal fistulae may be extremely debilitating. If the opening between the rectum and vagina is wide it will allow both flatulence and feces to escape through the vagina, leading to fecal incontinence. There is an association with recurrent urinary and vaginal infections. The fistula may also connect the rectum and urethra, which is called recto-urethral fistula. Either conditions can lead to labial fusion. This type of fistula can cause pediatricians to misdiagnose imperforate anus. The severity of the symptoms will depend on the size of fistula. Most often, it appears after about one week or so after delivery.
Causes
Rectovaginal fistulas are often the result of trauma during childbirth (in which case it is known as obstetric fistula), with increased risk associated with significant lacerations or interventions are used such as episiotomy or operative (forceps/vacuum extraction) deliveries or in situations where there is inadequate health care, such as in some developing countries. Rectovaginal fistula is said to be known as the leading cause in maternal death in developing countries. Risk factors include prolonged labour, difficult instrumental delivery and paramedian episiotomy. Rates in Eritrea are estimated as high as 350 per 100,000 vaginal births. Fistulas can also develop as a result of physical trauma to either the vagina or anus, including from rape. Women with rectovaginal fistulae are often stigmatized in developing countries, and become outcasts.Rectovaginal fistula can also be a symptom of various diseases, including infection by lymphogranuloma venereum, or the unintended result of surgery, such as episiotomy or sex reassignment surgery. They may present as a complication of vaginal surgery, including vaginal hysterectomy. They are a recognized presentation of rectal carcinoma or rarely diverticular disease of the bowel or Crohns disease. They are seen rarely after radiotherapy treatment for cervical cancer.
Treatment
After diagnosing rectovaginal fistula, it is best to wait for around three months to allow the inflammation to subside. For low fistulae, a vaginal approach is best, while an abdominal repair would be necessary for a high fistula at the posterior fornix.A circular incision is made around the fistula and vagina is separated from the underlying rectum with a sharp circumferential dissection. The entire fistulous tract, along with a small rim of rectal mucosa is incised. The rectal wall is then closed extramucosally.Most rectovaginal fistulas will need surgery to fix. Medications such as antibiotics and Infliximab might be prescribed to help close the rectovaginal fistula or prepare for surgery.
References
External links
Rectovaginal fistula at Curlie |
Familial eosinophilia | Familial eosinophilia is a rare congenital disorder characterized by the presence of sustained elevations in blood eosinophil levels that reach ranges diagnostic of eosinophilia (i.e. 500-1500/microliter) or, far more commonly, hypereosinophilia (i.e. >1,500/microliter). Although high eosinophil levels are associated with certain diseases and thought to contribute to the tissue destruction found in many other eosinophilia-related diseases (see clonal eosinophilia), clinical manifestations and tissue destruction related to the eosinophilia in familial eosinophilia is uncommon: this genetic disease typically has a benign phenotype and course compared to other congenital and acquired eosinophilic diseases.
Presentation
Individuals with familial eosinophilia exhibit hypereosinophilia presumably from birth (earliest documentation at 4 months of age). Elevated blood levels of eosinophils are remarkably stable over time in affected family members. These individuals are generally detected on routine blood cell counts and at the time of diagnosis present without symptoms or at least no symptoms related to their eosinophilia. Their blood cell counts are typically normal except for eosinophil numbers which range between ~2000 and 5000 cells/microliter (normal <450 cells/microliter). Peripheral blood smears revealed that eosinophils showed normal morphology, a finding distinctly different from many other types of hypereosinophilia in which blood smears commonly shown immature blood cells and eosinophils showing distinctly abnormal areas of cytoplasmic clearing. Ultrastructural changes characteristic of eosinophil activation (e.g. piecemeal degranulation of eosinophils and increases in the number of their lipid bodies), other eosinophil activation markers (e.g. elevated serum levels of eosinophil-derived neurotoxin and major basic protein), and increased expression of a marker for T cell activation, interleukin-2 receptor alpha chain, are absent in individuals with familial eosinophilia but common in other types of hypereosinophilia.
Accompanying diseases
In spite of being generally considered a benign expression of eosinophilia, isolated cases of family members with familial eosinophilia have been afflicted with tissue dysfunctions that are often associated with more pathological forms of eosinophilia. These dysfunctions include fatal endomyocardial fibrosis, valvular heart disease, and diminished motor and/or sensory function in skin areas served by peripheral nerves. Three patients with heart tissue for pathology examination had eosinophilic infiltration or fibrosis in their hearts endomyocardium. One patient who died suddenly had autopsy findings of eosinophilic infiltration not only in the heart but also in lungs, gastrointestinal tract, and meninges. It is unclear whether these tissue damages were due to primary eosinophil infiltrations or eosinophil infiltrations secondary to other causes.
Genetics
Familial eosinophilia is an autosomal dominant disorder. Genetic linkage gene mapping family studies localize the gene responsible for this disease to chromosome 5 at position q31-q33, between markers D5S642 and D5S816. Studies on other disorders associated with high levels of blood eosinophils (e.g. childhood asthma, schistosomiasis) have likewise linked eosinophilia to the q31-q33 area of chromosome 5. The 5q31-q33 region contains a cytokine gene cluster that includes genes for Interleukin 3, interleukin 5, and granulocyte-macrophage colony-stimulating factor. Each of these genes functions to promote the proliferation and differentiation of eosinophil precursor cells. Nonetheless, no gene polymorphisms were found within the promoters, exons, or introns of these 3 genes or in the regions IL-3/GM-CSF enhancer. In addition to these studies, 8 affected members of a family with familial eosinophilia had peripheral blood or bone marrow cells that carried the same chromosome abnormality, a pericentric inversion of chromosome 10, inv (10) (p11.2q21.2). The meaning and relationship, if any, of this inversion to familial eosinophilia is unclear.
Pathophysiology
Earlier studies found no evidence of abnormal blood levels of interleukin 5, interleukin 3, or granulocyte-macrophage colony stimulating factor. A more recent study used a more sensitive assay for interleukin 5 to compare members of a single extended family with some members lacking the disorder. The study found that members with the disorder had: a) peripheral blood mononuclear cells as well as T helper cells (major physiological source of interleukin 5), CD8+ cells, CD14+ cells, and CD19+ cells that expressed high levels of messenger RNA for interleukin 5 while their peripheral blood mononuclear cells expressed normal levels of messenger RNA for RAD50, a gene in close proximity to IL-5; b) elevated serum levels of interleukin 5 as well as soluble Interleukin 5 receptor alpha subunit; and c) innate lymphoid cells (also major physiological sources of interleukin 5) that produced increased amounts of interleukin 5 in response to stimulation. A second family with asymptomatic eosinophilia over three generations likewise exhibited increased production of interleukin 5. These studies suggest that the dis-regulated overproduction of interleukin 5 by blood mononuclear cells is an underlying cause of the eosinophilia found in at least some families with this disorder.
Diagnosis
The diagnosis of familial eosinophilia rest upon a) familial clustering of the disorder; b) exclusion of "family acquired eosinophilia" (i.e. eosinophilia due to chronic parasite or other infestations that afflict multiple members of a family); c) lack of eosinophil-induced tissue destruction such as that which occurs in the hypereosinophilic syndrome; d) absence of signs or symptoms of other hereditary eosinophilias (e.g. hyperimmunoglobulin E syndrome, Omenn syndrome), Wiskott–Aldrich syndrome, and numerous other primary immunodeficiency syndromes); and d) lack of evidence for reactive eosinophilias (e.g. allergy-related), neoplastic eosinophilias (e.g. eosinophilic leukemia, clonal eosinophilia), or eosinophila associated with various hematological and non-hematological malignancies as outlined in causes of eosinophilia.
Treatment
Since longitudinal data, including eosinophil counts obtained over a 20- to 30-year periods in some family members, show remarkable stability in the absolute eosinophil count with no evidence of disease attributable to eosinophil-related tissue injury, therapy to lower eosinophil counts such as corticosteroids, tyrosine kinase inhibitors, and antibodies directed against interleukin 5 have in general not been used to treat familial eosinophilia. One patient with severe heart damage was treated with a corticosteroid but soon thereafter died. Familial eosinophilia unassociated with possible eosinophil-related tissue injuries may not require drug treatment, those cases with such tissue injuries, it is suggested, should be considered for such interventions. In all cases, however, regular follow-up of the disorder is strongly recommended.
== References == |
Mallet finger | A mallet finger, also known as hammer finger or PLF finger or Hannan finger, is an extensor tendon injury at the farthest away finger joint. This results in the inability to extend the finger tip without pushing it. There is generally pain and bruising at the back side of the farthest away finger joint.A mallet finger usually results from overbending of the finger tip. Typically this occurs when a ball hits an outstretched finger and jams it. This results in either a tear of the tendon or the tendon pulling off a bit of bone. The diagnosis is generally based on symptoms and supported by X-rays.During injury, this tendon is torn from its attachment site on the bone (called a tendinous mallet finger). But, there are also cases whereby the force of impact causes a small fracture at the base of bone where the tendon is attached to (called a bony mallet finger). In both cases, the tendon is no longer attached to the last bone of the digit and is thus unable to pull the end joint into a straightened position, resulting in a fingertip that droops.Treatment is generally with a splint that holds the fingertip straight continuously for 8 weeks. The middle joint is allowed to move. This should be begun within a week of the injury. If the finger is bent during these weeks, healing may take longer. If a large piece of bone has been torn off surgery may be recommended. Without proper treatment a permanent deformity of the finger may occur.
Diagnosis
The diagnosis is generally based on symptoms and supported by X-rays. The injury can be accompanied by swelling and ecchymosis.
Treatment
The management goal is to restore extension of the joint. Treatment is generally with a splint that holds the first joint of the finger straight continuously for 8 weeks. This should begin within a week of the injury. The splint may be worn just at night for a few additional weeks after this. The splint acts to immobilize flexing of the joint.
Surgery generally does not improve outcomes. It may be required if the finger cannot be straightened by pushing on it or the break has pulled off more than 30% of the joint surface. Surgery may be preferred over the use of a split if a child is non-compliant. If the problem has been present a long time surgery may also be required. An open fracture may be another reason. Surgery will put the finger in a neutral position and drill a wire through the distal interphalangeal joint (DIP) to the proximal interphalangeal joint (PIP), forcing immobilization.
See also
Busch fracture
Jersey finger
References
== External links == |
Congenital heart block | The congenital heart block (CHB) is the heart block that is diagnosed in fetus (in utero) or within the first 28 days after birth (neonatal period), some studies also include the diagnosis during early childhood to the definition of CHB. It refers to the disorder in the electrical conduction system within the heart muscle, which leads to the failure in pumping the blood efficiently into the aorta and the pulmonary trunk. The result of CHB can be first, second, or third-degree (complete) atrioventricular block (a block in the atrioventricular node) in which no electric signals move from the atrium to the ventriclesThe congenital heart block is a rare disease that affects around 1 child in every 15,000–20,000 births. However, its high mortality (which can be as high as 85% in some severe cases) makes the early diagnosis and intervention very important. CHB can be isolated, where the fetus does not suffer from any other problems, or it can be a result of other diseases either in the child or in the mother.In most cases, the congenital heart block is associated with other diseases, and therefore, the symptoms vary a lot between patients. However, low heart rate is usually the main clinical presentation that leads to the diagnosis. Also, the treatment varies as well due to the associated diseases and it can be non-invasive (medications given to the pregnant woman or to the child), or a surgery in some cases when the CHB is resulted from anatomical disorders in the heart.
Presentation
The symptoms of the congenital heart block can vary due to the underlying problems that associate / lead to the CHB, and the features of CHB reflects the other manifestations of these diseases.Bradycardia is usually the first symptom of CHB to be detected in utero. Due to the block in the atrioventricular node, less electric signals move from the sinoatrial node to the bundle of his and its right and left branches, leading to a lower heart rate. The atrioventricular block can be first degree or much more severe like a complete atrioventricular block (third degree). In addition, several changes in the ECG can be detected.Other manifestations of the congenital heart block can be related to the impact of the maternal autoantibodies in the autoimmune-mediated CHB. Fibrosis of the myocardium (Endocardial fibroelastosis) (EFE) is the obvious one and it occurs due to the damage caused by the maternal autoantibodies to the cardiac tissue of the fetus, and can lead to death in some cases. However, it is not a common feature of CHB.Another rare symptom that might accompany the autoimmune CHB is the disorder in the valvular function, and this happens due to the damage in the papillary muscles as a result of the maternal autoantibodies.
Causes
In some cases the reason behind CHB remains unknown but in the great majority of affected kids, this disease is associated with the transference of autoantibodies from the mother during gestation or with major cardiac structural abnormalities that lead to a disturbance in the conducting signals in the atrioventricular node. Also, in some rare cases, the congenital heart block was linked with viral infections or treatment with specific medications.
Maternal autoimmune disease
In the autoimmune-mediated congenital heart block, autoantibodies are passively transferred through the placenta during gestation. The mother might be asymptomatic during or after pregnancy but she is usually positive to anti-Ro\SSA or anti-La\SSB antibodies. In this case, the fetuss heart is normally developed and shows no structural malformations. Just like other autoimmune diseases, the autoimmune CHB shows signs of damage resulted from the autoantibodies attacking the normal tissue of the body, inflammation and fibrosis in the fetal heart tissue are the most common ones, mainly in the atrioventricular node. These antibodies lead to irreversible injuries in the atrioventricular node which heavily compromise the efficiency of the electrical conduction system, and this results in around 18% mortality rate and 70% of the live-born kids will need early pacemaker implantation.
Anti-Ro\SSA autoantibody
This autoantibody is found in the serum of the majority of kids with autoimmune CHB, and therefore it is the one mostly linked with this disease. It attacks the proteins Ro52 and Ro60 in the antigen Ro\SSA in the fetal heart tissue.
Anti-La\SSB autoantibody
This antibody attacks the ribonucleoprotein La48 on the surface of the fetal cardiomyocytes, the links between this autoantibody and autoimmune CHB are less strong than the anti-Ro autoantibody and it usually accompanies it in the majority of cases.Although the autoimmune CHB has a relatively high mortality and morbidity rates, the chance of kids from -mothers positive to anti-Ro\SSA and/or anti-La\SSB antibodies- to suffer from CHB is only around 1-5%, which suggests the existence of other factors to influence the disease such as genetic and environmental factors.
Other autoantibodies
Several autoantibodies were suggested to have links with the autoimmune CHB, mainly the ones associated with the different autoimmune diseases that are common among women (such as the antibodies associated with Systemic lupus erythematosus (SLE), Rheumatoid arthritis, Progressive systemic sclerosis (PSS), and Mixed connective tissue disease). However, the role of these autoantibodies was not studied comprehensively.Also, some antigens of the fetal heart tissue (apart from the "Ro" and the "La") were studied, but no clear link with the autoimmune CHB was proven.
Congenital cardiac structural abnormalities
The presence of a cardiac structural abnormality is a major determination of the outcome of CHB. Its existence affects the conduction system of the heart and increases the mortality rate and the need for pace-maker implantation.The cardiac structural diseases that are usually associated with the congenital heart block include the left atrial isomerism with or without atrioventricular septal defect. In addition, levo transpositions of the great arteries can accompany CHB but this is less common than the first one.These developmental abnormalities can impair the conduction system of the heart by disrupting its anatomical structure.
Diagnosis
There is a difference in diagnosis between low risk pregnancies where mothers do not have (or are not aware of) any autoimmune disease, and the high risk ones where mothers are known to have a specific autoimmune disease and / or are positive to anti Ro/La autoanitbodies and / or had a CHB-affected pregnancy previously.In low risk pregnancies, testing the mothers serum is not part of the routine prenatal tests. Therefore, the congenital heart block is usually diagnosed during a routine obstetrical ultra sound. The first symptom in most cases is a slow heart rate which can be detected using fetal echocardiogram and Doppler ultra sound techniques between the weeks 18 - 30. The Doppler is very important to assess the level of AV block as well as to check for other cardiac structural abnormalities that might be associated with CHB such as left atrial isomerism, valvular damages and big arteries inversion, while the echocardiogram is useful to detect other complications such as the hydrops fetalis. In the absence of cardiac structural diseases, the second step to confirm the diagnosis is to test the serum of the mother for anti Ro/La autoantibodies using the enzyme-linked immunosorbent assay (ELISA).In high risk pregnancies, the diagnosis is relatively easier as fetal and maternal screenings are part of the routine monitoring of the pregnancy.
Screening
Although the chance of having kids with CHB in anti Ro/La positive mothers is relatively low (1-5%), it is recommended that all mothers with autoimmune disease to be screened and seek consultation when decide to get pregnant.For mothers with at least one CHB-affected pregnancy, with 16 - 18% recurrence chance for the directly following pregnancy and an overall 9% chance in following ones, monitoring both the mother and the fetus is crucial.
Treatment
Due to the rarity of this disease, there is a lack of comprehensive and high quality research about the different treatment options, and therefore, no specific treatment plan is followed globally. However, some studies have attempted to outline the most widely accepted approaches in dealing with CHB.
Fluorinated steroids
There is no agreement on using fluorinated steroids in treating CHB, and the results of the different studies are contradictory. These steroids (such as dexamethasone) are used when the disease is diagnosed in utero as they can cross the placenta without being deactivated. The main goal of using corticosteroids is to mitigate the inflammation by decreasing the amount of anti Ro/La autoantibodies in the fetal serum. Therefore, they are used in the autoimmune-mediated CHB. Both the mother and the fetus might suffer from their side effects which can include growth problems and adrenal insufficiency.
Beta-adrenergic agonist
Trebutaline and Sulbutamol are among the medications that have been used to treat CHB. They are used mainly to increase the heart rate in fetuses suffering from bradycardia. Although they showed positive results, some patients showed intolerance to their side effects.
Plasmapheresis
Plasma exchange in women positive to anti Ro/La autoantibodies has not been studied thoroughly, but it is suggested to have and effect on the titer of the antibodies in the mothers serum and therefore might have a preventive role.
Intravenous immunoglobulin
Using intravenous immunoglobulin showed some promising results in decreasing the possibility of having CHBs complications such as EFE and cardiomyopathy.
Hydroxychloroquine
Hydroxychloroquine is relatively new approach, but it showed promising results in preventing the inflammation and other injuries result from it such as fibrosis.Apart from these medications, a pace maker might be needed in around two thirds of the cases, and a procedure might be required when the heart has structural abnormalities.
Outcomes
The outcome of the congenital heart block varies a lot due to several factors, such as the associated diseases, severity of the atrioventricular block, maternal age...etc.
In terms of the severity of the AV block, newborn kids with heart rate lower than 55 bpm have a negative outcome and higher chance to need pace-maker implantation, as well as kids with symptomatic bradycardia such as lower tolerance of exercises.Isolated CHB has a better prognosis than the one associated with other disorders, the presence of congenital cardiac abnormalities increases the mortality rate. Also, kids presented with hydrops fetalis and / or EFE and / or cardiomyopathy have poor outcome.Some studies showed a genetic contribution to the autoimmune CHB.Among anti Ro/La positive women, older ones have higher possibility of having kids with heart block.Mortality rate in CHB increases with earlier deliveries.Kids with congenital heart block have higher chance to face health-related problems (such as infections) than other kids.
Epidemiology
The congenital heart block occurs in 1 child in every 15,000 to 20,000 births.More than 90% of the cases are associated with autoimmune disease and transference of maternal autoantibodies.Without considering the gender, the age of diagnosis or the associated diseases, mortality rate is around 20%. The majority of CHB-related deaths occur in the first 3 months after birth followed by fetal death, and it is less common to occur after the third month of age.Mortality rate is very high when the disease is diagnosed prenatally, and declines dramatically with older diagnosis ages.Around 60% - 70% of the patients will need pace-maker implantation regardless of the age of diagnosis.The disease seems to affect both males and females equally.The survival rate is heavily affected by the associated diseases, and it is higher in autoimmune-mediated CHB patients compared to CHB patients with congenital cardiac structural problems.Recurrence rate: mothers who had pregnancies associated with CHB, have a 16 - 18% chance of having kids with heart block in the following pregnancy.A study in the United States showed that the vast majority of the affected mothers are of a Caucasian ethnicity, despite the fact that Systemic Lupus Erythematosus (SLE) is more common among minorities.
== References == |
Large plaque parapsoriasis | Large plaque parapsoriasis are skin lesions that may be included in the modern scheme of cutaneous conditions described as parapsoriasis. These lesions, called plaques, may be irregularly round-shaped to oval and are 10 cm (4 in) or larger in diameter. They can be very thin plaques that are asymptomatic or mildly pruritic. Large-plaque parapsoriasis is a common associate of retiform parapsoriasis, can be accompanied by poikiloderma vasculare atrophicans, and can in rare occasions be a precursor to cutaneous T-cell lymphoma.
Cause
Diagnosis
Treatment
Parapsoriasis treatment consists primarily of light therapy (more specifically PUVA therapy or UVB therapy) possibly in combination with topical steroids.
Large plaque parapsoriasis is usually a chronic condition that needs long-term treatment.
See also
List of cutaneous conditions
Mycosis fungoides
References
== External links == |
Hyponatremia | Hyponatremia is a low sodium concentration in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be absent, mild or severe. Mild symptoms include a decreased ability to think, headaches, nausea, and poor balance. Severe symptoms include confusion, seizures, and coma.The causes of hyponatremia are typically classified by a persons body fluid status into low volume, normal volume, or high volume. Low volume hyponatremia can occur from diarrhea, vomiting, diuretics, and sweating. Normal volume hyponatremia is divided into cases with dilute urine and concentrated urine. Cases in which the urine is dilute include adrenal insufficiency, hypothyroidism, and drinking too much water or too much beer. Cases in which the urine is concentrated include syndrome of inappropriate antidiuretic hormone secretion (SIADH). High volume hyponatremia can occur from heart failure, liver failure, and kidney failure. Conditions that can lead to falsely low sodium measurements include high blood protein levels such as in multiple myeloma, high blood fat levels, and high blood sugar.Treatment is based on the underlying cause. Correcting hyponatremia too quickly can lead to complications. Rapid partial correction with 3% normal saline is only recommended in those with significant symptoms and occasionally those in whom the condition was of rapid onset. Low volume hyponatremia is typically treated with intravenous normal saline. SIADH is typically treated by correcting the underlying cause and with fluid restriction while high volume hyponatremia is typically treated with both fluid restriction and a diet low in salt. Correction should generally be gradual in those in whom the low levels have been present for more than two days.Hyponatremia is the most common type of electrolyte imbalance, and is often found in older adults. It occurs in about 20% of those admitted to hospital and 10% of people during or after an endurance sporting event. Among those in hospital, hyponatremia is associated with an increased risk of death. The economic costs of hyponatremia are estimated at $2.6 billion per annum in the United States.
Signs and symptoms
Signs and symptoms of hyponatremia include nausea and vomiting, headache, short-term memory loss, confusion, lethargy, fatigue, loss of appetite, irritability, muscle weakness, spasms or cramps, seizures, and decreased consciousness or coma. Lower levels of plasma sodium are associated with more severe symptoms. However, mild hyponatremia (plasma sodium levels at 131–135 mmol/L) may be associated with complications and subtle symptoms (for example, increased falls, altered posture and gait, reduced attention, impaired cognition, and possibly higher rates of death).Neurological symptoms typically occur with very low levels of plasma sodium (usually <115 mmol/L). When sodium levels in the blood become very low, water enters the brain cells and causes them to swell (cerebral edema). This results in increased pressure in the skull and causes hyponatremic encephalopathy. As pressure increases in the skull, herniation of the brain can occur, which is a squeezing of the brain across the internal structures of the skull. This can lead to headache, nausea, vomiting, confusion, seizures, brain stem compression and respiratory arrest, and non-cardiogenic accumulation of fluid in the lungs. This is usually fatal if not immediately treated.
Symptom severity depends on how fast and how severe the drop in blood sodium level is. A gradual drop, even to very low levels, may be tolerated well if it occurs over several days or weeks, because of neuronal adaptation. The presence of underlying neurological disease such as a seizure disorder or non-neurological metabolic abnormalities, also affects the severity of neurologic symptoms.
Chronic hyponatremia can lead to such complications as neurological impairments. These neurological impairments most often affect gait (walking) and attention, and can lead to increased reaction time and falls. Hyponatremia, by interfering with bone metabolism, has been linked with a doubled risk of osteoporosis and an increased risk of bone fracture.
Causes
The specific causes of hyponatremia are generally divided into those with low tonicity (lower than normal concentration of solutes), without low tonicity, and falsely low sodiums. Those with low tonicity are then grouped by whether the person has high fluid volume, normal fluid volume, or low fluid volume. Too little sodium in the diet alone is very rarely the cause of hyponatremia.
High volume
Both sodium and water content increase: Increase in sodium content leads to hypervolemia and water content to hyponatremia.
Cirrhosis of the liver
Congestive heart failure
Nephrotic syndrome in the kidneys
Excessive drinking of fluids
Normal volume
There is volume expansion in the body, no edema, but hyponatremia occurs
SIADH (and its many causes)
Hypothyroidism
Not enough ACTH
Beer potomania
Normal physiologic change of pregnancy
Reset osmostat
Low volume
Hypovolemia (extracellular volume loss) is due to total body sodium loss. Hyponatremia is caused by a relatively smaller loss in total body water.
Any cause of hypovolemia such as prolonged vomiting, decreased oral intake, severe diarrhea
Diuretic use (due to the diuretic causing a volume depleted state and thence ADH release, and not a direct result of diuretic-induced urine sodium loss)
Addisons disease and congenital adrenal hyperplasia in which the adrenal glands do not produce enough steroid hormones (combined glucocorticoid and mineralocorticoid deficiency)
Pancreatitis
Prolonged exercise and sweating, combined with drinking water without electrolytes is the cause of exercise-associated hyponatremia (EAH). It is common in marathon runners and participants of other endurance events.
The use of MDMA (ecstasy) can result in hyponatremia.
Medication
Antipsychotics have been reported to cause hyponatremia in a review of medical articles from 1946 to 2016.Available evidence suggests that all classes of psychotropics, i.e., antidepressants, antipsychotics, mood stabilizers, and sedative/hypnotics can lead to hyponatremia. Age is a significant factor for drug induced hyponatremia.
Other causes
Miscellaneous causes that are not included under the above classification scheme include the following:
False or pseudo hyponatremia is caused by a false lab measurement of sodium due to massive increases in blood triglyceride levels or extreme elevation of immunoglobulins as may occur in multiple myeloma.
Hyponatremia with elevated tonicity can occur with high blood sugar, causing an shift of excess free water into the serum.
Pathophysiology
The causes of and treatments for hyponatremia can only be understood by having a grasp of the size of the body fluid compartments and subcompartments and their regulation; how under normal circumstances the body is able to maintain the sodium concentration within a narrow range (homeostasis of body fluid osmolality); conditions can cause that feedback system to malfunction (pathophysiology); and the consequences of the malfunction of that system on the size and solute concentration of the fluid compartments.
Normal homeostasis
There is a hypothalamic-kidney feedback system which normally maintains the concentration of the serum sodium within a narrow range. This system operates as follows: in some of the cells of the hypothalamus, there are osmoreceptors which respond to an elevated serum sodium in body fluids by signalling the posterior pituitary gland to secrete antidiuretic hormone (ADH) (vasopressin). ADH then enters the bloodstream and signals the kidney to bring back sufficient solute-free water from the fluid in the kidney tubules to dilute the serum sodium back to normal, and this turns off the osmoreceptors in the hypothalamus. Also, thirst is stimulated. Normally, when mild hyponatremia begins to occur, that is, the serum sodium begins to fall below 135 mEq/L, there is no secretion of ADH, and the kidney stops returning water to the body from the kidney tubule. Also, no thirst is experienced. These two act in concert to raise the serum sodium to the normal range.
Hyponatremia
Hyponatremia occurs 1) when the hypothalamic-kidney feedback loop is overwhelmed by increased fluid intake, 2) the feedback loop malfunctions such that ADH is always "turned on", 3) the receptors in the kidney are always "open" regardless of there being no signal from ADH to be open; or 4) there is an increased ADH even though there is no normal stimulus (elevated serum sodium) for ADH to be increased.
Hyponatremia occurs in one of two ways: either the osmoreceptor-aquaporin feedback loop is overwhelmed, or it is interrupted. If it is interrupted, it is either related or not related to ADH. If the feedback system is overwhelmed, this is water intoxication with maximally dilute urine and is caused by 1) pathological water drinking (psychogenic polydipsia), 2) beer potomania, 3) overzealous intravenous solute free water infusion, or 4) infantile water intoxication. "Impairment of urine diluting ability related to ADH" occurs in nine situations: 1) arterial volume depletion 2) hemodynamically mediated, 3) congestive heart failure, 4) cirrhosis, 5) nephrosis, 6) spinal cord disease, 7) Addisons disease, 8) cerebral salt wasting, and 9) syndrome of inappropriate antidiuretic hormone secretion (SIADH).
If the feed-back system is normal, but an impairment of urine diluting ability unrelated to ADH occurs, this is 1) oliguric kidney failure, 2) tubular interstitial kidney disease, 3) diuretics, or 4) nephrogenic syndrome of antidiuresis.Sodium is the primary positively charged ion outside of the cell and cannot cross from the interstitial space into the cell. This is because charged sodium ions attract around them up to 25 water molecules, thereby creating a large polar structure too large to pass through the cell membrane: "channels" or "pumps" are required.
Cell swelling also produces activation of volume-regulated anion channels which is related to the release of taurine and glutamate from astrocytes.
Diagnosis
The history, physical exam, and laboratory testing are required to determine the underlying cause of hyponatremia. A blood test demonstrating a serum sodium less than 135 mmol/L is diagnostic for hyponatremia. The history and physical exam are necessary to help determine if the person is hypovolemic, euvolemic, or hypervolemic, which has important implications in determining the underlying cause. An assessment is also made to determine if the person is experiencing symptoms from their hyponatremia. These include assessments of alertness, concentration, and orientation.
False hyponatremia
False hyponatremia, also known as spurious, pseudo, hypertonic, or artifactual hyponatremia is when the lab tests read low sodium levels but there is no hypotonicity. In hypertonic hyponatremia, resorption of water by molecules such as glucose (hyperglycemia or diabetes) or mannitol (hypertonic infusion) occurs. In isotonic hyponatremia a measurement error due to high blood triglyceride level (most common) or paraproteinemia occurs. It occurs when using techniques that measure the amount of sodium in a specified volume of serum/plasma, or that dilute the sample before analysis.
True hyponatremia
True hyponatremia, also known as hypotonic hyponatremia, is the most common type. It is often simply referred to as "hyponatremia." Hypotonic hyponatremia is categorized in 3 ways based on the persons blood volume status. Each category represents a different underlying reason for the increase in ADH that led to the water retention and thence hyponatremia:
High volume hyponatremia, wherein there is decreased effective circulating volume (less blood flowing in the body) even though total body volume is increased (by the presence of edema or swelling, especially in the ankles). The decreased effective circulating volume stimulates the release of anti-diuretic hormone (ADH), which in turn leads to water retention. Hypervolemic hyponatremia is most commonly the result of congestive heart failure, liver failure, or kidney disease.
Normal volume hyponatremia, wherein the increase in ADH is secondary to either physiologic but excessive ADH release (as occurs with nausea or severe pain) or inappropriate and non-physiologic secretion of ADH, that is, syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH). Often categorized under euvolemic is hyponatremia due to inadequate urine solute (not enough chemicals or electrolytes to produce urine) as occurs in beer potomania or "tea and toast" hyponatremia, hyponatremia due to hypothyroidism or central adrenal insufficiency, and those rare instances of hyponatremia that are truly secondary to excess water intake.
Low volume hyponatremia, wherein ADH secretion is stimulated by or associated with volume depletion (not enough water in the body) due to decreased effective circulating volume.
Acute versus chronic
Chronic hyponatremia is when sodium levels drop gradually over several days or weeks and symptoms and complications are typically moderate. Chronic hyponatremia is often called asymptomatic hyponatremia in clinical settings because it is thought to have no symptoms; however, emerging data suggests that "asymptomatic" hyponatremia is not actually asymptomatic.Acute hyponatremia is when sodium levels drop rapidly, resulting in potentially dangerous effects, such as rapid brain swelling, which can result in coma and death.
Treatment
The treatment of hyponatremia depends on the underlying cause. How quickly treatment is required depends on a persons symptoms. Fluids are typically the cornerstone of initial management. In those with severe disease an increase in sodium of about 5 mmol/L over one to four hours is recommended. A rapid rise in serum sodium is anticipated in certain groups when the cause of the hyponatremia is addressed thus warranting closer monitoring in order to avoid overly rapid correction of the blood sodium concentration. These groups include persons who have hypovolemic hyponatremia and receive intravenous fluids (thus correcting their hypovolemia), persons with adrenal insufficiency who receive hydrocortisone, persons in whom a medication causing increased ADH release has been stopped, and persons who have hyponatremia due to decreased salt and/or solute intake in their diet who are treated with a higher solute diet. If large volumes of dilute urine are seen, this can be a warning sign that overcorrection is imminent in these individuals.Sodium deficit = (140 – serum sodium) x total body waterTotal body water = kilograms of body weight x 0.6
FluidsOptions include:
Mild and asymptomatic hyponatremia is treated with adequate solute intake (including salt and protein) and fluid restriction starting at 500 millilitres per day (mL/d) of water with adjustments based on serum sodium levels. Long-term fluid restriction of 1,200–1,800 mL/d may maintain the person in a symptom-free state.
Moderate and/or symptomatic hyponatremia is treated by raising the serum sodium level by 0.5 to 1 mmol per liter per hour for a total of 8 mmol per liter during the first day with the use of furosemide and replacing sodium and potassium losses with 0.9% saline.
Severe hyponatremia or severe symptoms (confusion, convulsions, or coma): consider hypertonic saline (3%) 1–2 mL/kg IV in 3–4 h. Hypertonic saline may lead to a rapid dilute diuresis and fall in the serum sodium. It should not be used in those with an expanded extracellular fluid volume.
Electrolyte abnormalities
In persons with hyponatremia due to low blood volume (hypovolemia) from diuretics with simultaneous low blood potassium levels, correction of the low potassium level can assist with correction of hyponatremia.
Medications
American and European guidelines come to different conclusions regarding the use of medications. In the United States they are recommended in those with SIADH, cirrhosis, or heart failure who fail limiting fluid intake. In Europe they are not generally recommended.There is tentative evidence that vasopressin receptor antagonists (vaptans), such as conivaptan, may be slightly more effective than fluid restriction in those with high volume or normal volume hyponatremia. They should not be used in people with low volume. They may also be used in people with chronic hyponatremia due to SIADH that is insufficiently responsive to fluid restriction and/or sodium tablets.Demeclocycline, while sometimes used for SIADH, has significant side effects including potential kidney problems and sun sensitivity. In many people it has no benefit while in others it can result in overcorrection and high blood sodium levels.Daily use of urea by mouth, while not commonly used due to the taste, has tentative evidence in SIADH. However, it is not available in many areas of the world.
Precautions
Raising the serum sodium concentration too rapidly may cause osmotic demyelination syndrome. Rapid correction of sodium levels can also lead to central pontine myelinolysis (CPM). It is recommended not to raise the serum sodium by more than 10 mEq/L/day.
Epidemiology
Hyponatremia is the most commonly seen water–electrolyte imbalance. The disorder is more frequent in females, the elderly, and in people who are hospitalized. The number of cases of hyponatremia depends largely on the population. In hospital it affects about 15–20% of people; however, only 3–5% of people who are hospitalized have a sodium level less than 130 mmol/L. Hyponatremia has been reported in up to 30% of the elderly in nursing homes and is also present in approximately 30% of people who are depressed on selective serotonin reuptake inhibitors.People who have hyponatremia who require hospitalisation have a longer length of stay (with associated increased costs) and also have a higher likelihood of requiring readmission. This is particularly the case in men and in the elderly.
References
Further reading
Sandy Craig; Erik D Schraga; Francisco Talavera; Howard A Bessen; John D Halamka (2010-04-13). "Hyponatremia in Emergency Medicine". Medscape.
Kugler JP, Hustead T (June 2000). "Hyponatremia and hypernatremia in the elderly". Am Fam Physician. 61 (12): 3623–30. PMID 10892634.
James L. Lewis, III, MD (May 2009). "Hyponatremia". Merck Manual of Diagnosis and Therapy.{{cite web}}: CS1 maint: multiple names: authors list (link)
Elizabeth Quinn (2011-03-07). "What Is Hyponatremia: Hyponatremia or water intoxication – Can Athletes Drink Too Much Water?". About.com.
External links
Hyponatremia at the Mayo Clinic
Sodium at Lab Tests Online
ICD-10 code for Hyponatremia - Diagnosis Code |
Bitlis | Bitlis (Armenian: Բաղեշ Baghesh/Paghesh; Kurdish: Bidlîs; Ottoman Turkish: بتليس) is a city in southeastern Turkey and the capital of Bitlis Province. The city is located at an elevation of 1,545 metres, 15 km from Lake Van, in the steep-sided valley of the Bitlis River, a tributary of the Tigris. The local economy is mainly based on agricultural products which include fruits, grain and tobacco. Industry is fairly limited, and deals mainly with leatherworking, manufacture of tobacco products as well as weaving and dyeing of coarse cloth. Bitlis is connected to other urban centres by road, including Tatvan on Lake Van, 25 km to the northeast, and the cities of Muş (Mush), 100 km northwest, and Diyarbakır, 200 km to the west. The climate of Bitlis can be harsh, with long winters and heavy snowfalls. Summers are hot, and often humid. Since the local elections of March 2019, the Mayor of Bitlis is Nesrullah Tanğlay.
History
Ancient and medieval
The origin of the name Bitlis is not known. A popular folk etymology explanation, without historical basis, is that it is derived from "Lis/Batlis", the name of a general said to have built Bitlis castle by the order of Alexander the Great. To Armenians, it was known as Balalesa or Baghaghesh, and later Baghesh. According to one popular Armenian folk story, on a cold, wintry day a donkey left its stable and wandered down the valley below. The donkey died of the freezing temperatures and was only discovered in the spring, once the ice had melted; thus, it received the name Pagh Esh, or "Cold Donkey."Baghesh was one of the most important cities of the Kingdom of Armenias province of Aghdznik, and it served as the primary fortress of the provinces canton of Salnodzor. Some medieval Armenian writers, such as Anania Shirakatsi and Vardan Areveltsi, later mention it as a part of the canton of Bznunik. The fortress guarded the Baghesh Pass, which linked the southern reaches of the Armenian Plateau to northern Mesopotamia. The Arabs conquered Baghesh at the end of the seventh century and it eventually became the capital of the Zurārid emirs of Arzan. Because it was on an important trade route, it prospered greatly.
The next two centuries, however, marked a turbulent period in the towns history. After Bugha al-Kabirs destructive 852-855 campaign in Armenia, the Shaybanid emirs wrested control of Baghesh from the Zurārids; thereafter, in the first quarter of the tenth century, it was taken by the Kaysite emirs of Manzikert. In his 929-30 campaign against the Kaysites, the Byzantine general John Curcuas was able to capture and annex Baghesh. Following the devastation of the Arab emirs in the second half of the tenth century, a great number of Kurds settled in Baghesh and at the end of the tenth century, the city fell into the hands of the Kurdish Marwanid dynasty after breaking from Buyid rule. At the end of the eleventh century, with the collapse of Byzantine power after the Battle of Manzikert, Bitlis fell under the control of Togan Arslan, a subject of the Shah Arman (Also called Ahlatshah) dynasty based in Akhlat after brief Dilmachoglu rule. It was also ruled by Ayyubid (1207–1231), Khwarezm Shahs (shortly rule in 1230), Sultanate of Rûm (1231–1243) and Ilkhanate (1243–1335).
Emirate
Bitlis was a Kurdish emirate from the 13th to the 19th century. Though often subordinate to a succession of larger powers that ruled the Van region, it always maintained a measure of independence. In the 14th century its emirs, the Kurdish Rusaki family, were vassals of the Karakoyunlu and the emirates territory also consisted of several smaller emirates: Ahlat, Mush, and Hinis. The emir of Bitlis submitted to Timur in 1394, but later helped the re-establishment of Karakoyunlu control in the region. After the collapse of the Karakoyunlu state, the Bitlis emirate disintegrated. However, in the 1470s it took the Aq Qoyunlu (White Sheep Turkomans) three successive sieges to capture Bitlis and in 1494/95 the Ruzaki recaptured the town. Armenians formed a large part of the citys population. A number of monasteries were permitted to be built by the Kurdish emirs and during the fifteenth century, Biltis flourished as a center for Armenian manuscript production.
Bitlis was forced to accept a Persian governor during the invasion of the Safavid Shah Ismail, but sided with the Ottoman forces as they approached the region. Its emir, Sheref, later changed his allegiance to the Persians. An Ottoman army besieged Bitlis for three months in 1531/32, but was forced to retire. Sheref was killed in battle in 1533 and his son and successor submitted to the Ottoman Empire. Mush and Hınıs were removed from the Bitlis emirate, becoming separate sanjaks but still with Ruzaki beys. A Jesuit mission was established in Bitlis in 1685. The Ruzakid Kurdish dynasty in Bitlis lasted until 1849, when an Ottoman governor evicted its last emir, Sheref Bey, who was taken to Constantinople as a prisoner. After this, Bitlis was governed by a Turkish pasha and formed the capital of a vilayet bearing its name.
Modern
In 1814 the population of Bitlis town was said to be 12,000 people - one half Muslim, the other half was constituted by Christian Armenians. By 1838 its population was said to be between 15,000 and 18,000 - two thirds Muslim, one third Armenian, and a small minority of Assyrians. In 1898 Lynch considered the population to be close to 30,000, comprising 10,000 Armenians, 300 [As]syrians, and the rest Muslim Kurds (both Alevis and Sunnis included). The Armenians had five schools for boys and three for girls. One third of the population of Bitlis was ethnic Armenian prior to World War I (1914, whereas the majority of the population was Kurdish Muslim (Alevi as well as Sunni Muslims). In 1915, during the Armenian genocide, Turks and Kurds, led by Jevdet Bey Pasha, massacred some 15,000 Armenians in Bitlis.In February 1916, as part of the Caucasus Campaign, Imperial Russian forces launched an offensive to capture Mush and Bitlis. Mush fell on February 16. At Bitlis, the Turkish positions were in a strong location on the outskirts of the town and could not be outflanked because of the narrowness of the valley. On the night of March 2–3, during a blizzard, the Russian 8th Caucasian Rifles advanced silently and, after several hours of hand-to-hand fighting, took the Turkish positions with 1,000 prisoners. The Turks then abandoned Bitlis, retreating towards Siirt. The Russian forces and intelligence officers found evidence of the massacres of Christians by the Kurdish and Turkish radicals in 1915.
In August 1916 the Turkish Second Army started an offensive against the Russian front in eastern Turkey. On August 2, the Ottoman 16th Corps, together with strong Kurdish irregulars support, attacked Bitlis and Mush. Fearing encirclement General Nazarbekov, the Russian commander, abandoned Bitlis on August 5. When Mush also fell, he decided to abandon Tatvan and the whole Mush valley and retreat to Ahlat. Around 18 August, the Russians having been reinforced, were able to counter-attack. By September the Turkish offensive was stalled and then turned. Nazarbekov advanced as the Turkish forces withdrew from Tatvan and Mush, but he did not have the available forces to hold Bitlis as winter approached. The Russian February Revolution in the spring of 1917 prevented any further Russian gains.
Description
Bitlis preserves more medieval and traditional architecture than any other town in eastern Turkey. They are of a high quality and are mostly constructed from locally quarried light-brown stone, sometimes called Ahlat stone.
The town contains a large number of late-medieval Islamic buildings in the form of mosques, madrassas, and tombs. Also commercial buildings such as "Hans Caravanserais. Commissioned mostly by its local Kurdish rulers, the architectural style of these buildings is very conservative and similar to much earlier Seljuq-period structures. Important monuments include the 12th-century Ulu Mosque with its 15th-century minaret, and the Gokmeydani Medresesi and Sherefiye Mosque from the sixteenth century. Until 1915 there were five Armenian monasteries and several churches in Bitlis – only a 19th-century Armenian church survives, now used as a warehouse.Bitlis is also notable for its many old houses. These are built of cut stone and are often large and impressive structures. Most have two stories, but three stories are also found. Ground floors were generally intended for storage and stables, with the residential quarters on the upper floors. Ground floor rooms have few windows, upper floors are well lit. Roofs are flat and covered with beaten clay. Unlike traditional houses in nearby Erzurum or Van, Bitlis houses do not have bay windows and balconies.
Gallery
Demographics
According to Encyclopædia Britannica Eleventh Edition from 1911, the town had 35 thousand people with 12 thousand Armenians, the rest being Kurdish.
Climate
Bitlis has a dry-summer humid continental climate according to the (Köppen climate classification: Dsa, or Trewartha climate classification: Dca). Bitlis has hot, dry summers and cold, very snowy winters.
Economy
Historically, Bitlis produced wheat, which the British, in 1920, described as being "particularly excellent." However, poor trade routes in the area during the early 20th century meant that the wheat was mainly produced and used by locals. During this time, the British stated that the people of Bitlis were unable to use all of the wheat they produced, and most was "left to rot in the underground storehouses."
Notable individuals
Badh ibn Dustak (died 991), Kurdish tribal leader
Arakel Paghishetsi (1380-1454) Armenian musician, hymnologist
Hovhannes Paghishetsi (1678-1741) 49th Armenian patriarch of Constantinople
Vardan Paghishetsi (???-1705) Armenian chronographer
Vardan Paghishetsi (16th century) Armenian medieval illuminatorThe city was the home of the sixteenth century Kurdish historian, Sherefxan Bedlisi (also: Sharaf al-Din Bitlisi), author of the Sharafnameh, and who was also an appointed prince of the Persian and later Ottoman Empires.
Hosam al-Din Ali Bitlisi was a Kurdish Sufi author. He was the father of the noted historian Idris Bitlisi.
Ottoman administrator and Kurdish religious scholar and author Idris-i Bitlisi is claimed to have been born in Bitlis also. He was instrumental in conquest, Ottomanization and administration of Ottoman lands from Urfa, Mardin to Egypt.
Said Nursi (Nurs, Bitlis, 1877) notable Kurdish Sunni Muslim Theologian. Writer of the Risale-i-Nur collection used as the foundation of movements such as the Nurcu in Turkey and the Gulenist movement founded by Fetullah Gulen.
Fuat Sezgin (Bitlis, 1924), a prominent Historian of Science, Orientalist was born in Bitlis. He is the author and editor of numerous publications. His 13-volume work Geschichte des Arabischen Schrifttums (1967-2000) is the cornerstone reference on the history of science and technology in the Islamic world. The 5-volume Natural Sciences of Islam documents the items in the Frankfurt museum. Since 1984 he has edited the Journal for the History of Arabic-Islamic Science.
American writer William Saroyans parents were immigrants from Bitlis to Fresno, California. He wrote a play entitled "Bitlis" about his "return" to the city he considered his homeland, which he actually did visit in later years.Kâmran İnan (Hizan, Bitlis, 1929), a well known Turkish politician, diplomat, and scholar was from Bitlis. He has written about the history of Bitlis.
International relations
Twin towns — sister cities
Bitlis is twinned with:
Notes
Further reading
Hovannisian, Richard G. (ed.) Armenian Baghesh/Bitlis and Taron/Mush. UCLA Armenian History and Culture Series: Historic Armenian Cities and Provinces, 2. Costa Mesa, California: Mazda Publishers, 2001.
External links
"Bitlis" . Colliers New Encyclopedia. 1921.
BitlisHaber13
Governors Office
Bitlis Haber
BitlisNews
Bitlis Article on Armeniapedia.org. Bitlis Armenian history, map and information. |
Identity disorder | Identity disorder in the DSM was first listed as a separate diagnosis in version III (1980). In the DSM-IV (1994), it was replaced by "Identity problem", which was not defined as a mental disorder per se, but was listed in a chapter containing problems that might be a focus of clinical attention. Identity disorder was downgraded to Identity problem as research indicated that distress over ones identity is so common that it might very well be considered part of the normality. In practice, if a persons distress persisted or worsened, an Identity problem would often be succeeded by a diagnosis of an actual disorder, such as a mood disorder or borderline personality disorder. In DSM-5 (2013), Identity problem was removed.
See also
Body integrity dysphoria, sometimes also called body integrity identity disorder
Dissociative identity disorder
Gender dysphoria, sometimes also called gender identity disorder
Self-concept
Self-image
== References == |
Melanotic neuroectodermal tumor of infancy | Melanotic neuroectodermal tumor of infancy is a very rare oral cavity tumor that is seen in patients usually at or around birth. It must be removed to be cured. Definitions: A rare, biphasic, neuroblastic, and pigmented epithelial neoplasm of craniofacial sites, usually involving the oral cavity or gums.
Signs and symptoms
Most patients present with a very rapidly growing mass that often gives a bluish appearance in the mouth. This is because the pigmentation in the cells appears blue through the overlying epithelium (mucosa). By imaging studies, there is usually a large expansive radiolucent (clear) mass without well defined borders. Calcifications within the mass may be seen. More than 70% involve the maxilla (usually maxillary anterior alveolar ridge), while the mandible and skull are affected less often. There is often an elevated vanilmandelic acid level.
Pathogenesis
It is considered to be a developmental anomaly, and thus is congenital in presentation. It is thought to be derived from neural crest, which is one of the embryologic tissue types. The reason for this postulation is based on the expression of melanotransferrin (melanoma-specific peptide that may play role in iron metabolism).
Diagnosis
Macroscopic
Usually there is a smooth, firm mass, with mottled white-gray to blue-black cut surfaces. The overall size ranges from 1–10 cm with a mean size 3.5 cm.
Microscopic
The tumor is usually very well circumscribed but not encapsulated. There are two cell types present (biphasic), arranged in alveolar or tubular configurations. There are centrally located, small, darkly staining cells comprising the majority of cells. These cells have a fibrillary cytoplasm surrounding round nuclei with coarse and heavy nuclear chromatin. These cells are surrounded by much larger polygonal cells that have open nuclear chromatin and abundant opaque cytoplasm that has granular melanin pigment. There is usually no hemorrhage, necrosis or increased mitoses.
Immunohistochemistry
The lesional cells will show cross reactivity with several different families of immunohistochemistry markers (polyphenotypic), including neural, melanocytic, and epithelial.
Large tumor cells: Keratin, vimentin, HMB-45, NSE, CD57
Small tumor cells: Synaptophysin, GFAP, NSE, CD57
There is usually a variable expression of EMA and S100 protein.
Differential diagnoses
It is important in this age group to exclude other tumors that can have a similar appearance, such as rhabdomyosarcoma, lymphoma, Ewing sarcoma (primitive neuroectodermal tumor), or even a melanoma (although they are very very rare in infants).
Management
Even though there is often a very dramatic and rapidly enlarging, destructive tumor, there is usually a benign clinical course after complete local excision (usually by partial maxillectomy) with clear or free surgical margins. In rare cases, chemotherapy may be used for recurrent or residual tumors. Overall, the outcome is good, although it is quite unpredictable, with about 30% of patients have a recurrence. In about 10% of cases, metastasis may be seen (lymph nodes, liver, bone and soft tissue).
Epidemiology
This tumor is extremely rare, with fewer than 500 cases reported world wide. More than 95% of patients are less than 1 year of age at presentation, with about 80% less than 6 months. Females are affected more often than males (2:1).
References
Further reading
Lester D. R. Thompson; Bruce M. Wenig (2016). Diagnostic Pathology: Head and Neck, 2nd edition. Elsevier. ISBN 978-0323392556.
== External links == |
Video game addiction | Video game addiction (VGA), also known as gaming disorder or internet gaming disorder, is generally defined as the problematic, compulsive use of video games that results in significant impairment to an individuals ability to function in various life domains over a prolonged period of time. This and associated concepts have been the subject of considerable research, debate, and discussion among experts in several disciplines and has generated controversy within the medical, scientific, and gaming communities. Such disorders can be diagnosed when an individual engages in gaming activities at the cost of fulfilling daily responsibilities or pursuing other interests without regard for the negative consequences. As defined by the ICD-11, the main criterion for this disorder is a lack of self control over gaming.The World Health Organization included gaming disorder in the 11th revision of its International Classification of Diseases (ICD). The American Psychiatric Association (APA), while stating there is insufficient evidence for the inclusion of Internet gaming disorder in the Diagnostic and Statistical Manual of Mental Disorders in 2013, considered it worthy of further study.Controversy around the diagnosis includes whether the disorder is a separate clinical entity or a manifestation of underlying psychiatric disorders. Research has approached the question from a variety of viewpoints, with no universally standardized or agreed definitions, leading to difficulties in developing evidence-based recommendations.
Definition and diagnosis
In its report, the Council on Science and Public Health to the American Medical Association (AMA) used this two-hour-per-day limit to define "gaming overuse", citing the American Academy of Pediatrics guideline of no more than one to two hours per day of "screen time". However, the ESA document cited in the Council report does not contain the two-hour-per-day data.
American Psychiatric Association
While the American Psychiatric Association (APA) does not recognise video game addiction as a disorder, in light of existing evidence, the organisation included video game addiction as a "condition requiring further study" in the DSM-5 as Internet gaming disorder. Video game addiction is a broader concept than internet gaming addiction, but most video game addiction is associated with internet gaming. APA suggests, like Khan, the effects (or symptoms) of video game addiction may be similar to those of other proposed psychological addictions. Video game addiction may be an impulse control disorder, similar to compulsive gambling The APA explains why Internet Gaming Disorder has been proposed as a disorder:This decision was based upon the large number of studies of this condition and the severity of its consequences.... Because of the distinguishing features and increased risks of clinically significant problems associated with gaming in particular, the Workgroup recommended the inclusion of only internet gaming disorder in Section 3 of the DSM-5.
Some players become more concerned with their interactions in the game than in their broader lives. Players may play many hours per day, neglect personal hygiene, gain or lose significant weight, disrupt sleep patterns resulting in sleep deprivation, play at work, avoid phone calls from friends, or lie about how much time they spend playing video games.The APA has developed nine criteria for characterising the proposed Internet Gaming Disorder:
Pre-occupation. Do you spend a lot of time thinking about games even when you are not playing, or planning when you can play next?
Withdrawal. Do you feel restless, irritable, moody, angry, anxious or sad when attempting to cut down or stop gaming, or when you are unable to play?
Tolerance. Do you feel the need to play for increasing amounts of time, play more exciting games, or use more powerful equipment to get the same amount of excitement you used to get?
Reduce/stop. Do you feel that you should play less, but are unable to cut back on the amount of time you spend playing games?
Give up other activities. Do you lose interest in or reduce participation in other recreational activities due to gaming?
Continue despite problems. Do you continue to play games even though you are aware of negative consequences, such as not getting enough sleep, being late to school/work, spending too much money, having arguments with others, or neglecting important duties?
Deceive/cover up. Do you lie to family, friends or others about how much you game, or try to keep your family or friends from knowing how much you game?
Escape adverse moods. Do you game to escape from or forget about personal problems, or to relieve uncomfortable feelings such as guilt, anxiety, helplessness or depression?
Risk/lose relationships/opportunities. Do you risk or lose significant relationships, or job, educational or career opportunities because of gaming?One of the most commonly used instruments for the measurement of addiction, the PVP Questionnaire (Problem Video Game Playing Questionnaire, Tejeiro & Moran, 2002), was presented as a quantitative measure, not as a diagnostic tool.
According to Griffiths, "all addictions (whether chemical or behavioral) are essentially about constant rewards and reinforcement". He proposes that addiction has six components: salience, mood modification, tolerance, withdrawal, conflict, and relapse. But the APAs nine criteria for diagnosing Internet Gaming Disorder were made by taking point of departure in eight different diagnostic/measuring tools proposed in other studies. Thus, the APAs criteria attempt to condense the scientific work on diagnosing Internet Gaming Disorder.
World Health Organization
The World Health Organization (WHO) had proposed and later included "gaming disorder" in the 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11), released in June 2018, which was approved by the World Health Assembly in May 2019. The use and enforcement of ICD-11 is expected to start on 1 January 2022.
Screening tools
The first psychometric test to assess IGD was the Internet Gaming Disorder Test (IGD-20). This test includes 20 questions designed to assess the extent of problems caused by disordered gaming and the degree of symptoms experienced by gamers. The test was first published in a journal article published in the PLoS ONE journal on 14 October 2014.
The Internet Gaming Disorder Scale–Short-Form (IGDS9-SF) is a short psychometric test to assess video game addiction according to the American Psychiatric Association framework for IGD. Recent review studies suggest that the IGDS9-SF presents with robust empirical and clinical evidence and is an effective tool to assess IGD. Moreover, the scale was adapted in several languages as Spanish, Chinese, Czech, German, and many more.
On 3 June 2019, a screening tool for Gaming Disorder, specifically as defined by the World Health Organization, called the "Gaming Disorder Test" was published in a journal article.
Risk factors
The Internet can foster various addictions including addiction to gameplaying.Addictive playing of MMORPGs is associated with negative effects, whereas normal play is not.Younger people and men are more likely to experience a gaming disorder than older people and women respectively. Research shows that the average age of a gamer is 30 years old, and 32% of players are under 18.Adolescents are at a higher risk of sustaining video game disorder over time than adults. An international meta-analysis over 34 jurisdictions quantified the effect size of gender as small, with most effect in Asia, lesser in Europe and Africa, and null in North America, and further finding that economic factors, internet availability, social norms and addiction-related health factors mediate the effect of gender, with nations with a greater GDP per capita having less differences in video game addiction between genders.Comorbid psychiatric disorders act as both risk factors and consequences. Indeed, there is a strong association between video game addiction and anxiety, depression, ADHD, social phobia, and poor psycho-social support. ADHD and its symptoms, such as impulsivity and conduct problems, also increase risks of developing video game disorder. Although internet gaming disorder has a strong relationship with obsessive-compulsive disorder, it is not specific and internet gaming disorder is both phenomenologically and neurobiologically distinct, which indicates that internet gaming disorder is more characterized by impulsivity than compulsivity. Familial factors appear to play an important role, although not well understood.Some personality traits, such as high neuroticism, high impulsivity, and high aggressiveness are consistently significant predictors of internet gaming disorder, and combination of personality traits seem to play a pivotal role in the acquisition, maintenance and development of the disorder.
Mechanisms
Although there is much research since the 1980s on problematic online gaming use, the mechanisms are not well understood, due to inconsistent definitions used in studies.
Video game structure
Some theories focus on the presumed built-in reward systems of video games, such as compulsion loops, to explain their potentially addictive nature. The anticipation of such rewards can create a neurological reaction that releases dopamine the body, so that once the reward is obtained, the person will remember it as a pleasurable feeling. This has been found to be similar to the neurological reaction of other behavioral addictions such as substance abuse and gambling disorder.Mark Griffiths has proposed another reason online video games are potentially addictive is because they "can be played all day every day." The fact there is no end to the game can feel rewarding for some, and hence players are further engaged in the game.
Addiction circuits in the brain
Long-term internet video/mobile game playing affects brain regions responsible for reward, impulse control and sensory-motor coordination. Structural analyses shown modifications in the volume of the ventral striatum, possibly as result of changes in rewards, and video game addicts had faulty inhibitory control and reward mechanisms. Video game playing is associated with dopamine release similar in magnitude to that of drug abuse and gambling, and the presentation of gaming pictures activates brain regions similarly to drug pictures for drug addicts. Treatment studies which used fMRI to monitor the brain connectivity changes found a decrease in the activity of the regions associated with cravings. Although there are evidences that video game addiction may be supported by similar neural mechanisms underlying drug abuse, as video game and internet addictions reduce the sensitivity of the dopaminergic reward system, it is still premature to conclude that this addiction is equivalent to substance addictions, as the research is in its early stages. There is evidence of a dual processing model of digital technology addictions characterized by an imbalance between the reactive and the reflective reward systems. Other studies shown increased difficulties in decision making in specific contexts, such as risky situations but not in ambiguous situations, and an increased preference for short-term rewards. Although the number of neuroimaging studies on internet gaming disorder is rising, there are several methodological shortcomings, particularly in the inconsistency of psychometric assessments. Furthermore, the conclusions on reduced inhibition should be moderated, as only one study included a functional control, which then showed no difference in inhibition.A meta-analytic review of the research concluded the evidence suggests video game addiction arises out of other mental health problems, rather than causing them. Thus it is unclear whether video game addiction should be considered a unique diagnosis.
Management
As concern over video game addiction grows, the use of psychopharmacology, psychotherapy, twelve-step programs, and use of continuing developing treatment enhancements have been proposed to treat this disorder. Empirical studies indeed indicate that internet gaming disorder is associated with detrimental health-related outcomes. However, the clinical trials of potential treatments remain of low quality, except for cognitive-behavioral therapies, which shows efficacy to reduce gaming disorder and depressive symptoms but not total time spent. Although there is a scientific consensus that cognitive-behavioral therapy is preferable to pharmacological treatment, it remains difficult to make definitive statements about its benefits and efficiency due to methodological inconsistencies and lack of follow-up. Since efficacious treatments have not been well established, prevention of video gaming disorder is crucial. Some evidence suggest that up to 50% of people affected by the internet gaming disorder may recover naturally.Some countries, such as South Korea, China, the Netherlands, Canada, and the United States, have responded to the perceived threat of video game addiction by opening treatment centres.
China
China was the first country to treat "internet addiction" clinically in 2008. The Chinese government operates several clinics to treat those who overuse online games, chatting and web surfing. Treatment for the patients, most of whom have been forced to attend by parents or government officials, includes various forms of pain including shock therapy. In August 2009, Deng Sanshan was reportedly beaten to death in a correctional facility for video game and Web addiction. Most of the addiction "boot camps" in China are actually extralegal militaristically managed centers, but have remained popular despite growing controversy over their practices.In 2019, China set up a curfew, banning minors from playing between certain hours. In 2021, China government published a new policy to force corporations to only serves underage teenagers on Friday, Saturday, and Sunday between 8 pm to 9 pm.
Netherlands
In June 2006, the Smith and Jones clinic in Amsterdam—which has now gone bankrupt—became the first treatment facility in Europe to offer a residential treatment program for compulsive gamers. Keith Bakker, founder and former head of the clinic, has stated that 90% of the young people who seek treatment for compulsive computer gaming are not addicted.
Canada
At a Computer Addiction Services center in Richmond, British Columbia, excessive gaming accounts for 80% of one youth counselors caseload.
United Kingdom
In 2018, the National Health Service announced its plans to open a treatment center, run by the Central and North West London NHS foundation trust, that will initially focus on gaming disorder, but is planned to expand to cover other internet-based addictions. The specialist treatment center opened in 2019 for treating adolescents and young people aged 13–25 who are addicted to video games.
Outcomes
Physical health
The most frequent physical health-related outcome are alterations in physical functioning such as somatisation and sleep disturbances. Preliminary evidence suggest that internet gaming disorder and the induced sedentarity may contribute to a lack of physical exercise, even though the relationship is not causal.
Epidemiology
The prevalence of internet gaming disorder range from 0.7% to 25.5% worldwide, or 1.0% to 26.8% worldwide, and 3.5% to 17% in China, and is higher among males than females and among younger than older people, with geographical region being an insignificant contributor. The prevalence was found to be 5.06% among a high-school student population from Sri Lanka, suggesting an increasing trend in low- and middle-income countries as well. A longer time spent on video games predicts a tendency towards pathological gaming in the future. The studies, however, used various methodologies and definitions, which renders consensus difficult to achieve and may explain the wide range of prevalence.
Research
Debates on the classification
A meta-analytic review of pathological gaming studies concluded that about 3% of gamers may experience some symptoms of pathological gaming. The report noted problems in the field with defining and measuring pathological gaming and concluded that pathological gaming behaviors were more likely the product of underlying mental health problems rather than the inverse.Barnett and Coulson expressed concern that much of the debate on the issue of addiction may be a knee jerk response stimulated by poor understanding of games and game players. Such issues may lead both society and scholars to exaggerate the prevalence and nature of problematic gaming, and over-focus on games specifically, while ignoring underlying mental health issues. However, Problem gamblers have a higher chance for getting mental illness as well.Other scholars have cautioned that comparing the symptoms of problematic gaming with problematic gambling is flawed, and that such comparisons may introduce research artifacts and artificially inflate prevalence estimates. For instance, Richard Wood has observed that behaviors which are problematic in regards to gambling may not be as problematic when put into the context of other behaviors that are rewarding such as gaming. Similarly, Barnett and Coulson have cautioned that discussions of problematic gaming have moved forward prematurely without proper understanding of the symptoms, proper assessment and consequences.Rather than video gaming disorder being a subtype of gambling disorder, a majority of researchers support the idea of video game addiction being a part of a more comprehensive framework of impulse control disorders with "pathological technology use" with similar characteristics, including the pathological use of video games, internet, computers and other interactive medias. Although internet and video game addictions are generally considered different from gambling disorder and substance abuse, there is a growing body of evidence indicating they share common features, including behavioral and neural features. Indeed, it is suggested that while behavioral addiction may differ with drug addictions in magnitude, they share several characteristics, with Hellman et al. proposing that the concept of addiction should be de-medicalized.On the contrary, a literature review found that as the video game addiction develops, online gaming addicts spend increasing amounts of time not only playing but also preparing for and organizing their playing sessions, suggesting this addiction may be behavioral rather than a disorder of impulse control. There is recent evidence suggesting that internet gaming disorder can cause two distinct types of dysfunctions: cognitive and metacognitive.Griffiths has suggested that psycho-social dependence may revolve around the intermittent reinforcements in the game and the need to belong. Hagedorn & Young have suggested that social dependence may arise due to video games occurring online where players interact with others and the relationships "often become more important for gamers than real-life relationships".
Controversy and alternative viewpoints
Common challenges involve the reliability of the methodology and validity of the results in some studies. Many rely on self-surveys from university students and also lack time frames making it difficult to study the impact, if any, of addiction on a long term scale. Other concerns also address the definition of addiction and how to measure it, questioning whether or not time is a proper unit to determine how addicted someone is to gaming. Daria Joanna Kuss and Mark D. Griffiths have argued the current scientific knowledge on internet gaming addiction is copious in scope and complexity. They state that instead, a simple framework should be provided to allow all current and future studies to be categorised, as internet gaming addiction lies on a continuum beginning with etiology and risk factors all the way through the development of "full-blown" addiction and ending with ramifications and potential treatment. In addition, they caution the deployment of the label "addiction" since it heavily denotes the use of substances or engagement in certain behaviors. Finally, the researcher promotes other researchers to assess the validity and reliability of existing measures instead of developing additional measurement instruments.Other challenges include the lack of context of the participants life and the negative portrayal of gaming addicts. Some state that gamers sometimes use video games to either escape from an uncomfortable environment or alleviate their already existing mental issues—both possibly important aspects in determining the psychological impact of gaming. Negative portrayal also deals with the lack of consistency in measuring addictive gaming. This leads to discussions that sometimes exaggerate the issue and create a misconception in some that they, themselves, may be addicted when they are not.The evidence of video game addiction to create withdrawal symptoms is very limited and thus debated, due to different definitions and low quality trials.The concept of video game disorder is itself being debated, with the overlap of its symptoms with other mental disorders, the unclear consensus on a definition and thresholds, and the lack of evidence raising doubts on whether or not this qualifies as a mental disorder of its own. Despite the lack of a unified definition, there is an emerging consensus among studies that Internet gaming disorder is mainly defined by three features: 1) withdrawal, 2) loss of control, and 3) conflict. Although the DSM-5 definition of video game disorder has a good fit to current methodological definitions used in trials and studies, there are still debates on the clinical pertinence.Michael Brody, M.D., head of the TV and Media Committee of the American Academy of Child and Adolescent Psychiatry, stated in a 2007 press release that "... there is not enough research on whether or not video games are addictive." However, Brody also cautioned that for some children and adolescents, "... it displaces physical activity and time spent on studies, with friends, and even with family."A major issue concerns the lack of consistent measures and definitions and of acquisition of follow-up data. Furthermore, the study design quality has not greatly improved between the 2000s and 2017. For instance, most studies measured internet gaming behaviors in terms of frequency of use (total time spent), without considering the type of game (e.g., MMORPG), the social context (e.g., physically or virtually with friends), nor the motivations (e.g., competitive, achievement-oriented "grinding"). Although the amount of time spent was postulated by Johanssonn and Götestam in 2004 to lead to pathological behaviors, it is unclear whether the time spent is a cause or a consequence of pathological use. These criticisms, however, mostly pertain to Western research since there is more data of higher quality available in Asian regions, where the Internet gaming disorder is more prevalent.A survey conducted in 2019 of 214 scholars shown that 60.8% agreed that pathological video game use could be a mental health problems, whereas 30.4% were skeptical. However, only 49.7% agreed with the DSM-5 definition of Internet gaming disorder, and 56.5% to the definition of the World Health Organization. Most scholars were worried that WHOs and DSM-5s inclusion of Internet gaming disorder was "overpathologizing normal youth" and "precipitated moral panic over video games". This indicates a lack of consensus on the issue as of 2019.
History
Video game addiction has been studied since the 1980s, and has seen a significant increase in the number of empirical studies since then.The press has reported concerns over online gaming since at least 1994, when Wired mentioned a college student who was playing a MUD game for 12 hours a day instead of attending class.Press reports have noted that some Finnish Defence Forces conscripts were not mature enough to meet the demands of military life and were required to interrupt or postpone military service for a year. One reported source of the lack of needed social skills is overuse of computer games or the internet. Forbes termed this overuse "Web fixations" and stated they were responsible for 13 such interruptions or deferrals over the five years from 2000 to 2005.In an April 2008 article, The Daily Telegraph reported that surveys of 391 players of Asherons Call showed that three percent of respondents experienced agitation when they were unable to play, or missed sleep or meals to play. The article reports that University of Bolton lead researcher John Charlton said, "Our research supports the idea that people who are heavily involved in game playing may be nearer to autistic spectrum disorders than people who have no interest in gaming."On 6 March 2009, the Canadian Broadcasting Corporations (CBC) national news magazine program the fifth estate aired an hour-long report on video game addiction and the Brandon Crisp story, titled "Top Gun", subtitled "When a video gaming obsession turns to addiction and tragedy."In August 2010, Wired reported that a man in Hawaii, Craig Smallwood, sued the gaming company NCSoft for negligence and for not specifying that their game, Lineage II, was so addictive. He alleged he would not have begun playing if he was aware he would become addicted. Smallwood says he has played Lineage for 20,000 hours between 2004 and 2009.In 2013, a man from China observed his sons addiction to video games, and decided to take action. He hired online assassins to kill his sons virtual avatar every time he logged in. He hoped that being relentlessly killed would help his son lose interest in this destructive habit.
Inclusion in the ICD-11
In the draft versions leading to the final ICD-11 document, gaming disorder was included alongside gambling disorder under "Disorders Due to Addictive Behaviors". The addition defines as "a pattern of persistent or recurrent gaming behaviour (digital gaming or video-gaming)", defined by three criteria: the lack of control over playing video games, priority given to video games over other interests, and the inability to stop playing video games even after being affected by negative consequences. For gaming disorder to be diagnosed, the behavior pattern must be of sufficient severity to result in significant impairment in personal, family, social, educational, occupational or other important areas of functioning and would normally have been evident for at least 12 months. Research shows gaming disorders can be associated with anxiety, depression, loneliness, obesity, sleeping disorders, attention problems, and stress.Vladimir Poznyak, the coordinator for the WHO Department of Mental Health and Substance Abuse, defended the addition of gaming disorder, believing the backlash against the addition to be a moral panic as they chose a very narrow definition that encompasses only the most extreme cases of gaming disorder. He said evaluating a disorder for inclusion is nominally done without any external feedback "to avoid interference from commercial and other entities which may have vested interest in the outcome of the process". Dr. Poznyak asserted that several medical professionals consulting on the ICD-11 did believe gaming disorder to be real, and by including it in the ICD-11, there can now be earnest efforts to define its causes and symptoms betters and methods to deal with it, and now include the video game industry within the conversation to help reduce the effects of video games on public health.The addition of "gaming disorder" to the ICD-11 was criticized by gamers and the video game industry, while some researchers remained skeptical. Some of these researchers said the evidence remains weak and "there is a genuine risk of abuse of diagnoses." A group of 26 scholars wrote an open letter to the WHO, suggesting that the proposed diagnostic categories lacked scientific merit and were likely to do more harm than good. In counter-argument, a group of fifty academic researchers in behavioral science agreed that the evidence to support gaming disorder was weak, but it would be best that WHO identify gaming disorder in ICD-11 so that it could be considered a clinical and public health need.A report, prepared by mental health experts at Oxford University, Johns Hopkins University, Stockholm University and the University of Sydney, sponsored by The Association for UK Interactive Entertainment argues that while there may be potential addiction associated with video gaming, it is premature to consider it a disorder without further study, given the stigmatisation that surrounds video, and ask the WHO to use caution when finalising the ICD draft. This report was promoted by 22 video game industry trade organizations including the Entertainment Software Association of the United States and Interactive Software Federation of EuropeAs the final approval of the ICD-11 neared, several video game trade associations issued a statement requesting WHO to reconsider the addition of "gaming disorder", stating that, "The evidence for its inclusion remains highly contested and inconclusive". The Entertainment Software Association had meetings with the WHO during December 2018 to try to convince them to hold off including gaming disorder within ICD-11, with more planned meetings to follow.
Society and culture
Parental concerns
According to ABC News, parents have many concerns about their children playing video games, including concerns about age appropriateness, the amount of time spent playing games, physical health, and aggressive behaviour.
Governmental concerns
The first video game to attract political controversy was the 1978 arcade game Space Invaders. In 1981, a political bill called the Control of Space Invaders (and other Electronic Games) Bill was drafted by British Labour Party MP George Foulkes in an attempt to ban the game for its "addictive properties" and for causing "deviancy". The bill was debated and only narrowly defeated in parliament by 114 votes to 94 votes.In August 2005, the government of the Peoples Republic of China, where more than 20 million people play online games, introduced an online gaming restriction limiting playing time to three hours, after which the player would be expelled from whichever game they were playing. In 2006, it relaxed the rule so only citizens under the age of 18 would face the limitation. Reports indicate underage gamers found ways to circumvent the measure. In July 2007, the rule was relaxed yet again. Internet games operating in China must require users identify themselves by resident identity numbers. After three hours, players under 18 are prompted to stop and "do suitable physical exercise". If they continue, their in-game points are "slashed in half". After five hours, all their points are automatically erased.In 2008 in the United States (US), one of the five Federal Communications Commission (FCC) Commissioners, Deborah Taylor Tate, stated that online gaming addiction was "one of the top reasons for college drop-outs". However, she did not mention a source for the statement nor identify its position in relation to other top reasons.In 2011, the South Korean government implemented a law, known as the Shutdown law or the Cinderella Law, which prohibits children under the age of 16 from playing online video games between the hours of 12:00 a.m. to 6:00 a.m. Later on, the law was amended and now children under the age of 16 can play after midnight if they have permission from their parents. In 2021, the South Korean government moved to abolish this law.A systematic review identified in 2017 three types of currently attempted |
Video game addiction | governmental policies: 1) limiting the availability of video games (shutdown, fatigue system, parental controls), 2) reduce the risks and harm (warning messages), 3) provide addiction help services to gamers. Most of these policies were either not as efficient as intended or not yet evaluated for efficiency, which lead some researchers to prompt for a global public health approach to prevent the onset and progression of this disorder. Some researchers suggest that the video game industry should itself place preventive measures against video game addiction.
Deaths
There have been at least a few deaths caused directly by exhaustion from playing games for excessive periods of time.
China
In 2005, thirteen-year-old Zhang Xiaoyi committed suicide by jumping from the top of a 24-story tower block in his home province Tianjin. After previously having spent two straight days playing online role-playing games in an Internet cafe, Zhang had told his parents that he had "been poisoned by games and could no longer control himself". His parents sued Aomeisoft, the China-region publisher of the game World of Warcraft. The head of a software association said to gaming website Play.tm that same year: "In the hypothetical world created by such games, [players] become confident and gain satisfaction, which they cannot get in the real world."In 2007, a 26-year-old man identified only as "Zhang" died of a heart attack due to lack of physical activity following a seven-day gaming binge, while a 30-year-old man died in a Guangzhou Internet cafe after playing online games for three straight days.
South Korea
In 2005, 28-year old industrial repairman Seungseob Lee (Hangul: 이승섭) visited an Internet cafe in the city of Daegu and played StarCraft almost continuously for fifty hours. He went into cardiac arrest and died at a local hospital. A friend reported: "... he was a game addict. We all knew about it. He couldnt stop himself." About six weeks before his death, his girlfriend, also an avid gamer, broke up with him. In addition, he was fired from his job.In 2009, Kim Sa-rang, a 3-month-old Korean girl, starved to death after both her parents spent hours each day in an Internet cafe, rearing a virtual child in an online game, Prius Online. The death is covered in the 2014 documentary Love Child.
United States
In November 2001, Shawn Woolley committed suicide; it has been inferred that his death was related to the popular computer game EverQuest. Shawns mother said the suicide was due to a rejection or betrayal in the game from a character Shawn called "iluvyou".Ohio teenager Daniel Petric shot his parents, killing his mother, after they took away his copy of Halo 3 in October 2007. In a sentencing hearing after the teen was found guilty of aggravated murder, the judge said, "I firmly believe that Daniel Petric had no idea at the time he hatched this plot that if he killed his parents they would be dead forever", in reference to his disconnection from reality caused by playing violent video games. On 16 June 2009, Petric was sentenced to 23 years to life in prison.
See also
Behavioral addiction
Digital media use and mental health
Internet addiction disorder
References
== Further reading == |
Parinauds syndrome | Parinauds syndrome is an inability to move the eyes up and down. It is caused by compression of the vertical gaze center at the rostral interstitial nucleus of medial longitudinal fasciculus (riMLF). The eyes lose the ability to move upward and down.
It is a group of abnormalities of eye movement and pupil dysfunction. It is caused by lesions of the upper brain stem and is named for Henri Parinaud (1844–1905), considered to be the father of French ophthalmology.
Signs and symptoms
Parinauds syndrome is a cluster of abnormalities of eye movement and pupil dysfunction, characterized by:
Paralysis of upwards gaze: Downward gaze is usually preserved. This vertical palsy is supranuclear, so dolls head maneuver should elevate the eyes, but eventually all upward gaze mechanisms fail.
Pseudo-Argyll Robertson pupils: Accommodative paresis ensues, and pupils become mid-dilated and show light-near dissociation.
Convergence-retraction nystagmus: Attempts at upward gaze often produce this phenomenon. On fast up-gaze, the eyes pull in and the globes retract. The easiest way to bring out this reaction is to ask the patient to follow down-going stripes on an optokinetic drum.
Eyelid retraction (Colliers sign)
Conjugate down gaze in the primary position: "setting-sun sign". Neurosurgeons see this sign most commonly in patients with failed hydrocephalus shunts.It is also commonly associated with bilateral papilledema. It has less commonly been associated with spasm of accommodation on attempted upward gaze, pseudoabducens palsy (also known as thalamic esotropia) or slower movements of the abducting eye than the adducting eye during horizontal saccades, see-saw nystagmus and associated ocular motility deficits including skew deviation, oculomotor nerve palsy, trochlear nerve palsy and internuclear ophthalmoplegia.
Causes
Parinauds syndrome results from injury, either direct or compressive, to the dorsal midbrain. Specifically, compression or ischemic damage of the mesencephalic tectum, including the superior colliculus adjacent oculomotor (origin of cranial nerve III) and Edinger-Westphal nuclei, causing dysfunction to the motor function of the eye.
Classically, it has been associated with three major groups:
Young patients with brain tumors in the pineal gland or midbrain: pinealoma (intracranial germinomas) are the most common lesion producing this syndrome.
Women in their 20s-30s with multiple sclerosis
Older patients following stroke of the upper brainstemHowever, any other compression, ischemia or damage to this region can produce these phenomena: obstructive hydrocephalus, midbrain hemorrhage, cerebral arteriovenous malformation, trauma and brainstem toxoplasmosis infection. Neoplasms and giant aneurysms of the posterior fossa have also been associated with the midbrain syndrome.
Vertical supranuclear ophthalmoplegia has also been associated with metabolic disorders, such as Niemann-Pick disease, Wilsons disease, kernicterus, and barbiturate overdose.
Diagnosis
Diagnosis can be made via combination of physical exam, particularly deficits of the relevant cranial nerves. Confirmation can be made via imaging, such as CT scan or MRI.
Treatment
Treatment is primarily directed towards etiology of the dorsal midbrain syndrome. A thorough workup, including neuroimaging is essential to rule out anatomic lesions or other causes of this syndrome. Visually significant upgaze palsy can be relieved with bilateral inferior rectus recessions. Retraction nystagmus and convergence movement are usually improved with this procedure as well.
Prognosis
The eye findings of Parinauds syndrome generally improve slowly over months, especially with resolution of the causative factor; continued resolution after the first 3–6 months of onset is uncommon. However, rapid resolution after normalization of intracranial pressure following placement of a ventriculoperitoneal shunt has been reported.
References
Further reading
Aguilar-Rebolledo F, Zárate-Moysén A, Quintana-Roldán G (1998). "Parinauds syndrome in children". Rev. Invest. Clin. (in Spanish). 50 (3): 217–20. PMID 9763886.
Waga S, Okada M, Yamamoto Y (1979). "Reversibility of Parinaud syndrome in thalamic hemorrhage". Neurology. 29 (3): 407–9. doi:10.1212/wnl.29.3.407. PMID 571990. S2CID 42247406.
== External links == |
Polymer fume fever | Polymer fume fever or fluoropolymer fever, also informally called Teflon flu, is an inhalation fever caused by the fumes released when polytetrafluoroethylene (PTFE, known under the trade name Teflon) reaches temperatures of 300 °C (572 °F) to 450 °C (842 °F). When PTFE is heated above 450 °C the pyrolysis products are different and inhalation may cause acute lung injury. Symptoms are flu-like (chills, headaches and fevers) with chest tightness and mild cough. Onset occurs about 4 to 8 hours after exposure to the pyrolysis products of PTFE. A high white blood cell count may be seen and chest x-ray findings are usually minimal.
The polymer fumes are especially harmful to certain animals whose breathing, optimized for rapidity, allows toxins which are excluded by human lungs. Fumes from Teflon in very high heat are fatal to parrots, as well as some other birds (PTFE toxicosis).
See also
Metal fume fever
References
Further reading
Shusterman DJ (1993). "Polymer fume fever and other fluorocarbon pyrolysis-related syndromes". Occup Med. 8 (3): 519–31. PMID 8272977.
== External links == |
Bromoderma | Bromoderma is a skin condition characterized by an eruption of papules and pustules on the skin.: 135 It is caused by hypersensitivity to bromides, such as those found in certain drugs. There is at least one reported case of bromoderma caused by excessive consumption of a soft drink (Ruby Red Squirt) containing brominated vegetable oil.
See also
Skin lesion
List of cutaneous conditions
References
== External links == |
Microvenular hemangioma | Microvenular hemangioma is an acquired benign vascular tumor that presents as an asymptomatic, slowly growing, 0.5- to 2.0 cm reddish lesion on the forearms or other sites of young to middle-aged adults.
See also
List of cutaneous conditions
References
== External links == |
Twin-to-twin transfusion syndrome | Twin-to-twin transfusion syndrome (TTTS), also known as feto-fetal transfusion syndrome (FFTS), twin oligohydramnios-polyhydramnios sequence (TOPS) and stuck twin syndrome, is a complication of monochorionic multiple pregnancies (the most common form of identical twin pregnancy) in which there is disproportionate blood supply between the fetuses. This leads to unequal levels of amniotic fluid between each fetus and usually leads to death of the undersupplied twin and, without treatment, usually death or a range of birth defects or disabilities for a surviving twin, such as underdeveloped, damaged or missing limbs, digits or organs (including the brain), especially cerebral palsy.The condition occurs when the vein–artery connections within the fetuses shared placenta allow the blood flow between each fetus to become progressively imbalanced. It usually develops between week 16 and 25 of pregnancy, during peak placental growth. The cause of the developmental effects on a surviving fetus may include necrotic embolisms from a dead fetus, low blood volume due to pooling in the dead fetus or velamentous cord insertion (insertion of the umbilical cord into the chorioamniotic membranes).The primary treatment of TTTS is fetoscopy and laser ablation of the interconnecting blood vessels to cut off the exchange of blood between the fetuses. This treatment is associated with an 85% survival rate of at least one fetus. Other treatments include periodic removal of amniotic fluid (serial amniocentesis), which is associated with a 66% survival rate of at least one fetus. Without treatment, there is an almost 100% mortality rate of one or all fetuses. Even with treatment, the condition is associated with premature birth and a risk of cerebral palsy in a surviving fetus.
Around 5–15% of identical twin fetuses will go on to develop TTTS. The condition was first described by German obstetrician Friedrich Schatz in 1875.
Cause
As a result of sharing a single placenta, the blood supplies of monochorionic twin fetuses can become connected, so that they share blood circulation: although each fetus uses its own portion of the placenta, the connecting blood vessels within the placenta allow blood to pass from one twin to the other. It is thought that most monochorionic placentae have these "shared connections" that cross the placenta, with the net flow volumes being equal between them. This state is sometimes referred to as "flow balance". When the placenta has deep vein–artery connection, this can cause blood flow to become unbalanced.Depending on the number, type and direction of the interconnecting blood vessels (anastomoses), blood can be transferred disproportionately from one twin (the "donor") to the other (the "recipient"), due to a state of "flow imbalance" imparted by new blood vessel growth across the placental "equator", the line that divides each babys proportion of the shared placenta. This state of transfusion causes the donor twin to have decreased blood volume, retarding the donors development and growth, and also decreased urinary output, leading to a lower than normal level of amniotic fluid (becoming oligohydramnios). The blood volume of the recipient twin is increased, which can strain the fetuss heart and eventually lead to heart failure, and also higher than normal urinary output, which can lead to excess amniotic fluid (becoming polyhydramnios). The demise of the fetus is typically a result of ischemia related to the lack of blood flow. The lack of blood flow causes bowel atresia, brain damage, and kidney failure.TTTS usually develops during the period of peak placental growth, starting in week 16 and proceeding through week 25; after this point, the placentas growth decelerates, essentially stopping just after week 30. While TTTS has occasionally been detected beyond this timepoint, it is thought that its occurrence beyond week 30 may be due to a placental embolism that upsets the flow balance of the shared connections between the babies. TTTS is potentially lethal to either or both twins, no matter when it is detected. However, when detected past week 25, emergency delivery may be considered to rescue the babies if the TTTS is severe.Other than requiring a monochorionic twin (or higher multiple) pregnancy, the underlying causes of TTTS are not known. It is not known to be hereditary or genetic.
Effects to the surviving fetus
The fetal demise of one of the twins during the second trimester of a monochorionic pregnancy can result in serious complications to the surviving fetus. Complications include gangrenous limbs, hands and feet, cerebral palsy and IQ deficits, constriction rings of limbs and digits, reduced digits, skin defects, brain cysts, hydranencephaly, multicystic encephalomalacia, microencephaly, renal agenesis and bowel atresia. There are three hypotheses explaining these complications.
Embolic Theory: The demise of the donor twin allows necrotic tissue, presumably thrombosis-plastin like material, to pass through the vasculature of the surviving twin via the placental vessels. The necrotic tissue embolizes the surviving twins mesenteric artery, resulting in bowel atresia, the renal artery, resulting in renal agenesis, or the peripheral arteries, resulting in limb ischemia and skin abnormalities.
Ischemic Theory: The demise of the donor twin creates a low-pressure state resulting in the shunting of blood into the low-resistance vascular system of the dead fetus. This state of low pressure acutely causes hypovolemia, resulting in ischemia and poor end-organ perfusion.
Placentation Theory: The incidence of velamentous cord insertion, an abnormal insertion of the umbilical cord into the placenta, is higher in TTTS. The exact mechanism of effect this has on fetal damage is unknown.
Diagnosis
Quintero stages
A staging system is commonly used to classify the severity of TTTS.Stage I: A small amount of amniotic fluid (oligohydramnios) is found around the donor twin and a large amount of amniotic fluid (polyhydramnios) is found around the recipient twin.
Stage II: In addition to the description above, the ultrasound is not able to identify the bladder in the donor twin.
Stage III: In addition to the characteristics of Stages I and II, there is abnormal blood flow in the umbilical cords of the twins.
Stage IV: In addition to all of the above findings, the recipient twin has swelling under the skin and appears to be experiencing heart failure (fetal hydrops).
Stage V: In addition to all of the above findings, one of the twins has died. This can happen to either twin. The risk to either the donor or the recipient is roughly equal & is quite high in Stage II or higher TTTS.
The Quintero staging does not provide information about prognosis, and other staging systems have been proposed.
Treatment
Various treatments exist for TTTS.
Non treatment
This is equivalent of zero intervention. It has been associated with almost 100% mortality rate of one or all fetuses. Exceptions to this include patients that are still in Stage 1 TTTS and are past 22 weeks gestation.
Adjustment of amniotic fluid
Serial amniocentesis
This procedure involves removal of amniotic fluid periodically throughout the pregnancy under the assumption that the extra fluid in the recipient twin can cause preterm labor, perinatal mortality, or tissue damage. In the case that the fluid does not reaccumulate, the reduction of amniotic fluid stabilizes the pregnancy. Otherwise, the treatment is repeated as necessary. There is no standard procedure for how much fluid is removed each time. There is a danger that if too much fluid is removed, the recipient twin could die. This procedure is associated with a 66% survival rate of at least one fetus, with a 15% risk of cerebral palsy, and average delivery occurring at 29 weeks gestation.
Septostomy, or iatrogenic disruption of the dividing membrane
This procedure involves the tearing of the dividing membrane between fetuses such that the amniotic fluid of both twins mixes, under the assumption that pressure is different in either amniotic sac and that its equilibration will ameliorate progression of the disease. It has not been proven that pressures are different in either amniotic sac. Use of this procedure can preclude use of other procedures as well as make difficult the monitoring of disease progression. In addition, tearing the dividing membrane has contributed to cord entanglement and demise of fetuses through physical complications.
Adjustment of blood supply
Laser therapy
This procedure involves endoscopic surgery using laser to interrupt the vessels that allow exchange of blood between fetuses under the assumption that the unequal sharing of blood through these vascular communications leads to unequal levels of amniotic fluid. Each fetus remains connected to its primary source of blood and nutrition, the placenta, through the umbilical cord. This procedure is conducted once, with the exception of all vessels not having been found. The use of endoscopic instruments allows for short recovery time. This procedure has been associated with 85% survival rate of at least one fetus, with a 6–7% risk of cerebral palsy and average delivery occurring at 32–33 weeks gestation.Twin anemia–polycythemia sequence (TAPS) may occur after laser surgery for TTTS (post-laser form). The spontaneous form of TAPS complicates approximately 3 to 5% of monochorionic twin pregnancies, whereas the post-laser form occurs in 2 to 13% of TTTS cases. The pathogenesis of TAPS is based on the presence of few, minuscule arterio-venous (AV) placental anastomoses (diameter <1mm) allowing a slow transfusion of blood from the donor to the recipient and leading gradually to highly discordant Hb levels.A 2014 review found that laser coagulation resulted in fewer fetal and perinatal deaths than amnioreduction and septostomy, and recommended its use for all states of TTTS.
Umbilical cord occlusion
This procedure involves the ligation or otherwise occlusion of the umbilical cord to interrupt the exchange of blood between the fetuses. The procedure is typically offered in cases where one of the fetuses is presumed moribund and endangering the life or health of the other twin through resultant hypotension. Use of this treatment has decreased as TTTS is identified and treated in earlier stages and with better outcomes. When used, it is associated with an 85% survival rate of the remaining fetuses with 5% risk of cerebral palsy and a 33–39 weeks of gestation at delivery.
Diet supplementation
Some doctors recommend complete bed rest for the mother coupled with massive intakes of protein as a therapy to try to counteract the syndrome. Research completed shows these nutritional supplements do work.Diet supplementation was associated with lower overall incidence of TTTS (20/52 versus 8/51, P = 0.02) and lower prevalence of TTTS at delivery (18/52 versus 6/51, P = 0.012) when compared with no supplementation. In the study, nutritional supplementation contained 250kcal, consisting of 6g of lipids, 40g of carbohydrates, 9g of protein, vitamins and minerals, consumed three times per day. Nutritional intervention also significantly prolonged the time between the diagnosis of TTTS and delivery (9.4 ± 3.7 weeks versus 4.6 ± 6.5 weeks; P = 0.014). The earlier nutritional regimen was introduced, the lesser chance of detecting TTTS ( P = 0.001). Although not statistically significant, dietary intervention was also associated with lower Quintero stage, fewer invasive treatments, and lower twin birth weight discordance.Diet supplementation appears to counter maternal metabolic abnormalities in monochorionic twin pregnancies and improve perinatal outcomes in TTTS when combined with the standard therapeutic options. Nutritional therapy appears to be most effective in mitigating cases that are caught in Quintero Stage I, little effect has been observed in those that are beyond Stage I.
Epidemiology
Based on recent (2005) US NCHS data, the rate of multiple births is now approximately 3.4% (4,138,349 total births, of which 139,816 were twins or higher-order multiple births). The majority of identical twins share a common (monochorionic) placenta, and of these approximately 15% go on to develop TTTS. By extrapolating the number of expected identical twins (about one-third) from annual multiple births, and the number of twins with monochorionic placentae (about two-thirds), and from these the number thought to develop TTTS (about 15%), there are at least 4,500 TTTS cases per year in the U.S. alone: 139,816 × .33 × .66 × .15 = 4,568 cases of TTTS per year in U.S. (involving more than 9,000 babies.) Since spontaneous pregnancy losses and terminations that occur prior to 20 weeks go uncounted by the C.D.C., this estimate of TTTS cases may be very conservative. Although infertility treatments have increased the rate of multiple birth, they have not appreciably diluted the expected incidence of identical twins. Studies show a higher rate of identical twins (up to 20 times with IVF) using these treatments versus spontaneous pregnancy rates.
One Australian study, however, noted an occurrence of only 1 in 4,170 pregnancies, or 1 in 58 twin gestations. This distinction could be partly explained by the "hidden mortality" associated with MC multifetal pregnancies—instances lost due to premature rupture of membrane (PROM) or intrauterine fetal demise before a thorough diagnosis of TTTS can be made.
History
TTTS was first described by a German obstetrician, Friedrich Schatz, in 1875. Once defined by neonatal parameters—differences in birth weight and cord hemoglobin at the time of delivery—TTTS is now defined differently. Today, it is known that discordant fetal weights will most likely be a late manifestation, and fetal hemoglobin through cordocentesis is often equivalent in the twin pair even in severe TTTS.
In art
A painting known as the De Wikkelkinderen (The Swaddled Children), from 1617, is thought to represent a depiction of TTTS. The drawing shows twins that appear to be identical, but one is pale, while the other is red. Analysis of the family histories of the owners of the painting suggests that the twins did not survive to adulthood, although whether that is due to TTTS is uncertain.
See also
Twin anemia-polycythemia sequence
Vanishing twin
Unequal placental sharing
References
External links
Connecting the World to Fight TTTS, including TAPS, SIUGR and TRAP |
Cestoda | Cestoda is a class of parasitic worms in the flatworm phylum (Platyhelminthes). Most of the species—and the best-known—are those in the subclass Eucestoda; they are ribbon-like worms as adults, known as tapeworms. Their bodies consist of many similar units known as proglottids—essentially packages of eggs which are regularly shed into the environment to infect other organisms. Species of the other subclass, Cestodaria, are mainly fish infecting parasites.
All cestodes are parasitic; many have complex life histories, including a stage in a definitive (main) host in which the adults grow and reproduce, often for years, and one or two intermediate stages in which the larvae develop in other hosts. Typically the adults live in the digestive tracts of vertebrates, while the larvae often live in the bodies of other animals, either vertebrates or invertebrates. For example, Diphyllobothrium has at least two intermediate hosts, a crustacean and then one or more freshwater fish; its definitive host is a mammal. Some cestodes are host-specific, while others are parasites of a wide variety of hosts. Some six thousand species have been described; probably all vertebrates can host at least one species.
The adult tapeworm has a scolex (head), a short neck, and a strobila (segmented body) formed of proglottids. Tapeworms anchor themselves to the inside of the intestine of their host using their scolex, which typically has hooks, suckers, or both. They have no mouth, but absorb nutrients directly from the hosts gut. The neck continually produces proglottids, each one containing a reproductive tract; mature proglottids are full of eggs, and fall off to leave the host, either passively in the feces or actively moving. All tapeworms are hermaphrodites, with each individual having both male and female reproductive organs.
Humans are subject to infection by several species of tapeworms if they eat undercooked meat such as pork (Taenia solium), beef (T. saginata), and fish (Diphyllobothrium), or if they live in, or eat food prepared in, conditions of poor hygiene (Hymenolepis or Echinococcus species). The unproven concept of using tapeworms as a slimming aid has been touted since around 1900.
Diversity and habitat
All 6,000 species of Cestoda are parasites, mainly intestinal; their definitive hosts are vertebrates, both terrestrial and marine, while their intermediate hosts include insects, crustaceans, molluscs, and annelids as well as other vertebrates.T. saginata, the beef tapeworm, can grow up to 20 m (65 ft); the largest species, the whale tapeworm Tetragonoporus calyptocephalus, can grow to over 30 m (100 ft). Species with small hosts tend to be small. For example, vole and lemming tapeworms are only 13–240 mm (0.5–9.4 in) in length, and those parasitizing shrews only 0.8–60 mm (0.03–2.36 in).
Anatomy
Cestodes have no gut or mouth and absorb nutrients from the hosts alimentary tract through their specialised neodermal cuticle, or tegument, through which gas exchange also takes place. The tegument also protects the parasite from the hosts digestive enzymes and allows it to transfer molecules back to the host.The body form of adult eucestodes is simple, with a scolex, or grasping head, adapted for attachment to the definitive host, a short neck, and a strobila, or segmented trunk formed of proglottids, which makes up the worms body. Members of the subclass Cestodaria, the Amphilinidea and Gyrocotylidea, are wormlike but not divided into proglottids. Amphilinids have a muscular proboscis at the front end; Gyrocotylids have a sucker or proboscis which they can pull inside or push outside at the front end, and a holdfast rosette at the posterior end.The Cestodaria have 10 larval hooks while Eucestoda have 6 larval hooks.
Scolex
The scolex, which attaches to the intestine of the definitive host, is often minute in comparison with the proglottids. It is typically a four-sided knob, armed with suckers or hooks or both. In some species, the scolex is dominated by bothria, or "sucking grooves" that function like suction cups. Cyclophyllid cestodes can be identified by the presence of four suckers on their scolices. Other species have ruffled or leaflike scolices, and there may be other structures to aid attachment.In the larval stage the scolex is similarly shaped and is known as the protoscoleces.
Body systems
Circular and longitudinal muscles lie under the neodermis, beneath which further longitudinal, dorso-ventral and transverse muscles surround the central parenchyma. Protonephridial cells drain into the parenchyma. There are four longitudinal collection canals, two dorso-lateral and two ventro-lateral, running along the length of the worm, with a transverse canal linking the ventral ones at the posterior of each segment. When the proglottids begin to detach, these canals open to the exterior through the terminal segment.The main nerve centre of a cestode is a cerebral ganglion in its scolex. Nerves emanate from the ganglion to supply the general body muscular and sensory endings, with two lateral nerve cords running the length of the strobila. The cirrus and vagina are innervated, and sensory endings around the genital pore are more plentiful than in other areas. Sensory function includes both tactoreception (touch) and chemoreception (smell or taste).
Proglottids
Once anchored to the hosts intestinal wall, tapeworms absorb nutrients through their surface as their food flows past them. Cestodes are unable to synthesise lipids, which they use for reproduction, and are therefore entirely dependent on their hosts.The tapeworm body is composed of a series of segments called proglottids. These are produced from the neck by mitotic growth, which is followed by transverse constriction. The segments become larger and more mature as they are displaced backwards by newer segments. Each proglottid contains an independent reproductive tract, and like some other flatworms, cestodes excrete waste through flame cells (protonephridia) located in the proglottids. The sum of the proglottids is called a strobila, which is thin and resembles a strip of tape; from this is derived the common name "tapeworm". Proglottids are continually being produced by the neck region of the scolex, as long as the scolex is attached and alive.Mature proglottids are essentially bags of eggs, each of which is infective to the proper intermediate host. They are released and leave the host in feces, or migrate outwards as independent motile proglottids. The number of proglottids forming the tapeworm ranges from three to four thousand. Their layout comes in two forms: craspedote, meaning any given proglottid is overlapped by the previous proglottid, or acraspedote, indicating the proglottids do not overlap.
Reproduction
Cestodes are exclusively hermaphrodites, with both male and female reproductive systems in each body. The reproductive system includes one or more testes, cirri, vas deferens, and seminal vesicles as male organs, and a single lobed or unlobed ovary with the connecting oviduct and uterus as female organs. The common external opening for both male and female reproductive systems is known as the genital pore, which is situated at the surface opening of the cup-shaped atrium. Though they are sexually hermaphroditic and cross-fertilization is the norm, self-fertilization sometimes occurs and makes possible the reproduction of a worm when it is the only individual in its hosts gut. During copulation, the cirri of one individual connect with those of the other through the genital pore, and then spermatozoa are exchanged.
Life cycle
Cestodes are parasites of vertebrates, with each species infecting a single definitive host or group of closely related host species. All but amphilinids and gyrocotylids (which burrow through the gut or body wall to reach the coelom) are intestinal, though some life-cycle stages rest in muscle or other tissues. The definitive host is always a vertebrate but in nearly all cases, one or more intermediate hosts are involved in the lifecycle, typically arthropods or other vertebrates. Infections can be long-lasting; in humans, tapeworm infection may last as much as 30 years. No asexual phases occur in the lifecycle, as they do in other flatworms, but the lifecycle pattern has been a crucial criterion for assessing evolution among Platyhelminthes.Cestodes produce large numbers of eggs, but each one has a low probability of finding a host. To increase their chances, different species have adopted various strategies of egg release. In the Pseudophyllidea, many eggs are released in the brief period when their aquatic intermediate hosts are abundant (semelparity). In contrast, in the terrestrial Cyclophyllidea, proglottids are released steadily over a period of years, or as long as their host lives (iteroparity). Another strategy is to have very long-lived larvae; for example, in Echinococcus, the hydatid larvae can survive for ten years or more in humans and other vertebrate hosts, giving the tapeworm an exceptionally long time window in which to find another host.Many tapeworms have a two-phase lifecycle with two types of host. The adult Taenia saginata lives in the gut of a primate such as a human, its definitive host. Proglottids leave the body through the anus and fall to the ground, where they may be eaten with grass by a grazing animal such as a cow. This animal then becomes an intermediate host, the oncosphere boring through the gut wall and migrating to another part of the body such as the muscle. Here it encysts, forming a cysticercus. The parasite completes its lifecycle when the intermediate host passes on the parasite to the definitive host, usually when the definitive host eats contaminated parts of the intermediate host, for example a human eating raw or undercooked meat. Another two-phase lifecycle is exhibited by Anoplocephala perfoliata, the definitive host being an equine and the intermediate host an oribatid mite.Diphyllobothrium exhibits a more complex, three-phase lifecycle. If the eggs are laid in water, they develop into free-swimming oncosphere larvae. After ingestion by a suitable freshwater crustacean such as a copepod, the first intermediate host, they develop into procercoid larvae. When the copepod is eaten by a suitable second intermediate host, typically a minnow or other small freshwater fish, the procercoid larvae migrate into the fishs flesh where they develop into plerocercoid larvae. These are the infective stages for the mammalian definitive host. If the small fish is eaten by a predatory fish, its muscles too can become infected.Schistocephalus solidus is another three-phase example. The intermediate hosts are copepods and small fish, and the definitive hosts are waterbirds. This species has been used to demonstrate that cross-fertilisation produces a higher infective success rate than self-fertilisation.
Host immunity
Hosts can become immune to infection by a cestode if the lining, the mucosa, of the gut is damaged. This exposes the hosts immune system to cestode antigens, enabling the host to mount an antibody defence. Host antibodies can kill or limit cestode infection by damaging their digestive enzymes, which reduces their ability to feed and therefore to grow and to reproduce; by binding to their bodies; and by neutralising toxins that they produce. When cestodes feed passively in the gut, they do not provoke an antibody reaction.
Evolution and phylogeny
Fossil history
Parasite fossils are rare, but recognizable clusters of cestode eggs, some with an operculum (lid) indicating that they had not erupted, one with a developing larva, have been discovered in fossil shark coprolites dating to the Permian, some 270 million years ago.The fossil Rugosusivitta, which was found in China at base of the Cambrian deposits in Yunnan just above the Ediacaran-Cambrian border, has great similarities to present day Cestodians. If correct, this would be the earliest example of a Platyzoan and also one of the earliest bilaterian body-fossils and might thus provide an insight to the living mode of Cestodians before they became specialized parasites.
External
The position of the Cestoda within the Platyhelminthes and other Spiralian phyla based on genomic analysis is shown in the phylogenetic tree. The non-parasitic flatworms, traditionally grouped as the "Turbellaria", are paraphyletic, as the parasitic Neodermata including the Cestoda arose within that grouping. The approximate times when major groups first appeared is shown in millions of years ago.
Internal
The evolutionary history of the Cestoda has been studied using ribosomal RNA, mitochondrial and other DNA, and morphological analysis and continues to be revised. "Tetraphyllidea" is seen to be paraphyletic; "Pseudophyllidea" has been broken up into two orders, Bothriocephalidea and Diphyllobothriidea. Hosts, whose phylogeny often mirrors that of the parasites (Fahrenholzs rule), are indicated in italics and parentheses, the life-cycle sequence (where known) shown by arrows as (intermediate host1 [→ intermediate host2 ] → definitive host). Alternatives, generally for different species within an order, are shown in square brackets.
The Taeniidae, including species such as the pork tapeworm and the beef tapeworm that often infect humans, may be the most basal of the 12 orders of the Cyclophyllidea.
Interactions with humans
Infection and treatment
Like other species of mammal, humans can become infected with tapeworms. There may be few or no symptoms, and the first indication of the infection may be the presence of one or more proglottids in the stools. The proglottids appear as flat, rectangular, whitish objects about the size of a grain of rice, which may change size or move about. Bodily symptoms which are sometimes present include abdominal pain, nausea, diarrhea, increased appetite and weight loss.There are several classes of anthelminthic drugs, some effective against many kinds of parasite, others more specific; these can be used both preventatively and to treat infections. For example, praziquantel is an effective treatment for tapeworm infection, and is preferred over the older niclosamide. While accidental tapeworm infections in developed countries are quite rare, such infections are more likely to occur in countries with poor sanitation facilities or where food hygiene standards are low.
History and culture
In ancient Greece, the comic playwright Aristophanes and philosopher Aristotle described the lumps that form during cysticercosis as "hailstones". In Medieval times, in The Canon of Medicine, completed in 1025, the Persian physician Avicenna recorded parasites including tapeworms. In the Early Modern period, Francesco Redi described and illustrated many parasites, and was the first to identify the cysts of Echinococcus granulosus seen in dogs and sheep as parasitic in origin; a century later, in 1760, Peter Simon Pallas correctly suggested that these were the larvae of tapeworms.Tapeworms have occasionally appeared in fiction. Peter Marren and Richard Mabey in Bugs Britannica write that Irvine Welshs sociopathic policeman in his 1998 novel Filth owns a talking tapeworm, which they call "the most attractive character in the novel"; it becomes the policemans alter ego and better self. Mira Grants 2013 novel Parasite envisages a world where peoples immune systems are maintained by genetically engineered tapeworms. Tapeworms are prominently mentioned in the System of a Down song "Needles": their inclusion within the song result in a lyrical dispute among band members.There are unproven claims that, around 1900, tapeworm eggs were marketed to the public as slimming tablets. A full-page coloured image, purportedly from a womens magazine of that period, reads "Fat: the enemy ... that is banished! How? With sanitized tape worms. Jar packed. No ill effects!" When television presenter Michael Mosley deliberately infected himself with tapeworms he gained weight due to increased appetite. Dieters still sometimes risk intentional infection, evidenced by a 2013 warning on American television.
Notes
References
Further reading
Merck Manual of Medication Information, Second Home Edition, Online Version, Tapeworm Infection 2005
Mayo Clinic Website on infectious diseases, Mayo Clinic - Tapeworm Infection, 2006
Medline Plus - Taeniasis (tapeworm infection)
University of South Carolina - School of Medicine - Cestodes (tapeworms) |
Urethrovaginal fistula | A urethrovaginal fistula is an abnormal passageway that may occur the urethra and the vagina. It is a sub-set of vaginal fistulas. It results in urinary incontinence as urine continually leaves the vagina. It can occur as an obstetrical complication, catheter insertion injury or a surgical injury.It is also called a urethral fistula and may be referred to as UVF. They are quite rare. In the developed world, they are typically due to injuries due to medical activity.
== References == |
Contact stomatitis | Contact stomatitis is inflammation or pain of the oral mucosa caused by external stimuli. It is characterized by cutaneous lesions that may be located where the offending agent contacts the mucosa for a prolonged time. Oftentimes it presents in the mouth after contact with hot food or from ill-fitted dentures or other irritant. Consequently, patients may seek resolve from their dentist rather than a dermatologist. Unlike with allergic contact stomatitis, the skin requires no previous exposure to a stimulant before crafting an immune reaction.
See also
Contact urticaria
List of cutaneous conditions
== References == |
Transmissible spongiform encephalopathy | Transmissible spongiform encephalopathies (TSEs) are a group of progressive and fatal conditions that are associated with prions and affect the brain and nervous system of many animals, including humans, cattle, and sheep. According to the most widespread hypothesis, they are transmitted by prions, though some other data suggest an involvement of a Spiroplasma infection. Mental and physical abilities deteriorate and many tiny holes appear in the cortex causing it to appear like a sponge when brain tissue obtained at autopsy is examined under a microscope. The disorders cause impairment of brain function, including memory changes, personality changes and problems with movement that worsen chronically.TSEs of humans include Creutzfeldt–Jakob disease, Gerstmann–Sträussler–Scheinker syndrome, fatal familial insomnia, kuru, as well as the recently discovered variably protease-sensitive prionopathy and familial spongiform encephalopathy. Creutzfeldt-Jakob disease itself has four main forms, the sporadic (sCJD), the hereditary/familial (fCJD), the iatrogenic (iCJD) and the variant form (vCJD). These conditions form a spectrum of diseases with overlapping signs and symptoms.
TSEs in non-human mammals include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle – popularly known as "mad cow disease" – and chronic wasting disease (CWD) in deer and elk. The variant form of Creutzfeldt–Jakob disease in humans is caused by exposure to bovine spongiform encephalopathy prions.Unlike other kinds of infectious disease, which are spread by agents with a DNA or RNA genome (such as virus or bacteria), the infectious agent in TSEs is believed to be a prion, thus being composed solely of protein material. Misshapened prion proteins carry the disease between individuals and cause deterioration of the brain. TSEs are unique diseases in that their aetiology may be genetic, sporadic, or infectious via ingestion of infected foodstuffs and via iatrogenic means (e.g., blood transfusion). Most TSEs are sporadic and occur in an animal with no prion protein mutation. Inherited TSE occurs in animals carrying a rare mutant prion allele, which expresses prion proteins that contort by themselves into the disease-causing conformation. Transmission occurs when healthy animals consume tainted tissues from others with the disease. In the 1980s and 1990s, bovine spongiform encephalopathy spread in cattle in an epidemic fashion. This occurred because cattle were fed the processed remains of other cattle, a practice now banned in many countries. In turn, consumption (by humans) of bovine-derived foodstuff which contained prion-contaminated tissues resulted in an outbreak of the variant form of Creutzfeldt–Jakob disease in the 1990s and 2000s.Prions cannot be transmitted through the air, through touching, or most other forms of casual contact. However, they may be transmitted through contact with infected tissue, body fluids, or contaminated medical instruments. Normal sterilization procedures such as boiling or irradiating materials fail to render prions non-infective. However, treatment with strong, almost undiluted bleach and/or sodium hydroxide, or heating to a minimum of 134 °C, does destroy prions.
Classification
Features
The degenerative tissue damage caused by human prion diseases (CJD, GSS, and kuru) is characterised by four features: spongiform change, neuronal loss, astrocytosis, and amyloid plaque formation. These features are shared with prion diseases in animals, and the recognition of these similarities prompted the first attempts to transmit a human prion disease (kuru) to a primate in 1966, followed by CJD in 1968 and GSS in 1981. These neuropathological features have formed the basis of the histological diagnosis of human prion diseases for many years, although it was recognized that these changes are enormously variable both from case to case and within the central nervous system in individual cases.The clinical signs in humans vary, but commonly include personality changes, psychiatric problems such as depression, lack of coordination, and/or an unsteady gait (ataxia). Patients also may experience involuntary jerking movements called myoclonus, unusual sensations, insomnia, confusion, or memory problems. In the later stages of the disease, patients have severe mental impairment (dementia) and lose the ability to move or speak.Early neuropathological reports on human prion diseases suffered from a confusion of nomenclature, in which the significance of the diagnostic feature of spongiform change was occasionally overlooked. The subsequent demonstration that human prion diseases were transmissible reinforced the importance of spongiform change as a diagnostic feature, reflected in the use of the term "spongiform encephalopathy" for this group of disorders.
Prions appear to be most infectious when in direct contact with affected tissues. For example, Creutzfeldt–Jakob disease has been transmitted to patients taking injections of growth hormone harvested from human pituitary glands, from cadaver dura allografts and from instruments used for brain surgery (Brown, 2000) (prions can survive the "autoclave" sterilization process used for most surgical instruments). It is also believed that dietary consumption of affected animals can cause prions to accumulate slowly, especially when cannibalism or similar practices allow the proteins to accumulate over more than one generation. An example is kuru, which reached epidemic proportions in the mid-20th century in the Fore people of Papua New Guinea, who used to consume their dead as a funerary ritual. Laws in developed countries now ban the use of rendered ruminant proteins in ruminant feed as a precaution against the spread of prion infection in cattle and other ruminants.There exists evidence that prion diseases may be transmissible by the airborne route.Note that not all encephalopathies are caused by prions, as in the cases of PML (caused by the JC virus), CADASIL (caused by abnormal NOTCH3 protein activity), and Krabbe disease (caused by a deficiency of the enzyme galactosylceramidase). Progressive Spongiform Leukoencephalopathy (PSL)—which is a spongiform encephalopathy—is also probably not caused by a prion, although the adulterant that causes it among heroin smokers has not yet been identified. This, combined with the highly variable nature of prion disease pathology, is why a prion disease cannot be diagnosed based solely on a patients symptoms.
Cause
Genetics
Mutations in the PRNP gene cause prion disease. Familial forms of prion disease are caused by inherited mutations in the PRNP gene. Only a small percentage of all cases of prion disease run in families, however. Most cases of prion disease are sporadic, which means they occur in people without any known risk factors or gene mutations. In rare circumstances, prion diseases also can be transmitted by exposure to prion-contaminated tissues or other biological materials obtained from individuals with prion disease.
The PRNP gene provides the instructions to make a protein called the prion protein (PrP). Under normal circumstances, this protein may be involved in transporting copper into cells. It may also be involved in protecting brain cells and helping them communicate. 24 Point-Mutations in this gene cause cells to produce an abnormal form of the prion protein, known as PrPSc. This abnormal protein builds up in the brain and destroys nerve cells, resulting in the signs and symptoms of prion disease.
Familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent.
In some people, familial forms of prion disease are caused by a new mutation in the PRNP gene. Although such people most likely do not have an affected parent, they can pass the genetic change to their children.
Protein-only hypothesis
Protein could be the infectious agent, inducing its own replication by causing conformational change of normal cellular PrPC into PrPSc. Evidence for this hypothesis:
Infectivity titre correlates with PrPSc levels. However, this is disputed.
PrPSc is an isomer of PrPC
Denaturing PrP removes infectivity
PrP-null mice cannot be infected
PrPC depletion in the neural system of mice with established neuroinvasive prion infection reverses early spongeosis and behavioural deficits, halts further disease progression and increases life-span
Multi-component hypothesis
While not containing a nucleic acid genome, prions may be composed of more than just a protein. Purified PrPC appears unable to convert to the infectious PrPSc form, unless other components are added, such as RNA and lipids. These other components, termed cofactors, may form part of the infectious prion, or they may serve as catalysts for the replication of a protein-only prion.
Viral hypothesis
This hypothesis postulates that an as of yet undiscovered infectious viral agent is the cause of the disease. Evidence for this hypothesis is as follows:
Incubation time is comparable to a lentivirus
Strain variation of different isolates of PrPSc
An increasing titre of PrPSc as the disease progresses suggests a replicating agent.
Diagnosis
There continues to be a very practical problem with diagnosis of prion diseases, including BSE and CJD. They have an incubation period of months to decades during which there are no symptoms, even though the pathway of converting the normal brain PrP protein into the toxic, disease-related PrPSc form has started. At present, there is virtually no way to detect PrPSc reliably except by examining the brain using neuropathological and immunohistochemical methods after death. Accumulation of the abnormally folded PrPSc form of the PrP protein is a characteristic of the disease, but it is present at very low levels in easily accessible body fluids like blood or urine. Researchers have tried to develop methods to measure PrPSc, but there are still no fully accepted methods for use in materials such as blood.In 2010, a team from New York described detection of PrPSc even when initially present at only one part in a hundred billion (10−11) in brain tissue. The method combines amplification with a novel technology called Surround Optical Fiber Immunoassay (SOFIA) and some specific antibodies against PrPSc. After amplifying and then concentrating any PrPSc, the samples are labelled with a fluorescent dye using an antibody for specificity and then finally loaded into a micro-capillary tube. This tube is placed in a specially constructed apparatus so that it is totally surrounded by optical fibres to capture all light emitted once the dye is excited using a laser. The technique allowed detection of PrPSc after many fewer cycles of conversion than others have achieved, substantially reducing the possibility of artefacts, as well as speeding up the assay. The researchers also tested their method on blood samples from apparently healthy sheep that went on to develop scrapie. The animals brains were analysed once any symptoms became apparent. The researchers could therefore compare results from brain tissue and blood taken once the animals exhibited symptoms of the diseases, with blood obtained earlier in the animals lives, and from uninfected animals. The results showed very clearly that PrPSc could be detected in the blood of animals long before the symptoms appeared.
Epidemiology
Transmissible spongiform encephalopathies (TSE) are very rare but can reach epidemic proportions. It is very hard to map the spread of the disease due to the difficulty of identifying individual strains of the prions. This means that, if animals at one farm begin to show the disease after an outbreak on a nearby farm, it is very difficult to determine whether it is the same strain affecting both herds—suggesting transmission—or if the second outbreak came from a completely different source.
Classic Creutzfeldt-Jakob disease (CJD) was discovered in 1920. It occurs sporadically over the world but is very rare. It affects about one person per million each year. Typically, the cause is unknown for these cases. It has been found to be passed on genetically in some cases. 250 patients contracted the disease through iatrogenic transmission (from use of contaminated surgical equipment). This was before equipment sterilization was required in 1976, and there have been no other iatrogenic cases since then. In order to prevent the spread of infection, the World Health Organization created a guide to tell health care workers what to do when CJD appears and how to dispose of contaminated equipment. The Centers for Disease Control and Prevention (CDC) have been keeping surveillance on CJD cases, particularly by looking at death certificate information.Chronic wasting disease (CWD) is a prion disease found in North America in deer and elk. The first case was identified as a fatal wasting syndrome in the 1960s. It was then recognized as a transmissible spongiform encephalopathy in 1978. Surveillance studies showed the endemic of CWD in free-ranging deer and elk spread in northeastern Colorado, southeastern Wyoming and western Nebraska. It was also discovered that CWD may have been present in a proportion of free-ranging animals decades before the initial recognition. In the United States, the discovery of CWD raised concerns about the transmission of this prion disease to humans. Many apparent cases of CJD were suspected transmission of CWD, however the evidence was lacking and not convincing.In the 1980s and 1990s, bovine spongiform encephalopathy (BSE or "mad cow disease") spread in cattle at an epidemic rate. The total estimated number of cattle infected was approximately 750,000 between 1980 and 1996. This occurred because the cattle were fed processed remains of other cattle. Then human consumption of these infected cattle caused an outbreak of the human form CJD. There was a dramatic decline in BSE when feeding bans were put in place. On May 20, 2003, the first case of BSE was confirmed in North America. The source could not be clearly identified, but researchers suspect it came from imported BSE-infected cow meat. In the United States, the USDA created safeguards to minimize the risk of BSE exposure to humans.Variant Creutzfeldt-Jakob disease (vCJD) was discovered in 1996 in England. There is strong evidence to suggest that vCJD was caused by the same prion as bovine spongiform encephalopathy. A total of 231 cases of vCJD have been reported since it was first discovered. These cases have been found in a total of 12 countries with 178 in the United Kingdom, 27 in France, five in Spain, four in Ireland, four in the United States, three in the Netherlands, three in Italy, two in Portugal, two in Canada, and one each in Japan, Saudi Arabia, and Taiwan.
History
In the 5th century BCE, Hippocrates described a disease like TSE in cattle and sheep, which he believed also occurred in man. Publius Flavius Vegetius Renatus records cases of a disease with similar characteristics in the 4th and 5th centuries AD. In 1755, an outbreak of scrapie was discussed in the British House of Commons and may have been present in Britain for some time before that. Although there were unsupported claims in 1759 that the disease was contagious, in general it was thought to be due to inbreeding and countermeasures appeared to be successful. Early-20th-century experiments failed to show transmission of scrapie between animals, until extraordinary measures were taken such as the intra-ocular injection of infected nervous tissue. No direct link between scrapie and disease in man was suspected then or has been found since. TSE was first described in man by Alfons Maria Jakob in 1921. Daniel Carleton Gajduseks discovery that Kuru was transmitted by cannibalism accompanied by the finding of scrapie-like lesions in the brains of Kuru victims strongly suggested an infectious basis to TSE. A paradigm shift to a non-nucleic infectious entity was required when the results were validated with an explanation of how a prion protein might transmit spongiform encephalopathy. Not until 1988 was the neuropathology of spongiform encephalopathy properly described in cows. The alarming amplification of BSE in the British cattle herd heightened fear of transmission to humans and reinforced the belief in the infectious nature of TSE. This was confirmed with the identification of a Kuru-like disease, called new variant Creutzfeldt–Jakob disease, in humans exposed to BSE. Although the infectious disease model of TSE has been questioned in favour of a prion transplantation model that explains why cannibalism favours transmission, the search for a viral agent was, as of 2007, being continued in some laboratories.
References
This entry incorporates public domain text originally from the National Institute of Neurological Disorders and Stroke, National Institutes of Health [1] and the U.S. National Library of Medicine [2]
External links
Transmissible spongiform encephalopathy at Curlie |
Diprosopus | Diprosopus (Greek: διπρόσωπος, "two-faced", from δι-, di-, "two" and πρόσωπον, prósopon [neuter], "face", "person"; with Latin ending), also known as craniofacial duplication (cranio- from Greek κρανίον, "skull", the other parts Latin), is an extremely rare congenital disorder whereby parts (accessories) or all of the face are duplicated on the head.
Development
Although classically considered conjoined twinning (which it resembles), diprosopus is not normally due to the fusion or incomplete separation of two embryos. It is the result of abnormal activity by the protein SHH (sonic hedgehog). (The name of this protein was inspired by the Sonic the Hedgehog video game character and is part of an idiosyncratic naming tradition in molecular biology research.)SHH and its corresponding genes have been found to play an important role in signaling craniofacial patterning during embryonic development. Among other things, SHH governs the width of facial features. In excess it leads to widening of facial features and to duplication of facial structures. The greater the widening, the more structures are duplicated, often in a mirror image form. This has been demonstrated in the laboratory by introducing pellets of the SHH protein into chicken embryos, resulting in chickens with duplicate beaks. Inadequate amounts of that protein lead to opposite conditions such as cyclopia where facial features are insufficiently developed.Healthy brain development is also dependent on the signaling function of SHH. During embryonic development, SHH directs embryonic cells to organize in specific areas that later become specialized neural tissues, thus controlling the size and shape of brain structures.
Occurrences
Diprosopus often occurs in combination with other congenital disorders, particularly anencephaly, neural tube defect and cardiac malformations. When present, the brain may show abnormalities ranging from partial to complete duplication of brain structures, and/or underdevelopment of brain tissues.
Humans
Most human infants with diprosopus are stillborn. Known instances of humans with diprosopus surviving for longer than minutes to hours past birth are very rare; only a few are recorded. In 2002 and 2003, two living male infants with partial diprosopus were described in the medical literature in separate case reports. One infant was born with duplication of the nose and the cerebral frontal lobes, two widely spaced eyes, a small, underdeveloped central eye socket, and a large, asymmetric mouth. The other infant was born with duplication of the upper and lower jaw, two tongues arising from the same base, cleft palate, a slightly divided tip of the nose, and two widely spaced eyes, as well as absence of the corpus callosum, duplication of the pituitary gland and stalk, and abnormalities in the midbrain. Because they were born with a milder, partial form of diprosopus, both infants were considered candidates for surgical correction of their abnormal facial features.
Spanish case
In January 1775, a Spanish family gave birth to a girl with diprosopus. She had 3 eyes (one a combination of 2), 2 noses, 2 mouths, and 3 chins. The child was taken on tour from village to village, and gained much attention in Spain and neighboring countries. Her case is mentioned in Nicolas-François and Geneviève Regnaults Les écarts de la nature, published that year. Her full lifespan is unknown, but is mentioned to still be alive in French publications as late as 1777.
Lali Singh
Lali Singh (10 March – 10 May 2008) was born to Sushma and Vinod Singh in Saini, Sunpura Sohanpur village, near Delhi; the birth was delayed by dystocia caused by her large head, and her birth in a hospital was facilitated by her mothers receiving an episiotomy. She was one of the very few infants with diprosopus to survive well past birth, and may have been the only known living individual with complete facial duplication. Her facial features included two pairs of eyes, two noses, and two mouths (but only one pair of ears). She was seen as the reincarnation of the goddess Durga, who is sometimes depicted with many limbs and eyes.
Sushma and Vinod Singh declined an offer from local doctors to evaluate their daughter through CT or MRI scanning. Without diagnostic imaging, it was not possible to know the full extent to which the childs condition might have affected her brain and other vital structures in her head and neck. Thus, any estimation of her ability to thrive or even survive could be only speculative, though Lalis family described her as functioning normally. It is also unknown whether neurosurgeons or craniofacial surgeons, if consulted, would have had feasible solutions to offer with respect to corrective surgery. A local doctor told reporters that the baby should be considered a healthy child who currently was living a normal life, a previously unknown occurrence among sufferers of the disorder.Lalis two middle eyes suffered from corneal opacity due to abnormal anatomy of the facial muscles, which prevented her from properly closing those eyes; initially, this was wrongly blamed on camera flashes.
A cleft palate caused difficulty in her feeding under village conditions. A poor diet of bottle-fed sugar solution and diluted milk, allowed to drip down her throat, as she could not suck properly due to her cleft palate, weakened her condition, and vomiting and infection ensued. Admission to hospital was delayed by discussion (including taking her back home from hospital) among her extended family and her villages headman. Finally, her parents, alarmed at her illness and dehydration, defied her other relatives and took her back to hospital, where under proper medical treatment including antibiotic and a saline drip she started to improve, stopped vomiting, started drinking milk and defecating normally. However, six hours later, at two months old to the day, she died of a heart attack. She was buried in her village, as is usual in Hinduism with children who die very young. Later a temple was built at the village in her memory.
Faith and Hope Howie
Faith Daisy and Hope Alice Howie (8 May – 27 May 2014) were born in Sydney, Australia, to parents Simon Howie and Renee Young. Faith and Hope shared one body and skull, but had complete duplication of the facial features, as well as duplication of the brain; both brains joined to one brain stem. Young and Howie had learned at nineteen weeks gestation of their childrens condition, but opted not to terminate the pregnancy. The children were born six weeks prematurely and appeared to be doing well, able to breathe unaided several days after their birth, and they were observed to sleep and cry at different times. They died nineteen days following their birth due to unknown causes, although some sources indicated that the girls died following an operation for unknown reasons.
Other animals
Janus, a goat with two faces on one body, survived from April 5 to May 5, 2020 in Wittenberg, Wisconsin.
Few two-faced animals have survived due to associated internal organ abnormalities and brain abnormalities. One of the most famous was Ditto, a pig. Ditto was raised to adulthood, but died of pneumonia caused by food inhalation when breathing through one muzzle while eating with the other.
Cats with the condition are known as Janus cats, after the Roman god. In July 2006, a six-year-old male Janus cat called "Frank and Louie" from Millbury, Massachusetts, USA, received publicity. In their case, only one esophagus (and possibly only one trachea) were functional; this aided survival. In September 2011, when Frank and Louie were twelve years old, it was announced that they would appear in the 2012 Guinness Book of World Records as the longest-surviving Janus cat on record. In 2014, Frank and Louie died at the age of fifteen.
See also
Conjoined twins
Craniopagus parasiticus
Cyclopia
Durga, a three-eyed Hindu goddess
Edward Mordake, a disputed story of a 19th-century man with a face on the back of his head
Futakuchi-onna, a female Japanese yōkai with mouth on back of her head/hair
Janus, a Roman god with two faces
Kara Mia, a Philippine TV series that tells the story of a young woman with two faces divided in one body.
Polycephaly
References
External links
Armand Marie, Leroi (2005). Mutants: On Genetic Variety and the Human Body. New York, NY: Penguin Books. ISBN 9780142004821. Retrieved March 13, 2014.
Howie, Sarah; Fisher, Carolyn Elaine, eds. (2010). Shh and Gli Signalling in Development. Molecular Biology Intelligence Unit. New York, NY: Springer Science+Business Media, Inc. doi:10.1007/978-0-387-39957-7. ISBN 978-0-387-39957-7. Retrieved March 13, 2014.
Tapadia MD, Cordero DR, Helms JA (November 2005). "Its all in your head: new insights into craniofacial development and deformation". J. Anat. 207 (5): 461–77. doi:10.1111/j.1469-7580.2005.00484.x. PMC 1571563. PMID 16313388.
‘Sonic Hedgehog’ sounded funny, at first. New York Times, 12 November 2006.
Rediscovering biology: Unit 7, Genetics of development. Expert interview transcripts, interview with John Incardona, PhD. explanation of the discovery and naming of the sonic hedgehog gene
Page for sonic hedgehog homolog (SHH) at The Human Genome Organisation (HUGO)
Two-faced kitten has image problem at Channel4000
Two-faced kitten shocks owner, veterinarian at OregonNews.com
Two-faced cat sets record as oldest living "Janus" cat at Reuters
diprosopus kitten
diprosopus piglet
diprosopus calf
Rescue Kitten Was Born With Two Face Who Rejected By Her Cat Mom diprosopus kitten
Baby with 2 faces born in north India MSNBC
Image:Diprosopus |
Trinucleotide repeat disorder | Trinucleotide repeat disorders, also known as microsatellite expansion diseases, are a set of over 50 genetic disorders caused by trinucleotide repeat expansion, a kind of mutation in which repeats of three nucleotides (trinucleotide repeats) increase in copy numbers until they cross a threshold above which they become unstable. Depending on its location, the unstable trinucleotide repeat may cause defects in a protein encoded by a gene; change the regulation of gene expression; produce a toxic RNA, or lead to chromosome instability. In general, the larger the expansion the faster the onset of disease, and the more severe the disease becomes.Trinucleotide repeats are a subset of a larger class of unstable microsatellite repeats that occur throughout all genomes.
The first trinucleotide repeat disease to be identified was fragile X syndrome, which has since been mapped to the long arm of the X chromosome. Patients carry from 230 to 4000 CGG repeats in the gene that causes fragile X syndrome, while unaffected individuals have up to 50 repeats and carriers of the disease have 60 to 230 repeats. The chromosomal instability resulting from this trinucleotide expansion presents clinically as intellectual disability, distinctive facial features, and macroorchidism in males. The second DNA-triplet repeat disease, fragile X-E syndrome, was also identified on the X chromosome, but was found to be the result of an expanded CCG repeat. The discovery that trinucleotide repeats could expand during intergenerational transmission and could cause disease was the first evidence that not all disease-causing mutations are stably transmitted from parent to offspring.There are several known categories of trinucleotide repeat disorder. Category I includes Huntingtons disease (HD) and the spinocerebellar ataxias. These are caused by a CAG repeat expansion in protein-coding portions, or exons, of specific genes. Category II expansions are also found in exons, and tend to be more phenotypically diverse with heterogeneous expansions that are generally small in magnitude. Category III includes fragile X syndrome, myotonic dystrophy, two of the spinocerebellar ataxias, juvenile myoclonic epilepsy, and Friedreichs ataxia. These diseases are characterized by typically much larger repeat expansions than the first two groups, and the repeats are located in introns rather than exons.
Types
Some of the problems in trinucleotide repeat syndromes result from causing alterations in the coding region of the gene, while others are caused by altered gene regulation. In over half of these disorders, the repeated trinucleotide, or codon, is CAG. In a coding region, CAG codes for glutamine (Q), so CAG repeats result in a polyglutamine tract. These diseases are commonly referred to as polyglutamine (or polyQ) diseases. The repeated codons in the remaining disorders do not code for glutamine, and these are classified as non-polyglutamine diseases.
Polyglutamine (PolyQ) diseases
Non-polyglutamine diseases
Symptoms and signs
A common symptom of polyQ diseases is the progressive degeneration of nerve cells, usually affecting people later in life. Although these diseases share the same repeated codon (CAG) and some symptoms, the repeats are found in different, unrelated genes. In all cases, the expanded CAG repeats are translated into an uninterrupted sequence of glutamine residues, forming a polyQ tract, and the accumulation of polyQ proteins damages key cellular functions such as the ubiquitin-proteasome system. However different polyQ-containing proteins damage different subsets of neurons, leading to different symptoms. As of 2017, ten neurological and neuromuscular disorders were known to be caused by an increased number of CAG repeats.The non-PolyQ diseases do not share any specific symptoms and are unlike the PolyQ diseases. In some of these diseases, such as Fragile X syndrome, the pathology is caused by lack of the normal function of the protein encoded by the affected gene. In others, such as Myotonic Dystrophy Type 1, the pathology is caused by a change in protein expression or function mediated through changes in the messenger RNA produced by the expression of the affected gene. In yet others, the pathology is caused by toxic assemblies of RNA in the nuclei of cells.
Genetics
Trinucleotide repeat disorders generally show genetic anticipation: their severity increases with each successive generation that inherits them. This is likely explained by the addition of CAG repeats in the affected gene as the gene is transmitted from parent to child. For example, Huntingtons disease occurs when there are more than 35 CAG repeats on the gene coding for the protein HTT. A parent with 35 repeats would be considered normal and would not exhibit any symptoms of the disease. However, that parents offspring would be at an increased risk of developing Huntingtons compared to the general population, as it would take only the addition of one more CAG codon to cause the production of mHTT (mutant HTT), the protein responsible for disease.
Huntingtons very rarely occurs spontaneously; it is almost always the result of inheriting the defective gene from an affected parent. However, sporadic cases of Huntingtons in individuals who have no history of the disease in their families do occur. Among these sporadic cases, there is a higher frequency of individuals with a parent who already has a significant number of CAG repeats in their HTT gene, especially those whose repeats approach the number (36) required for the disease to manifest. Each successive generation in a Huntingtons-affected family may add additional CAG repeats, and the higher the number of repeats, the more severe the disease and the earlier its onset. As a result, families that have had Huntingtons for many generations show an earlier age of disease onset and faster disease progression.
Non-trinucleotide expansions
The majority of diseases caused by expansions of simple DNA repeats involve trinucleotide repeats, but tetra-, penta- and dodecanucleotide repeat expansions are also known that cause disease. For any specific hereditary disorder, only one repeat expands in a particular gene.
Mechanism
Triplet expansion is caused by slippage during DNA replication or during DNA repair synthesis. Because the tandem repeats have identical sequence to one another, base pairing between two DNA strands can take place at multiple points along the sequence. This may lead to the formation of loop out structures during DNA replication or DNA repair synthesis. This may lead to repeated copying of the repeated sequence, expanding the number of repeats. Additional mechanisms involving hybrid RNA:DNA intermediates have been proposed.
Diagnosis
See also
C9orf72
RAN translation
References
External links
Trinucleotide+Repeat+Expansion at the US National Library of Medicine Medical Subject Headings (MeSH)
GeneReviews/NCBI/NIH/UW entry on DRPLA
National Institute of Neurological Disorders and Stroke
Genetics Home Reference |
Leydig cell hypoplasia | Leydig cell hypoplasia (or aplasia) (LCH), also known as Leydig cell agenesis, is a rare autosomal recessive genetic and endocrine syndrome affecting an estimated 1 in 1,000,000 genetic males. It is characterized by an inability of the body to respond to luteinizing hormone (LH), a gonadotropin which is normally responsible for signaling Leydig cells of the testicles to produce testosterone and other androgen sex hormones. The condition manifests itself as pseudohermaphroditism (partially or fully underdeveloped genitalia), hypergonadotropic hypogonadism (decreased or lack of production of sex steroids by the gonads despite high circulating levels of gonadotropins), reduced or absent puberty (lack of development of secondary sexual characteristics, resulting in sexual infantilism if left untreated), and infertility.Leydig cell hypoplasia does not occur in biological females as they do not have either Leydig cells or testicles. However, the cause of the condition in males, luteinizing hormone insensitivity, does affect females, and because LH plays a role in the female reproductive system, it can result in primary amenorrhea or oligomenorrhea (absent or reduced menstruation), infertility due to anovulation, and ovarian cysts.A related condition is follicle-stimulating hormone (FSH) insensitivity, which presents with similar symptoms to those of Leydig cell hypoplasia but with the symptoms in the respective sexes reversed (i.e., hypogonadism and sexual infantilism in females and merely problems with fertility in males). Despite their similar causes, FSH insensitivity is considerably less common in comparison to LH insensitivity.
Symptoms and signs
The symptoms of Leydig cell hypoplasia include pseudohermaphroditism, i.e., feminized, ambiguous, or relatively mildly underdeveloped (e.g., micropenis, severe hypospadias, and/or cryptorchidism [undescended testes]) external genitalia, a female gender identity or gender variance, hypergonadotropic hypogonadism (hypogonadism despite high levels of gonadotropins), delayed, impaired, or fully absent puberty with an associated reduction in or complete lack of development of secondary sexual characteristics (sexual infantilism), impaired fertility or complete sterility, tall stature (due to delayed epiphyseal closure), eunuchoid skeletal proportions, delayed or absent bone maturation, and osteoporosis.
Cause
Leydig cell hypoplasia is caused by genetic mutations in LHCGR, a gene which encodes the LH/hCG receptor. LH normally acts through the LH/hCG receptor to stimulate the growth of Leydig cells in the testicles and the production of androgens such as testosterone and dihydrotestosterone (DHT) by these cells. In Leydig cell hypoplasia however, there is a reduced capacity for the LH/hCG receptor to respond to LH. This results in hypoplasia or absence of Leydig cells, testicular atrophy, and lower than normal androgen levels. In the most severe form of the condition in which there is a complete lack of response of the Leydig cells to LH, androgen production by the testicles is virtually negligible and secondary sexual characteristics entirely fail to develop at puberty.
Diagnosis
Since the Sertoli cells are not affected by Leydig cell hypoplasia, anti-Müllerian hormone is secreted normally and so there are no Müllerian structures. Wolffian structures, such as the prostate, vasa deferentia, and epidydimides are present. In type I, abdominal testes are revealed on ultrasound; in type II testes may be descended or undescended.People with Leydig cell hypoplasia type I display no response to the hCG stimulation test; there is no increase in serum levels of testosterone and dihydrotestosterone. Leydig cell hypoplasia type II can display either a pronounced rise of testosterone levels or no rise.In any case, the diagnosis is confirmed on biopsy of the testes, revealing either absent or hypoplastic Leydig cells. The inside of the testis will be grayish and mucous, displaying arrested spermatogenesis and the presence of Sertoli cells. The diagnosis can also be confirmed by looking for mutations in the gene for the LH receptor.A diagnosis of Leydig cell hypoplasia is usually made in the neonatal period, following the discovery of ambiguous genitalia, or at puberty, when secondary sex characteristics fail to develop. Puberty is the most common time for Leydig cell hypoplasia to be diagnosed.
Treatment
Patients with Leydig cell hypoplasia may be treated with hormone replacement therapy (i.e., with androgens), which will result in normal sexual development and the resolution of most symptoms. In the case of 46,XY (genetically "male") individuals who are phenotypically female and/or identify as the female gender, estrogens should be given instead. Surgical correction of the genitals in 46,XY males may be required, and, if necessary, an orchidopexy (relocation of the undescended testes to the scrotum) may be performed as well.
See also
Disorders of sex development
Intersexuality, pseudohermaphroditism, and ambiguous genitalia
Hypogonadism and hypogonadotropic hypogonadism
Familial male-limited precocious puberty (or LH oversensitivity)
Follicle-stimulating hormone insensitivity
Gonadotropin-releasing hormone insensitivity
Inborn errors of steroid metabolism
Isolated 17,20-lyase deficiency
Combined 17α-hydroxylase/17,20-lyase deficiency
17β-Hydroxysteroid dehydrogenase III deficiency
Androgen insensitivity syndrome
References
== External links == |
Xerotic eczema | Xerotic eczema is a form of eczema that is characterized by changes that occur when skin becomes abnormally dry, red, itchy, and cracked. It tends to occur more often during the winter and in dry conditions.
Xerotic eczema is common in elderly people, though it is not uncommon for people in their 20s. It can appear in red, bumpy, pimple-like irritations.
Treatment
The first method that should be taken when treating xerotic eczema is attempting to re-hydrate the dry skin using a humidifier and bathing/showering less frequently. Mild and moisturizing soaps should be used to prevent further irritation. Scratching the affected area should be avoided. Applying moisturizing lotion or anti-itch ointment frequently should help in reducing dryness.
If the re-hydration process does not alleviate the symptoms, moisturizers such as Lac-Hydrin 5% or 12% moisturizer containing urea can be used; furthermore, if the skin becomes inflamed or cracked, mid- to high-potency corticosteroids can be used.A study published in 2005 found positive results from soaking the affected area in water for twenty minutes and then applying mid- to high-strength corticosteroid ointment.
See also
Skin lesion
== References == |
Papillary fibroelastoma | A papillary fibroelastoma is a primary tumor of the heart that typically involves one of the valves of the heart. Papillary fibroelastomas, while considered generally rare, make up about 10 percent of all primary tumors of the heart. They are the third most common type of primary tumor of the heart, behind cardiac myxomas and cardiac lipomas.
Signs and symptoms
A papillary fibroelastoma is generally considered pathologically benign, however outflow obstruction or embolism can be associated with syncope, chest pain, heart attack, stroke and sudden cardiac death.
Symptoms due to papillary fibroelastomas are generally due to either mechanical effects of the tumor or due to embolization of a portion of the tumor to a distal organ. In particular, chest pain or syncope may be due to transient occlusion of the left main coronary artery by the tumor, while a heart attack or sudden cardiac death may be due to embolization of a portion of the tumor into a coronary artery.
Diagnosis
Papillary fibroelastoma are typically found and accurately diagnosed by imaging. The diagnosis is confirmed by pathology. Histologically, papillary fibroelastomas have branching avascular papillae, composed of collagen, that are covered by endothelium.
Treatment
If the tumor is found incidentally in an asymptomatic person, the treatment approach is controversial. Certainly a conservative approach is warranted in certain individuals. If the tumor is large, greater than 1 cm in asymptomatic patients, and pedunculated, a case may be made for surgical excision prior to symptoms developing due to the higher risk of embolism. However, this is still considered controversial.If the papillary fibroelastoma is associated with symptoms, surgical excision is generally recommended for relief of symptoms. A minimally invasive approach may be possible if the tumor involves the aortic valve or right atrium. In the case of aortic valve involvement, excision of the tumor is often valve-sparing, meaning that replacement of the valve with a prosthetic valve is not necessary. Repair of the native valve with a pericardial patch has been described.
See also
Endocardial fibroelastosis
References
== External links == |
Retina | The retina (from Latin: rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then processes that image within the retina and sends nerve impulses along the optic nerve to the visual cortex to create visual perception. The retina serves a function which is in many ways analogous to that of the film or image sensor in a camera.
The neural retina consists of several layers of neurons interconnected by synapses and is supported by an outer layer of pigmented epithelial cells. The primary light-sensing cells in the retina are the photoreceptor cells, which are of two types: rods and cones. Rods function mainly in dim light and provide monochromatic vision. Cones function in well-lit conditions and are responsible for the perception of colour through the use of a range of opsins, as well as high-acuity vision used for tasks such as reading. A third type of light-sensing cell, the photosensitive ganglion cell, is important for entrainment of circadian rhythms and reflexive responses such as the pupillary light reflex.
Light striking the retina initiates a cascade of chemical and electrical events that ultimately trigger nerve impulses that are sent to various visual centres of the brain through the fibres of the optic nerve. Neural signals from the rods and cones undergo processing by other neurons, whose output takes the form of action potentials in retinal ganglion cells whose axons form the optic nerve. Several important features of visual perception can be traced to the retinal encoding and processing of light.
In vertebrate embryonic development, the retina and the optic nerve originate as outgrowths of the developing brain, specifically the embryonic diencephalon; thus, the retina is considered part of the central nervous system (CNS) and is actually brain tissue. It is the only part of the CNS that can be visualized non-invasively. Much like the rest of the brain is isolated from the vasular system via the Blood-brain barrier, the retina is similarly protected by the Blood-retinal barrier.
Structure
Inverted versus non-inverted retina
The vertebrate retina is inverted in the sense that the light sensing cells are in the back of the retina, so that light has to pass through layers of neurons and capillaries before it reaches the photosensitive sections of the rods and cones. The ganglion cells, whose axons form the optic nerve, are at the front of the retina; therefore the optic nerve must cross through the retina en route to the brain. In this region there are no photoreceptors, giving rise to the blind spot. In contrast, in the cephalopod retina the photoreceptors are in front, with processing neurons and capillaries behind them. Because of this, cephalopods do not have a blind spot.
Although the overlying neural tissue is partly transparent, and the accompanying glial cells have been shown to act as fibre-optic channels to transport photons directly to the photoreceptors, light scattering does occur. Some vertebrates, including humans, have an area of the central retina adapted for high-acuity vision. This area, termed the fovea centralis, is avascular (does not have blood vessels), and has minimal neural tissue in front of the photoreceptors, thereby minimizing light scattering.The cephalopods have a non-inverted retina which is comparable in resolving power to the eyes of many vertebrates. Squid eyes do not have an analog of the vertebrate retinal pigment epithelium (RPE). Although their photoreceptors contain a protein, retinochrome, that recycles retinal and replicates one of the functions of the vertebrate RPE, one could argue that cephalopod photoreceptors are not maintained as well as in vertebrates and that, as a result, the useful lifetime of photoreceptors in invertebrates is much shorter than in vertebrates. Having easily replaced stalk-eyes (some lobsters) or retinae (some spiders, such as Deinopis) rarely occurs.
The cephalopod retina does not originate as an outgrowth of the brain, as the vertebrate one does. It is arguable that this difference shows that vertebrate and cephalopod eyes are not homologous but have evolved separately. From an evolutionary perspective, a more complex structure such as the inverted retina can generally come about as a consequence of two alternate processes: (a) an advantageous "good" compromise between competing functional limitations, or (b) as a historical maladaptive relic of the convoluted path of organ evolution and transformation. Vision is an important adaptation in higher vertebrates.
A third view of the "inverted" vertebrate eye is that it combines two benefits: the maintenance of the photoreceptors mentioned above, and the reduction in light intensity necessary to avoid blinding the photoreceptors, which are based on the extremely sensitive eyes of the ancestors of modern hagfishes (a fish that lives in very deep, dark water).
Retinal layers
The vertebrate retina has ten distinct layers. From closest to farthest from the vitreous body:
Inner limiting membrane – basement membrane elaborated by Müller cells.
Nerve fibre layer – axons of the ganglion cell bodies (note that a thin layer of Müller cell footplates exists between this layer and the inner limiting membrane).
Ganglion cell layer – contains nuclei of ganglion cells, the axons of which become the optic nerve fibres, and some displaced amacrine cells.
Inner plexiform layer – contains the synapse between the bipolar cell axons and the dendrites of the ganglion and amacrine cells.
Inner nuclear layer – contains the nuclei and surrounding cell bodies (perikarya) of the amacrine cells, bipolar cells, and horizontal cells.
Outer plexiform layer – projections of rods and cones ending in the rod spherule and cone pedicle, respectively. These make synapses with dendrites of bipolar cells and horizontal cells. In the macular region, this is known as the Fiber layer of Henle.
Outer nuclear layer – cell bodies of rods and cones.
External limiting membrane – layer that separates the inner segment portions of the photoreceptors from their cell nuclei.
Inner segment / outer segment layer – inner segments and outer segments of rods and cones. The outer segments contain a highly specialized light-sensing apparatus.
Retinal pigment epithelium – single layer of cuboidal epithelial cells (with extrusions not shown in diagram). This layer is closest to the choroid, and provides nourishment and supportive functions to the neural retina, The black pigment melanin in the pigment layer prevents light reflection throughout the globe of the eyeball; this is extremely important for clear vision.These layers can be grouped into 4 main processing stages: photoreception; transmission to bipolar cells; transmission to ganglion cells, which also contain photoreceptors, the photosensitive ganglion cells; and transmission along the optic nerve. At each synaptic stage there are also laterally connecting horizontal and amacrine cells.
The optic nerve is a central tract of many axons of ganglion cells connecting primarily to the lateral geniculate body, a visual relay station in the diencephalon (the rear of the forebrain). It also projects to the superior colliculus, the suprachiasmatic nucleus, and the nucleus of the optic tract. It passes through the other layers, creating the optic disc in primates.Additional structures, not directly associated with vision, are found as outgrowths of the retina in some vertebrate groups. In birds, the pecten is a vascular structure of complex shape that projects from the retina into the vitreous humour; it supplies oxygen and nutrients to the eye, and may also aid in vision. Reptiles have a similar, but much simpler, structure.In adult humans, the entire retina is approximately 72% of a sphere about 22 mm in diameter. The entire retina contains about 7 million cones and 75 to 150 million rods. The optic disc, a part of the retina sometimes called "the blind spot" because it lacks photoreceptors, is located at the optic papilla, where the optic-nerve fibres leave the eye. It appears as an oval white area of 3 mm². Temporal (in the direction of the temples) to this disc is the macula, at whose centre is the fovea, a pit that is responsible for our sharp central vision but is actually less sensitive to light because of its lack of rods. Human and non-human primates possess one fovea, as opposed to certain bird species, such as hawks, who are bifoviate, and dogs and cats, who possess no fovea but a central band known as the visual streak. Around the fovea extends the central retina for about 6 mm and then the peripheral retina. The farthest edge of the retina is defined by the ora serrata. The distance from one ora to the other (or macula), the most sensitive area along the horizontal meridian is about 32 mm.In section, the retina is no more than 0.5 mm thick. It has three layers of nerve cells and two of synapses, including the unique ribbon synapse. The optic nerve carries the ganglion cell axons to the brain, and the blood vessels that supply the retina. The ganglion cells lie innermost in the eye while the photoreceptive cells lie beyond. Because of this counter-intuitive arrangement, light must first pass through and around the ganglion cells and through the thickness of the retina, (including its capillary vessels, not shown) before reaching the rods and cones. Light is absorbed by the retinal pigment epithelium or the choroid (both of which are opaque).
The white blood cells in the capillaries in front of the photoreceptors can be perceived as tiny bright moving dots when looking into blue light. This is known as the blue field entoptic phenomenon (or Scheerers phenomenon).
Between the ganglion cell layer and the rods and cones there are two layers of neuropils where synaptic contacts are made. The neuropil layers are the outer plexiform layer and the inner plexiform layer. In the outer neuropil layer, the rods and cones connect to the vertically running bipolar cells, and the horizontally oriented horizontal cells connect to ganglion cells.
The central retina predominantly contains cones, while the peripheral retina predominantly contains rods. In total, there are about seven million cones and a hundred million rods. At the centre of the macula is the foveal pit where the cones are narrow and long, and, arranged in a hexagonal mosaic, the most dense, in contradistinction to the much fatter cones located more peripherally in the retina. At the foveal pit the other retinal layers are displaced, before building up along the foveal slope until the rim of the fovea, or parafovea, is reached, which is the thickest portion of the retina. The macula has a yellow pigmentation, from screening pigments, and is known as the macula lutea. The area directly surrounding the fovea has the highest density of rods converging on single bipolar cells. Since its cones have a much lesser convergence of signals, the fovea allows for the sharpest vision the eye can attain.Though the rod and cones are a mosaic of sorts, transmission from receptors, to bipolars, to ganglion cells is not direct. Since there are about 150 million receptors and only 1 million optic nerve fibres, there must be convergence and thus mixing of signals. Moreover, the horizontal action of the horizontal and amacrine cells can allow one area of the retina to control another (e.g. one stimulus inhibiting another). This inhibition is key to lessening the sum of messages sent to the higher regions of the brain. In some lower vertebrates (e.g. the pigeon), there is a "centrifugal" control of messages – that is, one layer can control another, or higher regions of the brain can drive the retinal nerve cells, but in primates this does not occur.
Layers imagable with optical coherence tomography
Using optical coherence tomography (OCT) there are 18 layers that can be identified in the retina. The layers and anatomical correlation are as follows:
From innermost to outermost, the layers identifiable by OCT are as follows:
Development
Retinal development begins with the establishment of the eye fields mediated by the SHH and SIX3 proteins, with subsequent development of the optic vesicles regulated by the PAX6 and LHX2 proteins. The role of Pax6 in eye development was elegantly demonstrated by Walter Gehring and colleagues, who showed that ectopic expression of Pax6 can lead to eye formation on Drosophila antennae, wings, and legs. The optic vesicle gives rise to three structures: the neural retina, the retinal pigmented epithelium, and the optic stalk. The neural retina contains the retinal progenitor cells (RPCs) that give rise to the seven cell types of the retina. Differentiation begins with the retinal ganglion cells and concludes with production of the Muller glia. Although each cell type differentiates from the RPCs in a sequential order, there is considerable overlap in the timing of when individual cell types differentiate. The cues that determine a RPC daughter cell fate are coded by multiple transcription factor families including the bHLH and homeodomain factors.In addition to guiding cell fate determination, cues exist in the retina to determine the dorsal-ventral (D-V) and nasal-temporal (N-T) axes. The D-V axis is established by a ventral to dorsal gradient of VAX2, whereas the N-T axis is coordinated by expression of the forkhead transcription factors FOXD1 and FOXG1. Additional gradients are formed within the retina. This spatial distribution may aid in proper targeting of RGC axons that function to establish the retinotopic map.
Blood supply
The retina is stratified into distinct layers, each containing specific cell types or cellular compartments that have metabolisms with different nutritional requirements. To satisfy these requirements, the ophthalmic artery bifurcates and supplies the retina via two distinct vascular networks: the choroidal network, which supplies the choroid and the outer retina, and the retinal network, which supplies the retinas inner layer.
Circulatory mechanisms
At first glance, one may think that the vertebrate retina is "wired wrongly" or "badly designed"; but in fact, the retina could not function if it were not inverted. The photoreceptor layer must be embedded in the retinal pigment epithelium (RPE), which performs at least seven vital functions, one of the most obvious being to supply oxygen and other necessary nutrients needed for the photoreceptors to function. These nutrients include glucose, fatty acids, and retinal. The mammalian photoreceptor amplification process uses large quantities energy for vision in photopic conditions (requiring less under scotopic conditions) and, thus, requires the large supply nutrients supplied by the blood vessels in the choroid, which lies beyond the RPE. The choroid supplies about 75% of these nutrients to the retina and the retinal vasculature only 25%.When light strikes 11-cis-retinal (in the disks in the rods and cones), 11-cis-retinal changes to all-trans-retinal which then triggers changes in the opsins. Now, the outer segments do not regenerate the retinal back into the cis- form once it has been changed by light. Instead the retinal is pumped out to the surrounding RPE where it is regenerated and transported back into the outer segments of the photoreceptors. This recycling function of the RPE protects the photoreceptors against photo-oxidative damage and allows the photoreceptor cells to have decades-long useful lives.
In birds
The bird retina is devoid of blood vessels, perhaps to give unobscured passage of light for forming images, thus giving better resolution. It is, therefore, a considered view that the bird retina depends for nutrition and oxygen supply on a specialized organ, called the "pecten" or pecten oculi, located on the blind spot or optic disk. This organ is extremely rich in blood vessels and is thought to supply nutrition and oxygen to the bird retina by diffusion through the vitreous body. The pecten is highly rich in alkaline phosphatase activity and polarized cells in its bridge portion – both befitting its secretory role. Pecten cells are packed with dark melanin granules, which have been theorized to keep this organ warm with the absorption of stray light falling on the pecten. This is considered to enhance metabolic rate of the pecten, thereby exporting more nutritive molecules to meet the stringent energy requirements of the retina during long periods of exposure to light.
Biometric identification and diagnosis of disease
The bifurcations and other physical characteristics of the inner retinal vascular network are known to vary among individuals, and these individual variances have been used for biometric identification and for early detection of the onset of disease. The mapping of vascular bifurcations is one of the basic steps in biometric identification. Results of such analyses of retinal blood vessel structure can be evaluated against the ground truth data of vascular bifurcations of retinal fundus images that are obtained from the DRIVE dataset. In addition, the classes of vessels of the DRIVE dataset have also been identified, and an automated method for accurate extraction of these bifurcations is also available. Changes in retinal blood circulation are seen with aging and exposure to air pollution, and may indicate cardiovascular diseases such as hypertension and atherosclerosis. Determining the equivalent width of arterioles and venules near the optic disc is also a widely used technique to identify cardiovascular risks.
Function
The retina translates an optical image into neural impulses starting with the patterned excitation of the colour-sensitive pigments of its rods and cones, the retinas photoreceptor cells. The excitation is processed by the neural system and various parts of the brain working in parallel to form a representation of the external environment in the brain.
The cones respond to bright light and mediate high-resolution colour vision during daylight illumination (also called photopic vision). The rod responses are saturated at daylight levels and dont contribute to pattern vision. However, rods do respond to dim light and mediate lower-resolution, monochromatic vision under very low levels of illumination (called scotopic vision). The illumination in most office settings falls between these two levels and is called mesopic vision. At mesopic light levels, both the rods and cones are actively contributing pattern information. What contribution the rod information makes to pattern vision under these circumstances is unclear.
The response of cones to various wavelengths of light is called their spectral sensitivity. In normal human vision, the spectral sensitivity of a cone falls into one of three subtypes, often called blue, green, and red, but more accurately known as short, medium, and long wavelength-sensitive cone subtypes. It is a lack of one or more of the cone subtypes that causes individuals to have deficiencies in colour vision or various kinds of colour blindness. These individuals are not blind to objects of a particular colour, but are unable to distinguish between colours that can be distinguished by people with normal vision. Humans have this trichromatic vision, while most other mammals lack cones with red sensitive pigment and therefore have poorer dichromatic colour vision. However, some animals have four spectral subtypes, e.g. the trout adds an ultraviolet subgroup to short, medium, and long subtypes that are similar to humans. Some fish are sensitive to the polarization of light as well.
In the photoreceptors, exposure to light hyperpolarizes the membrane in a series of graded shifts. The outer cell segment contains a photopigment. Inside the cell the normal levels of cyclic guanosine monophosphate (cGMP) keep the Na+ channel open, and thus in the resting state the cell is depolarised. The photon causes the retinal bound to the receptor protein to isomerise to trans-retinal. This causes the receptor to activate multiple G-proteins. This in turn causes the Ga-subunit of the protein to activate a phosphodiesterase (PDE6), which degrades cGMP, resulting in the closing of Na+ cyclic nucleotide-gated ion channels (CNGs). Thus the cell is hyperpolarised. The amount of neurotransmitter released is reduced in bright light and increases as light levels fall. The actual photopigment is bleached away in bright light and only replaced as a chemical process, so in a transition from bright light to darkness the eye can take up to thirty minutes to reach full sensitivity.
When thus excited by light, the photoceptor sends a proportional response synaptically to bipolar cells which in turn signal the retinal ganglion cells. The photoreceptors are also cross-linked by horizontal cells and amacrine cells, which modify the synaptic signal before it reaches the ganglion cells, the neural signals being intermixed and combined. Of the retinas nerve cells, only the retinal ganglion cells and few amacrine cells create action potentials.
In the retinal ganglion cells there are two types of response, depending on the receptive field of the cell. The receptive fields of retinal ganglion cells comprise a central, approximately circular area, where light has one effect on the firing of the cell, and an annular surround, where light has the opposite effect. In ON cells, an increment in light intensity in the centre of the receptive field causes the firing rate to increase. In OFF cells, it makes it decrease. In a linear model, this response profile is well described by a difference of Gaussians and is the basis for edge detection algorithms. Beyond this simple difference, ganglion cells are also differentiated by chromatic sensitivity and the type of spatial summation. Cells showing linear spatial summation are termed X cells (also called parvocellular, P, or midget ganglion cells), and those showing non-linear summation are Y cells (also called magnocellular, M, or parasol retinal ganglion cells), although the correspondence between X and Y cells (in the cat retina) and P and M cells (in the primate retina) is not as simple as it once seemed.
In the transfer of visual signals to the brain, the visual pathway, the retina is vertically divided in two, a temporal (nearer to the temple) half and a nasal (nearer to the nose) half. The axons from the nasal half cross the brain at the optic chiasma to join with axons from the temporal half of the other eye before passing into the lateral geniculate body.
Although there are more than 130 million retinal receptors, there are only approximately 1.2 million fibres (axons) in the optic nerve. So, a large amount of pre-processing is performed within the retina. The fovea produces the most accurate information. Despite occupying about 0.01% of the visual field (less than 2° of visual angle), about 10% of axons in the optic nerve are devoted to the fovea. The resolution limit of the fovea has been determined to be around 10,000 points. The information capacity is estimated at 500,000 bits per second (for more information on bits, see information theory) without colour or around 600,000 bits per second including colour.
Spatial encoding
When the retina sends neural impulses representing an image to the brain, it spatially encodes (compresses) those impulses to fit the limited capacity of the optic nerve. Compression is necessary because there are 100 times more photoreceptor cells than ganglion cells. This is done by "decorrelation", which is carried out by the "centre–surround structures", which are implemented by the bipolar and ganglion cells.
There are two types of centre–surround structures in the retina – on-centres and off-centres. On-centres have a positively weighted centre and a negatively weighted surround. Off-centres are just the opposite. Positive weighting is more commonly known as excitatory, and negative weighting as inhibitory.
These centre–surround structures are not physical apparent, in the sense that one cannot see them by staining samples of tissue and examining the retinas anatomy. The centre–surround structures are logical (i.e., mathematically abstract) in the sense that they depend on the connection strengths between bipolar and ganglion cells. It is believed that the connection strength between cells is caused by the number and types of ion channels embedded in the synapses between the bipolar and ganglion cells.
The centre–surround structures are mathematically equivalent to the edge detection algorithms used by computer programmers to extract or enhance the edges in a digital photograph. Thus, the retina performs operations on the image-representing impulses to enhance the edges of objects within its visual field. For example, in a picture of a dog, a cat and a car, it is the edges of these objects that contain the most information. In order for higher functions in the brain (or in a computer for that matter) to extract and classify objects such as a dog and a cat, the retina is the first step to separating out the various objects within the scene.
As an example, the following matrix is at the heart of a computer algorithm that implements edge detection. This matrix is the computer equivalent to the centre–surround structure. In this example, each box (element) within this matrix would be connected to one photoreceptor. The photoreceptor in the centre is the current receptor being processed. The centre photoreceptor is multiplied by the +1 weight factor. The surrounding photoreceptors are the "nearest neighbors" to the centre and are multiplied by the −1/8 value. The sum of all nine of these elements is finally calculated. This summation is repeated for every photoreceptor in the image by shifting left to the end of a row and then down to the next line.
The total sum of this matrix is zero, if all the inputs from the nine photoreceptors are of the same value. The zero result indicates the image was uniform (non-changing) within this small patch. Negative or positive sums mean the image was varying (changing) within this small patch of nine photoreceptors.
The above matrix is only an approximation to what really happens inside the retina. The differences are:
The above example is called "balanced". The term balanced means that the sum of the negative weights is equal to the sum of the positive weights so that they cancel out perfectly. Retinal ganglion cells are almost never perfectly balanced.
The table is square while the centre–surround structures in the retina are circular.
Neurons operate on spike trains traveling down nerve cell axons. Computers operate on a single floating-point number that is essentially constant from each input pixel. (The computer pixel is basically the equivalent of a biological photoreceptor.)
The retina performs all these calculations in parallel while the computer operates on each pixel one at a time. The retina performs no repeated summations and shifting as would a computer.
Finally, the horizontal and amacrine cells play a significant role in this process, but that is not represented here.Here is an example of an input image and how edge detection would modify it.
Once the image is spatially encoded by the centre–surround structures, the signal is sent out along the optic nerve (via the axons of the ganglion cells) through the optic chiasm to the LGN (lateral geniculate nucleus). The exact function of the LGN is unknown at this time. The output of the LGN is then sent to the back of the brain. Specifically, the output of the LGN "radiates" out to the V1 primary visual cortex.
Simplified signal flow: Photoreceptors → Bipolar → Ganglion → Chiasm → LGN → V1 cortex
Clinical significance
There are many inherited and acquired diseases or disorders that may affect the retina. Some of them include:
Retinitis pigmentosa is a group of genetic diseases that affect the retina and cause the loss of night vision and peripheral vision.
Macular degeneration describes a group of diseases characterized by loss of central vision because of death or impairment of the cells in the macula.
Cone-rod dystrophy (CORD) describes a number of diseases where vision loss is caused by deterioration of the cones and/or rods in the retina.
In retinal separation, the retina detaches from the back of the eyeball. Ignipuncture is an outdated treatment method. The term retinal detachment is used to describe a separation of the neurosensory retina from the retinal pigment epithelium. There are several modern treatment methods for fixing a retinal detachment: pneumatic retinopexy, scleral buckle, cryotherapy, laser photocoagulation and pars plana vitrectomy.
Both hypertension and diabetes mellitus can cause damage to the |
Retina | tiny blood vessels that supply the retina, leading to hypertensive retinopathy and diabetic retinopathy.
Retinoblastoma is a cancer of the retina.
Retinal diseases in dogs include retinal dysplasia, progressive retinal atrophy, and sudden acquired retinal degeneration.
Lipaemia retinalis is a white appearance of the retina, and can occur by lipid deposition in lipoprotein lipase deficiency.
Retinal Detachment. The neural retina occasionally detaches from the pigment epithelium. In some instances, the cause of such detachment is injury to the eyeball that allows fluid or blood to collect between the neural retina and the pigment epithelium. Detachment is occasionally caused by contracture of fine collagenous fibrils in the vitreous humor, which pull areas of the retina toward the interior of the globe.
Night blindness: Night blindness occurs in any person with severe vitamin A deficiency. The reason for this is that without vitamin A, the amounts of retinal and rhodopsin that can be formed are severely depressed. This condition is called night blindness because the amount of light available at night is too little to permit adequate vision in vitamin A–deficient persons.In addition, the retina has been described as a "window" into the brain and body, given that abnormalities detected through an examination of the retina can discover both neurological and systemic diseases.
Diagnosis
A number of different instruments are available for the diagnosis of diseases and disorders affecting the retina. Ophthalmoscopy and fundus photography have long been used to examine the retina. Recently, adaptive optics has been used to image individual rods and cones in the living human retina, and a company based in Scotland has engineered technology that allows physicians to observe the complete retina without any discomfort to patients.The electroretinogram is used to non-invasively measure the retinas electrical activity, which is affected by certain diseases. A relatively new technology, now becoming widely available, is optical coherence tomography (OCT). This non-invasive technique allows one to obtain a 3D volumetric or high resolution cross-sectional tomogram of the fine structures of the retina, with histologic quality. Retinal vessel analysis is a non-invasive method to examine the small arteries and veins in the retina which allows to draw conclusions about the morphology and the function of small vessels elsewhere in the human body. It has been established as a predictor of cardiovascular disease and seems to have, according to a study published in 2019, potential in the early detection of Alzheimers disease.
Treatment
Treatment depends upon the nature of the disease or disorder.
Common treatment modalities
The following are commonly modalities of management for retinal disease:
Intravitreal medication, such as anti-VEGF or corticosteroid agents
Vitreoretinal surgery
Use of nutritional supplements
Modification of systemic risk factors for retinal disease
Uncommon treatment modalities
History
Around 300 BCE, Herophilos identified the retina from dissections of cadaver eyes. He called it the arachnoid layer, from its resemblance to a spider web, and retiform, from its resemblance to a casting net. The term arachnoid came to refer to a layer around the brain; the term retiform came to refer to the retina.Between 1011 and 1021 CE, Ibn Al-Haytham published numerous experiments demonstrating that sight occurs from light reflecting from objects into the eye. This is consistent with intromission theory and against emission theory, the theory that sight occurs from rays emitted by the eyes. However, Ibn Al-Haytham decided that the retina could not be responsible for the beginnings of vision because the image formed on it was inverted. Instead he decided it must begin at the surface of the lens.In 1604, Johannes Kepler worked out the optics of the eye and decided that the retina must be where sight begins. He left it up to other scientists to reconcile the inverted retinal image with our perception of the world as upright.In 1894, Santiago Ramón y Cajal published the first major characterization of retinal neurons in Retina der Wirbelthiere (The Retina of Vertebrates).George Wald, Haldan Keffer Hartline, and Ragnar Granit won the 1967 Nobel Prize in Physiology or Medicine for their scientific research on the retina.A recent University of Pennsylvania study calculated that the approximate bandwidth of human retinas is 8.75 megabits per second, whereas a guinea pigs retinal transfer rate is 875 kilobits per second.MacLaren & Pearson and colleagues at University College London and Moorfields Eye Hospital in London, in 2006, showed that photoreceptor cells could be transplanted successfully in the mouse retina if donor cells were at a critical developmental stage. Recently Ader and colleagues in Dublin showed, using the electron microscope, that transplanted photoreceptors formed synaptic connections.In 2012, Sebastian Seung and his laboratory at MIT launched EyeWire, an online Citizen science game where players trace neurons in the retina. The goals of the EyeWire project are to identify specific cell types within the known broad classes of retinal cells, and to map the connections between neurons in the retina, which will help to determine how vision works.
Additional images
See also
Adeno associated virus and gene therapy of the human retina
Charles Schepens – "the father of modern retinal surgery"
Evolution of the eye
Duplex retina
Retinal scan
Retinal vein occlusion
List of xanthoma variants associated with hyperlipoproteinemia subtypes
Rhodopsin
Persistence of vision
References
Further reading
S. Ramón y Cajal, Histologie du Système Nerveux de lHomme et des Vertébrés, Maloine, Paris, 1911.
Rodieck RW (1965). "Quantitative analysis of cat retinal ganglion cell response to visual stimuli". Vision Res. 5 (11): 583–601. doi:10.1016/0042-6989(65)90033-7. PMID 5862581.
Wandell, Brian A. (1995). Foundations of vision. Sunderland, Mass: Sinauer Associates. ISBN 978-0-87893-853-7.
Wässle H, Boycott BB (1991). "Functional architecture of the mammalian retina". Physiol. Rev. 71 (2): 447–480. doi:10.1152/physrev.1991.71.2.447. PMID 2006220.
Schulz HL, Goetz T, Kaschkoetoe J, Weber BH (2004). "The Retinome – Defining a reference transcriptome of the adult mammalian retina/retinal pigment epithelium". BMC Genomics (about a transcriptome for eye colour). 5 (1): 50. doi:10.1186/1471-2164-5-50. PMC 512282. PMID 15283859.
Dowling, John (2007). "Retina". Scholarpedia. 2 (12): 3487. Bibcode:2007SchpJ...2.3487D. doi:10.4249/scholarpedia.3487.
External links
Histology of the Eye, edited by William Krause, Dept. Pathology and Anatomical science, University of Missouri School of Medicine
Eye, Brain, and Vision – online book – by David Hubel
Kolb, H., Fernandez, E., & Nelson, R. (2003). Webvision: The neural organization of the vertebrate retina. Salt Lake City, Utah: John Moran Eye Center, University of Utah. Retrieved 22 July 2014.
Demo: Artificial Retina, MIT Technology Review, September 2004. Reports on implant research at Technology Review
Successful photoreceptor transplantation, MIT Technology Review, November 2006. How stem cells might restore sight Technology Review
Australian Vision Prosthesis Group, Graduate School of Biomedical Engineering, University of New South Wales
RetinaCentral, Genetics and Diseases of the Human Retina at University of Würzburg
Retinal layers image. NeuroScience 2nd Ed at United States National Library of Medicine
Jeremy Nathanss Seminars: "The Vertebrate Retina: Structure, Function, and Evolution"
Retina – Cell Centered Database
Histology image: 07901loa – Histology Learning System at Boston University
MedlinePlus Encyclopedia: 002291 |
Tinea imbricata | Tinea imbricata (also known in parts of Indonesia as “Kaskado”) is a superficial fungal infection of the skin limited to southwest Polynesia, Melanesia, Southeast Asia, India, and Central America.: 303 The skin lesions are often itchy, and mainly in the torso and limbs. The name is derived from the Latin for "tiled" (imbricata) since the lesions are often lamellar. It is often treated with griseofulvin or terbinafine.The risk of developing tinea imbricata is probably inherited as an autosomal recessive trait.Tinea imbricata is associated with Trichophyton concentricum.
Tinea pseudoimbricata
The term "tinea pseudoimbricata" synonymous with "tinea indecisiva", was coined to describe a form of tinea mimicking the concentric rings of tinea imbricata, but is caused by local or systemic immunosuppression. Since then, 3 cases of Trichophyton tonsurans have been associated with it, as well as Trichophyton rubrum which can trigger mycosis fungoides.
Mixed infections with scabies have been described to produce tinea pseudoimbricata.As of 2015 in India, corticosteroid–antifungal–antibacterial combinations sold as over-the-counter drug have led to an increase in chronic, recurrent, difficult to treat fungal infections of the skin, including tinea pseudoimbricata.
See also
Skin lesion
List of cutaneous conditions
References
== External links == |
Malnutrition | Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the bodys tissues and form.Malnutrition is a category of diseases that includes undernutrition and overnutrition. Undernutrition is a lack of nutrients, which can result in stunted growth, wasting, and underweight. A surplus of nutrients causes overnutrition, which can result in obesity. In some developing countries, overnutrition in the form of obesity is beginning to appear within the same communities as undernutrition.Most clinical studies use the term malnutrition to refer to undernutrition. However, the use of malnutrition instead of undernutrition makes it impossible to distinguish between undernutrition and overnutrition, a less acknowledged form of malnutrition. Accordingly, a 2019 report by The Lancet Commission suggested expanding the definition of malnutrition to include "all its forms, including obesity, undernutrition, and other dietary risks." The World Health Organization and The Lancet Commission have also identified "[t]he double burden of malnutrition," which occurs from "the coexistence of overnutrition (overweight and obesity) alongside undernutrition (stunted growth and wasting)."
Prevalence
It is estimated that nearly one in three persons globally has at least one form of malnutrition: wasting, stunting, vitamin or mineral deficiency, overweight, obesity, or diet-related noncommunicable diseases. Undernutrition is more common in developing countries. Stunting is more prevalent in urban slums than in rural areas. Studies on malnutrition have the population categorised into different groups including infants, under-five children, children, adolescents, pregnant women, adults and the elderly population. The use of different growth references in different studies leads to variances in the undernutrition prevalence reported in different studies. Some of the growth references used in studies include the
National Center for Health Statistics (NCHS) growth charts, WHO reference 2007, Centers for Disease Control and Prevention (CDC) growth charts, National Health and Nutrition Examination Survey (NHANES), WHO reference 1995, Obesity Task Force (IOTF) criteria and Indian Academy of Pediatrics (IAP) growth charts.
In children
The prevalence of undernutrition is highest among children under five. In 2020, 149 million children under five years old were stunted, 45 million were wasted, and 38.9 million were overweight or obese. The following year, an estimated 45% of deaths in children were linked to undernutrition. The prevalence of wasting among children under five in South Asia was reported to be 16% moderately or severely wasted. In Asia, India has one of the highest burden of wasting with over 20% wasted children. However, the burden of undernutrition among under-five children in African countries is much higher. A pooled analysis of the prevalence of chronic undernutrition among under-five children in East Africa was identified to be 33.3%. This prevalence of undernutrition among under-five children ranged from 21.9% in Kenya to 53% in Burundi. In Tanzania, the prevalence of stunting, among children under five varied from 41% in lowland and 64.5% in highland areas. Undernutrition by underweight and wasting was 11.5% and 2.5% in lowland and 22.% and 1.4% in the highland areas of Tanzania respectively. In South Sudan, the prevalence of undernutrition explained by stunting, underweight and wasting in under-five children were 23.8%, 4.8% and 2.3% respectively.Vitamin A deficiency affects one third of children under age 5 around the world, leading to 670,000 deaths and 250,000–500,000 cases of blindness.
In adults
As of June 2021, 1.9 billion adults were overweight or obese, and 462 million adults were underweight. Globally, two billion people had iodine deficiency in 2017. In 2020, 900 million women and children had anemia, which is often caused by iron deficiency.Certain groups have higher rates of undernutrition, including elderly people and women (in particular while pregnant or breastfeeding children under five years of age). Undernutrition is an increasing health problem in people aged over 65 years, even in developed countries, especially among nursing home residents and in acute care hospitals. In the elderly, undernutrition is more commonly due to physical, psychological, and social factors, not a lack of food. Age-related reduced dietary intake due to chewing and swallowing problems, sensory decline, depression, imbalanced gut microbiome, poverty and loneliness are major contributors to undernutrition in the elderly population.
Recent increase
There has been an increase in world hunger over the past decade. In 2015, 795 million people (about one in ten people on earth) had undernutrition. In 2020, one in nine people in the world—or 820 million people worldwide—was hungry.These increases are partially related to the ongoing COVID-19 pandemic, which continues to highlight the weaknesses of current food and health systems. It has contributed to food insecurity, increasing hunger worldwide; meanwhile, lower physical activity during lockdowns has contributed to increases in overweight and obesity. In 2020, experts estimated that by the end of the year, the pandemic could double the number of people at risk of suffering acute hunger. Similarly, experts estimate that the prevalence of moderate and severe wasting could increase by 14% due to COVID-19; coupled with reductions in nutrition and health services coverage, this could result in over 128,000 additional deaths among children under 5 in 2020 alone. Although COVID-19 is less severe in children than in adults, the risk of severe disease increases with undernutrition.Other major causes of hunger include manmade conflicts, climate changes, and economic downturns.
Definitions
Undernutrition
Undernutrition can occur either due to protein-energy wasting or as a result of micronutrient deficiencies. It adversely affects physical and mental functioning, and causes changes in body composition and body cell mass. Undernutrition is a major health problem, causing the highest mortality rate in children, and is responsible for long-lasting physiologic effects. It is a barrier to the complete physical and mental development of children.Undernutrition can manifest as stunting, wasting, and underweight. If undernutrition occurs during pregnancy, or before two years of age, it may result in permanent problems with physical and mental development. Extreme undernutrition can cause starvation, chronic hunger, Severe Acute Malnutrition (SAM), and/or Moderate Acute Malnutrition (MAM).
The signs and symptoms of micronutrient deficiencies depend on which micronutrient is lacking. However, undernourished people are often thin and short, with very poor energy levels; and swelling in the legs and abdomen is also common. People who are undernourished often get infections and frequently feel cold.
Micronutrient malnutrition
Micronutrient malnutrition results from inadequate intake of vitamins and minerals. Worldwide, deficiencies in iodine, Vitamin A, and iron are the most common. Children and pregnant women in low-income countries are at especially high risk for micronutrient deficiencies.Anemia is most commonly caused by iron deficiency, but can also result from other micronutrient deficiencies and diseases. This condition can have major health consequences.It is possible to have overnutrition simultaneously with micronutrient deficiencies; this condition is termed the double burden of malnutrition.
Protein-energy malnutrition
Undernutrition sometimes refers specifically to protein–energy malnutrition (PEM). This condition involves both micronutrient deficiencies and an imbalance of protein intake and energy expenditure. It differs from calorie restriction in that calorie restriction may not result in negative health effects. Hypoalimentation (underfeeding) is one cause of undernutrition.Two forms of PEM are kwashiorkor and marasmus; both commonly coexist.
Kwashiorkor is primarily caused by inadequate protein intake. Its symptoms include edema, wasting, liver enlargement, hypoalbuminaemia, and steatosis; the condition may also cause depigmentation of skin and hair. The disorder is further identified by a characteristic swelling of the belly, which disguises the patients undernourished condition. Kwashiorkor means displaced child and is derived from the Ga language of coastal Ghana in West Africa. It means "the sickness the baby gets when the next baby is born," as it often occurs when the older child is deprived of breastfeeding and weaned to a diet composed largely of carbohydrates.Marasmus (meaning to waste away) can result from a sustained diet that is deficient in both protein and energy. This causes their metabolism to adapt in order to prolong survival. The primary symptoms are severe wasting, leaving little or no edema; minimal subcutaneous fat; and abnormal serum albumin levels. It is traditionally seen in cases of famine, significant food restriction, or severe anorexia. Conditions are characterized by extreme wasting of the muscles and a gaunt expression.
Overnutrition
Excessive consumption of energy-dense foods and drinks and limited physical activity causes overnutrition. It causes overweight, defined as a body mass index (BMI) of 25 or more, and can lead to obesity (a BMI of 30 or more). Obesity has become a major health issue worldwide. Overnutrition is linked to chronic non-communicable diseases like diabetes, certain cancers, and cardiovascular diseases. Hence identifying and addressing the immediate risk factors has become a major health priority. The recent evidence on the impact of diet-induced obesity in fathers and mothers around the time of conception is identified to negatively program the health outcomes of multiple generations.
Classifying malnutrition
Definition by Gomez & Galvan
In 1956, Gómez and Galvan studied factors associated with death in a group of undernourished children in a hospital in Mexico City, Mexico. They defined three categories of malnutrition: first, second, and third degree. The degree of malnutrition is calculated based on a childs body size compared to the median weight for their age. The risk of death increases with increasing degrees of malnutrition.An adaptation of Gomezs original classification is still used today. While it provides a way to compare malnutrition within and between populations, this classification system has been criticized for being "arbitrary" and for not considering overweight as a form of malnutrition. Also, height alone may not be the best indicator of malnutrition; children who are born prematurely may be considered short for their age even if they have good nutrition.
Definition by Waterlow
In the 1970s, John Conrad Waterlow established a new classification system for malnutrition. Instead of using just weight for age measurements, Waterlows system combines weight-for-height (indicating acute episodes of malnutrition) with height-for-age to show the stunting that results from chronic malnutrition. One advantage of the Waterlow classification is that weight for height can be calculated even if a childs age is unknown.
The World Health Organization frequently uses these classifications of malnutrition, with some modifications.
Effects
Malnutrition weakens every part of the immune system. Protein and energy malnutrition increases susceptibility to infection; so do deficiencies of specific micronutrients (including iron, zinc, and vitamins). In communities or areas that lack access to safe drinking water, these additional health risks present a critical problem.
Malnutrition plays a major role in the onset of active tuberculosis. It also raises the risk of HIV transmission from mother to child, and increases replication of the virus. Malnutrition can cause vitamin-deficiency-related diseases like scurvy and rickets. As malnutrition worsens, those affected have less energy and experience impairment in brain functions. This can make it difficult (or impossible) for them to perform the tasks needed to acquire food, earn an income, or gain an education.
Malnutrition can also cause acute problems, like hypoglycemia (low blood sugar). This condition can cause lethargy, limpness, seizures, and loss of consciousness. Children are particularly at risk and can become hypoglycemic after 4 to 6 hours without food. Dehydration can also occur in malnourished people, and can be life-threatening, especially in babies and small children.
Signs
There are many different signs of dehydration in malnourished people. These can include sunken eyes; a very dry mouth; decreased urine output and/or dark urine; increased heart rate with decreasing blood pressure; and altered mental status.
Cognitive development
Protein-calorie malnutrition can cause cognitive impairments. This most commonly occurs in people who were malnourished during a "critical period... from the final third of gestation to the first 2 years of life". For example, in children under two years of age, iron deficiency anemia is likely to affect brain function acutely, and probably also chronically. Similarly, folate deficiency has been linked to neural tube defects.Iodine deficiency is "the most common preventable cause of mental impairment worldwide." "Even moderate [iodine] deficiency, especially in pregnant women and infants, lowers intelligence by 10 to 15 I.Q. points, shaving incalculable potential off a nations development." Among those affected, very few people experience the most visible and severe effects: disabling goiters, cretinism and dwarfism. These effects occur most commonly in mountain villages. However, 16 percent of the worlds people have at least mild goiter (a swollen thyroid gland in the neck)."
Causes & risk factors
Social and political
Social conditions have a significant influence on the health of people. The social determinants of undernutrition mainly include poor education, poverty, disease burden and lack of womens empowerment. Identifying and addressing these determinants can eliminate undernutrition in the long term. Identification of the social conditions that causes malnutrition in children under five has received significant research attention as it is a major public health problem.
Undernutrition most commonly results from a lack of access to high-quality, nutritious food. The household income is a socio-economic variable that influences the access to nutritious food and the probability of under and overnutrition in a community. In the study by Ghattas et al. (2020), the probability of overnutrition is significantly higher in higher-income families than in disadvantaged families. High food prices is a major factor preventing low income households from getting nutritious food For example, Khan and Kraemer (2009) found that in Bangladesh, low socioeconomic status was associated with chronic malnutrition since it inhibited purchase of nutritious foods (like milk, meat, poultry, and fruits). Food shortages may also contribute to malnutritions in countries which lack technology. However, in the developing world, eighty percent of malnourished children live in countries that produce food surpluses, according to estimates from the Food and Agriculture Organization (FAO). The economist Amartya Sen observes that, in recent decades, famine has always been a problem of food distribution, purchasing power, and/or poverty, since there has always been enough food for everyone in the world.There are also sociopolitical causes of malnutrition. For example, the population of a community might be at increased risk for malnutrition if government is poor and the area lacks health-related services. On a smaller scale, certain households or individuals may be at an even higher risk due to differences in income levels, access to land, or levels of education. Community plays a crucial role in addressing the social causes of malnutrition. For example, communities with high social support and knowledge sharing about social protection programs can enable better public service demands. Better public service demands and social protection programs minimise the risk of malnutrition in these communities.
It is argued that commodity speculators are increasing the cost of food. As the real-estate bubble in the United States was collapsing, it is said that trillions of dollars moved to invest in food and primary commodities, causing the 2007–2008 food price crisis.The use of biofuels as a replacement for traditional fuels raises the price of food. The United Nations special rapporteur on the right to food, Jean Ziegler proposes that agricultural waste, such as corn cobs and banana leaves, should be used as fuel instead of crops.In some developing countries, overnutrition (in the form of obesity) is beginning to appear in the same communities where malnutrition occurs. Overnutrition increases with urbanisation, food commercialisation and technological developments and increases physical inactivity. Variations in the health status of individuals in the same society are associated with the societal structure and an individuals socioeconomic status which leads to income inequality, racism, educational differences and lack of opportunities.
Diseases & conditions
Infectious diseases which increase nutrient requirements, such as gastroenteritis, pneumonia, malaria, and measles, can cause malnutrition. So can some chronic illnesses, especially HIV/AIDS.Malnutrition can also result from abnormal nutrient loss due to diarrhea or chronic small bowel illnesses, like Crohns disease or untreated coeliac disease. "Secondary malnutrition" can result from increased energy expenditure.In infants, a lack of breastfeeding may contribute to undernourishment. Anorexia nervosa and bariatric surgery can also cause malnutrition.
Dietary practices
Undernutrition
Undernutrition due to lack of adequate breastfeeding is associated with the deaths of an estimated one million children annually. Illegal advertising of breast-milk substitutes contributed to malnutrition and continued three decades after its 1981 prohibition under the WHO International Code of Marketing Breast Milk Substitutes.Maternal malnutrition can also factor into the poor health or death of a baby. Over 800,000 neonatal deaths have occurred because of deficient growth of the fetus in the mothers womb.Deriving too much of ones diet from a single source, such as eating almost exclusively potato, maize or rice, can cause malnutrition. This may either be from a lack of education about proper nutrition, or from only having access to a single food source.It is not just the total amount of calories that matters but specific nutritional deficiencies such as vitamin A deficiency, iron deficiency or zinc deficiency can also increase risk of death.
Overnutrition
Overnutrition caused by overeating is also a form of malnutrition. In the United States, more than half of all adults are now overweight—a condition that, like hunger, increases susceptibility to disease and disability, reduces worker productivity, and lowers life expectancy. Overeating is much more common in the United States, since most people have adequate access to food. Many parts of the world have access to a surplus of non-nutritious food. Increased sedentary lifestyles also contribute to overnutrition. Yale University psychologist Kelly Brownell calls this a "toxic food environment," where fat- and sugar-laden foods have taken precedence over healthy nutritious foods.In these developed countries, overnutrition can be prevented by choosing the right kind of food. More fast food is consumed per capita in the United States than in any other country. This mass consumption of fast food results from its affordability and accessibility. Fast food, which is low in cost and nutrition, is high in calories. Due to increasing urbanization and automation, people are living more sedentary lifestyles. These factors combine to make weight gain difficult to avoid.Overnutrition also occurs in developing countries. It has appeared in parts of developing countries where income is on the rise. It is also a problem in countries where hunger and poverty persist. Economic development, rapid urbanisation and shifting dietary patterns have increased the burden of overnutrition in the cities of low and middle-income countries. In China, consumption of high-fat foods has increased, while consumption of rice and other goods has decreased.
Overeating leads to many diseases, such as heart disease and diabetes, that may be fatal.
Agricultural productivity
Local food shortages can be caused by a lack of arable land, adverse weather, and/or poorer farming skills (like inadequate crop rotation). They can also occur in areas which lack the technology or resources needed for the higher yields found in modern agriculture. These resources include fertilizers, pesticides, irrigation, machinery, and storage facilities. As a result of widespread poverty, farmers and governments cannot provide enough of these resources to improve local yields.
Additionally, the World Bank and some wealthy donor countries have pressured developing countries to use free market policies. Even as the United States and Europe extensively subsidized their own farmers, they urged developing countries to cut or eliminate subsidized agricultural inputs, like fertilizer. Without subsidies, few (if any) farmers in developing countries can afford fertilizer at market prices. This leads to low agricultural production, low wages, and high, unaffordable food prices. Fertilizer is also increasingly unavailable because Western environmental groups have fought to end its use due to environmental concerns. The Green Revolution pioneers Norman Borlaug and Keith Rosenberg cited as the obstacle to feeding Africa by.
Future threats
In the future, variety of factors could potentially disrupt global food supply and cause widespread malnutrition.
Global warming is of importance to food security. Almost all malnourished people (95%) live in the tropics and subtropics, where the climate is relatively stable. According to the latest Intergovernmental Panel on Climate Change reports, temperature increases in these regions are "very likely." Even small changes in temperatures can make extreme weather conditions occur more frequently. Extreme weather events, like drought, have a major impact on agricultural production, and hence nutrition. For example, the 1998–2001 Central Asian drought killed about 80 percent of livestock in Iran and caused a 50% reduction in wheat and barley crops there. Other central Asian nations experienced similar losses. An increase in extreme weather such as drought in regions such as Sub-Saharan Africa would have even greater consequences in terms of malnutrition. Even without an increase of extreme weather events, a simple increase in temperature reduces the productivity of many crop species, and decreases food security in these regions.Another threat is colony collapse disorder, a phenomenon where bees die in large numbers. Since many agricultural crops worldwide are pollinated by bees, colony collapse disorder represents a threat to the global food supply.
Prevention
Reducing malnutrition is key part of the United Nations Sustainable Development Goal 2 (SDG2), "Zero Hunger," which aims to reduce malnutrition, undernutrition, and stunted child growth. Managing severe acute undernutrition in a community setting has received significant research attention.
Food security
In the 1950s and 1960s, the Green Revolution aimed to bring modern Western agricultural techniques (like nitrogen fertilizers and pesticides) to Asia. Investments in agriculture, such as fund fertilizers and seeds, increased food harvests and thus food production. Consequently, food prices and malnutrition decreased (as they had earlier in Western nations).The Green Revolution was possible in Asia because of existing infrastructure and institutions, such as a system of roads and public seed companies that made seeds available. These resources were in short supply in Africa, decreasing the Green Revolutions impact on the continent.
For example, almost five million of the 13 million people in Malawi used to need emergency food aid. However, in the early 2000s, the Malawian government changed its agricultural policies, and implemented subsidies for fertilizer and seed introduced against World Bank strictures. By 2007, farmers were producing record-breaking corn harvests. Corn production leaped to 3.4 million in 2007 compared to 1.2 million in 2005, making Malawi a major food exporter. Consequently, food prices lowered and wages for farmworkers rose. Such investments in agriculture are still needed in other African countries like the Democratic Republic of the Congo (DRC). Despite the countrys great agricultural potential, the prevalence of malnutrition in the DRC is among the highest in the world. Proponents for investing in agriculture include Jeffrey Sachs, who argues that wealthy countries should invest in fertilizer and seed for Africas farmers.Imported Ready to Use Therapeutic Food (RUTF) has been used to treat malnutrition in northern Nigeria. Some Nigerians also use soy kunu, a locally sourced and prepared blend consisting of peanut, millet and soybeans.New technology in agricultural production has great potential to combat undernutrition. It makes farming easier, thus improving agricultural yields. By increasing farmers incomes, this could reduce poverty. It would also open up area which farmers could use to diversify crops for household use.
The World Bank claims to be part of the solution to malnutrition, asserting that countries can best break the cycle of poverty and malnutrition by building export-led economies, giving them the financial means to buy foodstuffs on the world market. The role of the World Bank cannot be overemphasized in the prevention of malnutrition..
Economics
Many aid groups have found that giving cash assistance (or cash vouchers) is more effective than donating food. Particularly in areas where food is available but unaffordable, giving cash assistance is a cheaper, faster, and more efficient way to deliver help to the hungry. In 2008, the UNs World Food Program, the biggest non-governmental distributor of food, announced that it would begin distributing cash and vouchers instead of food in some areas, which Josette Sheeran, the WFPs executive director, described as a "revolution" in food aid. The aid agency Concern Worldwide piloted a method of giving cash assistance using a mobile phone operator, Safaricom, which runs a money transfer program that allows cash to be sent from one part of a country to another.However, during a drought, delivering food might be the most appropriate way to help people, especially those who live far from markets and thus have limited access to them. Fred Cuny stated that "the chances of saving lives at the outset of a relief operation are greatly reduced when food is imported. By the time it arrives in the country and gets to people, many will have died." U.S. law requires food aid to be purchased at home rather than in the countries where the hungry live; this is inefficient because approximately half of the money spent goes for transport. Cuny further pointed out that "studies of every recent famine have shown that food was available in-country—though not always in the immediate food deficit area" and "even though by local standards the prices are too high for the poor to purchase it, it would usually be cheaper for a donor to buy the hoarded food at the inflated price than to import it from abroad."
Food banks and soup kitchens address malnutrition in places where people lack money to buy food. A basic income has been proposed as a way to ensure that everyone has enough money to buy food and other basic needs. This is a form of social security in which all citizens or residents of a country regularly receive an unconditional sum of money, either from a government or some other public institution, in addition to any income received from elsewhere.
Successful initiatives
Ethiopia pioneered a program that later became part of the World Banks prescribed method for coping with a food crisis. Through the countrys main food assistance program, the Productive Safety Net Program, Ethiopia provided rural residents who were chronically short of food a chance to work for food or cash. Foreign aid organizations like the World Food Program were then able to buy food locally from surplus areas to distribute in areas with a shortage of food. Aid organizations now view the Ethiopian program as a model of how to best help hungry nations.
Successful initiatives also include Brazils recycling program for organic waste, which benefits farmers, the urban poor, and the city in general. City residents separate organic waste from their garbage, bag it, and then exchange it for fresh fruit and vegetables from local farmers. This reduces the countrys waste while giving the urban poor a steady supply of nutritious food.
World population
Restricting population size is a proposed solution to malnutrition. Thomas Malthus argues that population growth can be controlled by natural disasters and by voluntary limits through "moral restraint." Robert Chapman suggests that government policies are a necessary ingredient for curtailing global population growth. The United Nations recognizes that poverty and malnutrition (as well as the environment) are interdependent and complementary with population growth. According to the World Health Organisation, "Family planning is key to slowing unsustainable population growth and the resulting negative impacts on the economy, environment, and national and regional development efforts". However, more than 200 million women worldwide lack adequate access to family planning services.
There are different theories about what causes famine. Some theorists, like the Indian economist Amartya Sen, believe that the world has more than enough resources to sustain its population. In this view, malnutrition is caused by unequal distribution of resources and under- or unutilized arable land. For example, Sen argues that "no matter how a famine is caused, methods of breaking it call for a large supply of food in the public distribution system. This applies not only to organizing rationing and control, but also to undertaking work programmes and other methods of increasing purchasing power for those hit by shifts in exchange entitlements in a general inflationary situation."
Food sovereignty
Food sovereignty is one suggested policy framework to resolve access issues. In this framework, people (rather than international market forces) have the right to define their own food, agricultural, livestock, and fishery systems. Food First is one of the primary think tanks working to build support for food sovereignty. Neoliberals advocate |
Malnutrition | for an increasing role of the free market.
Health facilities
Another possible long-term solution to malnutrition is to increase access to health facilities in rural parts of the world. These facilities could monitor undernourished children, act as supplemental food distribution centers, and provide education on dietary needs. Similar facilities have already proven very successful in countries such as Peru and Ghana.
Breastfeeding
In 2016, estimates suggested that more widespread breastfeeding could prevent about 823,000 deaths annually of children under age 5. In addition to reducing infant deaths, breast milk provides an important source of micronutrients - which are clinically proven to bolster childrens immune systems - and provides long-term defenses against non-communicable and allergic diseases. Breastfeeding improves cognitive abilities in children, and correlates strongly with individual educational achievements. As previously noted, lack of proper breastfeeding is a major factor in child mortality rates, and is a primary determinant of disease development for children. The medical community recommends exclusively breastfeeding infants for 6 months, with nutritional whole food supplementation and continued breastfeeding up to 2 years or older for overall optimal health outcomes. Exclusive breastfeeding is defined as giving an infant only breast milk for six months as a source of food and nutrition. This means no other liquids, including water or semi-solid foods.
Barriers to breastfeeding
Breastfeeding is noted as one of the most cost-effective medical interventions benefiting child health. While there are considerable differences among developed and developing countries, there are universal determinants of whether a mother breastfeeds or uses formula; these include income, employment, social norms, and access to healthcare. Many newly made mothers face financial barriers; community-based healthcare workers have helped to alleviate these barriers, while also providing a viable alternative to traditional and expensive hospital-based medical care. Recent studies, based upon surveys conducted from 1995 to 2010, show that exclusive breastfeeding rates have risen globally, from 33% to 39%. Despite the growth rates, medical professionals acknowledge the need for improvement given the importance of exclusive breastfeeding.
21st century global initiatives
Starting around 2009, there was renewed international media and political attention focused on malnutrition. This resulted in part from spikes in food prices and the 2008 financial crisis. Additionally, there was an emerging consensus that combating malnutrition is one of the most cost-effective ways to contribute to development. This led to the 2010 launch of the UNs Scaling up Nutrition movement (SUN).In April 2012, a number of countries signed the Food Assistance Convention, the worlds first legally binding international agreement on food aid. The following month, the Copenhagen Consensus recommended that politicians and private sector philanthropists should prioritize interventions against hunger and malnutrition in order to maximize the effectiveness of aid spending. The Consensus recommended prioritizing these interventions ahead of any others, including the fights against malaria and AIDS.In June 2015, the European Union and the Bill & Melinda Gates Foundation launched a partnership to combat undernutrition, especially in children. The program was first implemented in Bangladesh, Burundi, Ethiopia, Kenya, Laos and Niger. It aimed to help these countries improve information and analysis about nutrition, enabling them to develop effective national nutrition policies.Also in 2015, the UNs Food and Agriculture Organization created a partnership aimed at ending hunger in Africa by 2025. The African Unions Comprehensive Africa Agriculture Development Programme (CAADP) provided the framework for the partnership. It includes a variety of interventions, including support for improved food production, a strengthening of social protection, and integration of the right to food into national legislation.The EndingHunger campaign is an online communication campaign whose goal is to raise awareness about hunger. The campaign has created viral videos depicting celebrities voicing their anger about the large number of hungry people in the world.
After the Millennium Development Goals expired in 2015, the Sustainable Development Goals became the main global policy focus to reduce hunger and poverty. In particular, Goal 2: Zero Hunger sets globally agreed-upon targets to wipe out hunger, end all forms of malnutrition, and make agriculture sustainable. The partnership Compact2025 develops and disseminates evidence-based advice to politicians and other decision-makers, with the goal of ending hunger and undernutrition by 2025. The International Food Policy Research Institute (IFPRI) led the partnership, with the involvement of UN organisations, non-governmental organizations (NGOs), and private foundations.
Treatment
Improving nutrition
Efforts to improve nutrition are some of the common forms of development aid. Interventions often promote breastfeeding in order to reduce rates of malnutrition and death in children. Some of these interventions have been successful. For example, interventions with commodities such as ready to use therapeutic foods, micronutrient intervention and vitamin supplementation were identified to significantly improve nutrition, reduce stunting and prevent diseases in communities with severe acute malnutrition. In young children, outcomes improve when children between six months and two years of age receive complementary food (in addition to breast milk). There is also good evidence that supports giving supplemental micronutrients to pregnant women and young children in the developing world.Sending food and money is a common form of development aid, aimed at feeding hungry people. Some strategies help people buy food within local markets. Simply feeding students at school is insufficient.Longer-term measures include improving agricultural practices, reducing poverty, and improving sanitation.
Identifying malnourishment
Measuring children is crucial to identifying malnourishment. In 2000, the United States Centers for Disease Control and Prevention (CDC) established the International Micronutrient Malnutrition Prevention and Control (IMMPaCt) program. It tested children for malnutrition by conducting a three-dimensional scan, using an iPad or a tablet. Its objective was to help doctors provide more efficient treatments. There may be some chance of error when using this method.A systematic review of 42 studies found that many approaches to mitigating acute malnutrition are equally effective; thus, intervention decisions can be based on cost-related factors. Overall, evidence for the effectiveness of acute malnutrition interventions is not robust. The limited evidence related to cost indicates that community and outpatient management of children with uncomplicated malnutrition may be the most cost-effective strategy.
Medical management
It is often possible to manage severe malnutrition within a persons home, using ready-to-use therapeutic foods. In people with severe malnutrition complicated by other health problems, treatment in a hospital setting is recommended. In-hospital treatment often involves managing low blood sugar, maintaining adequate body temperature, addressing dehydration, and gradual feeding.Routine antibiotics are usually recommended because malnutrition weakens the immune system, causing a high risk of infection. Additionally, broad spectrum antibiotics are recommended in all severely undernourished children with diarrhea requiring admission to hospital.A severely malnourished child who appears to have dehydration, but has not had diarrhea, should be treated as if they have an infection.Among malnourished people who are hospitalized, nutritional support improves protein intake, calorie intake, and weight.
Bangladeshi model
In response to child malnutrition, the Bangladeshi government recommends ten steps for treating severe malnutrition:
Prevent or treat dehydration
Prevent or treat low blood sugar
Prevent or treat low body temperature
Prevent or treat infection;
Correct electrolyte imbalances
Correct micronutrient deficiencies
Start feeding cautiously
Achieve catch-up growth
Provide psychological support
Prepare for discharge and follow-up after recovery
Therapeutic foods
Due in part to limited research on supplementary feeding, there is little evidence that this strategy is beneficial. A 2015 systematic review of 32 studies found that there are limited benefits when children under 5 receive supplementary feeding, especially among younger, poorer, and more undernourished children.However, specially formulated foods do appear to be useful in treating moderate acute malnutrition in the developing world. These foods may have additional benefits in humanitarian emergencies, since they can be stored for years, can be eaten directly from the packet, and do not have to be mixed with clean water or refrigerated. In young children with severe acute malnutrition, it is unclear if ready-to-use therapeutic food differs from a normal diet.Severely malnourished individuals can experience refeeding syndrome if fed too quickly. Refeeding syndrome can result regardless of whether food is taken orally or parenterally. It can present several days after eating with potentially fatal heart failure, dysrhythmias, and confusion.Some manufacturers have fortified everyday foods with micronutrients before selling them to consumers. For example, flour has been fortified with iron, zinc, folic acid, and other B vitamins like thiamine, riboflavin, niacin and vitamin B12. Baladi bread (Egyptian flatbread) is made with fortified wheat flour. Other fortified products include fish sauce in Vietnam and iodized salt.
Micronutrient supplementation
According to the World Bank, treating malnutrition - mostly by fortifying foods with micronutrients - improves lives more quickly than other forms of aid, and at a lower cost. After reviewing a variety of development proposals, The Copenhagen Consensus, a group of economists who reviewed a variety of development proposals, ranked micronutrient supplementation as its number-one treatment strategy.In malnourished people with diarrhea, zinc supplementation is recommended following an initial four-hour rehydration period. Daily zinc supplementation can help reduce the severity and duration of the diarrhea. Additionally, continuing daily zinc supplementation for ten to fourteen days makes diarrhea less likely to recur in the next two to three months.Malnourished children also need both potassium and magnesium. Within two to three hours of starting rehydration, children should be encouraged to take food, particularly foods rich in potassium like bananas, green coconut water, and unsweetened fresh fruit juice. Along with continued eating, many homemade products can also help restore normal electrolyte levels. For example, early during the course of a childs diarrhea, it can be beneficial to provide cereal water (salted or unsalted) or vegetable broth (salted or unsalted). If available, vitamin A, potassium, magnesium, and zinc supplements should be added, along with other vitamins and minerals.Giving base (as in Ringers lactate) to treat acidosis without simultaneously supplementing potassium worsens low blood potassium.
Treating diarrhea
Preventing dehydration
Food and drink can help prevent dehydration in malnourished people with diarrhea. Eating (or breastfeeding, among infants) should resume as soon as possible. Sugary beverages like soft drinks, fruit juices, and sweetened teas are not recommended as they may worsen diarrhea.Malnourished people with diarrhea (especially children) should be encouraged to drink fluids; the best choices are fluids with modest amounts of sugar and salt, like vegetable broth or salted rice water. If clean water is available, they should be encouraged to drink that too. Malnourished people should be allowed to drink as much as they want, unless signs of swelling emerge.
Babies can be given small amounts of fluids via an eyedropper or a syringe without the needle. Children under two should receive a teaspoon of fluid every one to two minutes; older children and adults should take frequent sips of fluids directly from a cup. After the first two hours, fluids and foods should be alternated, rehydration should be continued at the same rate or more slowly, depending on how much fluid the child wants and whether they are having ongoing diarrhea. Alternating between rehydration and food at this point is After the first two hours of rehydration it is recommended that to alternate between rehydration and food.If vomiting occurs, fluids can be paused for 5–10 minutes and then restarted more slowly. Vomiting rarely prevents rehydration, since fluids are still absorbed and vomiting is usually short-term.
Oral rehydration therapy
If prevention has failed and dehydration develops, the preferred treatment is rehydration through oral rehydration therapy (ORT). In severely undernourished children with diarrhea, rehydration should be done slowly, according to the World Health Organization.
Oral rehydration solutions consist of clean water mixed with small amounts of sugars and salts. These solutions help restore normal electrolyte levels, provide a source of carbohydrates, and help with fluid replacement.Reduced-osmolarity ORS is the current standard of care for oral rehydration therapy, with reasonably wide availability. Introduced in 2003 by WHO and UNICEF, reduced-osmolarity solutions contain lower concentrations of sodium and glucose than original ORS preparations. Reduced-osmolarity ORS has the added benefit of reducing stool volume and vomiting while simultaneously preventing dehydration. Packets of reduced-osmolarity ORS include glucose, table salt, potassium chloride, and trisodium citrate. For general use, each packet should be mixed with a liter of water. However, for malnourished children, experts recommend adding a packet of ORS to two liters of water, along with an extra 50 grams of sucrose and some stock potassium solution.People who have no access to commercially available ORS can make a homemade version using water, sugar, and table salt. Experts agree that homemade ORS preparations should include one liter (34 oz.) of clean water and 6 teaspoons of sugar; however, they disagree about whether they should contain half a teaspoon of table salt or a full teaspoon. Most sources recommend using half a teaspoon of salt per liter of water. However, people with malnutrition have an excess of body sodium. To avoid worsening this symptom, ORS for people with severe undernutrition should contain half the usual amount of sodium and more potassium.
Patients who do not drink may require fluids by nasogastric tube. Intravenous fluids are recommended only in those who have significant dehydration due to their potential complications, including congestive heart failure.
Low blood sugar
Hypoglycemia, whether known or suspected, can be treated with a mixture of sugar and water. If the patient is conscious, the initial dose of sugar and water can be given by mouth. Otherwise, they should receive glucose by intravenous or nasogastric tube. If seizures occur (and continue after glucose is given), rectal diazepam may be helpful. Blood sugar levels should be re-checked on two hour intervals.
Hypothermia
Hypothermia (dangerously low core body temperature) can occur in malnutrition, particularly in children. Mild hypothermia causes confusion trembling, and clumsiness; more severe cases can be fatal. Keeping malnourished children warm can prevent or treat hypothermia. Covering the child (including their head) in blankets is one method. Another method is to warm the child through direct skin-to-skin contact with their mother or father, then covering both parent and child.
Warming methods are usually most important at night. Prolonged bathing or prolonged medical exams can further lower body temperature and are not recommended for malnourished children at high risk of hypothermia.
Epidemiology
The figures provided in this section on epidemiology all refer to undernutrition even if the term malnutrition is used which, by definition, could also apply to too much nutrition.
The Global Hunger Index (GHI) is a multidimensional statistical tool used to describe the state of countries hunger situation. The GHI measures progress and failures in the global fight against hunger. The GHI is updated once a year. The data from the 2015 report shows that Hunger levels have dropped 27% since 2000. Fifty two countries remain at serious or alarming levels. In addition to the latest statistics on Hunger and Food Security, the GHI also features different special topics each year. The 2015 report include an article on conflict and food security.
People affected
The United Nations estimated that there were 821 million undernourished people in the world in 2017. This is using the UNs definition of undernourishment, where it refers to insufficient consumption of raw calories, and so does not necessarily include people who lack micro nutrients. The undernourishment occurred despite the worlds farmers producing enough food to feed around 12 billion people—almost double the current world population.Malnutrition, as of 2010, was the cause of 1.4% of all disability adjusted life years.
Mortality
Mortality due to malnutrition accounted for 58 percent of the total mortality in 2006: "In the world, approximately 62 million people, all causes of death combined, die each year. One in twelve people worldwide is malnourished and according to the Save the Children 2012 report, one in four of the worlds children are chronically malnourished. In 2006, more than 36 million died of hunger or diseases due to deficiencies in micronutrients".In 2010 protein-energy malnutrition resulted in 600,000 deaths down from 883,000 deaths in 1990. Other nutritional deficiencies, which include iodine deficiency and iron deficiency anemia, result in another 84,000 deaths. In 2010 malnutrition caused about 1.5 million deaths in women and children.According to the World Health Organization, malnutrition is the biggest contributor to child mortality, present in half of all cases. Six million children die of hunger every year. Underweight births and intrauterine growth restrictions cause 2.2 million child deaths a year. Poor or non-existent breastfeeding causes another 1.4 million. Other deficiencies, such as lack of vitamin A or zinc, for example, account for 1 million. Malnutrition in the first two years is irreversible. Malnourished children grow up with worse health and lower education achievement. Their own children tend to be smaller. Malnutrition was previously seen as something that exacerbates the problems of diseases such as measles, pneumonia and diarrhea, but malnutrition actually causes diseases, and can be fatal in its own right.
History
Hunger has been a perennial human problem. However, until the early 20th century, there was relatively little awareness of the qualitative aspects of malnutrition.
Throughout history, various peoples have known the importance of eating certain foods to prevent symptoms now associated with malnutrition. Yet such knowledge appears to have been repeatedly lost and then re-discovered. For example, the ancient Egyptians reportedly knew the symptoms of scurvy. Much later, in the 14th century, Crusaders sometimes used anti-scurvy measures - for example, ensuring that citrus fruits were planted on Mediterranean islands, for use on sea journeys. However, for several centuries, Europeans appear to have forgotten the importance of these measures. They rediscovered this knowledge in the 18th century, and by the early 19th century, the Royal Navy was issuing frequent rations of lemon juice to every crewman on their ships. This massively reduced scurvy deaths among British sailors, which in turn gave the British a significant advantage in the Napoleonic Wars. Later on in the 19th century, the Royal Navy replaced lemons with limes (unaware at the time that lemons are far more effective at preventing scurvy).According to historian Michael Worboys, malnutrition was essentially discovered, and the science of nutrition established, between World War I and World War II. Advances built on prior works like Casimir Funks 1912 formulisation of the concept of vitamins. Scientific study of malnutrition increased in the 1920s and 1930s, and grew even more common after World War II.
Non-governmental organizations and United Nations agencies began to devote considerable energy to alleviating malnutrition around the world. The exact methods and priorities for doing this tended to fluctuate over the years, with varying levels of focus on different types of malnutrition like Kwashiorkor or Marasmus; varying levels of concern on protein deficiency compared to vitamins, minerals and lack of raw calories; and varying priorities given to the problem of malnutrition in general compared to other health and development concerns. The green Revolution of the 1950s and 1960s saw considerable improvement in capability to prevent malnutrition.One of the first official global documents addressing Food security and global malnutrition was the 1948 Universal Declaration of Human Rights(UDHR). Within this document it stated that access to food was part of an adequate right to a standard of living. The Right to food was asserted in the International Covenant on Economic, Social and Cultural Rights, a treaty adopted by the United Nations General Assembly on December 16, 1966. The Right to food is a human right for people to feed themselves in dignity, be free from hunger, food insecurity, and malnutrition. As of 2018, the treaty has been signed by 166 countries, by signing states agreed to take steps to the maximum of their available resources to achieve the right to adequate food.
However, after the 1966 International Covenant the global concern for the access to sufficient food only became more present, leading to the first ever World Food Conference that was held in 1974 in Rome, Italy. The Universal Declaration on the Eradication of Hunger and Malnutrition was a UN resolution adopted November 16, 1974 by all 135 countries that attended the 1974 World Food Conference. This non-legally binding document set forth certain aspirations for countries to follow to sufficiently take action on the global food problem. Ultimately this document outline and provided guidance as to how the international community as one could work towards fighting and solving the growing global issue of malnutrition and hunger.
Adoption of the right to food was included in the Additional Protocol to the American Convention on Human Rights in the area of Economic, Social, and Cultural Rights, this 1978 document was adopted by many countries in the Americas, the purpose of the document is, "to consolidate in this hemisphere, within the framework of democratic institutions, a system of personal liberty and social justice based on respect for the essential rights of man."A later document in the timeline of global inititaves for malnutrition was the 1996 Rome Declaration on World Food Security, organized by the Food and Agriculture Organization. This document reaffirmed the right to have access to safe and nutritious food by everyone, also considering that everyone gets sufficient food, and set the goals for all nations to improve their commitment to food security by halving their amount of undernourished people by 2015. In 2004 the Food and Agriculture Organization adopted the Right to Food Guidelines, which offered states a framework of how to increase the right to food on a national basis.
Special populations
Undernutrition is an important determinant of maternal and child health, accounting for more than a third of child deaths and more than 10 percent of the total global disease burden according to 2008 studies.
Children
Undernutrition adversely affects the cognitive development of children, contributing to poor earning capacity and poverty in adulthood. The development of childhood undernutrition coincides with the introduction of complementary weaning foods which are usually nutrient deficient. The World Health Organization estimates that malnutrition accounts for 54 percent of child mortality worldwide, about 1 million children. There is a strong association between undernutrition and child mortality. Another estimate also by WHO states that childhood underweight is the cause for about 35% of all deaths of children under the age of five years worldwide. Over 90% of the stunted children below five years of age live in sub-Saharan Africa and South Central Asia. Although access to adequate food and improving nutritional intake is an obvious solution to tackling undernutrition in children, the progress in reducing children undernutrition is disappointing.
Women
Researchers from the Centre for World Food Studies in 2003 found that the gap between levels of undernutrition in men and women is generally small, but that the gap varies from region to region and from country to country. These small-scale studies showed that female undernutrition prevalence rates exceeded male undernutrition prevalence rates in South/Southeast Asia and Latin America and were lower in Sub-Saharan Africa. Datasets for Ethiopia and Zimbabwe reported undernutrition rates between 1.5 and 2 times higher in men than in women; however, in India and Pakistan, datasets rates of undernutrition were 1.5–2 times higher in women than in men. Intra-country variation also occurs, with frequent high gaps between regional undernutrition rates. Gender inequality in nutrition in some countries such as India is present in all stages of life.Studies on nutrition concerning gender bias within households look at patterns of food allocation, and one study from 2003 suggested that women often receive a lower share of food requirements than men. Gender discrimination, gender roles, and social norms affecting women can lead to early marriage and childbearing, close birth spacing, and undernutrition, all of which contribute to malnourished mothers.Within the household, there may be differences in levels of malnutrition between men and women, and these differences have been shown to vary significantly from one region to another, with problem areas showing relative deprivation of women. Samples of 1000 women in India in 2008 demonstrated that malnutrition in women is associated with poverty, lack of development and awareness, and illiteracy. The same study showed that gender discrimination in households can prevent a womans access to sufficient food and healthcare. How socialization affects the health of women in Bangladesh, Najma Rivzi explains in an article about a research program on this topic. In some cases, such as in parts of Kenya in 2006, rates of malnutrition in pregnant women were even higher than rates in children.Women in some societies are traditionally given less food than men since men are perceived to have heavier workloads. Household chores and agricultural tasks can in fact be very arduous and require additional energy and nutrients; however, physical activity, which largely determines energy requirements, is difficult to estimate.
Physiology
Women have unique nutritional requirements, and in some cases need more nutrients than men; for example, women need twice as much calcium as men.
Pregnancy and breastfeeding
During pregnancy and breastfeeding, women must ingest enough nutrients for themselves and their child, so they need significantly more protein and calories during these periods, as well as more vitamins and minerals (especially iron, iodine, calcium, folic acid, and vitamins A, C, and K). In 2001 the FAO of the UN reported that iron deficiency affected 43 percent of women in developing countries and increased the risk of death during childbirth. A 2008 review of interventions estimated that universal supplementation with calcium, iron, and folic acid during pregnancy could prevent 105,000 maternal deaths (23.6 percent of all maternal deaths). Malnutrition has been found to affect three quarters of UK women aged 16–49 indicated by them having less folic acid than the WHO recommended levels.Frequent pregnancies with short intervals between them and long periods of breastfeeding add an additional nutritional burden.
Educating children
"Action for healthy kids" has created several methods to teach children about nutrition. They introduce 2 different topics, self-awareness which teaches children about taking care of their own health and social awareness, which is how culinary arts vary from culture to culture. As well as its importance when it comes to nutrition. They include eBooks, tips, cooking clubs. including facts about vegetables and fruits.Team Nutrition has created "MyPlate eBooks" this includes 8 different eBooks to download for free. These eBooks contain drawings to color, audio narration, and a large number of characters to make nutrition lessons entertaining for children.According to the FAO, women are often responsible for preparing food and have the chance to educate their children about beneficial food and health habits, giving mothers another chance to improve the nutrition of their children.
Elderly
Malnutrition and being underweight are more common in the elderly than in adults of other ages. If elderly people are healthy and active, the aging process alone does not usually cause malnutrition. However, changes in body composition, organ functions, adequate energy intake and ability to eat or access food are associated with aging, and may contribute to malnutrition. Sadness or depression can play a role, causing changes in appetite, digestion, energy level, weight, and well-being. A study on the relationship between malnutrition and other conditions in the elderly found that malnutrition in the elderly can result from gastrointestinal and endocrine system disorders, loss of taste and smell, decreased appetite and inadequate dietary intake. Poor dental health, ill-fitting dentures, or chewing and swallowing problems can make eating difficult. As a result of these factors, malnutrition is seen to develop more easily in the elderly.Rates of malnutrition tend to increase with age with less than 10 percent of the "young" elderly (up to age 75) malnourished, while 30 to 65 percent of the elderly in home care, long-term care facilities, or acute hospitals are malnourished. Many elderly people require assistance in eating, which may contribute to malnutrition. However, the mortality rate due to undernourishment may be reduced. Because of this, one of the main requirements of elderly care is to provide an adequate diet and all essential nutrients. Providing the different nutrients such as protein and energy keeps even small but consistent weight gain. Hospital admissions for malnutrition in the United Kingdom have been related to insufficient social care, where vulnerable people at home or in care homes are not helped to eat.In Australia malnutrition or risk of malnutrition occurs in 80 percent of elderly people presented to hospitals for admission. Malnutrition and weight loss can contribute to sarcopenia with loss of lean body |
Malnutrition | mass and muscle function. Abdominal obesity or weight loss coupled with sarcopenia lead to immobility, skeletal disorders, insulin resistance, hypertension, atherosclerosis, and metabolic disorders. A paper from the Journal of the American Dietetic Association noted that routine nutrition screenings represent one way to detect and therefore decrease the prevalence of malnutrition in the elderly.
See also
References
External links
Malnutrition at Curlie
Action Against Hunger | ACF-USA
Action Against Hunger | ACF-UK
Hunger Relief International | HRI
Hunger Relief research on IssueLab
The Global Food Security and Nutrition Forum (FSN Forum)
Ten Things you can do to Fight World Hunger The Nation, May 13, 2009
United Nation 2007 report
World Food Programme | WFP
UN
WFP |
Follicular thyroid cancer | Follicular thyroid cancer accounts for 15% of thyroid cancer and occurs more commonly in women over 50 years of age. Thyroglobulin (Tg) can be used as a tumor marker for well-differentiated follicular thyroid cancer. Thyroid follicular cells are the thyroid cells responsible for the production and secretion of thyroid hormones.
Cause
Associated mutations
Approximately one-half of follicular thyroid carcinomas have mutations in the Ras subfamily of oncogenes, most notably HRAS, NRAS, and KRAS. Mutations in MINPP1 have likewise been observed, as well as germline PTEN gene mutations responsible for Cowden syndrome of which follicular thyroid cancer is a feature. Also, a chromosomal translocation specific for follicular thyroid carcinomas is one between paired box gene 8 (PAX-8), a gene important in thyroid development, and the gene encoding peroxisome proliferator-activated receptor γ 1 (PPARγ1), a nuclear hormone receptor contributing to terminal differentiation of cells. The PAX8-PPARγ1 fusion is present in approximately one-third of follicular thyroid carcinomas, specifically those cancers with a t(2;3)(q13;p25) translocation, permitting juxtaposition of portions of both genes. Tumors tend carry either a RAS mutation or a PAX8-PPARγ1 fusion, and only rarely are both genetic abnormalities present in the same case. Thus, follicular thyroid carcinomas seem to arise by two distinct and virtually nonoverlapping molecular pathways.
Hurthle cell variant
Hurthle cell thyroid cancer is often considered a variant of follicular cell carcinoma. Hurthle cell forms are more likely than follicular carcinomas to be bilateral and multifocal and to metastasize to lymph nodes. Like follicular carcinoma, unilateral hemithyroidectomy is performed for non-invasive disease, and total thyroidectomy for invasive disease.
Diagnosis
It is difficult to correctly diagnose follicular neoplasms (FNs) on fine-needle aspiration cytology (FNAC) because it shares many cytological features with other mimicking lesions.
Classification
It is impossible to distinguish between follicular adenoma and carcinoma on cytological grounds. If fine needle aspiration cytology (FNAC) suggests follicular neoplasm, thyroid lobectomy should be performed to establish the histopathological diagnosis. Features sine qua non for the diagnosis of follicular carcinoma are capsular invasion and vascular invasion by tumor cells. Still, focuses of the capsular invasion should be carefully evaluated and discriminated from the capsular rupture due to FNA penetration resulting in WHAFFT (worrisome histologic alterations following FNA of thyroid).
Follicular carcinoma tends to metastasize to lung and bone via the bloodstream.
Papillary thyroid carcinoma commonly metastasizes to cervical lymph nodes.HMGA2 has been proposed as a marker to identify malignant tumors.
Treatment
Treatment is usually surgical, followed by radioiodine.
Initial treatment
If follicular cells are found on cytological testing, it is common to carry out hemithyroidectomy to distinguish between follicular adenoma and follicular carcinoma on histopathological examination, proceeding to completion thyroidectomy and postoperative radioiodine ablation where carcinoma is confirmed. This way total thyroidectomy is not carried out unnecessarily.
Thyroidectomy is invariably followed by radioiodine treatment at levels from 50 to 200 millicuries following two weeks of a low iodine diet (LID). Occasionally treatment must be repeated if annual scans indicate remaining cancerous tissue. Some physicians favor administering the maximum safe dose (calculated based on a number of factors), while others favor administering smaller doses, which may still be effective in ablating all thyroid tissue. I-131 is used for ablation of the thyroid tissue.
Minimally invasive thyroidectomy has been used in recent years in cases where the nodules are small.
Finding disease recurrence
Some studies have shown that thyroglobulin (Tg) testing combined with neck ultrasound is more productive in finding disease recurrence than full- or whole-body scans (WBS) using radioactive iodine. However, current protocol (in the USA) suggests a small number of clean annual WBS are required before relying on Tg testing plus neck ultrasound. When needed, whole body scans consist of withdrawal from thyroxine medication and/or injection of recombinant human Thyroid stimulating hormone (TSH). In both cases, a low iodine diet regimen must also be followed to optimize the takeup of the radioactive iodine dose. Low dose radioiodine of a few millicuries is administered. Full body nuclear medicine scan follows using a gamma camera. Scan doses of radioactive iodine may be I131 or I123.
Recombinant human TSH, commercial name Thyrogen, is produced in cell culture from genetically engineered hamster cells.
Prognosis
The overall 5-year survival rate for follicular thyroid cancer is 91%, and the 10-year survival rate is 85%.By overall cancer staging into stages I to IV, follicular thyroid cancer has a 5-year survival rate of 100% for stages I and II, 71% for stage III, and 50% for stage IV.Compared to other variants of Follicular cell derived thyroid cancer, bone metastases are commonly associated with follicular carcinoma. In the present study a high rate of bone metastases of 34% was observed.
References
External links
Thyroid cancer at DMOZ Archived 2017-03-14 at the Wayback Machine
Cancer Management Handbook: Thyroid and Parathyroid Cancers
Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer The American Thyroid Association Guidelines Taskforce (2015). |
Stab wound | A stab wound is a specific form of penetrating trauma to the skin that results from a knife or a similar pointed object. While stab wounds are typically known to be caused by knives, they can also occur from a variety of implements, including broken bottles and ice picks. Most stabbings occur because of intentional violence or through self-infliction. The treatment is dependent on many different variables such as the anatomical location and the severity of the injury. Even though stab wounds are inflicted at a much greater rate than gunshot wounds, they account for less than 10% of all penetrating trauma deaths.
Management
Stab wounds can cause various internal and external injuries. They are generally caused by low-velocity weapons, meaning the injuries inflicted on a person are typically confined to the path it took internally, instead of causing damage to surrounding tissue, which is common of gunshot wounds. The abdomen is the most commonly injured area from a stab wound. Interventions that may be needed depending on severity of the injury include airway, intravenous access, and control of hemorrhage. The length and size of the knife blade, as well as the trajectory it followed, may be important in planning management as it can be a predictor of what structures were damaged. There are also special considerations to take into effect as given the nature of injuries, there is a higher likelihood that persons with these injuries might be under the influence of illicit substances which can make it harder to obtain a complete medical history. Special precautions should also be taken to prevent further injury from a perpetrator to the victim in a hospital setting. Similarly to treating shock, it is important to keep the systolic pressure above 90mmHg, maintain the persons core body temperature, and for prompt transport to a trauma center in severe cases.To determine if internal bleeding is present a focused assessment with sonography (FAST) or diagnostic peritoneal lavage (DPL) can be used. Other diagnostic tests such as a computed tomography scan or various contrast studies can be used to more definitively classify the injury in both severity and location. Local wound exploration is also another technique that may be utilized to determine how far the object penetrated. Observation can be used in place of surgery as it can substitute an unnecessary surgery, which makes it the preferred treatment of penetrating trauma secondary to a stab wound when hypovolemia or shock is not present. Laboratory diagnostic studies such as a hematocrit, white blood cell count and chemical tests such as liver function tests can also help to determine the efficiency of care.
Surgery
Surgical intervention may be required but it depends on what organ systems are affected by the wound and the extent of the damage. It is important for care providers to thoroughly check the wound site in as much as a laceration of an artery often results in delayed complications sometimes leading to death. In cases where there is no suspicion of bleeding or infection, there is no known benefit of surgery to correct any present injuries. Typically a surgeon will track the path of the weapon to determine the anatomical structures that were damaged and repair any damage they deem necessary. Surgical packing of the wounds is generally not the favored technique to control bleeding as it can be less useful than fixing the directly affected organs. In severe cases when homeostasis cannot be maintained the use of damage control surgery may be utilized.
Epidemiology
Stab wounds are one of the most common forms of penetrating trauma globally, but account for a lower mortality compared to blunt injuries due to their more focused impact on a person. Stab wounds can result from self-infliction, accidental nail gun injuries, and stingray injuries, however, most stab wounds are caused by intentional violence, as the weapons used to inflict such wounds are readily available compared to guns. Stabbings are a relatively common cause of homicide in Canada and the United States. Typically death from stab wounds is due to organ failure or blood loss. They are the mechanism of approximately 2% of suicides.In Canada, homicides by stabbing and gunshot occur relatively equally (1,008 to 980 for the years 2005 to 2009). In the United States guns are a more common method of homicide (9,484 versus 1,897 for stabbing or cutting in 2008).Stab wounds occur four times more than gunshot wounds in the United Kingdom, but the mortality rate associated with stabbing has ranged from 0-4% as 85% of injuries sustained from stab wounds only affect subcutaneous tissue. Most assaults resulting in a stab wound occur to and by men and persons of ethnic minorities.
History
Some of the first principles of wound care come from Hippocrates who promoted keeping wounds dry except for irrigation. Guy de Chauliac would promote removal of foreign bodies, rejoining of severed tissues, maintenance of tissue continuity, preservation of organ substance, and prevention of complications. The first successful operation on a person who was stabbed in the heart was performed in 1896 by Ludwig Rehn, in what is now considered the first case of heart surgery. In the late 1800s it was hard to treat stab wounds because of poor transportation of victims to health facilities and the low ability for surgeons to effectively repair organs. However, the use of laparotomy, which has been developed a few years earlier, had provided better patient outcomes than had been seen before. After its inception, the use of exploratory laparotomies was highly encouraged for "all deep stab wounds" in which surgeons were to stop active bleeding, repair damage, and remove "devitalized tissues". Because laparotomies were seen to benefit patients, they were used on most every person with an abdominal stab wound until the 1960s when doctors were encouraged to use them more selectivity in favor of observation. During the Korean war, a greater emphasis was put on the use of pressure dressings and tourniquets to initially control bleeding.
See also
Ballistic trauma
References
Bibliography
Feliciano, David V.; Mattox, Kenneth L.; Moore, Ernest J (2012). Trauma, Seventh Edition (Trauma (Moore)). McGraw-Hill Professional. ISBN 978-0-07-166351-9.
Marx, John A. Marx (2014). Rosens emergency medicine : concepts and clinical practice (8th ed.). Philadelphia, PA: Elsevier/Saunders. pp. Chapter. ISBN 978-1455706051.
== External links == |
Haemobilia | Haemobilia is a medical condition of bleeding into the biliary tree. Haemobilia occurs when there is a fistula between a vessel of the splanchnic circulation and the intrahepatic or extrahepatic biliary system. It can present as acute upper gastrointestinal (UGI) bleeding. It should be considered in upper abdominal pain presenting with UGI bleeding especially when there is a history of liver injury or instrumentation.First recorded in 1654 by Francis Glisson, a Cambridge professor.
Presentation
Quinckes triad of upper abdominal pain, upper gastrointestinal haemorrhage and jaundice is classical but only present in 22% cases.It can be immediately life-threatening in major bleeding. However, in minor haemobilia, patient is haemodynamically stable despite significant blood loss being apparent.
Causes
The causes of haemobilia include trauma (which can be accidental or iatrogenic due to procedures such as cholecystectomy), instrumentation (especially after ERCP), gallstone, inflammatory conditions ranging from ascariasis to PAN, vascular malformation, tumors, coagulopathy, and liver biopsy.
Diagnosis
Combination of EGD, CT scan and angiography depending on clinical situation, bearing in mind that haemobilia may present many days after injury. Cholangiography is performed if there is a percutaneous access or if ERCP is undertaken.
Management
Most bleeding from instrumentation are minor and would settle spontaneously.When indicated, management is directed towards stopping bleeding and relieving obstruction if present, which is achieved either by surgical ligation of hepatic artery or by endovascular embolisation. Endovasculartrans-arterial embolisation (TAE) is preferred initially because of high success rate and less complication. TAE involves the selective catheterization of a hepatic artery followed by embolic occlusion. Surgery is indicated when TAE has failed or sepsis present in biliary tree or drainage has failed.
References
External links
CT of the abdomen with hemobilia |
Thallium poisoning | Thallium poisoning is poisoning that is due to thallium and its compounds, which are often highly toxic. Contact with skin is dangerous and adequate ventilation should be provided when melting this metal. Many thallium compounds are highly soluble in water and are readily absorbed through the skin. Exposure to them should not exceed 0.1 mg per m2 of skin in an 8 hour time-weighted average (40- hour working week). Thallium is a suspected human carcinogen.Part of the reason for thalliums high toxicity is that when present in aqueous solution as the univalent thallium(I) ion (Tl+) it exhibits some similarities with essential alkali metal cations, particularly potassium (owing to similar ionic radii). It can thus enter the body via potassium uptake pathways. Other aspects of thalliums chemistry differ strongly from that of the alkali metals, such as its high affinity for sulfur ligands. Thus this substitution disrupts many cellular processes by interfering with the function of proteins that incorporate cysteine, an amino acid containing sulfur. Thalliums toxicity has led to its use (now discontinued in many countries) as a rat and ant poison.Among the distinctive effects of thallium poisoning are peripheral nerve damage (victims may experience a sensation of “walking on hot coals”) and hair loss (which led to its initial use as a depilatory before its toxicity was properly appreciated). However hair-loss generally occurs only with low doses; with high doses the thallium kills before hair loss can occur. Thallium was an effective murder weapon before its effects became understood and an antidote (Prussian blue) discovered. It has been called the "poisoners poison" since it is colorless, odorless and tasteless; its slow-acting, painful and wide-ranging symptoms are often suggestive of a host of other illnesses and conditions.
Cause
Bioconcentration
According to the United States Environmental Protection Agency (EPA), thallium release to the environment was reported in Texas and Ohio. This may indicate bioconcentration in aquatic ecosystems.
Thallium compounds
The odorless and tasteless thallium sulfate was also used as rat poison and ant killer. Since 1975, this use in the United States and many other countries is prohibited due to safety concerns.
Diagnosis
Thallium may be measured in blood or urine as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths. Normal background blood and urine concentrations in healthy persons are usually less than 1 μg/litre, but they are often in the 1–10 mg/litre range (1,000–10,000 times higher) in survivors of acute intoxication. Thallium is present in the blood for a very short time so urine testing is usually most appropriate. A quick way to assess possible thallium poisoning is to perform a microscopic analysis of a hair and its root. In thallium poisoning this analysis will show a tapered anagen hair with black pigmentation at the base (anagen effluvium). This is pathognomonic for thallium toxicity.
Treatment
There are two main methods of removing both radioactive and stable isotopes of thallium from humans. First known was to use Prussian blue, which is a solid ion exchange material, which absorbs thallium. Up to 20 g per day of Prussian blue is fed by mouth to the person, and it passes through their digestive system and comes out in the stool. Hemodialysis and hemoperfusion are also used to remove thallium from the blood stream. At later stage of the treatment additional potassium is used to mobilize thallium from the tissue.
Notable cases
There are numerous recorded cases of fatal thallium poisoning. Because of its use for murder, thallium has gained the nicknames "The Poisoners Poison" and "Inheritance Powder" (alongside arsenic).
Australias "Thallium Craze"
In Australia, in the early 1950s, there was a notable spate of cases of murder or attempted murder by thallium poisoning. At this time, due to the chronic rat infestation problems in overcrowded inner-city neighbourhoods (notably in Sydney), and thalliums effectiveness as a rat poison, it was still readily available over the counter in New South Wales, where thallium sulphate was marketed as a commercial rat bait, under the brand Thall-rat .
In September 1952 Yvonne Gladys Fletcher, a housewife and mother of two from the inner Sydney suburb of Newtown, was charged and tried for the murders of both her first husband, Desmond Butler (who died in 1948), and her abusive second husband, Bertrand "Bluey" Fletcher, a rat-bait layer, from whom she had obtained the thallium poison that she used to kill him earlier that year. Suspicions were raised after it became obvious to friends and neighbours that Bluey Fletcher was suffering from the same fatal illness that had killed Yvonnes first husband. A police investigation led to the exhumation and testing of Desmond Butlers remains, which showed clear evidence of thallium, and this led to Yvonne being convicted of Butlers murder. She was sentenced to death but the sentence was commuted to life imprisonment after the NSW Government abolished the death penalty; she was eventually released in 1964. At the time of the trial it was reported that this was the first known case in Australia of a person being convicted of murder by administering thallium. The Fletcher case is also notable for the fact that one of the arresting officers was Sydney detective Fred Krahe, who later became notorious for his suspected close involvement with elements of Sydneys organised crime scene and his alleged involvement in the disappearance of social activist Juanita Nielsen.
A month later, in October 1952, Bathurst grandmother Ruby Norton was tried for the murder of her daughters fiancé, Allen Williams, who died of thallium poisoning at Cowra Hospital in July 1952. Despite allegations that Norton hated all the men in her family and that she did not want Williams as a son-in-law, Norton was acquitted.
In 1953 Sydney woman Veronica Monty, 45, was tried for the attempted murder of her son-in-law, noted Balmain and Australian rugby league player Bob Lulham, who was treated for thallium poisoning in 1952. After separating from her husband Monty had moved in with her daughter Judy and Judys husband, Bob Lulham. The sensational trial revealed that Lulham and Monty had an "intimate relationship" while Lulhams wife was at Sunday mass. Monty was found not guilty; Judy Lulham divorced her husband as a result of the revelations about his affair and Monty killed herself with thallium in 1955.
In July 1953, Sydney woman Beryl Hague was tried for "maliciously administering thallium and endangering her husbands life". Hague confessed to buying Thall-rat from a corner shop and putting it in her husbands tea because she wanted to "give him a headache to repay the many headaches he had given me" in violent disputes.
In 1953 Australian Caroline Grills was sentenced to life in prison after three family members and a close family friend died. Authorities found thallium in tea that she had given to two other family members. Grills spent the rest of her life in Sydneys Long Bay Gaol, where fellow inmates dubbed her "Aunt Thally".The Australian TV documentary Recipe for Murder, released in 2011, examined three of the most sensational and widely reported Australian thallium poisonings, the Fletcher, Monty and Grills cases.
Others
Félix-Roland Moumié, a Cameroonian leader, was assassinated with thallium in Geneva on 3 November 1960 by a former agent of the SDECE (French secret service) probably at the request of Cameroonian authorities.
In 1971, thallium was the main poison that Graham Frederick Young used to poison around 70 people in the English village of Bovingdon, Hertfordshire, of whom three died.
From 1976 to late 1979, thallium was used as a chemical warfare agent, most notably by a unit of the British South Africa Police (BSAP) attached to the Selous Scouts during the Rhodesian Bush War.
In 1977, a 19 month-old girl living in Qatar fell ill due to thallium poisoning (from pesticides used by her parents). While doctors were unable to identify the cause, a nurse named Marsha Maitland managed to do it from the description of the symptoms given in The Pale Horse.
In summer 1981 the East German secret service "Stasi" poisoned dissident Wolfgang Welsch, who had previously been expelled to West Germany, during his holiday in Israel. He barely survived.
In 1985, spiritual leader Rajneesh was allegedly poisoned with small doses of poison, by Reagan Administration and Church, as per accounts of his followers. This allegation was never proven. He died after 5 years in 1990.
In 1987, in Kyiv, a woman named Tamara Ivanutina was arrested along with her older sister and parents. They were found guilty of 40 cases of poisoning (13 of them lethal) with Clerici solution obtained from an acquaintance working at a geology institute. Tamara (guilty of nine deaths, including four children) was executed in one of the three documented cases of women receiving the capital punishment in post-Stalin Soviet Union. Her relatives received prison terms, the parents dying in jail.
In 1988, members of the Carr family from Alturas, Polk County, Florida, fell ill from what appeared to be thallium poisoning. Peggy Carr, the mother, died slowly and painfully from the poison. Her son and stepson were critically ill but eventually recovered. The Carrs neighbor, chemist George J. Trepal, was convicted of murdering Mrs. Carr and attempting to murder her family, and sentenced to death. The thallium was slipped into bottles of Coca-Cola at the Carr and Trepal homes.
Thallium was the poison of choice for Saddam Hussein to use on dissidents, which even allowed for them to emigrate before dying.
In 1995, Zhu Ling was the victim of an unsolved attempted thallium poisoning in Beijing, China. In 1994, Zhu Ling was a sophomore studying physical chemistry at Tsinghua University in Beijing. She began to show strange and debilitating symptoms at the end of 1994, when she reported experiencing acute stomach pain and extensive hair loss. Ultimately she was diagnosed on Usenet with poisoning by thallium. To this day, there is still speculation among Chinese expatriates overseas as to the poisoners identity. The only suspect of the police investigation, Sun Wei, is a member of a family with high-level political connections, which may have been used to halt and suppress the results of the investigation. Sun Wei was Zhu Lings classmate and roommate in Tsinghua University from 1992–1997. Tsinghua University also said she was the only student who had access to thallium compounds at the school. The investigations results have never been released to Zhu Lings parents or the general public. However, Tsinghua University declined to issue Sun Weis B.S. certificate and refused to provide her with the documentation needed to get a passport or visa in 1997. In 2018 the victims hair has been examined by the University of Maryland geologist Richard Ash using laser ablation ICP-MS mass spectrometry. He was able to confirm the timeline and pattern of poisoning.
In 1999, Norwegian Terje Wiik was sentenced to 21 years imprisonment for poisoning his girlfriend with thallium.
In June 2004, 25 Russian soldiers earned Honorable Mentions in the Darwin Awards after becoming ill from thallium exposure when they found a can of mysterious white powder in a rubbish dump on their base at Khabarovsk in the Russian Far East. Oblivious to the danger of misusing an unidentified white powder from a military dump site, the conscripts added it to tobacco, and used it as a substitute for talcum powder on their feet.
In 2005, a 17 year-old girl in Izunokuni, Shizuoka, Japan admitted to attempting to murder her mother by lacing her tea with thallium, causing a national scandal.
In February 2007, two Americans, Marina and Yana Kovalevsky, a mother and daughter, visiting Russia were hospitalized for thallium poisoning. Both had emigrated from the Soviet Union to the United States in 1991 and had made several trips to Russia since then.
In January 2008, 10 members of two families associated with an Iraqi soccer club, including several children, were poisoned by cake contaminated with thallium. Four died, including two children.
In 2011, a chemist at Bristol-Myers Squibb in New Jersey, Li Tianle, was charged with the murder of her husband. According to an investigation by the Middlesex County Prosecutors Office, Li Tianle was able to obtain a chemical containing thallium and fed it to her husband. Li was a chemistry student at Beijing University at the time of the highly publicized thallium poisoning of Zhu Ling in 1995 at neighboring Tsinghua University.
In 2012 a chemistry postgraduate student at the University of Southampton, UK, was found to be suffering from the effects of thallium and arsenic poisoning after presenting with neurological symptoms. The student underwent an intensive course of treatment and, although he has shown improvement, faces an uncertain long-term prognosis for the recovery of full locomotion. Urine screening revealed elevated thallium levels in a small number of other members of the chemistry department, though none were at toxic levels. The source of the poisoning remains unknown, and although police investigations were fruitless, foul play is strongly suspected.
In 2018, authorities charged Yukai Yang, a student at Lehigh University, with the attempted murder of his roommate, Juwan Royal. Yang allegedly poisoned Royal with thallium and possibly other chemicals. Royal experienced vomiting, pain and numbness in his lower extremities, and a long-lasting burning sensation on his tongue.
In 2022, an English family court found an unnamed doctor guilty of using thallium in a pot of coffee to kill his partners father and injuring the partner and her mother in 2012. The case is unusual because it was in a family court, arising out of child-custody matters, rather than a criminal case.
In fiction
Ngaio Marsh used thallium acetate in her 1947 detective novel, Final Curtain. It was being used legitimately for scalp problems in a group of school children just after World War II, housed in a private estate. A relative living there used it in place of the heart medicine intended for the owner.
Agatha Christie, who worked as an apothecarys assistant, used thallium in 1961 as the agent of murder in her detective fiction novel The Pale Horse – the first clue to the murder method coming from the hair loss of the victims. This novel is notable as being credited with having saved at least two lives after readers recognised the symptoms of thallium poisoning that Christie described. The Pale Horse was found among possessions of convicted thallium poisoner George Trepals wife, the orthopedic surgeon Dr. Diana Carr (see above), who was herself considered a suspect in the Peggy Carr (no relation) murder for a time.
In Nigel Williams 1990 novel The Wimbledon Poisoner, Henry Far uses thallium to baste a roast chicken in a failed attempt to murder his wife.
Thallium figures prominently in the 1995 film The Young Poisoners Handbook, a dark comedy loosely based on the life of Graham Frederick Young.
In Big Nothing, Josie is the Wyoming Widow; a murderer who befriended men and killed them with whiskey laced with highly concentrated thallium.
In the 2007 episode "Whatever It Takes" of House, a character uses thallium to poison a patient to mimic the effects of polio, then appear to cure it with ultra-high doses of vitamin C.
In the NCIS episode "Dead Man Walking" (2007), thallium-laced cigars are used to murder a Naval officer.
"Page Turner", a 2008 episode of CSI: NY, has radioactive thallium poisoning as its central theme.
In the 2010 film Edge of Darkness, thallium is used to poison both the main character and his daughter.
In the 2015 James Bond film Spectre, the organisation of the same name used thallium to poison Mr. White by lacing his mobile phone with it.
In Season 3 of Royal Pains, the mysterious German billionaire Boris Kuester von Jurgens-Ratenicz was poisoned by thallium added to his pools water.
In Drop Dead Diva episode "Ashes to Ashes", thallium was used to murder a clients husband, affecting the client when she ate the cremation remains.
In the 2016 TVB drama Two Steps From Heaven, thallium was used to poison Bosco Wongs character.
In S6:E10 of the Father Brown Series, Hercule Flambeaus wife poisons Father Brown with thallium in order to induce Flambeau to exchange a religious relic for her giving Brown the antidote. Guessing the substance his wife used, Flambeau gives Brown clues as to the antidote, Prussian Blue.
In S6:E9 of Elementary, entitled "Nobody Lives Forever" (2018), a biology professor studying how to prolong life spans is poisoned with thallium. As he dies, he falls onto a shelf containing his lab rats, which escape and eventually eat part of his body. Some dead rats are found inside him, suggesting to the detectives that the cause of death was poisoning.
References
External links
"Thallium, elemental". National Institutes of Health. NLM hazardous substances databank. U.S. Department of Health and Human Services.
Curley, Robert. "Cyril Wecht, Thallium". crimelibrary.com. Archived from the original on 17 April 2008.
"ToxFAQs". Centers for Disease Control. ATSDR. U.S. Department of Health and Human Services.
"Two Iraqi children die from Thallium poisoning". The Guardian. reports. 9 February 2008. |
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