text1
stringlengths 11
17.4k
| text2
stringlengths 11
8.2k
| label
class label 2
classes |
|---|---|---|
Kidney complications such as angiomyolipoma and cysts are common and more frequent in females than males and in TSC2 than TSC1. Renal cell carcinoma is uncommon. Lymphangioleiomyomatosis is only a risk for females with angiomyolipomas. In the brain, the subependymal nodules occasionally degenerate to subependymal giant cell astrocytomas. These may block the circulation of cerebrospinal fluid around the brain, leading to hydrocephalus.Detection of the disease should be followed by genetic counselling. It is also important to realise that though the disease does not have a cure, symptoms can be treated symptomatically. Hence, awareness regarding different organ manifestations of TSC is important. Epidemiology
TSC occurs in all races and ethnic groups, and in both genders. The live-birth prevalence is estimated to be between 10 and 16 cases per 100,000. A 1998 study estimated total population prevalence between about 7 and 12 cases per 100,000, with more than half of these cases undetected. Prior to the invention of CT scanning to identify the nodules and tubers in the brain, the prevalence was thought to be much lower, and the disease associated with those people diagnosed clinically with learning disability, seizures and facial angiofibroma. Whilst still regarded as a rare disease, TSC is common when compared to many other genetic diseases, with at least 1 million individuals affected worldwide. History
TSC first came to medical attention when dermatologists described the distinctive facial rash (1835 and 1850). A more complete case was presented by von Recklinghausen (1862), who identified heart and brain tumours in a newborn who had only briefly lived. | Diagnosis
Computed Tomography (CT) is generally not a recommended modality for diagnosis and evaluation of spinal cord tumors. Evaluation with Magnetic Resonance (MR) most commonly demonstrates a circumscribed solid or mixed solid and cystic mass spanning a long segment of the cord with hypointense T1 signal and hyperintense T2 signal in the solid component. Enhancement patterns are highly variable, ranging from minimal to marked, and may be solid, rim, or nodular. Adjacent cord edema and syringomyelia and peritumoral cysts may be present in addition to reactive scoliosis. It is nearly impossible to differentiate ganglioglioma from other more common intramedullary neoplasms based on imaging alone. Astrocytoma and ependymoma are more familiar intramedullary tumors which share many similar features to ganglioglioma, including T2 hyperintensity, enhancement, tumoral cysts, and cord edema. Poorly defined margins may be more suggestive of astrocytoma, while a central location in the spinal cord, hemorrhage, and hemosiderin staining are often seen with ependymoma. Hemangioblastoma and paraganglioma are less usual intramedullary tumors, but since they are more frequently encountered than ganglioglioma, they should also be included in the differential diagnosis. Treatment
Definitive treatment for ganglioglioma requires gross total surgical resection, and a good prognosis is generally expected when this is achieved. However, indistinct tumor margins and the desire to preserve normal spinal cord tissue, motor and sensory function may preclude complete resection of tumor. According to a series by Lang et al., reviewing several patients with resected spinal cord ganglioglioma, the 5- and 10-year survival rates after total resection were 89% and 83%, respectively. | 0-1
|
Amifampridine is used as a drug, predominantly in the treatment of a number of rare muscle diseases. The free base form of the drug has been used to treat congenital myasthenic syndromes and Lambert–Eaton myasthenic syndrome (LEMS) through compassionate use programs since the 1990s and was recommended as a first line treatment for LEMS in 2006, using ad hoc forms of the drug, since there was no marketed form. Around 2000 doctors at Assistance Publique – Hôpitaux de Paris created a phosphate salt form, which was developed through a series of companies ending with BioMarin Pharmaceutical which obtained European approval in 2009 under the trade name Firdapse, and which licensed the US rights to Catalyst Pharmaceuticals in 2012. As of January 2017, Catalyst and another US company, Jacobus Pharmaceutical, which had been manufacturing and giving it away for free since the 1990s, were both seeking FDA approval for their iterations and marketing rights. Amifampridine phosphate has orphan drug status in the EU for Lambert–Eaton myasthenic syndrome and Catalyst holds both an orphan designation and a breakthrough therapy designation in the US. In May 2019 the U.S. Food and Drug Administration (FDA) approved amifampridine tablets under the trade name Ruzurgi for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in patients 6 to less than 17 years of age. This is the first FDA approval of a treatment specifically for pediatric patients with LEMS. The FDA granted the approval of Ruzurgi to Jacobus Pharmaceutical. | Congenital dermal sinus is an uncommon form of cranial or spinal dysraphism. It occurs in 1 in 2500 live births. It occurs as a dermal indentation, found along the midline of the neuraxis and often presents alongside infection and neurological deficit. Congenital dermal sinus form due to a focal failure of dysjunction between the cutaneous ectoderm and neuroectoderm during the third to eight week of gestation. Typically observed in the lumbar and lumbosacral region, congenital dermal sinus can occur from the nasion and occiput region down.Early diagnosis and treatment is crucial for cases of congenital dermal sinus. It ensures that neurological condition does not degrade and prevents infection. Diagnosis can be confirmed through the use of advanced neuroimaging to observe the tract and associated lesions. Embryogenesis
During normal development, cutaneous ectoderm separates from neuroectoderm to allow for the insertion of mesoderm. That is, the skin separates from the tissue of the spinal cord to allow proper formation of the vertebral column. In cases of congenital dermal sinus there is a failure in this process, resulting in formation of a persistent connection between the skin and neural tissue. This manifests as a tract extending from the surface of the skin to the spinal cord lined with stratified squamous epithelium, surrounded by dermal and neurological tissue. The tract may terminate in the deep fascia, or even make contact with neural elements. | 0-1
|
These metabolites show approximately 20% of the inhibitory activity of finasteride on 5α-reductase. Hence, the metabolites of finasteride are not particularly active. The drug has a terminal half-life of 5 to 6 hours in adult men (18–60 years of age) and a terminal half-life of 8 hours or more in elderly men (more than 70 years of age). It is eliminated as its metabolites 57% in the feces and 40% in the urine. Chemistry
Finasteride, also known as 17β-(N-tert-butylcarbamoyl)-4-aza-5α-androst-1-en-3-one, is a synthetic androstane steroid and 4-azasteroid. It is an analogue of androgen steroid hormones like testosterone and DHT. As an unconjugated steroid, finasteride is a highly lipophilic compound. History
In 1942, James Hamilton observed that prepubertal castration prevents the later development of male pattern baldness in mature men. In 1974, Julianne Imperato-McGinley of Cornell Medical College in New York attended a conference on birth defects. She reported on a group of intersex children in the Caribbean who appeared sexually ambiguous at birth, and were initially raised as girls, but then grew external male genitalia and other masculine characteristic after onset of puberty. These children, despite being raised as girls until puberty, were generally heterosexual, and were termed "Guevedoces" by their local community, which means "penis at twelve" in Spanish. Her research group found these children shared a genetic mutation, causing deficiency of the 5α-reductase enzyme and male hormone dihydrotestosterone (DHT), which was found to have been the etiology behind abnormalities in male sexual development. | Drug-induced purpura is a skin condition that may be related to platelet destruction, vessel fragility, interference with platelet function, or vasculitis. : 824
See also
Food-induced purpura
Rumpel-Leede sign
Skin lesion
== References == | 0-1
|
Transmission and life cycle
Infected individuals release Schistosoma eggs into water via their fecal material or urine. After larvae hatch from these eggs, the larvae infect a very specific type of freshwater snail. For example, in S. haematobium and S. intercalatum it is snails of the genus Bulinus, in S. mansoni it is Biomphalaria, and in S. japonicum it is Oncomelania. The Schistosoma larvae undergo the next phase of their lifecycles in these snails, spending their time reproducing and developing. Once this step has been completed, the parasite leaves the snail and enters the water column. The parasite can live in the water for only 48 hours without a mammalian host. Once a host has been found, the worm enters its blood vessels. For several weeks, the worm remains in the vessels, continuing its development into its adult phase. When maturity is reached, mating occurs and eggs are produced. Eggs enter the bladder/intestine and are excreted through urine and feces and the process repeats. If the eggs do not get excreted, they can become engrained in the body tissues and cause a variety of problems such as immune reactions and organ damage. While transmission typically occurs only in countries where the freshwater snails are endemic, a case in Germany was reported where a man got Schistosoma by an infected snail in his aquarium.Humans encounter larvae of the Schistosoma parasite when they enter contaminated water while bathing, playing, swimming, washing, fishing, or walking through the water. | See Hs and Ts
Hypovolemia
Hypoxia
Hydrogen ions (Acidosis)
Hyperkalemia or Hypokalemia
Hypoglycemia
Hypothermia
Tablets or Toxins
Cardiac Tamponade
Tension pneumothorax
Thrombosis (e.g., myocardial infarction, pulmonary embolism)
Tachycardia
Trauma (e.g., hypovolemia from blood loss)The possible mechanisms by which the above conditions can cause pulseless in PEA are the same as those recognized as producing circulatory shock states. These are (1) impairment of cardiac filling, (2) impaired pumping effectiveness of the heart, (3) circulatory obstruction and (4) pathological vasodilation causing loss of vascular resistance and excess capacitance. More than one mechanism may be involved in any given case. Diagnosis
The absence of a pulse confirms a clinical diagnosis of cardiac arrest, but PEA can only be distinguished from other causes of cardiac arrest with a device capable of electrocardiography (ECG/EKG). In PEA, there is organised or semi-organised electrical activity in the heart as opposed to asystole (flatline) or to the disorganised electrical activity of either ventricular fibrillation or ventricular tachycardia. Treatment
Cardiac resuscitation guidelines (ACLS/BCLS) advise that cardiopulmonary resuscitation should be initiated promptly to maintain cardiac output until the PEA can be corrected. The approach in treatment of PEA is to treat the underlying cause, if known (e.g. relieving a tension pneumothorax). Where an underlying cause for PEA cannot be determined and/or reversed, the treatment of pulseless electrical activity is similar to that for asystole. | 0-1
|
In patients that have a history of eating disorders, Rumination syndrome is grouped alongside eating disorders such as bulimia and pica, which are themselves grouped under non-psychotic mental disorder. In most healthy adolescents and adults who have no mental disability, Rumination syndrome is considered a motility disorder instead of an eating disorder, because the patients tend to have had no control over its occurrence and have had no history of eating disorders. Treatment and prognosis
There is presently no known cure for rumination. Proton pump inhibitors and other medications have been used to little or no effect. Treatment is different for infants and mentally disabled adults than for adults and adolescents of typical intelligence. Among infants and mentally disabled adults, behavioral and mild aversion training has been shown to cause improvement in most cases. Aversion training involves associating the ruminating behavior with negative results, and rewarding good behavior and eating. Placing a sour or bitter taste on the tongue when the individual begins the movements or breathing patterns typical of his or her ruminating behavior is the generally accepted method for aversion training,
although some older studies advocate the use of pinching. In patients of normal intelligence, rumination is not an intentional behavior and is habitually reversed using diaphragmatic breathing to counter the urge to regurgitate. Alongside reassurance, explanation and habit reversal, patients are shown how to breathe using their diaphragms prior to and during the normal rumination period. A similar breathing pattern can be used to prevent normal vomiting. | The different strategies for surgical management are controversial, and depend on factors such as patient fitness for surgery and comorbidities. Eponym
Bouverets syndrome refers to reverse gallstone ileus where the gallstone propagates proximally and causes gastric outlet obstruction by being impacted in first part of duodenum. References
== External links == | 0-1
|
HbC has been described as being more advantageous than HbS because, even in homozygous individuals, it is usually non-fatal. However, in contrast to HbS, it does not prevent malaria due to P. vivax, and is less effective in resistance to falciparum malaria in heterozygous conditions. Homozygous HbC is more resistant to heterozygous condition, or to thalassemias. But HbC mutation does not prevent the infection. P. falciparum do not survive in red blood cells with homozygous hemoglobins, but can survive in the presence of heterozygous hemoglobins. HbC reduced the binding force (cytoadherence) of P. falciparum by reducing the activity of PfEMP1. Evidences indicate that HbC reduced the level of PfEMP1, which is required for effective binding and invasion of RBC by the malarial parasite. It has been predicted that with the trend of HbC mutation and falciparum prevalence, HbC would replace HbS in central West Africa in the future. Diagnosis
Physical examination may show an enlarged spleen. Tests that may be done include: complete blood count (CBC), hemoglobin electrophoresis, and peripheral blood smear. Prevention
Genetic counseling may be appropriate for high-risk couples who wish to have a baby. Treatment
Usually no treatment is needed. Folic acid supplementation may help produce normal red blood cells and improve the symptoms of anemia
Prognosis
Overall, hemoglobin C disease is one of the more benign hemoglobinopathies. Mild-to-moderate reduction in RBC lifespan may accompany from mild hemolytic anemia. Individuals with hemoglobin C disease have sporadic episodes of musculoskeletal (joint) pain. People with hemoglobin C disease can expect to lead a normal life. | Hemoglobin C (abbreviated as HbC) is an abnormal hemoglobin in which glutamic acid residue at the 6th position of the β-globin chain is replaced with a lysine residue due to a point mutation in the HBB gene. People with one copy of the gene for hemoglobin C do not experience symptoms, but can pass the abnormal gene on to their children. Those with two copies of the gene are said to have hemoglobin C disease and can experience mild anemia. It is possible for a person to have both the gene for hemoglobin S (the form associated with sickle cell anemia) and the gene for hemoglobin C; this state is called hemoglobin SC disease, and is generally more severe than hemoglobin C disease, but milder than sickle cell anemia.HbC was discovered by Harvey Itano and James V. Neel in 1950 in two African-American families. It has since been established that it is most common among people in West Africa. It confers survival benefits as individuals with HbC are naturally resistant to malaria caused by Plasmodium falciparum, albeit incompletely. Symptoms and signs
People with one copy of the gene for hemoglobin C (termed heterozygous) do not experience significant symptoms, but can pass the abnormal gene onto their children; this condition is called hemoglobin C trait. When two hemoglobin C genes are present (termed homozygous), the individual is said to have hemoglobin C disease, and may develop mild anemia, as red blood cells containing hemoglobin C have a decreased lifespan. | 11
|
In the developed world, about 20% of people are affected by allergic rhinitis, about 6% of people have at least one food allergy, and about 20% have or have had atopic dermatitis at some point in time. Depending on the country, about 1–18% of people have asthma. Anaphylaxis occurs in between 0.05–2% of people. Rates of many allergic diseases appear to be increasing. The word "allergy" was first used by Clemens von Pirquet in 1906. Signs and symptoms
Many allergens such as dust or pollen are airborne particles. In these cases, symptoms arise in areas in contact with air, such as the eyes, nose, and lungs. For instance, allergic rhinitis, also known as hay fever, causes irritation of the nose, sneezing, itching, and redness of the eyes. Inhaled allergens can also lead to increased production of mucus in the lungs, shortness of breath, coughing, and wheezing.Aside from these ambient allergens, allergic reactions can result from foods, insect stings, and reactions to medications like aspirin and antibiotics such as penicillin. Symptoms of food allergy include abdominal pain, bloating, vomiting, diarrhea, itchy skin, and hives. Food allergies rarely cause respiratory (asthmatic) reactions, or rhinitis. Insect stings, food, antibiotics, and certain medicines may produce a systemic allergic response that is also called anaphylaxis; multiple organ systems can be affected, including the digestive system, the respiratory system, and the circulatory system. Depending on the severity, anaphylaxis can include skin reactions, bronchoconstriction, swelling, low blood pressure, coma, and death. | It concluded likewise in 2007 that allergy services were insufficient to deal with what the Lords referred to as an "allergy epidemic" and its social cost; it made several recommendations. Research
Low-allergen foods are being developed, as are improvements in skin prick test predictions; evaluation of the atopy patch test, wasp sting outcomes predictions, a rapidly disintegrating epinephrine tablet, and anti-IL-5 for eosinophilic diseases. See also
List of allergens
Allergic shiner
Histamine intolerance
Oral allergy syndrome
References
External links
Allergy at Curlie
"Allergy". MedlinePlus. U.S. National Library of Medicine. Types of Pollen Allergies | 11
|
It was developed and marketed by Melinta Therapeutics (formerly Rib-X Pharmaceuticals), which subsequently merged with Cempra.Key clinical trials for delafloxacin have been performed by Melinta regarding indications for skin and skin structure infections as well as complicated bacterial infections and uncomplicated gonorrhea. The trial on gonorrhea was terminated before data was released.Delafloxacin was approved by the FDA in June 2017, after it was noninferior to vancomycin plus aztreonam in two trials on 1042 patients with acute bacterial skin and skin structure infection. New Drug Applications (NDA) for delafloxacin (Baxdela) 450 mg tablets and 300 mg injections were approved by the FDA in June 2017.The FDA obligated Melinta to conduct further studies as follows:
a 5-year surveillance study to determine if resistance emerges, with the final report due in December 2022
a study of the IV form in pregnant rats to determine distribution to the reproductive tract, due June 2018, with further studies required if there is significant distribution.Melinta merged with Cempra in August, 2017.Melinta has entered into commercialization and distribution agreements with both Menarini Therapeutics (March 2017) and Eurofarma Laboratórios (January 2015) for international commercialization of delafloxacin. The agreement with Menarini allows them to commercialize and distribute in 68 countries, including Europe, China, and South Korea among others. A similar agreement with Eurofarma allows for commercialization in Brazil. References
External links
"Delafloxacin". Drug Information Portal. U.S. National Library of Medicine. "Delafloxacin meglumine". Drug Information Portal. U.S. National Library of Medicine. | Ciltacabtagene autoleucel, sold under the brand name Carvykti, is a medication used to treat multiple myeloma.The most common adverse reactions include pyrexia, cytokine release syndrome, hypogammaglobulinemia, musculoskeletal pain, fatigue, infections, diarrhea, nausea, encephalopathy, headache, coagulopathy, constipation, and vomiting. Additional common side effects include neutropenia (low levels of neutrophils), lymphopenia and leucopenia (low levels of lymphocytes or other white blood cells), anemia (low levels of red blood cells), thrombocytopenia (low levels of blood platelets), hypotension (low blood pressure), pain of the muscles and bones, high level of liver enzymes, upper respiratory tract infection (nose and throat infection), diarrhea, hypokalemia (low level of potassium), hypocalcemia (low levels of calcium), hypophosphatemia (low levels of phosphate in the blood), nausea, headache, cough, tachycardia (rapid heartbeat), encephalopathy (a brain disorder), edema (fluid retention), decreased appetite, chills, fever, tiredness, as well as cytokine release syndrome (a potentially life-threatening condition that can cause fever, vomiting, shortness of breath, pain and low blood pressure).Ciltacabtagene autoleucel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose is customized using the recipients own T-cells, which are collected and genetically modified, and infused back into the recipient.Ciltacabtagene autoleucel was approved for medical use in the United States in February 2022, and in the European Union in May 2022. | 0-1
|
Atovaquone/proguanil, sold under the brand name Malarone among others, is a fixed-dose combination medication used to treat and prevent malaria, including chloroquine-resistant malaria. It contains atovaquone and proguanil. It is not recommended for severe or complicated malaria. It is taken by mouth.Common side effects include abdominal pain, vomiting, diarrhea, cough, and itchiness. Serious side effects may include anaphylaxis, Stevens–Johnson syndrome, hallucinations, and liver problems. It is unclear if use during pregnancy or breastfeeding is safe for the baby. It is not recommended to prevent malaria in those with poor kidney function. Atovaquone works by interfering with the function of mitochondria in malaria while proguanil by blocking dihydrofolate reductase.Atovaquone/proguanil was approved for medical use in the United States in 2000. It has been available as a generic medication since 2011. Medical uses
Malaria treatment
Atovaquone/proguanil is not normally used to treat severe malaria, when an injectable drug such as quinine is used instead. Malaria prevention
Since some malaria strains are resistant to atovaquone/proguanil, it is not effective in all parts of the world. It must be taken with a fatty meal, or at least some milk, for the body to absorb it adequately—and to avoid painful stomach irritation, which proguanil frequently causes if taken without food. Also, stomach irritation may occur if one lies down within a half hour after taking this medicine. Resistance
Proguanil acts as a mitochondrial sensitiser and synergizes with atovaquone. When atovaquone is used as a sole agent, a high natural frequency of cytochrome b mutants leads to a high failure rate. | Because of the statistical probabilities that each sex inherits the syndrome, males are affected by Mohr-Tranebjærg more frequently than females are. Females who carry one copy of the TIMM8A gene (described in Genetics) are usually unaffected, however, may develop mild hearing loss and dystonia. Prognosis
Prognosis is poor. The combination of deafness and blindness severely affects communication, while the ongoing movement disorder results in an increasingly unstable gait. Life expectancy is highly variable and can range from death in the teenage years (after a rapidly progressive dystonia) to those that live into their 60s. History
This condition was first described in 1960. Epidemiology
Mohr-Tranebjᴂrg syndrome (MTS) prevalence is unknown. More than 90 cases (in 37 families) are known, but not all cases have been reported in the literature. See also
Mitochondrial disorders
TIMM13 and TIMM8A
References
External links
GeneReviews/NCBI/NIH/UW entry on Deafness–Dystonia–Optic Neuronopathy Syndrome
MTS — a page at NIH website | 0-1
|
Statins are not recommended in the treatment post-SCAD (in the absence of other indications for statins) as the myocardial infarctions in SCAD are not the result of atherosclerotic plaques. Cardiac rehabilitation is recommended for all patients after myocardial infarction due to SCAD and is associated with a reduction in anginal symptoms increased psychological well-being. Dual antiplatelet therapy should be started after percutaneous coronary intervention (stents) is used to treat SCAD and continued for at least 1 year afterwards. Dual antiplatelet therapy during the acute phase and for at least 1 year after medically treated SCAD may be also used, based on expert consensus.Physical stress is associated with SCAD recurrence but there are no heart rate, blood pressure or weight exercise parameters that are established in those with SCAD. In general, it is recommended that those with SCAD avoid isometric exercise, high intensity endurance training, exercising to the point of exhaustion and activities involving a prolonged Valsalva to reduce the risk of SCAD recurrence.After addressing the SCAD, people are often treated with typical post-heart attack care, though people who are pregnant may need altered therapy due to the possibility of some teratogenic cardiac medications affecting fetal development. Depending on the clinical situation, providers may screen for associated connective tissue diseases. Prognosis
People with SCAD have a low in-hospital mortality after treatment. However, the lesion may worsen after leaving the hospital within the first month. One study suggested a 1.2% mortality rate following SCAD but a 19.9% risk for either death, heart attacks, or strokes. | Type 3 SCAD, the least common type, is also due to an intramural hematoma causing coronary stenosis, but the lesions are shorter than as seen in type 2 SCAD, being less than 20 mm in length. Due to the short segment of coronary stenosis in type 3 SCAD, it is often difficult to differentiate type 3 SCAD lesions from coronary stenosis due to atherosclerotic plaques and intra-coronary imaging is often needed to distinguish between the two. Some authors have proposed a fourth designation of SCAD, type 4 SCAD, in which there is a complete intraluminal occlusion of the coronary artery due to any of the previously mentioned types (Type 1–3). Intracoronary imaging
Intracoronary imaging (ICI), consisting of intracoronary optical coherence tomography (OCT) and intravascular ultrasound (IVUS) can help distinguish SCAD from an atherosclerotic lesion when it is difficult to do so with angiography. ICI techniques provide a direct view of the walls of the coronary artery to confirm SCAD, but may actually worsen the dissection as the probes are inserted into the damaged area. ICI confers a 3.4% risk of iatrogenic dissection in people with SCAD compared to 0.2% risk in the general population. Between the two ICI methods, OCT - a newer technique - has superior spatial resolution than IVUS and is the preferred technique if ICI is required, but the need to inject extra contrast with OCT poses risk for worsening the dissection. Other methods
Some studies propose coronary CT angiography to evaluate SCAD in lower-risk people, with research into the approach ongoing. | 11
|
Pharmacology
Pharmacodynamics
Gabapentin is a ligand of the α2δ calcium channel subunit. α2δ is an auxiliary protein connected to the main α1 subunit (the channel-forming protein) of high voltage activated voltage-dependent calcium channels (L-type, N-type, P/Q type, and R-type). Gabapentin is not a direct channel blocker: it exerts its actions by disrupting the regulatory function of α2δ and its interactions with other proteins. Gabapentin prevents delivery of the calcium channels to the cell membrane, reduces the activation of the channels by the α2δ subunit, decreases signaling leading to neurotransmitters release, and disrupts interactions of α2δ with NMDA receptors, neurexins, and thrombospondins. Out of the four known isoforms of α2δ protein, gabapentin binds with similar high affinity to two: α2δ-1 and α2δ-2. Most of the pharmacological properties of gabapentin are explained by its binding to just one isoform – α2δ-1.The endogenous α-amino acids L-leucine and L-isoleucine, which resemble gabapentin in chemical structure, bind α2δ with similar affinity to gabapentin and are present in human cerebrospinal fluid at micromolar concentrations. They may be the endogenous ligands of the α2δ subunit, and they competitively antagonize the effects of gabapentin. Accordingly, while gabapentin has nanomolar affinity for the α2δ subunit, its potency in vivo is in the low micromolar range, and competition for binding by endogenous L-amino acids is likely to be responsible for this discrepancy.Gabapentin is a potent activator of voltage-gated potassium channels KCNQ3 and KCNQ5, even at low nanomolar concentrations. | Hepatic porphyrias is a form of porphyria in which toxic porphyrin molecules build up in the liver. Hepatic porphyrias can result from a number of different enzyme deficiencies.Examples include (in order of synthesis pathway):
Acute intermittent porphyria
Porphyria cutanea tarda and Hepatoerythropoietic porphyria
Hereditary coproporphyria
Variegate porphyria
See also
Erythropoietic porphyria
Givosiran
References
External links
Porphyrias,+Hepatic at the US National Library of Medicine Medical Subject Headings (MeSH)
www.drugs-porphyria.com
www.porphyria-europe.com | 0-1
|
Up to one third of women with Marfan syndrome have a history of vaginal wall collapse. Ehlers-Danlos syndrome in women is associated with a rate of 3 out of 4. Risk factors
Risk factors for developing a cystocele are:
Connective tissue disorders predispose women to developing cystocele and other pelvic organ prolapse. The tissues tensile strength of the vaginal wall decreases when the structure of the collagen fibers change and become weaker. Diagnosis
There are two types of cystocele. The first is distension. This is thought to be due to the overstretching of the vaginal wall and is most often associated with aging, menopause and vaginal delivery. It can be observed when the rugae are less visible or even absent. The second type is displacement. Displacement is the detachment or abnormal elongation of supportive tissue.The initial assessment of cystocele can include a pelvic exam to evaluate leakage of urine when the women is asked to bear down or give a strong cough (Valsalva maneuver), and the anterior vaginal wall measured and evaluated for the appearance of a cystocele. If a woman has difficulty emptying her bladder, the clinician may measure the amount of urine left in the womans bladder after she urinates called the postvoid residual. This is measured by ultrasound. A voiding cystourethrogram is a test that involves taking x-rays of the bladder during urination. This x-ray shows the shape of the bladder and lets the doctor see any problems that might block the normal flow of urine. | Women who have surgery to repair a cystocele have a 17% of needing another operation within the next ten years.The surgical treatment of cystocele will depend on the cause of the defect and whether it occurs at the top (apex), middle, or lower part of the anterior vaginal wall. The type of surgery will also depend on the type of damage that exists between supporting structures and the vaginal wall. One of the most common surgical repairs is colporrhaphy. This surgical procedure consists of making a longitudinal folding of the vaginal tissue, suturing it into place and creating a stronger point of resistance to the intruding bladder wall. Surgical mesh is sometimes used to strengthen the anterior vaginal wall. It has a 10–50% failure rate. In some cases a surgeon may choose to use surgical mesh to strengthen the repair.During surgery, the repair of the vaginal wall consists of folding over and then suturing the existing tissue between the vagina and bladder to strengthen it. This tightens the layers of tissue to promote the replacement of the pelvic organs into their normal place. The surgery also provides more support for the bladder. This surgery is done by a surgeon specializing in gynecology and is performed in a hospital. Anesthesia varies according to the needs of each woman. Recovery may take four to six weeks. Other surgical treatment may be performed to treat cystocele. Support for the vaginal wall is accomplished with the paravaginal defect repair. | 11
|
Anastrozole, sold under the brand name Arimidex among others, is a medication used in addition to other treatments for breast cancer. Specifically it is used for hormone receptor-positive breast cancer. It has also been used to prevent breast cancer in those at high risk. It is taken by mouth.Common side effects of anastrozole include hot flashes, altered mood, joint pain, and nausea. Severe side effects include an increased risk of heart disease and osteoporosis. Use during pregnancy may harm the baby. Anastrozole is in the aromatase-inhibiting family of medications. It works by blocking the production of estrogens in the body, and hence has antiestrogenic effects.Anastrozole was patented in 1987 and was approved for medical use in 1995. It is on the World Health Organizations List of Essential Medicines. Anastrozole is available as a generic medication. In 2019, it was the 176th most commonly prescribed medication in the United States, with more than 3 million prescriptions. Medical uses
Breast cancer
Anastrozole is used in the treatment and prevention of breast cancer in women. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial was of localized breast cancer and women received either anastrozole, the selective estrogen receptor modulator tamoxifen, or both for five years, followed by five years of follow-up. After more than 5 years the group that received anastrozole had better results than the tamoxifen group. The trial suggested that anastrozole is the preferred medical therapy for postmenopausal women with localized estrogen receptor-positive breast cancer. | Elvitegravir (EVG) is an integrase inhibitor used to treat HIV infection. It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008. The drug gained approval by the U.S. Food and Drug Administration on August 27, 2012 for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild. On September 24, 2014 the FDA approved Elvitegravir as a single pill formulation under the trade name Vitekta. On November 5, 2015 the FDA approved the drug for use in patients affected with HIV-1 as a part of a second fixed dose combination pill known as Genvoya.According to the results of the phase II clinical trial, patients taking once-daily elvitegravir boosted by ritonavir had greater reductions in viral load after 24 weeks compared to individuals randomized to receive a ritonavir-boosted protease inhibitor. Medical uses
In the United States, elvitegravir can be obtained either as part of the combination pills Stribild or Genvoya, or as the single pill formulation Vitekta.Vitekta is FDA approved to be used for the treatment of HIV-1 infection in adults who have previous treatment experience with antiretroviral therapy. It must be used in combination with a protease inhibitor that is coadministered with ritonavir as well as additional antiretroviral drug(s). Adverse effects
The most common side effects of taking elvitegravir are diarrhea (in 7% of patients) and nausea (4%). Other side effects that occurred in more than 1% of people are headache, tiredness, rashes, and vomiting. | 0-1
|
Interactions
As a MAO inhibitor, safinamide can theoretically cause hypertensive crises, serotonin syndrome and other severe side effects when combined with other MAO inhibitors or with drugs that are known to interact with MAO inhibitors, such as pethidine, dextromethorphan, selective serotonin reuptake inhibitors (SSRIs), serotonin–noradrenaline reuptake inhibitors (SNRIs), tricyclic and tetracyclic antidepressants. An interaction with tyramine, a substance found in various foods, could be expected by the same reasoning but has been excluded in studies.Safinamide should not be given with opioids; some fatal reactions have occurred.Another theoretical interaction is with drugs with affinity to the transporter protein ABCG2 (also known as BCRP), such as pitavastatin, pravastatin, ciprofloxacin, methotrexate, and diclofenac; a study with the latter has shown no clinical relevance. A study testing possible interactions with amidase inhibitors is part of the post-authorisation development plan. There are no relevant interactions related to cytochrome P450 (CYP) liver enzymes, although one inactivation pathway of safinamide seems to be mediated by CYP3A4. Pharmacology
Mechanisms of action
Like the older antiparkinson drugs selegiline and rasagiline, safinamide is a selective monoamine oxidase B inhibitor, reducing degradation of dopamine; in contrast to the other two, its action is reversible. Safinamide also inhibits glutamate release and dopamine and serotonin reuptake. It binds to the sigma receptors as well, with IC50 values for binding inhibition of 19 nM for σ1 and 1,590 nM for σ2. Additionally, it blocks sodium and calcium channels, the relevance of which for its antiparkinson action is however unknown. | Permanent neonatal diabetes mellitus (PNDM) is a newly identified and potentially treatable form of monogenic diabetes. This type of neonatal diabetes is caused by activating mutations of the KCNJ11 gene, which codes for the Kir6.2 subunit of the beta cell KATP channel. This disease is considered to be a type of maturity onset diabetes of the young (MODY). Cause
It can be associated with GCK, KCNJ11, INS, and ABCC8. Diagnosis
This results in congenital impairment of insulin release, although in the past, this was always being thought to be unusually early type 1 diabetes mellitus. The insulin deficiency results in intrauterine growth retardation with birth weight small for gestational age. The diabetes is usually diagnosed in the first 3 months of life due to continuing poor weight gain, polyuria, or diabetic ketoacidosis. Rare cases have been recognized as late as 6 months of age. Treatment
Remarkably, this type of diabetes often responds well to sulfonylureas and insulin may not be necessary. More severe mutations in the KCNJ11 gene can cause early-onset diabetes which does not respond to the sulfonylurea drugs, as well as a syndrome of developmental delay and neurological features called the DEND syndrome. These forms of diabetes are very rare conditions, appearing in about 1/100,000 to 1/200,000 live births, and accounting for about 1/1000 of type 1 diabetes cases. | 0-1
|
However, improved survival was observed when IFN-γ was administrated to patients with bladder carcinoma and melanoma cancers. The most promising result was achieved in patients with stage 2 and 3 of ovarian carcinoma. On the contrary, it was stressed: "Interferon-γ secreted by CD8-positive lymphocytes upregulates PD-L1 on ovarian cancer cells and promotes tumour growth." The in vitro study of IFN-γ in cancer cells is more extensive and results indicate anti-proliferative activity of IFN-γ leading to the growth inhibition or cell death, generally induced by apoptosis but sometimes by autophagy. In addition, it has been reported that mammalian glycosylation of recombinant human IFN-γ, expressed in HEK293, improves its therapeutic efficacy compared to the unglycosylated form that is expressed in E. coli. Interactions
Interferon-γ has been shown to interact with Interferon gamma receptor 1 and Interferon gamma receptor 2. Diseases
Interferon-γ has been shown to be a crucial player in the immune response against some intracellular pathogens, including that of Chagas disease. It has also been identified as having a role in seborrheic dermatitis.IFN-γ has a significant anti-viral effect in herpes simplex virus I (HSV) infection. IFN-γ compromises the microtubules that HSV relies upon for transport into an infected cells nucleus, inhibiting the ability of HSV to replicate. Studies in mice on acyclovir resistant herpes have shown that IFN-γ treatment can significantly reduce herpes viral load. The mechanism by which IFN-γ inhibits herpes reproduction is independent of T-cells, which means that IFN-γ may be an effective treatment in individuals with low T-cells.Chlamydia infection is impacted by IFN-γ in host cells. | Supernumerary roots is a condition found in teeth when there may be a larger number of roots than expected. The most common teeth affected are mandibular (lower) canines, premolars, and molars, especially third molars. Canines and most premolars, except for maxillary (upper) first premolars, usually have one root. Maxillary first premolars and mandibular molars usually have two roots. Maxillary molars usually have three roots. When an extra root is found on any of these teeth, the root is described as a supernumerary root. The clinical significance of this condition is associated with dentistry when accurate information regarding root canal anatomy is required when root canal treatment is required. References
== External links == | 0-1
|
In some cases, the presence or absence of sperm granulomas may determine the success rate for vasectomy reversal. It is believed that sperm granulomas may be protective because they can prevent the obstruction of the testicles and epididymis. Sperm granulomas are believed to reduce the pressure thats generated after vasectomy and prevent blockages of sperm output into the vas fluid during ejaculation. Therefore, there are no changes in the amount of sperm that are produced into the vas fluid. Sperm granulomas in animals
Additionally, sperm granulomas can exist in non-human species such as rats, dogs, horses, fish, etc. Non-human species exhibit the same causes for sperm granulomas, including infection, injury, and trauma to the epididymal region. For example, vasectomized rats were seen to also have high prevalence of sperm granulomas post-operation while general populations of rats experienced much lower prevalence of sperm granulomas. In the case of sperm granulomas within dogs, their presence is common amongst poorly performed vasectomies. This is consistent with the idea that these lesions form at the site where there is trauma or a chance for the sperm to leak outside of the vasa deferentia or epididymis. In multiple species, sperm granulomas have also been linked to the success rate of certain procedures such as vasectomy reversals, or vasovasostomy. There is also an association between sperm granuloma and antibodies produced against sperm antigens. | Additionally, in order to check sterility post-vasectomy, a semen analysis is performed after 3 months and 20 ejaculations to establish azoospermia (no sperm count in the ejaculate).Vasectomy can also be reversed, which is a more technically challenging procedure than a vasectomy that is performed by less urologists and is a heavier financial burden as it is usually not covered by insurances. Approximately 3-6% of people opt for a reversal due to the death of a child, change in partner, increase in financial abilities, or to find relief from postvasectomy pain syndrome. With advances in medical operations since the 1970s, there has since been increased interest in vasectomy reversals and greater chances of success for patency and pregnancy rates.Vasectomy reversal has a varying success rate. A recent study showed that the most important indicator of pregnancy after vasectomy reversal was the age of the female partner. The two most favorable predictors of success were having a female partner less than 40 years of age and having the reversal performed less than 15 years after vasectomy. Aside from the variation in success, vasectomy reversal also has major economic implications. The cost of a vasectomy reversal can range from $16,000-$30,000 and it is usually an out-of-pocket expense due to lack of insurance coverage. == References == | 11
|
Changes in the skull also occur causing a distinctive "square headed" appearance known as "caput quadratum". These deformities persist into adult life if not treated. Long-term consequences include permanent curvatures or disfiguration of the long bones, and a curved back. Cause
Maternal deficiencies may be the cause of overt bone disease from before birth and impairment of bone quality after birth. The primary cause of congenital rickets is vitamin D deficiency in the mothers blood, which the baby shares. Vitamin D ensures that serum phosphate and calcium levels are sufficient to facilitate the mineralization of bone. Congenital rickets may also be caused by other maternal diseases, including severe osteomalacia, untreated celiac disease, malabsorption, pre-eclampsia, and premature birth. Rickets in children is similar to osteoporosis in the elderly, with brittle bones. Pre-natal care includes checking vitamin levels and ensuring that any deficiencies are supplemented.Exclusively breast-fed infants may require rickets prevention by vitamin D supplementation or an increased exposure to sunlight.In sunny countries such as Nigeria, South Africa, and Bangladesh, there is sufficient endogenous vitamin D due to exposure to the sun. | Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brains cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side effects (EPSE). The symptoms can be acute (short-term) or chronic (long-term). They include movement dysfunction such as dystonia (continuous spasms and muscle contractions), akathisia (may manifest as motor restlessness), parkinsonism characteristic symptoms such as rigidity, bradykinesia (slowness of movement), tremor, and tardive dyskinesia (irregular, jerky movements). Extrapyramidal symptoms are a reason why subjects drop out of clinical trials of antipsychotics; of the 213 (14.6%) subjects that dropped out of one of the largest clinical trials of antipsychotics (the CATIE trial (Clinical Antipsychotic Trials for Intervention Effectiveness), which included 1460 randomized subjects), 58 (27.2%) of those discontinuations were due to EPS. Causes
Medications
Extrapyramidal symptoms are most commonly caused by typical antipsychotic drugs that antagonize dopamine D2 receptors. The most common typical antipsychotics associated with EPS are haloperidol and fluphenazine. Atypical antipsychotics have lower D2 receptor affinity or higher serotonin 5-HT2A receptor affinity which lead to lower rates of EPS.Other anti-dopaminergic drugs, like the antiemetic metoclopramide, can also result in extrapyramidal side effects. Short and long-term use of antidepressants such as selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), and norepinephrine-dopamine reuptake inhibitors (NDRI) have also resulted in EPS. Specifically, duloxetine, sertraline, escitalopram, fluoxetine, and bupropion have been linked to the induction of EPS. Non-medication-related
Other causes of extrapyramidal symptoms can include brain damage and meningitis. | 0-1
|
Pathophysiology
Precancer
Exocrine cancers are thought to arise from several types of precancerous lesions within the pancreas, but these lesions do not always progress to cancer, and the increased numbers detected as a byproduct of the increasing use of CT scans for other reasons are not all treated. Apart from pancreatic serous cystadenomas, which are almost always benign, four types of precancerous lesion are recognized. The first is pancreatic intraepithelial neoplasia (PanIN). These lesions are microscopic abnormalities in the pancreas and are often found in autopsies of people with no diagnosed cancer. These lesions may progress from low to high grade and then to a tumor. More than 90% of cases at all grades carry a faulty KRAS gene, while in grades 2 and 3, damage to three further genes – CDKN2A (p16), p53, and SMAD4 – are increasingly often found.A second type is the intraductal papillary mucinous neoplasm (IPMN). These are macroscopic lesions, which are found in about 2% of all adults. This rate rises to about 10% by age 70. These lesions have about a 25% risk of developing into invasive cancer. They may have KRAS gene mutations (40–65% of cases) and in the GNAS Gs alpha subunit and RNF43, affecting the Wnt signaling pathway. Even if removed surgically, a considerably increased risk remains of pancreatic cancer developing subsequently.The third type, pancreatic mucinous cystic neoplasm (MCN), mainly occurs in women, and may remain benign or progress to cancer. | Thus the psychopathologized individual for Freud was an immature individual, and the goal of psychoanalysis was to bring these fixations to conscious awareness so that the libido energy would be freed up and available for conscious use in some sort of constructive sublimation. Analytical psychology
According to Swiss psychiatrist Carl Gustav Jung, the libido is identified as the totality of psychic energy, not limited to sexual desire. As Jung states in "The Concept of Libido," "[libido] denotes a desire or impulse which is unchecked by any kind of authority, moral or otherwise. Libido is appetite in its natural state. From the genetic point of view it is bodily needs like hunger, thirst, sleep, and sex, and emotional states or affects, which constitute the essence of libido." The Duality (opposition) creates the energy (or libido) of the psyche, which Jung asserts expresses itself only through symbols: "It is the energy that manifests itself in the life process and is perceived subjectively as striving and desire." (Ellenberger, 697) These symbols may manifest as "fantasy-images" in the process of psychoanalysis which embody the contents of the libido, otherwise lacking in any definite form. Desire, conceived generally as a psychic longing, movement, displacement and structuring, manifests itself in definable forms which are apprehended through analysis. Defined more narrowly, libido also refers to an individuals urge to engage in sexual activity, and its antonym is the force of destruction termed mortido or destrudo. | 0-1
|
These angular crystals, which bond poorly to one another and the surrounding snow, often become a persistent weakness in the snowpack. When a slab lying on top of a persistent weakness is loaded by a force greater than the strength of the slab and persistent weak layer, the persistent weak layer can fail and generate an avalanche. Any wind stronger than a light breeze can contribute to a rapid accumulation of snow on sheltered slopes downwind. Wind slabs form quickly and, if present, weaker snow below the slab may not have time to adjust to the new load. Even on a clear day, wind can quickly load a slope with snow by blowing snow from one place to another. Top-loading occurs when wind deposits snow from the top of a slope; cross-loading occurs when wind deposits snow parallel to the slope. When a wind blows over the top of a mountain, the leeward, or downwind, side of the mountain experiences top-loading, from the top to the bottom of that lee slope. When the wind blows across a ridge that leads up the mountain, the leeward side of the ridge is subject to cross-loading. Cross-loaded wind-slabs are usually difficult to identify visually. Snowstorms and rainstorms are important contributors to avalanche danger. Heavy snowfall will cause instability in the existing snowpack, both because of the additional weight and because the new snow has insufficient time to bond to underlying snow layers. Rain has a similar effect. | He was carried nearly 2,000 feet to the base of the mountain and was not successfully rescued. Classification
European avalanche risk
In Europe, the avalanche risk is widely rated on the following scale, which was adopted in April 1993 to replace the earlier non-standard national schemes. Descriptions were last updated in May 2003 to enhance uniformity.In France, most avalanche deaths occur at risk levels 3 and 4. In Switzerland most occur at levels 2 and 3. It is thought that this may be due to national differences of interpretation when assessing the risks. [1] Stability:
Generally described in more detail in the avalanche bulletin (regarding the altitude, aspect, type of terrain etc. )[2] additional load:
heavy: two or more skiers or boarders without spacing between them, a single hiker or climber, a grooming machine, avalanche blasting
light: a single skier or snowboarder smoothly linking turns and without falling, a group of skiers or snowboarders with a minimum 10 m gap between each person, a single person on snowshoesGradient:
gentle slopes: with an incline below about 30°
steep slopes: with an incline over 30°
very steep slopes: with an incline over 35°
extremely steep slopes: extreme in terms of the incline (over 40°), the terrain profile, proximity of the ridge, smoothness of underlying ground
European avalanche size table
Avalanche size:
North American Avalanche Danger Scale
In the United States and Canada, the following avalanche danger scale is used. Descriptors vary depending on country. | 11
|
Some are in the form of pills and some are drops for children. Most forms of oral iron replacement therapy are absorbed well by the small intestine; however, there are certain preparations of iron supplements that are designed for longer release in the small intestine than other preparations. Oral iron supplements are best taken up by the body on an empty stomach because food can decrease the amount of iron absorbed from the small intestine. The dosing of oral iron replacement therapy is as much as 100–200 mg per day in adults and 3–6 mg per kilogram in children. This is generally spread out as 3-4 pills taken throughout the day. The various forms of treatment are not without possible adverse side effects. Iron supplementation by mouth commonly causes negative gastrointestinal effects, including constipation, nausea, vomiting, metallic taste to the oral iron and dark colored stools. Constipation is reported by 15-20% of patients taking oral iron therapy. Preparations of iron therapy that take longer to be absorbed by the small intestine (extended release iron therapy) are less likely to cause constipation. It can take six months to one year to get blood levels of iron up to a normal range and provide the body with iron stores. | Up to 15% of children ages 1–3 years have iron deficiency anemia. Mild iron deficiency anemia affects another 375 million. Iron deficiency affects up to 52% of pregnant women worldwide.The prevalence of iron deficiency as a cause of anemia varies among countries; in the groups in which anemia is most common, including young children and a subset of non-pregnant women, iron deficiency accounts for a fraction of anemia cases in these groups (25% and 37%, respectively). Iron deficiency is common in pregnant women.Within the United States, iron-deficiency anemia affects about 2% of adult males, 10.5% of White women, and 20% of African-American and Mexican-American women.A map provides a country-by-country listing of what nutrients are fortified into specified foods. Some of the Sub-Saharan countries shown in the deaths from iron-deficiency anemia map from 2012 are as of 2018 fortifying foods with iron. References
Zeglam A, Abugrara A, Kabuka M. Autosomal-recessive iron deficiency anemia, dystonia and hypermanganesemia caused by new variant mutation of the manganese transporter gene SLC39A14. Acta Neurol Belg. 2019 Sep;119(3):379-384. doi: 10.1007/s13760-018-1024-7. Epub 2018 Sep 19. PMID 30232769. External links
The Importance of Iron – From IronTherapy.Org
Interactive material on Iron Metabolism – From IronAtlas.com
Approach to chronic anemia : https://ashpublications.org/hematology/article/2012/1/183/83845/How-to-approach-chronic-anemia
Handout: Iron Deficiency Anemia – From the National Anemia Action Council
NPS News 70: Iron deficiency anaemia: NPS – Better choices, Better health – From the National Prescribing Service | 11
|
The process of using genetic markers to estimate CST rates should take into account several important factors to reduce bias. One is that the phylogenetic tree constructed in the analysis needs to capture the underlying epidemiological process generating the tree. The models need to account for how the genetic variability of a pathogen influences a disease in a species, not just general differences in genomic structure. Two, the strength of the analysis will depend on the amount of mutation accumulated since the pathogen was introduced in the system. This is due to many models using the number of mutations as an indicator of CST frequency. Therefore, efforts are focused on estimating either time since the introduction or the substitution rate of the marker (from laboratory experiments or genomic comparative analysis). This is important not only when using the MPR method but also for Likelihood approaches that require an estimation of the mutation rate. Three, CST will also affect disease prevalence in the potential host, so combining both epidemiological time series data with genetic data may be an excellent approach to CST study
Bayesian analysis
Bayesian frameworks are a form of maximum likelihood-based analyses and can be very effective in cross-species transmission studies. Bayesian inference of character evolution methods can account for phylogenetic tree uncertainty and more complex scenarios, with models such as the character diffusion model currently being developed for the study of CST in RNA viruses. A Bayesian statistical approach presents advantages over other analyses for tracking CST origins. | Computational techniques allow integration over an unknown phylogeny, which cannot be directly observed, and unknown migration process, which is usually poorly understood.The Bayesian frameworks are also well suited to bring together different kinds of information. The BEAST software, which has a strong focus on calibrated phylogenies and genealogies, illustrates this by offering a large number of complementary evolutionary models including substitution models, demographic and relaxed clock models that can be combined into a full probabilistic model. By adding spatial reconstruction, these models create the probability of biogeographical history reconstruction from genetic data. This could be useful for determining the origins of cross-species transmissions. The high effectiveness of Bayesian statistical methods has made them instrumental in evolutionary studies. Bayesian ancestral host reconstruction under discrete diffusion models can be used to infer the origin and effects of pathogens associated with CST. One study on Human adenoviruses using Bayesian supported a gorilla and chimpanzee origin for the viral species, aiding prevention efforts. Despite presumably rare direct contact between sympatric populations of the two species, CST events can occur between them. The study also determined that two independent HAdV-B transmission events to humans occurred and that the HAdV-Bs circulating in humans are of zoonotic origin and have probably affected global health for most of our species lifetime.Phylogenetic diffusion models are frequently used for phylogeographic analyses, with the inference of host jumping becoming of increasing interest. | 11
|
Fluid collects in the foot when standing and walking and this makes the condition worse. As small muscles lose their nerve supply they can create a cramping feeling. Symptoms
Some of the symptoms are:
Pain and tingling in and around ankles and sometimes the toes
Swelling of the feet and ankle area. Painful burning, tingling, or numb sensations in the lower legs. Pain worsens and spreads after standing for long periods; pain is worse with activity and is relieved by rest. Electric shock sensations
Pain radiating up into the leg, behind the shin, and down into the arch, heel, and toes
Hot and cold sensations in the feet
A feeling as though the feet do not have enough padding
Pain while operating automobiles
Pain along the posterior tibial nerve path
Burning sensation on the bottom of foot that radiates upward reaching the knee
"Pins and needles"-type feeling and increased sensation on the feet
A positive Tinels signTinels sign is a tingling electric shock sensation that occurs when you tap over an affected nerve. The sensation usually travels into the foot but can also travel up the inner leg as well. Causes
It is difficult to determine the exact cause of tarsal tunnel syndrome. It is important to attempt to determine the source of the problem. Treatment and the potential outcome of the treatment may depend on the cause. Anything that creates pressure in the tarsal tunnel can cause TTS. This would include benign tumors or cysts, bone spurs, inflammation of the tendon sheath, nerve ganglions, or swelling from a broken or sprained ankle. | Meaning that the program these patients were participated in consisted of physiotherapy exercises and orthopedic shoe inserts in addition to that program. There were fourteen patients that had supplementary tibial nerve mobilization exercises. They were instructed to sit on the edge of a table in a slumped position, have their ankle taken into dorsiflexion and ankle eversion then the knee was extended and flexed to obtain the optimal tibial nerve mobilization. Patients in both groups showed positive progress from both programs. The medial calcaneal, medial plantar and lateral plantar nerve areas all had a reduction in pain after successful nonoperative or conservative treatment. There is also the option of localized steroid or cortisone injection that may reduce the inflammation in the area, therefore relieving pain. Or just a simple reduction in the patients weight to reduce the pressure in the area. Surgical treatment
If non-invasive treatment measures fail, tarsal tunnel release surgery may be recommended to decompress the area. The incision is made behind the ankle bone and then down towards but not as far as the bottom of foot. The posterior tibial nerve is identified above the ankle. It is separated from the accompanying artery and vein and then followed into the tunnel. The nerves are released. Cysts or other space-occupying problems may be corrected at this time. If there is scarring within the nerve or branches, this is relieved by internal neurolysis. Neurolysis is when the outer layer of nerve wrapping is opened and the scar tissue is removed from within nerve. | 11
|
Alongside most cells there is either a basement membrane or a collagenous network made by fibroblasts that will guide the cells growth. Since ischaemia and most toxins do not destroy collagen, it will continue to exist even when the cells around it are dead. Example
Acute tubular necrosis (ATN) in the kidney is a case in which cells heal completely by regeneration. ATN occurs when the epithelial cells that line the kidney are destroyed by either a lack of oxygen (such as in hypovolemic shock, when blood supply to the kidneys is dramatically reduced), or by toxins (such as some antibiotics, heavy metals or carbon tetrachloride).Although many of these epithelial cells are dead, there is typically patchy necrosis, meaning that there are patches of epithelial cells still alive. In addition, the collagen framework of the tubules remains completely intact.The existing epithelial cells can replicate, and, using the basement membrane as a guide, eventually bring the kidney back to normal. After regeneration is complete, the damage is undetectable, even microscopically.Healing must happen by repair in the case of injury to cells that are unable to regenerate (e.g. neurons). Also, damage to the collagen network (e.g. by enzymes or physical destruction), or its total collapse (as can happen in an infarct) cause healing to take place by repair. Genetics
Many genes play a role in healing. For instance, in wound healing, P21 has been found to allow mammals to heal spontaneously. It even allows some mammals (like mice) to heal wounds without scars. | Spastic quadriplegia can be caused by a condition known as periventricular leukomalacia which results in the formation of lesions and holes in the white matter of the brain.Prior to the 26th week of maturation, the fetal brain is particularly susceptible to various toxins whose effects can ultimately hinder normal development. Exposure of the brain to infectious agents is especially dangerous because they can trigger immune responses that activate cytokines and lead to inflammation of the brain. Some infections that have been linked to the development of spastic quadriplegia include meningitis, herpes, rubella, and encephalitis. A difference in blood types between the mother and the fetus can also initiate a problematic immune response and cause brain damage. Severe jaundice, can also lead to brain damage and spastic quadriplegia due to a buildup of bilirubin in the blood.Bleeding in the brain caused by fetal strokes, blood clots, weak and malformed blood vessels, or high maternal blood pressure may also lead to brain damage causing spastic quadriplegia. Maternal infection, most specifically pelvic inflammatory disease, has been shown to increase the risk of fetal stroke.Hypoxia, lack of oxygen to the brain, can also cause damage in the cerebral motor cortex and other brain regions. This lack of oxygen can be the result of placenta malfunction, womb rupture, umbilical cord damage, low maternal blood pressure or asphyxia during labor and delivery.Children who experienced many complications during birth, such as, prematurity, insufficient oxygen, low birthweight, aspiration, head injury, or bleeding in the brain have a greater risk of developing spastic quadriplegia. | 0-1
|
In the HPG axis, gonadotropin-releasing hormone (GnRH) is secreted from the arcuate nucleus of the hypothalamus and stimulates the anterior pituitary to secrete the two gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH). In adult males, LH stimulates the Leydig cells in the testes to produce testosterone which is required to form new sperm through spermatogenesis. AAS consumption leads to dose-dependent suppression of gonadotropin release through suppression of GnRH from the hypothalamus (long-loop mechanism) or from direct negative feedback on the anterior pituitary to inhibit gonadotropin release (short-loop mechanism), leading to AAS-induced hypogonadism. Pharmacology
Mechanism of action
The pharmacodynamics of AAS are unlike peptide hormones. Water-soluble peptide hormones cannot penetrate the fatty cell membrane and only indirectly affect the nucleus of target cells through their interaction with the cells surface receptors. However, as fat-soluble hormones, AAS are membrane-permeable and influence the nucleus of cells by direct action. The pharmacodynamic action of AAS begin when the exogenous hormone penetrates the membrane of the target cell and binds to an androgen receptor (AR) located in the cytoplasm of that cell. From there, the compound hormone-receptor diffuses into the nucleus, where it either alters the expression of genes or activates processes that send signals to other parts of the cell. | The popularity of SSRIs also increased the case reports of patients with 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.Fume events on aircraft have been linked to cases of toxic encephalopathy, for example in the case of JetBlue Captain Andrew Myers, who as a result of exposure needed a cane to walk, experienced tremors and struggled to speak. In the following year, the Federal Aviation Administration revoked Myers medical certificate; the workers compensation board agreed that Myers experienced brain damage as a result of the event. Diagnosis
Rapid diagnosis is important to attempt to prevent further damage to the brain and further neurologic deficits. It is a diagnosis of exclusion, so a full work up for other possible etiologies (hepatic, uremic, infectious, oncologic) should be performed. In addition to the neurological examination, diagnostic testing could include MRI, PET or SPECT brain imaging, EEG, QEEG and most importantly, neuropsychological testing. Screening for heavy metals, as well as other toxins, should be done immediately as those are some of the most common causes and the patient can then remove themselves from the dangerous environment. In addition, a full examination of blood (CBC) and metabolites (CMP) should be done. | 0-1
|
Dasiglucagon, sold under the brand name Zegalogue, is a medication used to treat severe hypoglycemia in people with diabetes.The most common side effects include nausea, vomiting, headache, diarrhea, and injection site pain.Dasiglucagon was approved for medical use in the United States in March 2021. It was designated an orphan drug in August 2017. Medical uses
Dasiglucagon is indicated for the treatment of severe hypoglycemia in people aged six years of age and older with diabetes. Contraindications
Dasiglucagon is contraindicated in people with pheochromocytoma or insulinoma. References
External links
"Dasiglucagon". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT03378635 for "A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects" at ClinicalTrials.gov
Clinical trial number NCT03688711 for "Trial to Confirm the Clinical Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Subjects With T1DM" at ClinicalTrials.gov
Clinical trial number NCT03667053 for "Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in T1DM Children" at ClinicalTrials.gov | If this is not effective topical steroids or injected methylene blue may be tried. Another treatment option that has been met with success in small-scale trials is the application of a very mild (.006) topical capsaicin cream. This strength cream is not typically commercially available and therefore must be diluted by a pharmacist or end-user. If the itchiness is secondary to another condition such as infection or psoriasis these are typically treated.A successful treatment option for chronic idiopathic pruritus ani has been documented using a clean, dry and apply (if necessary) method. The person is instructed to follow this procedure every time the urge to scratch occurs. The treatment makes the assumption that there is an unidentified bacteria in the feces that causes irritation and itching when the feces makes contact with the anal and perianal skin during defecation, flatulation or anal leakage (particularly during sleep). Cleaning the area with warm water, avoiding all soaps and even baby wipes, then drying the area, ideally with a hair dryer to avoid irritation or failing that simply patting gently with a clean, dry, towel. If persons with pruritus ani do not need to scratch after these steps they are instructed to do nothing else. If the urge to scratch is still present they are instructed to apply a topical steroid cream which has antibiotic and antifungal properties. This will address a skin condition which may have become infected. Apply such a cream as directed by your medical professional but usually twice a day for one to two weeks. | 0-1
|
The word "delirium" is Latin for "going off the furrow," a plowing metaphor. It is also called the shaking frenzy and Saunders-Sutton syndrome. There are numerous nicknames for the condition, including "the DTs" and "seeing pink elephants" (see below). Signs and symptoms
The main symptoms of delirium tremens are nightmares, agitation, global confusion, disorientation, visual and auditory hallucinations, tactile hallucinations, fever, high blood pressure, heavy sweating, and other signs of autonomic hyperactivity (fast heart rate and high blood pressure). These symptoms may appear suddenly but typically develop two to three days after the stopping of heavy drinking, being worst on the fourth or fifth day.These symptoms are characteristically worse at night. In general, DT is considered the most severe manifestation of alcohol withdrawal and occurs 3–10 days following the last drink.Other common symptoms include intense perceptual disturbance such as visions of insects, snakes, or rats. These may be hallucinations or illusions related to the environment, e.g., patterns on the wallpaper or in the peripheral vision that the patient falsely perceives as a resemblance to the morphology of an insect, and are also associated with tactile hallucinations such as sensations of something crawling on the subject—a phenomenon known as formication. Delirium tremens usually includes extremely intense feelings of "impending doom". Severe anxiety and feelings of imminent death are common DT symptoms.DT can sometimes be associated with severe, uncontrollable tremors of the extremities and secondary symptoms such as anxiety, panic attacks, and paranoia. | It was particularly bad during the filming of the bridge of death scene where Chapman was visibly shaking, sweating and could not cross the bridge. His fellow Pythons were astonished as Chapman was an accomplished mountaineer. The Belgian beer "Delirium Tremens," introduced in 1988, is a direct reference and also uses a pink elephant as its logo to highlight one of the symptoms of delirium tremens.In the 1995 film Leaving Las Vegas, Nicolas Cage plays a suicidal alcoholic who rids himself of all his possessions and travels to Las Vegas to drink himself to death. During his travels, he experiences delirium tremens on a couch after waking up from a binge and crawls in pain to the refrigerator for more vodka. Cages performance as Ben Sanderson in the film won the Academy Award for Best Actor in 1996. Russian composer Modest Mussorgsky (1839-1881) died of delirium tremens. See also
Alcohol dementia
Alcohol detoxification
Delusional parasitosis
Excited delirium
On the wagon
References
External links
Why Does Alcohol Cause the Shakes? | Alcohol Withdrawal Syndrome Tremors | Dr Peter MCcann MCC, MBBS | Castle Craig Hospital | 11
|
Drugs most commonly implicated are penicillin, sulphonamides and thiazide diuretics. Methamphetamine and other sympathomimetics can cause a cerebral vasculitis alongside polyarteritis nodosa like systemic features. With other drugs,there is presence of skin vasculitis with palpable petechiae or purpura. Biopsy of these lesions reveal inflammation of the small vessels, termed leukocytoclastic vasculitis, which is most prominent in postcapillary venules. At least three out of five criteria yields sensitivity and specificity of 71 and 84%:
Age > 16
Use of possible triggering drug in relation to symptoms
Palpable purpura
Maculopapular rash
Skin biopsy showing neutrophils around vesselIgA vasculitis (formerly known as Henoch–Schonlein purpura). Systemic vasculitis due to tissue deposition of IgA-containing immune complexes. Biopsy of lesions shows inflammation of small vessels. It is considered a form of hypersensitivity vasculitis but is distinguished by prominent deposits of IgA. This is the most common vasculitis in children. Presence of three or more criteria yielded sensitivity of 87% while less than two criteria yielded hypersensitivity vasculitis in 74%:
Palpable purpura (usually of buttocks and legs)
Bowel angina
GI bleed
Hematuria
Onset < 20 years
No new medicationsEssential cryoglobulinemic vasculitis. Most often due to hepatitis C infection, immune complexes of cryoglobulins – proteins that consists of immunoglobulins and complement and precipitate in the cold while dissolving upon rewarming – are deposited in walls of capillaries, venules, or arterioles. Therefore, complement will be low with histology showing vessel inflammation with immune deposits. Other/ungrouped
Vasculitis secondary to connective tissue disorders. Usually secondary to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), relapsing polychondritis, Behçets disease, and other connective tissue disorders. Vasculitis secondary to viral infection. | Eletriptan, sold under the brand name Relpax and used in the form of eletriptan hydrobromide, is a second generation triptan medication intended for treatment of migraine headaches. It is used as an abortive medication, blocking a migraine attack which is already in progress. Eletriptan is marketed and manufactured by Pfizer Inc.
Approval and availability
Eletriptan was approved by the US Food and Drug Administration (FDA) on December 26, 2002, for the acute treatment of migraine with or without aura in adults. It is available only by prescription in the United States and Canada. It is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. It is available in 20 mg and 40 mg strengths. Eletriptan was covered by U.S. Patent no. 5545644 and U.S. Patent no. 6110940; both now expired. Mechanism of action
Eletriptan is believed to reduce swelling of the blood vessels surrounding the brain. This swelling is associated with the head pain of a migraine attack. Eletriptan blocks the release of substances from nerve endings that cause more pain and other symptoms like nausea, and sensitivity to light and sound. It is thought that these actions contribute to relief of symptoms by eletriptan. Eletriptan is a serotonin receptor agonist, specifically an agonist of certain 5-HT1 family receptors. Eletriptan binds with high affinity to the 5-HT[1B, 1D, 1F] receptors. It has a modest affinity to the 5-HT[1A, 1E, 2B, 7] receptors, and little to no affinity at the 5-HT[2A, 2C, 3, 4, 5A, 6] receptors. | 0-1
|
Ivacaftor is a medication used to treat cystic fibrosis in people with certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (primarily the G551D mutation), who account for 4–5% cases of cystic fibrosis. It is also included in combination medications, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor which are used to treat people with cystic fibrosis.Ivacaftor was developed by Vertex Pharmaceuticals in conjunction with the Cystic Fibrosis Foundation and is the first medication that treats the underlying cause rather than the symptoms of the disease. It was approved by the U.S. Food and Drug Administration (FDA) in January 2012. It is one of the most expensive drugs, costing over US$300,000 per year, which has led to criticism of the high cost. The combination drug lumacaftor/ivacaftor was approved by the FDA in July 2015.Cystic fibrosis is caused by any one of several defects in the CFTR protein, which regulates fluid flow within cells and affects the components of sweat, digestive fluids, and mucus. One such defect is the G551D mutation, in which the amino acid glycine (G) in position 551 is replaced with aspartic acid (D). G551D is characterized by a dysfunctional CFTR protein on the cell surface. In the case of G551D, the protein is trafficked to the correct area, the epithelial cell surface, but once there the protein cannot transport chloride through the channel. | There was negligible urinary excretion of ivacaftor as unchanged parent. The apparent terminal half-life was approximately 12 hours following a single dose in the fed state. The apparent clearance (CL/F) of ivacaftor was similar for healthy subjects and patients with CF. The mean (±SD) of CL/F for the 150 mg dose was 17.3 (8.4) L/h in healthy subjects at steady state. Society and culture
Legal status
The U.S. Food and Drug Administration (FDA) approved ivacaftor in January 2012, and soon afterwards so too did the European Medicines Agency (EMA) and Canada and across some European countries.Lumacaftor/ivacaftor was approved by the FDA in July 2015, under breakthrough therapy status and under a priority review. Economics
The cost of ivacaftor is US$311,000 per year, roughly similar to the price of other medications for extremely rare diseases. In the first nine months of its second year on the market (2014), ivacaftor sales were $339M, representing 54% of Vertexs product sales revenue. During the same period, total drug development expenses were $458M, most of which was spent on cystic fibrosis-related research.An editorial in JAMA called the price of ivacaftor "exorbitant", citing the support by the Cystic Fibrosis Foundation in its development and the contribution made by fundamental scientific research performed by the National Institutes of Health and relied upon by Vertex in its cystic fibrosis drug discovery programs. | 11
|
In severe chronic kidney disease (GFR<30), the EMB dose should be halved (or avoided altogether). The PZA dose is 20 mg/kg/day (UK recommendation) or three-quarters the normal dose (US recommendation), but not much published evidence is available to support this. When using 2HRZ/4HR in patients on dialysis, the drugs should be given daily during the initial high-intensity phase. In the continuation phase, the drugs should be given at the end of each haemodialysis session and no dose should be taken on non-dialysis days. HIV
In patients with HIV, treatment for the HIV should be delayed until TB treatment is completed, if possible. The current UK guidance (provided by the British HIV Association) is
CD4 count over 200—delay treatment until the six months of TB treatment are complete. CD4 count 100 to 200—delay treatment until the initial two-month intensive phase of therapy is complete
CD4 count less than 100—the situation is unclear and patients should be enrolled in clinical trials examining this question. There is evidence that if these patients are managed by a specialist in both TB and HIV then outcomes are not compromised for either disease.If HIV treatment has to be started while a patient is still on TB treatment, then the advice of a specialist HIV pharmacist should be sought. In general, there is no significant interactions with the NRTIs. Nevirapine should not be used with rifampicin. Efavirenz may be used, but dose used depends on the patients weight (600 mg daily if weight less than 50 kg; 800 mg daily if weight greater than 50 kg). | Implementation of DOTS-Plus requires the capacity to perform drug-susceptibility testing (not routinely available even in developed countries) and the availability of second-line agents, in addition to all the requirements for DOTS. DOTS-Plus is therefore much more resource-expensive than DOTS, and requires much greater commitment from countries wishing to implement it. Community engagement is a new approach that is being initiated alongside the DOTS individualized treatment. By creating a community for health workers to give support to patients and hospital faculty, the DOTS-plus model also incorporates psychological structural support treatments to help accommodate patients to ensure completion of treatment. Treatment with the new strategy is a total duration of 18–24 months.Monthly surveillance until cultures convert to negative is recommended for DOTS-Plus, but not for DOTS. If cultures are positive or symptoms do not resolve after three months of treatment, it is necessary to re-evaluate the patient for drug-resistant disease or nonadherence to drug regimen. If cultures do not convert to negative despite three months of therapy, some physicians may consider admitting the patient to hospital so as to closely monitor therapy. Extra-pulmonary tuberculosis
Tuberculosis not affecting the lungs is called extra-pulmonary tuberculosis. Disease of the central nervous system is specifically excluded from this classification. The United Kingdom and the World Health Organization (WHO) recommendation is 2HREZ/4HR; the US recommendation is 2HREZ/7HR. | 11
|
Prophet Jeremiah portrays a Queen mother as sharing in her sons rule over the kingdom in Jeremiah 13:18-20. The wife of Prophet Isaiah was a Prophetess. Isaiah 8:3
Expectation of fidelity and violence related to adultery
There is a widely held expectation, which has existed for most of recorded history and in most cultures, that a wife is not to have sexual relations with anyone other than her legal husband. A breach of this expectation of fidelity is commonly referred to as adultery or extramarital sex. Historically, adultery has been considered to be a serious offense, sometimes a crime, and a sin. Even if that is not so, it may still have legal consequences, particularly as a ground for a divorce. Adultery may be a factor to consider in a property settlement, it may affect the status of children, the custody of children; moreover, adultery can result in social ostracism in some parts of the world. In addition, affinity rules of Catholicism, of Judaism and of Islam prohibit an ex-wife or widow from engaging in sexual relations with and from marrying a number of relatives of the former husband. In parts of the world, adultery may result in violent acts, such as honor killings or stoning. Some jurisdictions, especially those that apply Sharia law, allow for such acts to take place legally.As of September 2010, stoning is a legal punishment in countries such as Saudi Arabia, Sudan, Iran, Yemen, the United Arab Emirates, and some states in Nigeria as punishment for zina al-mohsena ("adultery of married persons"). | See Women in Japan, Law of Japan
Wife in Abrahamic religions
Wife in Christianity
Christian marriage as based on biblical teachings and conditions, is to be between one woman and one man, that God Himself joined them and that no human is to separate them, according to Christs words (Matthew 19:4-6). The New Testament states that an unmarried Christian woman is to be celibate or is to become the Christian wife of one husband to avoid sexual immorality and for his sexual passion (1 Cor 7:1-2 & 8–9). The New Testament permits divorce of a Christian wife by a Christian husband only if she has committed adultery (Matthew 5:32). A Christian widow to (re)marry a man she chooses (1 Cor 7:39) but forbids a divorced Christian woman to remarry because she would be committing adultery if she did (Matthew 5:32). As such she is to remain unmarried and celibate or be reconciled with her husband (1 Cor 7:1-2 & 8-9 and 1 Cor 7:10-11). A Christian wife can divorce a non-Christian husband if he wants a divorce (1 Cor 7:12-16). Christian husbands are to love their Christian wives as Christ loved the Church (Ephesians 5:25) and as he loves himself (Ephesians 5:33). The Christian wife is to respect her husband (Ephesians 5:33). Christian husbands are to not be harsh with their Christian wives (Colossians 3:19) and to treat them as a delicate vessel and with honor (1 Peter 3:7). | 11
|
On a chest radiograph, subcutaneous emphysema may be seen as radiolucent striations in the pattern expected from the pectoralis major muscle group. Air in the subcutaneous tissues may interfere with radiography of the chest, potentially obscuring serious conditions such as pneumothorax. It can also reduce the effectiveness of chest ultrasound. On the other hand, since subcutaneous emphysema may become apparent in chest X-rays before a pneumothorax does, its presence may be used to infer that of the latter injury. Subcutaneous emphysema can also be seen in CT scans, with the air pockets appearing as dark areas. CT scanning is so sensitive that it commonly makes it possible to find the exact spot from which air is entering the soft tissues. In 1994, M.T. Macklin and C.C. Macklin published further insights into the pathophysiology of spontaneous Macklins Syndrome occurring from a severe asthmatic attack. The presence of subcutaneous emphysema in a person who appears quite ill and febrile after bout of vomiting followed by left chest pain is very suggestive of the diagnosis of Boerhaaves syndrome, which is a life-threatening emergency caused by rupture of the distal esophagus. Subcutaneous emphysema can be a complication of CO2 insufflation with laparoscopic surgery. A sudden rise in end-tidal CO2 following the initial rise that occurs with insufflation (first 15-30 min) should raise suspicion of subcutaneous emphysema. Of note, there are no changes in the pulse oximetry or airway pressure in subcutaneous emphysema, unlike in endobronchial intubation, capnothorax, pneumothorax, or CO2 embolism. Treatment
Subcutaneous emphysema is usually benign. | Most of the time, SCE itself does not need treatment (though the conditions from which it results may); however, if the amount of air is large, it can interfere with breathing and be uncomfortable. It occasionally progresses to a state "Massive Subcutaneous Emphysema" which is quite uncomfortable and requires surgical drainage. When the amount of air pushed out of the airways or lung becomes massive, usually due to positive pressure ventilation, the eyelids swell so much that the patient cannot see. Also the pressure of the air may impede the blood flow to the areolae of the breast and skin of the scrotum or labia. This can lead to necrosis of the skin in these areas. The latter are urgent situations requiring rapid, adequate decompression. Severe cases can compress the trachea and do require treatment.In severe cases of subcutaneous emphysema, catheters can be placed in the subcutaneous tissue to release the air. Small cuts, or "blow holes", may be made in the skin to release the gas. When subcutaneous emphysema occurs due to pneumothorax, a chest tube is frequently used to control the latter; this eliminates the source of the air entering the subcutaneous space. If the volume of subcutaneous air is increasing, it may be that the chest tube is not removing air rapidly enough, so it may be replaced with a larger one. Suction may also be applied to the tube to remove air faster. | 11
|
A 2020 study conducted by INRIX, private company that analyzes traffic patters, behaviors and congestion, showed that as traffic levels returned to normal during the three-month period August to October 2020, growth in collisions (57%), outpaced the growth in miles traveled (22%) resulting in a higher than normal collision rate during this period.In France, the Ministry of Interior reported that traffic incidents, crash-related injuries, and fatalities dropped in 2020 compared with 2019. Fatalities dropped 21.4%, injuries dropped 20.9%, and incidents overall dropped 20%. In the same report, the ministry reported that the number of vehicles on the road dropped by 75%, which would indicate that the rate (incidents per vehicle-mile) in fact increased. Other
Other possibly hazardous factors that may alter a drivers soundness on the road include:
Irritability
Following specifically distinct rules too bureaucratically, inflexibly or rigidly when unique circumstances might suggest otherwise
Sudden swerving into somebodys blind spot without first clearly making oneself visible through the wing mirror
Unfamiliarity with ones dashboard features, center console or other interior handling devices after a recent car purchase
Lack of visibility due to windshield design, dense fog or sun glare
People-watching. Traffic safety culture, a variety of aspects of safety culture could impact on the number of crashes. Prevention
A large body of knowledge has been amassed on how to prevent car crashes, and reduce the severity of those that do occur. | Types of collision include head-on, road departure, rear-end, side collisions, and rollovers. Many different terms are commonly used to describe vehicle collisions. The World Health Organization uses the term road traffic injury, while the U.S. Census Bureau uses the term motor vehicle accidents (MVA), and Transport Canada uses the term "motor vehicle traffic collision" (MVTC). Other common terms include auto accident, car accident, car crash, car smash, car wreck, motor vehicle collision (MVC), personal injury collision (PIC), road accident, road traffic accident (RTA), road traffic collision (RTC), and road traffic incident (RTI) as well as more unofficial terms including smash-up, pile-up, and fender bender. Some organizations have begun to avoid the term accident, instead preferring terms such as collision, crash or incident. This is because the term accident implies that there is no one to blame, whereas most traffic collisions are the result of driving under the influence, excessive speed, distractions such as mobile phones or other risky behavior.Historically, in the United States, the use of terms other than accident had been criticized for holding back safety improvements, based on the idea that a culture of blame may discourage the involved parties from fully disclosing the facts, and thus frustrate attempts to address the real root causes. Health effects
Physical
A number of physical injuries can commonly result from the blunt force trauma caused by a collision, ranging from bruising and contusions to catastrophic physical injury (e.g., paralysis), traumatic or non-traumatic cardiac arrest and death. Psychological
Following collisions, long-lasting psychological trauma may occur. | 11
|
Although fluent, the speech may lack in key substantive words (nouns, verbs, adjectives), and may contain incorrect words or even nonsense words. This subtype has been associated with damage to the posterior left temporal cortex, most notably Wernickes area. These individuals usually have no body weakness, because their brain injury is not near the parts of the brain that control movement. Conduction aphasia, where speech remains fluent, and comprehension is preserved, but the person may have disproportionate difficulty repeating words or sentences. Damage typically involves the arcuate fasciculus and the left parietal region. Transcortical motor aphasia and transcortical sensory aphasia, which are similar to Brocas and Wernickes aphasia respectively, but the ability to repeat words and sentences is disproportionately preserved.Recent classification schemes adopting this approach, such as the Boston-Neoclassical Model, also group these classical aphasia subtypes into two larger classes: the nonfluent aphasias (which encompasses Brocas aphasia and transcortical motor aphasia) and the fluent aphasias (which encompasses Wernickes aphasia, conduction aphasia and transcortical sensory aphasia). These schemes also identify several further aphasia subtypes, including: anomic aphasia, which is characterized by a selective difficulty finding the names for things; and global aphasia, where both expression and comprehension of speech are severely compromised. Many localizationist approaches also recognize the existence of additional, more "pure" forms of language disorder that may affect only a single language skill. | 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 | 0-1
|
Signs and symptoms
Some or all of the following symptoms may be present, though it is possible not to experience any symptoms:
Abdominal pain. Dull aching pain within the abdomen or pelvis, especially during intercourse. Uterine bleeding. Pain during or shortly after beginning or end of menstrual period; irregular periods, or abnormal uterine bleeding or spotting. Fullness, heaviness, pressure, swelling, or bloating in the abdomen. When a cyst ruptures from the ovary, there may be sudden and sharp pain in the lower abdomen on one side. Change in frequency or ease of urination (such as inability to fully empty the bladder), or difficulty with bowel movements due to pressure on adjacent pelvic anatomy. Constitutional symptoms such as fatigue, headaches. Nausea or vomiting
Weight gainOther symptoms may depend on the cause of the cysts:
Symptoms that may occur if the cause of the cysts is polycystic ovarian syndrome (PCOS) may include increased facial hair or body hair, acne, obesity and infertility. If the cause is endometriosis, then periods may be heavy, and intercourse painful.The effect of cysts not related to PCOS on fertility is unclear. Cyst rupture
A ruptured ovarian cyst is usually self-limiting, and only requires keeping an eye on the situation and pain medications. The main symptom is abdominal pain, which may last a few days to several weeks, but they can also be asymptomatic. Rupture of large ovarian cysts can cause bleeding inside the abdominal cavity and in some cases shock. | Men with BPD are more likely to recreationally use substances, have explosive temper, high levels of novelty seeking and have anti-social, narcissistic, passive-aggressive or sadistic personality traits. Women with BPD are more likely to have eating disorders, mood disorders, anxiety and post-traumatic stress. Manipulative behavior
Manipulative behavior to obtain nurturance is considered by the DSM-IV-TR and many mental health professionals to be a defining characteristic of borderline personality disorder. However, Marsha Linehan notes that doing so relies upon the assumption that people with BPD who communicate intense pain, or who engage in self-harm and suicidal behavior, do so with the intention of influencing the behavior of others. The impact of such behavior on others—often an intense emotional reaction in concerned friends, family members, and therapists—is thus assumed to have been the persons intention.However, their frequent expressions of intense pain, self-harming, or suicidal behavior may instead represent a method of mood regulation or an escape mechanism from situations that feel unbearable. Stigma
The features of BPD include emotional instability; intense, unstable interpersonal relationships; a need for intimacy; and a fear of rejection. As a result, people with BPD often evoke intense emotions in those around them. Pejorative terms to describe people with BPD, such as "difficult", "treatment resistant", "manipulative", "demanding", and "attention seeking", are often used and may become a self-fulfilling prophecy, as the negative treatment of these individuals triggers further self-destructive behavior. Physical violence
The stigma surrounding borderline personality disorder includes the belief that people with BPD are prone to violence toward others. | 0-1
|
Kyphosis is an abnormally excessive convex curvature of the spine as it occurs in the thoracic and sacral regions. Abnormal inward concave lordotic curving of the cervical and lumbar regions of the spine is called lordosis. It can result from degenerative disc disease; developmental abnormalities, most commonly Scheuermanns disease; Copenhagen disease, osteoporosis with compression fractures of the vertebra; multiple myeloma; or trauma. A normal thoracic spine extends from the 1st thoracic to the 12th thoracic vertebra and should have a slight kyphotic angle, ranging from 20° to 45°. When the "roundness" of the upper spine increases past 45° it is called kyphosis or "hyperkyphosis". Scheuermanns kyphosis is the most classic form of hyperkyphosis and is the result of wedged vertebrae that develop during adolescence. The cause is not currently known and the condition appears to be multifactorial and is seen more frequently in males than females.In the sense of a deformity, it is the pathological curving of the spine, where parts of the spinal column lose some or all of their lordotic profile. This causes a bowing of the back, seen as a slouching posture. Kyphosis is distinguished from scoliosis, a condition in which the spine has a sideways curve. While most cases of kyphosis are mild and only require routine monitoring, serious cases can be debilitating. High degrees of kyphosis can cause severe pain and discomfort, breathing and digestion difficulties, cardiovascular irregularities, neurological compromise and, in the more severe cases, significantly shortened life spans. | Idiopathic thoracic kyphosis due to vertebral wedging, fractures, or vertebral abnormalities is more difficult to manage, since assuming a correct posture may not be possible with structural changes in the vertebrae. Children who have not completed their growth may show long-lasting improvements with bracing. Exercises may be prescribed to alleviate discomfort associated with overstretched back muscles. A variety of gravity-assisted positions or gentle traction can minimize pain associated with nerve root impingement. Surgery may be recommended for severe idiopathic kyphosis. Brace
Body braces showed benefit in a randomised controlled trial.The Milwaukee brace is one particular body brace that is often used to treat kyphosis in the US. Modern CAD/CAM braces are used in Europe to treat different types of kyphosis. These are much easier to wear and have better in-brace corrections than reported for the Milwaukee brace. Since there are different curve patterns (thoracic, thoracolumbar, and lumbar), different types of brace are in use, with different advantages and disadvantages. Physical therapy
In Germany, a standard treatment for both Scheuermanns disease and lumbar kyphosis is the Schroth method, a system of physical therapy for scoliosis and related spinal deformities. It involves lying supine, placing a pillow under the scapular region and posteriorly stretching the cervical spine. In China, many people use spinal care mattresses to correct kyphosis while sleeping. Surgery
Surgical treatment can be used in severe cases. In patients with progressive kyphotic deformity due to vertebral collapse, a procedure called a kyphoplasty may arrest the deformity and relieve the pain. | 11
|
The sinoatrial node is a single specialized location in the atrium that has a higher automaticity (a faster pacemaker) than the rest of the heart and, therefore, is usually responsible for setting the heart rate and initiating each heartbeat.Any part of the heart that initiates an impulse without waiting for the sinoatrial node is called an ectopic focus and is, by definition, a pathological phenomenon. This may cause a single premature beat now and then, or, if the ectopic focus fires more often than the sinoatrial node, it can produce a sustained abnormal rhythm. Rhythms produced by an ectopic focus in the atria, or by the atrioventricular node, are the least dangerous dysrhythmias; but they can still produce a decrease in the hearts pumping efficiency because the signal reaches the various parts of the heart muscle with different timing than usual and can be responsible for poorly coordinated contraction.Conditions that increase automaticity include sympathetic nervous system stimulation and hypoxia. The resulting heart rhythm depends on where the first signal begins: If it is the sinoatrial node, the rhythm remains normal but rapid; if it is an ectopic focus, many types of dysrhythmia may ensue. Re-entry
Re-entrant arrhythmias occur when an electrical impulse recurrently travels in a tight circle within the heart, rather than moving from one end of the heart to the other and then stopping.Every cardiac cell can transmit impulses of excitation in every direction but will do so only once within a short time. | Normally, the action potential impulse will spread through the heart quickly enough that each cell will respond only once. However, if there is some essential heterogeneity of refractory period or if conduction is abnormally slow in some areas (for example in heart damage) so the myocardial cells are unable to activate the fast sodium channel, part of the impulse will arrive late and potentially be treated as a new impulse. Depending on the timing, this can produce a sustained abnormal circuit rhythm. As a sort of re-entry, vortices of excitation in the myocardium (autowave vortices) are considered to be the main mechanism of life-threatening cardiac arrhythmias. In particular, the autowave reverberator is common in the thin walls of the atria, sometimes resulting in atrial flutter. Re-entry is also responsible for most paroxysmal supraventricular tachycardia, and dangerous ventricular tachycardia. These types of re-entry circuits are different from WPW syndromes, which utilize abnormal conduction pathways. Although omega-3 fatty acids from fish oil can be protective against arrhythmias, they can facilitate re-entrant arrhythmias. Fibrillation
When an entire chamber of the heart is involved in multiple micro-reentry circuits and is, therefore, quivering with chaotic electrical impulses, it is said to be in fibrillation. Fibrillation can affect the atrium (atrial fibrillation) or the ventricle (ventricular fibrillation): ventricular fibrillation is imminently life-threatening. Atrial fibrillation affects the upper chambers of the heart, known as the atria. Atrial fibrillation may be due to serious underlying medical conditions and should be evaluated by a physician. It is not typically a medical emergency. | 11
|
In Australia and New Zealand there is a recommendation that PAL be replaced by guidance from VITAL 2.0 (Vital Incidental Trace Allergen Labeling). A review identified "the eliciting dose for an allergic reaction in 1% of the population" as ED01. This threshold reference dose for foods (such as cows milk, egg, peanut and other proteins) will provide food manufacturers with guidance for developing precautionary labeling and give consumers a better idea of what might be accidentally in a food product beyond "may contain." VITAL 2.0 was developed by the Allergen Bureau, a food industry sponsored, non-government organization. The European Union has initiated a process to create labeling regulations for unintentional contamination but is not expected to publish such before 2024.In Brazil, since April 2016, the declaration of the possibility of cross-contamination is mandatory when the product does not intentionally add any allergenic food or its derivatives, but the Good Manufacturing Practices and allergen control measures adopted are not sufficient to prevent the presence of accidental trace amounts. These allergens include wheat, rye, barley, oats and their hybrids, crustaceans, eggs, fish, peanuts, soybean, milk of all species of mammalians, almonds, hazelnuts, cashew nuts, Brazil nuts, macadamia nuts, walnuts, pecan nuts, pistachios, pine nuts, and chestnuts. | Two faces on one head
Where twinning of the head itself is only partial, it can result in the condition known as diprosopus—one head with two faces. Earliest known occurrence
The February 22, 2007, issue of the journal Biology Letters detailed the discovery of a 122 million-year-old fossil of a two-headed Hyphalosaurus lingyuanensis, marking the earliest known occurrence of axial bifurcation. List of notable occurrences
Humans
Dicephalic conjoined twins (dicephalus parapagus dipus)
Lycosthenes described a pair of adult female twins who had separate necks but one body. Both heads ate, drank, slept, and spoke. They had to beg from door to door, "everie one giveing (sic) to her freely". They were banished to Bavaria due to fears pregnant women who saw them would give birth to similar children; nothing else is known of them. In 1990 Abigail and Brittany Hensel were born in Minnesota, United States. In 2000 Ayse and Sema Tanrikulu were born in Kahramanmaraş, Turkey
In June 2000 Carmen and Lupita Andrade were born in Veracruz, Mexico. They later moved to the United States for healthcare with their parents. In 2003 Sohna and Mohna were born in India
On June 13, 2003, twin girls named Huda and Manal Abdel Nasser Mohammed Mahmoud, were born in Asyut, Egypt
In 2006 Syafitri was born in Indonesia
In 2007 Mary Grace and Mary Divine Asis were born in the Philippines with only one heart. They died on April 30, 2008. On August 25, 2008, a baby boy named Kiron was born with two heads in south-western Bangladesh. | 0-1
|
The catheter has a small lumen, allowing for small flush volumes to get medication to the rectum. Small volumes of medications (under 15mL) improve comfort by not stimulating the defecation response of the rectum and can increase the overall absorption of a given dose by decreasing pooling of medication and migration of medication into more proximal areas of the rectum where absorption can be less effective. Integrated pathways
Integrated care pathways are an organizational tool used by healthcare professionals to clearly define the roles of each team-member and coordinate how and when care will be provided. These pathways are utilized to ensure best practices are being utilized for end-of-life care, such as evidence-based and accepted health care protocols, and to list the required features of care for a specific diagnosis or clinical prolem. Many institutions have a predetermined pathway for end of life care, and clinicians should be aware of and make use of these plans when possible. In the United Kingdom, end-of-life care pathways are based on the Liverpool Care Pathway. Originally developed to provide evidence based care to dying cancer patients, this pathway has been adapted and used for a variety of chronic conditions at clinics in the UK and internationally. Despite its increasing popularity, the 2016 Cochrane Review, which only analyzed one trial, showed limited evidence in the form of high-quality randomized clinical trials to measure the effectiveness of end-of-life care pathways on clinical outcomes, physical outcomes, and emotional/psychological outcomes. | Dipygus is a severe congenital deformity where the body axis forks left and right partway along the torso with the posterior end (pelvis and legs) duplicated. Myrtle Corbin was a dipygus; she married and had five children. In human cases, the inner two of the four hindquarters develop much smaller than normal. This is a type of "teras catadidymum" ("monster twinned below"). Another sort of deformity with extra legs can happen from a degenerated conjoined twin, as may have happened with Frank Lentini with his third leg. Signs
Dipygus manifests as duplicated lower limbs and could include additional organs or bodily structures. Causes
Dipygus is caused by genetic, environmental, or teratogenic factors. It occurs early in intrauterine life. == References == | 0-1
|
In other cases, patients diagnosed with circumvallate placenta are able to carry their babies until term or near-term. Epidemiology
Circumvallate placenta is a very rare condition affecting pregnant women. This condition is a placental morphological abnormality, with the placenta being formed during the early periods of pregnancy. Women are able to become pregnant with the onset of ovulation and menstruation in early adolescence, with most women becoming pregnant during adulthood. Circumvallate placenta is currently known to affect about 1-2% of pregnancies. It is not virally transmissible to other individuals, nor can it be transferred through contact or respiration.There are no specific racial or ethnic groups that are more predisposed to acquiring a circumvallate placenta during pregnancy, however, as with all pregnancies, there are general risks factors that can put a pregnant woman at risk for complications, including circumvallate placenta. Notably, certain pregnancy complications, such as preeclampsia, tend to be almost three times as fatal in African American women compared to non-Hispanic white women, even though both groups tend to experience preeclampsia at almost the same rates. This is partially thought to be due to inequalities in accessing quality prenatal care in lower socioeconomic neighborhoods and the effect of structural racism within healthcare systems. Any woman residing in an area with a lower socioeconomic status, regardless of race or age, is predisposed to developing pregnancy complications like circumvallate placenta if quality prenatal care is not available. | More recently, the Group has suggested that values of 0.5x109 or 5%, respectively, may be more appropriate from a therapeutic viewpoint and therefore should be studied as a definitive criterion for the disease. A recent study supported this suggestion in finding that multiple myeloma patients with >5% circulating plasma cells had a prognosis much worse than that for multiple myeloma and similar to that for plasma cell leukemia. Flow cytometry immunophenotyping of blood cells to detect clonal phenotypes of plasma cells seen in multiple myeloma (e.g. the CD138+, CD38+, CD19−, CD45+/- phenotype) may be a more sensitive method to enumerate circulating clonal plasma cells and diagnose plasma cell leukemia. Treatments
Prior to the use of newly developed drugs and treatment regimens, median survival rates from the time of diagnosis for pPCL and sPCL were 8–11 months and 2–8 months, respectively, even when treated very aggressively with the VAD regimen of vincristine, doxorubicin, and dexamethasone or the VCMP regimen of vincristine, carmustine, melphalan, and prednisone alternating with vincristine, carmustine, doxorubicin, and prednisone. The treatment of PCL patients, particularly pPCL patients, with newer methods appears to have made modest improvements in survival rates. However, the rarity of these two leukemias has limited individual studies to case reports on a small number of patients or retrospective analyses of patient records. Randomized controlled trials on these patients have not been reported. One flaw of these methods is patient selection bias, i.e. | 0-1
|
For my part, I would consign the label MSBP to the history books and however useful FII may apparently be to the child protection practitioner I would caution against its use other than as a factual description of a series of incidents or behaviors that should then be accurately set out (and even then only in the hands of the pediatrician or psychiatrist/psychologist). I cannot emphasis too strongly that my conclusion cannot be used as a reason to re-open the many cases where facts have been found against a carer and the label MSBP or FII has been attached to that carers behavior. What I seek to caution against is the use of the label as a substitute for factual analysis and risk assessment. In his book Playing Sick (2004), Marc Feldman notes that such findings have been in the minority among U.S. and even Australian courts. Pediatricians and other physicians have banded together to oppose limitations on child-abuse professionals whose work includes FII detection. The April 2007 issue of the journal Pediatrics specifically mentions Meadow as an individual who has been inappropriately maligned. In the context of child protection (a child being removed from the custody of a parent), the Australian state of New South Wales uses a "on the balance of probabilities" test, rather than a "beyond reasonable doubt" test. | My whole life I was made to believe I was sick, when I wasn’t ‘til I grew up and blew up..." His mothers illness resulted in Eminem receiving custody of his younger brother, Nathan.In 2013, when Justina Pelletier was 14, her parents took her to the emergency room at Boston Childrens Hospital where doctors diagnosed her problems as psychiatric, but when her parents rejected the diagnosis and attempted to have her released, the hospital filed a report with Massachusetts Department of Children and Families alleging medical child abuse. This resulted in her being housed for 18 months in the psychiatric hospital, with her parents having limited access, until a judge ordered her returned to her parents. In 2016 her parents sued Boston Childrens for medical malpractice, alleging that their civil rights were violated. At the trial, Pelletiers treating neurologist stated that several of her doctors suspected factitious disorder by proxy, and wanted her parents to stop encouraging her to be sick. Her parents lost the lawsuit, with one juror stating that Pelletiers parents thought of psychiatry as "psychological baloney". Directed towards animals
Medical literature describes a subset of FDIA caregivers, where the proxy is a pet rather than another person. These cases are labeled Munchausen syndrome by proxy: pet (MSbP:P). In these cases, pet owners correspond to caregivers in traditional FDIA presentations involving human proxies. No extensive survey has yet been made of the extant literature, and there has been no speculation as to how closely FDIA:P tracks with human FDIA. | 11
|
Arguments have been made for allowing diagnosis through the presence of some, but not all of the characteristics of DID rather than the current exclusive focus on the two least common and noticeable features. The DSM-IV-TR criteria have also been criticized for being tautological, using imprecise and undefined language and for the use of instruments that give a false sense of validity and empirical certainty to the diagnosis. The DSM-5 updated the definition of DID in 2013, summarizing the changes as:
Several changes to the criteria for dissociative identity disorder have been made in DSM-5. First, Criterion A has been expanded to include certain possession-form phenomena and functional neurological symptoms to account for more diverse presentations of the disorder. Second, Criterion A now specifically states that transitions in identity may be observable by others or self-reported. Third, according to Criterion B, individuals with dissociative identity disorder may have recurrent gaps in recall for everyday events, not just for traumatic experiences. Other text modifications clarify the nature and course of identity disruptions. Between 1968 and 1980, the term that was used for dissociative identity disorder was "Hysterical neurosis, dissociative type". The APA wrote in the second edition of the DSM: "In the dissociative type, alterations may occur in the patients state of consciousness or in his identity, to produce such symptoms as amnesia, somnambulism, fugue, and multiple personality." The number of cases sharply increased in the late 1970s and throughout the 80s, and the first scholarly monographs on the topic appeared in 1986. | Treatment and epidemiology
Treatment generally involves supportive care and psychotherapy. The condition usually persists without treatment. It is believed to affect about 1.5% of the general population (based on a small US community sample) and 3% of those admitted to hospitals with mental health issues in Europe and North America. DID is diagnosed about six times more often in women than in men. The number of recorded cases increased significantly in the latter half of the 20th century, along with the number of identities reported by those affected. Society and culture
DID is controversial within both the field of psychiatry and the legal system. Claims of DID have been used only rarely to argue criminal insanity in court.It is unclear whether increased rates of the disorder are due to better recognition or sociocultural factors such as mass media portrayals. The typical presenting symptoms in different regions of the world may also vary depending on culture, for example alter identities taking the form of possessing spirits, deities, ghosts, or mythical figures in cultures where normative possession states are common. (pp 295, 801) The possession form of dissociative identity disorder is involuntary and distressing, and occurs in a way that violates cultural or religious norms. (p 295)
Definitions
Dissociation, the term that underlies dissociative disorders including DID, lacks a precise, empirical, and generally agreed upon definition.A large number of diverse experiences have been termed dissociative, ranging from normal failures in attention to the breakdowns in memory processes characterized by the dissociative disorders. | 11
|
British authorities banned the term shell shock during World War II to avoid an epidemic of cases, and the term posttrauma concussion state was coined in 1939 to describe "disturbance of consciousness with no immediate or obvious pathologic change in the brain". The term postconcussion syndrome was in use by 1941.In 1961, H. Miller first used the term "accident neurosis" to refer to the syndrome which is now called PCS and asserted that the condition only occurs in situations where people stand to be compensated for the injury. The real causes of the condition remain unclear. Controversy
Though no universally accepted definition of postconcussive syndrome exists, most of the literature defines the syndrome as the development of at least three of the following symptoms: headache, dizziness, fatigue, irritability, impaired memory and concentration, insomnia, and lowered tolerance for noise and light. One complication in diagnosis is that symptoms of PCS also occur in people who have no history of head injury, but who have other medical and psychological complaints. In one study 64% of people with TBI, 11% of those with brain injuries, and 7% of those with other injuries met the DSM-IV criteria for post-concussion syndrome. Many of these individuals with PCS were misdiagnosed as having other unrelated conditions due to commonality of symptoms. (see diagnosis above).Headache is one of the criteria for PCS, but it is notably undetermined where the headache comes from. | With their focus on psychological factors, the ICD-10 criteria support the idea that the cause of PCS is functional. Like the ICD-10, the ICD-9-CM defines PCS in terms of subjective symptoms and discusses the greater frequency of PCS in people with histories of mental disorders or a financial incentive for a diagnosis.The DSM-IV lists criteria for diagnosis of PCD in people who have had a head trauma with persistent post-traumatic amnesia, loss of consciousness, or post-traumatic seizures. In addition, for a diagnosis of PCD, patients must have neuropsychological impairment as well as at least three of the symptoms marked with a check mark in the table at right under "DSM-IV". These symptoms must be present for three months after the injury and must have been absent or less severe before the injury. In addition, the patient must experience social problems as a result, and must not meet criteria for another disorder that explains the symptoms better.Neuropsychological tests exist to measure deficits in cognitive functioning that can result from PCS. The Stroop Color Test and the 2&7 Processing Speed Test (which both detect deficits in speed of mental processing) can predict the development of cognitive problems from PCS. A test called the Rivermead Postconcussion Symptoms Questionnaire, a set of questions that measure the severity of 16 different post-concussion symptoms, can be self-administered or administered by an interviewer. Other tests that can predict the development of PCS include the Hopkins Verbal Learning A test (HVLA) and the Digit Span Forward examination. | 11
|
Safety
Natamycin does not have acute toxicity. In animal studies, the lowest LD50 found was 2.5-4.5 g/kg. In rats, the LD50 is ≥2300 mg/kg, and doses of 500 mg/kg/day over 2 years caused no detectable differences in survival rate, growth, or incidence of tumors. The metabolites of natamycin also lack toxicity. The breakdown products of natamycin under various storage conditions may have a lower LD50 than natamycin, but in all cases, the numbers are quite high. In humans, a dose of 500 mg/kg/day repeated over multiple days caused nausea, vomiting, and diarrhea.No evidence shows natamycin, at either pharmacological levels or levels encountered as a food additive, can harm normal intestinal flora, but definitive research may not be available. However, some people are allergic to natamycin.The EFSA has concluded that the use of natamycin as a food additive has no relevant risk for the development of resistant fungi. Mechanism of action
Natamycin inhibits the growth of fungi by specifically binding to ergosterol present in fungal cell membranes. Natamycin inhibits amino acid and glucose transport proteins leading to a loss of nutrient transport across the plasma membrane. While this binding is reversible, ergosterol binding acts as a universal mechanism of fungal inhibition, allowing natamycin to act on diverse fungal pathogens from Saccharomyces yeast to Aspergillus moulds. Natamycin is unique amongst related antifungals specifically because it does not directly cause membrane permeabilization. | It can be applied in a variety of ways: as an aqueous suspension (such as mixed into a brine) sprayed on the product or into which the product is dipped, or in powdered form (along with an anticaking agent such as cellulose) sprinkled on or mixed into the product. While not currently approved for use on meats in the United States, some countries allow natamycin to be applied to the surface of dry and fermented sausages to prevent mold growth on the casing. Also, natamycin is approved for various dairy applications in the United States. More specifically, natamycin is commonly used in products such as cream cheeses, cottage cheese, sour cream, yogurt, shredded cheeses, cheese slices, and packaged salad mixes. One of the reasons for food producers to use natamycin is to replace the artificial preservative sorbic acid.As a food additive, it has E number E235. Throughout the European Union, it is approved only as a surface preservative for certain cheese and dried sausage products. It must not be detectable 5 mm below the rind. While natamycin is approved in different applications at different levels in the world, it is approved in over 150 countries worldwide.The European Food Safety Authority (EFSA) panel took over the responsibilities of providing scientific food safety advice to the EU from the Scientific Committee on Food in 2002. In 2009, the EFSA considered the proposed use levels of natamycin are safe if it is used for the surface treatment for these cheese and sausage types. | 11
|
The products are nearly identical in composition, efficacy, and cost, varying primarily in the formulations and delivery devices.Somapacitan-beco (Sogroya) is first once-per week subcutaneous human growth hormone (hGH) therapy that was approved in the United States. It was approved for medical use in the United States in August 2020. Terminology
Growth hormone (GH l) is also called somatotropin (British: somatotrophin). The human form of growth hormone is known as human growth hormone, or hGH (ovine growth hormone, or sheep growth hormone, is abbreviated oGH). GH can refer either to the natural hormone produced by the pituitary (somatotropin), or biosynthetic GH for therapy.Cadaver growth hormone is the term for GH extracted from the pituitary glands of human cadavers between 1960 and 1985 for therapy of deficient children. In the U.S., cadaver GH, also referred to as NPA growth hormone, was provided by the National Pituitary Agency, and by other national programs and commercial firms as well. In 1985 it was associated with the development of Creutzfeldt–Jakob disease, and was withdrawn from use.RHGH (rHGH, rhGH) refers to recombinant human growth hormone, that is, somatropin (INN). Its amino acid sequence is identical with that of endogenous human GH.It is coincidental that RHGH also refers to rhesus monkey GH (RhGH), using the accepted naming convention of Rh for rhesus. | The medical literature of the decade contains hundreds of reports of small trials of GH use in nearly every type of growth failure and shortness imaginable. In most cases, the growth responses were modest. For conditions with a large enough potential market, more rigorous trials were sponsored by pharmaceutical companies that were making growth hormone to achieve approval to market for those specific indications. Turner syndrome and chronic kidney failure were the first of these “nonGH-deficient causes of shortness” to receive FDA approval for GH treatment, and Prader-Willi syndrome and intrauterine growth retardation followed. Similar expansion of use occurred in Europe.One obvious potential market was adult GH deficiency. By the mid-1990s, several GH companies had sponsored or publicized research into the quality of life of adults with severe GH deficiency. Most were people having been treated with GH in childhood for severe deficiency. Although the injections are painless, many of them had been happy to leave injections behind as they reached final heights in the low-normal range. However, as adults in their 30s and 40s, these people, who had been children with growth hormone deficiency, were now adults with growth hormone deficiency and had more than their share of common adult problems: reduced physical, mental, and social energy, excess adipose and diminished muscle, diminished libido, poor bone density, higher cholesterol levels, and higher rates of cardiovascular disease. Research trials soon confirmed that a few months of GH could improve nearly all of these parameters. However, despite marketing efforts, most GH-deficient adults remain untreated. | 11
|
Edrophonium is a readily reversible acetylcholinesterase inhibitor. It prevents breakdown of the neurotransmitter acetylcholine and acts by competitively inhibiting the enzyme acetylcholinesterase, mainly at the neuromuscular junction. It is sold under the trade names Tensilon and Enlon (according to FDA Orange Book). Clinical uses
Edrophonium (by the so-called Tensilon test) is used to differentiate myasthenia gravis from cholinergic crisis and Lambert-Eaton. In myasthenia gravis, the body produces autoantibodies which block, inhibit or destroy nicotinic acetylcholine receptors in the neuromuscular junction. Edrophonium—an effective acetylcholinesterase inhibitor—will reduce the muscle weakness by blocking the enzymatic effect of acetylcholinesterase enzymes, prolonging the presence of acetylcholine in the synaptic cleft. It binds to a Serine-103 allosteric site, while pyridostigmine and neostigmine bind to the AchE active site for their inhibitory effects. In a cholinergic crisis, where a person has too much neuromuscular stimulation, edrophonium will make the muscle weakness worse by inducing a depolarizing block. However, the edrophonium and ice pack tests are no longer recommended as first-line tests due to false positive results. In practice, the edrophonium test has been replaced by testing for autoantibodies, including acetylcholine receptor (AchR) autoantibodies and muscle specific tyrosine kinase (MuSK) autoantibodies.Lambert-Eaton myasthenic syndrome (LEMS), is similar to myasthenia gravis in that it is an autoimmune disease. However, in LEMS the neuron is unable to release enough acetylcholine for normal muscle function due to autoantibodies attacking P/Q-type calcium channel that are necessary for acetylcholine release. This means there is insufficient calcium ion influx into presynaptic terminal resulting in reduced exocytosis of acetylcholine containing vesicles. | Consequently, there will typically be not as much increase in muscle strength observed after edrophonium injection, if any with LEMS. The Tensilon test may also be used to predict if neurotoxic paralysis caused by snake envenomation is presynaptic or postsynaptic. If it is a postsynaptic then paralysis will be temporally reversed, indicating that can be reversed by adequate antivenom therapy. If the neurotoxic is presynaptic then the Tensilon test will show no response and antivenom will not reverse such paralysis. In this instance reversal of paralysis will not occur until the damaged terminal axons at the neuromuscular junction have recovered, this may take days or weeks.The drug may also be used for reversal of neuromuscular blockade at the end of a surgical procedure. Chemistry
Edrophonium, ethyl-(3-hydroxyphenyl)dimethylammonium chloride, is made by reacting 3-dimethylaminophenol with ethyl bromide, which forms ethyl(3-hydroxyphenyl)dimethylammonium bromide, the bromine atom of which is replaced with a chlorine atom by reacting it with silver chloride, giving edrophonium. Pharmacokinetics
The drug has a brief duration of action, about 10–30 mins. References
== Further reading == | 11
|
This ANA test was easier to perform and led not only to a definitive diagnosis of lupus but also many other related diseases. This discovery led to the understanding of what is now known as autoimmune diseases.To ensure that the person has lupus and not another autoimmune disease, the American College of Rheumatology (ACR) established a list of clinical and immunologic criteria that, in any combination, point to SLE. The criteria include symptoms that the person can identify (e.g. pain) and things that a physician can detect in a physical examination and through laboratory test results. The list was originally compiled in 1971, initially revised in 1982, and further revised and improved in 2009.Medical historians have theorized that people with porphyria (a disease that shares many symptoms with SLE) generated folklore stories of vampires and werewolves, due to the photosensitivity, scarring, hair growth, and porphyrin brownish-red stained teeth in severe recessive forms of porphyria (or combinations of the disorder, known as dual, homozygous, or compound heterozygous porphyrias).Useful medication for the disease was first found in 1894 when quinine was first reported as an effective therapy. Four years later, the use of salicylates in conjunction with quinine was noted to be of still greater benefit. This was the best available treatment until the middle of the twentieth century when Hench discovered the efficacy of corticosteroids in the treatment of SLE. Research
A study called BLISS-76 tested the drug belimumab, a fully human monoclonal anti-BAFF (or anti-BLyS) antibody. | Treatment
The treatment of SLE involves preventing flares and reducing their severity and duration when they occur. Treatment can include corticosteroids and anti-malarial drugs. Certain types of lupus nephritis such as diffuse proliferative glomerulonephritis require intermittent cytotoxic drugs. These drugs include cyclophosphamide and mycophenolate. Cyclophosphamide increases the risk of developing infections, pancreas problems, high blood sugar, and high blood pressure.Hydroxychloroquine was approved by the FDA for lupus in 1955. Some drugs approved for other diseases are used for SLE off-label. In November 2010, an FDA advisory panel recommended approving belimumab (Benlysta) as a treatment for the pain and flare-ups common in lupus. The drug was approved by the FDA in March 2011.In terms of healthcare utilization and costs, one study found that "patients from the US with SLE, especially individuals with moderate or severe disease, utilize significant healthcare resources and incur high medical costs." Medications
Due to the variety of symptoms and organ system involvement with SLE, its severity in an individual must be assessed to successfully treat SLE. Mild or remittent disease may, sometimes, be safely left untreated. If required, nonsteroidal anti-inflammatory drugs and antimalarials may be used. Medications such as prednisone, mycophenolic acid and tacrolimus have been used in the past. Disease-modifying antirheumatic drugs
Disease-modifying antirheumatic drugs (DMARDs) are used preventively to reduce the incidence of flares, the progress of the disease, and the need for steroid use; when flares occur, they are treated with corticosteroids. DMARDs commonly in use are antimalarials such as hydroxychloroquine and immunosuppressants (e.g. methotrexate and azathioprine). | 11
|
Contraindications
Combining the drug with pimozide or ergot alkaloids (such as ergotamine or methylergometrine) is contraindicated because these drugs are metabolized by the liver enzyme CYP3A4, and letermovir inhibits this enzyme. In people who also take ciclosporin, which increases letermovir concentrations in the body, combination with the cholesterol lowering drugs simvastatin and pitavastatin is also contraindicated. In Canada, this also applies to bosentan, lovastatin and rosuvastatin; and in the EU, to dabigatran, atorvastatin, and rosuvastatin. Adverse effects
Side effects from the use of letermovir are uncommon, but gastrointestinal symptoms such as gastritis and nausea may occur, as can dyspnea (difficulties breathing) and hepatitis. In general, side effects of the drug are comparable to those under placebo treatment. Overdose
In studies, giving the threefold therapeutic dose for 14 days resulted in no additional adverse effects. It is unknown whether the substance can be removed from the system by hemodialysis. Pharmacology
Mechanism of action
Letermovir is a viral terminase inhibitor. It specifically inhibits the CMV viral terminase complex which is encoded by the CMV genes UL56, UL51 and UL89. This inhibition has the effect of preventing cleavage of CMV DNA concatamers, resulting in long uncleaved DNA and noninfectious viral particles. Letermovir is only active against CMV and has no effect on other herpesviruses. Pharmacokinetics
Letermovir is quickly absorbed from the gut, reaching its highest concentrations in the blood plasma after 1.5 to 3 hours. Its bioavailability is estimated to be 37%. Ciclosporin increases this bioavailability to about 85%. When in the bloodstream, the substance is almost completely (98.2%) bound to plasma proteins. | Letermovir (INN; trade name Prevymis) is an antiviral drug for the treatment of cytomegalovirus (CMV) infections. It has been tested in CMV infected patients with allogeneic stem cell transplants and may also be useful for other patients with a compromised immune system such as those with organ transplants or HIV infections. The drug was initially developed by the anti-infective division at Bayer, which became AiCuris Anti-infective Cures AG through a spin-out and progressed the development to end of Phase 2 before the project was sold to Merck & Co for Phase 3 development and approval.The drug was granted fast track status by the US Food and Drug Administration (FDA) and orphan drug status by the European Medicines Agency. It is now approved for prevention of CMV infection and disease in recipients of an allogeneic stem cell transplant.The FDA considers it to be a first-in-class medication. Medical use
In the US as well as in the EU, letermovir is used for the prevention of cytomegalovirus infection and disease in adult CMV-seropositive recipients of an allogeneic stem cell transplant. The therapy is started shortly after the transplantation and typically lasts for 100 days. Although letermovir is a relatively new antiviral, CMV resistance has been documented in stem cell transplantation recipients; although rare, breakthrough infections of prophylactic treatment with letermovir underscores the ongoing selective pressure on CMVs viral evolution and its continued ability to evade therapeutic suppression through mutations in critical gene regions such as within the UL56 amplicon. | 11
|
Unlike other mechanisms of injury in which pulmonary contusion is often found alongside other injuries, explosions can cause pulmonary contusion without damage to the chest wall.In addition to blunt trauma, penetrating trauma can cause pulmonary contusion. Contusion resulting from penetration by a rapidly moving projectile usually surrounds the path along which the projectile traveled through the tissue. The pressure wave forces tissue out of the way, creating a temporary cavity; the tissue readily moves back into place, but it is damaged. Pulmonary contusions that accompany gun and knife wounds are not usually severe enough to have a major effect on outcome; penetrating trauma causes less widespread lung damage than does blunt trauma. An exception is shotgun wounds, which can seriously damage large areas of lung tissue through a blast injury mechanism. Mechanism
The physical processes behind pulmonary contusion are poorly understood. However, it is known that lung tissue can be crushed when the chest wall bends inward on impact. Three other possible mechanisms have been suggested: the inertial effect, the spalling effect, and the implosion effect. In the inertial effect, the lighter alveolar tissue is sheared from the heavier hilar structures, an effect similar to diffuse axonal injury in head injury. It results from the fact that different tissues have different densities, and therefore different rates of acceleration or deceleration. In the spalling effect, lung tissue bursts or is sheared where a shock wave meets the lung tissue, at interfaces between gas and liquid. | Intubation and mechanical ventilation further increase the risk of developing pneumonia; the tube is passed through the nose or mouth into the airways, potentially tracking bacteria from the mouth or sinuses into them. Also, intubation prevents coughing, which would clear bacteria-laden secretions from the airways, and secretions pool near the tubes cuff and allow bacteria to grow. The sooner the endotracheal tube is removed, the lower the risk of pneumonia, but if it is removed too early and has to be put back in, the risk of pneumonia rises. People who are at risk for pulmonary aspiration (e.g. those with lowered level of consciousness due to head injuries) are especially likely to get pneumonia. As with ARDS, the chances of developing pneumonia increase with the size of the contusion. Children and adults have been found to have similar rates of complication with pneumonia and ARDS. Associated injuries
A large amount of force is required to cause pulmonary contusion; a person injured with such force is likely to have other types of injuries as well. In fact, pulmonary contusion can be used to gauge the severity of trauma. Up to three quarters of cases are accompanied by other chest injuries, the most common of these being hemothorax and pneumothorax. Flail chest is usually associated with significant pulmonary contusion, and the contusion, rather than the chest wall injury, is often the main cause of respiratory failure in people with these injuries. | 11
|
Some mercury vapor is absorbed dermally, but uptake by this route is only about 1% of that by inhalation.In humans, approximately 80% of inhaled mercury vapor is absorbed via the respiratory tract, where it enters the circulatory system and is distributed throughout the body. Chronic exposure by inhalation, even at low concentrations in the range 0.7–42 μg/m3, has been shown in case–control studies to cause effects such as tremors, impaired cognitive skills, and sleep disturbance in workers.Acute inhalation of high concentrations causes a wide variety of cognitive, personality, sensory, and motor disturbances. The most prominent symptoms include tremors (initially affecting the hands and sometimes spreading to other parts of the body), emotional lability (characterized by irritability, excessive shyness, confidence loss, and nervousness), insomnia, memory loss, neuromuscular changes (weakness, muscle atrophy, muscle twitching), headaches, polyneuropathy (paresthesia, stocking-glove sensory loss, hyperactive tendon reflexes, slowed sensory and motor nerve conduction velocities), and performance deficits in tests of cognitive function. Mechanism
The toxicity of mercury sources can be expected to depend on its nature, i.e., salts vs. organomercury compounds vs. elemental mercury. The primary mechanism of mercury toxicity involves its irreversible inhibition of selenoenzymes, such as thioredoxin reductase (IC50 = 9 nM). Although it has many functions, thioredoxin reductase restores vitamins C and E, as well as a number of other important antioxidant molecules, back into their reduced forms, enabling them to counteract oxidative damage. | Mercury poisoning is a type of metal poisoning due to exposure to mercury. Symptoms depend upon the type, dose, method, and duration of exposure. They may include muscle weakness, poor coordination, numbness in the hands and feet, skin rashes, anxiety, memory problems, trouble speaking, trouble hearing, or trouble seeing. High-level exposure to methylmercury is known as Minamata disease. Methylmercury exposure in children may result in acrodynia (pink disease) in which the skin becomes pink and peels. Long-term complications may include kidney problems and decreased intelligence. The effects of long-term low-dose exposure to methylmercury are unclear.Forms of mercury exposure include metal, vapor, salt, and organic compound. Most exposure is from eating fish, amalgam-based dental fillings, or exposure at a workplace. In fish, those higher up in the food chain generally have higher levels of mercury, a process known as biomagnification. Less commonly, poisoning may occur as a method of attempted suicide. Human activities that release mercury into the environment include the burning of coal and mining of gold. Tests of the blood, urine, and hair for mercury are available but do not relate well to the amount in the body.Prevention includes eating a diet low in mercury, removing mercury from medical and other devices, proper disposal of mercury, and not mining further mercury. In those with acute poisoning from inorganic mercury salts, chelation with either dimercaptosuccinic acid (DMSA) or dimercaptopropane sulfonate (DMPS) appears to improve outcomes if given within a few hours of exposure. Chelation for those with long-term exposure is of unclear benefit. | 11
|
If only one of these nerves is damaged, the patients voice may be impaired (dysphonia); if both of the nerves are damaged, the patient will be unable to speak (aphonia). In the acute setting, indications for tracheotomy are similar to those for cricothyrotomy. In the chronic setting, indications for tracheotomy include the need for long-term mechanical ventilation and removal of tracheal secretions (e.g., comatose patients, or extensive surgery involving the head and neck). Children
There are significant differences in airway anatomy and respiratory physiology between children and adults, and these are taken into careful consideration before performing tracheal intubation of any pediatric patient. The differences, which are quite significant in infants, gradually disappear as the human body approaches a mature age and body mass index.For infants and young children, orotracheal intubation is easier than the nasotracheal route. Nasotracheal intubation carries a risk of dislodgement of adenoids and nasal bleeding. Despite the greater difficulty, nasotracheal intubation route is preferable to orotracheal intubation in children undergoing intensive care and requiring prolonged intubation because this route allows a more secure fixation of the tube. As with adults, there are a number of devices specially designed for assistance with difficult tracheal intubation in children. Confirmation of proper position of the tracheal tube is accomplished as with adult patients.Because the airway of a child is narrow, a small amount of glottic or tracheal swelling can produce critical obstruction. Inserting a tube that is too large relative to the diameter of the trachea can cause swelling. | A specific test for parathyroid adenoma is sestamibi parathyroid scintigraphy, the sestamibi scan. This nuclear imaging technique reveals the presence and location of pathological parathyroid tissue.4DCT is used as second line investigation to diagnose parathyroid adenoma. In addition to the three dimensional imaging of a conventional CT scan, 4DCT provides imaging on the changes of iodinated contrast enhancement overtime and present them in a video format (from plain imaging to arterial to venous and delay phases). Parathyroid adenoma would show low density on non contrast image, with peak enhancement during the arterial phase, then slowly fade away until the delay phase. Treatment
Surgery is the only cure for parathyroid adenomas. It is successful about 95% of the time. Parathyroidectomy is the removal of the affected gland(s). The standard of treatment of primary hyperparathyroidism was formerly a surgical technique called bilateral neck exploration, in which the neck was opened on both sides, the parathyroids were identified, and the affected tissue was removed. By the 1980s, unilateral exploration became more common. Parathyroidectomy can now be performed in a minimally invasive fashion, mainly because imaging techniques can pinpoint the location of the tissue. Minimally invasive techniques include smaller open procedures, radio-guided and video-assisted procedures, and totally endoscopic surgery.Before surgery is attempted, the affected glandular tissue must be located. Though the parathyroid glands are usually located on the back of the thyroid, their position is variable. Some people have one or more parathyroid glands elsewhere in the neck anatomy or in the chest. | 0-1
|
[PubMed]
Krishnan M, Kumar S, Ali S, Iyer RS. Sudden bilateral anterior cerebral infarction: unusual stroke associated with unusual vascular anomalies. Postgrad Med J. 2013 Feb;89(1048):120-1. [PubMed]
Arboix A, García-Eroles L, Sellarés N, Raga A, Oliveres M, Massons J. Infarction in the territory of the anterior cerebral artery: clinical study of 51 patients. BMC Neurol. 2009 Jul 09;9:30. [PMC free article] [PubMed]
Kang SY, Kim JS. Anterior cerebral artery infarction: stroke mechanism and clinical-imaging study in 100 patients. Neurology. 2008 Jun 10;70(24 Pt 2):2386-93. [PubMed]
Hensler J, Jensen-Kondering U, Ulmer S, Jansen O. Spontaneous dissections of the anterior cerebral artery: a meta-analysis of the literature and three recent cases. Neuroradiology. 2016 Oct;58(10):997-1004. [PubMed]
Mohindra S, Kovai P, Chhabra R. Fatal Bilateral ACA Territory Infarcts after Pituitary Apoplexy: A Case Report and Literature Review. Skull Base. 2010 Jul;20(4):285-8. [PMC free article] [PubMed]
Kurre W, Vorlaender K, Aguilar-Pérez M, Schmid E, Bäzner H, Henkes H. Frequency and relevance of anterior cerebral artery embolism caused by mechanical thrombectomy of middle cerebral artery occlusion. AJNR Am J Neuroradiol. 2013 Aug;34(8):1606-11. [PubMed]
Nagaratnam N, Davies D, Chen E. Clinical effects of anterior cerebral artery infarction. J Stroke Cerebrovasc Dis. 1998 Nov-Dec;7(6):391-7. [PubMed]
Bogousslavsky J, Martin R, Moulin T. Homolateral ataxia and crural paresis: a syndrome of anterior cerebral artery territory infarction. J. Neurol. Neurosurg. Psychiatry. 1992 Dec;55(12):1146-9. [PMC free article] [PubMed]
Honig A, Eliahou R, Auriel E. Confined anterior cerebral artery infarction manifesting as isolated unilateral axial weakness. J. Neurol. Sci. 2017 Feb 15;373:18-20. [PubMed]
Kobayashi S, Maki T, Kunimoto M. Clinical symptoms of bilateral anterior cerebral artery territory infarction. | The National Institutes of Health Stroke Scale (NIHSS) is a standardized method for quantifiable assessment of stroke symptoms. It is the preferred scoring system, and scores range from 0 to 42. A patient with a higher score on this scale is more likely to be considered disabled; however, the definition of "disabling" depends on age, occupation, underlying life-limiting comorbidities, advance directives. The crucial step in the evaluation of stroke patients is to obtain brain imaging to ascertain the type and characteristics of the stroke. In this regard, non-contrast CT of the head is the imaging modality of choice. Ischemic changes may classify as acute, subacute, and chronic, depending on the time in which they present after the onset of stroke. CT scan can also rule out intracranial hemorrhage. [18] If an intracranial hemorrhage is present, aneurysmal rupture should be investigated given its association with arterial vasospasm resulting in stroke. [3] Anterior cerebral artery strokes could be missed on imaging studies depending on their location or size. One case series found that 37.5% (6 of 16) of ACA infarcts evaluated by CT were identifiable only after using contrast injection or angiography. If the area of hypodensity is small and localized over a sulcus, the infarct could be overlooked. [1] [13] Noncontrast head CT should be quickly followed by CT angiography of the head and neck to expedite identification of intracranial large vessel occlusion. | 11
|
Roflumilast, sold under the trade name Daxas among others, is a drug that acts as a selective, long-acting inhibitor of the enzyme phosphodiesterase-4 (PDE-4). It has anti-inflammatory effects and is used as an orally administered drug for the treatment of inflammatory conditions of the lungs such as chronic obstructive pulmonary disease (COPD).In June 2010, it was approved in the European Union for severe COPD associated with chronic bronchitis. In February 2011, it gained FDA approval in the United States for reducing COPD exacerbations. Medical uses
Roflumilast is indicated for the treatment of severe chronic obstructive pulmonary disease (COPD) and for the treatment of plaque psoriasis.It is used in the prevention of exacerbations (lung attacks) in severe chronic obstructive pulmonary disease (COPD).A topical formulation of Rolflumilast was recently approved by the U.S. Food and Drug Administration for plaque psoriasis. Adverse effects
Common (1–10% incidence) adverse effects include:
Diarrhea
Weight loss
Nausea
Headache
Insomnia
Decreased appetite
Abdominal pain
Rhinitis
Sinusitis
Urinary tract infection
Depression
References
External links
"Roflumilast". Drug Information Portal. U.S. National Library of Medicine. | A common single-nucleotide polymorphism of BRCA2 is associated with severe oligospermia.Men with mild oligospermia (semen concentration of 15 million to 20 million sperm/ml) were studied for an association of sperm DNA damage with life style factors. A significant association was found between sperm DNA damage and factors such as age, obesity and occupational stress. Treatment
Treatment takes place within the context of infertility management and needs also to consider the fecundity of the female partner. Thus the choices can be complex. In a number of situations direct medical or surgical intervention can improve the sperm concentration, examples are use of FSH in men with pituitary hypogonadism, antibiotics in case of infections, or operative corrections of a hydrocele, varicocele, or vas deferens obstruction. In most cases of oligospermia including its idiopathic form there is no direct medical or surgical intervention agreed to be effective. Empirically many medical approaches have been tried including clomiphene citrate, tamoxifen, HMG, FSH, HCG, testosterone, Vitamin E, Vitamin C, anti-oxidants, carnitine, acetyl-L-carnitine, zinc, high-protein diets. In a number of pilot studies some positive results have been obtained. Clomiphene citrate has been used with modest success. The combination of tamoxifen plus testosterone was reported to improve the sperm situation.The use of carnitine showed some promise in a controlled trial in selected cases of male infertility improving sperm quality and further studies are needed.In many situations, intrauterine inseminations are performed with success. | 0-1
|
Between 70% and 90% of common cancers are due to environmental factors and therefore potentially preventable.Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: tobacco, excess weight/obesity, poor diet, physical inactivity, alcohol, sexually transmitted infections and air pollution. Further, poverty could be considered as an indirect risk factor in human cancers. Not all environmental causes are controllable, such as naturally occurring background radiation and cancers caused through hereditary genetic disorders and thus are not preventable via personal behavior. Dietary
While many dietary recommendations have been proposed to reduce cancer risks, the evidence to support them is not definitive. The primary dietary factors that increase risk are obesity and alcohol consumption. Diets low in fruits and vegetables and high in red meat have been implicated but reviews and meta-analyses do not come to a consistent conclusion. A 2014 meta-analysis found no relationship between fruits and vegetables and cancer. Coffee is associated with a reduced risk of liver cancer. Studies have linked excessive consumption of red or processed meat to an increased risk of breast cancer, colon cancer and pancreatic cancer, a phenomenon that could be due to the presence of carcinogens in meats cooked at high temperatures. | Such environments can include the presence of disruptive substances called carcinogens, repeated physical injury, heat, ionising radiation or hypoxia.The errors that cause cancer are self-amplifying and compounding, for example:
A mutation in the error-correcting machinery of a cell might cause that cell and its children to accumulate errors more rapidly. A further mutation in an oncogene might cause the cell to reproduce more rapidly and more frequently than its normal counterparts. A further mutation may cause loss of a tumor suppressor gene, disrupting the apoptosis signaling pathway and immortalizing the cell. A further mutation in the signaling machinery of the cell might send error-causing signals to nearby cells.The transformation of a normal cell into cancer is akin to a chain reaction caused by initial errors, which compound into more severe errors, each progressively allowing the cell to escape more controls that limit normal tissue growth. This rebellion-like scenario is an undesirable survival of the fittest, where the driving forces of evolution work against the bodys design and enforcement of order. Once cancer has begun to develop, this ongoing process, termed clonal evolution, drives progression towards more invasive stages. Clonal evolution leads to intra-tumour heterogeneity (cancer cells with heterogeneous mutations) that complicates designing effective treatment strategies and requires an evolutionary approach to designing treatment. Characteristic abilities developed by cancers are divided into categories, specifically evasion of apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signals, sustained angiogenesis, limitless replicative potential, metastasis, reprogramming of energy metabolism and evasion of immune destruction. | 11
|
Other serotonergic pharmacologics in question
The SSRI antidepressants raise blood serotonin levels, and thus may be capable of the same risks, though it is thought that the risk is substantially lower with such drugs. The amino acid L-tryptophan also raises blood serotonin, and may present the same risk as well; though, again, the risk is considered to be low.However, the tryptophan derivative 5-HTP (5-hydroxytryptophan), used in the treatment of depression, raises blood serotonin level considerably. It has yet to be reported to be associated with valve disease or other fibrosis, but for the previous theoretical reasons, it has been suggested as a possible danger.When 5-HTP is used in medicine, it is generally administered along with carbidopa, which prevents the peripheral decarboxylation of 5-HTP to serotonin and so ensures that only brain serotonin levels are increased without producing peripheral side effects, however 5-HTP is also sold without carbidopa as a dietary supplement, and may have increased risks when taken by itself without carbidopa. In non-human great apes
Cardiac fibrosis is common in non-human great apes in human care. The term idiopathic myocardial fibrosis was coined to emphasize this disease is likely different from the above described forms of cardiac fibrosis in humans. The etiology is not known, though vitamin D deficiency is a potential suspected cause at least in chimpanzees. Possible treatments
The most obvious treatment for cardiac valve fibrosis or fibrosis in other locations, consists of stopping the stimulatory drug or production of serotonin. | In the case of a functional neuroendocrine tumor, somatostatin analogs such as octreotide are used to reduce the production of serotonin by tumor cells, which often highly express inhibitory somatostatin receptors.Surgical tricuspid valve replacement, sometimes combined with a pulmonary valve replacement, can be necessary in some patients.A compound found in red wine, resveratrol has been found to slow the development of cardiac fibrosis. More sophisticated approaches of countering cardiac fibrosis like microRNA inhibition (miR-21, for example) are being tested in animal models. == References == | 11
|
In normal muscle cells, the various parts of the muscle fibers that make up the sarcomere are distributed evenly in a pattern for effective muscle contraction. Evidence suggests that some kinds of NM affect the arrangement of these muscle fibers, causing the muscles to be unable to contract as efficiently or effectively. Nemaline myopathy is usually genetic and shows traits in the affected individual from birth or an early age. However, there are some cases of symptoms of nemaline myopathy not showing up until adulthood. These cases are usually not genetic. Of the genes that have been linked to nemaline myopathy, most are also involved in encoding proteins in the sarcomeres in the muscle cells. Respiratory muscles are often more affected than other skeletal muscle groups. Cardiac muscle is usually not affected in nemaline myopathy; however, in cases where it does, patients often present with dilated cardiomyopathy. The ocular muscles are usually spared.The different genes whose mutations lead to the different kinds of nemaline myopathies affect the cells and the persons body differently. The first kind of nemaline myopathy identified is due to the Slow α-Tropomyosin Gene TPM3 and varies from case to case with its severity. In this kind of nemaline myopathy, affected people are weaker and more affected in their lower limbs than their upper limbs.As stated above, the most common genetic form of NM is caused by a mutation in the nebulin gene, called Nebulin, and has a range of severity levels. | Many more conferences and social events have been held since, and all events organized since 2008 have been co-sponsored by A Foundation Building Strength for Nemaline Myopathy (AFBS), the only foundation focused on supporting treatment development and social events for the NM community. In March 2006, Niki Shisler released a book, Fragile, in which she recounted her experiences surrounding the birth of twin sons with severe NM. In 2014, a team of experts collaborated with affected individuals and families caring for someone with a congenital myopathy to develop the first guidebook on managing life with a congenital myopathy
References
External links
GeneReview/NCBI/NIH/UW entry on Nemaline Myo\ | 11
|
The outermost layer, known as the mantle dentin layer, is found in the crown of the tooth. It can and can be identified by the presence of various characteristics, including collagen fibres found perpendicular to the enamel-dentin junction and it is slightly less mineralized (by approximately 5%, compared to the enamel. The dentin undergoes mineralization in the presence of matrix vesicles ("hydroxyapatite-containing, membrane-enclosed vesicles secreted by odontoblasts, osteoblasts, and some chondrocytes; believed to serve as nucleation centers for the mineralization process in dentin, bone, and calcified cartilage.") The dentinal tubules in this region branch profusely. In the root of the tooth there are two morphologically distinguishable outer layers: the hyaline layer on the periphery of dentin and the granular layer of Tomes beneath this. The granular layer has a dark, granular appearance which occurs due to the branching and looping back of dentinal tubules in this region. This appearance, specific to root dentin, is possibly due to differences in the rates of formation of coronal and root dentin. The hyaline layer, which has an obscure origin, is a clear layer, unlike the granular layer, with a width of up to 20μm. It can have clinical significance during periodontal regeneration. Circumpulpal dentin forms the majority of the dentin and is generally constant in structure. Peripherally, mineralization can be seen to be incomplete, whereas centrally the mineralizing front shows ongoing mineralizing. The innermost layer of dentin is known as predentin, and is the initial dentin matrix that is laid down prior to mineralization. | It can be distinguished by its pale color when stained with haematoxylin and eosin. The presence of odontoblastic processes here allows the secretion of matrix components. Predentin can be 10-40μm in width, depending on its rate of deposition. : 134–137
Types
There are three types of dentin, primary, secondary and tertiary. Secondary dentin is a layer of dentin produced after the root of the tooth is completely formed. Tertiary dentin is created in response to a stimulus, such as a carious attack or wear. Primary dentin
Primary dentin, the most prominent dentin in the tooth, lies between the enamel and the pulp chamber (near dentinoenamel junction). The outer layer closest to enamel is known as mantle dentin. This layer is unique to the rest of primary dentin. Mantle dentin is formed by newly differentiated odontoblasts and forms a layer consistently 15-20 micrometers (µm) wide. Unlike primary dentin, mantle dentin lacks phosphorylation, has loosely packed collagen fibrils and is less mineralized. Below it lies the circumpulpal dentin, more mineralized dentin which makes up most of the dentin layer and is secreted after the mantle dentin by the odontoblasts. Circumpulpal dentin is formed before the root formation is completed. Newly secreted dentin is unmineralized and is called predentin. It is easily identified in hematoxylin and eosin stained sections since it stains less intensely than dentin. It is usually 10-47μm and lines the innermost region of the dentin. It is unmineralized and consists of collagen, glycoproteins, and proteoglycans. It is similar to osteoid in bone and is thickest when dentinogenesis is occurring. | 11
|
Although the numerous factors contributing to the progression of this disease have made discovering the exact origin and cause difficult, major advances over the past decade have contributed to a proposed set of pathogenic events that occur prior to the diagnosis of Sjögrens syndrome.Sjögrens syndrome was originally proposed as a specific, self-perpetuating, immune system-mediated loss of exocrine glands, specifically acinar and ductal cells. Although this explains the more obvious symptoms (such as the lack of saliva and lacrimal fluid), it does not explain the more widespread systemic effects seen in the progression of the disease.In the presence of a susceptible genetic background, both environmental and hormonal factors are thought capable of triggering the infiltration of lymphocytes, specifically CD4+ T cells, B cells, and plasma cells, causing glandular dysfunction in the salivary and lacrimal glands.Sjögrens syndrome is associated with increased levels in cerebrospinal fluid (CSF) of IL-1RA, an interleukin 1 antagonist. This suggests that the disease begins with increased activity in the interleukin 1 system, followed by an autoregulatory upregulation of IL-1RA to reduce the successful binding of interleukin 1 to its receptors. Interleukin 1 likely is the marker for fatigue, but increased IL-1RA is observed in the CSF and is associated with increased fatigue through cytokine-induced sickness behavior. However, Sjögrens syndrome is characterized by decreased levels of IL-1ra in saliva, which could be responsible for mouth inflammation and dryness. Patients with secondary Sjögrens syndrome also often exhibit signs and symptoms of their primary rheumatic disorders, such as systemic lupus erythematosus, rheumatoid arthritis, or systemic sclerosis. | Salagen, a manufactured form of pilocarpine, can be used to help produce tears, as well as saliva in the mouth and intestines. It is derived from the jaborandi plant. Vaginal dryness
In women with Sjögrens syndrome, vaginal dryness, vulvodynia and dyspareunia (painful sexual intercourse) are often reported; personal lubricants are recommended to help lessen irritation or pain that may result from dryness in the vaginal and vulval areas. Musculoskeletal
Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs may be prescribed, and sometimes intravenous immunoglobulins. Also, disease-modifying antirheumatic drugs such as methotrexate may be helpful. Hydroxychloroquine (Plaquenil) is another option and is generally considered safer than methotrexate. However, these prescribed drugs have a range of side effects such as nausea, loss of appetite, dizziness, hair loss, stomach aches/cramps, headache, liver toxicity and increased risk of infections. Also, those who take drugs to suppress the immune system are more likely to develop cancer later. Systemic
For systemic symptoms, including fatigue, joint pain, myositis and neuropathy, biologic immunosuppressant drugs such as rituximab and belimumab that work via B-cell pathology are often used and have less toxic profiles than traditional immunosuppressive regimens. Dental care
Preventive dental treatment is also necessary (and often overlooked by the patient), as the lack of saliva associated with xerostomia creates an ideal environment for the proliferation of bacteria that cause cavities. Treatments include at-home topical fluoride application to strengthen tooth enamel and frequent teeth cleanings by a dental hygienist. | 11
|
These symptoms may be described in infantile beriberi:
Hoarseness, where the child makes moves to moan, but emits no sound or just faint moans caused by nerve paralysis
Weight loss, becoming thinner and then marasmic as the disease progresses
Vomiting
Diarrhea
Pale skin
Edema
Ill temper
Alterations of the cardiovascular system, especially tachycardia (rapid heart rate)
Convulsions occasionally observed in the terminal stages
Cause
Beriberi is often caused by eating a diet with a very high proportion of calorie rich polished rice (common in Asia) or cassava root (common in sub-Saharan Africa), without much if any thiamine containing animals or vegetables.It may also be caused by shortcomings other than inadequate intake - diseases or operations on the digestive tract, alcoholism, dialysis or genetic deficiencies. All those causes mainly affect the central nervous system, and provoke the development of Wernickes encephalopathy. Wernickes disease is one of the most prevalent neurological or neuropsychiatric diseases. In autopsy series, features of Wernicke lesions are observed in approximately 2% of general cases. Medical record research shows that about 85% had not been diagnosed, although only 19% would be asymptomatic. In children, only 58% were diagnosed. In alcohol abusers, autopsy series showed neurological damages at rates of 12.5% or more. Mortality caused by Wernickes disease reaches 17% of diseases, which means 3.4/1000 or about 25 million contemporaries. The number of people with Wernickes disease may be even higher, considering that early stages may have dysfunctions prior to the production of observable lesions at necropsy. In addition, uncounted numbers of people can experience fetal damage and subsequent diseases. | Before beginning treatment, prisoners exhibited symptoms of dry or wet beriberi with neurological signs (tingling: 41%), cardiovascular signs (dyspnoea: 42%, thoracic pain: 35%), and edemas of the lower limbs (51%). With treatment, the rate of healing was about 97%.Populations under extreme stress may be at higher risk for beriberi. Displaced populations, such as refugees from war, are susceptible to micronutritional deficiency, including beriberi. The severe nutritional deprivation caused by famine also can cause beriberis, although symptoms may be overlooked in clinical assessment or masked by other famine-related problems. An extreme weight-loss diet can, rarely, induce a famine-like state and the accompanying beriberi. History
Earliest written descriptions of thiamine deficiency are from ancient China in the context of Chinese medicine. One of the earliest is by Ge Hong in his book Zhou hou bei ji fang (Emergency Formulas to Keep up Your Sleeve) written sometime during the third century. Hong called the illness by the name jiao qi, which can be interpreted as "foot qi". He described the symptoms to include swelling, weakness, and numbness of the feet. He also acknowledged that the illness could be deadly, and claimed that it could be cured by eating certain foods, such as fermented soybeans in wine. | 11
|
Human case reports suggest that injecting more than 100 mL of air into the venous system at rates greater than 100 mL/s can be fatal. Very large and symptomatic amounts of venous air emboli may also occur in rapid decompression in severe diving or decompression accidents, where they may interfere with circulation in the lungs and result in respiratory distress and hypoxia.Gas embolism in a systemic artery, termed arterial gas embolism (AGE), is a more serious matter than in a vein, because a gas bubble in an artery may directly stop blood flow to an area fed by the artery. The symptoms of AGE depend on the area of blood flow, and may be those of stroke for a cerebral arterial gas embolism (CAGE) or heart attack if the heart is affected. The amount of arterial gas embolism that causes symptoms depends on location — 2 mL of air in the cerebral circulation can be fatal, while 0.5 mL of air into a coronary artery can cause cardiac arrest. Prevention and screening
If a patent foramen ovale (PFO) is suspected, an examination by echocardiography may be performed to diagnose the defect. In this test, very fine bubbles are introduced into a patients vein by agitating saline in a syringe to produce the bubbles, then injecting them into an arm vein. A few seconds later, these bubbles may be clearly seen in the ultrasound image, as they travel through the patients right atrium and ventricle. | See also
Ebullism – Formation of gas bubbles in bodily fluids due to reduced environmental pressure
References
External links
Arterial Gas Embolism | 11
|
In 2017 the death rate rose over 100% with 368 overdose-related deaths in British Columbia between January and April 2017.Fentanyl has started to make its way into heroin as well as illicitly manufactured opioids and benzodiazepines. Fentanyl contamination in cocaine, methamphetamine, ketamine, MDMA, and other drugs is common. A kilogram of heroin laced with fentanyl may sell for more than US$100,000, but the fentanyl itself may be produced far more cheaply, for about US$6,000 per kilogram. Fentanyl was often produced in China and exported illegally to the U.S. The UK illicit drug market is no longer reliant on China, as domestic fentanyl production is replacing imports.As of 2018, fentanyl was the most commonly listed opioid in overdose drug deaths, surpassing heroin. From 2013 until 2016, overdose deaths involving fentanyl were increasing by 113% per year. In 2021, the Public Health Agency of Canada noted that 87% of accidental apparent opioid toxicity deaths involved fentanyl.The intravenous dose causing 50% of opioid-naive experimental subjects to die (LD50) is "3 mg/kg in rats, 1 mg/kg in cats, 14 mg/kg in dogs, and 0.03 mg/kg in monkeys." The LD50 in mice has been given as 6.9 mg/kg by intravenous administration, 17.5 mg/kg intraperitoneally, 27.8 mg/kg by oral administration. The LD50 in humans is unknown, but its estimated that the lethal dose may be as low as 2 mg in some people depending on body size, tolerance, and past usage. | Myths and moral panic
In the late 2010s, some media outlets began to report stories of police officers being hospitalised after touching powdered fentanyl, or after brushing it from their clothing. Topical (or transdermal; via the skin) and inhalative exposure to fentanyl is extremely unlikely to cause intoxication or overdose (except in cases of prolonged exposure with very large quantities of fentanyl), and first responders such as paramedics and police officers are at minimal risk of fentanyl poisoning through accidental contact with intact skin. A 2020 article from the Journal of Medical Toxicology stated that "the consensus of the scientific community remains that illness from unintentional exposures is extremely unlikely, because opioids are not efficiently absorbed through the skin and are unlikely to be carried in the air." The effects being reported in these cases, including rapid heartbeat, hyperventilation and chills, were not symptoms of a fentanyl overdose, and were more commonly associated with a panic attack.A 2021 paper expressed concern that these physical fears over fentanyl may inhibit effective emergency response to overdoses by causing responding officers to spend additional time on unnecessary precautions. The media coverage could also perpetuate a wider social stigma that people who use drugs are dangerous to be around. Prevention
Many public health initiatives have been started to prevent the misuse and overdose of fentanyl. One of the initiatives that have been started to prevent fentanyl overdose is from the CDC [1]. | 11
|
At least 9 IMF cases described in the English literature were diagnosed in fetuses based on the findings of fetal spectrogram and/or magnetic resonance imaging. IMF tumors in the viscera or deep tissues may present with serious or life-threatening signs and symptoms of organ and/or deep tissue damage due to these tumors space-filling and pressuring effects.Some individuals with IMF present with a family history of IMF tumors. To date (2021), 20 families have been reported to carry various germline (i.e. inherited) mutations in one of their two PDGFRB genes. All of these mutations were gain of function mutations (i.e. the mutant genes product is overactive) and inherited in an autosomal dominant manner with incomplete penetrance. Among 36 identified familial carriers of these mutant genes, 4 had no history of IMF, 3 had developed a solitary IMF, 29 had developed multiple tumors (no viscera involvement) or multiple tumors (with viscera involvement) IMF, and 2 had died. Most of these individuals were diagnosed with IMF in their infancy or early childhood. Subsequent studies have found that up to 70% of individuals with IMF and no family history of the disease also carry mutations in one of their two PDGFRB genes in the cells of their tumor tissues. These mutations are somatic mutations (i.e. non-inherited mutations developing only after conception) that are identical or similar to those seen in familial cases. The familial and non-familial mutated PDGFRB genes produce highly overactive platelet-derived growth factor receptor beta (i.e. | Infantile myofibromatosis (IMF) is a rare tumor found in 1 in 150,000 to 1 in 400,000 live births. It is nonetheless the most common tumor derived from fibrous connective tissue that occurs primarily in infants and young children. IMF tumors are benign in the sense that they do not metastasize to distant tissues although when occurring in the viscera, i.e. internal organs, carry guarded to poor prognoses and can be life-threatening, particularly in newborns and young infants.IMF tumors occur in three clinical patterns: 1) solitary IMF tumors (also called myofibromas) which often regress spontaneously and rarely cause serious issues; 2) multiple tumors (no viscera involvement) which consists of numerous (i.e. dozens to >100) IMF lesions most of which are located in the skin, subcutaneous tissues, and non-visceral but not visceral organs, may regress spontaneously, and rarely cause serious issues; and 3) multiple tumors (with viscera involvement) (also called generalized myofibromatosis) which rarely regress spontaneously and consist of numerous IMF lesions in non-visceral tissues plus one or more visceral tumors that may be life-threatening.A minority of infantile myofibromatosis tumors present in individuals with a strong family history of the disease. These familial cases are associated with mutations in either the PDGFRB or NOTCH3 gene. However, most IMF cases have no family history of the disease but nonetheless have PDGFRB gene mutations in their tumor cells; these mutations are similar to those occurring in the familial PDGFRB gene mutations. Regardless of these genetic variations, all IMF tumors consist of bland-appearing, benign (i.e. non-malignant) myofibroblasts, i.e. | 11
|
The Institute seeks to improve medical treatment of Minamata disease patients and conducts research on mercury compounds and their impact on organisms as well as potential detoxification mechanisms. In April, 2008 the Institute invented a method for absorbing gaseous mercury in order to prevent air pollution and enable recycling of the metal. Environmental protection
The movement for redress by Minamata victims and activists and the national outrage their movement elicited played a central role in the rise of environmental protection in Japan. The 1970 session of the Japanese Diet became remembered as the "Pollution Diet", as the Japanese government took action under rising pressure from the Minamata disease movement as well as other major environmental catastrophes such as Yokkaichi asthma and itai-itai disease. Fourteen new environmental laws were passed in a single session, giving Japan what at the time were the most stringent environmental protection laws in the world. These new laws included a Water Pollution Act and nationwide regulations of toxic discharges. The "polluter pays" principle was introduced. A national Environmental Agency, which later developed into the Ministry of Environment, was founded in 1971. National governmental expenditures on environmental issues almost doubled between 1970 and 1975 and tripled at the local government level. Democratizing effects
According to historian Timothy S. George, the environmental protests that surrounded the disease appeared to aid in the democratization of Japan. When the first cases were reported and subsequently suppressed, the rights of the victims were not recognised, and they were given no compensation. | creatine kinase
Anti-Jo-1 antibody testing
Electromyography
Muscle biopsy
Pulmonary function testing
Lung biopsy
Imaging such as High Resolution computed tomography In certain situations, testing of other antibodies, specific imaging (MRI, thoracic high resolution computed tomography), and swallowing evaluation may be needed. Treatment
Unfortunately, treatment for the anti-synthetase syndrome is limited, and usually involves immunosuppressive drugs such as glucocorticoids. For patients with pulmonary involvement, the most serious complication of this syndrome is pulmonary fibrosis and subsequent pulmonary hypertension.Additional treatment with azathioprine and/or methotrexate may be required in advanced cases. Prognosis
Prognosis is largely determined by the extent of pulmonary damage. References
== External links == | 0-1
|
Cerebral palsy (CP) is a group of movement disorders that appear in early childhood. Signs and symptoms vary among people and over time, but include poor coordination, stiff muscles, weak muscles, and tremors. There may be problems with sensation, vision, hearing, and speaking. Often, babies with cerebral palsy do not roll over, sit, crawl or walk as early as other children of their age. Other symptoms include seizures and problems with thinking or reasoning, which each occur in about one-third of people with CP. While symptoms may get more noticeable over the first few years of life, underlying problems do not worsen over time.Cerebral palsy is caused by abnormal development or damage to the parts of the brain that control movement, balance, and posture. Most often, the problems occur during pregnancy, but they may also occur during childbirth or shortly after birth. Often, the cause is unknown. Risk factors include preterm birth, being a twin, certain infections during pregnancy, such as toxoplasmosis or rubella, exposure to methylmercury during pregnancy, a difficult delivery, and head trauma during the first few years of life, among others. About 2% of cases are believed to be due to an inherited genetic cause. A number of sub-types are classified, based on the specific problems present. For example, those with stiff muscles have spastic cerebral palsy, those with poor coordination in locomotion have ataxic cerebral palsy, and those with writhing movements have dyskinetic cerebral palsy. Diagnosis is based on the childs development over time. | It is also considered reasonable to treat at-risk persons with vitamin D supplementation without checking the level of 25(OH)D in the serum, as vitamin D toxicity has only been rarely reported to occur.Levels of 25(OH)D that are consistently above 200 nanograms per milliliter (ng/mL) (or 500 nanomoles per liter, nmol/L) are potentially toxic. Vitamin D toxicity usually results from taking supplements in excess. Hypercalcemia is often the cause of symptoms, and levels of 25(OH)D above 150 ng/mL (375 nmol/L) are usually found, although in some cases 25(OH)D levels may appear to be normal. Periodic measurement of serum calcium in individuals receiving large doses of vitamin D is recommended. Screening
The official recommendation from the United States Preventive Services Task Force is that for persons that do not fall within an at-risk population and are asymptomatic, there is not enough evidence to prove that there is any benefit in screening for vitamin D deficiency. Treatment
UVB exposure
Vitamin-D overdose is impossible from UV exposure: the skin reaches an equilibrium where the vitamin degrades as fast as it is created. Sun tanning
Light therapy
Exposure to photons (light) at specific wavelengths of narrowband UVB enables the body to produce vitamin D to treat vitamin D deficiency. Supplement
In the United States and Canada as of 2016, the amount of vitamin D recommended is 400 IU per day for children, 600 IU per day for adults, and 800 IU per day for people over age 70. | 0-1
|
Mitral stenosis is a valvular heart disease characterized by the narrowing of the opening of the mitral valve of the heart. It is almost always caused by rheumatic valvular heart disease. Normally, the mitral valve is about 5 cm2 during diastole. Any decrease in area below 2 cm2 causes mitral stenosis. Early diagnosis of mitral stenosis in pregnancy is very important as the heart cannot tolerate increased cardiac output demand as in the case of exercise and pregnancy. Atrial fibrillation is a common complication of resulting left atrial enlargement, which can lead to systemic thromboembolic complications like stroke. Signs and symptoms
Signs and symptoms of mitral stenosis include the following:
Heart failure symptoms, such as dyspnea on exertion, orthopnea and paroxysmal nocturnal dyspnea (PND)
Palpitations
Chest pain
Hemoptysis
Thromboembolism in later stages when the left atrial volume is increased (i.e., dilation). The latter leads to increase risk of atrial fibrillation, which increases the risk of blood stasis (motionless). This increases the risk of coagulation. Ascites and edema and hepatomegaly (if right-side heart failure develops)Fatigue and weakness increase with exercise and pregnancy. Natural history
The natural history of mitral stenosis secondary to rheumatic fever (the most common cause) is an asymptomatic latent phase following the initial episode of rheumatic fever. This latent period lasts an average of 16.3 ± 5.2 years. | Fechtner syndrome is a variant of Alport syndrome characterized by leukocyte inclusions, macrothrombocytopenia, thrombocytopenia, nephritis, and sensorineural hearing loss. Some patients may also develop cataracts. References
== External links == | 0-1
|
These polymers or particles have a negligible or null systemic biological availability and they are designed to form stable complexes with Fe2+ and Fe3+ in the GIT and thus limiting the uptake of these ions and their long-term accumulation. Although this method has only a limited efficacy, unlike small-molecular chelators, such an approach has virtually no side effects in sub-chronic studies. Interestingly, the simultaneous chelation of Fe2+ and Fe3+ increases the treatment efficacy. Prognosis
Persons with symptomatic haemochromatosis have somewhat reduced life expectancy compared to the general population, mainly due to excess mortality from cirrhosis and liver cancer. Patients who were treated with phlebotomy lived longer than those who were not. Patients without liver disease or diabetes had similar survival rate to the general population. Epidemiology
Haemochromatosis is one of the most common heritable genetic conditions in people of Northern Europe, with a prevalence of 1:200. The disease has a variable penetration, and about one in 10 people of this demographic carry a mutation in one of the genes regulating iron metabolism. In the U.S., the frequency of the C282Y and H63D mutations is 5.4% and 13.5%, respectively. Whereas, the worldwide frequency of the C282Y and H63D mutations is about 1.9% and 8.1%, respectively, so mutation in H63D allele are more than C282Y allele. The prevalence of mutations in iron-metabolism genes varies in different populations. | The amount of iron in the sample is then quantified and compared to normal, and evidence of liver damage, especially cirrhosis, is measured microscopically. Formerly, this was the only way to confirm a diagnosis of haemochromatosis, but measures of transferrin and ferritin along with a history are considered adequate in determining the presence of the malady. Risks of biopsy include bruising, bleeding, and infection. Now, when a history and measures of transferrin or ferritin point to haemochromatosis, whether a liver biopsy is still necessary to quantify the amount of accumulated iron is debatable. MRI
MRI-based testing is a noninvasive and accurate alternative to measure liver iron concentrations. Other imaging
Clinically, the disease may be silent, but characteristic radiological features may point to the diagnosis. The increased iron stores in the organs involved, especially in the liver and pancreas, result in characteristic findings on unenhanced CT and a decreased signal intensity in MRI scans. Haemochromatosis arthropathy includes degenerative osteoarthritis and chondrocalcinosis. The distribution of the arthropathy is distinctive, but not unique, frequently affecting the second and third metacarpophalangeal joints of the hand. The arthropathy can, therefore, be an early clue as to the diagnosis of haemochromatosis. Functional testing
Based on the history, a physician might consider specific tests to monitor organ dysfunction, such as an echocardiogram for heart failure, or blood glucose monitoring for patients with haemochromatosis diabetes. | 11
|
30 Day Results
The incidence of net adverse clinical events (9.2% vs. 12.1%) and major bleeding (4.9% vs. 8.3%) was significantly reduced by bivalirudin monotherapy versus unfractionated heparin (UFH) plus a GP IIb/IIIa inhibitor with similar rates of major adverse cardiovascular events (5.4 vs. 5.5%) at 30 days. A significant reduction in the rate of cardiac mortality in patients treated with bivalirudin monotherapy versus UFH plus a GP IIb/IIIa inhibitor was observed (1.8% vs. 2.9%) at 30 days. | The cause of vestibular migraines is currently unclear; however, one hypothesized cause is that the stimulation of the trigeminal nerve leads to nystagmus in individuals with migraines. Approximately 40% of all migraine patients will have an accompanying vestibular syndrome, such as vertigo, dizziness, or disruption of the balance system.Other suggested causes of vestibular migraines include the following: unilateral neuronal instability of the vestibular nerve, idiopathic asymmetric activation of the vestibular nuclei in the brainstem, and vasospasm of the blood vessels supplying the labyrinth or central vestibular pathways resulting in ischemia to these structures. Vestibular migraines are estimated to affect 1–3% of the general population and may affect 10% of people with migraine . Additionally, vestibular migraines tend to occur more often in women and rarely affect individuals after the sixth decade of life. Motion sickness
Motion sickness is common and is related to vestibular migraine. It is nausea and vomiting in response to motion and is typically worse if the journey is on a winding road or involves many stops and starts, or if the person is reading in a moving car. It is caused by a mismatch between visual input and vestibular sensation. For example, the person is reading a book that is stationary in relation to the body, but the vestibular system senses that the car, and thus the body, is moving. Alternobaric vertigo
Alternobaric vertigo is caused by a pressure difference between the middle ear cavities, usually due to blockage or partial blockage of one eustachian tube, usually when flying or diving underwater. | 0-1
|
Position
Another study observed 12 different positions of movements and their relative correlation with injuries occurred during those movements. The evidence shows that putting the arm in a neutral position relieves tension on all ligaments and tendons. Stretching
One article observed the influence of stretching techniques on preventive methods of shoulder injuries. Increased velocity of exercise increases injury, but beginning a fast-movement exercise with a slow stretch may cause muscle/tendon attachment to become more resistant to tearing. Muscle groups
When exercising, exercising the shoulder as a whole and not one or two muscle groups is also found to be imperative. When the shoulder muscle is exercised in all directions, such as external rotation, flexion, and extension, or vertical abduction, it is less likely to develop a tear of the tendon. Treatment
A rotator cuff tear can be treated operatively or non-operatively. No benefit is seen from early rather than delayed surgery, and many with partial tears and some with complete tears will respond to nonoperative management. Consequently, an individual may begin with nonsurgical management. However, early surgical treatment may be considered in significant (>1 cm – 1.5 cm) acute tears, or in young individuals with full-thickness tears who have a significant risk for the development of irreparable rotator cuff damage.Rotator-cuff surgery appears to result in similar benefits as nonoperative management. As a conservative approach has less complications and is less expensive it is recommended as initial treatment. Non-operative treatment
Those with pain but reasonably maintained function are suitable for nonoperative management. | The role of X-ray, MRI, and ultrasound, is adjunctive to clinical assessment and serves to confirm a diagnosis provisionally made by a thorough history and physical examination. Over-reliance on imaging may lead to overtreatment or distract from the true dysfunction causing symptoms. Symptoms
Symptoms may occur immediately after trauma (acute) or develop over time (chronic). Acute injury is less frequent than chronic disease, but may follow bouts of forcefully raising the arm against resistance, as occurs in weightlifting, for example. In addition, falling forcefully on the shoulder can cause acute symptoms. These traumatic tears predominantly affect the supraspinatus tendon or the rotator interval and symptoms include severe pain that radiates through the arm, and limited range of motion, specifically during abduction of the shoulder. Chronic tears occur among individuals who constantly participate in overhead activities, such as pitching or swimming, but can also develop from shoulder tendinitis or rotator cuff disease. Symptoms arising from chronic tears include sporadic worsening of pain, debilitation, and atrophy of the muscles, noticeable pain during rest, crackling sensations (crepitus) when moving the shoulder, and inability to move or lift the arm sufficiently, especially during abduction and flexion motions.Pain in the anterolateral aspect of the shoulder is not specific to the shoulder, and may arise from, and be referred from, the neck, heart or gut. | 11
|
The severity of the condition may depend on the timing of infection during pregnancy.Microcephaly is a feature common to several different genetic disorders arising from a deficiency in the cellular DNA damage response. Individuals with the following DNA damage response disorders exhibit microcephaly: Nijmegen breakage syndrome, ATR-Seckel syndrome, MCPH1-dependent primary microcephaly disorder, xeroderma pigmentosum complementation group A deficiency, Fanconi anemia, ligase 4 deficiency syndrome and Bloom syndrome. These findings suggest that a normal DNA damage response is critical during brain development, perhaps to protect against induction of apoptosis by DNA damage occurring in neurons. Treatment
There is no known cure for microcephaly. Treatment is symptomatic and supportive. Because some cases of microcephaly and its associated symptoms may be a result of amino acid deficiencies, treatment with amino acids in these cases has been shown to improve symptoms such as seizures and motor function delays. History
People with small heads were displayed as a public spectacle in ancient Rome.People with microcephaly were sometimes sold to freak shows in North America and Europe in the 19th and early 20th centuries, where they were known by the name "pinheads". Many of them were presented as different species (e.g., "monkey man") and described as being the missing link. Famous examples include Zip the Pinhead (although he may not have had microcephaly), Maximo and Bartola, and Schlitzie the Pinhead,. Zip the Pinhead and Schlitzie the Pinhead, also stars of the 1932 film Freaks, were cited as influences on the development of the long-running comic strip character Zippy the Pinhead, created by Bill Griffith. | Filgrastim, sold under the brand name Neupogen among others, is a medication used to treat low neutrophil count. Low neutrophil counts may occur with HIV/AIDS, following chemotherapy or radiation poisoning, or be of an unknown cause. It may also be used to increase white blood cells for gathering during leukapheresis. It is given either by injection into a vein or under the skin.Common side effects include fever, cough, chest pain, joint pain, vomiting, and hair loss. Severe side effects include splenic rupture and allergic reactions. It is unclear if use in pregnancy is safe for the baby. Filgrastim is a recombinant-DNA form of the naturally occurring granulocyte colony-stimulating factor (G-CSF). It works by stimulating the body to increase neutrophil production.Filgrastim was approved for medical use in the United States in 1991. It is on the World Health Organizations List of Essential Medicines. Filgrastim biosimilar medications are available. Medical uses
Filgrastim is used to treat neutropenia, stimulating the bone marrow to increase production of neutrophils. Causes of neutropenia include chemotherapy and bone marrow transplantation. Adverse effects
The most commonly observed adverse effect is mild bone pain after repeated administration, and local skin reactions at the site of injection. Other observed adverse effects include serious allergic reactions (including a rash over the whole body, shortness of breath, wheezing, dizziness, swelling around the mouth or eyes, fast pulse, and sweating), ruptured spleen (sometimes resulting in death), alveolar hemorrhage, acute respiratory distress syndrome, and hemoptysis. | 0-1
|
Therefore, many tracers that may reach tumors in other areas of the body easily would be unable to reach brain tumors until there was a disruption of the BBB by the tumor. Disruption of the BBB is well imaged via MRI or CT scan, and is therefore regarded as the main diagnostic indicator for malignant gliomas, meningiomas, and brain metastases.Swelling or obstruction of the passage of cerebrospinal fluid (CSF) from the brain may cause (early) signs of increased intracranial pressure which translates clinically into headaches, vomiting, or an altered state of consciousness, and in children changes to the diameter of the skull and bulging of the fontanelles. More complex symptoms such as endocrine dysfunctions should alarm doctors not to exclude brain tumors.A bilateral temporal visual field defect (due to compression of the optic chiasm) or dilation of the pupil, and the occurrence of either slowly evolving or the sudden onset of focal neurologic symptoms, such as cognitive and behavioral impairment (including impaired judgment, memory loss, lack of recognition, spatial orientation disorders), personality or emotional changes, hemiparesis, hypoesthesia, aphasia, ataxia, visual field impairment, impaired sense of smell, impaired hearing, facial paralysis, double vision, or more severe symptoms such as tremors, paralysis on one side of the body hemiplegia, or (epileptic) seizures in a patient with a negative history for epilepsy, should raise the possibility of a brain tumor. Imaging
Medical imaging plays a central role in the diagnosis of brain tumors. | It is divided into the midbrain, pons, and medulla oblongata. Spinal cord
The spinal cord is considered a part of the central nervous system. It is made up of the same cells as the brain: neurons and glial cells. Diagnosis
Although there is no specific or singular symptom or sign, the presence of a combination of symptoms and the lack of corresponding indications of other causes can be an indicator for investigation towards the possibility of a brain tumor. Brain tumors have similar characteristics and obstacles when it comes to diagnosis and therapy with tumors located elsewhere in the body. However, they create specific issues that follow closely to the properties of the organ they are in.The diagnosis will often start by taking a medical history noting medical antecedents, and current symptoms. Clinical and laboratory investigations will serve to exclude infections as the cause of the symptoms. Examinations in this stage may include the eyes, otolaryngological (or ENT) and electrophysiological exams. The use of electroencephalography (EEG) often plays a role in the diagnosis of brain tumors.Brain tumors, when compared to tumors in other areas of the body, pose a challenge for diagnosis. Commonly, radioactive tracers are uptaken in large volumes in tumors due to the high activity of tumor cells, allowing for radioactive imaging of the tumor. However, most of the brain is separated from the blood by the blood-brain barrier (BBB), a membrane that exerts a strict control over what substances are allowed to pass into the brain. | 11
|
In Knuths up-arrow notation, 2 ↑↑ 2 = 2 ↑↑↑ 2 = 4, and so forth, for any number of up arrows. By consequence, four is the only square one more than a prime number, specifically three. The sum of the first four prime numbers two + three + five + seven is the only sum of four consecutive prime numbers that yields an odd prime number, seventeen, which is the fourth super-prime. Four lies between the first proper pair of twin primes, three and five, which are the first two Fermat primes, like seventeen, which is the third. | The complex numbers
C
{\displaystyle \mathbb {C} }
share all four multiplicative algebraic properties of the reals
R
{\displaystyle \mathbb {R} }
, without being ordered. The quaternions loose a further commutative algebraic property, while holding associative, alternative, and power-associative properties. The octonions are alternative and power-associative, while the sedenions are only power-associative. The sedenions and all further extensions of these four normed division algebras are solely power-associative with non-trivial zero divisors, which makes them non-division algebras. | 11
|
Cognitive impairment may also range from mild to so severe that the person is nonverbal and dependent on others for basic care. Thought and reflexes are slower. Cause
Around the world, the most common cause of congenital iodine deficiency syndrome (endemic cretinism) is dietary iodine deficiency. Iodine is an essential trace element, necessary for the synthesis of thyroid hormones. Iodine deficiency is the most common preventable cause of neonatal and childhood brain damage worldwide. Although iodine is found in many foods, it is not universally present in all soils in adequate amounts. Most iodine, in iodide form, is in the oceans, where the iodide ions are reduced to elemental iodine, which then enters the atmosphere and falls to earth in rain, introducing iodine to soils. Soil deficient in iodine is most common inland, in mountainous areas, and in areas of frequent flooding. It can also occur in coastal regions, where iodine might have been removed from the soil by glaciation, as well as leaching by snow, water and heavy rainfall. Plants and animals grown in iodine-deficient soils are correspondingly deficient. Populations living in those areas without outside food sources are most at risk of iodine deficiency diseases. Diagnosis
Differential diagnosis
Dwarfism may also be caused by malnutrition or other hormonal deficiencies, such as insufficient growth hormone secretion, hypopituitarism, decreased secretion of growth hormone-releasing hormone, deficient growth hormone receptor activity and downstream causes, such as insulin-like growth factor 1 (IGF-1) deficiency. Prevention
There are public health campaigns in many countries which involve iodine administration. | The most common derivation provided in English dictionaries is from the Alpine French dialect pronunciation of the word Chrétien ("(a) Christian"), which was a greeting there. According to the Oxford English Dictionary, the translation of the French term into "human creature" implies that the label "Christian" is a reminder of the humanity of the affected, in contrast to brute beasts. Other sources suggest that Christian describes the persons "Christ-like" inability to sin, stemming, in such cases, from an incapacity to distinguish right from wrong.Other speculative etymologies have been offered:
From creta, Latin for chalk, because of the pallor of those affected. From cretira, Grison-Romanche creature, from Latin creatus. From cretine, French for alluvium (soil deposited by flowing water), an allusion to the conditions suspected origin in inadequate soil. See also
Moron (psychology)
References
External links
Media related to Congenital iodine deficiency syndrome at Wikimedia Commons | 11
|
Airway clearance
Coughing, and huffing are important ways of removing mucus as sputum in many conditions such as cystic fibrosis, and chronic bronchitis. Pathophysiology
A cough is a protective reflex in healthy individuals which is influenced by psychological factors. The cough reflex is initiated by stimulation of two different classes of afferent nerves, namely the myelinated rapidly adapting receptors, and nonmyelinated C-fibers with endings in the lung. Diagnostic approach
The type of cough may help in the diagnosis. For instance, an inspiratory "whooping" sound on coughing almost doubles the likelihood that the illness is pertussis. Blood may occur in small amounts with severe cough of many causes, but larger amounts suggests bronchitis, bronchiectasis, tuberculosis, or primary lung cancer.Further workup may include labs, x-rays, and spirometry. Classification
A cough can be classified by its duration, character, quality, and timing. The duration can be either acute (of sudden onset) if it is present less than three weeks, subacute if it is present between three or eight weeks, and chronic when lasting longer than eight weeks. A cough can be non-productive (dry) or productive (when phlegm is produced that may be coughed up as sputum). It may occur only at night (then called nocturnal cough), during both night and day, or just during the day.A number of characteristic coughs exist. While these have not been found to be diagnostically useful in adults, they are of use in children. A barky cough is part of the common presentation of croup. A staccato cough has been classically described with neonatal chlamydial pneumonia. | Epidemiology
While isosporiasis occurs throughout the world, it is more common in tropical and subtropical areas. Cystoisospora infections are more common in individuals with compromised immune systems, such as HIV or leukemia. See also
List of parasites (human)
References
== External links == | 0-1
|
The prolonged sedation from lorazepam may, however, be an acceptable trade-off for its reliable duration of effects, particularly if the person needs to be transferred to another facility. Although lorazepam is not necessarily better than diazepam at initially terminating seizures, lorazepam is, nevertheless, replacing diazepam as the intravenous agent of choice in status epilepticus.Lorazepam serum levels are proportional to the dose administered. Giving 2 mg oral lorazepam will result in a peak total serum level of around 20 ng/mL around two hours later, half of which is lorazepam, half its inactive metabolite, lorazepam-glucuronide. A similar lorazepam dose given intravenously will result in an earlier and higher peak serum level, with a higher relative proportion of unmetabolised (active) lorazepam. On regular administration, maximum serum levels are attained after three days. Longer-term use, up to six months, does not result in further accumulation. On discontinuation, lorazepam serum levels become negligible after three days and undetectable after about a week. Lorazepam is metabolized in the liver by conjugation into inactive lorazepam-glucuronide. This metabolism does not involve liver oxidation, so is relatively unaffected by reduced liver function. Lorazepam-glucuronide is more water-soluble than its precursor, so gets more widely distributed in the body, leading to a longer half-life than lorazepam. Lorazepam-glucuronide is eventually excreted by the kidneys, and, because of its tissue accumulation, it remains detectable, particularly in the urine, for substantially longer than lorazepam. Pharmacodynamics
Relative to other benzodiazepines, lorazepam is thought to have high affinity for GABA receptors, which may also explain its marked amnesic effects. | In the United Kingdom, it is a Class C, Schedule 4 Controlled Drug under the Misuse of Drugs Regulations 2001. Pricing
In 2000, the U.S. drug company Mylan agreed to pay $147 million to settle accusations by the FTC that they had raised the price of generic lorazepam by 2600% and generic clorazepate by 3200% in 1998 after having obtained exclusive licensing agreements for certain ingredients. References
External links
inchem.org – Lorazepam data sheet
benzo.org.uk – Ashton H. Benzodiazepines: How They Work And How to Withdraw. August 2002 (The "Ashton Manual"). "Lorazepam". Drug Information Portal. U.S. National Library of Medicine. | 11
|
The sacral vertebrae are fused with the lumbar vertebrae, and some thoracic and caudal vertebrae, to form a single structure, the synsacrum, which is thus of greater relative length than the sacrum of mammals. In living birds, the remaining caudal vertebrae are fused into a further bone, the pygostyle, for attachment of the tail feathers.Aside from the tail, the number of vertebrae in mammals is generally fairly constant. There are almost always seven cervical vertebrae (sloths and manatees are among the few exceptions), followed by around twenty or so further vertebrae, divided between the thoracic and lumbar forms, depending on the number of ribs. There are generally three to five vertebrae with the sacrum, and anything up to fifty caudal vertebrae. Dinosaurs
The vertebral column in dinosaurs consists of the cervical (neck), dorsal (back), sacral (hips), and caudal (tail) vertebrae. Saurischian dinosaur vertebrae sometimes possess features known as pleurocoels, which are hollow depressions on the lateral portions of the vertebrae, perforated to create an entrance into the air chambers within the vertebrae, which served to decrease the weight of these bones without sacrificing strength. These pleurocoels were filled with air sacs, which would have further decreased weight. In sauropod dinosaurs, the largest known land vertebrates, pleurocoels and air sacs may have reduced the animals weight by over a ton in some instances, a handy evolutionary adaption in animals that grew to over 30 metres in length. In many hadrosaur and theropod dinosaurs, the caudal vertebrae were reinforced by ossified tendons. | The vertebral column, also known as the backbone or spine, is part of the axial skeleton. The vertebral column is the defining characteristic of a vertebrate in which the notochord (a flexible rod of uniform composition) found in all chordates has been replaced by a segmented series of bone: vertebrae separated by intervertebral discs. Individual vertebrae are named according to their region and position, and can be used as anatomical landmarks in order to guide procedures such as lumbar punctures. The vertebral column houses the spinal canal, a cavity that encloses and protects the spinal cord. There are about 50,000 species of animals that have a vertebral column. The human vertebral column is one of the most-studied examples. Many different diseases in humans can affect the spine, with spina bifida and scoliosis being recognisable examples. The general structure of human vertebrae is fairly typical of that found in mammals, reptiles, and birds. The shape of the vertebral body does, however, vary somewhat between different groups. Structure
The number of vertebrae in a region can vary but overall the number remains the same. In a human vertebral column, there are normally 33 vertebrae. The upper 24 pre-sacral vertebrae are articulating and separated from each other by intervertebral discs, and the lower nine are fused in adults, five in the sacrum and four in the coccyx, or tailbone. The articulating vertebrae are named according to their region of the spine. There are 7 cervical vertebrae, 12 thoracic vertebrae and 5 lumbar vertebrae. | 11
|
Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individuals better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment– visual impairment may cause the individual difficulties with normal daily tasks including reading and walking. Low vision is a functional definition of visual impairment that is chronic, uncorrectable with treatment or correctable lenses, and impacts daily living. As such low vision can be used as a disability metric and varies based on an individuals experience, environmental demands, accommodations, and access to services. The American Academy of Ophthalmology defines visual impairment as the best-corrected visual acuity of less than 20/40 in the better eye, and the World Health Organization defines it as a presenting acuity of less than 6/12 in the better eye. The term blindness is used for complete or nearly complete vision loss. In addition to the various permanent conditions, fleeting temporary vision impairment, amaurosis fugax, may occur, and may indicate serious medical problems. The most common causes of visual impairment globally are uncorrected refractive errors (43%), cataracts (33%), and glaucoma (2%). Refractive errors include near-sightedness, far-sightedness, presbyopia, and astigmatism. Cataracts are the most common cause of blindness. Other disorders that may cause visual problems include age-related macular degeneration, diabetic retinopathy, corneal clouding, childhood blindness, and a number of infections. Visual impairment can also be caused by problems in the brain due to stroke, premature birth, or trauma, among others. These cases are known as cortical visual impairment. | Isolated cases of gallstone formation have been associated with use of lanreotide, particularly over long periods of time. Pharmacology
Lanreotide is a synthetic analogue of somatostatin, a naturally occurring inhibitory hormone which blocks the release of several other hormones, including growth hormone, thyroid-stimulating hormone (TSH), insulin and glucagon. Lanreotide binds to the same receptors as somatostatin, although with higher affinity to peripheral receptors, and has similar activity. However, while somatostatin is quickly broken down in the body (within minutes), lanreotide has a much longer half-life, and produces far more prolonged effects. Formulations
Lanreotide is available in two formulations: a sustained release formulation (sold under the trade name Somatuline LA), which is injected intramuscularly every ten or fourteen days, and an extended release formulation (UK trade name Somatuline Autogel, or Somatuline Depot in the US), which is administered subcutaneously once a month. Self-assembling properties
Lanreotide has been shown to spontaneously self-assemble into monodisperse nanotubes of 24.4 nm diameter and has been thereafter used as a fruitful and versatile model system in several biophysical studies. References
External links
"Lanreotide". Drug Information Portal. U.S. National Library of Medicine. | 0-1
|
It could affect patients who take some prescription medicines that are able to cross the blood-brain barrier and cause abnormal thirst reception - in this scenario the central pontine myelinolysis is caused by polydipsia leading to low blood sodium levels (hyponatremia).In schizophrenic patients with psychogenic polydipsia, inadequate thirst reception leads to excessive water intake, severely diluting serum sodium. With this excessive thirst combined with psychotic symptoms, brain damage such as central pontine myelinolysis may result from hyperosmolarity caused by excess intake of fluids, (primary polydipsia) although this is difficult to determine because such patients are often institutionalised and have a long history of mental health conditions.It has been observed following hematopoietic stem cell transplantation.Central pontine myelinolysis may also occur in patients prone to hyponatremia affected by:
Severe liver disease (e.g., cirrhosis)
Liver transplant
Alcoholism
Hypokalemia
People with serum sodium <105 mEq/L
Severe burns
Malnutrition
Anorexia nervosa
Severe electrolyte disorders
HIV/AIDS
hyperemesis gravidarum
Hyponatremia due to peritoneal dialysis
Wernicke encephalopathy
Pathophysiology
The currently accepted theory states that the brain cells adjust their osmolarities by changing levels of certain osmolytes like inositol, betaine, and glutamine in response to varying serum osmolality. In the context of chronic low plasma sodium (hyponatremia), the brain compensates by decreasing the levels of these osmolytes within the cells, so that they can remain relatively isotonic with their surroundings and not absorb too much fluid. The reverse is true in hypernatremia, in which the cells increase their intracellular osmolytes so as not to lose too much fluid to the extracellular space.With correction of the hyponatremia with intravenous fluids, the extracellular tonicity increases, followed by an increase in intracellular tonicity. | Berotralstat, sold under the brand name Orladeyo, is a medication used to prevent attacks of hereditary angioedema (HAE) in people aged twelve years and older.The most common side effects include abdominal pain, vomiting, diarrhea, back pain, and heartburn.Berotralstat was approved for medical use in the United States in December 2020, and in the European Union in April 2021. History
Berotralstat was approved based on evidence from one clinical trial (Trial 1 /NCT03485911) of 120 participants with hereditary angioedema. The trial was conducted at 40 sites in the United States, the European Union, and Canada. Trial investigators evaluated participants 12 years and older with hereditary angioedema for eight weeks to determine the number of attacks for each participant. The trial enrolled only participants who had at least two attacks during the eight-week period. Participants were assigned to receive one of two doses of berotralstat or placebo once every day for 24 weeks. Neither the participants nor the investigators knew which treatment was being given until after the trial was completed. All participants could use other medications for treatment of attacks. References
External links
"Berotralstat". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT03485911 for "Efficacy and Safety Study of BCX7353 as an Oral Treatment for the Prevention of Attacks in HAE (APeX-2)" at ClinicalTrials.gov | 0-1
|
A focal lung pneumatosis, is an enclosed pocket of air or gas in the lung and includes blebs, bullae, pulmonary cysts, and lung cavities. Blebs and bullae can be classified by their wall thickness. A bleb has a wall thickness of less than 1 mm. By radiology definition, it is up to 1 cm in total size. By pathology definition, it originates in the pleurae (rather than in the lung parenchyma). A bulla has a wall thickness of less than 1 mm. By radiology definition, it has a total size of greater than 1 cm. By pathology definition, it originates in the lung parenchyma (rather than in the pleurae). A lung cyst has a wall thickness of up to 4 mm. A minimum wall thickness of 1 mm has been suggested, but thin-walled pockets may be included in the definition as well. A cavity has a wall thickness of more than 4 mm.The terms above, when referring to sites other than the lungs, often imply fluid content. Lung cysts are seen in about 8% of the general population, with an increased prevalence in older people, and are not associated with emphysema. They may be part of the aging changes of the lungs, and cause a slight decrease in their diffusing capacity. The presence of multiple pulmonary cysts may indicate a need to evaluate the possibility of bullous or cystic lung diseases. Cavitation indicates workup for serious infection or lung cancer. | Although infection is not the reason or cause of chronic bronchitis, it is seen to aid in sustaining the bronchitis. Diagnosis
A physical examination will often reveal decreased intensity of breath sounds, wheezing, rhonchi, and prolonged expiration. During examination for physicians rely on history and the presence of persistent or acute onset of cough, followed by a URTI with no traces of pneumonia. Acute bronchitis is typically a clinical diagnosis that relies on patients history and exam, and should be suspected in patients with an acute onset of cough, which often follows a URTI without traces of pneumonia.Although there is no universally-accepted clinical definition for acute bronchitis, there is a proposed set of practical criteria (Macfarlane, 2001) that include:
An acute illness of less than three weeks. Cough as the predominant symptom. At least one other lower respiratory tract symptom, such as sputum production, wheezing, chest pain. No alternative explanation for the symptoms.A variety of tests may be performed in people presenting with cough and shortness of breath:
A chest X-ray is useful to exclude pneumonia which is more common in those with a fever, fast heart rate, fast respiratory rate, or who are old. A sputum sample showing neutrophil granulocytes (inflammatory white blood cells) and culture showing that has pathogenic microorganisms such as Streptococcus species. A blood test would indicate inflammation (as indicated by a raised white blood cell count and elevated C-reactive protein).Decreased breath sounds, crackles, wheezing, and rhonchi that clears with coughs may be heard in the chest. | 0-1
|
Bepotastine (Talion, Bepreve) is a 2nd generation antihistamine. It was approved in Japan for use in the treatment of allergic rhinitis and urticaria/pruritus in July 2000 and January 2002, respectively. It is currently marketed in the United States as an eye drop under the brand-name Bepreve, by ISTA Pharmaceuticals, a subsidiary of Bausch + Lomb. Pharmacology
Bepotastine is available as an ophthalmic solution and oral tablet. It is a direct H1-receptor antagonist that inhibits the release of histamine from mast cells. The ophthalmic formulation has shown minimal systemic absorption, between 1 and 1.5% in healthy adults. Common side effects are eye irritation, headache, unpleasant taste, and nasopharyngitis. The main route of elimination is urinary excretion, 75-90% excreted unchanged. Marketing history
It is marketed in Japan by Tanabe Seiyaku under the brand name Talion. Talion was co-developed by Tanabe Seiyaku and Ube Industries, the latter of which discovered bepotastine. In 2001, Tanabe Seiyaku granted Senju, now owned by Allergan, exclusive worldwide rights, with the exception of certain Asian countries, to develop, manufacture and market bepotastine for ophthalmic use. Senju, in turn, has granted the United States rights for the ophthalmic preparation to ISTA Pharmaceuticals. Sales and patents
In 2011, ISTA pharmaceuticals experienced a 2.4% increase in net revenues from 2010, which was driven by the sales of Bepreve. Their net revenue for 2011 was $160.3 million. ISTA Pharmaceuticals was acquired by Bausch & Lomb in March 2012 for $500 million. Bausch & Lomb hold the patent for bepotastine besilate (https://www.accessdata.fda.gov/scripts/cder/ob/docs/temptn.cfm. | On November 26, 2014, Bausch & Lomb sued Micro Labs USA for patent infringement. Bausch & Lomb was recently bought out by Valeant Pharmaceuticals in May 2013 for $8.57 billion, Valeants largest acquisition to date, causing the companys stock to rise 25% when the deal was announced. Clinical trials
A Phase III clinical trial was carried out in 2010 to evaluate the effectiveness of bepotastine besilate ophthalmic solutions 1.0% and 1.5%. These solutions were compared to a placebo and evaluated for their ability to reduce ocular itchiness. The study was carried out with 130 individuals and evaluated after 15 minutes, 8 hours, or 16 hours. There was a reduction in itchiness at all-time points for both ophthalmic solutions. The study concluded that bepotastine besilate ophthalmic formulations reduced ocular itchiness for at least 8 hours after dosing compared to placebo. Phase I and II trials were carried out in Japan. Studies have been performed in animals and bepotastine besilate was not found to be teratogenic in rats during fetal development, even at 3,300 times more that typical use in humans. Evidence of infertility was seen in rats at 33,000 times the typical ocular dose in humans. The safety and efficacy has not been established in patients under 2 years of age and has been extrapolated from adults for patients under 10 years of age. == References == | 11
|
Instead, the emphasis tends to be on the patients understanding and a variety of psychotherapeutic techniques. In some cases, the onset of conversion disorder correlates to a traumatic or stressful event. There are also certain populations that are considered at risk for conversion disorder, including people with a medical illness or condition, people with personality disorders or dissociative identity disorder. However, no biomarkers have yet been found to support the idea that conversion disorder is caused by a psychiatric condition. There has been much recent interest in using functional neuroimaging to study conversion. As researchers identify the mechanisms which underlie conversion symptoms, it is hoped they will enable the development of a neuropsychological model. A number of such studies have been performed, including some which suggest the blood-flow in patients brains may be abnormal while they are unwell. However, the studies have all been too small to be confident of the generalisability of their findings, so no neuropsychological model has been clearly established. An evolutionary psychology explanation for conversion disorder is that the symptoms may have been evolutionarily advantageous during warfare. A non-combatant with these symptoms signals non-verbally, possibly to someone speaking a different language, that she or he is not dangerous as a combatant and also may be carrying some form of dangerous infectious disease. | Conversion disorder (CD), or functional neurologic symptom disorder, is a diagnostic category used in some psychiatric classification systems. It is sometimes applied to patients who present with neurological symptoms, such as numbness, blindness, paralysis, or fits, which are not consistent with a well-established organic cause, which cause significant distress, and can be traced back to a psychological trigger. It is thought that these symptoms arise in response to stressful situations affecting a patients mental health or an ongoing mental health condition such as depression. Conversion disorder was retained in DSM-5, but given the subtitle functional neurological symptom disorder. The new criteria cover the same range of symptoms, but remove the requirements for a psychological stressor to be present and for feigning to be disproved. ICD-10 classifies conversion disorder as a dissociative disorder while DSM-IV classifies it as a somatoform disorder. Signs and symptoms
Conversion disorder begins with some stressor, trauma, or psychological distress. Usually the physical symptoms of the syndrome affect the senses or movement. Common symptoms include blindness, partial or total paralysis, inability to speak, deafness, numbness, difficulty swallowing, incontinence, balance problems, seizures, tremors, and difficulty walking. The symptom of feeling unable to breathe, but where the lips are not turning blue, can indicate conversion disorder or sleep paralysis. Sleep paralysis and narcolepsy can be ruled out with sleep tests. These symptoms are attributed to conversion disorder when a medical explanation for the conditions cannot be found. Symptoms of conversion disorder usually occur suddenly. | 11
|
The supplier, Greenyard Frozen UK, reported to the UKs Food Standards Agency that the factory in which the food was processed had been shut down by the Hungarian Food Chain Safety Office, after which the European Food Safety Authority and the European Centre for Disease Prevention and Control issued updates stating that at least five EU member states (UK, Austria, Denmark, Finland and Sweden) were affected. Between June 2015 and July 2018, 9 people had reportedly died as a result of listeriosis, of a total of 47 confirmed cases.In an update on the EFSA website, it was stated that the contamination had supposedly been present since at least 2015, and as a result the Hungarian Food Chain Safety Office had prohibited the marketing of all affected frozen vegetables and frozen vegetable packs produced by the plant in Baja between August 2016 and June 2018. This followed a previous study that found the majority of L. monocytogenes isolates had been found in a 2017 sample of various frozen vegetables, with a minority found in a 2016 sample and a small number found in a 2018 sample. The study suggested that the strain identified (L. monocytogenes serogroup IVb, multi-locus sequence type 6 (ST6)) was likely persisting through standard cleaning operations and disinfection procedures, and that since common production lines were in operation, cross-contamination was an additional concern. 2017–18 South African listeriosis outbreak
In early December 2017 an outbreak of listeriosis was reported by the South African Department of Health. | There is some evidence that small subpopulations of clinical isolates are more capable of colonizing the heart throughout the course of infection, but cardiac manifestations are usually sporadic and may rely on a combination of bacterial factors and host predispositions, as they do with other strains of cardiotropic bacteria. Recent outbreaks
According to the Centers for Disease Control and Prevention (CDC) there are about 1,600 cases of listeriosis annually in the United States. Compared to 1996–1998, the incidence of listeriosis had declined by about 38% by 2003. However, illnesses and deaths continue to occur. On average from 1998 to 2008, 2.4 outbreaks per year were reported to the CDC.Some notable ones are listed below. 2002 United States outbreak
A large outbreak occurred in 2002, when 54 illnesses, 8 deaths, and 3 fetal deaths in 9 states were found to be associated with consumption of contaminated turkey deli meat. 2008 Canadian listeriosis outbreak
An outbreak of listeriosis in Canada linked to a Maple Leaf Foods plant in Toronto, Ontario killed 22 people. 2011 United States listeriosis outbreak
On September 14, 2011, the U.S. Food and Drug Administration warned consumers not to eat cantaloupes shipped by Jensen Farms from Granada, Colorado due to a potential link to a multi-state outbreak of listeriosis. | 11
|
Other common esters of estradiol in use include estradiol cypionate, estradiol enantate, and estradiol acetate, the former two of which are C17β esters of estradiol similarly to estradiol valerate and the latter of which is the C3 acetate ester of estradiol.The experimental log octanol/water partition coefficient (log P) of estradiol valerate is 5.6. History
Estradiol valerate was patented by Ciba in 1940 and 1941, with a priority date of 1936. It was synthesized and studied, along with a variety of other estradiol esters, by Karl Junkmann of Schering AG in 1953. The medication was first introduced for medical use via intramuscular injection in 1954 by Schering in Europe under the brand name Progynon Depot and by Squibb in the United States under the brand name Delestrogen. In 1966, oral estradiol valerate was introduced by Schering for medical use in Europe under the brand name Progynova. A report of its metabolism was published in 1967. Esterification of estradiol, as in estradiol valerate, has been claimed to improve its metabolic stability with oral administration. In 1968, micronized preparations of oral estradiol valerate were first introduced under the brand names Progynova 21 and Progynova 21 mite. Along with estradiol benzoate (1933) and estradiol cypionate (1952), estradiol valerate is one of the most widely used esters of estradiol. Society and culture
Generic names
Estradiol valerate is the generic name of the drug and its INN, USAN, BANM, and JAN, while oestradiol valerate was formerly its BANM. | Yersinia is a genus of bacteria in the family Yersiniaceae. Yersinia species are Gram-negative, coccobacilli bacteria, a few micrometers long and fractions of a micrometer in diameter, and are facultative anaerobes. Some members of Yersinia are pathogenic in humans; in particular, Y. pestis is the causative agent of the plague. Rodents are the natural reservoirs of Yersinia; less frequently, other mammals serve as the host. Infection may occur either through blood (in the case of Y. pestis) or in an alimentary fashion, occasionally via consumption of food products (especially vegetables, milk-derived products, and meat) contaminated with infected urine or feces. Speculations exist as to whether or not certain Yersinia can also be spread by protozoonotic mechanisms, since Yersinia species are known to be facultative intracellular parasites; studies and discussions of the possibility of amoeba-vectored (through the cyst form of the protozoan) Yersinia propagation and proliferation are now in progress. Microbial physiology
An interesting feature peculiar to some of the Yersinia bacteria is the ability to not only survive, but also to actively proliferate at temperatures as low as 1–4 °C (e.g., on cut salads and other food products in a refrigerator). Yersinia bacteria are relatively quickly inactivated by oxidizing agents such as hydrogen peroxide and potassium permanganate solutions. Genetics
Database
The creation of YersiniaBase, a data and tools collection for the reporting and comparison of Yersinia species genome sequence data, was reported in January 2015. | 0-1
|
Combined an individual should gain a positive emotional reaction when choices have beneficial consequences and will have negative emotional responses tied to choices that have greater negative consequences. In general, healthy responders to the IGT will begin to drift to the lower gain decks as they realize that they are gaining more money than they lose both through an ability to recognize that one is more consistently providing rewards as well as through the emotions related to winning consistently. However, those who have emotional deficits will fail to recognize that they are losing money over time and will continue to be more influenced by the exhilaration of higher value rewards without being influenced by the negative emotions of the loses associated with them.For more information concerning these process refer to the Somatic marker hypothesis
Differential Reinforcement of Low Response Rate Task
Differential reinforcement of low response rate (DRL) described by Ferster and Skinner is used to encourage low rates of responding. It is derived from research in operant conditioning that provides an excellent opportunity to measure the hyperactive childs ability to inhibit behavioral responding. Hyperactive children were relatively unable to perform efficiently on the task, and this deficit endured regardless of age, IQ, or experimental condition. Therefore, it can be used to discriminate accurately between teacher rated and parent rated hyperactive and nonhyperactive children. | Resisting the urge to act on impulses is important to teach children, because it teaches the value of delayed gratification. Many psychological problems are characterized by a loss of control or a lack of control in specific situations. Usually, this lack of control is part of a pattern of behavior that also involves other maladaptive thoughts and actions, such as substance abuse problems or sexual disorders like the paraphilias (e.g. pedophilia and exhibitionism). When loss of control is only a component of a disorder, it usually does not have to be a part of the behavior pattern, and other symptoms must also be present for the diagnosis to be made. (Franklin)
The five traits that can lead to impulsive actions
For many years it was understood that impulsivity is a trait but with further analysis it can be found that there were five traits that can lead to impulsive actions:
positive urgency,
negative urgency,
sensation seeking,
lack of planning, and
lack of perseverance. Associated behavioral and societal problems
Attention-deficit hyperactivity disorder
Attention deficit-hyperactivity disorder (ADHD) is a multiple component disorder involving inattention, impulsivity, and hyperactivity. The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) breaks ADHD into three subtypes according to the behavioral symptoms:
Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Type,
Attention-Deficit/Hyperactivity Disorder Predominantly Hyperactive-Impulsive Type, and
Attention-Deficit/Hyperactivity Disorder Combined Type. Predominantly hyperactive-impulsive type symptoms may include
fidgeting and squirming in seats,
talking nonstop,
dashing around and touching or playing with anything in sight,
having trouble sitting still during dinner/school/story time,
being constantly in motion, and
having difficulty doing quiet tasks or activities. | 11
|
A carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) are associated with carcinoid syndrome. Carcinoid tumors are the most common malignant tumor of the appendix, but they are most commonly associated with the small intestine, and they can also be found in the rectum and stomach. They are known to grow in the liver, but this finding is usually a manifestation of metastatic disease from a primary carcinoid occurring elsewhere in the body. They have a very slow growth rate compared to most malignant tumors. The median age at diagnosis for all patients with neuroendocrine tumors is 63 years. Signs and symptoms
While most carcinoids are asymptomatic through the natural life and are discovered only upon surgery for unrelated reasons (so-called coincidental carcinoids), all carcinoids are considered to have malignant potential. About 10% of carcinoids secrete excessive levels of a range of hormones, most notably serotonin (5-HT), causing:
Flushing (serotonin itself does not cause flushing). Potential causes of flushing in carcinoid syndrome include bradykinins, prostaglandins, tachykinins, substance P, and/or histamine, diarrhea, and heart problems. Because of serotonins growth-promoting effect on cardiac myocytes, a serotonin-secreting carcinoid tumour may cause a tricuspid valve disease syndrome, due to the proliferation of myocytes onto the valve. Diarrhea
Wheezing
Abdominal cramping
Peripheral edemaThe outflow of serotonin can cause a depletion of tryptophan leading to niacin deficiency. | Niacin deficiency, also known as pellagra, is associated with dermatitis, dementia, and diarrhea. This constellation of symptoms is called carcinoid syndrome or (if acute) carcinoid crisis. Occasionally, haemorrhage or the effects of tumor bulk are the presenting symptoms. The most common originating site of carcinoid is the small bowel, particularly the ileum; carcinoid tumors are the most common malignancy of the appendix. Carcinoid tumors may rarely arise from the ovary or thymus.They are most commonly found in the midgut at the level of the ileum or in the appendix. The next most commonly affected area is the respiratory tract, with 28% of all cases—per PAN-SEER data (1973–1999). The rectum is also a common site. Gastrointestinal
Carcinoid tumors are apudomas that arise from the enterochromaffin cells throughout the gut. Over two-thirds of carcinoid tumors are found in the gastrointestinal tract. Lung
Carcinoid tumors are also found in the lungs. Other sites and metastases
Metastasis of carcinoid can lead to carcinoid syndrome. This is due to the over-production of many substances, including serotonin, which are released into the systemic circulation, and which can lead to symptoms of cutaneous flushing, diarrhea, bronchoconstriction, and right-sided cardiac valve disease. It is estimated that less than 6% of carcinoid patients will develop carcinoid syndrome, and of these, 50% will have cardiac involvement. Goblet cell carcinoid
This is considered to be a hybrid between an exocrine and endocrine tumor derived from crypt cells of the appendix. Histologically, it forms clusters of goblet cells containing mucin with a minor admixture of Paneth cells and endocrine cells. | 11
|
It has moderate liability among addictive drugs; accordingly, addiction and psychological dependence are possible and likely when methylphenidate is used at high doses as a recreational drug. When used above the medical dose range, stimulants are associated with the development of stimulant psychosis. As with all addictive drugs, the overexpression of ΔFosB in D1-type medium spiny neurons in the nucleus accumbens is implicated in methylphenidate addiction. Biomolecular mechanisms
Methylphenidate has the potential to induce euphoria due to its pharmacodynamic effect (i.e., dopamine reuptake inhibition) in the brains reward system. At therapeutic doses, ADHD stimulants do not sufficiently activate the reward system, or the reward pathway in particular, to the extent necessary to cause persistent increases in ΔFosB gene expression in the D1-type medium spiny neurons of the nucleus accumbens; consequently, when taken as directed in doses that are commonly prescribed for the treatment of ADHD, methylphenidate use lacks the capacity to cause an addiction. However, when methylphenidate is used at sufficiently high recreational doses through a bioavailable route of administration (e.g., insufflation or intravenous administration), particularly for use of the drug as a euphoriant, ΔFosB accumulates in the nucleus accumbens. Hence, like any other addictive drug, regular recreational use of methylphenidate at high doses eventually gives rise to ΔFosB overexpression in D1-type neurons which subsequently triggers a series of gene transcription-mediated signaling cascades that induce an addiction. Interactions
Methylphenidate may inhibit the metabolism of vitamin K anticoagulants, certain anticonvulsants, and some antidepressants (tricyclic antidepressants, and selective serotonin reuptake inhibitors). | By increasing the effects of norepinephrine and dopamine, methylphenidate increases the activity of the central nervous system and produces effects such as increased alertness, reduced fatigue, and improved attention.Methylphenidate is most active at modulating levels of dopamine (DA) and to a lesser extent norepinephrine (NE). Methylphenidate binds to and blocks dopamine transporters (DAT) and norepinephrine transporters (NET). Variability exists between DAT blockade, and extracellular dopamine, leading to the hypothesis that methylphenidate amplifies basal dopamine activity, leading to nonresponse in those with low basal DA activity. On average, methylphenidate elicits a 3–4 times increase in dopamine and norepinephrine in the striatum and prefrontal cortex. Magnetic resonance imaging (MRI) studies suggest that long-term treatment with ADHD stimulants (specifically, amphetamine and methylphenidate) decreases abnormalities in brain structure and function found in subjects with ADHD.There exist some paradoxical findings that oppose the notion that methylphenidate acts primarily through DAT inhibition. 80% occupancy of the DAT is necessary for methphenidates euphoriant effect, but re-administration of methylphenidate beyond this level of DAT occupancy has been found to still produce euphoriant effects. More potent DAT inhibitors such as bupropion have not been observed to cause this effect. These observations help corroborate the hypothesis that methylphenidate may act as a "DAT inverse agonist" by reversing the direction of the dopamine efflux by the DAT.Both amphetamine and methylphenidate are predominantly dopaminergic drugs, yet their mechanisms of action are distinct. Methylphenidate acts as a norepinephrine–dopamine reuptake inhibitor, while amphetamine is both a releasing agent and reuptake inhibitor of dopamine and norepinephrine. | 11
|
Christopher Snow, the protagonist of Dean Koontzs Moonlight Bay Trilogy, has XP and therefore must live most of his life during the night. The first two entries of the trilogy, Fear Nothing and Seize the Night, were both published in 1998. The final entry in the trilogy, tentatively titled Ride the Storm, has yet to be published as of August 2020.The 2011 French drama film The Moon Child is based on a 13-year-old child with XP, which prevents him from exposing himself to daylight. The 2012 documentary Sun Kissed explores the XP problem on the Navajo Indian Reservation, and links it to the genetic legacy of the Long Walk of the Navajo, when the Navajo people were forced to move to a new location.The 2018 romance film Midnight Sun, based on a 2006 Japanese film, A Song to the Sun, tells the story of a girl named Katie Price with XP and the impact of her sickness on her life and relationships, following the story of Prices accidental exposure to sunlight and subsequent neurological degeneration. Research directions
Research into XP has had two main results: better understanding the disease itself, and also better understanding the normal biological mechanisms involved in DNA repair. Research into XP has produced insights that have been translated into treatments and prevention for cancer. See also
DeSanctis–Cacchione syndrome
Genetic disorder
Biogerontology
Cockayne syndrome
List of cutaneous conditions
List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer
Photophobia
Senescence
References
External links
GeneReviews/NCBI/NIH/UW entry on xeroderma pigmentosum | Bexarotene, sold under the brand Targretin, is an antineoplastic (anti-cancer) agent used for the treatment of cutaneous T cell lymphoma (CTCL). It is a third-generation retinoid.It was approved by the U.S. Food and Drug Administration (FDA) in December 1999, and the European Medicines Agency (EMA) in March 2001. It is available as a generic medication. Medical uses
Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in people who are refractory to at least one prior systemic therapy (oral) and for the topical treatment of cutaneous lesions in patients with CTCL who have refractory or persistent disease after other therapies or who have not tolerated other therapies (topical).It has been used off-label for non-small cell lung cancer and breast cancer. Contraindications
Known contraindications include:
Adverse effects
Overall the most common adverse effects are skin reactions (mostly itchiness and rashes), leucopenia, headache, weakness, thyroid anomalies (which seem to be mediated by RXR-mediated downregulation of thyroid stimulating hormone) and blood lipid anomalies such as hypercholesterolaemia (high blood cholesterol) and hyperlipidaemia, hypothyroidism. Interactions
Its plasma concentration may be increased by concomitant treatment with CYP3A4 inhibitors such as ketoconazole. It may also induce CYP3A4, and hence CYP3A4 substrates like cyclophosphamide may have their plasma concentrations reduced. Likewise consumption of grapefruit juice might increase bexarotenes plasma concentrations, hence potentially altering its therapeutic effects. Mechanism
Bexarotene is a retinoid that selectively activates retinoid X receptors (RXRs), as opposed to the retinoic acid receptors, the other major target of retinoic acid (the acid form of vitamin A). | 0-1
|
25%-75% recovery index: an indicator of the rate of skeletal muscle recovery - essentially, the difference in time between the time to recovery to 25% and time to recovery to 75% of baseline value
T4:T1 ≥ 0.7: a 70% ratio of the fourth twitch to the first twitch in a TOF - provides a measure of the recovery of neuromuscular function
T4:T1 ≥ 0.9: a 90% ratio of the fourth twitch to the first twitch in a TOF - provides a measure of the full recovery of neuromuscular function
History
Atracurium besilate was first made in 1974 by George H. Dewar, a pharmacist and a medicinal chemistry doctoral candidate in John B. Stenlakes medicinal chemistry research group in the Department of Pharmacy at Strathclyde University, Scotland. Dewar first named this compound "33A74" before its eventual emergence in the clinic as atracurium. Atracurium was the culmination of a rational approach to drug design to produce the first non-depolarizing non-steroidal skeletal muscle relaxant that undergoes chemodegradation in vivo. The term chemodegradation was coined by Roger D. Waigh, Ph.D., also a pharmacist and a postdoctoral researcher in Stenlakes research group. Atracurium was licensed by Strathclyde University to the Wellcome Foundation UK, which developed the drug (then known as BW 33A) and its introduction to first human trials in 1979, and then eventually to its first introduction (as a mixture of all ten stereoisomers) into clinical anesthetic practice in the UK, in 1983, under the tradename of Tracrium. | A Li-ion battery is a kind of flow battery which can be seen in the image on the right. Furthermore, a Li-ion battery is an example of a secondary cell since it is rechargeable. It can both act as a galvanic or electrolytic cell. Li-ion batteries use lithium ions as the solute in the electrolyte which are dissolved in an organic solvent. Lithium electrodes were first studied by G.N. Lewis and F.G. Keyes in 1913. In the following century these electrodes were used to create and study the first Li-ion batteries. Li-ion batteries are very popular due to their great performance. Applications include mobile phones and electric cars. Due to their popularity, much research is being done to reduce the cost and increase the safety of Li-ion batteries. An integral part of the Li-ion batteries are their anodes and cathodes, therefore much research is being done into increasing the efficiency, safety and reducing the costs of these electrodes specifically. Cathodes
In Li-ion batteries the cathode consists of a intercalated lithium compound (a layered material consisting of layers of molecules composed of lithium and other elements). A common element which makes up part of the molecules in the compound is cobalt. Another frequently used element is manganese. The best choice of compound usually depends on the application of the battery. Advantages for cobalt-based compounds over manganese-based compounds are their high specific heat capacity, high volumetric heat capacity, low self-discharge rate, high discharge voltage and high cycle durability. | 0-1
|
In humans, the P antigen (also known as globoside), one of many cellular receptors that contribute to a persons blood type, is the cellular receptor for parvovirus B19, which causes erythema infectiosum (fifth disease) in children. Because it infects red blood cells as a result of the affinity for the P antigen, parvovirus causes complete cessation of red blood cell production. In most cases, this goes unnoticed, as red blood cells live on average 120 days, and the drop in production does not significantly affect the total number of circulating cells. However, in people with conditions where the cells die early (such as sickle cell disease), parvovirus infection can lead to severe anemia.More frequently, parvovirus B19 is associated with aplastic crisis, which involves only red blood cells (despite the name). Aplastic anemia involves all cell lines. Other viruses that have been linked to the development of aplastic anemia include hepatitis, Epstein-Barr, cytomegalovirus, and HIV. In some animals, aplastic anemia may have other causes. For example, in the ferret (Mustela putorius furo), it is caused by estrogen toxicity, because female ferrets are induced ovulators, so mating is required to bring the female out of heat. Intact females, if not mated, will remain in heat, and after some time the high levels of estrogen will cause the bone marrow to stop producing red blood cells. Diagnosis
Aplastic anemia must be differentiated from pure red cell aplasia. In aplastic anemia, the patient has pancytopenia (i.e., also leukopenia and thrombocytopenia) resulting in a decrease of all formed elements. | Similarly, an enlarged right supraclavicular lymph node tends to drain thoracic malignancies such as lung and esophageal cancer, as well as Hodgkins lymphoma. History
Virchows nodes are named after Rudolf Virchow (1821–1902), the German pathologist who first described the nodes and their association with gastric cancer in 1848. The French pathologist Charles Emile Troisier noted in 1889 that other abdominal cancers, too, could spread to the nodes. Additional images
References
This article incorporates text in the public domain from page 697 of the 20th edition of Grays Anatomy (1918)
Further reading
Cervin, J. R.; Silverman, J. F.; Loggie, B. W.; Geisinger, K. R. (1995). "Virchows node revisited. Analysis with clinicopathologic correlation of 152 fine-needle aspiration biopsies of supraclavicular lymph nodes". Archives of Pathology & Laboratory Medicine. 119 (8): 727–30. PMID 7646330. INIST:3670181 NAID 10026546830. Negus, D; Edwards, J M; Kinmonth, J B (7 December 2005). "Filling of cervical and mediastinal nodes from the thoracic duct and the physiology of virchows node—studies by lymphography". British Journal of Surgery. 57 (4): 267–271. doi:10.1002/bjs.1800570407. PMID 5437920. S2CID 19698597. Mizutani, Masaomi; Nawata, Shin-ichi; Hirai, Ichiro; Murakami, Gen; Kimura, Wataru (December 2005). "Anatomy and histology of Virchows node". Anatomical Science International. 80 (4): 193–198. doi:10.1111/j.1447-073x.2005.00114.x. PMID 16333915. S2CID 40130186. External links
synd/1222 at Who Named It? Image at umich.edu - must rollover
https://web.archive.org/web/20080216031919/http://www.med.mun.ca/anatomyts/head/hnl3a.htm
http://www.aafp.org/afp/20021201/2103.html | 0-1
|
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." | 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. | 11
|
Sleep inertia is a physiological state of impaired cognitive and sensory-motor performance that is present immediately after awakening. It persists during the transition of sleep to wakefulness, where an individual will experience feelings of drowsiness, disorientation and a decline in motor dexterity. Impairment from sleep inertia may take several hours to dissipate. In the majority of cases, morning sleep inertia is experienced for 15 to 30 minutes after waking.Sleep inertia is of concern with decision-making abilities, safety-critical tasks and the ability to operate efficiently soon after awakening. In these situations, it poses an occupational hazard due to the cognitive and motor deficits that may be present. Symptoms
"Grogginess", as defined by a drowsy or disoriented state in which there is a dampening of sensory acuity and mental processing. Impaired motor dexterity and decrease in cognitive ability. These gross impairments may be responsible for the associated increase in reaction time and drop in attentiveness. Deficits in spatial memory
Reports of heightened subjective fatigueThese symptoms are expressed with the greatest intensity immediately after waking, and dissipate following a period of extended wakefulness. The duration of symptoms varies on a conditional basis, with primary expression during the first 15–60 minutes after waking and potentially extending for several hours. Tasks that require more complex cognitive operations will feature greater deficits as compared to a simple motor task; the accuracy of sensory and motor functioning is more impaired by sleep inertia as compared to sheer speed. | Treatments / countermeasures
There has been a great deal of research into potential methods to relieve the effects of sleep inertia. The demand for remedies is driven by the occupational hazards of sleep inertia for employees who work extended shifts such as medical professionals, emergency responders, or military personnel. The motor functioning and cognitive ability of these professionals who must immediately respond to a call can pose a safety hazard in the workplace. Below are some of the various methods that have been suggested to combat sleep inertia. Napping
When a person is sleep deprived, re-entering sleep may provide a viable route to reduce mental and physical fatigue but it can also induce sleep inertia. In order to limit sleep inertia, one should avoid waking from the deeper stages of slow-wave sleep. The onset of slow-wave sleep occurs approximately 30 minutes after falling asleep, therefore a nap should be limited to under 30 minutes to prevent waking during slow-wave sleep and enhancing sleep inertia. Furthermore, self-awakening from a short nap was shown to relieve disorientation of sleep inertia as opposed to a forced awakening, but these results may warrant more research into the nature of arousal after sleep periods. Caffeine
Caffeine is a xanthine derivative that can cross the blood-brain barrier. The caffeine present in coffee or tea exerts its stimulating action by blocking adenosine receptors in the brain. By antagonizing the adenosine receptors caffeine limits the effects of adenosine buildup in the brain and increases alertness and attentiveness. | 11
|
A possible complication arises through the fact that cancerous tumors may be more difficult to detect in women with fibrocystic changes. Breast cancer risk
Breast cancer risk is elevated in a defined fraction of the lesions. Except for people with a strong family history of breast cancer, where the risk is two-fold, nonproliferative lesions have no increased risk. Proliferative lesions also have approximately a two-fold risk. In particular, atypical hyperplasia which is associated with an increased risk of developing breast cancer. Theres two types of atypical hyperplasia: lobular and ductal; the lobular type is associated a greater cancer risk of approximately 5-fold and especially high relative risk in premenopausal women. Atypical ductal hyperplasia is associated with 2.4-fold risk. In contrast, a New England Journal of Medicine article states that for women with a strong familial history of breast cancer, the risk of future breast cancer is roughly doubled, independent of histological status. The article further states "The relative risk of breast cancer for the cohort was 1.56 (95 percent confidence interval, 1.45 to 1.68), and this increased risk persisted for at least 25 years after biopsy. The relative risk associated with atypia was 4.24 (95 percent confidence interval, 3.26 to 5.41), as compared with a relative risk of 1.88 (95 percent confidence interval, 1.66 to 2.12) for proliferative changes without atypia and of 1.27 (95 percent confidence interval, 1.15 to 1.41) for nonproliferative lesions. | An acute exacerbation of chronic obstructive pulmonary disease, or acute exacerbations of chronic bronchitis (AECB), is a sudden worsening of chronic obstructive pulmonary disease (COPD) symptoms including shortness of breath, quantity and color of phlegm that typically lasts for several days. It may be triggered by an infection with bacteria or viruses or by environmental pollutants. Typically, infections cause 75% or more of the exacerbations; bacteria can roughly be found in 25% of cases, viruses in another 25%, and both viruses and bacteria in another 25%. Airway inflammation is increased during the exacerbation resulting in increased hyperinflation, reduced expiratory air flow and decreased gas exchange.Exacerbations can be classified as mild, moderate, and severe. As COPD progresses, exacerbations tend to become more frequent, the average being about three episodes per year. Signs and symptoms
An acute exacerbation of COPD is associated with increased frequency and severity of coughing. It is often accompanied by worsened chest congestion and discomfort. Shortness of breath and wheezing are present in many cases. Exacerbations may be accompanied by increased amount of cough and sputum productions, and a change in appearance of sputum. An abrupt worsening in COPD symptoms may cause rupture of the airways in the lungs, which in turn may cause a spontaneous pneumothorax.In infection, there is often weakness, fever and chills. If due to a bacterial infection, the sputum may be slightly streaked with blood and coloured yellow or green. | 0-1
|
Drug interactions
Chloroquine has a number of drug–drug interactions that might be of clinical concern:
Ampicillin- levels may be reduced by chloroquine;
Antacids- may reduce absorption of chloroquine;
Cimetidine- may inhibit metabolism of chloroquine; increasing levels of chloroquine in the body;
Cyclosporine- levels may be increased by chloroquine; and
Mefloquine- may increase risk of convulsions. Overdose
Chloroquine, in overdose, has a risk of death of about 20%. It is rapidly absorbed from the gut with an onset of symptoms generally within an hour. Symptoms of overdose may include sleepiness, vision changes, seizures, stopping of breathing, and heart problems such as ventricular fibrillation and low blood pressure. Low blood potassium may also occur.While the usual dose of chloroquine used in treatment is 10 mg/kg, toxicity begins to occur at 20 mg/kg, and death may occur at 30 mg/kg. In children as little as a single tablet can cause problems.Treatment recommendations include early mechanical ventilation, cardiac monitoring, and activated charcoal. Intravenous fluids and vasopressors may be required with epinephrine being the vasopressor of choice. Seizures may be treated with benzodiazepines. Intravenous potassium chloride may be required, however this may result in high blood potassium later in the course of the disease. Dialysis has not been found to be useful. Pharmacology
Absorption of chloroquine is rapid and primarily happens in the gastrointestinal tract. It is widely distributed in body tissues. Protein binding in plasma ranges from 46% to 79%. Its metabolism is partially hepatic, giving rise to its main metabolite, desethylchloroquine. Its excretion is ≥50% as unchanged drug in urine, where acidification of urine increases its elimination. | It is recommended to check if chloroquine is still effective in the region prior to using it. In areas where resistance is present, other antimalarials, such as mefloquine or atovaquone, may be used instead. The Centers for Disease Control and Prevention recommend against treatment of malaria with chloroquine alone due to more effective combinations. Amebiasis
In treatment of amoebic liver abscess, chloroquine may be used instead of or in addition to other medications in the event of failure of improvement with metronidazole or another nitroimidazole within 5 days or intolerance to metronidazole or a nitroimidazole. Rheumatic disease
As it mildly suppresses the immune system, chloroquine is used in some autoimmune disorders, such as rheumatoid arthritis and has an off label indication for lupus erythematosus. Side effects
Side effects include blurred vision, nausea, vomiting, abdominal cramps, headache, diarrhea, swelling legs/ankles, shortness of breath, pale lips/nails/skin, muscle weakness, easy bruising/bleeding, hearing and mental problems. Unwanted/uncontrolled movements (including tongue and face twitching)
Deafness or tinnitus. Nausea, vomiting, diarrhea, abdominal cramps
Headache. Mental/mood changes (such as confusion, personality changes, unusual thoughts/behavior, depression, feeling being watched, hallucinating)
Signs of serious infection (such as high fever, severe chills, persistent sore throat)
Skin itchiness, skin color changes, hair loss, and skin rashes.Chloroquine-induced itching is very common among black Africans (70%), but much less common in other races. It increases with age, and is so severe as to stop compliance with drug therapy. It is increased during malaria fever; its severity is correlated to the malaria parasite load in blood. | 11
|
Centrifugal abdominal lipodystrophy is a skin condition characterized by areas of subcutaneous fat loss that slowly enlarge. : 496–7
See also
Lipodystrophy
List of cutaneous conditions
Skin lesion
== References == | Oxytocin was added to the Institute for Safe Medication Practicess list of High Alert Medications in Acute Care Settings in 2012. The list includes medications that have a high risk for harm if administered incorrectly.During pregnancy, increased uterine motility has led to decreased heart rate, cardiac arrhythmia, seizures, brain damage, and death in the fetus or neonate.Use is linked to an increased risk of postpartum depression in the mother.Certain learning and memory functions are impaired by centrally administered oxytocin. Also, systemic oxytocin administration can impair memory retrieval in certain aversive memory tasks. However, oxytocin does seem to facilitate learning and memory specifically for social information. Healthy males administered intranasal oxytocin show improved memory for human faces, in particular happy faces. Pharmacokinetics
Routes of administration
One IU of oxytocin is the equivalent of about 2 μg or mcg of pure peptide. Injection: Clinical doses of oxytocin are given by injection either into a muscle or into a vein to cause contraction of the uterus. Very small amounts (< 1%) do appear to enter the central nervous system in humans when peripherally administered. The compound has a half-life of typically about 3 minutes in the blood when given intravenously. Intravenous administration requires 40 minutes to reach a steady-state concentration and achieve maximum uterine contraction response. Buccal: Oxytocin was delivered in buccal tablets, but this is not common practice any more. Under the tongue: Oxytocin is poorly absorbed sublingually. | 0-1
|
The pigmentation involves the trunk and extremities, is slate-grey, blue or brown, and is distributed in irregular marbled or wavy lines. The discoloration sometimes fades with age.Neurological problems can include cerebral atrophy, the formation of small cavities in the central white matter of the brain, and the loss of neurons in the cerebellar cortex. About 20% of children with IP will have slow motor development, muscle weakness in one or both sides of the body, intellectual disability, and seizures. They are also likely to have visual problems, which can include: crossed eyes, cataracts, retinal detachment, and severe visual loss. Dental problems are also common, and can include hypodontia, abnormally shaped teeth, and delayed tooth eruption.Breast anomalies can occur in 1% of patients and can include hypoplasia or supernumerary nipples. Skeletal and structural anomalies can occur in approximately 14% of patients, including:
Somatic asymmetry
Hemivertebrae
Scoliosis
Spina bifida
Syndactyly
Acheiria (congenital absence of the hands—note: other limbs may be affected)
Ear anomalies
Extra ribs
Skull deformities
Genetics
IP is inherited in an X-linked dominant manner. IP is lethal in most, but not all, males. A female with IP may have inherited the IKBKG mutation from either parent or have a new gene mutation. Parents may either be clinically affected or have germline mosaicism. Affected women have a 50% risk of transmitting the mutant IKBKG allele at conception; however, most affected male conceptuses miscarry. Thus, the effective ratio for liveborn children from a mother carrying the mutation is 33% unaffected females, 33% affected females, and 33% unaffected males. | Incontinentia pigmenti (IP) is a rare X-linked dominant genetic disorder that affects the skin, hair, teeth, nails and central nervous system. It is named from its appearance under a microscope.The disease is characterized by skin abnormalities that begin in childhood, usually a blistering rash which heals, followed by the development of harder skin growths. The skin may develop grey or brown patches which fade with time. Other symptoms can include hair loss, dental abnormalities, eye abnormalities that can lead to vision loss and lined or pitted fingernails and toenails. Associated problems can include delayed development, intellectual disability, seizures and other neurological problems. Most males with the disease do not survive to childbirth. Incontinentia pigmenti is caused by a mutation in the IKBKG gene, which encodes the NEMO protein, which serves to protect cells against TNF-alpha-induced apoptosis. A lack of IKBKG therefore makes cells more prone to apoptosis. There is no specific treatment; individual conditions must be managed by specialists. Presentation
The skin lesions evolve through characteristic stages:
blistering (from birth to about four months of age),
a wart-like rash (for several months),
swirling macular hyperpigmentation (from about six months of age into adulthood), followed by
linear hypopigmentation.Alopecia, dental anomalies, and dystrophic nails are observed. Some patients have retinal vascular abnormalities predisposing to retinal detachment in early childhood. Cognitive delays or intellectual disability are occasionally seen.The discolored skin is caused by excessive deposits of melanin (normal skin pigment). Most newborns with IP will develop discolored skin within the first two weeks. | 11
|
Of the 205 hospitals in the DSOs central region—which includes the large cities of Frankfurt and Mainz—only six had more organ donors than LRMC in 2010.Scotland conforms to the Human Tissue Authority Code of Practice, which grants authority to donate organs, instead of consent of the individual. This helps to avoid conflict of implications and contains several requirements. In order to participate in organ donation, one must be listed on the Organ Donor Registry (ODR). If the subject is incapable of providing consent, and is not on the ODR, then an acting representative, such as a legal guardian or family member can give legal consent for organ donation of the subject, along with a presiding witness, according to the Human Tissue Authority Code of Practice. Consent or refusal from a spouse, family member, or relative is necessary for a subject is incapable. Austria participates in the "opt-out" consent process, and have laws that make organ donation the default option at the time of death. In this case, citizens must explicitly "opt out" of organ donation. Yet in countries such as U.S.A. and Germany, people must explicitly "opt in" if they want to donate their organs when they die. In Germany and Switzerland there are Organ Donor Cards available.In May 2017, Ireland began the process of introducing an "opt-out" system for organ donation. Minister for Health, Simon Harris, outlined his expectations to have the Human Tissue Bill passed by the end of 2017. | United Network for Organ Sharing, the organization that coordinates available organs with recipients, does not factor a patients prison status when determining suitability for a transplant. An organ transplant and follow-up care can cost the prison system up to one million dollars. If a prisoner qualifies, a state may allow compassionate early release to avoid high costs associated with organ transplants. However, an organ transplant may save the prison system substantial costs associated with dialysis and other life-extending treatments required by the prisoner with the failing organ. For example, the estimated cost of a kidney transplant is about $111,000. A prisoners dialysis treatments are estimated to cost a prison $120,000 per year.Because donor organs are in short supply, there are more people waiting for a transplant than available organs. When a prisoner receives an organ, there is a high probability that someone else will die waiting for the next available organ. A response to this ethical dilemma states that felons who have a history of violent crime, who have violated others basic rights, have lost the right to receive an organ transplant, though it is noted that it would be necessary "to reform our justice system to minimize the chance of an innocent person being wrongly convicted of a violent crime and thus being denied an organ transplant".Prisons typically do not allow inmates to donate organs to anyone but immediate family members. | 11
|
Randomized controlled trials have shown that DBT and MBT may be the most effective, and the two share many similarities. Researchers are interested in developing shorter versions of these therapies to increase accessibility, to relieve the financial burden on patients, and to relieve the resource burden on treatment providers.Some research indicates that mindfulness meditation may bring about favorable structural changes in the brain, including changes in brain structures that are associated with BPD. Mindfulness-based interventions also appear to bring about an improvement in symptoms characteristic of BPD, and some clients who underwent mindfulness-based treatment no longer met a minimum of five of the DSM-IV-TR diagnostic criteria for BPD. Medications
A 2010 review by the Cochrane collaboration found that no medications show promise for "the core BPD symptoms of chronic feelings of emptiness, identity disturbance, and abandonment". However, the authors found that some medications may impact isolated symptoms associated with BPD or the symptoms of comorbid conditions. A 2017 review examined evidence published since the 2010 Cochrane review and found that "evidence of effectiveness of medication for BPD remains very mixed and is still highly compromised by suboptimal study design". A 2020 review found that research into pharmacological treatments had declined, with more results confirming no benefits. The review found "moderate to large, statistically significant effects for both doses of quetiapine (150 mg/day and 300 mg/day) regarding BPD severity, psychosocial impairment and aggression, and an additional effect for the higher dose regarding manic symptoms." | The majority of individuals with BPD who are in treatment continue to use outpatient treatment in a sustained manner for several years, but the number using the more restrictive and costly forms of treatment, such as inpatient admission, declines with time.Experience of services varies. Assessing suicide risk can be a challenge for clinicians, and patients themselves tend to underestimate the lethality of self-injurious behaviors. People with BPD typically have a chronically elevated risk of suicide much above that of the general population and a history of multiple attempts when in crisis. Approximately half the individuals who commit suicide meet criteria for a personality disorder. Borderline personality disorder remains the most commonly associated personality disorder with suicide.After a patient with BPD died, The National Health Service (NHS) in England was criticized by a coroner in 2014 for the lack of commissioned services to support those with BPD. Evidence was given that 45% of female patients had BPD and there was no provision or priority for therapeutic psychological services. At the time, there were only a total of 60 specialized inpatient beds in England, all of them located in London or the northeast region. Prognosis
With treatment, the majority of people with BPD can find relief from distressing symptoms and achieve remission, defined as a consistent relief from symptoms for at least two years. A longitudinal study tracking the symptoms of people with BPD found that 34.5% achieved remission within two years from the beginning of the study. | 11
|
However, multiple other NMDA receptor antagonists, including memantine, lanicemine, rislenemdaz, rapastinel, and 4-chlorokynurenine, thus far have failed to demonstrate sufficient effectiveness for depression. Furthermore, animal research indicates that arketamine, the enantiomer with a weaker NMDA receptor antagonism, as well as (2R,6R)-hydroxynorketamine, the metabolite with negligible affinity for the NMDA receptor, but a potent alpha-7 nicotinic receptor antagonist may have antidepressive action. It is now argued that NMDA receptor antagonism may not be primarily responsible for the antidepressant effects of ketamine. Molecular targets
Ketamine principally acts as an antagonist of the NMDA receptor, an ionotropic glutamate receptor. The S(+) and R(–) stereoisomers of ketamine bind to the dizocilpine site of the NMDA receptor with different affinities, the former showing approximately 3- to 4- fold greater affinity for the receptor than the latter. As a result, the S isomer is a more potent anesthetic and analgesic than its R counterpart.Ketamine may interact with and inhibit the NMDAR via another allosteric site on the receptor.With a couple of exceptions ketamine actions at other receptors are far weaker than ketamines antagonism of the NMDA receptor (see the activity table to the right).Although ketamine is a very weak ligand of the monoamine transporters (Ki > 60 μM), it has been suggested that it may interact with allosteric sites on the monoamine transporters to produce monoamine reuptake inhibition. However, no functional inhibition (IC50) of the human monoamine transporters has been observed with ketamine or its metabolites at concentrations of up to 10,000 nM. | Desogestrel/ethinylestradiol (EE/DSG), sold under the brand name Marvelon among others, is a fixed-dose combination of desogestrel (DSG), a progestin, and ethinylestradiol (EE), an estrogen, which is used as a birth control pill to prevent pregnancy in women. It is taken by mouth.It was approved for medical use in the United Kingdom in 1981, and in the United States in 1992. In 2019, it was the 128th most commonly prescribed medication in the United States, with more than 5 million prescriptions. See also
List of combined sex-hormonal preparations § Estrogens and progestogens
== References == | 0-1
|
These aisle ends are used to lure customers into making a snap purchase and to also entice them to shop down the aisle. The most obvious place supermarket layout influences consumers are at the checkout. Small displays of chocolates, magazines, and drinks are located at each checkout to tempt shoppers while they wait to be served. Criticisms
The large scale of supermarkets, while often improving cost and efficiency for customers, can place significant economic pressure on suppliers and smaller shopkeepers. Supermarkets often generate considerable food waste, although modern technologies such as biomethanation units may be able to process the waste into an economical source of energy. Also, purchases tracking may help as supermarkets then become better able to size their stock (of perishable goods), reducing food spoilage. See also
Hypermarket
List of grocers
Short food supply chains
Farmers markets
Types of retail outlets
Effects of the car on societies
References
Further reading
Greer, William R.; Logan, John A.; Willis, Paul S. (1986). America the Bountiful: How the Supermarket Came to Main Street : an Oral History. Washington, D.C.: Food Marketing Institute in cooperation with Beatrice Companies. OCLC 14357784. Longstreth, R. W. (1999). The Drive-In, the Supermarket, and the Transformation of Commercial Space in Los Angeles, 1914-1941. The MIT Press. Lorr, B. (2020). The Secret Life of Groceries: The Dark Miracle of the American Supermarket. Avery. Newman, K. (2012). The Secret Financial Life of Food: From Commodities Markets to Supermarkets (Illustrated edition). Columbia University Press. Petroski, Henry (November–December 2005). "Shopping by Design". American Scientist 93 (6): 491. Sowell, Thomas. Basic Economics (Third Edition, 2007 Basic Books). | Cortical desmoid (also called tug lesion or periosteal desmoid) is an irregularity of the distal femoral cortex caused by repetitive stress at the attachment of the adductor magnus aponeurosis. It is most commonly seen in adolescents and is usually asymptomatic. It is a benign and self-limiting lesion. References
Gould CF, Ly JQ, Lattin GE, Beall DP, Sutcliffe JB (2007). "Bone tumor mimics: avoiding misdiagnosis". Curr Probl Diagn Radiol. 36 (3): 124–41. doi:10.1067/j.cpradiol.2007.01.001. PMID 17484955. | 0-1
|
A review into giving antibiotics in pregnancy for asymptomatic bacteriuria (urine infection with no symptoms) found the research was of very low quality but that it did suggest that taking antibiotics reduced the numbers of preterm births and babies with low birth weight. Another review found that one dose of antibiotics did not seem as effective as a course of antibiotics but fewer women reported side effects from one dose. This review recommended that more research is needed to discover the best way of treating asymptomatic bacteriuria.A different review found that preterm births happened less for pregnant women who had routine testing for low genital tract infections than for women who only had testing when they showed symptoms of low genital tract infections. The women being routinely tested also gave birth to fewer babies with a low birth weight. Even though these results look promising, the review was only based on one study so more research is needed into routine screening for low genital tract infections.Also periodontal disease has been shown repeatedly to be linked to preterm birth. In contrast, viral infections, unless accompanied by a significant febrile response, are considered not to be a major factor in relation to preterm birth. Genetics
There is believed to be a maternal genetic component in preterm birth. Estimated heritability of timing-of-birth in women was 34%. However, the occurrence of preterm birth in families does not follow a clear inheritance pattern, thus supporting the idea that preterm birth is a non-Mendelian trait with a polygenic nature. | For seizures further randomized controlled trials are needed to evaluate the efficacy of antiepileptic drugs (AED) for seizure prevention in patients with symptoms other than seizures and the duration of AED treatment in these cases. Epidemiology
The epidemiology of Taenia solium cysticercosis is associated with poor sanitation and is highly prevalent in Sub-Saharan Africa, Latin America and Asia. Cysticercosis in the United States, which commonly presents in the form of neurocysticercosis, has been classified as a "neglected tropical disease", which commonly affects the poor and homeless, particularly those without access or in the habit of inadequate hand-washing and in the habit of eating with their hands. == References == | 0-1
|
Amoxapine is also a weak GlyT2 blocker, as well as a weak (Ki = 2.5 μM, EC50 = 0.98 μM) δ-opioid receptor partial agonist.7-Hydroxyamoxapine, a major active metabolite of amoxapine, is a more potent dopamine receptor antagonist and contributes to its neuroleptic efficacy, whereas 8-hydroxyamoxapine is a norepinephrine reuptake inhibitor but a stronger serotonin reuptake inhibitor and helps to balance amoxapines ratio of serotonin to norepinephrine transporter blockade. Pharmacokinetics
Amoxapine is metabolised into two main active metabolites: 7-hydroxyamoxapine and 8-hydroxyamoxapine. Where:
- t1/2 is the elimination half life of the compound. - tmax is the time to peak plasma levels after oral administration of amoxapine. - CSS is the steady state plasma concentration. - protein binding is the extent of plasma protein binding. - Vd is the volume of distribution of the compound. Society and culture
Brand names
Brand names for amoxapine include (where † denotes discontinued brands):
Adisen (KR)
Amolife (IN)
Amoxan (JP)
Asendin† (previously marketed in CA, NZ, US)
Asendis† (previously marketed in IE, UK)
Défanyl (FR)
Demolox (DK†, IN, ES†)
Oxamine (IN)
Oxcap (IN)
See also
Loxapine
== References == | Early infection is characterized by a well demarcated, usually pale, skin lesion which has lost its hair, and there may be many of these lesions if the infection is more severe (most commonly found on the cooler parts of the body such as the elbows, knees, fingers, or scrotum, as the bacteria thrive in cooler environments). This early presentation is the same for both tuberculous and lepromatous forms of leprosy as they are a spectrum of the same disease (lepromatous being the more contagious and severe form in patients with impaired Th1 response). Disease progression is extremely slow, and signs of infection may not appear for years.Family members of those with the disease, and especially children, are most at risk. The disease is believed to be spread through respiratory droplets in close quarters like its relative Mycobacterium tuberculosis, and similarly requires extended exposure to an individual in most situations, so outsiders and healthcare workers are normally not infected (except with the most infective individuals such as those in the most progressed lepromatous forms, as those patients have the highest bacterial loads). See also
Tuberculoid leprosy
Diffuse leprosy of Lucio and Latapí
References
== External links == | 0-1
|
Juvenile hyaline fibromatosis (also known as "Fibromatosis hyalinica multiplex juvenilis," "Murray–Puretic–Drescher syndrome") is a very rare, autosomal recessive disease due to mutations in capillary morphogenesis protein-2 (CMG-2 gene). It occurs from early childhood to adulthood, and presents as slow-growing, pearly white or skin-colored dermal or subcutaneous papules or nodules on the face, scalp, and back, which may be confused clinically with neurofibromatosis. The World Health Organization, 2020, reclassified the papules and nodules that occur in juvenile hyaline firbromatosis as one of the specific benign types of tumors in the category of fibroblastic and myofibroblastic tumors. Presentation
This condition is characterised by abnormal growth of hyalinized fibrous tissue with cutaneous, mucosal, osteoarticular and systemic involvement. Clinical features include extreme pain at minimal handling in a newborn, gingival hypertrophy, subcutaneous nodules, painful joint stiffness and contractures, muscle weakness and hypotonia. Genetics
This condition is due to mutations in the anthrax toxin receptor-2 (ANTXR2) gene. This gene is also known as capillary morphogenesis protein-2. This gene is located on the long arm of chromosome 4 (4q21.21). Management
There is no presently known curative treatment for this condition.Management is supportive
Prognosis
This is very poor with a median age at death of 15 months. Epidemiology
84 cases have been reported as of 2018. See also
List of cutaneous conditions
References
== External links == | Concentrations reached in the blood plasma are so low that they are generally not detectable. To judge from animal models, the drug acts for at least 24 hours. Its elimination half-life is 16 to 17 hours (in rabbits). Chemistry
The drug is used in form of a salt, netarsudil dimesilate, which is a white to light yellow crystalline powder. It is a weak acid and moderately hygroscopic, freely soluble in water and soluble in methanol. See also
Netarsudil/latanoprost, a combination drug
References
External links
"Netarsudil". Drug Information Portal. U.S. National Library of Medicine. "Netarsudil mesylate". Drug Information Portal. U.S. National Library of Medicine. | 0-1
|