Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MuS110 is a BiTE antibody bispecific for murine EpCAM (CD326) and murine CD3. A recent study has shown that microS110 has significant anti tumor activity at well-tolerated doses as low as 5 microg/kg in orthotopic breast and lung cancer models (Amann et al. in Cancer Res 68:143-151, 2008). Here, we have explored the safety profile of microS110 at higher doses. Escalation to 50 microg/kg microS110 caused in mice transient loss of body weight, and transient piloerection, hypomotility, hypothermia and diarrhoea. These clinical signs coincided with serum peaks of TNF-alpha, IL-6, IL-2, IFN-gamma and IL-4, and an increase of surface markers for T cell activation. Because activation of T cells in response to BiTE antibodies is typically dependent on target cells, we analyzed mouse blood for the presence of EpCAM(+) cells. Various mouse strains presented with a subpopulation of 2-3% EpCAM(+) blood cells, mostly B and T lymphocytes, which was not detected in human blood samples. In vitro experiments in which the number of EpCAM(+) cells in blood samples was either reduced or increased suggested that both T cell activation and cytokine release in response to microS110 was dependent on the number of target-expressing cells. In support for a role of EpCAM(+) lymphocytes in the observed side effects, reduction of EpCAM(+) blood cells in mice via a low-dose pre treatment with microS110 dramatically increased the tolerability of animals up to at least 500 microg/kg of the BiTE antibody. This high tolerability to microS110 occurred in the presence of non-compromised T cells. No damage to EpCAM(+) epithelial tissues was evident from histopathological examination of animals daily injected with 100 microg/kg microS110 for 28 days. In summary, these observations suggest that side effects of microS110 in mice were largely caused by an acute T cell activation that was triggered by a subpopulation of EpCAM(+) lymphocytes. Because humans have extremely low numbers of EpCAM(+) cells in blood, this toxicity of an EpCAM-specific BiTE may be specific for mice.
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PMID:Therapeutic window of an EpCAM/CD3-specific BiTE antibody in mice is determined by a subpopulation of EpCAM-expressing lymphocytes that is absent in humans. 1859 18

Autosomal dominant episodic ataxia type 2 (EA2) results from mutations of the CACNA1A gene. We describe EA2 with unusual features in a father and daughter with a novel CACNA1A mutation coding for Y248C. Both patients showed severe cerebellar atrophy in MRI and clinical signs of progressive spinocerebellar atrophy type 6. Most disabling were the very frequent episodes of ataxia with migraine (with aura in the father and without aura in the daughter) and nystagmus in our patients. Additionally, they suffered from ictal hyperhidrosis with acute hypothermia of the extremities. Lastly, the father presented with interictal chronic diarrhea not associated to a known primary gastrointestinal disorder. Both ictal hyperhidrosis and interictal diarrhea ameliorated upon acetazolamide intake, the typical treatment for EA2. The significance of these findings is discussed and the phenotype correlated to previously reported cases.
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PMID:Episodic ataxia type 2 showing ictal hyperhidrosis with hypothermia and interictal chronic diarrhea due to a novel CACNA1A mutation. 1860 18

We compared the socio-demographic and clinical outcomes as predictors in severely ill hospitalized under-five diarrheal children with and without pneumonia. We studied 496 under-five children with diarrhea admitted to the Special Care Ward (SCW) of Dhaka Hospital of International Center for Diarrheal Disease Research, Bangladesh from 1999 to 2004. Children with pneumonia, in addition to their diarrhea, constituted the study group (cases), and those who did not have pneumonia constituted the comparison (control) group. The individual predictors of pneumonia in children were a history of cough (OR 2.19, 95% CI 1.30-3.72, p=0.002), fever (OR 1.73, 95% CI 1.19-2.53, p=0.003), and rapid breathing (OR 2.45, 95% CI 1.49-4.03, p<0.001). Hypothermia (6% vs 2%; p=0.02), hyponatremia (41% vs 27%; p=0.003) and dehydrating diarrhea (81% vs 69%, p=0.003) were more frequent in control children. On logistic regression analyses, the case fatality among children with pneumonia was nearly two times (OR, 1.88 CI, 1.12-3.15, p= 0.02) than that of controls. Formulation of guidelines and implementation of a more comprehensive approach to managing pneumonia among severely ill diarrheal children is necessary to reduce childhood deaths in Bangladesh.
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PMID:Predictors of severe illness in children under age five with concomitant infection with pneumonia and diarrhea at a large hospital in Dhaka, Bangladesh. 1905 11

A 5-day-old quarter horse colt with a history of hypothermia, agonal breathing, and diarrhea was euthanized. At necropsy, numerous slightly raised, discrete, closely approximated submucosal nodules were observed in the colon and small intestine. Histologically, these nodules were composed of expanded submucosal mesenchyme that contained numerous neurons either individually or in ganglia. Thirty-two percent of these ganglia included 8 or more neurons, in contrast to 6% in an age-matched foal. Some nodules had necrosuppurative inflammation with vasculitis, thrombosis, and bacterial colonization. A few heterotopic neurons were randomly distributed in the mucosa and the muscularis mucosa. Histologic changes were most consistent with intestinal neuronal dysplasia, a disease of the submucosal plexus described in humans.
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PMID:Enteric dysganglionosis resembling intestinal neuronal dysplasia in a foal with bacterial colitis. 2046 64

A 56-year-old woman with Graves' disease presented with the complaints of diarrhea and palpitations. Physical examination and laboratory data revealed hypothermia and signs of mild hyperthyroidism, heart failure, hepatic dysfunction with jaundice, hypoglycemia, and lactic acidosis. The patient was diagnosed as having developed the complication of thyroid storm in the absence of marked elevation of the thyroid hormone levels, because of the potential hepatic and cardiac dysfunctions caused by heavy alcohol drinking. A year later, after successful treatment, the patient remains well without any clinical evidence of heart failure or hepatic dysfunction. Thyroid storm associated with lactic acidosis and hypothermia is a serious condition and has rarely been reported. Prompt treatment is essential even if the serum thyroid hormone levels are not markedly elevated. We present a report about this patient, as her life could eventually be saved.
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PMID:A patient with Graves' disease who survived despite developing thyroid storm and lactic acidosis. 2073 31

This case-control study was conducted in the Dhaka Hospital of ICDDR,B to identify the risk factors of mortality in severely-malnourished children hospitalized with diarrhoea. One hundred and three severely-malnourished children (weight-for-age <60% of median of the National Center for Health Statistics standard) who died during hospitalization were compared with another 103 severely-malnourished children who survived. These children were aged less than three years and admitted to the hospital during 1997. On admission, characteristics of the fatal cases and non-fatal controls were comparable, except for age. The median age of the cases and controls were six and eight months respectively (p = 0.05). Patients with low pulse rate or imperceptible pulse had three times the odds of death compared to the control group (p < 0.01). The presence of clinical septicaemia and clinical severe anaemia had 11.7 and 4.2 times the odds of death respectively (p < 0.01). Patients with leukocytosis (> 15,000/cm3) had 2.5 times the odds of death (p < 0.01). Using logistic regression, clinical septicaemia [adjusted odds ratio (AOR) = 8.8, confidence interval (CI) 3.7-21.1, p = 0.01], hypothermia (AOR = 3.5, CI 1.3-9.4, p < 0.01), and bronchopneumonia (AOR=3.0, CI 1.2-7.3, p < 0.01) were identified as the significant risk factors of mortality. Severely-malnourished children (n=129) with leukocytosis, imperceptible pulse, pneumonia, septicaemia, and hypothermia had a high risk of mortality. The identified risk factors can be used as a prognostic guide for patients with diarrhoea and severe malnutrition.
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PMID:Risk factors of mortality in severely-malnourished children hospitalized with diarrhoea. 2176 58

A 4-year-old male German Hunting Terrier presented with tremor, dyspnea, trismus, spasms of the musculature of the larynx and pharynx, and hypothermia and subsequently died despite intensive clinical care. Prior clinical signs included vomitus and diarrhea. Microscopic examination of the brain revealed a multifocal nonsuppurative brain stem encephalitis; a few intralesional neurons contained intranuclear inclusions. By immunohistochemistry, Aujeszky disease virus (Suid herpesvirus 1) antigen was detected in neurons in the brain and in ganglion cells of the trigeminal ganglia. Viral culture of brain tissue confirmed the presence of Aujeszky disease virus. Histopathologic findings in the brain with the identification of Aujeszky disease virus by immunohistochemistry and polymerase chain reaction are consistent with Aujeszky disease virus-induced encephalitis. Sequencing revealed a 100% homology of the isolated Aujeszky disease virus with Aujeszky disease virus isolates of wild boar from Eastern Germany.
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PMID:Nonsuppurative encephalitis in a dog. 2230 32

Mushroom toxicosis is rarely diagnosed in dogs and is poorly reported in the veterinary literature. This report suggests that mushroom toxicosis is a potentially under-diagnosed condition in first opinion practice in the UK. Nine dogs with clinical signs consistent with mushroom toxicosis were identified from the records of an out-of-hours emergency service between August 2010 and January 2011. Four dogs were later excluded because of clinical inconsistencies. Clinical signs included acute profuse ptyalism (5/5), diarrhoea (5/5), vomiting (4/5), hypovolaemia (4/5), stuporous (3/5) or obtunded mentation (1/5), miosis (2/5) and hypothermia (2/5). Serum lipase activity was elevated in 4/4 dogs; canine-specific pancreatic lipase was elevated in the remaining dog. Four dogs recovered with aggressive intravenous fluid therapy, analgesia and supportive care; the remaining dog was euthanased due to severe clinical signs and financial constraints. Mushroom toxicosis is an important differential diagnosis for acute gastroenteritis and one possible cause of some cases of "Seasonal Canine Illness". Affected dogs may demonstrate elevated pancreatic enzymes and mushroom toxicosis should be considered in cases of elevated lipase or abnormal semi-quantitative canine-specific pancreatic lipase activities.
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PMID:Mushroom toxicosis in dogs in general practice causing gastroenteritis, ptyalism and elevated serum lipase activity. 2390 18

We report a case of an 8-year-old girl with fulminant myocarditis successfully treated with percutaneous cardiopulmonary support (PCPS). She was first taken to our hospital for treatment of suspected infective enterocolitis since her main symptoms were fever, vomiting and diarrhea. On day 2 after admission, her ECG showed wide QRS and echocardiography demonstrated severe hypokinesis. She was transferred to the ICU with suspected acute myocarditis. On admission to the ICU, circulatory collapse was not detected. ECG showed severe bradycardia and ventricular fibrillation after intubation. Cardiopulmonary resuscitation was performed immediately for 50 minutes prior to initiation of PCPS. She was treated intensively with catecholamines, plasma exchange, continuous hemodiafiltration, high-dose gamma-globulin, and high dose methylprednisolone. Hypothermia therapy was also performed. She was weaned from PCPS on day 6 after initiation of PCPS. The patient was finally discharged from the hospital without any neurological complications on day 68 after weaning from PCPS. The proportion of patients in whom cardiopulmonary resuscitation was performed or having ventricular tachycardia or fibrillation were higher in non-survivors than in survivors.
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PMID:[A case of fulminant myocarditis successfully treated by percutaneous cardiopulmonary support after 50 minuite-cardiopulmonary resuscitation]. 2347 19

The in vivo preclinical pharmacodynamic profile of TD-1211, a selective opioid receptor antagonist currently under development for the treatment of opioid-induced constipation, was compared to that of the clinically studied opioid antagonists, naltrexone, alvimopan, and ADL 08-0011 (the primary active metabolite of alvimopan). The oral activity of TD-1211 was evaluated in models of gastrointestinal (GI) and central nervous system (CNS) function in the rat and dog. Oral administration of TD-1211, naltrexone, and ADL 08-0011 reversed loperamide-induced inhibition of gastric emptying and castor oil-induced diarrhea in rats and nonproductive GI circular smooth muscle contractility in dogs. Alvimopan was only efficacious in the castor oil model. Oral administration of naltrexone and ADL 08-0011, but not TD-1211 or alvimopan, was associated with a CNS withdrawal response in morphine-dependent mice, inhibition of morphine-induced anti-nociception in rat and dog hot plate tests, and hypothermia and sedation in dogs. It is concluded that TD-1211 has potent in vivo GI activity, consistent with opioid receptor antagonism, but has no significant CNS activity. The data from these studies support the clinical development of TD-1211 as a novel treatment for opioid-induced GI dysfunction.
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PMID:The in vivo pharmacodynamics of the novel opioid receptor antagonist, TD-1211, in models of opioid-induced gastrointestinal and CNS activity. 2351 67


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