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)

A 24-year-old female presented in hospital following self-poisoning with a dose of greater than 30 g of paracetamol (acetaminophen), taken both as co-proxamol (dextropropoxyphene and paracetamol) and paracetamol. She arrived in hospital more than 18 h after ingestion of the drug. On admission, she was profoundly hypothermic, with a rectal temperature of 19 degrees C. Her paracetamol level was 943 mumol.l-1 which, when related to the time of ingestion, implied a very high risk of hepatocellular damage as well as fulminant liver failure, even if she was treated with the antioxidant n-acetylcysteine. The patient's condition was stabilised by initial resuscitation with fluids, vasoactive drugs, and active rewarming. N-acetylcysteine therapy was begun promptly. This patient's liver function tests remained entirely normal in spite of the delay in presentation and she made a rapid and complete recovery. This remarkable clinical course indicates a possible role for therapeutically induced hypothermia in the management of severe paracetamol overdose, particularly in the group of patients who seek medical attention some hours after ingestion of the drug and who therefore remain at high risk, despite treatment with n-acetylcysteine.
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PMID:Does hypothermia protect against the development of hepatitis in paracetamol overdose? 141 76

A 1-year-old child with severe acetaminophen (APAP) poisoning after ingestion of 10 gm APAP demonstrated central nervous system depression, shock, hypothermia, and metabolic acidosis. There was dramatic improvement during treatment with intravenously administered N-acetylcysteine (NAC) and hemodialysis, and the patient recovered without sequelae. A detailed study of APAP metabolism was carried out during the initial 72 hours after ingestion. APAP-sulfate and APAP-glucuronide accounted for 29% and 33%, respectively, of total drug in urine, whereas cysteine and NAC conjugates accounted for only 12%. The low incidence of severe toxicity in children after overdoses of APAP may be related to greater capacity to metabolize APAP via a nontoxic pathway.
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PMID:Metabolism and pharmacokinetics of acetaminophen in a severely poisoned young child. 673 27

Acetaminophen (750 mg/kg) toxicity and its modification by N-acetylcysteine (NAC, 1200 mg/kg) have been compared in fed and fasted mice. There was no significant difference between fed and fasted animals with respect to microsomal protein content, cytochrome(s) P-450 content, and aryl hydrocarbon hydroxylase activity. Glucuronyl transferase activity was significantly higher in fasted mice. Hepatotoxicity, as determined histologically and by liver enlargement was greater in fasted than fed mice. Covalent binding of [3H]acetaminophen metabolite(s) to liver proteins was also greater in fasted animals. NAC administration prevented acetaminophen-induced microscopic changes and liver enlargement and reduced the magnitude of covalent binding of acetaminophen metabolites. Fasting caused a marked fall in liver reduced sulfhydryl concentration. The incidence of acetaminophen-induced hypothermia was greater in fasted than in fed animals. NAC administration reduced hypothermia in fasted mice and abolished it in fed animals. It is concluded that enhanced acetaminophen toxicity in fasted mice compared with fed mice is unlikely to be a consequence of increased reactive metabolite formation, but rather a result of reduced inactivation of reactive metabolite(s) due to reduced hepatic glutathione stores in fasted mice.
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PMID:Acetaminophen toxicity in fed and fasted mice. 680 76

Human NTera2 teratocarcinoma cells were differentiated into postmitotic NT2-N neurons and exposed to hypoxia for 6 h. The cultures were evaluated microscopically, and percent lactate dehydrogenase (LDH) release after 24 and 48 h was used as an assay for cell death. After 48 h LDH release was 24.3 +/- 5.6% versus 13.8 +/- 3.7% in controls (p < 0.001). Cell death was greatly diminished by MK-801 pretreatment (15.4 +/- 5.1%, p < 0.001). If glutamine was omitted from the medium, glutamate levels after 6 h of hypoxia were reduced from 101 +/- 63 to 2.3 +/- 0.3 microM, and cell death at 48 h was also markedly reduced (15.4 +/- 4.5%, p < 0.001). The alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (18.7 +/- 5.1%, p < 0.001) and mild hypothermia (33.5-34 degrees C) during hypoxia (19.5 +/- 2.7%, p < 0.05) were moderately protective. Basic fibroblast growth factor (24.1 +/- 3.2%), the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (22.8 +/- 8.1%), the antioxidant N-tert-butyl-o-phenyinitrone (18.9 +/- 5.9%), and the 21-aminosteroid U74389G (24.0 +/- 3.4%) did not protect the cells. N-Acetyl-L-cysteine even tended to increase cell death (30.1 +/- 2.5%, p = 0.06). Treatment with MK-801 at the end of hypoxia did not reduce cell death (23.3 +/- 2.3%). In separate experiments, a 15-min exposure to 1 mM glutamate without hypoxia did not result in significant cell death (14.7 +/- 2.4 vs. 12.2 +/- 2.1%, p = 0.07). We conclude that, although somewhat resistant to glutamate toxicity when normoxic, NT2-N neurons die via an ionotropic glutamate receptor-mediated mechanism when exposed to hypoxia in the presence of glutamate. As far as we know, this is the first reported analysis of the mechanism of hypoxic cell death in cultured human neuronlike cells.
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PMID:Hypoxic cell death in human NT2-N neurons: involvement of NMDA and non-NMDA glutamate receptors. 975 Nov 88

It is well recognized that acetaminophen overdose can cause severe hepatic injury. However, extra-hepatic manifestations may also develop following inappropriate use or ingestion of large amounts of acetaminophen. We present a 44-y-o female who manifested coma, metabolic acidosis, shock, hypothermia, hyperglycemia, rhabdomyolysis, hepatotoxicity, and renal insufficiency after suicidal ingestion of an unknown amount of acetaminophen. Although her consciousness and hemodynamic status gradually improved after treatment with N-acetylcysteine and other supportive measures, she was found to have pancytopenia, pancreatitis and hepatorenal failure during the hospitalization and eventually died 18 d post-admission. Review of relevant literature reports and the clinical findings in our patient suggests that direct toxic effects mediated by acetaminophen or its metabolites were most likely responsible for most of the observed clinical features.
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PMID:Pancytopenia, hyperglycemia, shock, coma, rhabdomyolysis, and pancreatitis associated with acetaminophen poisoning. 1175 93

The purpose of this study was to investigate the effect of N-acetylcysteine (NAC) on spinal cord ischemia-reperfusion (I-R) in rabbits. Thirty rabbits were divided into five equal groups, group I (sham-operated, no I-R), group II (control, only I-R), group III (I-R+NAC), group IV (I-R+hypothermia), group V (I-R+NAC+hypothermia). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the aortic bifurcation. Forty-eight hours postoperatively, the motor function of the lower limbs was evaluated in each animal according to Tarlov Score. Spinal cord samples were taken to evaluate the histopathological changes. The sham-operated rabbits (group I) showed no neurologic deficit (Score=4). Paraplegia (Score=0) developed in all rabbits in the control group (group II). Administration of 50 mg/kg of NAC (group III) resulted in significant reduction of motor dysfunction (Score=3.1+/-1.3, p=0.002). Application of hypothermia alone (group IV) showed significant recovery of motor functions (Score=3.0+/-1.1, p=0.002), and combination of hypothermia and 50 mg/kg of NAC (group V) showed complete recovery of lower limb motor function (Score=4, p=0.001). Histologic examination of the spinal cord in rabbits with paraplegia revealed several injured neurons. The cords of animals with no motor function deficits showed only minimal cellular infiltrates in the gray matter, and there was good preservation of nerve cells. NAC showed protective effects of the spinal cord. Moderate hypothermia alone also showed protective effects. Combined use of NAC and hypothermia resulted in highly significant recovery of spinal cord function.
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PMID:Neuroprotective effect of N-acetylcysteine and hypothermia on the spinal cord ischemia-reperfusion injury. 1295 48

Increased intracranial pressure (ICP) in patients with acute liver failure (ALF) remains a major cause of morbidity and mortality. Conventional methods of ammonia reduction such as the use of lactulose do not improve outcome, and metabolic substrates such as L-ornithine L aspartate may offer more promise. Mannitol remains the mainstay of therapy. An important role for cerebral hyperemia in the pathogenesis of increased ICP has led to a reevaluation of established therapies such as hyperventilation, N-acetylcysteine, thiopentone sodium, and propofol. Recent studies have focused on the role of systemic inflammatory response in the pathogenesis of increased ICP and support the use of antibiotics prophylactically. Moderate hypothermia reduces ICP in patients with uncontrolled intracranial hypertension and prevents increases in ICP during orthotopic liver transplantation (OLT). Advances in understanding the pathophysiological basis of intracranial hypertension in ALF have outstripped appropriate testing of the newly generated ideas in appropriate clinical trials, and more effort should be mounted at a national level to organize the appropriate multicenter studies required.
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PMID:Intracranial hypertension in acute liver failure: pathophysiological basis of rational management. 1452 80

Our objective was to evaluate intestinal ischemia-reperfusion injury in growing rats, modulated by hypothermia (I/RH) and N-acetylcysteine (NAC). We used 30 EPM-1 Wistar male rats, aged around 35 days, weighing 90 g. Rats were randomized into 5 groups with 6 animals in each: I/RH group, intestinal ischemia under hypothermia for 40 min and reperfusion for 30 min; I/RH-NAC group, same procedure but adding NAC (150 mg x kg(-1)), previously with ischemia; S-H group, topic hypothermia for 40 min, and observation for 30 min; I/R H-Ve group; and S-NAC group, NAC administration and observation for 70 min. All animals were heparinized and anesthetized with ketamine (60 mg kg(-1)) and xylazine (10 mg kg(-1)) intramuscularly. Surgical procedures were done under microsurgical technique (augmentation, 10x). After laparotomy, the superior mesenteric artery was dissected and clamped to promote ischemia. Topic hypothermia was obtained by using plastic bags at 4 degrees C, changed every 10 min. Rats were sacrificed by exsanguination, and blood samples were utilized to measure D(-)lactate. Intestinal fragments were removed for morphological study. Statistical analysis was done with nonparametric tests (P <or= 0.05). Concerning to D(-)lactate, the data showed biochemical tissue injury, with hypothermia only (S-H = 27 mg/dl), and this became more important when intestinal ischemia and reperfusion were associated to hypothermia (I/RH = 36 mg/dl). NAC decreased ischemia-reperfusion injury (I/RH-NAC = 19 mg/dl). Morphologic tissue injuries, evaluated by hematoxylin-eosin staining, showed grades 4 and 5 for the I/RH and I/RH-Ve groups, respectively, in contrast with other groups (I/RH-NAC = 2, S-H = 1, and S-NAC = 1). Based on our data, we conclude that intestinal ischemia reperfusion injury occurred morphologically as well as functionally, even under hypothermia. However, NAC showed a protective effect on the small bowel from ischemia-reperfusion injury.
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PMID:Intestinal ischemia and reperfusion injury in growing rats: hypothermia and N-acetylcysteine modulation. 1455 14

Acute liver failure (ALF) is an uncommon medical emergency whose rapid progression and high mortality demand early diagnosis and expert management, including immediate transfer of any potential case to facilities for intensive care and orthotopic liver transplantation (OLT). All patients with ALF must be screened aggressively for acetaminophen toxicity (history, serum levels, "hyperacute" presentation with renal failure), for other drugs, and viral hepatitis; rare causes of ALF should also be considered. After an acetaminophen overdose, N-acetylcysteine must be given as early as possible, preferably in the emergency room, but any patient with ALF should promptly receive N-acetylcysteine if there is suspicion of acetaminophen toxicity irrespective of the time of ingestion. Supportive care for all patients with ALF includes adequate enteral nutrition, aggressive screening and treatment of infection, prophylactic broad-spectrum antibiotics, and antifungal agents. Sedation with propofol is given for severe agitation or mechanical ventilation. With advanced coma grades, intensive care is needed with hemodynamic monitoring, ventilatory support, continuous renal replacement for renal failure, and intracranial pressure monitoring. Intracranial hypertension is treated with mannitol and/or acute short-term hyperventilation, but if the patient is refractory to treatment, mild-moderate hypothermia is achieved by a cooling blanket that is continued throughout OLT. Barbiturate coma is only used in refractory cases as the last treatment modality. Seizures are aggressively treated with phenytoin, with additional diazepam as needed. Candidacy and activation for OLT should be completed as early as possible in the course of ALF, especially in "hyperacute" cases such as acetaminophen toxicity. The final decision to proceed with OLT is made when a donor organ becomes available. King's College Hospital criteria for OLT are still the best prognostic assessment for fatal outcome in ALF, but the criteria fail to identify some patients who will die.
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PMID:Acute Liver Failure. 1552 12

In acute liver failure (ALF) patients that have raised increased intracranial pressure (ICP), mortality remains unacceptably high. There has been an explosion in the knowledge about the pathophysiological basis of raised ICP but treatment modalities are limited. Current therapy is aimed at reducing the circulating ammonia levels and attempts to reduce brain swelling which are only moderately effective. More recently, cerebral hyperemia has been suggested as being of major importance in the pathogenesis of increased ICP providing a new look at interventions such as hyperventilation, N-acetylcysteine, thiopentone sodium and propofol. More recently studies have focused upon the role of systemic inflammatory response in the pathogenesis of increased ICP and support the use of antibiotics prophylactically. The application of moderate hypothermia to treat uncontrolled intracranial hypertension seems promising and its exact place will be decided in a large trial being planned in USA and Europe. Early data from studies in an animal model suggests that albumin dialysis is a promising new tool to treat intracranial hypertension in patients with ALF. The recent advance in our understanding of the pathophysiological basis of intracranial hypertension has provided the platform for the discovery of new treatments.
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PMID:Pathophysiological basis of therapy of raised intracranial pressure in acute liver failure. 1592 6


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