Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines are polypeptides which possess various biological properties affecting host defense function and response to disease. Two cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF) induce fever, hypotension and inflammation when injected into animals or human subjects. In humans injected with either IL-1 or TNF, sleepiness, generalized myalgias and headache are commonly reported. Therefore, the production of IL-1 and TNF as a consequence of hemodialysis was hypothesized to explain, in part, the signs and symptoms of the dialysis patient. Laboratory studies confirmed that the activation of complement and the passage of microbial products from the dialysate into the blood compartment induces the synthesis of IL-1 and TNF. Although elevated production of IL-1 and TNF in the mononuclear cells and in the circulation of patients during and after hemodialysis have been reported, these levels have not been a consistent finding and are low compared to the amount of dialysis related symptoms. Recent studies, however, demonstrate that IL-1 and TNF have naturally occurring antagonists which specifically block the biological activities of these two cytokines. The IL-1 receptor antagonist blocks IL-1 binding to cells but has no IL-1 activity of itself. Soluble TNF receptors prevent TNF from binding to its cellular receptors and hence serve as anti-TNF mechanisms. These inhibitors are currently in clinical trials for sepsis where efficacy has been demonstrated; however, the IL-1 receptor antagonist (IL-1Ra) and soluble TNF receptors (sTNFR) are likely candidates for use in dialysis patients with symptomatic hypotension. Although levels of IL-1Ra and sTNFR are elevated in patients on HD, these levels reflect the host response to inflammation. It is unclear whether acute or chronic administration of IL-1Ra or sTNFR will be beneficial in treating some of the acute or chronic changes seen in dialysis patients.
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PMID:Interleukin-1 and tumor necrosis factor and their naturally occurring antagonists during hemodialysis. 132 57

Doxifluridine, a new fluorouracil analog with a low myelosuppressive effect, has recently been subject to various disease-oriented, Phase II trials. For the present evaluation of drug tolerance, the Phase II data of 114 patients having received 376 doxifluridine cycles has been used. The treatment cycles consisted of 5 daily intravenous injections of 4,000 mg/m2 non-pretreated patients, and 3,000 mg/m2 in pretreated patients. Previous observations showing that doxifluridine is less myelotoxic than fluorouracil have been confirmed. 54% of the patients had no leucopenia (maintaining WBC counts over 3,000/mm3 and 90% had no thrombopenia (platelets not lower than 100,000/mm3) throughout treatment. However, a WHO grade 4 hematologic toxicity was observed in 9 patients, and 2 toxic deaths were related to severe granulocytopenia and sepsis. Digestive tract toxicity was similar and equally frequent as the one observed with fluorouracil: mucositis with oral ulcerations (19%), nausea and vomiting requiring specific treatment (8%) and severe but never hemorrhagic diarrhoea (5%). Neurologic toxicity was frequent, with 20% of patients complaining of somnolence and/or peripheral neuropathy, 7% of impaired consciousness and 1% of WHO grade 4 cerebellar ataxia. Among the 10% of patients with cardiac symptoms, 6% were benign and transient arrhythmias, and 4% were severe, including 1 myocardial infarction, 1 spontaneously reversible cardiac arrest and 2 ventricular fibrillations successfully treated with cardioversion. In spite of its encouraging antitumor activity and its good hematologic tolerance, intravenous doxifluridine, as used in this study, cannot be recommended because of the observed neurologic and cardiac toxicity. Oral doxifluridine is presently under investigation with preliminary results suggesting a lack of neuro- or cardiotoxicity.
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PMID:[Doxifluridine toxicity, a fluorouracil analog with low myelosuppressive effect]. 214 Feb 80

The clinical, pathomorphological and microbiological findings during meat inspection in 599 pigs with endocarditis at slaughter were studied. Clinical signs were observed in 41 per cent of the pigs on ante-mortem inspection. Lameness was the most common sign. However, this symptom is not very specific of endocarditis. This is also true of various other symptoms. Only dyspnoea and drowsiness were indicative of endocarditis to some extent, but occurred only sporadically. Extracardial lesions were observed in 66 per cent of the pigs with endocarditis on post-mortem inspection. Metastatic processes (infarction or inflammatory foci) were most frequently detected in the kidneys. These were highly specific of endocarditis. In addition, the following changes were observed in decreasing incidence: signs of sepsis (hyperplastic splenitis, petechiae and degradation of organs), inflammatory lesions of the joints and legs, metastatic pneumonia and inflammation of the tail. Bacteriological examination was positive in 62 per cent of the cases. Streptococci were the organisms most frequently isolated (36 per cent), followed by Corynebacterium pyogenes (19 per cent) and Erysipelothrix rhusiopathiae (14 per cent). The discussion is concerned with the significance of these bacteria to meat-consumers.
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PMID:[Endocarditis and meat inspection in slaughtering pigs. 1. Clinical, pathological and microbiological aspects]. 368 3

Twelve fatal cases of encephalopathy associated with sepsis were examined in a ten-year retrospective study. The sources of infection and organisms isolated were variable. Six of the patients had focal neurologic signs; five had seizures. The level of consciousness varied from drowsiness to deep coma, and electroencephalograms revealed diffuse or multifocal abnormalities. Computed tomographic head scans and cerebrospinal fluid examinations were usually unremarkable. Eight patients had disseminated microabscesses in the brain at autopsy. Four patients had proliferation of astrocytes and microglia in the cerebral cortex, a feature associated with metabolic encephalopathies. Additional findings included cerebral infarcts, brain purpura, multiple small white matter hemorrhages, and central pontine myelinolysis. Although sepsis may cause encephalopathy by producing disturbances in cerebral synaptic transmission and cerebral energy production through a toxic mechanism, bacterial invasion of the brain with the formation of disseminated microabscesses is also an important cause.
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PMID:The encephalopathy of sepsis. 408 65

The first reported case, in an adult, of cholestyramine induced hyperchloremic metabolic acidosis is a 70 year old female with a two year history of primary biliary cirrhosis confirmed by histologic and immunologic criteria. After taking cholestyramine II sachets twice daily for two months she presented with lethargy, confusion and drowsiness. Examination revealed confusion, jaundice, signs of chronic liver disease, portal hypertension and hepatic encephalopathy. Laboratory investigations confirmed a metabolic acidosis (pH 7.15) and hyperchloremia. Multiple cultures failed to reveal sepsis and a urinary pH of 4.85 together with tests of renal acidification, excluded renal tubular acidosis. She received 600 mEq of sodium bicarbonate intravenously over 36 hours by which time her mentation, electrolytes and pH were normal. It is presumed that her hyperchloremic metabolic acidosis was secondary to cholestyramine because of the similarity to pediatric reports; the rapid and lasting response to intravenous sodium bicarbonate; the absence of another etiology; normal serum potassium, chloride and bicarbonate despite continued spironolactone therapy after recovery.
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PMID:Cholestyramine induced hyperchloremic metabolic acidosis. 659 13

We studied prospectively the syndrome of brain edema after a large infarction in 12 patients. The major symptom was drowsiness, which began on the first to fourth day after the ictus and which was accompanied by asymmetry in pupillary size of 0.5 to 2.0 mm in eight patients, periodic breathing in seven, and Babinski's sign contralateral to the hemiparesis in five. These accompanying signs appeared several hours after drowsiness in some patients. Seven patients had brain death, one died of sepsis after recovering from brain swelling, and only four survived. In six patients in whom intracranial pressure was continuously measured, levels persistently above 15 mm Hg were associated with eventual brain death (four patients) and levels below 15 mm Hg were associated with survival (two patients).
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PMID:Brain edema after stroke. Clinical syndrome and intracranial pressure. 660 14

Results of CNS prophylaxis of 43 LLA children are studied. Prognostic characteristics of the group, follow-up time, and controls made are reported. Prophylaxis was made with intrathecal methotrexate associated to craneal (24 patients) or craneospinal irradiation. There was a 13% of meningosis between three and 27 months of the first complete remission. There were no differences of effectiveness between the two methods of treatment. The side effects were mild. Fifty five percent of patients showed fever, and vomits after intrathecal methotrexate injections, and 16% somnolence postradiotherapy syndrome. There were two more severe complications, one sepsis and one necrotizing leukoencephalopathy.
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PMID:[CNS prophylaxis in acute lymphoblastic leukemia (author's transl)]. 692 75

The authors report on a case of sepsis due to E. coli in a newborn baby with galactose intolerance. The immature immunological state of the newborn child in combination with a disorder of galactose metabolism obviously favour the development of bacterial infections. Galactose-free formulas should be applied quickly together with an adequate antibiotic therapy in the case of newborn babies with suspected bacterial infection. The prognosis may be influenced favourably by early clarification of the cause of severe impairment including jaundice, vomiting, loss of weight and somnolence in the first three weeks of life.
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PMID:[Sepsis due to E. coli in newborns with galactose intolerance (author's transl)]. 701 51

Patients with sepsis often manifest disorientation, somnolence, asterixis and coma, symptoms also seen in portasystemic encephalopathy. Altered plasma concentrations of the neutral amino acids and in creased blood-brain transport of these acids may play a role in portasystemic encephalopathy. Plasma amino acids and blood-brain barrier transport of neutral amino acids were investigated in a rat model of abdominal sepsis, cecal ligation and puncture. The blood-brain transport was studied by the technique of Oldendorf with carbon-14-amino acids 12 and 24 hours after the induction of sepsis. In similar groups of animals, isolation of brain capillaries was carried out by the technique of Hjelle and the capillaries were incubated with carbon-14-amino acids to study transport activity. Plasma and brain amino acids were deranged in a fashion similar to the derangements seen in portasystemic encephalopathy, with a decrease in plasma branched chain amino acids and an increase in most neutral amino acids in brain. The changes were most pronounced after 24 hours. The brain uptake of several neutral amino acids was increased in the septic rats, while the uptake of lysine, a basic amino acid, was normal. In the brain capillaries isolated from septic rats, tyrosine and leucine transport was also greater than in sham-operated animals. Elevated neutral amino acids may play a role in the encephalopathy encountered in septic patients similar to its role in patients with portasystemic encephalopathy, as similar mechanisms appear to be operating.
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PMID:Blood-brain barrier derangement in sepsis: cause of septic encephalopathy? 745 18

Amifostine (WR-2721) was originally developed as a radioprotective agent. In animals, it protects normal tissues from the damaging effects of irradiation and, as shown in more recent studies, of several cytotoxic agents. Protection of tumours is generally reduced compared with that of normal tissues in animals, suggesting that amifostine may increase the therapeutic window of cytotoxic therapies. Clinical data concerning amifostine suggest that cytotoxic chemotherapy-induced haematological toxicity and cisplatin-induced neurotoxicity, nephrotoxicity and ototoxicity are decreased upon administration of amifostine prior to cytotoxic drugs. Similarly, amifostine reduces damage to normal tissues caused by radiotherapy. Available data show that this protection is achieved without adversely affecting tumour response or patient survival. In 1 large trial, the reduction in cyclophosphamide- and cisplatin-related toxicities manifested as a decrease in the incidence and severity of neutropenia-related fever and sepsis and in the number of patients with ovarian cancer who discontinue therapy before completion of treatment, thus improving the tolerability of this antineoplastic regimen. In addition, the incidences of cisplatin-induced nephro- and neurotoxicity were reduced. Increased doses of cytotoxic therapy have also been administered when amifostine was given prior to therapy, which may increase tumour response. The predominant adverse effect associated with amifostine are hypotension, nausea and vomiting, somnolence and sneezing. Thus, amifostine is likely to be a useful adjuvant to the treatment of patients with malignancy, particularly those receiving cyclophosphamide plus cisplatin. discontinued therapy before completion of treatment, thus improving the tolerability of this antineoplastic regimen. In addition, the incidences of cisplatin-induced.
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PMID:Amifostine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential as a radioprotector and cytotoxic chemoprotector. 861 69


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