Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six forms of reversible adverse reactions to adenine arabinoside (vidarabine) were observed in a two-year period among 42 patients (19 of whom had lymphomas, leukemias, or other malignancies) who were treated for complicated infections with varicella-zoster or herpes simplex virus. Six patients received placebo. Ten patients received 10 mg of adenine arabinoside/kg per day; three received 15 mg/kg; 22 received 20 mg/kg; and one received 30 mg/kg. Patients were treated (by continuous intravenous injection) for an average of seven days. Toxic effects were nausea and vomiting, weight loss, weakness (often with impaired ambulation), megaloblastosis in erythroid series in bone marrow, tremors five to seven days after the start of therapy (including tremors in one patient with abnormal electroencephalograms that were consistent with toxic-metabolic encephalopathy), and thrombophlebitis at the intravenous site. Side effects clearly predominated in patients who received 20 mg/kg per day. Therefore, treatment with 10 mg/kg per day appears preferable until the relation of toxicity to dosage level can be clarified.
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PMID:Toxicity of adenine arabinoside in humans. 18 Jan 99

We undertook this phase II study to evaluate the efficacy and toxicity of epidoxorubicin and ifosfamide in the treatment of locally advanced and/or metastatic soft-tissue sarcomas. We used escalating doses of epidoxorubicin (from 60 to 75 mg/m2) on day 1 and 1.2 g/m2 ifosfamide on days 1-5. Chemotherapy courses were repeated every 3-4 weeks. A total of 16 patients--13 who had not previously been treated and 3 who had undergone prior therapy with anthracyclines--entered the study. In all, 15 patients were evaluable for response and 16, for toxicity. At least two courses of chemotherapy were given. A complete remission (CR) was seen in 1 patient, a partial remission (PR) in 5, and a minor response (MR) in 1, for an objective response rate (CR + PR) of 40% (6/15); this value reached 50% in non-pretreated patients (6/12). Stable disease (SD) was observed in 40% (6/15) of patients. The relative dose intensity of epidoxorubicin ranged from 10 to 23.3 mg/m2 (median, 16.6 mg/m2). The time to objective response ranged from 4 to 12 weeks (median, 8.5 weeks). The duration of response was 4 months for the single CR, and that for the five PRs was 6+ months (range, 4-18 months). Toxicity was evaluated according to WHO criteria in 16 patients; it was mild and consisted mainly of alopecia, nausea and vomiting, and leucopenia. In only three patients did we observe grade 3 leucopenia. In one case an ifosfamide-associated encephalopathy occurred, but it regressed after 24 h. Neither chronic nor acute cardiac toxicity was reported. In this preliminary analysis, the response rate obtained with the combination of epidoxorubicin and ifosfamide was encouraging and the toxicity was acceptable.
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PMID:Epidoxorubicin plus ifosfamide in advanced and/or metastatic soft-tissue sarcomas. 212 78

The authors report on thirteen patients who developed a variety of symptoms after transurethral resection of the prostate; confusion, seizures, blurred vision with mydriasis, nausea and vomiting, bradycardia, and hypotension. This post-resection syndrome is caused by resorption of a large amount of the hypotonic solution used during the surgical procedure and containing 1.5% glycine. Postoperative sodium levels were assayed in all patients and consistently found to be low (105 to 124 mEq/l). Serum glycine was measured in three patients and the very high levels found suggest that absorption of glycine during transurethral resection of the prostate may contribute to the symptoms of encephalopathy.
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PMID:[Resorption of the lavage fluid during transurethral resection of the prostate. Apropos of 13 cases]. 229 46

Calcium hopantenate (HOPA) has been widely used as an activator of cerebral metabolism in Japan. However, several cases of acute encephalopathy during HOPA administration were recently reported, which were characterized by marked metabolic acidosis and hypoglycemia. The encephalopathy in these patients was named Reye-like syndrome because of the similarity to Reye's syndrome in children. The purposes of this presentation are to report on 5 patients with acute encephalopathy developing during HOPA administration, to summarize their symptoms and clinical courses, and to discuss the pathogenesis of metabolic acidosis and hypoglycemia. Initial characteristics of the clinical course in all patients were loss of appetite, nausea and vomiting, followed by unconsciousness. Laboratory examinations revealed marked metabolic acidosis, severe hypoglycemia, hyperlactacidemia, leukocytosis, ketonuria, and increased Ht and BUN. A few days after development of the initial symptoms, mild renal and liver dysfunction, and elevation of serum amylase were observed in all patients. Hyperlactacidemia was present in 4 in the initial period. Blood concentration of HOPA was 2.131 micrograms/ml in patient 1 (8-10 hours after final administration), and 10.7 micrograms/ml in patient 5 (24 hours after final administration). These values are extremely high, because usually HOPA concentration is almost negligible 7 hours after the drug is taken. As the pathogenesis of acute encephalopathy due to HOPA administration, the failure of fatty acid beta-oxidation has been proposed by some investigators. However, the serum concentrations of CoA, pantothenic acid and carnitine during the initial stage were not reduced in our patients. Furthermore, it is very difficult to explain the severe hypoglycemia in terms of the beta-oxidation theory.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Metabolic acidosis and hypoglycemia during calcium hopantenate administration--report on 5 patients]. 258 87

To augment the antitumor effect of high-dose melphalan and determine pharmacokinetics we conducted a phase I trial of escalating doses of high-dose IV melphalan with the chemosensitizer misonidazole for patients with advanced colorectal carcinoma. Fourteen patients with modified Dukes D adenocarcinoma of the colorectum were treated with a single course of melphalan (40-60 mg/m2 i.v. bolus q.d. X 3 days) and misonidazole (1-3 g/m2 p.o. q.d. X 3 days) followed by autologous bone marrow transplantation. Toxicity consisted of severe myelosuppression, moderate nausea and vomiting, and mild mucositis and diarrhea. One patient developed unexplained renal tubular acidosis, and a diffuse encephalopathy occurred in another patient. Three patients died within the first 30 days after the start of treatment, two due to tumor progression and one due to sepsis and disseminated intravascular coagulation-induced intracerebral hemorrhage. Six of 14 patients achieved a partial response, and the median response duration was 4 months (range 3-10 months). Analysis of misonidazole serum concentrations showed similar pharmacokinetics to those previously reported, suggesting no significant drug interaction with intravenous melphalan. Mean peak serum concentrations ranged from 81.8 micrograms/ml to 115.2 micrograms/ml at the second and third misonidazole dose levels, which approximate those known to provide effective chemosensitization with melphalan in animal models. In this phase I study, we showed that maximally tolerated doses of intravenous melphalan can safely be combined with oral misonidazole. In view of the large volumes of oral misonidazole required at the highest dose level, subsequent studies to determine the maximally tolerated dose of misonidazole should employ the intravenous form.
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PMID:High-dose melphalan, misonidazole, and autologous bone marrow transplantation for the treatment of metastatic colorectal carcinoma. A phase I study. 265 May 27

Twenty patients with advanced epithelial ovarian carcinoma who had failed alkylating agent treatment were given cisplatin 60 mg/m2 together with ifosfamide 4 g/m2 and mesna 6 g/m2 every 4 weeks for 4-6 cycles. The overall response rate was 45% and the complete response rate 20%. The median time to disease progression was 9 months and 4 of the 9 responding patients are alive at more than 2 years. WHO Grade 3 or 4 myelosuppression was seen in 7 patients, nephrotoxicity in 4, and encephalopathy in 1 patient. Nausea and vomiting of moderate severity (WHO Grade 3) was seen in the majority of patients. While a dose escalation of 25% of both drugs was possible in 4 patients, myelosuppression became limiting at the higher dose. The combination of cisplatin and ifosfamide is effective in relapsed ovarian cancer even in this group of patients with heavy pretreatment.
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PMID:A study of cis-platinum and ifosfamide in alkylating agent-resistant ovarian cancer. 291 Jul 85

One hundred and seventy-one patients with advanced soft tissue sarcoma entered a randomized crossover phase II study comparing cyclophosphamide (CYCLO) with a new analogue, ifosfamide (IFOS), both administered as 24 h i.v. infusions every 3 weeks. The doses used were CYCLO 1.5 g/m2 and IFOS 5 g/m2, with provision for dose escalation. All patients received mesna 400 mg/m2 as an i.v. bolus 4 hourly X 9 doses, commencing at the start of the oxazophosphorine infusion. Patients who had received previous chemotherapy were eligible provided this did not include a classical alkylating agent. There were 22 patients who were ineligible, and response could not be evaluated in 12 additional patients. IFOS produced two complete and ten partial remissions, for an overall response rate of 18%. CYCLO was significantly (P = 0.04) less active, producing one complete and five partial remissions, an overall response rate of 9%. Stabilization of disease was similar in both arms (27% and 24% respectively), but fewer patients showed progression on IFOS. The response rate was higher (20% vs 5%) for patients who had not received previous chemotherapy, and also for female compared with male patients (21% vs 5%). When only patients who had not received previous chemotherapy were considered, the respective response rates for IFOS and CYCLO were 24% and 15%. There were no responses in previously treated patients receiving CYCLO. There were four partial responses in 33 patients crossing from CYCLO to IFOS, but no responses in 18 patients receiving CYCLO after IFOS. Leucopenia was significantly more pronounced (P = 0.0004) with CYCLO, both after the first course and throughout treatment, although the incidence of severe infections, 6%, was the same in both arms. Nausea and vomiting were more severe with IFOS (P = 0.022), but other toxicities were mild. Grade 1 or 2 bladder (haematuria) or renal (rise in serum creatinine) toxicity was slightly more frequent with IFOS (7 vs 3 patients) and was a reason for stopping treatment for one patient in each arm. Three episodes of mild to moderate drowsiness after IFOS were reported, but no severe encephalopathy. A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination with such active agents as adriamycin.
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PMID:Cyclophosphamide versus ifosfamide: preliminary report of a randomized phase II trial in adult soft tissue sarcomas. 310 89

The first cases of fulminant hepatic failure due to paracetamol poisoning were reported in 1966, and in the United Kingdom this condition is now responsible for more cases of acute hepatic failure than any other cause. Adults account for the majority of serious and fatal cases of paracetamol poisoning and it is extremely rare for young children to ingest sufficient paracetamol to cause more than minimal liver damage. A single measurement of the plasma paracetamol concentration is an accurate predictor of liver damage provided that it is taken not earlier than 4 hours after ingestion of the overdose. Peak disturbance of liver function occurs 2 to 4 days after the overdose, often accompanied by mild jaundice, after which recovery is usually rapid and complete. In a few patients, fulminant hepatic failure, manifested by increasing jaundice and encephalopathy, may develop by the third to fifth day. Acute renal failure may complicate paracetamol poisoning, often in the context of severe liver damage. Renal failure, which is often non-oliguric, typically becomes apparent 24 to 72 hours after overdosage. The treatment of paracetamol intoxication should include gastric lavage, which has been shown to be of value for up to 6 hours after ingestion of a paracetamol overdose. Further general treatment may include parenteral fluid replacement and a prophylactic infusion of dextrose (5-10%) in patients at risk of hepatic failure. Specific protective agents in those patients at risk of paracetamol-induced liver damage include N-acetylcysteine and methionine which are most effective if given within 8 to 10 hours of ingestion of the overdose. Hepatic and renal failure should be managed conventionally. In recent years in the United Kingdom there has been a gradual decline in the number of hospital admissions and the number of deaths from aspirin poisoning. Salicylates in overdose directly stimulate the respiratory centre and so cause a respiratory alkalosis. Metabolic acidosis occurs in severe poisoning because of impairment of the oxidative metabolism of energy substrates. At very high salicylate concentrations respiratory depression may occur, possibly associated with neuroglycopenia, adding respiratory acidosis to the worsening metabolic acidosis. In addition to a mixed acid-base disturbance, hypokalaemia and hypoglycaemia may be present. Nausea and vomiting increase the fluid deficit. If dehydration is sufficiently severe, decreasing cardiac output may hasten development of lactic acidosis and acute renal failure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Non-narcotic analgesics. Problems of overdosage. 355 83

Ifosfamide (IFOS) 5 g/m2 and its parent analog Cyclophosphamide (CYCLO) 1.5 g/m2 were studied in a randomized phase II study, accruing 171 patients with advanced soft tissue sarcoma. Both drugs were administered as 24 hr infusions, every 3 weeks, with comcomitant Mesna 400 mg/m2 i.v. bolus 4 hourly X 9 doses. Twenty-four patients were ineligible and 12 were not evaluable. The groups were well matched for age, previous chemotherapy (42% of the total) or radiotherapy, the presence of distant metastases and performance status, but there were more females (59% vs. 45%) in the IFOS arm. Among the 68 evaluable patients receiving IFOS, there were 2 CR, 10 PR (overall response 18%), 27 SD and 29 PD. For CYCLO, the corresponding results in 67 patients were 1 CR, 4 PR (overall response 8%), 23 SD and 39 PD. Using the chi-square test the P values for response rate and linear trend were 0.13 and 0.04 respectively. Response rates were higher for females (20% vs. 5%, P = 0.01) and patients who had not received previous chemotherapy (19% vs. 4%, P = 0.01). Fourteen of the 17 responses came from a group of 43 females, who had not received previous chemotherapy, for whom the overall response rate was 37.5%. Remissions were noted in only 4 histological subtypes (centrally reviewed material), i.e., 5 of 17 synovial sarcomas, 7 of 13 mixed mesodermal sarcomas and 2 of 7 fibrosarcomas. One of the 31 leiomyosarcomas responded to Cyclophosphamide. Durations of response did not differ significantly between the 2 arms--median 26, range 10-81+ weeks. Leucopenia was significantly more severe on CYCLO, particularly in patients who had received previous chemotherapy (P = 0.007). Serious infections occurred in approx. 7% of patients with no difference between the two drugs, although there was one toxic death on CYCLO. Nausea and vomiting were significantly worse on IFOS and alopecia, related in extent to dose, was seen in both arms. Other side-effects, such as hematuria or rises in serum creatinine and encephalopathy, were infrequent and mild. A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination therapy.
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PMID:Cyclophosphamide versus ifosfamide: final report of a randomized phase II trial in adult soft tissue sarcomas. 359 91

In a comparative randomized double-blind study, 73 patients underwent myelography using iopamidol (36 patients) or metrizamide (37 patients) as contrast medium. The overall diagnostic adequacy of iopamidol myelography was found to be comparable to that of metrizamide myelography. The incidence of examinations graded as superior (64%) or adequate (36%) with iopamidol was equivalent to that with metrizamide (57% superior, 43% adequate). Adverse reactions after iopamidol myelography were fewer, less severe, and generally of shorter duration than those associated with metrizamide. In the iopamidol group, adverse reactions occurred in nine (25%) patients, all of whom experienced mild or moderate headache, one with nausea, vomiting, and fatigue. In the metrizamide group, adverse reactions occurred in 17 (46%) patients, all of whom experienced mild or moderate headache, six with nausea and vomiting and four with back and leg pain. Of nine individuals who underwent myelography using 300 mg 1/ml metrizamide injected via lateral C1-C2 puncture, three experienced a toxic encephalopathy with confusion, dysphasia, headache, nausea, and vomiting, and a fourth individual suffered severe nausea, vomiting, fever, and irregular pulse. Encephalopathy was not observed in any of the 11 patients in whom myelography was performed via lateral C1-C2 puncture with a similar concentration of iopamidol. No seizures were encountered, and no clinically significant changes in laboratory studies were observed with either contrast medium.
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PMID:Iopamidol and metrizamide for myelography: prospective double-blind clinical trial. 638 81


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