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)

Acute changes in mental status (AMS) develop in children with cancer from a multitude of cancer- and treatment-related complications. To determine the incidence, etiology, and outcome of children with cancer who had AMS, the medical records of all children under 18 years of age with systemic cancer (excluding primary central nervous system tumors) who had AMS in our institution during the years 1981 through 1987 were reviewed. AMS developed in 89 of 815 children at risk (11%). The AMS was caused by seizures in 53 (60%), an encephalopathy in 24 (27%), and a stroke syndrome in 12 (13%). AMS occurred in 42 of 305 (14%) with leukemia, 16 of 139 (12%) with lymphoma, 14 of 136 (10%) with sarcoma, 10 of 104 (9%) with neuroblastoma, and 7 of 104 (5%) with other malignancies. Children with acute lymphocytic leukemia were more prone to having seizures (61%), while children with nonacute lymphocytic leukemia were almost equally likely to have encephalopathies, strokes, or seizures. Children with lymphoma were admitted for treatment most often with an encephalopathy (44%). Etiologies for AMS were evaluated vigorously, and one or more etiologies were identified in 80 of 89 (89%) patients. Dependent on the type of tumor, the anticancer treatment used and, timing during the course of illness AMS occurred, specific diagnoses were more likely. Neurologic morbidity and mortality were dependent on the cause of AMS. Children with seizures that were initially difficult to control were more likely to require long-term anticonvulsant therapy.
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PMID:Acute mental status changes in children with systemic cancer. 230 89

Early results with ifosfamide plus mesna in soft tissue sarcoma showed an initial response rate of 38% in 42 patients. All these patients treated at The Royal Marsden Hospital plus 30 more (total 67) have now been analysed. Single doses of 5 or 8 g/m2 ifosfamide were given over 24 h by infusion in dextrose saline together with 400 mg/m2 or 600 mg/m2, respectively, of mesnum every 4 h to give a total of 9 doses. A diuresis of 200 ml/hour was maintained during therapy. Treatment was repeated 3-weekly. CR was seen in 6 and PR in 10 patients. More recently doxorubicin was added to ifosfamide therapy in an attempt to improve on these results. At first only 20 mg/m2 doxorubicin was given but this was escalated to 40 mg/m2 and 60 mg/m2. Mesna has been given in higher dosage (5 g/m2 over 24 h), but otherwise the schedule is as above. In all 60 patients have been treated and most are now evaluable for response. Encephalopathy has been seen with both regimens. The incidence and patient characteristics are reported.
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PMID:Ifosfamide plus mesna with and without adriamycin in soft tissue sarcoma. 310 88

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

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

To determine the maximum tolerated dose (MTD) of escalating doses of interferon-alpha-2b (IFN, Intron A) with 5-fluorouracil (5-FU) and cisplatin (DDP) in patients with advanced cancer, 15 patients were accrued between May 1990 and July 1991. Primary sites were unknown (3), colorectal (3), head and neck (2), lung (2), gynecologic (1), gallbladder (1), sarcoma (1), anal canal (1) and pancreas (1). IFN was given s.c. on days 1-5 and then three times weekly with DDP (75 mg/m2, day 1) and 5-FU [750 mg/m2, days 1-5, continuous infusion (CI) on a 28-day cycle. The first two patients treated at level I (3 x 10(6) U/m2 s.c.) experienced possible neurotoxic deaths [massive cerebrovascular accident (CVA) and metabolic encephalopathy], and patient 3 had a grade 4 toxicity of performance status decline. Analysis of these events led us to exclude the enrollment of patients on i.v. morphine and of those with prior exposure to DDP. This resulted in grade 3 toxicity in terms of nausea, vomiting, fatigue and leukopenia but in no further CNS event. All patients were evaluable for toxicity but only ten were evaluable for response. Only two partial responses were seen, one in a patient with an unknown primary tumour and one in a patient with head and neck cancer. The combination of IFN is possible with 5-FU and DDP. The recommended dose of IFN is 2 x 10(6) U/m2 s.c. in patients with no prior exposure to DDP or i.v. morphine, given together with 5-FU (750 mg/m2, days 1-5, CI) and DDP (75 mg/m2, day 1) on a 28-day cycle.
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PMID:A phase I study of recombinant human interferon alpha-2b combined with 5-fluorouracil and cisplatin in patients with advanced cancer. 788 58

Administration of vitamins or metals may cause severe side effects. Retinoids (derivatives of vitamin A) used for the treatment of various skin disorders are teratogenic, hepatotoxic and may induce a substantial increase in serum lipids. A case report demonstrates that vitamin D supplementation in a patient under total parenteral nutrition can cause hypercalcemia. The isolated administration of vitamin B1, without concomitant vitamin B6 and nicotinamide may precipitate potentially life-threatening pellagra encephalopathy. Repeat blood transfusions may produce clinically overt organ hemosiderosis, e.g. cirrhosis of the liver, diabetes mellitus or myocardiopathy. The literature contains reports on a few cases of sarcoma associated with orthopedic metal implants. The controversial issue of the potential dangers of dental amalgams is briefly mentioned.
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PMID:[Vitamins and metals: possible hazards for humans]. 866 74

Among 47 patients with thrombotic thrombocytopenic purpura (TTP), 8 patients were diagnosed to have postoperative-TTP. Two patients underwent vascular surgery, 5 patients coronary artery bypass grafts, and 1 patient resection of myocardial sarcoma. Prior to surgery, all patients except one had normal hemograms and platelet counts, and blood smears showed no schistocytes. Five to 19 days after surgery, all 8 patients developed postoperative TTP, which clinical feature was characterized by unexplained progressive encephalopathy, thrombocytopenia, and microangiopathic hemolytic anemia. In addition, in 3 patients, progressive gangrene of the toes also developed. Four patients achieved complete remission following exchange plasmapheresis and 1 patient spontaneous remission. Due to complicated surgical settings after surgery, recognition of TTP was often delayed and it contributed to death in 3 patients despite treatment with exchange plasmapheresis. In view of occurrence of postoperative TTP following cardiac and vascular surgeries, pathogenic mechanism for postoperative TTP may be explained on the basis of injury of diseased endothelial surface and release of a humoral factor(s) that results in platelet aggregation in the capillaries and arterioles. Our experience with these cases indicates that TTP may occur as a serious complication of cardiac and vascular surgeries, and early recognition of the diagnosis and institution of exchange plasmapheresis are of paramount importance for favorable outcome.
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PMID:Postoperative thrombotic thrombocytopenic purpura following cardiovascular surgeries. 881 90

The increasing doses of 2.4-3.5 g/m2 ifosfamide, i/v, dropwise, were administered for 40 min, on days 1-5 each week, for 3 weeks, in 4 courses. Simultaneously, MESNA was given in a dose two-thirds of that of ifosfamide. The maximum single tolerable dose of ifosfamide was 3.2 g/m2. The dose of 3.5 g/m2 proved neurotoxic causing encephalopathy. The other toxic effects were stage III-IV neutropenia (47%), nausea and vomiting (91%) and weakness (33%). No clinical evidence of renal failure was attributed to the high dosage of the drug in the course of assays of biochemical components of the blood, blood- and urine-beta-2-microglobulins, N-acetyl-D-hexoaminidase (NAG) level in urine, creatinine clearance and complex renoscintigraphy data. On days 3-5, ifosfamide treatment was followed by increase in NAG and beta-2-microglobulin levels in urine which pointed to the toxic effect exerted on the epithelium of renal tubules. The antitumor effect was apparent in 5 (29%) patients for 6 months, which testifies to the high effectiveness of ifosfamide treatment for soft-tissue sarcoma.
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PMID:[High-dose ifosfamide in the treatment of patients with soft tissue sarcoma]. 912 96

Actinomycin-D (Act-D) is a rare cause of veno-occlusive disease (VOD). Between 1993 and 1998, we managed 6 patients, all male, median age 19 months (range 6-48 months) who received Act-D for Wilms' tumour (n=4), clear cell sarcoma (n=1) or rhabdomyosarcoma (n=1). VOD presented with a median platelet count of 12 x 10(9)/l, INR 3.8, fibrinogen 16 mg/l, fibrinogen degradation products (FDPs) > or =80 microg/l, aspartate aminotransferase (AST) 6922 IU/l, bilirubin 47 micromol/l. In 3 cases, transient liver dysfunction and thrombocytopenia without neutropenia had been observed after a previous course of Act-D. All six children developed encephalopathy, hepatomegaly, ascites, reversed portal flow and renal impairment. All received mechanical ventilation and two required haemofiltration. The treatment was supportive. Severe Adult Respiratory Distress Syndrome developed in 3 patients, all of whom died. 3 patients recovered. The outcome of VOD with multi-organ failure is poor. Intravascular coagulopathy precedes and characterises severe VOD during Act-D treatment.
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PMID:Veno-occlusive disease with multi-organ involvement following actinomycin-D. 1137 45

Neurotoxicity is a clinically relevant adverse event observed with the use of ifosfamide. It is usually mild, occasionally severe and seldom fatal. Ifosfamide-induced encephalopathy requires interruption of chemotherapy, intravenous hydration and administration of methylene blue. Less is known about the efficacy of methylene blue in avoiding a second episode of ifosfamide-induced encephalopathy while maintaining chemotherapy with ifosfamide. We report a case of a different clinical manifestation of ifosfamide-induced encephalopathy after continued ifosfamide use and despite methylene blue in a patient with retroperitoneal sarcoma.
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PMID:Ifosfamide encephalopathy and use of methylene blue. A case report of different sequential neurotoxicity. 1985 74


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