Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted a phase II evaluation of edatrexate in 17 previously untreated patients with advanced adenocarcinoma of the pancreas; 14 patients had at least one month of therapy. The initial dose was 80 mg/m2iv. Treatment was administered weekly for 5 weeks, then every other week. Toxicity was generally mild. The median WBC nadir was 5.4 (range 0.6-7.4) x 10(3)/microliters, and the median platelet nadir was 164.0 (range 62.0-341.0) x 10(3)/microliters. One patient died with sepsis and gastrointestinal bleeding associated with pancytopenia. Five patients had a mild rash. Nausea occurred in 6 patients, including 3 who had vomiting. In addition, 11 patients complained of vague malaise which seemed to begin within 24-48 hours after administration of edatrexate, and lasted for 2 to 3 days, resolving within 6 days of drug administration. Median survival was 85 days. Although 5 patients had stable disease, including one with relief of pain, no major responses were seen, excluding, with 95% confidence, a response rate in excess of 20%.
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PMID:Phase II trial of edatrexate in patients with advanced pancreatic adenocarcinoma. 148 6

Aim of the study was to assess the activity of dihydroergocristine (DHEC, CAS 17479-19-5) in aged patients with impaired cognitive function. Twenty-five university hospital centres and 250 physicians participated in the study. 2,600 patients (1,104 males and 1,496 females, age range 50-80 years) were admitted to the study. Each patient was administered 6 mg/d DHEC for 120 days. Clinical evaluation was made through the SCAG Rating Scale registered at basal time, after 60 and 120 days. Responsivity to treatment was considered high when the final score was reduced by 30% and none if less than 10%. Analysis of results demonstrated that at the end of the study responsivity was high in 73% of cases, moderate in 20.4% and absent in 6.5%. Tolerability was very good as side effects were reported only in 3.16% of patients. Most frequent side effects were: nausea (1.23%), gastralgia (1.11%), headache (0.29%), hypotension (0.12%), vertigo (0.12%) and rash (0.08%). Drop-outs for gastralgia were reported only in 0.53% of the patients.
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PMID:[Epidemiologic study on the effectiveness and safety of dihydroergocristine in impaired memory and behavioral functions in aged humans]. 149 66

To define the maximum tolerated dose and to study whether recombinant human interleukin-3 (rhIL-3) reduced chemotherapy-induced neutropenia and thrombocytopenia, 20 chemotherapy-naive patients with advanced ovarian cancer eligible for treatment with 6 cycles of carboplatin-cyclophosphamide every 4 weeks (day 1) were entered in a phase I/II open, single-center trial. Cohorts of five patients received during 7 days 1, 5, 10, or 15 micrograms/kg/d rhIL-3 (days 5 through 11) in cycles 1, 3, and 5 by continuous intravenous (IV) infusion or once daily subcutaneous (SC) administration. In control cycles 2, 4, and 6, no rhIL-3 was administered. rhIL-3 significantly increased the recovery of leukocyte, neutrophil, and platelet counts, especially at 5, 10, and 15 micrograms/kg rhIL-3. rhIL-3 also increased basophil, eosinophil, monocyte, and lymphocyte counts at this dose steps. Effects on reticulocytes were limited. No difference in efficacy between SC and IV rhIL-3 treatment was found. Chemotherapy postponement for insufficient bone marrow recovery was necessary in 22 of 45 control cycles versus 2 of 49 rhIL-3 cycles (P less than .001). Platelet transfusions were required in 7 of 45 control cycles versus 3 of 50 rhIL-3 cycles (P less than .5). rhIL-3 up to 10 micrograms/kg/d could be administered without severe side effects. At 15 micrograms/kg/d, rhIL-3 headache was dose-limiting. Other side effects were fever, flu-like symptoms, nausea, skin rash, flushing, facial erythema, and urticaria. Liver toxicity occurred in rhIL-3 and control cycles. rhIL-3 slightly increased tumor necrosis factor alpha, C-reactive protein, and serum amyloid A plasma levels, whereas no effect on IL-6 plasma levels was observed. rhIL-3 administered SC appears to be an interesting hematopoietic growth factor for reduction of chemotherapy-induced myelotoxicity.
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PMID:Effects of interleukin-3 after chemotherapy for advanced ovarian cancer. 151 36

A 39-year-old woman was evaluated for possible liver transplantation due to rapidly developing hepatic failure 4 weeks after initiation of oral minocycline 100 mg twice a day for the treatment of acne. The patient developed a maculopapular rash, malaise, fever, nausea, and vomiting 2 weeks prior to admission to the hospital. On admission, her symptoms rapidly progressed to liver failure characterized by rapidly rising liver enzyme levels, worsening encephalopathy, and coagulopathy. Viral hepatitis serologies and blood cultures were all negative. After intensive supportive care for 2 weeks, the patient's condition gradually improved and she was discharged with mildly elevated liver enzyme levels and pruritus, without need of liver transplantation. Minocycline-induced hepatic injury is an idiosyncratic reaction with a sensitization period that appears to be 3-4 weeks in duration. The characteristic features include rash, fever, lymphadenopathy, and eosinophilia, as well as severe alterations in liver function. The high liver enzyme levels and the significant prolongation of the prothrombin time suggest massive hepatocellular damage. In light of the profound liver damage that occurs with this adverse reaction, care should be taken in administering minocycline to patients who have concomitant liver disease. It is recommended that patients should be instructed as to the possible signs and symptoms of toxicity and be monitored for evidence of idiosyncratic reaction or liver failure.
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PMID:Acute hepatic failure associated with oral minocycline: a case report. 153 50

Scombroid poisoning is a form of ichthyosarcotoxism caused by the consumption of 'spoiled' fish of the dark meat varieties. It can be considered a mild-to-moderate form of 'food poisoning' and it occurs world-wide. Ten incidents, involving 22 patients, were reported to Tygerberg Hospital Pharmacology and Toxicology Consultation Centre in the first quarter of 1990. Cape yellowtail (Seriola lalandii) was involved in all the cases. The presenting symptoms and signs (in order of frequency) were: skin rash, diarrhoea, palpitations, headache, nausea and abdominal cramps, paraesthesia, an unusual taste sensation and breathing difficulties. The patients responded well to anti-histamines and, in most, the condition resolved within 12-24 hours. Although histamine plays an important role in the pathogenesis of scombroid poisoning, the exact mechanism is still unresolved. The condition should be recognised and not confused with a true seafood allergy. Health workers are urged to alert the authorities when outbreaks of suspected cases of scombroid poisoning are encountered in order to establish the possible cause and to prevent further cases.
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PMID:Scombroid poisoning. Case series of 10 incidents involving 22 patients. 156 20

DAB486IL-2 is a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with human interleukin-2 (IL-2). It selectively binds and intoxicates only cells that bear the high-affinity receptor for IL-2. In the first clinical trial of a genetically engineered ligand fusion-toxin, we have treated 18 patients with chemotherapy-resistant IL-2 receptor expressing hematologic malignancies with escalating doses of DAB486IL-2. The maximal tolerated dose of a daily intravenous bolus of DAB486IL-2 was 0.1 mg/kg per day for 10 doses, established by asymptomatic, reversible elevations of hepatic transaminases without changes in other tests of liver function. Other mild reversible side effects noted were rash, nausea, elevated creatinine, chest tightness, and fever. Pharmacokinetic analysis showed a monophasic clearance of 5.8 +/- 0.7 minutes with peak levels of 3,549 +/- 1,041 mg/mL at the 0.1 mg/kg dose. Approximately 50% of patients developed an antibody response to diphtheria toxin or DAB486IL-2. The presence of such antibodies did not preclude patients from experiencing an antitumor response as four of the six patients with antitumor effect had detectable antibody titers. Although this was a phase I trial designed to define the safety of DAB486IL-2, remissions were observed in three patients lasting from 5 to over 18 months. The ability to achieve significant tumor reductions in this group of heavily treated patients is encouraging and suggests additional trials are warranted in hematologic malignancies.
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PMID:Phase I trial of an interleukin-2 (IL-2) fusion toxin (DAB486IL-2) in hematologic malignancies expressing the IL-2 receptor. 158 7

Eleven patients with beta thalassemia major were entered into the trial of the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). Their ages ranged from 17 to 26 years (mean +/- SD, 22.3 +/- 2.7). Six were male and five were female. L1 was administered at an initial daily dose of 42.5 to 60 mg/kg as a single dose. After 4 weeks, the dose was increased to 85 to 119 (102 +/- 10.7) mg/kg for 191 to 352 days divided into either two or four doses daily, except for one patient who developed agranulocytosis after 11 weeks and was taken off the trial. Initial serum ferritin values in the remaining 10 patients ranged between 1,000 and 9,580 (5,549 +/- 3,333) micrograms/L and at end of the trial their mean serum ferritin was significantly lower (4,126 +/- 2,278; P less than .05 using the paired t-test). Urinary iron excretion at a daily dose of 85 to 119 mg/kg administered as two divided doses ranged between 0.14 and 0.82 (0.44 +/- 0.26) mg/kg/24 h. In three patients, the four doses per day schedule caused substantially more iron excretion than the same total dose divided into two. During the course of the trial, several possible adverse effects have been encountered. One patient (female, aged 20) developed agranulocytosis 11 weeks after starting treatment and 6 weeks after beginning treatment with a daily dose of 105 mg/kg. This patient's neutrophil count recovered spontaneously 7 weeks after the discontinuation of L1. A decrease in serum zinc levels to subnormal levels was observed in four patients with symptoms of dry skin, with an itchy scaly rash in two that was associated with low serum zinc levels that responded to zinc therapy. Urinary zinc levels ranged from 4.7 to 23.4 (13 +/- 5.5) mumol/24 h and were above 9 mumol/24 h (upper limit of normal) in eight patients. Mild nausea occurred in three patients and transient diarrhea in a fourth. Mild musculoskeletal symptoms occurred in three patients but settled without discontinuation of L1 therapy in two and with temporary discontinuation of L1 in the third. A transient increase in serum aspartate transaminase was also noted in five patients, but serum aspartate transaminase levels subsequently decreased in all of them. No cardiovascular, neurologic, renal, or retinal toxicities were demonstrable. These results confirm that L1 is an effective oral iron chelator. Further clinical trials are needed to determine the incidence and severity of adverse effects.
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PMID:Efficacy and possible adverse effects of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in thalassemia major. 846 82

To determine the efficacy and toxicity of two systemically active antifungal agents in the treatment of buccal and oesophageal candidiasis 111 HIV-infected patients with microscopically-confirmed candidiasis were randomized to receive either 200 mg itraconazole once a day or 200 mg ketoconazole twice a day for 28 days in a double blind study. After 1 week of treatment, 75 and 82% of the patients on itraconazole and ketoconazole, respectively, had responded clinically. After 4 weeks of treatment, this had risen to 93% in each group. One patient discontinued itraconozole because of toxicity (rash), five patients discontinued ketaconazole (two nausea, two hepatotoxicity and one rash). Despite successful clinical and mycological clearance, 80% patients had a further episode of candidosis within the next 3 months.
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PMID:Itraconazole versus ketaconazole in the treatment of oral and oesophageal candidosis in patients infected with HIV. 166 59

The efficacy and tolerability of low, intermittent doses of co-trimoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole given Monday, Wednesday, Friday) for prophylaxis against Pneumocystis carinii pneumonia (PCP) was assessed retrospectively in 116 patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex at high risk of PCP. 92% were receiving concomitant zidovudine. 71 with previous episode(s) of PCP were followed a mean of 18.5 months (range 3-42). 45 without past PCP but with depletion of CD4 cells to less than 200/microliters were observed for a mean of 24.2 months (range 9-40). PCP did not develop in any patient on co-trimoxazole. 33 (28%) had side-effects, mainly rash, pruritus, and nausea. 15 discontinued co-trimoxazole, but only 11 (9%), who withdrew in the first month, were clearly drug-intolerant. Thus, low-dose, thrice weekly co-trimoxazole completely prevents AIDS-associated PCP, is cost-effective, and well tolerated by more than 85% of patients. Controlled comparisons of this regimen with other prophylactic agents are warranted.
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PMID:Low-dose co-trimoxazole for prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus disease. 167 73

Preclinical and clinical studies demonstrate that the selective antitumor activity of fluorouracil (5-FU) is enhanced by agents which perturb certain intracellular nucleotide pools. We previously demonstrated that the combination of N-phosphonacetyl-L-aspartate (PALA), which depletes pyrimidine nucleotide pools, and 5-FU yielded a 43% response rate among 37 assessable patients with colorectal carcinoma. In preclinical tumor models, 6-methylmercaptopurine riboside (MMPR), an inhibitor of purine synthesis, elevates phosphoribosylpyrophosphate (PRPP) pools and promotes the anabolism of 5-FU to fluorinated nucleotides. In vivo, the addition of MMPR enhances the therapeutic efficacy of PALA-5-FU. In a phase I trial, we sought to determine the optimal dose and schedule of MMPR in combination with PALA (250 mg/m2 on day 1) and 5-FU (1300 mg/m2 by 24-hour infusion on day 2). MMPR (75-225 mg/m2) was given intravenously on day 1 to 27 patients with solid tumors (15 colorectal, seven breast, five other). Toxic effects were mild to moderate and included leukopenia, mucositis, nausea, or rash. Two of seven patients given MMPR at 225 mg/m2 had grade 3 diarrhea. PRPP was measured using a [14C]orotic acid 14CO2 release assay in tumor biopsy specimens obtained before and 12 hours and 24 hours after MMPR doses were given to 20 patients. The addition of MMPR elevated PRPP pools in human solid tumors. At 12 hours after treatment, two (50%) of four patients showed a twofold or greater elevation of PRPP at the MMPR dose level of 75 mg/m2; a similar elevation was observed in five (71%) of seven patients given 150 mg/m2 MMPR and in three (43%) of seven patients given 225 mg/m2 MMPR. At 24 hours after treatment, results for the respective dose levels of MMPR were two (33%) of six patients, one (20%) of five patients, and four (57%) of seven patients. Administration of the two highest MMPR dose levels appeared to result in a greater increase in tumor PRPP levels. However, toxicity was greater at the 225 mg/m2 dose level; therefore, the 150 mg/m2 dose level was favored. Tumor levels of PRPP decreased between 12 hours and 24 hours in nine (56%) of 16 patients. This time course indicates that MMPR should be administered at the beginning of the 24-hour infusion of 5-FU.
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PMID:Phase I trial of fluorouracil modulation by N-phosphonacetyl-L-aspartate and 6-methylmercaptopurine riboside: optimization of 6-methylmercaptopurine riboside dose and schedule through biochemical analysis of sequential tumor biopsy specimens. 171 7


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