Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 31-year-old female was well until few years ago when she was diagnosed as having Graves' disease. Methimazole (MMI) and Lugol's solution were prescribed. But 7 months later, she stopped taking them arbitrarily. Three months later, thirst and general fatigue appeared. Therefore insulin (60u/day) and MMI (30 mg/day) were administered and continued for 40 days. However no remarkable effect was brought about. She was then transferred to the radioisotope ward of Kumamoto Univ. Hospital and was treated with regular insulin only. Ten days later, she fell into thyroid storm associated with diabetic ketoacidosis and was transferred to our ward. We began to administer large volumes of transfusion, regular insulin, MMI, Lugol's solution, propranolol, hydrocortisone and digitalis. In 24 hours, ketoacidosis disappeared and she became alert. For hyperthyroidism, the dosage of MMI was increased to 60 approximately 45 mg/day and was continued for a month; however, her thyroid function did not normalize and agranulocytosis developed. MMI was discontinued, and she was treated with 131I. About a year later, she became euthyroid. Her diabetes mellitus was difficult to control during the hyperthyroid state but it was under good control with monocomponent lente insulin (36u/day) when the euthyroid state was resumed.
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PMID:[A case of thyroid storm associated with diabetic ketoacidosis (author's transl)]. 677 5

Nineteen patients with metastatic adenocarcinoma of the colon or rectum were treated with alpha (human leukocyte) interferon (alpha IFN). Patients received 3 X 10(6) IU/day of interferon im 5 days/week. Eighteen patients are evaluable for response and toxicity. There were no objective responses. All evaluable patients demonstrated progression of disease during therapy. Toxicity consisted primarily of mild granulocytopenia, thrombocytopenia, fatigue, weakness, and fever. This trial demonstrates that while alpha IFN can be administered safely as scheduled, this regimen has no activity against adenocarcinoma of the colon/rectum.
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PMID:Phase II trial of alpha (human leukocyte) interferon administered daily in adenocarcinoma of the colon/rectum. 685 Jun 64

In summary, procainamide is a useful agent for suppressing premature depolarization frequency. Its short half-life of elimination requires a dosing frequency of every 3 hours with regular dosage forms or every 6-8 hours with a sustained action dosage. Because of the extreme unpredictability of plasma concentration, the dosage must be titrated in each patient with electrocardiographic monitoring serving as the most useful method of evaluating efficacy. Maximum and minimum plasma concentrations are helpful in monitoring the achievement of therapeutic plasma levels and adjusting the frequency of dosing, especially in the presence of impaired renal function or low cardiac output. Adverse effects of procainamide include anorexia, nausea, vomiting, fatigue, insomnia, visual hallucinations, and disorientation; these are minor and cease with discontinuation of the drug. Agranulocytosis has rarely been reported. Long-term treatment has resulted in the occurrence of a lupus-like syndrome that is reversible when the drug is stopped. Procainamide is excreted in breast milk and infants of mothers receiving procainamide should not be nursed.
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PMID:Pharmacokinetics of a sustained release procainamide preparation. 703 27

17 patients (13 males and 4 females) were examined for side effects due to long-term treatment with 8-chloro-11-(4-methylpiperazin-1-yl)-5H-dibenzo(b,e)(1,4)diazepine (clozapine) with emphasis on alterations in bone marrow, liver, and kidney function. 16 patients were schizophrenic, one patient was diagnosed psychosis e causa dubia. The age range was 25-68 years, with an average of 38.2 years. The daily clozapine dose varied from 225 to 800 mg with a total intake during the trial period of 149.1-891.6 g yielding an average of 479.8 g. The treatment period varied from 20 to 51 months, with an average of 35.9 months. None of the patients had to discontinue the treatment because of side effects. The laboratory data including hematological, and nephrological parameters revealed no significant changes related to clozapine treatment within the treatment period. No changes were observed in ECG. 12 patients experienced side effects, 8 of them receiving concomitant psycholeptic medication. 9 patients complained of temporary fatigue and 5 of these experienced continuous drowsiness. There were 8 cases of nocturnal hypersalivation and two cases of increased appetite. One patient developed light tachycardia and one patient orthostatic hypotension. Clozapine is known to be an effective anti-psychotic drug, but due to reports of agranulocytosis in 16 Finnish patients the drug was withdrawn from the Danish market in 1975 although later its use was merely restricted to special cases. This study does not indicate that clozapine contains greater risk of clinical side effects than commonly used psycholeptic drugs.
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PMID:Evaluation of side effects due to clozapine in long-term treatment of psychosis. 720 18

Based on the superior response rates (21% to 24%) of patients treated with single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in Eastern Cooperative Oncology Group and M.D. Anderson Cancer Center trials in non-small cell lung cancer (NSCLC) and on the superior 1-year survival rates of NSCLC patients treated with carboplatin in a randomized study of cisplatin combination and analogues, we initiated a phase II trial of paclitaxel/carboplatin in patients with stage IV or effusion-positive stage III NSCLC. Eligibility stipulated chemotherapy-naive patients with measurable disease, good performance status, and adequate hematologic, hepatic, and renal function. Previous radiotherapy was restricted to < or = 30% of marrow-bearing bone. Paclitaxel was initially given at 135 mg/m2 over 24 hours followed by carboplatin dosed to a targeted area under the concentration versus time curve (AUC) of 7.5, with treatment repeated at 3-week intervals for six cycles. Granulocyte colony-stimulating factor was introduced during the second and subsequent cycles, with the paclitaxel dose sequentially escalated in 40 mg/m2 increments to a maximum dose of 215 mg/m2 in patients with less than grade 4 granulocytopenia and less than grade 3 thrombocytopenia. Of 54 patients enrolled, 30 currently are evaluable for response, 23 for toxicity. Myelosuppression has been the principal toxicity, with grade 3 or 4 granulocytopenia occurring in 70% of patients after the first cycle. After the introduction of granulocyte colony-stimulating factor, granulocytopenia decreased to 37% during the second cycle and then consistently to 20% or lower during subsequent cycles. Only 22% of cycles have been delayed for 1 week or more. Neutropenic fever has occurred in five (5%) of 100 evaluable cycles. Other grade 3 or 4 toxicities include thrombocytopenia (13%), anemia (9%), fatigue (9%), and hemorrhagic cystitis (1%). The paclitaxel dose was boosted to 215 mg/m2 in 12 (70%) of 17 patients by cycle 3 or 4. At an AUC of 7.5, the median first-cycle carboplatin dose was 434 mg/m2 (range, 293 to 709 mg/m2). The objective response rate is 50%, with three complete, 12 partial, and five minor responses. We conclude that the paclitaxel/carboplatin combination is active in advanced NSCLC and, with AUC-based dosing of carboplatin, can be given at 3-week intervals. Although dose limiting at a paclitaxel dose of 135 mg/m2, granulocytopenia can be reduced substantially with granulocyte colony-stimulating factor, allowing sequential dose escalation of paclitaxel to 175 mg/m2 and 215 mg/m2 in 70% of patients receiving three or more cycles.
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PMID:Paclitaxel and carboplatin in the treatment of advanced non-small cell lung cancer. 754 Nov 56

Phase II trials of the novel biologic combination isotretinoin (13-cis-retinoic aid) plus recombinant interferon alfa-2a have demonstrated this combination's major activity against advanced squamous cell carcinoma of the skin and cervix. Because this combination has had limited study in other tumors, we initiated a phase II trial of this regimen in patients with metastatic colorectal adenocarcinoma. Sixteen patients with measurable metastatic colon carcinoma who had received no previous chemotherapy were entered on the trial. Patients received recombinant interferon alfa-2a, 6 million units a day subcutaneously, and isotretinoin, 1 mg/kg per day orally in two divided doses. Patients were evaluated for response after 8 weeks of treatment and then continued on therapy until progressive disease was documented. We did not observe complete or partial responses. Two patients experienced minor responses in measurable pulmonary metastases lasting 12 and 8 weeks. Grade 3-4 toxic reactions included fatigue (5 patients), granulocytopenia (6 patients), neurotoxicity (2 patients), and elevated serum triglyceride levels (2 patients). Although this combination has demonstrated significant activity in squamous cell carcinomas of the skin and cervix, our results suggest that it has little therapeutic activity against advanced colorectal adenocarcinomas.
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PMID:Phase II trial of isotretinoin and recombinant interferon alfa-2a in metastatic colorectal carcinoma. 757 63

Methoxymorpholinyldoxorubicin (FCE 23762) is a novel, highly lipophilic doxorubicin analogue. It possesses potent in vitro and in vivo antitumor activity including efficacy in multidrug-resistant tumor cell lines. It is also metabolically activated in vivo resulting in an 80-fold increase in potency over the parent drug. In this phase I study the drug was administered by i.v. bolus injection at 3-week intervals. Fifty-three patients with refractory solid tumors were treated; 133 courses of FCE 23762 were administered at doses ranging from 30 to 2250 micrograms/m2. The dose limiting toxicity was reversible myelo-suppression (granulocytopenia and thrombocytopenia), demonstrating a delayed nadir and recovery in comparison to doxorubicin. Other toxicities included transient elevation of hepatic transaminases, delayed and prolonged nausea and vomiting, mucositis, anorexia, fatigue, and diarrhea. Heavily pretreated patients demonstrated more myelosuppression than previously untreated patients at 1250 micrograms/m2. No cardiotoxicity was observed. Four objective tumor responses were seen: one complete response in a patient with pelvic recurrence of cervical cancer; one partial response in a patient with cutaneous and lymph gland metastases from head and neck cancer; and two minor responses in patients with liver metastases from colorectal cancer. Plasma concentrations of FCE 23762 and its 13-dihydro metabolite, FCE 26176, were measured in 20 patients at doses > or = 675 micrograms/m2, using HPLC with fluorescence detection. The area under the plasma concentration-time curve ranged from 30 to 80 ng/h/ml; plasma data suggested linear kinetics in the range of tested doses (although there was considerable interpatient variability). The maximum tolerated dose defined in this study using this schedule is 1500 micrograms/m2. A safe phase II dose for previously untreated patients using this schedule is 1250 micrograms/m2; however, this may actually be below the optimal dose for this patient population.
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PMID:Phase I clinical and pharmacokinetic study of 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762). 774 8

Preclinical studies of 2-chlorodeoxyadenosine (2-CdA) against solid tumors in the human tumor cloning assay and evidence that 2-CdA is active against slow-growing or resting tumor cells have stimulated interest in the clinical activity of this agent against solid tumors. This study sought to estimate the maximum tolerated dose, dose-limiting toxicity, and plasma and urine pharmacokinetics accompanying the intravenous administration of 2-CdA by 120-h continuous infusion in patients with solid tumors. Treated patients were also assessed for other toxicities of therapy and for antitumor response. A total of 23 patients received 35 courses of treatment given at doses of 3.5, 5.3, 6.5 and 8.1 mg/m2 per day by continuous intravenous infusion for 5 days and repeated every 28 days. Blood and urine specimens were collected before, during, and after drug infusion. The dose-limiting toxicity at 8.1 mg/m2 per day manifested as granulocytopenia in 2 of 5 patients (3 of 7 courses of treatment) and as thrombocytopenia in 3 of 5 patients (3 of 7 courses of treatment). At the dose levels of 6.5 and 8.1 mg/m2 per day, recovery from thrombocytopenia was often delayed. Severe lymphocytopenia (< 1,000/microliters) was observed at all dose levels of 2-CdA. Dose-related anemia and leukopenia were observed and were infrequently severe. Non-hematological toxicities were confined to mild-to-moderate nausea, vomiting, fatigue, and anorexia. Fever of 37 degrees-40 degrees C was induced during drug infusion in 19 patients. No antitumor response was observed. Average plasma concentrations at steady-state (Cpss) ranged from 3 ng/ml at the initial dose level to 13 ng/ml at the dose level of 8.1 mg/m2 per day. Both the Cpss and the area under the plasma concentration-time curve (AUC) were proportional to the dose. A relationship was observed between the percentage of change in absolute neutrophil count and the AUC. Renal excretion accounted for only 18% of the elimination of 2-CdA over the 5-day infusion period. The maximum tolerated dose for 2-CdA given by 5-day continuous infusion was 8.1 mg/m2 per day in this study. The recommended dose on this schedule for phase II studies is 6.5 mg/m2 per day. Granulocytopenia and thrombocytopenia were dose-limiting. No antitumor activity was observed during this study. On the basis of the plasma concentrations of 2-CdA observed, it is unlikely that this schedule of drug administration will permit achievement of the concentrations consistent with antitumor activity observed in preclinical studies.
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PMID:A phase I and pharmacokinetics study of 2-chlorodeoxyadenosine in patients with solid tumors. 785 Sep 21

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m2 IV continuous infusion days 1-5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1-15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.
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PMID:Phase II evaluation of merbarone in renal cell carcinoma. 786 Feb 33

Piroxantrone, a synthetic intercalating agent, was studied in patients with advanced, measurable gastric adenocarcinoma who had not received prior chemotherapy. The starting piroxantrone dose was 150 mg/m2 given intravenously over 1 hour on day 1 and repeated every 21 days. Response and toxicity could be evaluated in 15 patients. No complete, partial, or minor responses were observed. Toxic effects included granulocytopenia, anemia, vomiting, nausea, anorexia, fatigue, stomatitis, alopecia, hyperbilirubinemia, and increased alkaline phosphatase levels. At the stated dose and schedule, piroxantrone does not possess significant activity against advanced gastric cancer.
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PMID:Phase II trial of piroxantrone in metastatic gastric adenocarcinoma. 789 47


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