Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thalicarpine, a plant alkaloid of novel structure, was evaluated in a phase II clinical trial. Fourteen previously treated patients with advanced malignant disease were given thalicarpine at a dose of 1100 mg/m2 weekly as a constant 2-hour iv infusion. Common toxic effects included nausea, ECG changes, arm pain, and lethargy; less frequent effects included vomiting, tachycardia, hypotension, pain distant from infusion site, urticaria, chills, diarrhea, and mydriasis. There was no hematologic, hepatic, or renal toxicity. There were no complete or partial objective responses. Although the drug's true response rate in any given tumor type cannot be determined, its absence of activity in man, to date, and the recent closing of its IND, make further clinical investigation with thalicarpine unlikely.
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PMID:An abbreviated phase II trial of thalicarpine. 645 Dec 89

This study was designed to evaluate the clinical tolerance to multiple IM injections of rDNA-produced human alpha-2 interferon (IFN) (Schering-Plough 30500) in patients with solid tumours. IFN was administered in escalating IM doses in separate groups of patients daily for 14 days and then twice weekly for a further 10 weeks. The dosage levels were 1, 3, 10, and 30 million U/injection. Subjective toxicity could be divided into two types, acute and chronic. The acute reactions took the form of an influenza-like syndrome consisting in chills, rigors, headache, tremor, nausea, vomiting, and myalgia. These symptoms were dose-related but tachyphylaxis developed with continued dosing. The chronic toxicity consisted of malaise, lethargy, fatigue, anorexia, and confusion. These symptoms were not so dose-dependent and tended to become more severe with prolonged treatment. Objective toxicity consisted of myelosuppression and liver dysfunction. Granulocyte counts below 1.0 X 10(9)/l were seen in three patients at the 30-million-U level, with platelet counts less than 100 X 10(9)/l in two of these. Elevation of the liver enzymes were seen in all five patients treated at 30 million U, but returned to normal after 1 week without IFN in all but one patient. A tolerable dose (IM) for phase II/III studies lies between 3 and 10 million U for daily scheduling and between 10 and 30 million U for twice-weekly injections.
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PMID:A phase I toxicity study of human rDNA interferon in patients with solid tumours. 646 93

Two hundred and thirteen unselected postmenopausal women with advanced breast cancer were treated with aminoglutethimide and hydrocortisone. There were 6 complete responses (CR), 47 partial responses (PR), 25 stable disease (SD) and 3 mixed response. Overall objective response rate was 28%, and with SD 41%. Median duration of objective response was 14 months. Years after menopause, age and tumour-free interval did not affect response rates. Main side-effects were drowsiness and lethargy (33%), rash (23%) and nausea (15%). Eleven patients (5%) stopped treatment because of toxicity. Median survival from start of treatment was 28 months and was the same for CRs, PRs and SD, compared with 10 months for progressive disease (P less than 0.001). Median survival from first metastasis was 43 months for PR/CR, 40 months for SD (not significantly different) and 22 months for progressive disease (P less than 0.001). Aminoglutethimide is an effective endocrine therapy in advanced postmenopausal breast cancer, particularly for bone deposits. Disease stabilization is associated with symptomatic and survival benefit similar to CR/PR.
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PMID:Aminoglutethimide for the treatment of advanced postmenopausal breast cancer. 668 69

A prospective study was carried out to determine the effectiveness and tolerance of ftorafur (2.25 g/m2 daily for 5 days, repeated every 4 weeks) in previously treated patients with advanced squamous cell cancers of the head and neck. Seventeen patients were entered in the study; 15 were evaluable for drug toxicity, and 14 were evaluable for response. Three patients had mild nausea, three had mild-to-moderate lethargy, two had nonspecific generalized weakness, and two had severe stomatitis. Of 15 patients three experienced leukopenia (causing death in one) and four had thrombocytopenia (life-threatening to one). Response to treatment included: progressive disease (nine patients), stable disease (four), and complete response (one with no previous radiotherapy or chemotherapy).
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PMID:Phase II ftorafur therapy in previously treated squamous cell cancers of the head and neck. 677 5

The case of a 24-year-old man who accidentally ingested liquid zinc chloride is presented. Local caustic effects included erosive pharyngitis and esophagitis. Nausea, vomiting and abdominal pain, as well as hypocalcemia and hyperamylasemia, suggested acute pancreatitis. Microhematuria occurred, but renal function did not deteriorate. Lethargy and confusion, noted previously in another case of hyperzincemia, were present. Chelation therapy was instituted, with reversal of the clinical and biochemical effects of zinc poisoning.
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PMID:Accidental ingestion of liquid zinc chloride: local and systemic effects. 678 11

Acivicin, an L-glutamine antagonist, was administered to 37 evaluable patients with refractory advanced solid tumors in a phase I trial. A total of 67 evaluable 72-hr iv infusions were given at 3- to 4-week intervals. Doses ranged from 3.0 to 90 mg/m2/course. Reversible CNS toxicity was dose-limiting and included lethargy, somnolence, anxiety, hallucinations, and paranoid psychoses. Four of five patients experienced unacceptable CNS toxicity at 90 mg/m2. Three of eight patients experienced reversible diaphoresis and chills without fever at 75 mg/m2, and two had dizziness and ataxia. Hematopoietic toxicity, nausea, emesis, and diarrhea were mild and dose-related. One patient developed a blue-green discoloration of the infusion arm. Serial plasma and urine specimens from 13 patients were assayed for acivicin using a microbiologic method. Peak plasma levels at the end of the 72-hr infusions correlated with dose and ranged from 0.09 to 1.10 microgram/ml. When data from six patients were fitted to a two-compartment open model, alpha-half-life ranged from 1.1 to 63 mins, while beta-half-life ranged fro 338 to 629 mins. Renal clearance ranged from 6 to 24 mL/min, and nonrenal clearance accounted for 58%-83% of the total drug clearance. CNS toxicity correlated with plasma acivicin levels which exceeded 0.9 microgram/ml for greater than 16 hrs, but not with peak plasma levels or with the integrals of the concentration x time curves. Minor responses were seen in one patient with melanoma, in one with epidermoid pulmonary carcinoma, and in two with colon carcinoma. A starting dose of 60 mg/m2/course was recommended for phase II trials, with possible escalation to 75 mg/m2 in the second course if the drug was well-tolerated.
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PMID:Phase I trial and pharmacokinetics of acivicin administered by 72-hour infusion. 687 83

Dural sinus thrombosis developed in two children with acute lymphoblastic leukemia during induction treatment with vincristine sulfate, prednisone, and asparaginase. Headache, nausea, emesis, and lethargy were the presenting signs. The diagnosis was confirmed by arteriography. The cause is presumed to be secondary to hypercoagulability due to asparaginase-induced antithrombin III deficiency. The patients received anticoagulation therapy and recovered completely. Only two of the six reported patients without heparinization survived.
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PMID:Dural sinus thrombosis in children with acute lymphoblastic leukemia. 694 95

More than 1200 patients who received pindolol for the treatment of hypertension, angina pectoris, and various arrhythmias in studies conducted in the United States were included in the New Drug Application submitted to the FDA. Nearly 1000 of these patients received pindolol as monotherapy. The side effects reported were generally transient and of mild or moderate severity. The most frequently reported side effects seen after pindolol administration, compared to those seen after placebo, were in decreasing order of incidence: headache, dizziness, insomnia, muscle pain, fatigue, weakness, nervousness, joint pain, edema, nausea, and muscle cramps. Other side effects that occurred more frequently with pindolol than with placebo but at a rather low incidence induced weight gain, bizarre dreams, visual disturbances, lethargy, and diarrhea. Nasal congestion, throat discomfort, nocturia, impotence, pruritus, anxiety, hypotension, bradycardia, and heart failure occurred only rarely. Of the 323 patients who received pindolol alone for the treatment of mild to moderate hypertension, only 20 (6.2%) were withdrawn from the study because of side effects. Overall, 3.4% of the patients treated with pindolol were withdrawn because of side effects, most of which involved the central nervous system, that is, insomnia, anxiety, dizziness, and headache. However, a few patients manifested some edema and weight gain while receiving pindolol alone. Review of the side effects data did not reveal a tendency for the incidence of side effects to be dose related. One placebo-controlled, double-blind study designed to evaluate the fixed dosages of 15, 30, and 60 mg in the treatment of mild to moderate hypertension suggested that only the incidences of insomnia and nervousness increased with increasing doses. However, these side effects were generally transient and of mild or moderate severity. The evidence indicates that pindolol has an acceptable safety profile and that any side effects that appear are generally well tolerated and disappear with continued treatment.
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PMID:Adverse reactions to pindolol administration. 704 82

Ten women ages 22 to 39 years were treated with a single injection of Delestrogen on day 19 of the menstrual cycle and increasing doses of Parlodel on days 19 to 23. This treatment resulted in a shortening of the luteal phase and a decrease in the production of progesterone and had no effect on serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), or prolactin levels. Side effects reported with this therapy included lethargy, dizziness, nausea, vomiting, hot flashes, depression, and nasal congestion. These preliminary clinical data suggest a combination of estrogen and bromocriptine regimen is luteolytic and may be useful as an interceptive abortifacient preparation in the human being.
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PMID:Evaluation of Delestrogen and Parlodel as a luteolytic agent in humans. 706 Jul 69

50% of hospitalized medical emergency cases are cardiological and respiratory emergencies. Myocardial infarction, cardiogenic shock, ventricular arrhythmias and left ventricular failure often cause sudden death occurring within 1 or 2 hours. Therefore immediate management is necessary already in the prehospital phase of cardiovascular events. This does also apply for acute respiratory failure due to obstructive ventilatory disorders. Acute exacerbations of chronic obstructive pulmonary disease frequently are masked and may be misinterpreted as encephalopathy or alcohol withdrawal syndrome. Sedation may be dangerous. Also neuroglucopenic syndrome and hyperosmolar coma are occasionally interpreted wrongly. Thyrotoxic crisis, adrenal crisis and hypercalcemia are characterized by lethargy, mental disturbance and weakness, by dehydration, myopathy, nausea, constipation, diarrhea or tenesms or arrhythmias. In this situation of varied symptoms the most important action is to think of endocrine emergency, which may have multiple etiologies.
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PMID:[Cardiovascular emergencies--endocrine and metabolic crises. Practical hints for the physician in emergency service]. 711 36


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