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)

Altogether 117 patients with advanced breast cancer were treated with either tamoxifen 10 mg by mouth twice daily or aminoglutethimide 250 mg by mouth four times daily with hydrocortisone 20 mg twice daily in a randomised cross-over trial in which patients who failed to respond to the first treatment or relapsed while receiving it were switched to the other. Eighteen (30%) out of 60 patients initially treated with tamoxifen achieved an objective response and 11 (18%) showed stable disease. Seventeen (30%) out of 57 patients treated initially with aminoglutethimide achieved an objective response and 13 (23%) achieved stable disease. Objective responses in bone metastases were achieved more commonly with aminoglutethimide (11 patients (35%)) than with tamoxifen (five (17%)). The predicted median duration of response for tamoxifen was 15 months and for aminoglutethimide over 15 months (no significant difference). Five (15%) out of 34 patients who failed to respond to tamoxifen and four out of six patients who relapsed after responding to tamoxifen subsequently responded to aminoglutethimide. In contrast, only two (6%) out of 31 patients who failed to respond to aminoglutethimide and none out of four patients who relapsed while receiving aminoglutethimide subsequently responded to tamoxifen. The main side effects occurring in the 97 patients who received aminoglutethimide as first- or second-line treatment were lethargy and drowsiness (36 patients) and rash (29); seven patients had to stop treatment because of side effects. In contrast, side effects were rare and mild with tamoxifen and no patient had to stop treatment because of them. Both tamoxifen and aminoglutethimide appeared from this study to be equally effective in the medical endocrine treatment of advanced breast cancer.
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PMID:Tamoxifen versus aminoglutethimide in advanced breast carcinoma: a randomized cross-over trial. 679 71

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

The efficacy and safety of methsuximide were evaluated for 12 weeks in 21 patients with complex partial (psychomotor) seizures refractory to conventional anticonvulsants. After addition of methsuximide to the previous anticonvulsant regimens, the number of complex partial seizures per patient decreased from a weekly average of 5.8 to 0.9 seizures. A 90 to 100% control of complex partial seizures was achieved in 15 (71%) of the patients. Dose reduction or discontinuation of one or more previous medications was possible in 42%. Seizure control was optimal at methsuximide doses of 9.5 to 11.0 mg per kilogram per day and plasma levels of 20 to 24 micrograms per milliliter. Adverse experiences, particularly somnolence and lethargy, were reported by 12 patients. Methsuximide appeared to be an effective and generally well tolerated adjunct medication in the management of complex partial seizures.
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PMID:Methsuximide for refractory complex partial seizures. 689 34

Single and repetitive tryptophan loads were consumed by normal, adult male volunteers, and blood concentrations of tryptophan, serotonin, and kynurenine, their time courses, and their distributions within blood were measured. Repeated measures of basal and tryptophan-induced changes in tryptophan and serotonin blood concentrations were characteristic for individual subjects. Tryptophan dose-responsive increases in measured substances returned to basal levels within 24 hours after single tryptophan loads. However, cumulative increases in serotonin concentration in early-morning, predose blood samples were seen following repetitive daily tryptophan administration. Extra-platelet serotonin could be detected in blood samples taken after tryptophan loading and after repetitive daily tryptophan consumption but not in baseline samples taken before short-term loading. Neither platelet number nor size was altered by the loading procedures. Tryptophan loading produced lethargy and drowsiness within 30 minutes of ingestion under all loading conditions. Subjects with the slowest kynurenine response to tryptophan were most behaviorally affected.
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PMID:Short-term and repetitive administration of oral tryptophan in normal men. Effects on blood tryptophan, serotonin, and kynurenine concentrations. 724 25

Aminoglutethimide (Elipten), at a dosage between 250 and 1500 mg/d by mouth, was administered in a clinical phase II study to 17 patients with metastasizing carcinoma of the breast resistant to hormones and cytostatic drugs. Results of this treatment were available for 14 patients. Nine women were given the drug alone, eight in combination with cytostatic drugs. In 11 women the drug significantly decreased pain within 3-14 days. Used alone aminoglutethimide produced objective regression of the metastases in two women, two further instances of regression occurred when the drug was combined with cytostatic agents. Five women developed urticarial rash, while six had somnolence and nausea or lethargy. Aminoglutethimide is suitable for symptomatic treatment of metastasizing treatment-resistant carcinoma of the breast, either alone or in combination with cytostatic drugs.
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PMID:[Aminoglutethimide in metastasizing carcinoma of the breast resistant to hormonal and cytostatic treatment (author's transl)]. 727 74

A 3 1/2-year-old boy presented at three months of age with an acute episode of lethargy, somnolence, hypoglycemia, hepatomegaly, and cardiomegaly, which responded poorly to restoration of the blood sugar level to normal. The absence of ketonuria during subsequent episodes of severe hypoglycemia prompted a search for a defect in fatty acid oxidation. Plasma carnitine (2.0 to 5.0 mumol per liter), muscle carnitine (0.01 to 0.02 mumol per gram, wet weight) and liver carnitine (0.021 to 0.065 mumol per gram, wet weight) were all less than 5 per cent of the normal mean. During a 36-hour fast, ketones were barely detectable. Prolonged treatment with oral carnitine over a six-month period resulted in increased muscle strength, a dramatic reduction in cardiac size, relief of cardiomyopathy, partial repletion of carnitine levels in plasma and muscle, and complete repletion in the liver. Systemic carnitine deficiency is an easily treatable cause of recurrent Reye's-like syndrome. Its diagnosis requires measurement of carnitine levels.
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PMID:Systemic carnitine deficiency--a treatable inherited lipid-storage disease presenting as Reye's syndrome. 743 84

Child abuse by whiplash-shaking can lead to severe injury in infants, including cerebral damage, neurological defects, blindness, and mental retardation. These findings are seen often without external evidence of head injury. Nurses should suspect shaken baby syndrome (SBS) in infants less than 1 year of age who present with apnea, seizures, lethargy or drowsiness, bradycardia, respiratory difficulty, coma, or death. Subdural and retinal hemorrhages accompanied by the absence of external signs of trauma are hallmarks of the syndrome.
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PMID:Shaken baby syndrome: a nursing perspective. 771 67

We report intermittent seizures, lethargy, and Cohen's syndrome in a 4-year-old girl with hyper-beta-alaninemia and a partial deficiency of beta-alanyl-alpha-ketoglutarate transaminase (AKT). To examine the role of beta-alanine (beta ALA) in cellular metabolism, we cultured her skin fibroblasts in medium containing increasing amounts of beta ALA. At concentrations of 10 to 25 mM, beta ALA caused more than a 50% reduction in the growth of her cells compared with normal control skin fibroblasts. The addition of 0.1 mM of pyridoxine to the culture medium abolished these toxic effects and increased her skin fibroblast AKT enzyme activity more than twofold. During a 2-year period of clinical observation, there were no further episodes of seizures or somnolence in our patient while she received oral pyridoxine therapy.
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PMID:Pyridoxine-responsive hyper-beta-alaninemia associated with Cohen's syndrome. 793 5

Humans spend one-third of their lives sleeping, yet the role of this phase of the circadian rhythm is not clear. Theories postulating the purpose of sleep include the restorative theory and the humeral theory. Both theories have identified weaknesses. What is known is that chronic disruption of sleep and/or sleep deprivation causes significant physiological and psychological symptoms. These include fatigue, lethargy and daytime somnolence accompanied by irritability, memory loss, decrease in judgment and paranoia. Obstructive sleep apnea (OSA) imposes another, more life-threatening dimension for the client.
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PMID:Obstructive sleep apnea. 798 95

The neuropsychological effects of the GABA-reuptake blocker, tiagabine-HCl, were tested in an open trial of 22 adult patients with refractory partial epilepsy followed by a double-blind, placebo-controlled, cross-over trial in 12 subjects. Nineteen patients completed the initial open titration and fixed-dose phase of the study and 11 patients completed the double-blind phase. The median daily tiagabine dose was 32 mg during the open fixed dose and 24 mg during the double-blind periods. Neuropsychological evaluation did not show any significant effect on cognitive function in the open or double-blind phases. In this group of patients no statistically significant difference in the frequency of the total number of seizures or complex partial seizures was found in the open or double-blind stages. Seizure severity was significantly less in the open fixed dose than in the baseline period, but was not significantly different between the two double-blind periods. Reported side effects were transient, most commonly aggression/irritability, lethargy, headache and drowsiness. No significant EEG changes were observed.
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PMID:Neuropsychological effects of tiagabine, a potential new antiepileptic drug. 804 51


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