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Biomedical subjects

V S Shu

Publications and source records attributed to V S Shu.

8 recordsLinked to original sources
PubMed1997

Tiagabine therapy for complex partial seizures. A dose-frequency study. The Tiagabine Study Group.

OBJECTIVE: To evaluate the efficacy and safety of 2 regimens of tiagabine as add-on therapy for patients with complex partial seizures (CPSs) that are refractory to other treatment. DESIGN: Randomized, double-blind, placebo-controlled, add-on, parallel-group trial with an 8-week baseline period, 12-week experimental period (4 weeks of dose titration and 8 weeks of fixed-dose therapy), and 4-week termination period. SETTING: Twenty-six centers throughout the United States. PATIENTS: Three hundred fifty-one patients were enrolled, 318 were entered in the double-blind period, and 271 completed the study. INTERVENTIONS: Tiagabine, 16 mg 2 times per day (106 patients); tiagabine, 8 mg 4 times daily (105 patients); and placebo (107 patients). The doses of tiagabine were titrated in 3 steps to the fixed dose. MAIN OUTCOME MEASURE: The median change in the 4-week rate of CPSs from baseline to experimental period. RESULTS: The median change from baseline was -1.6 CPSs per 4 weeks in the group of patients who were given tiagabine 2 times per day, and it was -1.2 CPSs in the group of patients who were given tiagabine 4 time per day (P = .06 and P = .02, respectively, compared with placebo). The 4-week seizure frequency was reduced by 50% or more in 31% of the patients who were given tiagabine 2 times per day and in 27% of the patients who were given tiagabine 4 times per day vs 10% of the placebo-treated patients (P < or = .001 for each tiagabine-treated group compared with the placebo group). The most frequent adverse events involved the central nervous system and occurred in comparable proportions in the 3 treatment groups. Similar proportions of patients discontinued the study prematurely for adverse events. CONCLUSIONS: Tiagabine administered 2 and 4 times daily as add-on pharmacotherapy was effective in reducing CPSs in patients with epilepsy whose conditions were refractory to treatment with other antiepileptic agents, and it was well tolerated.

Adolescent↗
PubMed1991

Estazolam treatment of insomnia in generalized anxiety disorder: a placebo-controlled study.

Estazolam, a triazolobenzodiazepine with an intermediate elimination half-life, has been shown previously to be an effective and safe hypnotic in insomniacs without concomitant psychiatric illness. Our study of the efficacy of estazolam in patients with insomnia associated with generalized anxiety disorder began when 108 patients meeting criteria for generalized anxiety disorder (mean total score of Hamilton Rating Scale for Anxiety [HAM-A] = 22.0 +/- 3.1 [SD]) and insomnia were given single-blind placebo for 7 nights. Nine patients whose anxiety and/or insomnia improved were dropped as placebo responders. The remaining 99 patients were randomly allocated (1:1) to double-blind treatment with either estazolam 2.0 mg or matching placebo for 7 nights. Hypnotic efficacy, as determined by patient-completed sleep questionnaires, was statistically significant for estazolam 2.0 mg versus placebo for all sleep indices (p less than 0.01). Patients treated with estazolam 2.0 mg showed significantly greater improvement in anxiety than those receiving placebo on the mean total score of HAM-A ([placebo, -3.4; estazolam, -7.1; p less than 0.001] and without the insomnia item [placebo, -2.7; estazolam, -5.5; p less than 0.001]). Anxiety scores on the State-Trait Anxiety Inventory showed greater improvement in the estazolam group, but without statistical significance (p = 0.237). Estazolam 2.0 mg is an effective hypnotic in patients with generalized anxiety disorder and appears to have a favorable anxiolytic action.

Adult↗
PubMed1990

Efficacy of estazolam. The United States clinical experience.

The hypnotic efficacy of estazolam, a triazolobenzodiazepine, has been established in well-controlled sleep laboratory and outpatient clinical trials. Estazolam 1.0 mg and 2.0 mg significantly improves sleep latency, total sleep time, number of nocturnal awakenings, depth of sleep, and sleep quality in adults with chronic insomnia. Long-term studies indicate that estazolam 2.0 mg remains an effective hypnotic for at least six weeks of continuous nightly administration with no evidence of clinically significant tolerance. Estazolam is an effective treatment for situational insomnia and significantly improves sleep in patients with insomnia associated with moderately severe anxiety or depression.

Adolescent↗
PubMed1990

Safety of estazolam. The United States clinical experience.

The safety profile of estazolam, a new triazolobenzodiazepine hypnotic medication, has been developed in 1,320 normal volunteers and patients with insomnia. No clinically significant effects of estazolam on vital signs or laboratory values were detected. Drug-specific adverse effects such as somnolence, dizziness, hypokinesia, and abnormal coordination occurred, but these are expected extensions of benzodiazepine pharmacologic activity. No consistent effects on psychomotor performance, including memory, were seen at the recommended hypnotic doses in insomniac subjects. These data, combined with the evidence for hypnotic activity, indicate that estazolam is a safe and effective treatment for insomnia.

Adolescent↗
PubMed1986

Difloxacin metabolism and pharmacokinetics in humans after single oral doses.

By using high-performance liquid chromatography, the metabolism and pharmacokinetics of difloxacin were characterized in humans after single oral doses of 200, 400, and 600 mg. Group mean peak levels in plasma were obtained 4 h after administration. The means of the individual peak levels for the 200-, 400-, and 600-mg groups were 2.17, 4.09, and 6.12 micrograms/ml, respectively. The mean respective terminal-phase half-lives were 20.6, 27.1, and 28.8 h; the mean half-life for all subjects was 25.7 h. Within the dose range studied, the behavior of difloxacin could be well described by a set of linear pharmacokinetic parameters with a one-compartment open model. Levels of unconjugated metabolites in plasma were negligible. The major urinary components were difloxacin and its glucuronide, each accounting for roughly 10% of the dose. Also present were the N-desmethyl and N-oxide metabolites, accounting for 2 to 4%. Trace levels of other metabolites were observed. Group mean renal clearances ranged from 4.1 to 5.6 ml/min, indicating extensive reabsorption from the glomerular filtrate. As a result, the terminal phase half-life and the dose-normalized area under the curve were substantially greater than those of other members of the class.

Administration, Oral↗
PubMed1983

Comparative genotoxicity of adriamycin and menogarol, two anthracycline antitumor agents.

Adriamycin and menogarol are anthracyclines which cause more than 100% increase in life span of mice bearing P388 leukemia and B16 melanoma. Unlike Adriamycin, menogarol does not bind strongly to DNA, and it minimally inhibits DNA and RNA synthesis at lethal doses. Adriamycin is a clinically active drug, and menogarol is undergoing preclinical toxicology at National Cancer Institute. In view of the reported mutagenicity of Adriamycin, we have compared the genotoxicity of the two drugs. Our results show that, although Adriamycin and menogarol differ significantly in their bacterial mutagenicity (Ames assay), they have similar genotoxic activity in several mammalian systems. Adriamycin is strongly mutagenic in the Ames assay with TA98 and TA100. Menogarol is nonmutagenic to TA98 and TA100. For the mammalian cell culture systems, V79 (Chinese hamster) cells are exposed for 2 hr to drug, following which cell survival, induction of sister chromatid exchanges, chromosome damage, and production of mutants resistant to 6-thioguanine are measured. The percentage of survival obtained with the two drugs ranges between 25 and 50% at 0.15 microgram/ml and 5 to 15% at 0.3 microgram/ml. At 0.15 microgram/ml, Adriamycin and menogarol increase the percentage of cells with chromosome damage from a background level of 8.8 to 30 and 22.5%, respectively. The same drug concentration causes a small but significant increase in sister chromatid exchange rate. Both drugs are equally active (increase mutation frequency about 3- to 6-fold above background) in producing 6-thioguanine-resistant mutants. The induction of micronuclei in polychromatic erythrocytes of rats is the most sensitive assay system. Both drugs cause 10- to 15-fold increase in micronuclei at nontoxic doses.

Animals↗
PubMed1982

Use of statistics in the analysis of side effect data from clinical trials of psychoactive agents.

1. Evaluation of the side effects of psychoactive drugs presents a special statistical situation because many of the symptoms of psychiatric disorders are also potential side effects. 2. Reported incidences of adverse events can be viewed as being a combination of psychoactive drug effects, disease state effects and other concomitant effects. 3. An intriguing statistical problem is to develop methodology to separate these effects. 4. This paper discussed four methodologies for estimating incidence of side effects assessed with a symptom and side effect check list.

Alprazolam↗