ABSTRACT
A series of diverse beta-lactam analogues of nocardicins with interesting antimicrobial properties were prepared. Coupling of glucosamine to these compounds improved their water solubility. Aminoacid derivatives produced a stereoinduction on the quaternary enantiotopic carbon of the starting compound 1. Evaluation of their antimicrobial activity showed that the introduction of alpha-amninoacids to monobactams increased their activity. The importance of asymmetric carbon is exemplified by the higher antibiotic activity of L-alpha-aminoacids than the D-series. No significant difference was observed between fluorinated and non-fluorinated monobactams.
Subject(s)
Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Lactams , Monobactams/chemical synthesis , Monobactams/pharmacology , Ampicillin/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Candida albicans/drug effects , Chemistry, Pharmaceutical/methods , Isomerism , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Models, Chemical , Monobactams/chemistry , Penicillins/pharmacologyABSTRACT
In a double-blind trial 40 patients with bulimia nervosa according to DSM III-R criteria were randomly assigned either to a 60 mg fluoxetine group or to a placebo control group. Fluoxetine or placebo was given over a period of 35 days. Parallel to the drug trial, patients participated in an intensive inpatient behavioral psychotherapy program. There were no dropouts at all in the study. Fluoxetine was well tolerated and had only minor adverse effects. In self-ratings and expert ratings concerning attitudes towards eating, eating behavior, and general psychopathology, significant improvements over time were observed in both groups. Using analysis of variance (ANOVA), however, there were no statistically significant "group by time" differences. Results show that the intensive inpatient-care and psychotherapy program was highly effective in changing eating behavior and attitudes as well as general psychopathology. Fluoxetine showed a significant reduction in body weight, especially during the first three weeks of fluoxetine treatment. It was not possible to demonstrate a statistically significant improvement in eating attitudes, eating behavior, and general psychopathology beyond that elicited by intensive inpatient psychotherapy and general inpatient care. These results can possibly be explained by the existence of a "ceiling effect".
Subject(s)
Bulimia/drug therapy , Fluoxetine/therapeutic use , Psychotherapy , Adult , Body Weight/drug effects , Bulimia/psychology , Bulimia/therapy , Double-Blind Method , Female , Fluoxetine/adverse effects , Fluoxetine/blood , Humans , Male , Psychiatric Status Rating ScalesABSTRACT
In a placebo-controlled double-blind crossover study of 21 patients chronically treated with neuroleptics and suffering from tardive dyskinesia, tiapride (600 mg/day, mean plasma level: 682 ng/ml) exhibited a transient efficacy during 12 weeks of treatment, most distinct in the 6th week (p less than 0.01). Tiapride induced an increase of prolactin plasma levels, on the average, from 1,195 to 2,179 microIU/ml (p less than 0.01). Tiapride was well tolerated. Increase of parkinsonism was only mild and not significant. The results underline the difficulty in treating tardive dyskinesia and, thus, confirm the importance of prevention.
