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Biomedical subjects

E Schweizer

Publications and source records attributed to E Schweizer.

At least 127 records · Page 7Linked to original sources
PubMed1990

What constitutes an adequate antidepressant trial for fluoxetine?

One hundred and eight patients with major depression were treated with fluoxetine 20 mg/day for 3 weeks. Patients who failed to respond to this open-label treatment were randomly assigned either to receive fluoxetine 60 mg/day for 5 weeks or to continue treatment with fluoxetine 20 mg/day for an additional 5 weeks. Both treatment groups demonstrated a statistically significant reduction in depressive symptoms, indicating that continued treatment with low-dose fluoxetine may be as effective as an increase in dose in achieving a favorable clinical outcome.

Adult↗
PubMed1989

A placebo-controlled, double-blind, clinical trial of paroxetine in depressed outpatients.

A placebo-controlled, randomized, double-blind study was carried out in outpatients suffering from major unipolar depressive disorder to assess the efficacy and tolerability of paroxetine in the treatment of depression. The study lasted for six weeks. After a placebo washout period of 4 to 14 days patients took 20mg of paroxetine or matched placebo as a morning dose for one week; thereafter the dose of paroxetine could be titrated between 10 and 50mg/day. Patients were evaluated at baseline, weekly during the first four weeks of the study, and at the end of six weeks; patients who entered a six-week extension phase were evaluated at 9 and 12 weeks. Evaluations were carried out using HAMD (including ECDEU factors), MADRS, HSCL, Covi anxiety and Raskin depression scales, CGI, and a seven-point rating of global improvement. Adverse events and laboratory values were also recorded at each assessment. One hundred and eleven patients entered the study, and efficacy data were available for 102 of these (49 on paroxetine and 53 on placebo). Efficacy measurements demonstrated significantly greater clinical improvement with paroxetine than placebo after two weeks of treatment, and this became even more marked after six weeks. Patients who continued treatment for a further six weeks maintained their clinical improvement. When adverse events were examined, statistically significant differences between paroxetine and placebo were seen only for sweating, diarrhoea, nausea, and somnolence. No significant changes were seen in any of the laboratory parameters measured. If these results are confirmed in future studies, paroxetine will represent an important addition to the treatments available for depression.

Adult↗
PubMed1989

Benzodiazepine dependence and withdrawal in elderly patients.

Severity of withdrawal symptoms and clinical outcome were compared in 19 elderly and 22 younger benzodiazepine-dependent patients matched for benzodiazepine half-life, dosage, and duration of treatment. During gradual taper of benzodiazepine doses, the elderly patients showed significantly less severe withdrawal symptoms on several clinical measures and a comparably favorable outcome. Approximately half of each group remained benzodiazepine free for at least 4 weeks. Both groups of patients tolerated drug discontinuation without serious consequences such as seizures or psychosis. Tapered benzodiazepine withdrawal did not appear to be more risky for the elderly group than for the younger patients.

Adult↗
PubMed1988

Isolation and sequence analysis of the fatty acid synthetase FAS2 gene from Penicillium patulum.

The fatty acid synthetase complex of Penicillium patulum was isolated and shown to be structurally similar to other known fungal fatty acid synthetases. It is composed of two subunit, alpha and beta, each with a molecular mass of about 200 kDa. P. patulum genomic and cDNA libraries were constructed in lambda gt11 and EMBL3 vectors. From these libraries, the P. patulum FAS2 gene together with its flanking DNA was isolated. The cloned genomic DNA was sequenced over a length of 6357 base pairs. The coding sequence of fatty acid synthetase subunit alpha, being 5571 nucleotides long, was identified within this DNA segment. The FAS2 gene is a mosaic of three exons (514, 4949 and 108 base pairs) and two introns, each of 54 base pairs in length. Both introns were absent in the corresponding cDNA sequences. Like other fungal introns both contain an internal CTAAC sequence, located 10 base pairs upstream of their 3'-exon/intron boundaries. In addition, they have, at their ends, the GTCAAGT and TAG consensus sequences characteristic of all eucaryotic introns. Furthermore, two pairs of direct repeats, of as yet unknown significance, were found in the two P. patulum introns. The P. patulum FAS2 gene encodes a protein of 1857 amino acids and 204.5 kDa molecular mass. It is 90 nucleotides shorter than the corresponding S. cerevisiae gene. In both organisms, the FAS2 genes and their products exhibit a high degree of overall sequence similarity at both the DNA (63%) and protein (68%) levels. Therefore, the fatty acid synthetase alpha subunits of P. patulum and S. cerevisiae obviously contain the same catalytic domains in an identical sequential order.

Amino Acid Sequence↗
PubMed1988

Long-term treatment of anxiety and risk of withdrawal. Prospective comparison of clorazepate and buspirone.

Risk of withdrawal was investigated in a prospective, double-blind comparison of clorazepate dipotassium, a benzodiazepine with a long half-life, and the nonbenzodiazepine buspirone hydrochloride in the long-term treatment of anxious outpatients. Patients were treated with therapeutic doses of clorazepate dipotassium (15 to 60 mg/d) or buspirone hydrochloride (10 to 40 mg/d) for six continuous months before their tranquilizer therapy was blindly and abruptly stopped. There was a significant increase in symptom severity consistent with a withdrawal reaction for the clorazepate group but not the buspirone group. For the clorazepate group, there was a suggestion that previous discontinuous exposure to benzodiazepines might sensitize patients to subsequent withdrawal effects. For the buspirone group, a higher dropout rate raised questions about patient satisfaction with therapy in this rather chronically anxious population.

Adult↗
PubMed1988

Genetic control of Yarrowia lipolytica fatty acid synthetase biosynthesis and function.

Yarrowia lipolytica, like other lower fungi, has a fatty acid synthetase complex (FAS) with an alpha 6 beta 6 molecular structure. Both subunits are multifunctional proteins each with a molecular weight of more then 200,000 daltons. A collection of FAS-deficient) Y. lipolytica mutants was isolated and characterized by both genetic complementation and enzyme activity measurements. It was found that the three acyl transferases (acetyl-, malonyl- and palmityl-transacylation) together with the enoyl reductase domain are located on subunit beta and, therefore, are encoded by the gene locus FAS1. beta-Ketoacyl reductase, beta-ketoacyl synthase and acyl carrier protein functions are part of the FAS2-encoded subunit alpha. Thus, the functional organization of FAS1 and FAS2 is identical in both yeasts, Saccharomyces cerevisiae and Yarrowia lipolytica. Nevertheless, the two yeasts differ significantly with respect to the intragenic complementation characteristics of fas1 and fas2 mutants. This finding is discussed in terms of a specific inter- or intramolecular reaction mechanism within the oligomeric FAS complex. The pentafunctional Y. lipolytica FAS1 gene was isolated from a lambda gt11 expression library using polyclonal antisera against the purified FAS complex. At present, sequencing of FAS1, which is more than 5 kilobases long, is almost completed. Available data indicate approx. 60 percent sequence homology together with an identical order of catalytic domains within subunit beta of the two yeasts, Y. lipolytica and S. cerevisiae.

Base Sequence↗
PubMed1988

Analogues of aminoglutethimide based on 1-phenyl-3-azabicyclo[3.1.0]hexane-2,4-dione: selective inhibition of aromatase activity.

In exploring the structural features responsible for the inhibitory activity of aminoglutethimide [3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione] (1) toward the cholesterol side chain cleavage (CSCC) enzyme from bovine adrenals and the human placental aromatase enzyme, analogues have been synthesized in which the piperidine-2,6-dione ring is replaced by substituted or unsubstituted azabicyclo[3.1.0]hexane-2,4-dione rings. The unsubstituted analogue 1-(4-aminophenyl)-3-azabicyclo[3.1.0]hexane-2,4-dione (9a) is a slightly more potent inhibitor of aromatase than 1 (Ki = 1.2 microM, cf. 1.8 microM for 1) but is noninhibitory toward the CSCC enzyme. The substituted analogues 1-(4-aminophenyl)-3-butyl-3-azabicyclo[3.1.0]hexane-2,4-dione (9e) and 1-(4-aminophenyl)-3-pentyl-3-azabicyclo[3.1.0]hexane-2,4-dione (9f) are approximately 100 times more potent than 1 (Ki values of 1, 9e, and 9f are 1.8, 0.015, and 0.02 microM, respectively) in inhibiting aromatase, with no significant activity toward the CSCC enzyme. Type II difference spectra were exhibited by 1, 9a, and 9f in their interaction with the aromatase enzyme (respective Ks values of 1, 9a, and 9f are 0.13, 0.08, and 0.01 microM). Modification of the para amino function by alkylation, its relocation, replacement by H, or replacement by a methyl, aldehyde, or secondary alcohol group produced analogues that were inactive toward both enzyme systems.

Aminoglutethimide↗
PubMed1988

Suicide upon recovery from depression. A clinical note.

We present two cases of suicide upon recovery from severe depression. In both cases a hypomanic phase followed by a switch down into depression appeared to be the clinical context of the impulsive suicidal act. We offer a critique of the hypothesis that accounts for suicidality during early remission from depression in terms of "mobilization of energy."

Adult↗
PubMed1988

[Effect of various weather parameters on the incidence of inpatient treated children with stenosing laryngotracheitis (pseudocroup)].

A total of 1470 hospitalized children with croup in the cities of Bochum and Herne were examined over a period of 19 years, with the aim of checking whether there was any relationship between croup incidence and changes in different weather parameters such as temperature, air pressure, absolute and relative air humidity, and wind speed. The incidence of croup was seasonal, being higher in the months of January, February, and March and from September to December. Statistical evaluation by discriminant analysis, t-test and chi 2-test showed a significant correlation (alpha greater than or equal to 0.95) between croup incidence and individual weather parameters in some months. The results seem to indicate a higher frequency of croup after decreases in temperature and influx of dry air masses (decreases in absolute humidity). In some months an increased incidence of hospitalized children with croup was observed after decreases in air pressure and during weather with extremely high (w greater than 4.5) or low (w less than 1.5) wind speed. In summary, no clear and consistent relationship between incidence of croup and particular weather parameters could be found.

Adolescent↗