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S Kasper

Publications and source records attributed to S Kasper.

At least 199 records · Page 11Linked to original sources
PubMed1996

Induction of cell-free, in vitro transcription by recombinant androgen receptor peptides.

An in vitro, cell-free transcription system, based on prostate-derived transcriptional machinery and very powerful androgen response elements (AREs), has been developed. Multiple (p(ARR3)LovTATA) AREs from the androgen-regulated probasin gene were linked to G-free cassettes and used in nuclear extracts prepared from prostate carcinoma cell lines (PC3 and LNCaP cells) to test specific induction of transcription by full-length AR and by glutathione-S-transferase (GST)-fusion peptides in which the androgen receptor (AR) DNA-binding domain alone (AR524-649), or together with the ligand-binding domain (AR524-902), or a portion of the NH2-terminal domain (AR232-649) were incorporated. In the presence of AR, nuclear extracts from PC3 cells had greater activity in supporting transcription than those from LNCaP cells; and lower background activity than those from HeLa cells. All of the AR forms correctly initiated in vitro transcription of ARE-templates in an androgen-independent manner. The amount of specific, inducible transcript was dependent on the concentration of AR peptide present. AR524-902 was the most potent transactivator tested, with the maximal level of specific transcript over 900-fold higher than the minimal level. At all concentrations this peptide was three to four times more active than either AR524-649 or AR232-649. In conclusion, we have developed a very specific and sensitive cell-free transcription system for delineating trans-activational regions of the AR.

Androgen-Binding Protein↗
PubMed1996

Low plasma thyroid indices of depressed patients are attenuated by antidepressant drugs and influence treatment outcome.

Decreased turnover of thyroid indices and blunting of TSH release after TRH administration has been associated with depressive disorder. A further decrease in plasma thyroid hormone; during antidepressant treatment has been reported. However, the putative association between the plasma thyroid indices' concentration and response has not been addressed. In the present study 21 depressed inpatients underwent a four-week double blind antidepressant with amitriptyline and mianserin; their plasma thyroid hormone indices (total thyroxine [TT4], free thyroxine [FT4], total triiodothyronine [TT3], free triiodothyronine [FT3], thyrotropin [TSH], and thyroglobulin [TBG]) were quantified to elucidate their involvement in depression and during antidepressant drug treatment. Depressed patients' plasma TSH, when corrected for age, was significantly lower than that of healthy subjects. During antidepressant treatment the entire patient cohort showed a significant decrease in plasma TT4 and FT4 concentrations. Responders showed a significant drop in TT4 FT4, FT3, and T4/TBG, but nonresponders only a decrease in FT4. During mianserin treatment, a decrease was observed in TT4, FT4, FT3, and T4/TBG. FT4 and FT3 baseline levels correlated positively with the improvement in the Hamilton Depression Rating Score (HDRS). These findings show that depressed inpatients' serum TSH levels are within the reference range, but significantly lower than those of healthy subjects, and those patients who turn out to be nonresponders have potentially lower availability of thyroid hormones than responders. Therefore, we hypothesize that in order to assure clinical improvement in depression, an adequate capacity of the thyroid hormone pool is necessary to compensate for the additional antidepressant-provoked decrease in serum thyroid hormone availability.

Adult↗
PubMed1996

Carbohydrate-deficient transferrin as a screening marker for drinking in a general hospital population.

We investigated the usefulness of the laboratory marker of alcohol consumption carbohydrate-deficient transferrin (CDT) in 101 consecutively admitted patients in a surgical and internal medical ward of a hospital in a rural wine-growing area. Four major aspects were considered: the influence of liver disease, the method of expression of CDT values (relative % vs absolute units/1), level and pattern of alcohol consumption and comparison with y-glutamyl transferase (GGT). The results show that %CDT is a more valuable discriminating marker of high alcohol consumption than absolute CDT values and its usefulness in this respect is independent of changes in serum total transferrin levels, as in liver disease. Sensitivity and specificity of % CDT were 70 and 98% respectively, compared with 65 and 83% respectively for GGT.

Adult↗
PubMed1996

Carbohydrate-deficient transferrin as a marker of alcohol intake: a study with healthy subjects.

This paper reports the results of a 3-week drinking experiment in 51 healthy male subjects, examining the value of %CDT (carbohydrate-deficient transferrin) in the context of different levels of alcohol intake. All healthy persons were urine-tested drug-free and underwent daily breath alcohol tests for the 7 days preceding, and during the whole 3 weeks of, the experiment. Subjects were divided into five groups, consuming different amounts of alcohol daily over a 3-h period in the presence of the investigators. The five groups consisted of 10, 9, 10, 16 and 6 subjects respectively and consumed a daily dose of ethanol of 20, 40, 60, 80 and 80 g respectively for 3 weeks. No significant changes in %CDT were detected in most subjects, even in the 80 g alcohol-consuming groups. The results suggest that CDT is not sensitive for the detection of short-term heavy drinking by healthy subjects.

Adult↗
PubMed1996

Comparative studies with milnacipran and tricyclic antidepressants in the treatment of patients with major depression: a summary of clinical trial results.

Milnacipran is a novel antidepressant agent which selectively inhibits the reuptake of serotonin and noradrenaline. Seven randomized, double-blind trials with a comparable design have compared the efficacy and tolerability of milnacipran with that of tricyclic antidepressants (TCAs) in patients with major depression. At a dose of 50 mg twice a day, milnacipran therapy is associated with a response rate (50% reduction in Hamilton Depression Rating Scale) of 64%. The rate of response to TCAs in these studies was 67%. In contrast to the TCAs, milnacipran was very well tolerated by the patients. The only adverse event that occurred more frequently in milnacipran-treated patients than in TCA-treated patients was dysuria (2.1% of patients treated with milnacipran). Milnacipran is as effective as TCAs in the treatment of patients with major depression and is better tolerated. Milnacipran's lack of effects on cardiovascular function offers improved safety in cases of overdose.

Adrenergic Uptake Inhibitors↗
PubMed1996

Schizophrenia and the dopamine-beta-hydroxylase gene: results of a linkage and association study.

Alterations in dopamine neurotransmission and disturbed norepinephrine activity have been implicated in the pathogenesis of schizophrenia. We considered the dopamine-beta-hydroxylase (DBH) gene located on the long arm of chromosome 9 (9q34.3) as a candidate gene for schizophrenia. DBH catalyzes the synthesis of norepinephrine from dopamine in noradrenergic neurons. In addition to DBH we used in the linkage study DNA markers ABL (centromeric) and D9S114 (telomeric). The aim of this study was to test linkage and association between PCR-based genotyped markers and schizophrenia. A simulation was done to investigate the power of our sample. In 34 Austrian families we could not detect linkage between schizophrenia and schizophrenia spectrum disorders and the three genetic markers. We could not find any significant deviation in allelic or genotypic distribution from expectations. Based on our results we conclude that the DBH gene seems to have no strong contribution in the etiology of schizophrenia.

Alleles↗
PubMed1996

[123I]IBZM SPECT for imaging of striatal D2 dopamine receptors in 56 schizophrenic patients taking various neuroleptics.

OBJECTIVE: The purpose of this study was to compare the binding of various typical and atypical neuroleptics to striatal D2 dopamine receptors in schizophrenic patients. METHOD: Fifty-six inpatients with schizophrenia, including 14 with schizoaffective disorder and one with schizophreniform disorder, were evaluated. Fourteen patients were neuroleptic free. Single photon emission computed tomography (SPECT) was performed 90 minutes after intravenous injection of [123I]benzamide ([123I]IBZM). Subsequent semiquantitative analysis of D2 receptor binding was done with the use of the basal ganglia (striatum)/frontal cortex (BG/FC) ratio of activity. Clinical symptoms were rated with the Positive and Negative Syndrome Scale and the Hamilton Depression Rating Scale. RESULTS: The BG/FC ratios in patients taking typical neuroleptics were significantly lower than those in the neuroleptic-free subjects but not lower than those in the patients taking atypical neuroleptics (clozapine, remoxipride). For atypical antipsychotics, a dose-dependent relationship with striatal D2 receptor binding could not be demonstrated. BG/FC ratios were not significantly correlated with clinical symptoms or with duration of illness. CONCLUSIONS: The results indicate that [123I]IBZM SPECT is useful for semiquantitative imaging of striatal D2 dopamine receptors and for estimating their blockade by neuroleptics. Thus, it may improve drug monitoring in psychiatric patients. Furthermore, the findings suggest a complex relationship between the antipsychotic effect of atypical neuroleptics and D2 receptor blockade.

Adult↗
PubMed1996

[Therapy of post-stroke depression with fluoxetine. A pilot project].

Depression is a common but often unrecognized complication after cerebrovascular stroke. Tricyclic antidepressants (TCA) have been found to be effective in poststroke depression, but side effects such as orthostatic hypotension, arrhythmia limit their wider use. In this pilot study the effects of treatment with the specific serotonin reuptake inhibitor (SSRI) fluoxetine (20 mg) in 10 severely depressed patients (HAM-D score between 27 and 35) after cerebrovascular stroke were investigated. Four patients dropped out of the study prematurely because of worsening of their condition (n = 4) and one patient discontinued the study because of transfer to a nursing home. After 3 weeks of fluoxetine treatment there was a significant amelioration in all the measured scores (HAM-D, Beck, CGI and Barthel: P < 0.05). At the end of the study one patient with recurrent cerebrovascular lesions still had an HAM-D score of 25, but the other four patients had HAM-D scores between 6 and 11. The physical rehabilitation scores measured with the Barthel Index showed negative correlations with the HAM-D, Beck and CGI scores for most items; this has to be interpreted with caution considering the number of patients involved in this investigation. The authors suggest that future double blind trials are warranted to test the efficacy of fluoxetin therapy for poststroke depression. Methodological problems in connection with pharmacological trials in these severely ill patients are discussed.

Aged↗
PubMed1996

Risk of suicide in depression and its implication for psychopharmacological treatment.

Suicide is one of the leading causes of death among adults in the general population. There is a well-established relationship between suicide and mood disorders and it has been estimated that 50-80% of completed suicides are associated with mood disorders. About 15% of depressed patients commit suicide, with tablet poisoning (mostly antidepressants) often chosen as the suicide method. Naturally, this presents the doctor with a dilemma since certain antidepressants are suitable both for the treatment of depression and for a suicide attempt. Two questions seem to be of particular practical relevance in this respect, which will be reviewed and discussed in more detail in this paper: (1) can antidepressants induce a suicidal tendency? and (2) can the degree of toxicity of antidepressants be estimated in cases of overdosage? There is no evidence that newer antidepressants, like the selective serotonin reuptake inhibitors (SSRIs), induce a suicidal tendency as has been suggested by a spectacularly written case report. In fact, it seems likely that antidepressants with a predominantly serotonergic mechanism of action may be of particular benefit in patients with suicidal problems, which is in line with neurobiological theories about suicidal behaviour. This and the decreased toxicity of SSRIs makes them an attractive choice for treatment of depressed patients who are at risk for suicide.

Antidepressive Agents↗
PubMed1996

Pharmacokinetics of chlorprothixene after single intravenous and oral administration of three galenic preparations.

The absolute and relative bioavailability of chlorprothixene (CAS 113-59-7, Truxal) was studied in eight healthy male volunteers with three different formulations: solution, suspension and coated tablet. An intravenous infusion and an oral aqueous solution served as references. Single doses of 100 mg were administered in a randomized complete-block design with washout periods of two weeks. Serum concentrations of chlorprothixene were assayed using a high-performance liquid chromatographic method with electrochemical detection. After a 1-h infusion period the maximum serum concentration (Cmax) of chlorprothixene was 430 +/- 81 ng/ml (mean +/- S.D.) and subsequently decreased with a terminal elimination half-life (t1/2) of 25.8 +/- 13.6 h. The total serum clearance (Cl) and the apparent volume of distribution at steady state (Vss) were 867 +/- 167 ml/min and 1035 +/- 356 l, respectively. The profiles of the chlorprothixene serum concentration vs. time and the resulting pharmacokinetic parameters were similar for all orally administered formulations. The absolute oral bioavailability of 17% of the solution indicated a marked presystemic metabolism. The bioavailability of chlorprothixene relative to the oral solution was 56.4% with the coated tablet and 67.7% with the suspension. All pharmacokinetic parameters showed wide inter-subject variations, partly attributable to the respective formulation.

Administration, Oral↗
PubMed1996

[Psychopathological phenomena in long-term follow-up of acute psychosis after preventive mefloquinine (Lariam) administration].

There are some reports about neuropsychiatric side effects associated with the intake of the antimalarial drug mefloquine. We report a long-term observation of a patient suffering for his first time on an acute psychosis under mefloquine prophylaxis. Mefloquine's role as a drug possibly inducing psychosis and the influence of vulnerability therefore will be discussed.

Adult↗
PubMed1996

[Pregnancy and drug dependence].

A major problem in the treatment of opiate-dependent patients arises due to illicit drug abuse capted with drug dependence and pregnancy. Drug abuse during pregnancy involves a high risk for the mother as well as for the unborn child. Twenty-three pregnant, opiate-dependent women, were enrolled in a 19-month study of the outpatient clinic for drug addiction. The mean age of the subjects was 26.7 years (SD +/- 4.8; range: 20-37 years), the mean duration of opiate dependence was 61.8 months (SD +/- 47.5; range: 12-204 months). Seventeen women were enrolled in a methadone maintenance program and six women were treated with morphine. The babies mean weight at birth was 2746 g (SD +/- 830.1; range: 940-4370), they had no congenital anomalies and all the maintained babies showed an opiate withdrawal syndrome. The treatment yielded in five subjects to a drug-free condition at delivery. The application of morphine might be an alternative in opiate dependent pregnant women and might reduce the additional consumption of illicit drugs during pregnancy.

Administration, Oral↗
PubMed1995

Seasonal affective disorder in a tropical country: a case report.

Seasonality and affective disorders in the Southern Hemisphere were investigated in populations living in latitudes (40 degrees S) equivalent to those of the studies conducted in the Northern Hemisphere. The authors describe a patient with bipolar II affective disorder who was living in a low-latitude area (São Paulo, latitude: 23 degrees 39' S). The patient experienced five episodes of affective disorder that began in the summer and were characterized by symptoms typical of an autumn-winter depression. During the last two depressive episodes, the symptoms remitted after a 4-week course of evening light therapy. The case calls attention to the possibility that seasonality may influence the natural history of affective disorders even in lower latitude regions.

Adult↗
PubMed1995

beta-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo.

The cocaine analogue 2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (beta-CIT) is a potent ligand for both dopamine- and serotonin uptake sites which in its 123I labeled form can be used for single photon emission computerized tomography (SPECT). It was demonstrated previously by SPECT-studies in non-human primates that 123I-beta-CIT binds to dopamine transporters in the striatum and to serotonin transporters in hypothalamus and midbrain. The aim of the present study was to compare 123I-beta-CIT binding in the brain stem of normal controls and a group of subjects under treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram. 123I-beta-CIT-SPECT was performed in 12 depressed patients under 20 mg (n = 5), 40 mg (n = 6) and 60 mg (n = 1) citalopram daily, in one untreated depressed patient and in 11 controls at regular time intervals up till 24 hours p.inj. A highly significant reduction of beta-CIT binding was found in an area including mesial thalamus, hypothalamus, midbrain and pons in patients under citalopram compared to controls (44.1 +/- 14.4 vs. 82.3 +/- 18.6cpm's/mCi x kg body weight; specific binding 4 hrs p.inj.; p = 0.0001). No differences were seen between the high and low dose group and no changes were found in the striatum. 123I-beta-CIT binding in the brain stem and striatum in one untreated depressed patient fell within the range of control values. To our knowledge this is the first report directly demonstrating the effect of a selective serotonin uptake inhibitor in the brain in humans in vivo. SPECT measurements of serotonin uptake sites in patients with depression and other psychiatric disorders might provide better insights into the pathophysiology of these disorders and into mechanisms of drug action.

Adult↗
PubMed1995

A controlled study of the efficacy and safety of mianserin and amitriptyline in depressive inpatients.

As with other second-generation antidepressants, the antidepressive efficacy of mianserin was investigated in double-blind control group studies, mostly under outpatient conditions. This study tested the antidepressive efficacy and safety of mianserin as compared to amitriptyline in a sample of 51 depressed inpatients suffering from major depression. No statistically significant difference was found with regard to the main efficacy outcome criterion, the HAMD. The tolerability results demonstrated a superiority of mianserin with respect to vegetative symptoms and especially with respect to dryness of the mouth.

Adult↗