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Biomedical subjects

S Kasper

Publications and source records attributed to S Kasper.

At least 163 records · Page 9Linked to original sources
PubMed1998

Transcultural study of schizophrenic delusions. Tokyo versus Vienna and Tübingen (Germany).

Schizophrenic delusions of 324 inpatients in Tokyo, 101 in Vienna, and 150 in Tübingen (Germany) were compared according to the same classifications. Among the three areas, about 80% of the patients had equally 'negative' delusions (injury and/or belittlement), and about one-fourth had 'positive' delusions of grandeur. Transcultural influences were found in the detailed contents of the 'negative' delusions; specific and direct themes of persecutory delusion, i.e., delusions of poisoning, and religious themes of guilt/sin were conspicuous in Europe, while amorphous delusions of reference such as 'being slandered' were predominant in Japan. The latter may derive from the group-oriented self in Japanese 'shame culture'.

Adult↗
PubMed1998

Comparison of buprenorphine and methadone maintenance in opiate addicts.

As a maintenance agent for opioid dependency, buprenorphine offers advantages such as a lower level of dependence and minimal withdrawal symptoms, due to its partial agonist properties at the micro-opioid receptor. Previous studies have shown 8 mg sublingual buprenorphine to be equivalent to 60 mg oral methadone in terms of retention rate and opioid-negative urine levels. In a 24-week, ongoing European study, 34 opioid-dependent subjects were assessed; 16 receiving buprenorphine and 18 methadone. A free dosing schedule was used with no upper limit for methadone dosing but with a maximum buprenorphine dose of 8 mg. Screening prior to the study excluded subjects with polysubstance dependence, somatic disease and/or HIV infection. Primary outcome measures were abstinence from other drugs, for which subjects provided weekly urine samples for analysis of opioids, cocaine and benzodiazepines, and retention in treatment. Patients in the buprenorphine group provided a greater proportion of negative urine samples, in particular cocaine-negative samples, compared with the methadone group, although this was not statistically significant. Retention in the buprenorphine group was significantly lower than in the methadone group, suggesting that the 8 mg buprenorphine limit may have biased the results in favour of methadone, and that this dose may have been too low for those subjects with high levels of dependence. However, buprenorphine is clearly effective in the more motivated subjects and further investigation in this subgroup is recommended.

Adolescent↗
PubMed1998

Molecular cloning and hormonal regulation of a murine epididymal retinoic acid-binding protein messenger ribonucleic acid.

A complementary DNA encoding the mouse epididymal secretory protein MEP 10 (mouse epididymal protein 10) was cloned and is now renamed murine epididymal retinoic acid binding protein (mE-RABP). The analysis of the predicted primary amino acid sequence showed that mE-RABP has a 75% identity with rat ESP I (epididymal secretory protein I), another epididymal retinoic acid-binding protein. The homology strongly suggests that mE-RABP is the mouse orthologue of rat ESP I. A computer analysis of the predicted three-dimensional structure confirmed that mE-RABP can accommodate retinoic acid as ligand. In the rat, ESP I messenger RNA (mRNA) is expressed in the efferent ducts and in the entire caput epididymidis. However, in the mouse, the expression of a 950-bp mE-RABP mRNA was detected only in principal cells of the mid/distal caput epididymidis, suggesting that the regulation of region-specific expression is different in rat and mouse. Northern blot analyses showed that mE-RABP gene expression is no longer detected 10 days after castration but progressively rebounds between days 15 and 60. However, mE-RABP protein could not be detected by Western blot 30 days after castration. Androgen replacement, begun 5 days after castration and continued for 4 days restored significant expression of mE-RABP mRNA. Efferent duct ligation for 10 days did not affect gene expression. Taken together, these results indicate that mE-RABP mRNA expression is regulated by androgens but not by testicular factors. The overall similarity in the primary amino acid sequence of mE-RABP with ESP I and other members of the lipocalin superfamily suggests that they are evolutionarily related.

Amino Acid Sequence↗
PubMed1998

Structure and putative function of a murine epididymal retinoic acid-binding protein (mE-RABP).

Vitamin A is required to maintain the epididymal epithelium. In this report, the characterization and putative functions of a murine epididymal retinoic acid-binding protein (mE-RABP) that is secreted into the lumen from the mid-/distal caput epididymidis are discussed. The amino acid sequence analysis of the mE-RABP preprotein shows that mE-RABP is the mouse orthologue of the rat epididymal secretory protein I (ESPI). These proteins belong to the lipocalin superfamily and bind to active retinoids but not to retinol. Therefore, we propose that mE-RABP may function as an extracellular retinoid carrier-protein involved in the paracrine regulation of epididymal function by retinoids.

Amino Acid Sequence↗
PubMed1998

Development, progression, and androgen-dependence of prostate tumors in probasin-large T antigen transgenic mice: a model for prostate cancer.

Probasin (PB) gene product is prostate-specific, epithelial cell in origin, and androgen-regulated. A large 12-kb promoter fragment of the PB gene (LPB) was linked to the simian virus 40 (SV40) large T antigen (Tag) deletion mutant (that removes the expression of the small t antigen) to deliver consistently high levels of transgene expression to the transgenic mouse prostate. Seven male founders, their male offspring, and all the male offspring from two female founders developed at least prostatic epithelial cell hyperplasia by 10 weeks of age, indicating that the incidence of transformation was 100%. Tumorigenesis in the LPB-Tag animals progressed in a manner similar to that observed in the human prostate. Initially, multifocal proliferating lesions were detected in the prostatic epithelium, which continued to progress into hyperplasia involving the entire epithelium and then low-grade dysplasia. Reactive stromal proliferation was induced and continued to develop throughout the progression to high-grade dysplasia, carcinoma in situ, and adenocarcinoma. Immunohistochemical studies indicated that most stromal cells stained positively for both androgen receptor and smooth muscle alpha-actin, suggesting that stromal overgrowth largely represented mesenchymal cells that had differentiated into smooth muscle cells. Epithelial cell transformation was accompanied by the down-regulation of differentiated function, as suggested by the loss of dorsolateral prostate-specific secretory proteins. Tumor growth was regarded as androgen-dependent because tumors regressed in animals castrated at 11 weeks of age, and androgen treatment restored both epithelial/stromal cell ratio and tumor growth. Furthermore, small populations of prostatic epithelial cells in castrated animals continued to proliferate, suggesting the potential for androgen-independent growth. Although prostatic metastasis to other organs was not observed, local invasion was detected. In summary, the LPB-Tag animal model is unique in that it is the only model generated with the Tag alone, thereby eliminating any influences of the small t antigen on prostate tumor formation. Moreover, this model undergoes molecular changes similar to those found in human prostate including: (a) the multi-focal nature of tumorigenesis, (b) the progressive histopathologic changes from low- to high-grade dysplasia similar to human prostatic intraepithelial neoplasia, (c) stimulation of reactive stromal proliferation, and (d) the androgen-dependent growth of the primary tumor. Thus, the LPB-Tag prostate tumor model will be useful for studying the sequential mechanisms underlying the development of multistep tumorigenesis.

Androgen-Binding Protein↗
PubMed1998

Development, progression, and androgen-dependence of prostate tumors in probasin-large T antigen transgenic mice: a model for prostate cancer.

Probasin (PB) gene product is prostate-specific, epithelial cell in origin, and androgen-regulated. A large 12-kb promoter fragment of the PB gene (LPB) was linked to the simian virus 40 (SV40) large T antigen (Tag) deletion mutant (that removes the expression of the small t antigen) to deliver consistently high levels of transgene expression to the transgenic mouse prostate. Seven male founders, their male offspring, and all the male offspring from two female founders developed at least prostatic epithelial cell hyperplasia by 10 weeks of age, indicating that the incidence of transformation was 100%. Tumorigenesis in the LPB-Tag animals progressed in a manner similar to that observed in the human prostate. Initially, multifocal proliferating lesions were detected in the prostatic epithelium, which continued to progress into hyperplasia involving the entire epithelium and then low-grade dysplasia. Reactive stromal proliferation was induced and continued to develop throughout the progression to high-grade dysplasia, carcinoma in situ, and adenocarcinoma. Immunohistochemical studies indicated that most stromal cells stained positively for both androgen receptor and smooth muscle alpha-actin, suggesting that stromal overgrowth largely represented mesenchymal cells that had differentiated into smooth muscle cells. Epithelial cell transformation was accompanied by the down-regulation of differentiated function, as suggested by the loss of dorsolateral prostate-specific secretory proteins. Tumor growth was regarded as androgen-dependent because tumors regressed in animals castrated at 11 weeks of age, and androgen treatment restored both epithelial/stromal cell ratio and tumor growth. Furthermore, small populations of prostatic epithelial cells in castrated animals continued to proliferate, suggesting the potential for androgen-independent growth. Although prostatic metastasis to other organs was not observed, local invasion was detected. In summary, the LPB-Tag animal model is unique in that it is the only model generated with the Tag alone, thereby eliminating any influences of the small t antigen on prostate tumor formation. Moreover, this model undergoes molecular changes similar to those found in human prostate including: (a) the multi-focal nature of tumorigenesis, (b) the progressive histopathologic changes from low- to high-grade dysplasia similar to human prostatic intraepithelial neoplasia, (c) stimulation of reactive stromal proliferation, and (d) the androgen-dependent growth of the primary tumor. Thus, the LPB-Tag prostate tumor model will be useful for studying the sequential mechanisms underlying the development of multistep tumorigenesis.

Androgen-Binding Protein↗
PubMed1998

Consensus statement on panic disorder from the International Consensus Group on Depression and Anxiety.

OBJECTIVE: To provide primary care clinicians with a better understanding of management issues in panic disorder and guide clinical practice with recommendations for appropriate pharmacotherapy. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Four faculty invited by the chairman also participated: David S. Baldwin, Johan A. den Boer, Siegfried Kasper, and M. Katherine Shear. EVIDENCE: The consensus statement is based on the 6 review papers that are published in this supplement and on the scientific literature relevant to these issues. CONSENSUS PROCESS: There were group meetings held during a 2-day period. On day 1, the group discussed each review paper and the chairman and discussant (Dr. Kasper) identified key issues for further debate. On day 2, the group discussed these key issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chairman and approved by all attendees. CONCLUSIONS: The consensus statement provides standard definitions for response and remission and identifies appropriate strategy for the management of panic disorder in a primary care setting. Serotonin selective reuptake inhibitors are recommended as drugs of first choice with a treatment period of 12 to 24 months. Pharmacotherapy should be discontinued slowly over a period of 4 to 6 months.

Antidepressive Agents↗
PubMed1998

Depression: a long-term illness and its treatment.

Depression is a common illness that is frequently chronic or recurring. It is associated with substantial disability and therefore treatment strategies need to take into account its long-term course. The risk of relapse can be reduced provided therapy is adequate, in terms of both duration and dose, and there is now good evidence for some antidepressants that long-term treatment also reduces the risk of recurrence (i.e. new episodes of depression). This aspect of efficacy has been investigated most thoroughly with the tricyclic antidepressant imipramine and with the selective serotonin reuptake inhibitors. The clearest demonstration of the ability to reduce the risk of new episodes of depression is obtained from studies designed to test prophylaxis specifically in patients who have responded to antidepressant treatment and who have maintained their response during a period of continuation treatment to ensure resolution of the episode. The long-term efficacy of imipramine and fluoxetine was demonstrated using this design. More recently fluvoxamine was shown to be effective in reducing the risk of new episodes in a 1-year study in patients whose acute episode of depression had responded to treatment with fluvoxamine and who had remained well for 18 weeks. These prophylactic studies show that antidepressants reduce the risk of new episodes of depression, and prophylactic treatment should therefore be continued as long as the risk persists.

Antidepressive Agents↗
PubMed1998

Risperidone and olanzapine: optimal dosing for efficacy and tolerability in patients with schizophrenia.

Schizophrenia is a chronic and debilitating disorder whose effective pharmacological management is often less than optimal. For several decades, pharmaceutical treatment for this disorder consisted of conventional neuroleptics such as haloperidol and chlorpromazine. However, the limitations of these drugs have driven the development of newer antipsychotics that are designed to be more efficacious and more tolerable than conventional agents. Newer agents available for consideration as first-line treatment options now include risperidone, olanzapine, sertindole and, more recently, quetiapine. Proper dosing has emerged as a vital factor in the effective use of these newer drugs. This report examines data derived from clinical trials and market research with risperidone and olanzapine to help clinicians determine the appropriate dose for efficacy and to appraise the adverse events associated with that efficacious dose. Current information suggests that, for most patients with schizophrenia, the optimal dose with respect to efficacy and tolerability of risperidone is < or = 6 mg/day. The optimal dose of olanzapine is less clear and may be 15 mg/day or higher. With the advent of these newer antipsychotics, clinicians now have more treatment options for the management of patients with psychotic disorders. Knowledge gained through clinical experience is needed to augment clinical trial results and to help define the most effective use of each of these agents.

Antipsychotic Agents↗
PubMed1997

Large fragment of the probasin promoter targets high levels of transgene expression to the prostate of transgenic mice.

BACKGROUND: Androgen regulation and prostate-specific expression of targeted genes in transgenic mice can be controlled by a small DNA fragment of the probasin (PB) promoter (-426 to +28 base pairs, bp). Although the small PB fragment was sufficient to direct prostate-specific expression, the low levels of transgene expression suggested that important upstream regulatory sequences were missing. METHODS: To enhance transgene expression, a large fragment of the PB promoter (LPB, -11,500 to +28 bp) was isolated, linked to the bacterial chloramphenicol acetyl transferase (CAT) gene, and microinjected into CD1 mouse oocytes to generate transgenic mouse lines. RESULTS: As shown by the immunohistochemical studies, CAT gene expression was restricted to the prostatic epithelial cells in a tissue-specific manner. High levels of CAT gene expression were observed in two of the six LPB-CAT transgenic lines. In Line 1, developmental regulation of LPB-CAT was detected early, from 1 to 4 weeks of age, with the activity of CAT increasing from 3 to 40,936 dpm/min/mg protein. Upon sexual maturation and elevated serum androgen levels (7 weeks of age), a further 18-fold rise in CAT activity occurred. Hormone ablation by castration in mature mice dramatically reduced transgene expression, whereas treatment with androgens returned LPB-CAT expression to precastration levels. In contrast, treatment with glucocorticoids had no significant effect on CAT gene expression. Zinc treatment of the castrated animals also increased LPB-CAT expression three- to four-fold in two prostatic lobes. CONCLUSIONS: This study demonstrates that important regulatory DNA sequences located in the LPB fragment contribute to tissue-specific expression and greatly increase levels of transgene expression induced by androgens and zinc.

Aging↗
PubMed1997

[Maintenance therapy with 20 mg fluoxetine. Results of an administration study of 1,737 depressed patients].

An application study was carried out in 1993/94 on the use of fluoxetine for the continuation therapy of depression. 1737 patients received fluoxetine at a dosage of 20 mg per day over a period of 6 months. Diagnosis was made by clinical evaluation of phenomenology and ICD-10 classification. Over the observation period physicians rated the course of illness according to severity of the depression, somatic complaints and therapeutic efficacy on a scale graded 1-4. Side effects and concomitant medication were also noted. Coincidentally, patients recorded subjective satisfaction with therapy, as well as side effects. In a subsample of 423 patients the physicians additionally used a modified version of the Hamilton Depression Rating Scale (HRDS) for behavioural ratings. Standard assessment was performed after the 2nd and 6th weeks of treatment and again after the 3rd and 6th months. The rating scale showed a decrease in depressive symptomatology and somatic complaints at the end of treatment in 53% and 44% of patients, respectively. Treatment efficacy was rated as excellent in 82% of cases, as evaluated by the physicians; patients were satisfied in 89% of cases. These results are strengthened by the reduction from 22.4 +/- 7.0 to 9.2 +/- 6.4 in the subsample of 423 patients according to the HRDS, equivalent to a decrease in depression symptomatology of 59%. This study is the first open phase IV trial in Austria investigating continuation therapy with 20 mg fluoxetine per day and confirms results obtained in international multicentre placebo-controlled studies involving considerably smaller numbers of patients.

Adolescent↗
PubMed1997

Effects of tryptophan depletion on drug-free patients with seasonal affective disorder during a stable response to bright light therapy.

BACKGROUND: A dysfunction of the serotonin system may play a major role in the pathogenesis of seasonal affective disorder. Bright light therapy has been shown to be effective in the treatment of winter depression in patients with seasonal affective disorder. Light therapy-induced remission from depression may be associated with changes in brain serotonin function. METHODS: After at least 2 weeks of clinical remission, 12 drug-free patients who had had depression with seasonal affective disorder underwent tryptophan depletion in a double-blind, placebo-controlled, balanced cross-over design study. RESULTS: Short-term tryptophan depletion induced a significant decrease in plasma free and total tryptophan levels (P < .001 for both, repeated measures analysis of variance), with peak effects occurring 5 hours after ingestion of a tryptophan-free amino acid drink. It emerged that tryptophan depletion leads to a transient depressive relapse, which was most pronounced on the day after the tryptophan-depletion testing. No clinically relevant mood changes were observed in the control testing. CONCLUSIONS: The maintenance of light therapy-induced remission from depression in patients with seasonal mood cycles seems to depend on the functional integrity of the brain serotonin system. Our results suggest that the serotonin system might be involved in the mechanism of action of light therapy.

Adult↗
PubMed1997

Risperidone in the treatment of schizophrenia: results of a study of patients from Germany, Austria, and Switzerland.

Results of a subanalysis of data from the multinational risperidone trial (RIS-INT-2) are reported. Patients with chronic schizophrenia were treated with risperidone at 1 mg/day (n = 25), 4 mg/day (n = 27), 8 mg/day (n = 29), 12 mg/day (n = 31), or 16 mg/day (n = 29), or 10 mg/day of haloperidol for 8 weeks. According to the Positive and Negative Syndrome Scale (PANSS) total and subscale scores, improvements were noted in each treatment group from baseline to treatment endpoint. On each scale the magnitude of improvement was greater in the risperidone patients than in the haloperidol patients. The onset of action of risperidone was faster than haloperidol. By treatment week 2, over half of the patients receiving > or = 4 mg/day of risperidone were clinically improved (> or = 20% reduction in total PANSS scores). This rate of improvement was not seen until week 6 in the haloperidol patients. Severity of extrapyramidal symptoms (scores on the Extrapyramidal Symptom Scale) was significantly lower in patients receiving 1 or 4 mg/day of risperidone than in patients receiving higher risperidone doses and in haloperidol patients. The optimal dose of risperidone, in terms of both efficacy and safety, was 4 mg/day. These results confirm the findings of the controlled trials of risperidone conducted in North America and the multinational trial.

Adult↗
PubMed1997

[Electroconvulsive therapy in clinical practice].

Between September 1st, 1994, and the end of August, 1995, 3% of all inpatients (21 of 731) were treated with electroconvulsive therapy (ECT) at the Department of General Psychiatry at the University Hospital for Psychiatry in Vienna. These patients suffered from psychotic and/or therapy-resistant depression (n = 15), therapy-resistant schizoaffective psychosis (n = 3), and catatonic schizophrenia (n = 3). ECT was administered in short-time anaesthetised and muscle relaxed patients. On average, each patient was treated with ECT on 9 non-consecutive days. As a rule, electrodes were placed unilaterally over the non-dominant hemisphere at the beginning. In four cases electrodes were placed bifronto-temporally. To be considered as effective the seizure had to last for at least 25 s. In shorter seizure duration ECT was repeated up to a maximum of three times in one session. With this procedure a reduction in clinical global impressions of -3.7 points was achieved in ECT-treated patients, who had been considered to be "severely" to "most severely" ill according to CGI before starting ECT. ECT proved to be effective for treating severe depression and catatonic schizophrenia, with only minor and reversible side effects. For establishing a favorable relation between good clinical outcome and remarkable few side effects, the following factors seem to be of importance, in accordance with the literature: (1) application of biphasic short-impulse stimuli in anaesthetised and muscle relaxed patients; (2) measurement of static impedance to avoid high skin impedance and short circuits. (3) at the beginning of each ECT series unilateral electrode placement over the non-dominant hemisphere; (4) ECT three times weekly on non-consecutive days.

Adult↗
PubMed1997

[The tryptophan depletion test. Basic principles and clinical relevance].

The application of a tryptophan-free amino acid mixture (tryptophan depletion test) induces a rapid and substantial lowering of both total and free plasma tryptophan. Consequently, the brain serotonin content and also cerebral serotonin function are decreased. This method provides a paradigm to study the role of serotonin in the pathobiology of depressive disorders and their treatment modalities. Untreated depressed patients show few behavioral effects during tryptophan depletion. In depressed patients during an antidepressant or light-therapy-induced stable remission, a transient depressive relapse was induced by tryptophan depletion. Healthy subjects with a genetic risk for affective disorder show worsening of their condition induced by tryptophan depletion. These findings indicate the relevance of altered brain serotonin function in the pathophysiology of affective disorders and strengthen the importance of serotonin in the mechanism of action of antidepressants. Since recently published studies revealed some evidence that the serotonergic system is directly involved in the pathophysiology of various psychiatric syndromes besides depression, it seems to be reasonable to evaluate the validity of the tryptophan depletion test also in non-depressed patients.

Brain↗
PubMed1997

[Premenstrual dysphoric disorder. An overview of diagnosis, epidemiology and therapeutic approaches].

Even though premenstrual symptoms had been already described by Hippocrates, premenstrual dysphoric disorder (PMDD) was first mentioned as a special psychiatric diagnosis in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) in 1994. In DSM-III-R-Appendix A is was called late luteal phase dysphoric disorder (LLPDD), Appendix A. Before this diagnosis was established based on operationalized criteria, the term premenstrual syndrome (PMS) was used for patients with severe premenstrual mood disturbances and physical symptoms. Many hypotheses about the pathophysiological mechanisms underlying PMS and PMDS led to different therapeutic strategies. While PMS was mainly treated by gynecologists, PMDD became of interest in psychiatric research. Several antidepressants, psychotherapy, sleep deprivation and light therapy have been investigated regarding their effectiveness in combatting premenstrual symptoms such as depression, tension, dysphoria and anxiety. Within the anti-depressants the best findings were for selective serotonin reuptake inhibitors (SSRIs).

Antidepressive Agents↗