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Biomedical subjects

S Kasper

Publications and source records attributed to S Kasper.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of the growth-promoting effects of testosterone and 7-alpha-methyl-19-nor-testosterone (MENT) on the prostate and levator ani muscle of LPB-tag transgenic mice.

BACKGROUND: 7-alpha-methyl-19-nortestosterone (MENT) is being considered for androgen replacement in testosterone deficient men and as a male contraceptive. Because androgenic effects on the prostate are a major concern, we have evaluated MENT in a transgenic model of prostate cancer. METHODS: LPB-Tag mice were castrated and infused with testosterone (T; 5 or 30 microg/day) or MENT (5 or 30 microg/day) for 4 weeks. Prostate, seminal vesicle, and levator ani muscle (LAM) weights were compared. RESULTS: At an equivalent dose, MENT maintained or stimulated the mean weights of these organs more than T. However, the dorsolateral prostate/LAM ratio of weights did not favor MENT, but DNA/mg tissue and Ki 67 immunostaining suggested that MENT may increase DNA less than T. CONCLUSIONS: MENT is more potent than T in maintaining or stimulating prostate, seminal vesicle, and LAM. Using doses that resulted in comparable stimulation of the levator ani muscle, MENT had similar effect on prostate weight, but increased DNA/mg prostate less than T in this transgenic mouse model of prostate cancer.

Animals↗
PubMed2006

Intravenous mirtazapine is safe and effective in the treatment of depressed inpatients.

Mirtazapine is a third-generation antidepressant with a dual mode of action. The oral administration has been shown to be effective and safe in the treatment of depressed patients. In this multicenter naturalistic study, we assessed the safety, tolerability, and therapeutic efficacy of intravenously administered mirtazapine in 80 moderately to severely depressed inpatients during a treatment period of 14 days. We found a significant decrease of the Hamilton Depression Rating Scale total score compared to baseline. Side effects were mild and transient. Our data indicate that intravenous mirtazapine is an effective, safe and well-tolerated treatment for depressed inpatients.

Adolescent↗
PubMed2006

[Early recognition and intervention for schizophrenia].

Studies dealing with the prodromal stage of schizophrenia point to the possibility of early detection and early intervention. Major socioeconomic and social consequences are associated with this disorder. The duration of untreated psychosis seems to play an important role in the course of the disease; i.e. a prolonged duration until adequate treatment is obtained correlates to poorer prognosis. Social, cognitive, affective, and structural brain variations appear in the early prodromal stage. Recent early intervention studies show the possibility of reducing transition rates by preventive treatment of patients at a higher risk of psychosis and already manifesting impaired function. In this review, prodromal signs and possibilities for early detection and intervention in schizophrenia are presented.

Affective Disorders, Psychotic↗
PubMed2005

No association of clock gene T3111C polymorphism and affective disorders.

CLOCK was hypothesised to be related to susceptibility of affective disorders. To test subsamples of affectively disordered patients, we examined age of onset (AoO), numbers of episodes and melancholic type of clinical manifestation. Using PCR and RFLP, we investigated in patients with unipolar depression and bipolar disorder (BP) whether the CLOCK T3111C SNP is associated with affective disorders (n=102) compared to healthy controls (n=103). No differences were found either in genotype or allele frequency distributions of T3111C polymorphism between patients compared to healthy controls (p>0.2). No deviations from Hardy-Weinberg Equilibrium (HWE) were detected either in patients, or healthy controls. Results suggest that there is no association between the T3111C SNP and affective disorders in general. Data of our sample replicate prior findings of Desan et al. [Am. J. Med. Genet. 12 (2000) 418]. Subsamples of patients with high numbers of affective episodes did show some deviations in genotypes (p=0.0585).

Adult↗
PubMed2005

[Neuroimaging in schizophrenia].

This overview is focused on functional neuroimaging including functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT). Recent evidence for the "dopamine hypothesis of schizophrenia" is summarized including alterations of presynaptic dopamine metabolism and postsynaptic receptor binding potential. Emphasis is given to dopaminergic challenge studies using amphetamine and AMPT. Several PET and SPECT studies have shown a pronounced increase of amphetamine-induced dopamine release as well as decrease of AMPT-induced dopamine depletion in drug-naive schizophrenic patients, indicating a dysregulation of dopaminergic neurotransmission. Results of studies combining amphetamine challenge and the NMDA receptor antagonist ketamine are related to glutaminergic dysfunction and neurotransmitter interactions. FMRI and PET results demonstrating alterations in task-specific functional connectivity between brain areas are discussed with a focus on the prefrontal cortex and temporal structures. Increase of serotonin-1A receptor binding potential in prefrontal and mesotemporal cortex is related to the serotonin-dopamine interaction. Genetic neuroimaging techniques, including voxel-based morphometry (VBM) and fMRI, revealing significant effects of the dopamine metabolizing enzyme COMT on functional activation in prefrontal areas are also discussed. Functional neuroimaging based on challenge-paradigms in PET as well as task-specific state- or trait-dependent alterations of activation patterns in fMRI, seems to be a promising candidate for the development of biological marker tests for schizophrenia.

Brain↗
PubMed2005

A comparative, randomised, double-blind study of trazodone prolonged-release and paroxetine in the treatment of patients with major depressive disorder.

OBJECTIVES: To evaluate the efficacy and safety of trazodone prolonged release compared with paroxetine in the treatment of patients with major depression. RESEARCH DESIGN AND METHODS: A total of 108 patients aged 20-68 years were enrolled in this multicentre, double-blind, double-dummy, randomised, paroxetine-controlled study. Each patient received 3 days single-blind placebo treatment followed by 6 weeks double-blind treatment with either trazodone prolonged release 150-450 mg/day (n = 55) or paroxetine 20-40 mg/day (n = 53). OUTCOME MEASURES: Efficacy was evaluated by the rate of patients responding to each treatment and considered to be in remission, and by mean changes from baseline in the Hamilton Depression Rating scale scores (HAM-D), Montgomery Asberg Depression Rating Scale scores (MADRS), and Clinical Global Impression (CGI)--Severity and Global Improvement scores. Time to onset of efficacy and safety were assessed. RESULTS: Trazodone and paroxetine were equally effective at reducing symptoms of depression and promoting remission. Onset of efficacy was slightly faster for patients treated with paroxetine. Overall, there were no significant differences between the groups at endpoint in efficacy measures, and in percentage of responders (> 85%) or patients in remission (> 65%). Sleep disorders (HAM-D subset) were significantly less evident for patients in the trazodone group at the end of the study (p < 0.05). Adverse drug reactions were reported by 35% of trazodone-treated patients (mainly of the nervous system) and 26% of paroxetine-treated patients (mainly gastrointestinal), although none was considered to be serious. CONCLUSIONS: This study showed that after a 6-week period trazodone and paroxetine are not different in reducing the symptoms of depression and, in many patients, in producing the remission of the illness. The known divergence in tolerability profile of the two medications, related to their differing pharmacological properties, was also confirmed. Trazodone may be of advantage in depressed patients with sleep difficulties.

Adult↗
PubMed2004

Placebo-controlled trials in major depression are necessary and ethically justifiable: how to improve the communication between researchers and ethical committees.

Despite numerous placebo-controlled clinical trials with antidepressants were conducted in humans and a large amount of data was already published in the last two decades, the members of the 4th European Expert Forum on Ethical Evaluation of Placebo-Controlled Studies in Depression were agreed that placebo-controlled trials with antidepressants also in the future are essential. Placebo-controlled studies measure the effect size in a reliable way and establish sensitivity and internal validity. They are scientifically sound and interpretable in terms of efficacy and are, therefore, clinically more relevant than non-placebo-controlled clinical trials. The "Note of Clarification" of the Declaration of Helsinki opens up where such trials are acceptable. This statement of the members of the 4th European Expert Forum is directed to academia, members of Ethic Committees, regulators, and industry to facilitate their decisions towards clinical studies with antidepressants. "Checklists" for the contents of patients information are given as well as for the investigator.Placebo-controlled clinical trials are scientifically necessary, ethical and feasible. The administration of the placebo is in itself a non-specific treatment and experts agree that there appears to be no increased suicidal risk in the placebo-group of carefully selected and monitored study patients.

Antidepressive Agents↗
PubMed2004

Continuation and long-term maintenance treatment with Hypericum extract WS 5570 after successful acute treatment of mild to moderate depression--rationale and study design.

Unipolar major depression is often a chronic disease that may require lifelong prophylaxis. Recovery from an acute episode is followed by 4-6 months of relapse prevention. After that, long-term maintenance treatment is administered to avoid recurrence. We present the rationale and design of an ongoing double-blind, randomized, placebo-controlled trial investigating the efficacy of Hypericum extract WS 5570 in relapse prevention in recurrent unipolar depression. An estimated sample of 425 adults with recurrent, mild to moderate major depression (ICD-10 and DSM-IV criteria), > or = 3 previous episodes (last 5 years) and a total score > or = 20 points on the 17-item Hamilton Rating Scale for Depression (HAMD) will be included. After a one-week wash out patients receive 3 x 300 mg/day WS 5570 single-blind for 6 weeks. Responders are randomized to 26 weeks of double-blind continuation treatment with 3 x 300 mg/day WS 5570 or placebo. Patients completing continuation treatment without relapse enter 52 weeks of doubleblind maintenance treatment, where those treated with WS 5570 are re-randomized to 3 x 300 mg/day WS 5570 or placebo. The primary outcome measure is the time to relapse during continuation treatment (HAMD > or = 16, clinical diagnosis of depression, or premature treatment termination for inefficacy). Hypericum extract, with its favourable tolerability profile, could be an interesting option for long-term prophylaxis. The trial was designed according to current consensus and guidance. Notably, it includes long-term prophylactic treatment with the same drug and the same therapeutic dose applied during acute treatment, uses well-defined outcome measures and provides a clear distinction between relapse and recurrence.

Acute Disease↗
PubMed2004

[Drug therapy of acute manias. A retrospective data analysis of inpatients from 1997 to 1999].

The aim of the present retrospective chart analysis was to compare published treatment algorithms with the treatment patterns of 90 consecutive inpatients suffering from acute mania or hypomania at the Department of General Psychiatry, University of Vienna, from 1997 to 1999. Treatment strategies during the first 14 days and on discharge as well as sociodemographic and illness related data were evaluated. The results of our study reflect that international guidelines were not included in daily practice from 1997 to 1999 with regard to the usage pattern of atypical antipsychotics versus typical neuroleptics. Also, recommendations have not been taken into account about monotherapy with a mood stabilizer as first-line treatment for acute mania (polypharmacia was the predominant treatment scheme) and the advice to taper off benzodiazepines (at discharge).

Acute Disease↗
PubMed2004

[Neuroimaging in substance abuse disorders].

The use of neuroimaging techniques in research on substance abuse disorders has advanced our understanding of the underlying pathophysiological and neuropsychological mechanisms. While initial structural imaging techniques were applied to investigate substance abuse-related cerebral atrophy, the functional techniques of SPECT, PET, and later fMRT and MRS provide a much broader range of possible research in this field. Besides their use in characterizing the pharmacology of abused substances and their relations to the pathophysiology of substance abuse disorders, they have also played an essential role in examining the neuropsychiatric underpinnings of the illness and their manifestation in changes of cerebral metabolism. Here, the influence of these techniques on the developing picture of substance abuse disorders is discussed by examining areas of particular scientific interest and reviewing exemplary findings.

Alcoholism↗
PubMed2004

Biophotons, microtubules and CNS, is our brain a "holographic computer"?

Several experiments show that there is a cell to cell communication by light in different cell types. This article describes theoretical mechanisms and subcellular structures that could be involved in this phenomenon. Special consideration is given to the nervous system, since it would have excellent conditions for such mechanisms. Neurons are large colourless cells with wide arborisations, have an active metabolism generating photons, contain little pigment, and have a prominent cytoskeleton consisting of hollow microtubules. As brain and spinal cord are protected from environmental light by bone and connective tissue, the signal to noise ratio should be high for photons as signal. Fluorescent and absorbing substances should interfere with such a communication system. Of all biogenic amines nature has chosen the ones with the strongest fluorescence as neurotransmitters for mood reactions: serotonin, dopamine and norepinephrine. If these mechanisms are of relevance our brain would have to be looked upon as a "holographic computer".

Animals↗
PubMed2004

[Flunitrazepam and driving ability].

Major contributions to the investigation of the influence of drugs on driving ability come from experimental studies as apart from epidemiological studies. Regarding experimental studies, the results of a single study are essentially determined by the experimental design. An established assessment of the risk of a drug in regard to driving ability should not be based on either a single study or on synopses, which record only a few studies without detailed information. This article presents an overview of published studies that directly or indirectly deal with the influence of flunitrazepam on driving ability. Benzodiazepines in particular, and amongst these especially flunitrazepam are brought into connection with the impairment of driving ability. This approach emphasises differences regarding the dosages used, the experimental designs and the methods of testing. For reasons of clarity the article on flunitrazepam is subdivided into the topics of acute effects, residual effects, and effects after subchronic application. Different results are reported. A statistical analysis in terms of a meta-analysis was not carried out due to a lack of standardization of the studies.

Anti-Anxiety Agents↗
PubMed2003

Cognitive effects and antipsychotic treatment.

Cognitive impairment has long been recognized as central to the abnormalities that occur in schizophrenia, since neurocognitive deficits are predictive of a number of outcome indices, and they pose a significant obstacle to any attempts at social rehabilitation. This raises the possibility that treatments producing improvements in cognitive function might, in turn, prove to have synergistic effects with psychosocial interventions. Rather than improving cognitive deficits, conventional antipsychotics may instead contribute to the impairment seen in many patients with schizophrenia. These damaging effects on cognition might be expected not only when antipsychotic drugs with intrinsic anticholinergic properties are used but also when anticholinergic drugs are prescribed for the relief of treatment-emergent extrapyramidal symptoms. The atypical antipsychotic drugs may be effective in this area, either in amelioration of the cognitive impairments that occur in schizophrenia or in arresting any continuing decline. New-generation atypical agents, such as quetiapine and risperidone, have minimal intrinsic anticholinergic effects, which suggest that some of the additional negative effects on cognition can be avoided. A number of large-scale, long-term follow-up studies of atypical antipsychotics are currently underway, in 'real world' settings, to assess not only control of symptoms of schizophrenia but also improvement in social, occupational, and inter-personal functioning.

Antipsychotic Agents↗
PubMed2003

Recurrent brief depressive disorder reinvestigated: a community sample of adolescents and young adults.

BACKGROUND: This article presents prospective lower bound estimations of findings on prevalence, incidence, clinical correlates, severity markers, co-morbidity and course stability of threshold and subthreshold recurrent brief depressive disorder (RBD) and other mood disorders in a community sample of 3021 adolescents. METHOD: Data were collected at baseline (age 14-17) and at two follow-up interviews within an observation period of 42 months. Diagnostic assessment was based on the Munich Composite International Diagnostic Interview (M-CIDI). RESULTS: Our data suggest that RBD is a prevalent (2.6%) clinical condition among depressive disorders (21.3%) being at least as prevalent as dysthymia (2.3%) in young adults over lifetime. Furthermore, RBD is associated with significant clinical impairment sharing many features with major depressive disorder (MDD). Suicide attempts were reported in 7.8% of RBD patients, which was similar to MDD (11.9%). However, other features, like gender distribution or co-morbidity patterns, differ essentially from MDD. Furthermore, the lifetime co-occurrence of MDD and RBD or combined depression represents a severe psychiatric condition. CONCLUSIONS: This study provides further independent support for RBD as a clinically significant syndrome that could not be significantly explained as a prodrome or residual of major affective disorders.

Adolescent↗
PubMed2003

The serotonin transporter promoter repeat length polymorphism, seasonal affective disorder and seasonality.

BACKGROUND: Conflicting results have been reported in previous association studies of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR), seasonal affective disorder (SAD) and seasonality (seasonal variations in mood and behaviour). The aim of this study was to test for association in new case-control and population-based materials, and to perform a combined analysis of all published studies of 5-HTTLPR and SAD. METHOD: One hundred and forty-seven new SAD cases and 115 controls were genotyped for 5-HTTLPR and in total 464 patients and 414 controls were included in the pooled analysis. In addition, 226 individuals selected for unusually high or low seasonality scores from a population based material and 46 patients with non-seasonal depression were analysed. Different genetic models were tested and seasonality was analysed both as a qualitative (high v. low) and as a quantitative trait in the different sample sets. RESULTS: No association between 5-HTTLPR and SAD was found in the new case-control material, in the combined analysis of all samples, or when only including 316 patients with controls (N = 298) selected for low seasonality. A difference was detected between the population based high and low seasonality groups, when assuming a recessive effect of the short allele (20% and 10% short allele homozygotes, respectively, OR (95% CI): 2.24 (1.03-4.91)). Quantitative analysis of seasonality revealed no association with 5-HTTLPR in any sample set. CONCLUSIONS: These results do not suggest a major role of the short variant of 5-HTTLPR in susceptibility to SAD, but provide modest evidence for an effect on seasonality.

Adult↗