Biomedical subjects

S Kasper

Publications and source records attributed to S Kasper.

At least 127 records · Page 7Linked to original sources

PubMed1999

[Osteoporosis in anorexia nervosa. New aspects of pathogenesis and therapy].

Osteoporosis has been shown to be a relatively common complication of anorexia nervosa (AN). So far the exact mechanisms which are implicated are not fully clarified. Several factors such as malnutrition, reduced body weight, amenorrhea, and hypercortisolaemia seem to be involved. There is a strong relationship with the duration of amenorrhea and--in some studies--with the age of onset. Osteoporosis is for a long time a "silent" disease and the first symptoms such as back pain, loss of height, kyphosis, and fractures are late complications. Therefore, routine screening methods for bone density measurements should be established. The most accurate is the dual energy X-ray absorptiometry (DEXA). Therapeutically the primary aim should be to reach restoration of both normal body weight and regular menses. As AN is a chronic disease clinicians should be aware of the dangers of osteoporosis and start with the treatment and/or prevention of osteoporosis early. However, at this stage it is difficult to provide an evidence-based management plan for osteoporosis in AN. Hormone replacement therapy (HRT) as well as calcium and vitamin D-supplementation are under discussion, however, further controlled investigations are warranted.

Absorptiometry, Photon↗

PubMed1999

In vivo 123I IBZM SPECT imaging of striatal dopamine-2 receptor occupancy in schizophrenic patients treated with olanzapine in comparison to clozapine and haloperidol.

We investigated the degree of striatal dopamine-2 (D2) receptor occupancy in six schizophrenic patients receiving clinically effective antipsychotic treatment with olanzapine 10-25 mg/day in comparison to patients treated with clozapine 300-600 mg/day (n = 6) or haloperidol 5-20 mg/day (n = 10). 123I Iodobenzamide (IBZM) and single photon emission computerized tomography (SPECT) were used for the visualization of striatal D2 receptors. For the quantification of striatal D2 receptor occupancy, striatal IBZM binding in patients treated with antipsychotics was compared to that in untreated healthy controls (n = 8) reported earlier. Olanzapine led to a mean striatal D2 receptor occupancy rate of 75% (range 63-85). Haloperidol-treated patients showed dose-dependently (Pearson r = 0.64; P < 0.05) a significantly higher (P < 0.05) mean occupancy rate of 84% (range 67-94). During clozapine treatment, the mean D2 receptor occupancy of 33% (range < 20-49) was significantly lower than with olanzapine (P < 0.005). The higher striatal D2 receptor occupancy of haloperidol was correlated with the incidence and severity of extrapyramidal motor side-effects (EPS). No clinical relevant EPS occurred during treatment with olanzapine or clozapine. There was no correlation between the degree of striatal D2 receptor occupancy and clinical improvement.

Adult↗

PubMed1999

15-lipoxygenase-2 (15-LOX-2) is expressed in benign prostatic epithelium and reduced in prostate adenocarcinoma.

Human 15S-lipoxygenase-2 (15-LOX-2) is a recently identified lipoxygenase that has approximately 40% sequence identity to the known human 5S-, 12S-, and 15S-lipoxygenases. 15-LOX-2 has a limited tissue distribution, with mRNA detected in prostate, lung, skin, and cornea, but not in numerous other tissues, including peripheral blood leukocytes. In the current study, we have characterized the distribution of 15-LOX-2 in the human prostate by immunohistochemistry, demonstrated the ability of benign prostate tissue to form 15S-hydroxyeicosatetraenoic acid (15S-HETE) from exogenous arachidonic acid (AA), and begun characterizing possible alterations in 15-LOX-2 in prostate adenocarcinoma. Incubation of benign prostate tissue with [14C]AA resulted in formation of [14C]15-HETE, as determined by reverse- and straight-phase high-performance liquid chromatography. 15-HETE was the major AA metabolite formed. By immunohistochemistry, 15-LOX-2 is located in secretory cells of peripheral zone glands and large prostatic ducts and somewhat less uniformly in apical cells of transition and central zone glands. 15-LOX-2 was not detected in the basal cell layer, stroma, ejaculatory ducts, seminal vesicles, or transitional epithelium. Immunostaining of 18 radical prostatectomy specimens showed a loss of 15-LOX-2 in the majority of prostate adenocarcinomas; 14 of 18 cases showed loss of 15-LOX-2 in >25% of the tumor (mean, 74.9% negative for 15-LOX-2; range, 38.9% to 100%). Incubation of paired pure benign and pure malignant prostate tissue from the same radical prostatectomies showed that 15-HETE formation was markedly reduced (>90%) or undetectable in incubations of prostate adenocarcinoma. 15-LOX-2 is a novel human lipoxygenase with a limited tissue distribution that is strongly expressed in benign prostate glandular epithelium and lost to a variable degree in the majority of prostate adenocarcinomas.

Adenocarcinoma↗

PubMed1999

In vivo visualization of serotonin transporters in the human brain during fluoxetine treatment.

Beta-CIT can be used as a tracer for SPECT to visualize serotonin transporters in the human brain. We present a case of bulimia nervosa and major depressive disorder, who had been treated with up to 60 mg/d fluoxetine for several weeks. Four hours after injection of the tracer more than 40% of serotonin transporters were blocked. To our knowledge, this is the first direct documentation of the pharmacodynamic action of fluoxetine in the human brain in vivo.

Adolescent↗

PubMed1999

Dopamine D3 receptor gene polymorphism and response to clozapine in schizophrenic Pakastani patients.

The dopamine D3 receptor (DRD3) appears to play an important role in the mediation of antipsychotic drug action. Genetic association of treatment response to the atypical antipsychotic drug clozapine with the DRD3 polymorphism Ser9Gly was investigated in a sample of 32 schizophrenic patients. We found association of treatment response with allele Gly-9 (P=0.0058) and with genotypes consisting of Gly-9 (P=0.033) by this pharmacogenetic approach. A combined analysis with two previous studies (Shaikh et al., Hum. Genet. 97 (1996) 714-719; Malhotra et al., Mol. Psychiatry 3 (1998) 72-75) further substantiates these results (P=0.0041).

Adult↗

PubMed1999

Buprenorphine versus methadone maintenance for the treatment of opioid dependence.

AIMS: To evaluate the effectiveness of buprenorphine compared with methadone maintenance therapy in opiate addicts over a treatment period of 24 weeks. DESIGN: Subjects were randomized to receive either buprenorphine or methadone in an open, comparative study. SETTING: Subjects were recruited and treated at the drug addiction outpatient clinic at the University of Vienna. PARTICIPANTS: Sixty subjects (19 females and 41 males) who met DSM-IV criteria for opioid dependence and were seeking treatment. INTERVENTION: Subjects received either sublingual buprenorphine (2-mg or 8-mg tablets; maximum daily dose 8 mg) or oral methadone (racemic D -/+ L-methadone; maximum daily dose 80 mg). A stable dose was maintained following the 6-day induction phase. MEASUREMENT: Assessment of treatment retention and illicit substance use (opiates, cocaine and benzodiazepines) was made by urinalysis. FINDINGS: The retention rate was significantly better in the methadone maintained group (p < 0.05) but subjects completing the study in the buprenorphine group had significantly lower rates of illicit opiate consumption (p = 0.04). CONCLUSION: The results support the superiority of methadone with respect to retention rate. However, they also confirm previous reports of buprenorphine use as an alternative in maintenance therapy for opiate addiction, suggesting that a specific subgroup may be benefiting from buprenorphine. This is the first comparative trial to use sublingual buprenorphine tablets: previously published comparison studies refer to 30% solutions of buprenorphine in alcohol.

Adolescent↗

PubMed1999

From symptoms to social functioning: differential effects of antidepressant therapy.

Significant impairments in social functioning frequently occur simultaneously with depressive symptoms. The implications of such impairments extend beyond the depressed individual to their family, friends and society at large. Classical rating scales such as the Hamilton rating scale for depression primarily assess the core symptoms of depression. A range of rating scales are available, both self-reporting and administered by clinician; however, many have been criticised for their unspecified conceptual background and for being complex and time-consuming. While antidepressants in general appear to improve social functioning, no clear advantage for any single class of agent has been reported. Recently, a new self-report rating scale, the Social Adaptation Self-evaluation Scale, has been developed and used to compare the novel selective noradrenaline reuptake inhibitor, reboxetine, with the selective serotonin re-uptake inhibitor, fluoxetine. The noradrenergic agent, reboxetine, was shown to be significantly more effective in improving social functioning than the serotonergic agent, fluoxetine. These findings are consistent with previous observations that noradrenaline may preferentially improve vigilance, motivation and self-perception.

Adrenergic Uptake Inhibitors↗

PubMed1999

Selective activation of the probasin androgen-responsive region by steroid hormones.

Glucocorticoid and androgen receptors have been shown to function through the same palindromic glucocorticoid response element (GRE) and yet have differential effects on gene transcription. In this study, we examined the functional and structural relationship of the androgen and glucocorticoid receptors with the androgen responsive region (ARR) of the probasin (PB) gene containing two androgen receptor binding sites, ARBS-1 and ARBS-2. Transfection studies indicated that one copy of each cis-acting DNA element was essential for maximal androgen-induced chloramphenicol acetyltransferase (CAT) activity and that androgen selectivity was maintained when multiple copies of the minimal wild type (wt) androgen responsive region containing both ARBS-1 and ARBS-2 (-244 to -96) were subcloned in front of the thymidine kinase promoter. Furthermore, replacing the androgen response region with 1, 2 or 3 copies of either ARBS-1 or ARBS-2 restored less than 4% of the biological activity seen with the wt PB ARR. Multiple copies of either ARBS-1 or ARBS-2 did not result in glucocorticoid-induced CAT gene activity. By comparison, 1 or 2 copies of the tyrosine aminotransferase (TAT) GRE, as well as the mouse mammary tumour virus GRE, were strong inducers of CAT activity in response to both androgen and glucocorticoid treatment. In addition, band shift assays demonstrated that although the synthetic glucocorticoid receptor, GR-DNA binding domain (GR-DBD), and the synthetic androgen receptor, AR2, could interact with the TAT GRE (dissociation constants Kd of 63.9 and 14.1 respectively), only AR2 but not GR-DBD binding could be detected on ARBS-1 and ARBS-2. Our findings provide further evidence that androgen-induced regulation of gene transcription can occur through androgen-specific DNA binding sites that are distinct from the common GRE.

Androgen-Binding Protein↗

PubMed1999

[High dose St. John's wort extract as a phytogenic antidepressant].

In 1998 a special standardized high-dose hypericum extract has been approved in Austria and Germany for treatment of mild and moderate depression. The efficacy has been already recognized since 1984 from the German Health Authorities based on traditional knowledge. However, this has been substantiated in the subsequent years in controlled clinical trials. 20 of these studies including a total of 1,787 patients have been filed, among them 10 older studies in which hypericum was extracted with ethanol compared to newer studies in which the extract was methanol (LI 160). In the past 10 years several controlled clinical trials have been conducted compared with placebo as well as synthetic antidepressants. These studies have shown that the effective dosage is within a range of 600 to 900 mg extract. The side effects are substantially fewer than with synthetic antidepressants and range within 3%. The most important risk is photosensitization, which is however without clinical relevance in the recommended dosages. Recent pharmacological studies revealed that hypericum extracts have a similar mechanism of action like the selective serotonin reuptake inhibitors (SSRI), however, very likely to a smaller extent.

Antidepressive Agents↗

PubMed1999

Pharmacokinetic-pharmacodynamic modeling of tolerance to the prolactin-secreting effect of chlorprothixene after different modes of drug administration.

The objective of this study was the construction of a pharmacokinetic-pharmacodynamic model to describe the effects of chlorprothixene on prolactin secretion and the time-dependent alterations in the concentration-effect relationship due to tolerance development. Prolactin and chlorprothixene serum concentrations were determined in eight healthy men for up to 72 h after the intravenous and oral administration of chlorprothixene. An integrated pharmacokinetic model and a physiological indirect pharmacodynamic/tolerance model were applied to describe the prolactin-secreting effect of chlorprothixene. A three-compartment model served as pharmacokinetic model. The pharmacodynamic and tolerance model accounted for the baseline effect, the effect induced by the drug, and the regulatory mechanism that opposes the effect of the drug. This model adequately characterized the prolactin response after intravenous and oral drug administration of each individual by the sensitivity (dissociation constant), the efficacy (maximal prolactin secretion rate), the extent, and the rate of tolerance development. We speculate that this approach improves the quality of neuroendocrine challenge tests to determine the subject's sensitivity to drugs and the time course of adaptation.

Administration, Oral↗

PubMed1999

Tryptophan depletion: a predictor of future depressive episodes in seasonal affective disorder?

Patients with seasonal affective disorder (SAD) do not necessarily experience depressive episodes every winter. We assessed whether the behavioural response to tryptophan depletion in summer when patients are fully remitted and off therapy is capable of predicting a future depressive episode of SAD. In a prospective study design, we followed up 11 consenting SAD patients who had undergone tryptophan depletion during summer. We evaluated how many of these patients would develop a depressive episode in the subsequent fall/winter. Seven out of eight patients who relapsed during tryptophan depletion in summer developed a depressive episode in the subsequent winter. Two out of the three patients who did not relapse during tryptophan depletion remained well during the follow-up period. Our preliminary findings suggest that those SAD patients who develop depressive symptoms during tryptophan depletion when they are fully remitted and off therapy remain at high risk to experience a depressive episode of SAD also in the subsequent winter.

Adult↗

PubMed1999

First-episode schizophrenia: the importance of early intervention and subjective tolerability.

The majority of patients with schizophrenia are likely to experience multiple episodes. Furthermore, because schizophrenia may be a progressive encephalopathy, the longer patients experience symptoms, the more likely they are to suffer lasting impairment. Early identification and pharmacologic intervention to relieve symptoms and prevent relapse are likely to have a profound effect on the long-term clinical outcomes. The choice of antipsychotic can be critical in determining long-term treatment outcomes for first-episode patients who are often particularly sensitive to the potential side effects of treatment such as extrapyramidal symptoms (EPS). Atypical antipsychotics have proven efficacy against both the positive and negative symptoms of schizophrenia, have a lower propensity to cause EPS than conventional agents, and may also improve cognitive functioning. Their use is therefore recommended, particularly for those patients experiencing their first episode.

Adult↗

PubMed1999

[Depression and anxiety].

Depression and anxiety disorders are among the most common psychiatric disorders in the general population and in daily practice of a general practitioner. Only a few years ago these disorders have been diagnosed either as "depression" or as "neurosis" in case of anxiety disorders. Since standardised diagnostic manuals have been available, it has been possible to differentiate between several depressive and anxiety disorders, which need a specific treatment. This change in the psychiatric diagnostic system is basing on psychiatric research results in the field of clinical diagnostics, biological psychiatry and epidemiology. This article provides guidance in diagnosis, differential diagnosis of depression and anxiety disorders and their therapy basing on international accepted treatment algorithms. Reviewed topics should make easy recognition and therapy possible for the general practitioner.

Anti-Anxiety Agents↗

PubMed1999

[Therapeutic sleep deprivation and phototherapy].

Since ancient times the influence of chronobiological factors on the pathogenesis, course, and treatment of depression has been well known. Amongst antidepressive treatment strategies two are based on chronobiological knowledge: therapeutic sleep deprivation, which exerts a rapid and dramatic, albeit usually short-lasting, improvement of mood in the majority of patients with major depressive disorder, and light therapy with full-spectrum bright light. About sixty percent of all depressed patients improve after a single night of total or partial sleep deprivation. It has been shown that a combination of pharmacotherapy with antidepressants and sleep deprivation is superior to pharmacotherapy alone. Moreover, sleep deprivation has proved to hasten the onset of action of antidepressant medication and repeated sleep deprivation can also be an efficient treatment strategy in drug refractory depression. Light therapy with bright artificial light is especially beneficial in patients with a fall/winter pattern of depressive symptomatology that has been termed seasonal affective disorder. Similar to sleep deprivation, bright light therapy is characterized by a fast onset of antidepressant action and by the exertion of additive properties to antidepressive medication. Bright light therapy, beginning in the morning after partial sleep deprivation, is able to prevent the depressive relapse after the next night of sleep in sleep deprivation responders.

Antidepressive Agents↗

PubMed1998

[Mirtazapine in inpatient treatment of depressed patients].

Mirtazapine is a new antidepressant with a specific pharmacological profile which is different from all other currently available antidepressants. It is a so-called noradrenergic and specific serotonergic antidepressant (NaSSA). 46 in-patients were treated with mirtazapine. The mean dose was 56 mg mirtazapine per day (SD: 23; range: 15 to 90). The duration of treatment was 3.6 weeks (SD +/- 3.4). Patients presented with following diagnosis: 29 (= 63%) were diagnosed as having a unipolar depression, 26% (n = 12) suffered from a depression in the course of a bipolar disorder. 37% (n = 17) were moderately depressed, 52% (n = 24) were severely depressed. 2 patients (= 4%) met ICD-10 (international Classification of Diseases) criteria for a schizoaffective disorder, 2 patients (= 4%) suffered from dysthymia. 1 patient suffered from an organic depressive disorder. The efficacy of the treatment was evaluated with CGI (Clinical Global Impression), when patients were discharged from hospital. 68% of the patients were in partial or full remission (CGI 2, 3 and 4), 17% were unimproved (CGI 5 and 6), in 15% of the patients the treatment was stopped before. Our observations are indicative that mirtazapine is effective in the treatment of moderately and severely depressed patients and therefore confirm the data obtained in phase III-trials. Furthermore we found mirtazapine in either mono- or combination-therapy with various other antidepressants to be tolerated well. Side effects did not cause in a single patient a discontinuation in treatment.

Adult↗

PubMed1998

Cerebral CT findings in male opioid-dependent patients: stereological, planimetric and linear measurements.

Cerebrospinal fluid (CSF) space enlargement has been demonstrated in substance-related disorders like alcohol and cocaine dependence. Experimental animal studies showed a reduction in shape and size of mesolimbic dopaminergic neurons after chronic morphine administration. Other studies indicated a change of neurofilament and glial fibrillary acid proteins after chronic opiate administration. Furthermore, frequent overdosing and toxicological effects of 'street'-heroin may lead to CSF space enlargement in opioid dependence. In our study the pericortical and ventricular CSF space of 21 male opioid-dependent patients was compared with an age- and sex-matched normal control group. Considering serious problems with ratio and proportion measures, we used a battery of linear (cella media index, Huckman number, frontal horn index), planimetric (cortical atrophy score) and stereological volumetric measures in order to detect differences in cranial computerized tomography scans. We found a significant ventricular and cortical volume loss of the brain in opioid-dependent patients. A higher degree of frontal lobe volume loss seemed to be associated with a shorter period of abstinence before relapse. However, the etiology of volume loss of the brain in opioid-dependent patients is still unclear, but experimental animal studies provide some evidence that long-term, chronic opiate exposure is associated with visible changes of specific structures in the brain.

Adult↗

PubMed1998

Low frontal electroencephalographic coherence in neuroleptic-free schizophrenic patients.

BACKGROUND: Electroencephalographic (EEG) coherence analysis is a noninvasive technique for studying corticocortical associations. As there is evidence for a dysfunction of the prefrontal dorsolateral cortex in schizophrenia, we hypothesized to find lower frontal EEG coherence in schizophrenia. METHODS: EEG amplitude and coherence analysis was performed in 16 antipsychotic-free schizophrenic patients and 16 healthy controls. EEG recordings were done with 19 gold-plated electrodes placed according to the International 10/20 system against averaged signals from both earlobes. Local coherence was computed for 22 adjacent electrode pairs within the hemispheres and interhemispheric coherence for eight corresponding electrode pairs of both hemispheres in the delta, theta, alpha, and beta-I band. RESULTS: Amplitude and interhemispheric coherence analysis revealed no differences. Local EEG coherence was significantly lower in schizophrenic patients for Fpl-F7 in the delta (p = .001) and the theta band (p = .002), and at F7-F3 in the alpha band (p = .002). In the delta band coherence of Fpl-F7 was inversely correlated to the Positive and Negative Syndrome Scale positive symptoms subscore (R = -.74, p = .014). CONCLUSIONS: Assuming that EEG coherence can be used to index functional coupling between brain areas under the electrodes, the low EEG coherence in Fpl-F7 and F7-F3 in schizophrenic patients might reflect impaired information processing in the left dorsolateral prefrontal cortex.

Adult↗

PubMed1998

Differential transactivation by the androgen receptor in prostate cancer cells.

BACKGROUND: The purpose of this study was to determine the contribution of different transactivating regions of the androgen receptor (AR) to the induction of androgen-regulated promoters in poorly (PC3 cells) and well-differentiated (LNCaP cells) prostate cancer cell lines. METHODS: PC3 and LNCaP cells were co-transfected with plasmids expressing full-length AR or deletion mutants together with luciferase reporters linked to the probasin (PB) and PSA promoters; as well as to ARR3tk, a PB-derived recombinant promoter. RESULTS: Androgen induction of the ARR3tk promoter in the presence of AR was 8- to 10-fold higher than that seen with the PB promoter. Activation of ARR3tk was greatest with an androgen-independent construct in which the first 231 amino acids and the ligand binding domain had been removed, indicating that this promoter is more responsive to activating functions in the N-terminal domain than in the ligand binding domain. By comparison, induction of the PB promoter was greatest with the full-length AR, which suggests that the ligand binding domain also makes a major contribution to the activation of this promoter. In similar analyses with the PSA promoter, AR regions required for promoter induction was dependent on the host cell type. In PC3 cells, the predominant AR transactivation function was androgen-independent and resided in the N-terminal domain, whereas in LNCaP cells, the highest level of induction was androgen dependent and also required participation of the ligand binding domain. CONCLUSIONS: Our results indicate that the relative utilization of transactivating functions in N-terminal and ligand binding domains of the AR is promoter and cell specific.

Androgen-Binding Protein↗