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A Klimke

Publications and source records attributed to A Klimke.

18 recordsLinked to original sources
PubMed1998

Imaging dopamine D4 receptors in the living primate brain: a positron emission tomography study using the novel D1/D4 antagonist [11C]SDZ GLC 756.

The dopamine D4 receptor has lately attracted interest since it has been hypothesized to be involved in the pathogenesis and pharmacotherapy of neuropsychiatric diseases. The present study provides first in vivo evidence of dopamine D4 receptors in primate brain using a [11C]benzo[g]quinoline, the novel radioligand [11C]SDZ GLC 756 ([11C]GLC: in vitro dissociation constants at human receptor clones [nM]: 1.10 at D1; 0.40 at D2; 25 at D3; 0.18 at D4.2; 6.03 at D5). Dynamic positron emission tomography scans were performed on healthy baboons (Papio hamadryas, n = 3). Specific receptor binding (SB) was calculated for striatum and neocortex (frontal, temporal, parietal, and occipital) based on the differences between the regional and the cerebellar concentration of [11C]. Blockade of D1 and D5 receptors by SCH23390 (1.7 pmol/kg) diminished SB in the striatum by 55 +/- 4% (mean +/- standard deviation, P < 0.05) and in the frontal cortex by 13 +/- 8% (P < 0.05) when compared to SB in the unblocked state (SB(D1-D5)). In the presence of the dopamine antagonists SCH23390 (1.7 micromol/kg) and raclopride (5.7 pmol/kg)--which mask the D1, D2, D3, and D5 subtypes--SB of [11C]GLC to D4 receptors (SB(D4)) was demonstrated in the striatum and all cortical regions of interest. In the striatum, the ratio of SB(D4)/SB(D1-D5) was 0.13 +/- 0.07. In the neocortex, SB(D4)/SB(D1-D5) was notably higher (0.77 +/- 0.29; mean of all cortical regions of interest). The widespread distribution of dopamine D4 receptors suggests a basic functional role of this receptor subtype in the modulation of cortical and subcortical neuronal activity.

Animals↗
PubMed1998

[Electroconvulsive therapy in psychiatric clinics in Germany in 1995].

A total of 451 German psychiatric hospitals were asked in 1995 about their use of electroconvulsive therapy (ECT). As ECT nowadays is well accepted as a therapeutic tool, we wanted to compare our data with data collected in former inquiries in 1977 and 1985 and to acquire information from the new German States. Since 1977, the use of ECT has evidently increased. The psychiatric hospitals that often use ECT are for scattered throughout the whole country. ECT is mainly indicated for febrile catatonia/febrile stupor and depressive stupor, not for schizophrenia. ECT is applied especially when depressive patients are resistant or intolerant of psychopharmacotherapy. The preparation and application correspond to the standards. One focus in the present study was the attitudes of the managing directors towards ECT. Data were collected by open questionnaires. When these data were compared with data from a standardized inquiry of 1985, a similar trend was found regarding positive statements about ECT. Statements are emphasized even more when using open questionnaires. If there is a strong indication for ECT, the basic attitudes of the managing directors toward ECT are very positive. However, its application is in fact much more influenced by social factors than by indication because of negative attitudes by colleagues and nursing staff and political and stereotypic thinking of the general population.

Attitude of Health Personnel↗
PubMed1998

Active [3H]-dopamine uptake displayed by native lymphocyte suspensions is mainly due to contaminating platelets.

Kinetic and pharmacologic properties of specific [3H]-dopamine uptake by native human lymphocytes were investigated. Our results suggest that uptake of [3H]-dopamine measured with lymphocytes after separation over Ficoll-Paque or Percoll is mainly caused by platelets which are always part of freshly prepared lymphocyte suspensions. The investigations were extended to well-defined cell lines in order to compare the pharmacological properties of native and immortalized cells regarding the uptake of [3H]-dopamine without any influence of contaminating cells such as platelets. Using the human neuroblastoma cell line IMR32 we demonstrate a GBR-12909 and cocaine-sensitive specific uptake of dopamine, whereas dopamine uptake in platelets is performed by an imipramine-sensitive serotonin transporter. Blood-derived stable cell lines (MOLT-3 and EBV-transformed B-lymphocytes) exhibited no [3H]-dopamine uptake. The view that specific [3H]-dopamine uptake on native human lymphocytes is mainly caused by platelets and not specific for lymphocytes is supported by the finding that homogenous B- and T-lymphoblastoids (MOLT-3 and EBV-transformed B-lymphocytes) exhibited no comparable uptake.

Blood Platelets↗
PubMed1998

Left-right asymmetry of striatal dopamine D2 receptors.

Brain functions may be lateralized to the right or the left hemisphere. However, the biochemical characteristics accompanying these functions are largely unknown. To test possible lateralization of striatal dopamine D2 receptors, we examined 18 volunteers using 123I-iodobenzamide and single photon emission tomography. The striatum-to-cerebellum D2 binding ratio was 1.93 +/- 0.22 (mean +/- S.D.) on the right side and 1.85 +/- 0.19 on the left side. In 14 subjects, D2 binding was higher in the right compared to the left striatum (P < 0.05). These results are supported by a meta-analysis performed on 15 studies reported in the literature. We conclude that side differences of striatal dopamine D2 receptors exist. We propose that motor activity could be responsible for our findings.

Adult↗
PubMed1998

[Clinical impact of cerebral dopamine-D2 receptor scintigraphy].

The present review describes findings and clinical indications for the dopamine D2 receptor scintigraphy. Methods for the examination of D2 receptors are positron emission tomography (PET) using 11C- or 18F-labelled butyrophenones or benzamides or single photon emission tomography (SPECT) using 123l-iodobenzamide (IBZM) respectively. The most important indication in neurology is the differential diagnosis of Parkinsonism: patients with early Parkinson's disease show an increased D2 receptor binding (D2-RB) compared to control subjects. However, patients suffering from Steele-Richardson-Olszewski-Syndrome or Multiple System Atrophy show a decreased D2-RB and are generally non-responsive to treatment. Postsynaptic blockade of D2 receptors results in a drug induced Parkinsonian syndrome, which can be diagnosed by D2 scintigraphy. Further possible indications occur in psychiatry: the assessment of receptor occupancy is useful in schizophrenic patients treated with neuroleptics. Additionally, D2 receptor scintigraphy might help to clarify the differential diagnosis between neuroleptic malignant syndrome and lethal catatonia. The method might be useful for supervising neurobiochemical changes in drug dependency and during withdrawal. Assessment of dopamine D2 receptor binding can simplify the choice of therapy in depressive disorder: patients showing a low D2 binding are likely to improve following an antidepressive drug treatment whereas sleep deprivation is promising in patients with high D2 binding.

Benzamides↗
PubMed1997

In vivo evidence for the involvement of dopamine-D2 receptors in striatum and anterior cingulate gyrus in major depression.

The dopaminergic system is a candidate neurotransmitter system thought to be involved in the pathogenesis of depression. This study addresses the issue whether the antidepressant efficacy of serotonin reuptake inhibition is related to changes in the cerebral dopaminergic system. Cerebral dopamine-D2 receptors were characterized in 13 patients with major depression using the dopamine-D2 receptor antagonist iodobenzamide and single photon emission tomography. Dopamine receptor binding was assessed twice, before and during serotonin reuptake inhibition. An increase in dopamine-D2 receptor binding during serotonin reuptake inhibition was found in striatum and anterior cingulate gyrus in treatment responders, but not in nonresponders. The increase in dopamine-D2 receptor binding correlated significantly with clinical recovery from depression as assessed with the Hamilton depression scale (r = 0.59 for right and left striatum respectively, P < 0.05; r = 0.79 for the anterior cingulate gyrus, P < 0.05 after Bonferroni correction). Qualitatively similar correlations were observed in the precentral gyrus, the medial frontal gyrus, the inferior frontal gyrus, and the frontal part of the opercular gyrus, but these correlations failed to reach statistical significance after correction for the effects of multiple testing. No such correlations were found in the superior frontal gyrus, the orbitofrontal gyrus, the gyrus rectus, the superior parietal gyrus, or the superior temporal gyrus. The data strengthen the concept that the striatum and the anterior cingulate gyrus are involved in mood regulation. Dopamine-D2 receptors may constitute a central role in this domain.

Adult↗
PubMed1995

[The atypical neuroleptic clozapine (Leponex)--current knowledge and recent clinical aspects].

The dibenzoepine derivative clozapine is seen as a prototype of an atypical neuroleptic, because clozapine has good antipsychotic efficacy but only minimal dopamine antagonistic properties in common animal paradigms. The latter is reflected by the observation that extrapyramidal symptoms during clozapine are a rare phenomenon. Furthermore, recent studies in the USA demonstrated a superior efficacy of clozapine in schizophrenic patients who are nonresponsive to classic neuroleptics. Therefore, the introduction of clozapine in the USA was performed in 1990 despite the well-known risk of agranulocytosis (1-2% during the first year of treatment); however, under restricted conditions regarding the mandatory weekly control of the white blood cell count. For the use of clozapine in Europe, it should be underlined that in 1992 the indication was restricted to "acute and chronic forms of schizophrenia" whereas formerly it was permitted to treat several other neuroleptic resistant syndromes with clozapine, e.g. severe psychotic excitement, aggressive behavior or manic or atypical psychosis. The usage of clozapine in these indications is now only permitted under the restricted legal conditions of a "therapeutic trial" in selected patients. However, several indications for which clozapine has been used successfully in Europe are currently re-investigated in the USA, hopefully leading to a redefinition and extension of the indication spectrum. On the other hand, the American multicenter trials lead to the conclusion that the treatment with clozapine is not furthermore the treatment of last choice but a serious therapeutic alternative which should be available for all schizophrenic patient in case of neuroleptic resistance or of severe side effects of standard neuroleptics. Clozapine treatment leads to an improvement of the quality of life in one third of these schizophrenics and, moreover, results in a marked reduction of costs mainly by reducing the rehospitalisation rates. On the other hand, the list of well-known side effects of clozapine (e.g. agranulocytosis, increased risk of seizures, initial sedation) has to be extended (e.g. transient leucocytosis or eosinophilia, rare but severe complications like cardiorespiratory arrest and "sudden death" during combination with benzodiazepines, case reports of pericarditis, pancreatitis or polyserositis). On the background of possible cardiorespiratory complications we recommend to start the first treatment with clozapine in high risk patients (e.g. those in older age or in case of organic brain impairment) only in restricted indications and only in centers with sufficient clozapine experience.

Clozapine↗
PubMed1994

[Therapy of depression].

Somatic treatment and psychotherapy are available for the treatment of depressive episodes. Regarding the side-effect profile, tetrazyclic antidepressants, selective serotonin reuptake inhibitors and selective MAO inhibitors are recommended as therapy of first choice. In less severe cases phytopharmaca and major tranquilizers in low dosage are possible alternatives. In case of resistance to therapy with high subjective strain electroconvulsive therapy may be indicated. Psychotherapy can also be applied as treatment of first choice. The cognitive behavioural therapy intends a normalization of activity rate, cognitive attitude and social competence, which are characteristically changed in depressives. The combination of drug therapy with psychotherapy has no clear advantage over monotherapy, but it possibly reduces the relapse rate.

Antidepressive Agents↗
PubMed1993

Initial improvement as a criterion for drug choice in acute schizophrenia.

Several investigators have found that the initial improvement of acute schizophrenia after some days of neuroleptic treatment is correlated in a statistically significant way to the outcome after four weeks. In all these studies the question arises as to whether the correlation between early response and subsequent outcome is due to a specific response to a certain neuroleptic, or whether patients who respond early simply have a better prognosis. In order to isolate the specific drug effect from prognostic influences we performed a controlled double-blind study in 50 newly admitted schizophrenic inpatients. All patients were treated over three days with 15 mg haloperidol i.v., following which they were classified as 'early responders (ER)' (markedly improved or improved) or as 'early nonresponders (EN)' and then randomly assigned to group 1 (3 x 5 mg haloperidol p.o./d) or to group 2 (3 x 100 mg perazin p.o./d). If there was a specific drug effect on the correlation between early response and subsequent outcome a therapeutic superiority of perazin in EN and no superiority in ER was expected. Independently of the treatment condition the mean BPRS score had decreased from 61.2 (Sx = 12.1) to 38.1 (Sx = 13.9) at the end of the study. ER and EN were evenly distributed in the haloperidol and perazin group. The analysis of variance revealed no significant interactions of the factors 'treatment condition' x 'duration' x 'early response' (p = 0.27) and 'treatment condition' x 'early response' (p = 0.88) on the outcome (BPRS, CGI). This means that the initial hypothesis of this study has to be rejected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Use of an immunoenzyme histochemical method for the improvement of the etiologic diagnosis of Aujeszky's disease in swine].

With regard to the legal regulations for the diagnosis of Aujeszky's disease in pigs, a retrospective immunoenzymatic study was performed on brains of 20 pigs, in which Aujeszky's disease had been diagnosed based only on clinical, macroscopical and histological findings, although the etiological agent could not be demonstrated neither by immunofluorescent technique nor by virological cultivation. Applying the peroxidase-antiperoxidase-(PAP) method, in 6 of 20 animals (30%) viral antigen of porcine herpesvirus type 1 was demonstrated in situ in at least two of five different locations of the brain. Reasons for negative results in immunohistological and virological investigations are discussed and the significance of the performed immunoenzymatic technique is pointed out.

Animals↗
PubMed1991

[Effectiveness of neuro-electric therapy in drug resistant endogenous psychoses].

A retrospective chart review of 50 pharmacotherapeutically resistant patients was performed after treatment with NET in 1986-1988. 28 patients suffered from schizophrenia and 22 from affective psychosis. In contrast to literature where NET as therapy of first choice has favourable results in depression in this study 60.7% of the treatment resistant acute schizophrenics responded well to NET. 3 months after discharge from hospital 9 schizophrenics (32.1%) but only 3 patients with affective psychosis (13.6%) presented a 'good' outcome (full remission). A longer duration of schizophrenia (more than 5 years since first manifestation) and a good response to neuroleptics in history was predictive for a good actual NET response (14 of 17 patients), whereas 7 of 11 patients suffering from schizophrenia less than 3 years without any period of full remission on neuroleptics were also non-responders to NET.

Adult↗
PubMed1991

Antipsychotic efficacy of the dopaminergic autoreceptor agonist EMD 49980 (Roxindol). Results of an open clinical study.

EMD 49980 is a dopamine agonist with selective affinity to dopamine autoreceptors. Following pharmacological findings in animal studies, it was postulated that a hyperactivity of dopaminergic neurons, which is possibly present in acute schizophrenia, may be reduced by autoreceptor stimulation. To investigate the antipsychotic efficacy of EMD 49980, 20 acutely ill schizophrenics (ICD No. 295.3) were treated over four weeks with dosage increasing up to 3 mg or 9 mg. According to previously defined criteria four patients were clear responders, but clinically none of them revealed a full remission. Ten patients were nonresponders, and three of these patients were drop-outs because of marked deterioration of schizophrenic symptoms. The explorative analysis of BPRS subscales shows a statistically significant reduction of anxiety/depression and anergia, but no clear influence on the subscales THOT, HOST, and ACTV, which are the more specific scales for acute schizophrenia. EMD 49980 was subjectively well tolerated and there was no case of drug-induced extrapyramidal side-effects. In view of the only moderate antipsychotic efficacy in acute schizophrenia and the fact that antidepressant and anxiolytic effects were also observed, a clinical investigation of EMD 49980 in affective disorders and in schizophrenia with depression or anergia should be performed.

Acute Disease↗
PubMed1990

[Suicide in psychiatric clinic patients].

Psychiatric inpatients who commit suicide differ characteristically from other inpatients. Nearly 60% of them are between 30 and 60 years old and belong to the age group of those who are usually employed. Diagnostically most of them suffer from endogenous psychoses like schizophrenia or major depression. The distribution of the duration of illness shows two peaks: one during the first years and a second after many years of illness. A nearly constant percentage of 40% presents a striking life history, including psychiatric disorders in the family, retardation during childhood, interrupted school education and lack of vocational training. Suicidal attempts in the past are predictive for suicidal behaviour and suicide in the future. The rate of suicides (per 100,000 psychiatric inpatients) is increasing, however there is no evidence for a connection with treatment under open or closed conditions. In case of serious suicidal risk it may be necessary to take antisuicidal measures like temporally limited treatment in a closed ward. On the other hand the liberality which has been established in psychiatric hospitals over the last ten years might be reduced, if restrictive measures are taken in any case of suicidal risk.

Adolescent↗
PubMed1989

The efficacy of Cavain in patients suffering from anxiety.

The therapeutical efficacy of Cavain should be proved in the treatment of patients suffering from abnormal anxiety, psychosomatic complaints and psychoreactive disorder. Thus two randomized groups of patients (26 each) were treated in double-blind technique with either 2 x 200 mg daily Cavain or placebo for a period of 28 days. Prior to the beginning of the investigations and within 14 days intervals the Hamilton Anxiety Scale (HAMA) and the Adjective Check List (Janke and Debus) were applied. The global therapeutical improvement and compatibility were documented after 14 and 28 days. A significant superiority of Cavain in comparison to placebo could be found. Cavain acted anxiolytically and promotive on the subjective vitality-related performance. Therapeutical conclusions are discussed.

Adult↗