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Biomedical subjects

O M Lesch

Publications and source records attributed to O M Lesch.

61 records · Page 4Linked to original sources
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Dopamine and alcohol relapse: D1 and D2 antagonists increase relapse rates in animal studies and in clinical trials.

A considerable number of animal studies on the effects of dopaminergic agents on alcohol intake behavior have been performed. Acute alcohol administration in rats induces dopamine release in the caudate nucleus and in the nucleus accumbens, an effect related among others to reinforcement. It has been repeatedly suggested that D1 and D2 receptor activation mediates reward. As alcohol consumption and dopaminergic transmission seem to have a close relationship, all kinds of dopaminergic agents may be regarded as putative therapeutics for preventing relapse. In a prospective European double-blind multicenter clinical trial, comparing the D1, D2, D3 antagonist flupenthixol and placebo in 281 chronic alcohol-dependent patients (27.4% women), the application of the Lesch typology made an outcome differentiation possible. It could be shown in which patients flupenthixol administration was followed by a significantly higher relapse rate and in which patient groups no differences were found when compared to placebo.

Alcoholism↗
PubMedDate not supplied

The European acamprosate trials: conclusions for research and therapy.

In an excellent methodological approach, the European acamprosate study project showed that acamprosate increases sobriety times. In one randomized prospective study (n = 260) comparing acamprosate and placebo, with a 1-year treatment phase and 1-year follow-up phase, the authors found that acamprosate is effective only in Lesch type I and type II patients. To investigate the possible influence of diagnostic subgrouping, we applied the Lesch typology in a co-work with the main researchers of the UK study. The UK results concerning acamprosate's effects in the types do not mirror the Vienna results, but the numbers of type I and type II patients, retrospectively found as included in the UK centers, were too small for any conclusions. The distribution of the types points to the fact that too many type III and IV patients had been included to give acamprosate the chance to be effective. Following our typology and also these studies, we developed special treatment approaches. For relapse prevention studies, the cumulative abstinence duration together with the Lesch typology seems to be promising.

Acamprosate↗
PubMedDate not supplied

Regional brain function in hallucinations: a study of regional cerebral blood flow with 99m-Tc-HMPAO-SPECT in patients with auditory hallucinations, tactile hallucinations, and normal controls.

From the supposition that there exists a possible connection between certain psychopathological symptoms, and/or syndromes (e.g., hallucinations) and regional cerebral dysfunction, patients suffering from auditory and tactile hallucinations were investigated, in a symptom-oriented study, using the method of technetium-99m-Hexamethyl-propylenamine Oxime (99m-Tc-HMPAO)-Single Photon Emission Computed Tomography (SPECT) and compared with normal controls. The results support Jackson's hypothesis to the effect that hallucinatory phenomena will primarily occur when the normally inhibitive influence of the upper cortical centers over the lower brain structures diminishes, resulting in relative hyperactivity in the basal regions. In addition to the brain activity-changes generally observed in hallucinating patients, it was possible to identify regional cerebral blood flow (rCBF)-distribution patterns characteristic in certain forms of hallucinatory phenomena, i.e., a significant increase of activity in the hippocampal regions (including hippocampus, parahippocampus, and amygdala) only in patients with auditory hallucinations, and a significant reduction of rCBF in the inferior temporal regions in patients with tactile hallucinations.

Adult↗
PubMedDate not supplied

Psychophysiological diagnostics in alcohol dependency: Fourier analysis of pupillary oscillations and the receptor test for determination of cholinergic deficiency.

Mnestic disturbances in alcoholics may be related to cholinergic deficiency as well as to central nervous system inactivation. After instillation of tropicamide, cholinergic receptors are blocked and pupillary dilatation occurs. It is assumed that the more severe the cognitive deterioration, the wider the pupillary dilatation. Pupillary oscillations reflect central activation. Changes of pupillary diameter after topical instillation of tropicamide and pupillary oscillations were measured in 44 alcohol-dependent patients aged 40-55 years, diagnosed according to the DSM-III-R as severe alcoholics (>7 symptoms), having been abstinent for at least 3 weeks (objectively tested with carbohydrate-deficient transferrin), compared with 18 healthy controls. The pupillary diameter of the left eye was measured eight times within 103 min, as were pupillary oscillations. Using Fourier analysis, the amplitudes of oscillations were measured in five frequency bands and the sum of the frequency bands was calculated. In addition, central activation was measured during a calculation test at 3 and 103 min. The pupillary dilatation of 22% in alcoholics compared to 14% of normal controls after tropicamide raises the question of a cholinergic deficit in alcohol dependence. With regard to basic activation, measured by Fourier analysis of pupillary oscillations, alcoholics demonstrated significantly lower power (sum of the frequency bands) than controls at baseline and at 3, 20, and 40 min (P < 0.01) as well as at 60, 80, 100, and 103 min (P < 0.05). After a cognitive task, a difference between alcoholics and healthy controls was found at 3 min. Alcoholics showed lower basic activation and decreased cognitive activation. By means of cross-validation, a differentiation between alcohol-dependent patients (n = 44 and n = 42 respectively) and normal controls (n = 18) was possible.

Adult↗
PubMedDate not supplied

Flupenthixol decanoate and relapse prevention in alcoholics: results from a placebo-controlled study.

Flupenthixol, with its broad receptor profile, interacts with a variety of dopamine and serotonin binding sites which are important in the neurobiology of alcohol dependence. Its pharmacology, together with encouraging results from both animal studies and clinical trials with cocaine users, led us to postulate that flupenthixol would significantly prevent relapse in detoxified alcohol-dependent individuals. We conducted a prospective, randomized, double-blind, placebo-controlled, multi-centre trial with two parallel groups and appropriate statistical evaluation. Subjects met criteria for moderate to severe alcohol dependence (DSM-III-R), without any concomitant psychiatric disorder. After complete detoxification, 281 women and men received either 10 mg of flupenthixol decanoate or placebo as i.m. injection every second week for 6 months on an out-patient basis, followed by 6 months of follow-up. Efficacy was based on absolute abstinence, with relapse being defined as consumption of any alcohol after inclusion in the study. In contrast to the hypothesis, flupenthixol did not reduce, but was associated with more, relapses. Though well tolerated, relapse rates after 6 months of treatment were 85.2% (flupenthixol) versus 65.5% (placebo), a highly significant difference from the medication. Flupenthixol was also inferior to placebo with regard to other secondary criteria of efficacy (cumulative abstinence duration, relapse rate after 12 months). These results indicate that a 10 mg dose of flupenthixol decanoate does not have a beneficial effect on abstinence maintenance in alcohol-dependent individuals.

Adult↗
PubMedDate not supplied

[Epidemiology of drug use and abuse. Physician's role].

Drug use in a given population, whether justified by a medical prescription or not, is a subject that is often emotionally rather than objectively discussed. In this study, objective data from the Austrian population are collected in order to provide a more comprehensible view of that complex phenomenon: drug use, abuse or addition seem to relate to various factors such as gender, age, profession and local differences. Physician's role in drug use in more or less important, depending on the nature of the substance. Indeed, tranquillizers and hypnotics are medically prescribed drugs although laxatives, geriatric and homeopathic medicines are rarely prescribed by a physician. However, these factors could account for only a part of this subject and other research should focus on the relations between physician, patient and the drug.

Adolescent↗