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Biomedical subjects

L G Schmidt

Publications and source records attributed to L G Schmidt.

At least 73 records · Page 4Linked to original sources
PubMed1995

Antisocial tendencies and cortical sensory-evoked responses in alcoholism.

Alcohol-dependent patients with antisocial, aggressive, and impulsive behaviors form a subgroup, in which a dysfunction of the brain serotonin system is discussed as a pathogenetic factor. Early onset and a transmission from fathers to sons (type II alcoholism; Cloninger, 1987) are supposedly further characteristics of this subgroup. The response pattern of primary auditory cortices to auditory stimuli with different intensities is discussed as a noninvasive indicator of the level of central serotonergic neurotransmission. A strong intensity dependence of these responses is supposed to indicate low serotonergic neurotransmission and vice versa. A strong intensity dependence is therefore expected to characterize patients with antisocial tendencies. Auditory-evoked potentials (N1/P2 component) to stimuli in five different intensities were recorded in 53 hospitalized patients after 1 week of withdrawal. Dipole source analysis was performed to separate responses of primary and secondary auditory cortices. Patients with antisocial tendencies showed a significantly stronger intensity dependence of their evoked responses of primary auditory cortices (tangential dipoles). Age at onset and family history were not related to the intensity dependence of the evoked responses. The results support the notion that alcohol-dependent patients with strong intensity dependence and antisocial tendencies form a subgroup with a serotonergic hypofunction. These patients may respond favorably to a relapse prevention with serotonergic drugs.

Adult↗
PubMed1995

Dopaminergic responsivity in alcoholism: trait, state, or residual marker?

OBJECTIVE: In order to classify neuroendocrine abnormalities in alcohol-dependent patients as trait, state, or residual markers, growth hormone (GH) secretion was assessed longitudinally. METHOD: GH secretion, stimulated by the dopaminergic agonist apomorphine, was evaluated in 21 alcohol-dependent patients (16 men, five women) and 10 healthy comparison subjects (eight men, two women). The patients were tested during early withdrawal, after 8 days of abstinence, and after 3 months. RESULTS: Patients who relapsed within 3 months (N = 8) showed significantly less GH secretion in all neuroendocrine tests than did either the patients who abstained from ethanol consumption for 6 months (N = 13) or the healthy comparison subjects. The relapsers and abstainers did not differ significantly in any of their clinical or pathophysiological data, in the severity of their withdrawal symptoms, or in antecedent or concomitant illnesses associated with alcoholism. CONCLUSIONS: GH blunting appears to be a residual marker of clinical relevance in alcoholism.

Adult↗
PubMed1995

[Optical and tactile hallucinosis as clinical onset of Creutzfeld-Jakob disease].

A patient suffering from Creutzfeld-Jakob disease (CJD) complained of optical hallucinations, followed by feelings of persecution. Clinical, encephalographic and neuropathological findings pointed towards a focalized beginning of the disease process in the right frontal and temporal lobe. The hypothesized further spread of the infectious agent, as indicated by electroencephalographic and neuropathological findings, was accompanied by periacute manifestation of dementia and an irreversible disturbance of vigilance. The diagnosis of CJE can be especially difficult in the early stages of the disease, with dementia, myocloni and typical electroencephalographic findings still absent.

Aged↗
PubMed1995

[Current aspects of pharmacotherapy of alcoholism].

There is increasing evidence that "anticraving" drugs are promising agents in the treatment of alcoholics. Clinical studies indicate favorable effects of drugs with different pharmacological profiles (e.g., dopaminergic, serotonergic, anti-opioidergic, antiglutamatergic) on abnormal drinking behavior and relapse tendencies. Interactions with the limbic reward system seem to be involved. As several drugs will probably be registered in Germany, the need for integrating these drugs in a complex rehabilitation program is emphasized. Many clinical issues regarding the practical use of these drugs await further clarification.

Alcohol Deterrents↗
PubMed1995

Changes of G-protein levels in platelet membranes from alcoholics during short-term and long-term abstinence.

The levels of G alpha i2-protein and the G beta gamma-heterodimer were measured in platelet membranes of non-alcoholics, non-alcoholics after an ethanol load (1 g/kg body weight) and of alcoholics under various conditions. The findings were correlated with the activation of the adenylyl cyclase (AC) by various agents. The activation of AC was facilitated by acute ingestion of ethanol. This could not be explained by changes of the G-proteins determined because the levels of the G alpha i2-protein increased, whereas those of the G beta gamma-proteins remained in the control range. The alcoholics were divided into two groups on the day of admission: those with ethanol still present in the blood (intoxicated alcoholics) and those acutely withdrawn within the last 48 h (ethanol absent from the blood). The intoxicated alcoholics had elevated G alpha i2-protein levels in contrast to the acutely withdrawn patients, who did not. This observation suggests rapid changes of the G-protein levels. By analysing the inhibitory efficacy of the G-proteins on AC, it was found that the concentration of the G beta gamma-heterodimer, but not that of the G alpha i2-proteins, correlated with the inhibitory efficacy. The basal activity of the AC was reduced as well as the activation by some compounds. Eight days later (short-term withdrawal) both the levels of G alpha i2 and G beta gamma were elevated. Again, the inhibitory efficacy of the G-proteins correlated with the G beta gamma-heterodimer levels but not with those of the G alpha i2-protein. Furthermore, the changes of the G beta gamma-protein levels between the first and the eighth day correlated with the changes of the inhibiting efficacy. Only a trend was observed with respect to a lowered basal activity if compared with the intoxicated non-alcoholics. The activation of AC by guanylylimidyldiphosphate [Gpp(NH)p] and Gpp(NH)p + ethanol (200 mM in vitro) was still reduced. Observations after 3 and 6 months of abstinence demonstrated elevated G alpha i2- and G beta gamma-protein levels. This suggests residual marker properties of the G-proteins whereby the activity of AC was normal. Only the reduced stimulation by Gpp(NH)p + ethanol in vitro (200 mM), compared with the respective stimulation of AC of intoxicated non-alcoholics, suggested some residual disturbances of the signal transduction during long-term abstinence.

Adenylyl Cyclases↗
PubMed1994

Auditory-evoked dipole source activity as indicator of withdrawal severity in alcoholic patients.

The relationship between auditory-evoked potentials and the ethanol withdrawal syndrome was investigated in alcoholic inpatients using dipole source analysis. It was found that the increase in N1/P2 amplitude during withdrawal was positively correlated to the general severity of the withdrawal, but not to single symptoms such as seizures. Monitoring of initial changes in the auditory-evoked N1/P2 amplitude may be of predictive value concerning the withdrawal severity of alcoholic patients.

Adult↗
PubMed1994

Anhedonia in schizophrenic, depressed, or alcohol-dependent patients--neurobiological correlates.

Anhedonia, dysphoria, and avolition are common symptoms of schizophrenic, depressive, and alcohol-dependent patients during withdrawal. These symptoms may be caused by a functional deficit of dopaminergic transmission in the dopaminergic reward system, ascending from the mesencephalon to the ventral striatum (nucleus accumbens). The dopaminergic reward system is functionally and anatomically closely connected with the ascending extrapyramidal pathways from the substantia nigra to the dorsal striatum. A dysfunction of both ascending dopaminergic pathways is therefore expected to cause both psychomotor slowing and dysphoria and anhedonia. This hypothesis is supported by PET and SPECT findings, which show that a reduced striatal density of unoccupied dopamine D2-receptors is correlated with extrapyramidal side-effects in neuroleptic-treated schizophrenics and with craving and dysphoria in drug-dependent patients. In order to further investigate the correlation of anhedonia, psychomotor slowing, and the status of the dopaminergic reward system, the density of striatal dopamine D2-receptors can be measured by IBZM-SPECT and related to psychomotor slowing and anhedonia in different states of schizophrenic, depressive, and alcohol-dependent patients.

Alcoholism↗
PubMed1994

Molecular biological perspectives in treating neuropsychiatric disorders with dopaminergic drugs.

This review aims to present perspectives of molecular neuropharmacology in the development of more targeted drugs that modulate dopaminergic functions in various neuropsychiatric disorders. Recent advances in molecular neurobiology have revealed five distinct dopamine receptor (DR) genes and multiple allelic variations encoding DR subtypes with functional diversity. Depending on the different biophysical and pharmacological properties and the various cerebral distributions of the DR subtypes, the action profile of subtype-specific dopaminergic drugs can be predicted. In vitro expression of DR gene variants in mammalian cell lines will facilitate the screening and pharmacological characterization of dopaminergic ligands. Molecular modeling of the DR subtypes by three-dimensional computer models will be useful for establishing structure-function relationships between ligands and the DRs, and could provide a template for the design of receptor-specific drugs. In the near future, drugs modulating dopamine turnover and transport or involving the successive effector systems will increase the current therapeutical spectrum.

Dopamine↗
PubMed1994

Relapse prevention in alcoholics with an anticraving drug treatment: first results of the Berlin Study.

Lisuride--a compound with mainly dopamine d2-agonistic, but also dl-antagonistic and serotonergic properties was choosen in 1.0 mg daily dose as an anticraving drug for keeping alcoholics abstinent who had been included in a randomized double-blind placebo-controlled trial for 6 months. Preliminary results indicate that in the first 55 recruited patients the overall abstinence-rate dropped from 85% after 3 months to 47% after 6 months. Predictors of relapse were early onset of alcohol-related problems, a high number of preceding detoxification and rehabilitation treatments, intermittant drinking habits, less feeling of guilt and low harm avoidance in the TPQ by Cloninger. More details will be given after completing the study when the code is lifted.

Adult↗
PubMed1994

Hypothalamic-pituitary-thyroid (HPT) axis in chronic alcoholism. I. HPT axis in chronic alcoholics during withdrawal and after 3 weeks of abstinence.

Thyroxine (T4), free T4 (fT4), triiodothyronine (T3), free T3 (fT3), reverse T3 (rT3), thyrotropin (TSH), thyroxine binding globulin (TBG), and T3 uptake were measured in 14 chronic alcoholics during withdrawal and after 21 days of abstinence. Results were compared with those of 16 healthy volunteers. During withdrawal, the fT4 and fT3 concentrations were subnormal, whereas the respective protein-bound fractions were normal. T4, T3, and TBG increased during the abstinence period, T3 and TBG being significantly higher than in normals at the second measuring time. T3 uptake values fell, but remained well within the normal range at both measuring times. During abstinence, the fT3 levels remained significantly lower than in healthy subjects. rT3 concentrations decreased, but not significantly. The TSH values were normal throughout. These results showed numerous abnormalities in the hypothalamic-pituitary-thyroid axis in alcoholics, the reasons for which are as yet unclear. The following possible interpretations are suggested: 1. The abnormally low serum fT3 and fT4 levels during withdrawal might reflect an increase in tissue uptake. 2. The increases in T4--and partly those in T3--during abstinence seem to reflect increased binding by TBG, the level of which rose markedly for reasons as yet unknown. 3. If increases in TBG during abstinence are taken into account, the decreases in rT3 concentrations may reach the level of statistical significance. These falls in rT3 concentrations may reflect an increase in rT3 metabolization (deiodination) in various tissues, including the CNS, leading to a reduction in serum rT3 bioavailability. 4. Factors such as liver disease, protein caloric malnutrition, and "psychological stress" do not fully explain all these abnormalities. A direct effect of ethanol on intracellular thyroid hormone metabolism and/or function seems conceivable.

Adult↗
PubMed1994

Longitudinal observations of monoamine oxidase B in alcoholics: differentiation of marker characteristics.

The marker characteristics of monoamine oxidase B (MAO B) in human platelets were investigated in a clinical study of 59 alcoholics (diagnosed according to the criteria of ICD-10) observed over a period of 6 months. Demographic and family history were obtained by a structured interview, including the substance abuse section of CIDI (Composite International Diagnostic Interview). The patient's personality was assessed by Cloninger's Tridimensional Personality Questionnaire (TPQ). Blood samples were first drawn during chronic intoxication (day of admission to the hospital for detoxication), after short-term abstinence (8 days later), medium-term (3 months later), and long-term abstinence (6 months later). A group of 22 matched healthy nonalcoholics served as controls studied under sober conditions and during acute intoxication (4 hr after ingestion of 1 g ethanol/kg body weight). All platelet samples were investigated with 6 kynuramine concentrations as substrate (fluorometric assay) in the absence and presence of 200 mM ethanol (ETOH) in vitro. MAO B activity was significantly reduced in alcoholics during chronic intoxication (Vmax: 2.70 +/- 0.15 nmol/mg protein) compared with sober (Vmax: 3.25 +/- 0.23 nmol/min/mg protein) and acutely intoxicated controls that turned to normal during abstinence. However, MAO B activity obtained during medium- and long-term abstinence was significantly lowered in patients with high novelty-seeking and impulsiveness scores in the TPQ, a history of suicide attempts, or an alcoholic mother. The affinity of MAO B (Km values) was unchanged in alcoholics at any time investigated. Addition of ETOH in vitro reduced the affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

["Neuroadaptation" in long-term cannabis abuse. A clinical and electroencephalographic case study].

This report is about electroencephalographic changes in a twenty-eight year old patient with longterm heavy cannabis use. He was admitted to our hospital after he had developed a depressive-apathetic syndrome. Two days after the last cannabis-intake, the patient had recovered from initial psychopathology and his EEG was completely inconspicuous at this day. Some days later however the patient's behavior became increasingly impulsive and unstable, while his EEG showed a marked disturbed regulation of vigilance. In the following weeks his impulsiveness became less and his EEG returned to normal. We suggest that these alterations may reflect a discontinuation of the initial neuroadaption of the central nervous system to the drug.

Adult↗
PubMed1993

Adverse psychic reactions to psychotropic drugs--a report from the AMUP study.

The AMUP study (AMUP = Arzneimittelüberwachung in der Psychiatrie (Drug Monitoring in Psychiatry)) was conducted from 1979 to 1989 in order to provide for a systematic and standardized assessment of all adverse reactions to psychotropic drugs under the conditions of routine clinical treatment at two psychiatric hospitals. This paper presents data from the AMUP study on the type and frequency of adverse psychic reactions to psychotropic drug groups and relevant single drugs. Psychic ADR leading to drug discontinuation were observed in 4.5% of 15,264 inpatients monitored over an eight-year period. Only neurological ADR were more frequent (4.9%). Neuroleptics and antidepressants were involved with similar frequencies in ADR that were at least "probably" drug-related (3.3 and 3.5%). Lithium salts and benzodiazepines were only rarely involved in psychic ADR. Toxic delirium (1.0%), agitation (0.9%), and sedation (0.8%) were the most frequent single events, usually rated as "probably" drug-related. Depression and psychotic states were next in frequency, but judged as only "possibly" drug-related in a considerable proportion of cases. Haloperidol, the most common high-potency neuroleptic, was imputed mainly for depression, sedation, agitation, and (malignant) neuroleptic syndrome; with medium-potency perazine, toxic delirium and sedation prevailed; among the most common antidepressants, amitriptyline was above all connected with toxic delirium, while with clomipramine agitation predominated. The paper discusses the particular difficulties encountered in the field of psychic ADR in psychiatric patients regarding causality assessment, and emphasizes the need for continuous ADR assessment studies including state hospitals.

Adult↗
PubMed1993

[Diagnosis of alcohol dependence].

The dependence syndrome has gained central importance in diagnosing alcohol abuse disorders, as shown by its incorporation in ICD-10 and DSM-III-R. After dealing with historical concepts of alcoholism, the concurrent and predictive validity of the dependency syndrome is discussed in relation to aspects of typology and comorbidity, and to neurobiological variables. Diagnostic instruments are assessed and research perspectives indicated.

Alcohol Drinking↗
PubMed1991

Plasma levels of luteinizing hormone and androgens in relation to age and breeding status among cooperatively breeding Australian magpies (Gymnorhina tibicen Latham).

Plasma levels of luteinizing hormone (LH), testosterone (T), and 5 alpha-dihydrotestosterone (DHT) were measured in relation to age and social/breeding status among free-living male Australian magpies. Magpies live in territorial groups of up to 20 individuals and due to a largely age-related dominance hierarchy among males, many individuals are prevented from breeding. Adult plumage is not attained until the fourth year, but males can produce motile sperm in their first year. Plasma levels of LH and T peaked just prior to egg-laying among breeding males, but DHT levels remained steady or declined slightly during the breeding period. Adults (greater than 3.5 years) had significantly higher levels of both LH and androgens than did subadults (less than 3.5 years) during the breeding season. Nonbreeding adults had similar levels to those found among the breeding adults, but breeding subadults had higher levels of both LH and androgens than the nonbreeding subadults. These results are interpreted in terms of the opportunities for each of these classes to obtain copulations and are discussed in relation to age-related hormonal secretion in other species.

Aging↗
PubMed1991

Low melanin content of substantia nigra in a case of neuroleptic malignant syndrome.

A 19-year-old man suffering from a first episode of schizophrenia developed a neuroleptic malignant syndrome (NMS) after administration of haloperidol and levomepromazine. After five weeks of neuroleptic treatment he died of an unknown cause. Histological examination of the brain revealed a low melanin content in neurons in the substantia nigra (SN). Since neuromelanin in SN is the end-product of nonenzymatic dopamine degradation, the amount of melanin probably depends on the overall amount of dopamine produced during life. Thus, dopamine production must have been low in the reported case. In addition, ectopic neurons were found in subcortical white matter.

Adult↗
PubMed1991

Plasma norharman (beta-carboline) levels are elevated in chronic alcoholics.

Based on the hypothesis that condensation products of neurotransmitters with aldehydes are involved in the pathogenesis of alcoholism, aromatic beta-carbolines (norharman and harman) were measured in the blood plasma of alcoholics and nonalcoholics. The identity of the extracted compounds was confirmed by various elution conditions of the high performance liquid chromatography (HPLC), newly developed radioreceptor assays, and the mass spectrum of norharman. The levels of norharman and harman in nonalcoholics were unchanged after a load with ethanol (1 g/kg body weight). The norharman levels of the alcoholics were significantly higher than that of the nonalcoholic controls (99.5 +/- 26.6 pg/ml vs. 26.9 +/- 10.7 pg/ml; p less than 0.001) and did not change significantly during a 3-week detoxication period. In the subgroup of alcoholics with delirium or hallucinosis, a slight increase of norharman during detoxication could be detected while in alcoholics with vegetative withdrawal symptoms norharman levels dropped slightly over time (p = 0.07). No difference was found with respect to harman between nonalcoholics and alcoholics. These results suggest disturbed regulatory processes in the formation and/or metabolism of norharman in alcoholics. Further investigations are needed to reveal a possible marker function of norharman in alcoholic patients.

Adolescent↗