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Biomedical subjects

A Heinz

Publications and source records attributed to A Heinz.

At least 91 records · Page 5Linked to original sources
PubMed1997

Serotonergic dysfunction in addiction: effects of alcohol, cigarette smoking and heroin on platelet 5-HT content.

The impact of ethanol, cigarette smoking and heroin on serotonin function was evaluated, first in alcoholics during chronic ethanol intoxication and in opiate addicts after long-term heroin consumption, and secondly in both patient groups after detoxification treatment (i.e. a short-term abstinence of 8 days). Our results showed that the 5-hydroxytryptamine (5-HT) content in platelets was: (1) increased in the subgroup of anti-social alcoholics; (2) transiently and differently altered in alcoholics compared to opiate addicts; and (3) lowered in drinking alcoholics and normal in alcoholics who were drinking as well as smoking (that may occur via MAO-B inhibition by smoke). The findings indicate that alterations of the peripheral and possibly the central serotonin system may occur as predisposing factors for alcoholism in individuals with anti-social traits; they may also have some impact on the progression of alcoholism due to its lowered function during chronic ethanol intoxication that is substantially modified by smoking.

Adult↗
PubMed1997

Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels.

Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.

Adult↗
PubMed1997

Analysis of the metabolites of [I-123] beta-CIT in plasma of human and nonhuman primates.

[I-123] beta-CIT is a single photon emission computed tomography (SPECT) radioligand that has been used for in vivo studies of the dopamine and serotonin transporters. Two metabolite peaks of beta-CIT have been observed by high performance liquid chromatography (HPLC), but neither has been chemically identified. One major metabolite is clearly hydrophilic. Previous reports have not agreed on the amount of the second metabolite and the extent to which it may cross the blood-brain barrier. To clarify this controversy, we have studied beta-CIT metabolites using a protein precipitation method and an organic extraction method followed by HPLC separation. Plasma from both human and nonhuman (rhesus) primates was analyzed. Concentrations of the second metabolite were substantially lower in rhesus than in human for nearly equal parent concentrations. Furthermore, in rhesus the second metabolite is partially soluble in the organic solvent ethyl acetate, whereas in human it is essentially insoluble. These observations account for the contradictions in the literature. The hydrophilic nature of the human metabolite renders it unlikely that it crosses the blood-brain barrier in sufficient quantities to interfere with the quantitative assessment of dopamine transporter densities.

Animals↗
PubMed1997

[Complications with portable ESWL--a multicenter study].

An increasing number of urological departments are taking advantage of portable lithotripsy units if a system is not available in their clinic or purchase does not seem feasible; however, infrequent application of ESWL in such a setting should not increase the rate of complications. From 1993 to 1995, up to 54 urological departments using mobile lithotripsy units collected data concerning all major complications. A total of 12,901 treatments were performed which led to 85 major complications (0.66%). Of them 64 were intrarenal or perirenal hematomas. There was no fatal complication. In three patients nephrectomy had to be performed subsequently. The probability of complications can be calculated according to these data. Overall, less frequent application of ESWL does not yield higher complication rates than those at ESWL centers where larger numbers of treatments are performed.

Equipment Design↗
PubMed1997

Influence of the dopamine D2 receptor (DRD2) genotype on neuroadaptive effects of alcohol and the clinical outcome of alcoholism.

The present study was performed to test the hypotheses that allelic variants at the human dopamine D2 receptor gene locus (DRD2) confer susceptibility to alcoholism or are associated with clinical subtypes of alcoholism. We investigated an A --> G substitution polymorphism in the 3'-untranslated region of exon 8 (E8) of DRD2 with allele frequencies of f(G) = 0.295 - 0.329. No significant association of the DRD2 genotype or allele frequencies with alcoholism was found in an association study including 283 alcoholics and 146 non-alcoholic controls. However, the frequent homozygous E8 A/A genotype with f(AA) = 0.47 - 0.48 was associated with increased anxiety and depression scores in alcoholics during the follow up after clinical detoxification treatment. In addition, E8 A/A was associated with increased suicide attempts and showed a tendency towards more severe withdrawal symptoms, early relapse and reduced responsiveness to the dopaminergic agonist apomorphine. Regression analysis revealed the DRD2 E8 genotype as the only significant factor determining withdrawal severity in female alcoholics. The findings suggest an influence of the DRD2 genotype on the neuropharmacological effects of chronic alcohol exposure and the clinical course of alcoholism.

Adaptation, Physiological↗
PubMed1997

Altered dopaminergic function and negative symptoms in drug-free patients with schizophrenia. [123I]-iodobenzamide SPECT study.

BACKGROUND: Previous in vivo studies of schizophrenia with dopamine D2 receptor radioligands have yielded contradictory results. No prior study has used multiple scans to examine within-subject clinical change. METHOD: Twenty-one patients were studied with [123I]-iodobenzamide single photon emission computed tomography about two weeks after neuroleptic withdrawal. Thirteen of the 21 completed a second scan about four weeks after neuroleptic withdrawal. Sixteen controls were scanned for comparison. RESULTS: There was no significant difference between groups in [123I]-iodobenzamide uptake at either scanning session. No significant correlations with demographic variables (age, illness duration, drug-free period), or clinical ratings (positive and negative symptoms, movement disorder) were observed at either scanning session. There was a significant correlation between change in [123I]-iodobenzamide uptake and change in negative symptom ratings for the subjects who underwent two scans (r = 0.72, P < 0.05). CONCLUSIONS: Worsening of negative symptoms may be associated with increased availability of striatal D2 receptors, perhaps because of decreased concentrations of endogenous dopamine.

Adult↗
PubMed1996

Modulation of auditory responses during oddball tasks.

The modulation of auditory input processing in relation to slow event-related potentials was examined in two studies. A steady-state response (SSR) was evoked by a stimulus train delivered at 40 Hz. Slow potentials were elicited by an oddball task implemented as changes in the pitch of single stimuli within this 40-Hz train. In study 1, subjects responded to rare targets by means of a button press. In study 2, subjects responded to targets by means of a motor response in one session and by silent counting in another session. In both studies, the oddball task elicited a P300 to targets. SSR amplitude was reduced 100 ms following each stimulus, while a second amplitude reduction around 350-400 ms was discovered following targets, in particular, following a button press. Parallel to SSR amplitude reductions, the latencies between stimulus and subsequent SSR peak were reduced. Results indicate that processing of oddball stimuli and motor responding alters 'automatic' auditory processing at the level of the primary auditory cortex; the second SSR amplitude reduction which develops in parallel to P300 might support the hypothesis that slow positive potentials indicate widespread (disfacilitation) inhibition of cortical neural excitability.

Adult↗
PubMed1996

Reduced dopaminergic function in alcoholics is related to severe dependence.

With a view to the role of dopamine (DA) systems in reward processes and considering recent studies linking specific alleles at the DA-D2 receptor gene locus with alcoholism (especially with severe types) dopaminergic functions were evaluated in 49 alcoholics using growth hormone (GH) response to DA receptor agonist apomorphine (0.01 mg/kg subcutaneously). neuroendocrine testing was performed (during intoxication) at the time of admission to an inpatient alcohol treatment program and was repeated 7 days later (in a postintoxicated state). Patients underwent clinical examination, detoxification treatment and a subsequent rehabilitation program for abstinence including follow-up evaluation of outcome for 6 months. A two-factor analysis of variance (ANOVA) revealed a significant change of GH response (peak values corrected for baseline) over time (between intoxication and postintoxication; p < 0.001) and between abstainers and relapsers (p = 0.032). Relapse was also associated with paternal alcoholism, early onset of disease, and a more complete dependence syndrome and cerebellar atrophy. Standardized canonical discriminant coefficient was highest for reduced GH response compared to other relapse predictors in the model used. It is concluded that reduced GH response to dopaminergic stimulation corresponds to a progressed stage or syndrome of severe alcohol dependence; however, if reduced, dopaminergic function is one cause or consequence of addiction in this particular subgroup of patients that remains to be elucidated.

Adult↗
PubMed1996

Psychopathological and behavioral correlates of dopaminergic sensitivity in alcohol-dependent patients.

OBJECTIVES: To explore 2 facets of dopamine receptor sensitivity in alcoholics: (1) whether reduced sensitivity of central dopamine receptors is correlated with anxiety, depression, or novelty seeking and (2) whether this reduction is associated with poor treatment outcome. METHOD: Sixty-four alcohol-dependent patients were assessed according to their clinical outcome, sensitivity of central dopamine receptors (apomorphine-induced growth hormone secretion), mood states, and personality traits before and after detoxification. RESULTS: Patients with poor treatment outcome displayed a blunted growth hormone response before, but not after, detoxification. Growth hormone response was not significantly correlated with novelty seeking. Relapsing patients tended to be less depressed than patients who remained abstinent during observation. CONCLUSION: This study did not support the hypothesis that reduced sensitivity of dopamine receptors is associated with anxiety, depressed mood, or high novelty seeking in alcoholism.

Adult↗
PubMed1996

Lack of allelic association of dopamine D1 and D2 (TaqIA) receptor gene polymorphisms with reduced dopaminergic sensitivity to alcoholism.

Our study tested the hypothesis of whether the sensitivity of central dopamine receptors corresponds to the genotypic constitution of DNA-polymorphisms of the dopamine D1 and D2 receptor (DRD1, DRD2) genes and is associated with poor treatment outcome. Therefore, 97 alcohol-dependent patients were assessed according to their sensitivity of central dopamine receptors (apomorphine-induced secretion of growth hormone), clinical outcome during a 6-month observation period, and genotypic constitution of the TaqIA restriction fragment length polymorphism (RFLP) at the DRD2 locus and of the Bsp1286I RFLP at the DRD1 locus. On the 1st day of detoxification, dopamine receptor hyposensitivity was found in treatment nonresponders, but not in responders. Apomorphine-induced growth hormone release did not differ significantly in alcoholics with different genotypes of the DRD1 and DRD2 RFLPs. Neither did we find a significant allelic association with treatment response. Thus, we did not find evidence for a genetic determination of dopamine receptor hyposensitivity in alcoholics with poor treatment outcome.

Adult↗
PubMed1996

Long-term observation of the hypothalamic-pituitary-thyroid (HPT) axis in alcohol-dependent patients.

Thyroid hormone levels and thyrotrophin (TSH) were measured in 45 alcohol-dependent patients before detoxification and 8 days, 3 months and 6 months after detoxification, and compared to levels in healthy controls. Before detoxification, levels of thyroxine (T4) and thyroxine-binding globulin (TBG) were significantly reduced in patients compared with healthy controls, while triiodothyronine (T3), reverse T3, and TSH levels did not differ from those in healthy controls. During the entire observation period, free T4 (fT4) and free T3 (fT3) levels were slightly elevated compared with those in healthy controls. T4 and TBG levels increased significantly during the first week of abstinence. Severity of withdrawal symptoms was negatively correlated with the total T4 levels after 8 days of abstinence. Three months after detoxification, relapsers displayed significantly lower T4 and TBG levels compared with abstinent patients. The increase in T3 levels was most pronounced between 8 days and 3 months of abstinence in both relapsing and abstinent patients. Six months after detoxification, only abstinent patients could be assessed, and they displayed increased TBG and T3 levels compared to healthy controls. Our findings suggest a different time-course for T3 and T4 levels after detoxification in alcohol-dependent patients, and indicate that T4 levels after detoxification interact with withdrawal symptoms.

Adult↗
PubMed1996

Influence of dopaminergic transmission on severity of withdrawal syndrome in alcoholism.

OBJECTIVE: Dysfunction of dopaminergic transmission has been suggested as influencing withdrawal syndrome in alcohol-dependent patients. Therefore, dopamine levels and sensitivity of dopamine receptors were correlated with the severity of withdrawal syndrome in 40 alcoholics. METHOD: Dopamine blood plasma levels and apomorphine-induced Growth Hormone (GH) release were measured on the first day of detoxification (Day 1) and after 8 days of abstinence (Day 8). Severity of withdrawal syndrome was assessed daily by the Clinical Institute Withdrawal Assessment (CIWA) score. In the 22 patients (out of the 40) treated by chlormethiazole, severity of withdrawal was measured by the required chlormethiazole dose. RESULTS: A positive correlation was found between dopamine levels on Day 1 and the total CIWA score and necessary chlormethiazole dose, respectively. Correlation with the CIWA score was even stronger when the sensitivity of post-synaptic dopamine receptors was taken into account. No significant correlation between dopamine levels on Day 8 and withdrawal syndrome was found. CONCLUSIONS: Our findings indicate an influence of dopaminergic transmission on withdrawal syndrome during early withdrawal.

Adult↗
PubMed1996

Dopamine D2 receptor imaging and neuroleptic drug response.

Studies with positron emission tomography and single photon emission computed tomography have yielded important findings concerning the relationship between dopamine D2 receptor occupancy and neuroleptic dose, plasma neuroleptic levels, and clinical response. For "typical" neuroleptics, therapeutic response is associated with occupancy levels as low as 60%-70%, which can be achieved at lower doses than are routinely used. For these drugs, extrapyramidal side effects increase, and therapeutic response remains unchanged with higher occupancy levels. Although the mechanisms responsible for the improved clinical efficacy and tolerability of atypical neuroleptics are still poorly understood, antipsychotic efficacy has been observed at lower D2 receptor occupancy rates than with typical neuroleptics. It is unclear whether the lower incidence of extrapyramidal side effects observed with the atypical neuroleptic clozapine can be attributed to its lower D2 occupancy, its relatively specific effects on the ventral striatum, or its nondopaminergic effects. There are a number of additional unresolved issues, including the high interindividual variation in scan outcome measurements, possible effects of concomitant medication, possible effects of endogenous dopamine, and assumptions in various strategies used to model receptor densities and occupancy rates.

Antipsychotic Agents↗
PubMed1995

Hypothalamic-pituitary-gonadal axis, prolactin, and cortisol in alcoholics during withdrawal and after three weeks of abstinence: comparison with healthy control subjects.

Serum concentrations of luteinizing hormone, follicle-stimulating hormone, testosterone, androstenedione, estradiol, sex hormone-binding globulin, cortisol, and prolactin were measured in 12 male chronic alcoholics once during withdrawal and once after 21 days of abstinence. The results were compared with those of 14 healthy volunteers. During withdrawal, luteinizing hormone, estradiol, and cortisol levels were significantly enhanced. Estradiol and cortisol concentrations fell significantly during abstinence, whereas luteinizing hormone concentrations remained elevated. The results may be interpreted as follows: the well-known inhibitory effect of alcohol on the biosynthesis of testosterone may have led to a compensatory increase in luteinizing hormone secretion, so that normal serum concentrations of testosterone were maintained. On the other hand, peripheral conversion from androstenedione to estradiol via aromatase pathways seemed to be enhanced in chronic alcoholics, at least during withdrawal. Whether this marked increase in estradiol concentrations is implicated in different clinical and psychological symptoms seen in chronic alcoholics remains to be investigated.

Adult↗
PubMed1995

Evidence for prolonged recovery of dopaminergic transmission after detoxification in alcoholics with poor treatment outcome.

It has been hypothesized that dysfunction of dopaminergic neurotransmission is involved in the pathogenesis of alcohol addiction. Therefore, peripheral dopamine levels, sensitivity of central dopamine receptors (apomorphine-induced Growth Hormone (GH) secretion), and the inhibitory efficacy of G-proteins on adenylyl cyclase activity (as an indicator for dopamine D2-receptor coupled second messenger mechanisms) were measured in 45 alcohol-dependent patients before and after detoxification and in 10 healthy controls. The time needed to adjust to abstinence conditions differed between patients with good and poor treatment outcome. In subsequent abstainers, effects of alcohol withdrawal were already found during the first 24 hours of abstinence (normalisation of GH response, increases in dopamine levels and the inhibitory efficacy of G-proteins). During the next 7 days of abstinence, no more significant changes were observed in the assessed variables. In subsequent relapsers, no significant effect of acute ethanol withdrawal on the same measures was found. However, at day 8 of abstinence, increases in apomorphine-induced GH secretion (towards normalisation), in dopamine plasma levels, and in the inhibitory efficacy of G-proteins (towards above-normal levels) were observed. This retarded adjustment of dopaminergic signal transduction seems to reflect the relapse risk of treatment nonresponders.

Adult↗