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Biomedical subjects

M Hoehe

Publications and source records attributed to M Hoehe.

13 recordsLinked to original sources
PubMed1999

QT interval is linked to 2 long-QT syndrome loci in normal subjects.

BACKGROUND: The rate-corrected QT interval (QTc) is heritable, and the discovery of quantitative trait loci that influence the QTc would be an important step in identifying the genes responsible for life-threatening arrhythmias in the general population. We studied 66 pairs of unselected normal dizygotic (DZ) twin subjects and their parents in a sib-pair analysis. We tested for linkage of gene loci harboring genes known to cause the long-QT syndrome (LQT) to the quantitative trait QTc. METHODS AND RESULTS: We found genetic variance on QRS duration, QRS axis, T-wave axis, and QTc. Women had a longer QTc than men. Microsatellite markers were tested in the vicinity of the gene loci for the 5 known LQT genes. We found significant linkage of QTc with the loci for LQT1 on chromosome 11 and LQT4 on chromosome 4 but not to LQT2, LQT3, or LQT5. We also found linkage of the QRS axis with LQT2 and LQT3. CONCLUSIONS: We suggest that these quantitative trait loci may represent the presence of variations in LQT genes that could be important to the risk for rhythm disturbances in the general population.

Adult↗
PubMed1998

Serotonin transporter gene variants in alcohol-dependent subjects with dissocial personality disorder.

BACKGROUND: We tested the hypothesis that a functional biallelic repetitive element in the 5' regulatory region of the human serotonin transporter gene (SLC6A4) confers susceptibility to serotonin-related personality traits underlying alcohol dependence with dissocial behavior. METHODS: The association study was focused on 64 alcohol-dependent subjects with a dissocial personality disorder (according to ICD-10) who were derived from 315 German alcohol-dependent subjects. The Tridimensional Personality Questionnaire (TPQ) was applied to assess personality dimensions in 101 alcohol-dependent men, including 39 dissocial alcoholics. RESULTS: Our association analyses revealed a trend towards a higher frequency of the short (S) allele of the SLC6A4 polymorphism in dissocial alcoholics compared to 216 German controls (chi 2 = 2.81, df = 1, p = 0.094). Dissocial alcoholics carrying the S/S genotype exhibited significant lower scores of harm avoidance compared to those lacking it (U-test, p = 0.015). Significantly higher novelty seeking scores were obtained in dissocial alcoholics carrying the S allele relative to those lacking it (U-test, p = 0.021). CONCLUSIONS: Our tentative association findings in dissocial alcoholics suggest that the S allele of the 5' regulatory SLC6A4 polymorphism confers susceptibility to a temperamental profile of high novelty seeking and low harm avoidance that has been postulated to underlie dissocial (type-2) alcoholism according to Cloninger's neurogenetic theory of personality.

Adult↗
PubMed1998

Possible allelic association of a tyrosine hydroxylase polymorphism with vulnerability to alcohol-withdrawal delirium.

Recently, an association has been reported between schizophrenia and a rare allele containing 10-repeats (A10) of a polymorphic tetranucleotide motif in the first intron of the tyrosine hydroxylase (TH) gene. The present association analysis tested the hypothesis that the A10 candidate allele confers vulnerability to alcohol-withdrawal delirium with visual hallucinations. The genotype of the TH tetranucleotide polymorphism was assessed in 204 German controls and 311 German alcohol-dependent subjects, including 63 alcoholics with a history of visual hallucinations during withdrawal delirium. The frequency of the A10 allele was significantly increased in the alcoholics with withdrawal delirium (3.2%) compared with that in the controls (0.5%; Fisher's exact test: P = 0.03, two-tailed; OR (A10+) = 6.85, 95% confidence interval: 1.52-30.79). The possible allelic association suggests that allelic variation at the TH locus mediates vulnerability to alcohol-withdrawal delirium in a small proportion of alcohol-dependent subjects.

Adult↗
PubMed1997

Association analysis of a regulatory variation of the serotonin transporter gene with severe alcohol dependence.

The present study tested the hypothesis that the short, low activity variant of a biallelic polymorphism in the 5' regulatory region of the human serotonin transporter (5-HTT) gene confers susceptibility to severe alcohol dependence marked by severe withdrawal symptoms. Applying a phenotype-genotype strategy, our population-based association analysis included 216 German controls and an extreme sample of 103 severely affected alcoholics who were selected from 315 German alcohol-dependent subjects by a history of alcohol withdrawal seizure or delirium. The frequency of the short allele (S) was significantly increased in the severely affected alcoholics, compared with that in the controls (X2 = 3.87, df = 1, nominal p = 0.049). The post-hoc exploration indicated that this allelic association resulted exclusively from a significant excess of the S/S genotype in the severely affected alcoholics (p = 0.035), suggesting a recessively acting effect. Consistently, we found a weak but significant correlation (p = 0.013) between the frequency of the S/S genotype and severity of withdrawal symptoms (WDS): no WDS [18.3%, odds ratio (OR) = 1.16], vegetative WDS only (21.8%, OR = 1.44), and severe WDS with either withdrawal seizure only or delirium only (25.0%, OR = 1.69), and both withdrawal seizure and delirium (30.8%, OR = 2.30). Further studies are required to test whether the tentative genotype-phenotype relationship occurred by chance or reflects a real genotypic association between a recessively modifying effect of the short variant of the functional 5-HTT promoter polymorphism and alcohol withdrawal vulnerability.

Adult↗
PubMed1993

Opiates increase plasma catecholamines in humans.

Evidence from animal studies suggests that centrally acting opiates and opioid peptides increase catecholamine (CA) plasma concentrations, reflecting a central activation of sympathetic outflow. We describe here similar opiate actions in humans. Increasing doses of the potent mu opioid receptor agonist fentanyl (FE), 0.1, 0.2, and 0.25 mg/70 kg body weight (bw), induced a significant, dose-dependent increase of noradrenaline (NA) and adrenaline (A) plasma concentrations in healthy male individuals. Whereas NA increased continuously with increasing FE dose, a maximum A response was already reached at the lowest dose. These dose-related NA and A response patterns, showing a higher A sensitivity to opiate receptor stimulation, corresponded closely to those reported from animal studies. Furthermore, comparing the CA releasing potency of 0.2 mg FE/70 kg bw to analgetically equipotent doses of the less selective mu opioid receptor agonist morphine and the kappa agonist/mu antagonist nalbuphine in different groups of male individuals, we found similar effects of these opiates on CA plasma concentrations. These data suggest that the opiate-induced CA release in humans is not only mediated by mu opioid receptors, but may also involve kappa opioid receptor subtypes.

Adult↗
PubMed1989

Endocrinological studies in alcoholics during withdrawal and after abstinence.

Several endocrine parameters were assessed in 35 alcoholic inpatients after admission to hospital, and 17 of the 35 were retested after several weeks of sobriety. No difference was found in clonidine-stimulated growth hormone (GH) secretion between male alcoholics and male healthy controls, but significant positive correlations of GH secretion and alcohol content in expired breath on admission and gamma-GT values after abstinence were observed. Nonsuppression in the dexamethasone suppression test was found in 17% of the patients on admission, which seemed to be due to alcohol withdrawal. Postdexamethasone cortisol levels were significantly positively correlated with the "apathic syndrome" (r = 0.40; p less than or equal to 0.05). About one-third of the patients showed a blunted response in the TRH-test both on admission and after abstinence. No significant influence of alcohol intake, withdrawal or familial disposition on prolactin values could be detected. The results of the TRH test and the DST point to similar endocrinological patterns in alcoholics as in depressive patients and thus support the hypothesis of a link between alcoholism and depression.

Adrenocorticotropic Hormone↗
PubMed1989

Investigations with the specific mu-opiate receptor agonist fentanyl in depressive patients: growth hormone, prolactin, cortisol, noradrenaline and euphoric responses.

15 depressive patients and 15 controls, 9 of them age- and sex-matched, were administered 0.2 mg/70 kg i.v. fentanyl, a specific and highly potent mu-opiate receptor agonist. Growth hormone response was significantly reduced in depressive patients in comparison to controls, whereas prolactin response did not significantly differ between the two groups. Cortisol plasma concentration increased in depressive patients and decreased in controls. The difference between the groups failed to reach statistical significance. Only in patients, but not in controls, fentanyl led to a significant increase in plasma noradrenaline. In contrast, a significant increase in the visual analogue scale for the evaluation of psychotropic drug effects was found only in controls after fentanyl administration. From these preliminary results in connection with other studies we conclude a possible involvement of a disturbed opioid system at least in a subgroup of depressive patients.

Adult↗
PubMed1988

Human studies on the mu opiate receptor agonist fentanyl: neuroendocrine and behavioral responses.

The neuroendocrine and behavioral responses to the potent mu opiate receptor agonist Fentanyl (FE) have been systematically investigated in healthy male volunteers. These volunteers received, according to a randomized block design, different doses of FE: 0.1 mg/70 kg (n = 11), 0.2 mg/70 kg (n = 11), 0.25 mg/70 kg (n = 8), and saline (n = 11). FE induced a pronounced dose-dependent increase of plasma prolactin concentrations, which was significant at the lowest dose. In contrast, growth hormone was significantly stimulated by the highest FE dose only. Moreover, FE induced a maximum reduction of plasma cortisol concentrations at the lowest dose (0.1 mg/70 kg). In parallel, marked euphoric responses were also observed at this lowest FE dose. These results suggest a mu specific influence on all neuroendocrine and behavioral parameters investigated. Different responses of these parameters to different doses of FE, however, suggest a differential modulation of these parameters by the mu receptor agonist FE.

Adult↗
PubMed1988

Growth hormone, noradrenaline, blood pressure and cortisol responses to clonidine in healthy male volunteers: dose-response relations and reproducibility.

The growth hormone (GH) response to clonidine (CLON) has been investigated to date mostly with CLON doses of 2.0 micrograms/kg or 150 micrograms intravenously (IV). The present study investigated GH and blood pressure (BP) responses to CLON (2.0 and 1.5 micrograms/kg IV) (Study I). Twelve healthy male volunteers were tested with the two CLON doses and saline in a cross-randomized design. Plasma GH, noradrenaline (NA) and cortisol concentrations, BP and sedation were determined. CLON (1.5 and 2.0 micrograms/kg) induced a significant dose-dependent GH increase, but only the 2.0 micrograms/kg dose differentiated GH responders from nonresponders. In contrast to GH, NA, cortisol, and BP did not differ significantly after either CLON dose. We also studied GH responses to repeated CLON stimulation (Study II). Ten healthy male volunteers were given four CLON tests (2.0 micrograms/kg) at three-week intervals. The nine volunteers who participated in both studies were investigated over a time course up to 21 months. The subjects could be classified into those who showed consistent GH responses greater than 5 ng/ml, those who showed consistent GH responses less than 5 ng/ml, and those who showed both degrees of responses.

Adult↗
PubMed1988

Influence of the menstrual cycle on neuroendocrine and behavioral responses to an opiate agonist in humans: preliminary results.

Growth hormone (GH), prolactin (PRL), cortisol, noradrenaline (NA) and euphoric responses to the mu opiate receptor agonist Fentanyl (FE) (0.2 mg/70 kg intravenously) were investigated in five healthy, drug-free, female volunteers at menstruation and at ovulation. The plasma GH response to FE was blunted at menstruation relative to the GH response at ovulation. Basal and maximal PRL concentrations were about 1.5 times higher at ovulation than at menstruation. Cortisol and NA concentrations as well as mood and behavioral responses were not influenced by the menstrual cycle. These results confirm earlier reports of a reduced GH response at menstruation to other pharmacological agents. They also demonstrate that the menstrual cycle is an important influence on neuroendocrine responses to opiate challenge.

Adult↗
PubMed1987

Influence of the histaminergic system on opiate-induced neurosecretion and behaviour.

The influence of the histaminergic system on fentanyl (Fe)-induced growth hormone (GH) and prolactin (PRL) release as well as on Fe-induced increase of noradrenaline (NA) plasma levels has been studied in male volunteers. These volunteers received, according to a randomized block design, different pretreatments: the H1-antagonist dimethindene (Di) (0.1 mg/kg i.v.), or the H2-antagonist cimetidine (Ci)(5 mg/kg i.v.), or a combination of dimethindene and cimetidine (Di + Ci), or saline. The PRL increase caused by Fe (0.2 mg/70 kg) was not altered by pretreatment with the H1-antagonist Di, the H2-antagonist Ci, or the combination of both. The increase of NA plasma levels after Fe also was not modified by the histamine antagonists. In contrast, the maximum GH increase after Fe was blunted by the combination of Ci and Di, but not by either Ci or Di alone. These results suggest an involvement of the histaminergic system in opiate-induced GH-release.

Adult↗
PubMed1984

Dose-dependent influence of fentanyl on prolactin, growth hormone, and mood.

The effect of Fentanyl (FE), an opioid agonist, on neurosecretion and mood was investigated in normal volunteers using doses of 0.1, 0.2, 0.25 mg/70 kg. FE caused a strong dose-dependent increase in prolactin (PRL) secretion in every subject. In contrast, growth hormone (GH) was stimulated significantly at the highest dose only. Additionally, FE induced a significant increase in feeling of wellbeing measured by the Visual Analogue Scale (VAS).

Adult↗