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Biomedical subjects

G Höflich

Publications and source records attributed to G Höflich.

At least 19 recordsLinked to original sources
PubMed1999

Pharmacokinetic-pharmacodynamic modeling of tolerance to the prolactin-secreting effect of chlorprothixene after different modes of drug administration.

The objective of this study was the construction of a pharmacokinetic-pharmacodynamic model to describe the effects of chlorprothixene on prolactin secretion and the time-dependent alterations in the concentration-effect relationship due to tolerance development. Prolactin and chlorprothixene serum concentrations were determined in eight healthy men for up to 72 h after the intravenous and oral administration of chlorprothixene. An integrated pharmacokinetic model and a physiological indirect pharmacodynamic/tolerance model were applied to describe the prolactin-secreting effect of chlorprothixene. A three-compartment model served as pharmacokinetic model. The pharmacodynamic and tolerance model accounted for the baseline effect, the effect induced by the drug, and the regulatory mechanism that opposes the effect of the drug. This model adequately characterized the prolactin response after intravenous and oral drug administration of each individual by the sensitivity (dissociation constant), the efficacy (maximal prolactin secretion rate), the extent, and the rate of tolerance development. We speculate that this approach improves the quality of neuroendocrine challenge tests to determine the subject's sensitivity to drugs and the time course of adaptation.

Administration, Oral↗
PubMed1998

Effects of fluoxetine versus bright light in the treatment of seasonal affective disorder.

BACKGROUND: Disturbances of serotonergic neurotransmission appear to be particularly important for the pathophysiology of winter depression. This study investigated whether fluoxetine has antidepressant effects comparable to bright light in the treatment of seasonal affective disorder (winter type). METHOD: A randomized, parallel design was used with rater and patients blind to treatment conditions. One week of placebo (phase I) was followed by 5 weeks of treatment (phase II) with fluoxetine (20 mg per day) and a placebo light condition versus bright light (3000 lux, 2 h per day) and a placebo drug. There were 40 patients (20 in each treatment condition) suffering from seasonal affective disorder (SAD) according to DSM-III-R who had a total score on the Hamilton Depression Scale of at least 16. RESULTS: Forty patients entered phase II and 35 completed it (one drop-out in the fluoxetine group and four in the bright light group). Fourteen (70%) of the patients treated with bright light and 13 (65%) of those treated with fluoxetine were responders (NS). The remission rate in the bright light group tended to be superior (bright light 50%, fluoxetine 25%; P = 0.10). Light therapy improved HDRS scores significantly faster, while fluoxetine had a faster effect on atypical symptoms. Light treatment in the morning produced a significantly faster onset of improvement, but at the end of treatment the time of light application seemed not to be crucial. CONCLUSION: Both treatments produced a good antidepressant effect and were well tolerated. An apparently better response to bright light requires confirmation in a larger sample.

Adult↗
PubMed1998

Pathological regional cerebral blood flow in opiate-dependent patients during withdrawal: a HMPAO-SPECT study.

The aims of the present study were to investigate regional cerebral blood flow (rCBF) in heroin-dependent patients during withdrawal and to assess the relation between these changes and duration of heroin consumption and withdrawal data. The rCBF was measured using brain SPECT with 99mTc-HMPAO in 16 heroin-dependent patients during heroin withdrawal. Thirteen patients received levomethadone at the time of the SPECT scans. The images were analyzed both visually and quantitatively. A total of 21 hypoperfused brain regions were observed in 11 of the 16 patients. The temporal lobes were the most affected area, hypoperfusions of the right and left temporal lobe were observed in 5 and 5 patients, respectively. Three of the patients had a hypoperfusion of the right frontal lobe, 2 patients showed perfusion defects in the left frontal lobe, right parietal lobe and left parietal lobe. The results of the quantitative assessments of the rCBF were consistent with the results of the qualitative findings. The stepwise regression analysis showed a significant positive correlation (r = 0.54) between the dose of levomethadone at the time of the SPECT scan and the rCBF of the right parietal lobe. Other significant correlations between clinical data and rCBF were not found. The present results suggest brain perfusion abnormalities during heroin withdrawal in heroin-dependent patients, which are not due to the conditions of withdrawal.

Adult↗
PubMed1997

Root colonization of different plants by plant-growth-promoting Rhizobium leguminosarum bv. trifolii R39 studied with monospecific polyclonal antisera.

Monospecific polyclonal antisera raised against Rhizobium leguminosarum bv. trifolii R39, a bacterium which was isolated originally from red clover nodules, were used to study the colonization of roots of leguminous and nonleguminous plants (Pisum sativum, Lupinus albus, Triticúm aestivum, and Zea mays) after inoculation. Eight weeks after inoculation of soil-grown plants, between 0.1 and 1% of the total bacterial population in the rhizospheres of all inoculated plants were identified as R. leguminosarum bv. trifolii R39. To characterize the associative colonization of the nonleguminous plants by R.leguminosarum bv. trifolii R39 in more detail, a time course study was performed with inoculated roots of Z. mays. R. leguminosarum bv. trifolii R39 was found almost exclusively in the rhizosphere soil and on the rhizoplane 4 weeks after inoculation. Colonization of inner root tissues was detected only occasionally at this time. During the process of attachment of R. leguminosarum bv. trifolii R39 to the rhizoplane, bacterial lipopolysaccharides were overexpressed, and this may be important for plant-microbe interaction. Fourteen weeks after inoculation, microcolonies of R. leguminosarum bv. trifolii R39 were detected in lysed cells of the root cortex as well as in intracellular space of central root cylinder cells. At the beginning of flowering (18 weeks after inoculation), the number of R. leguminosarum bv. trifolii R39 organisms decreased in the rhizosphere soil, rhizoplane, and inner root tissue.

Antigens, Bacterial↗
PubMed1996

Low serum levels of tricyclic antidepressants in amitriptyline- and doxepin-treated inpatients with depressive syndromes are associated with nonresponse.

Nonresponse to tricyclic antidepressant (TCA) treatment is observed in about one-third of depressed patients. The cause(s) for nonresponse - apart from disease-specific effects - might be the failure to build up sufficiently high serum TCA levels due to noncompliance, substance abuse, rapid metabolism, or low dose. We carried out a retrospective analysis relating antidepressant serum levels to patient data obtained in the naturalistic setting of the Psychiatric Hospital of the Bonn University during the introductory phase of drug-monitoring. Case reports of 110 depressed inpatients who were treated with amitriptyline or doxepin were analyzed with respect to the following: medication and comedication, daily dose, type and duration of treatment, serum TCA concentrations (analyzed by the fluorescence polarization immunoassay), age, sex, body weight, abuse of nicotine or alcohol intake, serum transaminases (ALT, alanine aminotransferase, and AST, aspartate amino transferase), gamma-glutamyltranspeptidase (gamma-GT) and creatinine, compliance, and response. The salient findings were: 1. Serum TCA concentrations increased linearly with the daily amitriptyline dose but not with that of doxepin. 2. Interindividually, there was an eight to ten-fold difference in serum TCA concentrations at steady-state with 150 mg/day of either drug; longitudinally, we observed intraindividually a coefficient of variation of 8% and 12% for amitriptyline and doxepin respectively. 3. With amitriptyline (150 mg/day), the correlation between age and serum TCA concentrations was low (r = 0.33, p < 0.055) and no correlation was found after the administration of doxepin (150 mg/day), nor was there any correlation between age and dose-adjusted serum TCA concentrations after the administration of either drug. 4. Nonresponders had significantly lower serum levels than responders. These results suggest that patients should not qualify as nonresponders unless it can be demonstrated (and it is clinically applicable) that the steady-state serum TCA levels are stable within the upper limit of the recommended therapeutic range and serum level.

Adult↗
PubMed1996

[Psychopathological concepts of induced insanity exemplified by folie a deux].

We report on a case of a "folie à deux" between sister and brother (56 and 61 years of age). Based on a definition of the concept of the induced psychoses, we focus attention on some special aspects of these double psychoses. Special consideration is given to psychopathological constellations and their meaning, with etiogenetic aspects of "process" and "development" with regard to the concept of vulnerability. We could show that in such cases the new operationalised diagnostic manuals like DSM-IV and ICD-10 are based on traditional concepts.

Communication↗
PubMed1996

[Dementia-paranoid syndrome as the initial manifestation of AIDS. Case report and diagnostic overview].

A 33-year-old HIV-1-positive man developed dementia and a paranoid symptomatology with auditory hallucinations as the first manifestation of AIDS. The immunodeficiency syndrome is currently represented only by the immunohistochemical findings (CD4 216/microliters; CD4/CD8 ratio 0.12); no other manifestations of the disease are present. According to the literature about 15% of patients suffering from AIDS are likely to develop dementia during the course of the disease, usually after preceding opportunistic infections, severe systemic illness, or neoplasm. The manifestation of the disease solely by dementia is a rare phenomenon and represents, particularly if the incident of infection is cryptic, a diagnostic challenge.

AIDS Dementia Complex↗
PubMed1996

Pharmacokinetics of chlorprothixene after single intravenous and oral administration of three galenic preparations.

The absolute and relative bioavailability of chlorprothixene (CAS 113-59-7, Truxal) was studied in eight healthy male volunteers with three different formulations: solution, suspension and coated tablet. An intravenous infusion and an oral aqueous solution served as references. Single doses of 100 mg were administered in a randomized complete-block design with washout periods of two weeks. Serum concentrations of chlorprothixene were assayed using a high-performance liquid chromatographic method with electrochemical detection. After a 1-h infusion period the maximum serum concentration (Cmax) of chlorprothixene was 430 +/- 81 ng/ml (mean +/- S.D.) and subsequently decreased with a terminal elimination half-life (t1/2) of 25.8 +/- 13.6 h. The total serum clearance (Cl) and the apparent volume of distribution at steady state (Vss) were 867 +/- 167 ml/min and 1035 +/- 356 l, respectively. The profiles of the chlorprothixene serum concentration vs. time and the resulting pharmacokinetic parameters were similar for all orally administered formulations. The absolute oral bioavailability of 17% of the solution indicated a marked presystemic metabolism. The bioavailability of chlorprothixene relative to the oral solution was 56.4% with the coated tablet and 67.7% with the suspension. All pharmacokinetic parameters showed wide inter-subject variations, partly attributable to the respective formulation.

Administration, Oral↗
PubMed1995

Bioequivalence and absolute bioavailability of oblong and coated levomepromazine tablets in CYP2D6 phenotyped subjects.

The bioequivalence and absolute bioavailability of oblong and coated levomepromazine tablets were studied in 12 healthy volunteers. A 1-hour intravenous infusion served as the reference. Serum concentrations of levomepromazine were quantified with a specific high-performance liquid chromatographic method and electrochemical detection. The 2 oral formulations were bioequivalent. After oral administration of oblong and coated levomepromazine tablets the mean serum concentration versus time profiles were similar and the pharmacokinetic parameters showed wide interindividual variations. There was a 21% absolute bioavailability of levomepromazine, indicating a pronounced presystemic metabolism. The total serum clearance and the apparent volume of distribution at steady state were 48 +/- 14 l/min and 980 +/- 213 l, respectively. These pharmacokinetic parameters were also investigated with respect to the CYP2D6 polymorphism, i.e. via dextromethorphan phenotyping of 9 subjects, 3 subjects were poor metabolizers, and 6 extensive metabolizers. The Spearman's rank-ordered correlation analysis did not reveal a significant correlation between the pharmacokinetic parameters AUC, Cmax and t1/2 after oral administration of oblong and coated levomepromazine tablets and the metabolic ratios of dextromethorphan, suggesting that levomepromazine is not metabolized to any major extent by the isoenzyme CYP2D6.

Administration, Oral↗
PubMed1994

Quantification of chlorprothixene, levomepromazine and promethazine in human serum using high-performance liquid chromatography with coulometric electrochemical detection.

Isocratic reversed-phase high-performance liquid chromatography with coulometric electrochemical detection was optimised to quantify the neuroleptic drugs chloroprothixene, levomepromazine, and promethazine in human serum. The method involves extraction of the neuroleptic drugs in n-heptane-isoamylalcohol from the alkalinized serum, followed by chromatographic separation on a Nucleosil CN column with acetonitrile-pyridine-sodium acetate buffer as the mobile phase. The extraction recovery was > 85% for each neuroleptic drug. The sensitivity and selectivity required for pharmacokinetic studies was obtained with a dual coulometric analytical cell operating in the oxidative screen mode. The lower limit of detection in human serum for chlorprothixene, levomepromazine, and promethazine, was 0.5, 0.2 and 0.1 ng/ml, respectively. A linear relationship (r2 > 0.99) was obtained between the concentrations of each neuroleptic drug and the detector signal. The accuracy of the quality control samples was +/- 7% for each neuroleptic drug with a precision within 9.5%, 8.1% and 13.5% for chlorprothixene, levomepromazine, and promethazine, respectively. The neuroleptic drugs were stable in acetonitrile and human serum for at least six months when stored at -20 degrees C. This method is applicable to analyze a large number of serum samples for pharmacokinetic studies of the neuroleptic drugs.

Chlorprothixene↗
PubMed1994

Clinical response to sleep deprivation and auditory-evoked potentials--preliminary results.

The biological substrate of the antidepressant effect of total sleep deprivation (TSD) has not yet been elucidated. Furthermore, electrophysiological predictors for the response to TSD have not been studied extensively. The aim of present study was to examine the changes in acoustically evoked potentials (N1, P2, N2, P300) after a night of sleep deprivation and to analyze differences between responders and nonresponders. 17 depressive inpatients were studied. The most prominent changes in auditory evoked potentials (responders and nonresponders) were found for the amplitude of the P300 component. Differences between responders and nonresponders could be established for the amplitude and latencies in the N1 component. Responders showed smaller N1 amplitudes before TSD but a higher increase after TSD than nonresponders.

Adult↗
PubMed1994

[Electroconvulsive therapy in comorbidity of treatment refractory paranoid hallucinatory psychoses with Parkinson disease].

We report the case of a 49-year-old woman with a therapy resistant paranoid hallucinatory psychosis and coexisting severe symptoms of Parkinson's disease. Over a 3-week period she received electroconvulsive therapy (ECT) 10 times, while the medication of haloperidol 8 mg/day, thioridazin 90 mg/day, metixen 17.5 mg/day and biperiden 6 mg/day was continued. There was a general improvement of the clinical picture, more pronounced for the parkinson symptomatology than for the psychotic disorder.

Antiparkinson Agents↗
PubMed1992

[Successful treatment of seasonal compulsive syndrome with phototherapy].

We report the case of a 40-year-old woman with a seasonal form of obsessive compulsive disorder (OCD) which was usually accompanied by obsessions and occurred only in autumn or winter. Frequently, the OCD symptomatology was accompanied by depression. After a 12-day treatment with full spectrum bright light (3000 lux; 2 hours a day between 9 and 11 am) without changing the long-term antidepressive medication (125 mg amitriptyline/day) there was a complete remission of OCD symptomatology, with no relapse during the next months.

Adult↗
PubMed1978

[The importance of antagonistic soil micro-flora for eliminating soil-born fungal pathogens in intensive corn-growing (author's transl)].

In a sandy soil, the antagonistic bacterial and fungal flora was analysed and their effectivity with respect to corn foot and stem rot was investigated. Measures that promoted total micro-flora in soil (organic fertilization) stimulated, in most cases, the antagonists as well. Different organic substances supported various types of antagonists. In soil with inhibited aeration the antagonists were reduced. A full effectivity of the antagonistic biological soil component presupposes the absence of host plants.

Anaerobiosis↗