Biomedical subjects

G Laux

Publications and source records attributed to G Laux.

At least 91 records · Page 5Linked to original sources

PubMed1990

Urinary dopamine sulfate: regulations and significance in neurological disorders.

Dopamine-3-O-sulfate (DA-3-O-S) and dopamine-4-O-sulfate (DA-4-O-S) are important end products of L-dopa metabolism. Therefore they may give indications of disturbances in the peripheral metabolism of catecholamines, when measured in urine samples of patients with Parkinson's disease (PD). In addition, information about the reliability of DA sulfatation after L-dopa therapy may be of significance for its role in the elimination of DA from the peripheral nervous system. Although DA-3-O-S appears to be the predominant sulfo-conjugate in urine, there are no changes in PD nor in depression syndrome compared to controls with or without other neurological disorders. By contrast, DA-4-O-S is significantly decreased in de novo PD subjects. However, a similar reduction is notable in patients with other neurological disorders. In depressed persons the loss of this compound was less pronounced as compared to de novo PD. Treatment with combined L-dopa therapy caused increased excretion of DA-3-O-S, while changes in DA-4-O-S were only marginal. It is concluded that urinary DA-3-O-S cannot be used as marker for PD, while DA-4-O-S is significantly reduced in a variety of neurological disorders and in particular in de novo PD. Further studies are necessary to elucidate its role as possible peripheral marker to distinguish preclinical PD and depression syndrome.

Adult↗

PubMed1990

Brofaromine (CGP 11 305 A) in treatment of depression: biological estimation of plasma concentrations.

In an open clinical trial, 13 depressives were treated with the reversible and selective type-A monoamine oxidase (MAO)-inhibitor brofaromine (CGP 11 305 A), the inhibitory potency of deproteinated plasma on a crude MAO preparation from human placenta was measured as a parameter for plasma brofaromine and possibly active metabolites of brofaromine. Patients significantly (p less than 0.01) improved under brofaromine. There were, however, no significant differences in plasma MAO-inhibitory potency between responders (improvement greater than 50%; n = 5) and nonresponders and no correlations with the change from baseline of the total Hamilton Depression Score (HAMD) or with changes of sleep (change from baseline of the HAMD sleep items). MAO-inhibitory potency significantly (p less than 0.05) increased parallel to the increase of the dosage from 50 mg b.i.d. to t.i.d., confirming the validity of this technique. The biological assay applied is a simple and reliable alternative when estimating the plasma concentrations of brofaromine and, possibly, other reversible MAO inhibitors.

Adult↗

PubMed1990

Guidelines for the dosage of antipsychotic drugs.

When commonly recommended guidelines for the dosage of neuroleptic drugs are critically reviewed, unanswered questions outnumber accepted rules. The relationship between dose and therapeutic efficacy remains far from clear, and despite lack of data there has been a trend in recent years to escalate dosage. Average clinical antipsychotic potency correlates closely with the affinity of the drug for dopamine (D2) receptors. Correlations of blood levels of neuroleptics with clinical efficacy are inconsistent. Assessments of immediate and follow-up treatment indicate that moderate doses are adequate for most psychotic patients and fail to support the use of high doses (more than the approximate equivalent of 300-600 mg chlorpromazine daily). Occasionally however, patients, perhaps because of idiosyncratic pharmacokinetics, require higher doses and do not conform to the statistical data for outcome. More precise results for determining the optimum dose of antipsychotic compounds in schizophrenics in the future, may be available from positron emission tomographic (PET) techniques.

Antipsychotic Agents↗

PubMed1990

A double-blind multicentre study comparing remoxipride, two and three times daily, with haloperidol in schizophrenia.

A double-blind multicentre study comparing the efficacy and safety of remoxipride in relation to haloperidol was conducted in 160 inpatients with schizophrenic illness diagnosed according to DSM-III. The study period was 4 weeks. The mean daily dose of remoxipride (whether given twice or three times daily) during the last week of treatment was 395 mg; the corresponding dose of haloperidol was 17 mg per day. No significant difference in therapeutic efficacy was found; Brief Psychiatric Rating Scale (BPRS) median total scores dropped from 41 to 20 (remoxipride twice daily, n = 51), 43 to 20 (remoxipride three times daily, n = 44) 40 to 19 (haloperidol three times daily, n = 48) at last valid rating. According to Clinical Global Impression (CGI) 68% in the remoxipride twice daily, 58% in the three times daily and 60% in the haloperidol group were very much or much improved. Treatment-emergent extrapyramidal checklist symptoms (hypokinesia, rigidity and tremor) were statistically significantly more frequent and more severe during haloperidol than during remoxipride treatment despite a statistically significantly higher concurrent use of anticholinergic drugs in the haloperidol group. Haloperidol treated patients reported more tiredness and drowsiness than remoxipride treated patients. Also, haloperidol treated patients had a significantly higher frequency of extrapyramidal symptoms on 8 out of 10 items of the Simpson and Angus scale.

Acute Disease↗

PubMed1990

Identification of the Epstein-Barr virus terminal protein gene products in latently infected lymphocytes.

The terminal protein (TP) gene produces two overlapping mRNAs in latently infected lymphocytes that are predicted to encode the similar polypeptides TP1 (497 amino acids) and TP2 (378 amino acids), with TP1 exon 1 providing 119 extra unique residues at the N terminus. Rabbit antisera were raised to procaryotic fusion proteins and used to detect expression of a predicted 53-kilodalton (kDa) TP product in transfected 293 cells and latently infected lymphocytes. Fractionation of transfected 293 cells showed this protein to be localized to an integral membrane preparation. The same fraction of latently infected lymphocytes contained proteins of 53 and 27 to 39 kDa as determined by Western immunoblotting with the TP-specific rabbit antisera. Immunoprecipitation of TP products from 35S-labeled human lymphoblastoid cells (CR/B95-8) was used in pulse-chase experiments and showed that TP1 was a labile protein with a half-life of approximately 2 to 4 h. The anti-fusion protein serum detected a 53-kDa TP1 and degradation products in the range of 25 to 35 kDa. A panel of Burkitt's lymphoma cell lines and cell lines established with virus recovered from the BL cells were analyzed by Western immunoblotting and found to contain the 53-kDa TP1 product, its degradation products, or both. Only two EBV-positive BL cell lines (BL72 and Wewak II) were negative in this assay. The results suggest that a labile TP1 protein may be expressed by most, if not all, EBV-infected cell lines.

Antibodies, Monoclonal↗

PubMed1989

[Intravenous versus oral treatment of endogenously depressed patients with doxepin--a double-blind study with plasma level determination].

A double-blind study was conducted involving 45 "therapy-resistant" endogenous depressive inpatients who were treated with Doxepin intravenously or orally. After a period of 3 weeks there was no significant difference in the clinical ratings (HRSD, SDS). In the parenteral treatment group, however there was a statistically significant quicker onset of action (day 3). Compared to oral application higher Doxepin plasma concentrations during day 1 to 6 could be obtained by drip-infusion in spite of lower dosage.

Administration, Oral↗

PubMed1989

[Benzodiazepine abuse--findings from a German state mental hospital].

During the past few years the problem of over-prescribing of benzodiazepines has been increasingly discussed. However, up to now exact data on the extent of an abuse of these substances are relatively scarce and controversial. An analysis done at a German Psychiatric State Hospital from 1974 to 1983 regarding the frequency of the diagnosis "Benzodiazepine-dependence" showed that in only 150 cases (0.5%) out of almost 33,000 admitted patients was the diagnosis benzodiazepine-abuse justified, with an increase since the year 1980. During a prospective study of the quarterly incidence in 1984, 18.5% of the patients admitted met the criterion of long-term use of benzodiazepines (continuous use for more than three months). Sociodemographic and clinical data of these benzodiazepine-long term users are presented.

Adult↗

PubMed1989

Plasma moclobemide and metabolites: lack of correlation with clinical response and biogenic amines.

The concentration of the reversible monoamine oxidase type-A (MAO-A) inhibitor moclobemide (Ro 11-1163) was determined by high pressure liquid chromatography (HPLC) in the plasma of 16 depressives treated with moclobemide. Moreover, the inhibitory potency of organic extracts of the plasma on a standard MAO-A preparation from human placenta was measured spectrophotometrically. The inhibitory potency significantly correlated with the HPLC results. However, it overestimated the concentration of moclobemide by one order of magnitude possibly due to the presence of yet unknown metabolites more active than moclobemide itself. These have already been suggested in view of the higher inhibitory potency of moclobemide ex vivo than in vitro. This new methodological approach might represent a comfortable alternative to HPLC procedures in pharmacokinetic studies on reversible MAO inhibitors. Plasma biogenic amines and their metabolites might be indicative of the biologic activity of moclobemide. Plasma homovanillic acid (HVA) decreased and norepinephrine (NE) increased under moclobemide, although insignificantly. There was no significant correlation between the plasma concentration of moclobemide as estimated by either method and the therapeutic response and the change of plasma HVA and NE.

Adult↗

PubMed1989

The influence of human corticotropin-releasing hormone on somatostatin secretion in depressed patients and controls.

Twenty subjects (10 patients with a major depressive episode and 10 individually matched healthy controls) received 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) as an i.v. bolus dose. Healthy subjects and depressed patients exhibited a significant increase of plasma somatostatin (SRIH) concentrations with no difference between both comparison groups. Compared to controls, depressed patients showed a significant attenuation of corticotropin (ACTH) responses, while cortisol secretion in response to hCRH was normal. No correlations were found among basal plasma concentrations of SRIH, ACTH or cortisol and SRIH, ACTH or cortisol responses following hCRH. These findings are compatible with the hypothesis that hypothalamic-pituitary-adrenal (HPA) hyperactivity in the depressive state may primarily be due to central hypersecretion of CRH and support the view of a hCRH-induced SRIH secretion which is not related to HPA dysfunction associated with major depression.

Adrenocorticotropic Hormone↗

PubMed1989

The terminal protein gene 2 of Epstein-Barr virus is transcribed from a bidirectional latent promoter region.

The intact terminal protein genes (TP1 and TP2) of Epstein-Barr virus (EBV) are created upon infection by circularization of the linear viral genome at its terminal repeats. The structure of the 1.7 kb TP2 latent mRNA has been determined by cDNA analysis and Northern blotting, revealing its close relation to TP1 mRNA. The 1.7 kb transcript is expressed from a different promoter and has a different 5' exon from TP1 but is also spliced across the terminal repeats. The last eight exons are common to the TP1 and TP2 RNAs. The TP2 promoter is 3.3 kb downstream of the TP1 promoter and is part of a bidirectional latent EBV promoter region transcribing the TP2 and the latent membrane protein RNAs in opposite directions.

Cloning, Molecular↗

PubMed1989

Comparison of sensorimotor and cognitive performance of acute schizophrenic inpatients treated with remoxipride or haloperidol.

29 acute schizophrenic patients according to DSM III and ICD-9 underwent examination of performance regarding cognitive and sensorimotor tasks at the beginning and the end of a 28-day neuroleptic treatment with remoxipride or haloperidol in a double-blind design. Psychopathological symptoms were assessed by Brief Psychiatric Rating Scale and Clinical Global Impression, extrapyramidal side effects (ESE) were rated by Simpson-Angus scale. A significant treatment effect for acoustic reaction time tasks, naming of colored stripes and interference could be demonstrated, whereas tapping revealed a significant effect of duration of treatment. Interaction effects regarding time of faults in line tracing, visual sensorimotor reaction time task and interference factor (Stroop test) could be observed. ESE and impairment of performance occurred simultaneously and ESE vanished with clinical improvement. Performance deficits were more pronounced in patients assigned to remoxipride treatment. Possible differential effects on performance under neuroleptic drug treatment will be discussed.

Acute Disease↗

PubMed1989

[Moclobemide in the long-term treatment of depressed patients].

13 patients with major depressive disorder, who responded well to the reversible MAO-A-inhibitor moclobemide after unsuccessful initial treatment with tri- or tetracyclic antidepressants were monitored under naturalistic outpatient therapy conditions with moclobemide plasma level control for an average of 7.4 months. Due to depressive relapse moclobemide treatment had to be discontinued for 6 patients. Increased dosages or the addition of a tricyclic antidepressant did not bring about any sufficient improvement. The relapse occurred after an average of 2-3 months of treatment with moclobemide administration. In the case of 7 patients it was possible to discontinue treatment with moclobemide after an average of 9.7 months with an incremental reduction in dosage. Recurring depressive symptoms were counteracted in the case of 2 patients by increasing dosages and adding a tricyclic antidepressant. The patients reported good tolerance of the drug as compared to tri- or tetracyclics.

Adult↗

PubMed1989

Moclobemide and maprotiline in the treatment of inpatients with major depressive disorder.

A double-blind study with the substituted benzamide moclobemide, a novel reversible, short acting MAOI with predominant inhibition of MAO-A, and maprotiline, the most selective noradrenaline reuptake inhibitor available at present has been conducted in n = 40 severely depressed inpatients suffering from predominantly endogenous depressions. No significant differences between the two drugs were found using global HRSD, HAMA and self rating scales. Regarding the clinical profile moclobemide seemed to be more effective in retarded depressives, maprotiline was superior in alleviating depressive agitation and sleep disturbances. The latter symptoms were responsible for three cases of treatment withdrawal in the moclobemide group. No case of hypertensive crisis could be registered, though patients were not subject to food restrictions. Maximal concentrations of moclobemide in CSF were reached two hours after oral application, compared to tricyclic antidepressants a high CSF/plasma ratio could be detected.

Anthracenes↗

PubMed1989

[Moclobemide in the treatment of depression--an overview].

Moclobemide, a benzamidederivate, is a reversible, selective MAOI with a predominant effect upon MAO-A. In clinical trials with moclobemide so far no clearcut tyramine interaction leading to a hypertensive crisis has been reported and no case of hepatotoxicity has been observed. Open and double-blind studies have shown moclobemide to be an activating antidepressant whose efficacy is superior to placebo and comparable to standard tricyclics. The global tolerance has been shown to be better than in tricyclics, frequency of (anticholinergic) side effects has been lower compared to tricyclics. Our data confirmed the antidepressant efficacy of moclobemide with a rapid onset of action and activating properties devoid of clinically relevant tyramine interactions. As side-effects restlessness, paraesthesias, nausea and sleep disturbances were noted; sleep disturbances could not be improved in most cases. In the light of existing clinical data moclobemide may become an exponent of the "renaissance" of MAOI in the treatment of retarded depression.

Antidepressive Agents↗

PubMed1989

[Treatment of depression using MAO-A inhibitors: an open study of a direct switch from moclobemide to tri-/tetracyclic antidepressants].

In an open study 13 depressed inpatients received moclobemide, a selective and reversible MAO-A-inhibitor (300 mg/d) for one week and subsequently were switched to a three-week course of a tricyclic or tetracyclic antidepressant (TCA) without medication-free interval. There were no drop-out, two patients needed additional ECT. Depressive symptomatology declined during treatment which was well tolerated. Mild adverse CNS effects and gastrointestinal symptoms prevailed under moclobemide. Subsequent TCA prompted autonomic symptoms. Overall adverse drug effects decreased over the treatment period. Cardiovascular monitoring revealed no clinically relevant side effects.

Adult↗

PubMed1988

A spliced Epstein-Barr virus gene expressed in immortalized lymphocytes is created by circularization of the linear viral genome.

Epstein-Barr virus (EBV) immortalizes B-lymphocytes efficiently in vitro and in most or all of the cells a latent infection is established. Only a few viral genes are expressed during latency and these apparently maintain cell immortalization by EBV. A 1.9 kb cDNA clone of an EBV mRNA has been isolated from a B95-8 cDNA library and this cDNA corresponds to a new member of the group of EBV latent cycle genes. On Northern blots two polyadenylated transcripts 1.7 and 2.0 kb in length have been detected by the cDNA clone in B95-8 cells as well as in latently infected cell lines and in various cell lines derived from Burkitt's lymphomas. The cDNA sequence showed that this gene consists of nine exons and showed that this gene consists of nine exons and that the transcription unit crosses the terminal repeats. Thus, the intact gene is created upon infection by the circularization of the linear viral DNA molecule at the terminal repeats. One major open reading frame is present in the cDNA apparently coding for a 53 kd protein. A strongly hydrophilic part of the protein is followed by a very hydrophobic C-terminus, perhaps suggesting a membrane protein. The gene is unrelated to the other latent cycle genes, the EBV nuclear antigens (EBNA 1-4), the leader protein (LP), and the latent membrane protein (LMP) genes. This is the first example of a viral gene whose coding sequence is only created by joining of the ends of a linear virus.

Amino Acid Sequence↗

PubMed1988

Delta sleep-inducing peptide response to human corticotropin-releasing hormone (CRH) in major depressive disorder. Comparison with CRH-induced corticotropin and cortisol secretion.

Twenty-four subjects (12 patients with major depressive disorder and 12 controls matched for sex and age) received 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) as an iv bolus dose. Healthy subjects exhibited a slight, but sustained, increase of plasma delta sleep-inducing peptide (DSIP) concentrations, whereas a marked reduction of DSIP levels was found in depressives. Compared to controls, depressed patients showed a significant attenuation of corticotropin (ACTH) responses, whereas cortisol secretion in response to hCRH was normal. Basal DSIP and cortisol concentrations were highly correlated and were higher in depressives than in controls. Both were negatively correlated with the DSIP responses to hCRH. These findings are compatible with the hypothesis that hypothalamic-pituitary-adrenal (HPA) overactivity in the depressive state is primarily due to central hypersecretion of CRH and support the view of a modulatory function of DSIP in the complex regulatory mechanism of the HPA system and of its pathophysiological significance for aberrant HPA axis function in major depressive disorder.

Adrenocorticotropic Hormone↗

PubMed1988

TPA-inducible Epstein-Barr virus genes in Raji cells and their regulation.

A number of agents including the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) can induce an abortive virus cycle in the EBV nonproducer Burkitt's lymphoma line Raji. We describe the pattern of viral RNAs transcribed in uninduced cells and in cells treated with TPA for 8 hr, as analyzed by Northern blotting. By comparing the patterns of RNAs observed in cells treated with TPA, TPA plus cycloheximide, or cycloheximide alone, we have tested whether any EBV gene in TPA-treated Raji cells would be inducible directly by TPA in the presence of protein synthesis inhibitors, similarly to immediate-early genes induced by superinfection of Raji cells with P3HR-1 virus in the presence of cycloheximide. We demonstrate here that induction of all early EBV genes is dependent on ongoing protein synthesis. The experiments do not provide an answer to whether TPA acts by activating an initial step in the cascade of virus production or whether TPA has a simultaneous pleiotropic effect on the regulation of a large number of viral genes.

Genes, Viral↗