Search PubMed⌕ Search

Biomedical subjects

G Laux

Publications and source records attributed to G Laux.

At least 73 records · Page 4Linked to original sources
PubMed1994

Brofaromine in non-endogenous major depressed inpatients--results of a preliminary dose-finding trial versus tranylcypromine.

In a controlled, double-blind, comparative four-week trial on reactive or neurotic major depressed inpatients, the efficacy and safety of the new selective and reversible inhibitor of monoamine oxidase type A, brofaromine, was evaluated in three dose steps (50 mg/day [N = 13], 100 mg/day [N = 12], and 150 mg/day [N = 11]) versus 20 mg tranylcypromine/day (N = 11). In the four groups a pronounced reduction of the depressive symptomatology (measured by the Hamilton Depression Scale, the Zung Self-Rating Scale of Depression, and by a global evaluation of efficacy) was found, but it was not possible to show any differential effect. The safety parameters in all groups were comparable. The results of the trial are compared with other trials of monoamine oxidase inhibitors in this patient group and the possible reasons for the lack of a clear dose-response relationship are discussed.

Adolescent↗
PubMed1994

[Transesophageal echocardiography for determining left-ventricular end-diastolic myocardial tension].

OBJECTIVE: Left ventricular end-diastolic wall stress (EDWS) ist an index for left ventricular preload. Utilising transoesophageal echocardiography, left ventricular dimensions can be obtained by two-dimensional (2d-) as well as M-Mode measurements, and each can be combined with pulmonary capillary wedge pressure (PCWP) for the calculation of EDWS. In the present examination, both methods were compared with regard to their technical accomplishment and reproducibility under clinical conditions. METHODS: EDWS was obtained in 24 ventilated patients by 2d-echocardiography (2d-EDWS) and M-mode-echocardiography (M-EDWS) before and after a change in PCWP by 3mmHg. In 12 patients, volume therapy with hydroxyethylstarch (HAES) was started when PCWP < 11 mmHg; in another 12 patients, continuous intravenous administration of nitroglycerine was begun, when PCWP > 14 mmHg. 2d-EDWS and M-EDWS were compared and their relation to thermodilution stroke volume and stroke work index analysed. RESULTS: 2d-EDWS and M-EDWS correlated well in both groups (HAES: r = 0.91; NITRO: r = 0.93), with M-EDWS being systematically lower than 2d-EDWS. The relative difference between 2d-EDWS and M-EDWS, and their mean value--calculated as the mean per cent error--was 11.2%. Directional changes in preload were reflected in all patients by 2d-EDWS and M-EDWS in accordance. Both correlated better with stroke volume and stroke work index than PCWP. Determination of 2d-EDWS showed better inter- and intraobserver variability in the echocardiographic measurements. CONCLUSIONS: With regard to direction and quantity, changes of preload as seen with echocardiographic EDWS were according reflected by the 2d- and the M-mode technique. Determination of 2d-EDWS compared to M-EDWS was superior in reproducibility and more useful for the estimation of stroke volume changes.

Adult↗
PubMed1994

Identification and characterization of an Epstein-Barr virus nuclear antigen 2-responsive cis element in the bidirectional promoter region of latent membrane protein and terminal protein 2 genes.

Epstein-Barr virus (EBV) transforms resting B cells in vitro very efficiently. The nuclear viral protein EBV nuclear antigen 2 (EBNA2) is absolutely required for this process and also acts as a transcriptional activator of cellular and viral genes. As shown previously, EBNA2 transactivates the promoters of the viral latent membrane proteins. It interacts indirectly with an EBNA2-responsive cis element of the terminal protein 1 (TP1) promoter. To identify the sequences mediating EBNA2 transactivation of the bidirectional promoter region driving expression of the latent membrane proteins LMP and TP2 in opposite directions, we assayed the effects of EBNA2 on the activities of promoter deletion and site-directed mutants of TP2 and LMP promoter luciferase reporter gene constructs by cotransfections into EBNA2-negative Burkitt's lymphoma cells. We were able to delineate an 80-bp EBNA2-responsive region (EBNA2RE) between -232 and -152 relative to the LMP RNA start site which could also mediate EBNA2-dependent activation on a heterologous promoter. Sequences of 20 and 32 bp located at the 5' and 3' ends, respectively, of the EBNA2RE were both essential for EBNA2 responsiveness. Full transactivation of the LMP and TP2 promoters seemed to require 20 bp of 5' adjacent sequences in addition to the 80-bp element. Electrophoretic mobility shift assays revealed specific protein-DNA complexes formed at the EBNA2RE. Oligonucleotides from -181 to -152 and -166 to -132 relative to the LMP RNA start site visualized one B-cell and one B-cell-plus-HL60-specific retarded protein-DNA complex, respectively. Additionally, an oligonucleotide from -253 to -210 revealed two specific protein-DNA complexes with nuclear extracts from different B and non-B cells, suggesting also the binding of ubiquitously expressed proteins on the EBNA2RE. Thus, these experiments defined a 80-bp cis element sufficient for conferring EBNA2 inducibility and demonstrated specific interactions of cellular proteins at DNA sequences within the EBNA2RE, which are critical for transactivation by EBNA2.

Antigens, Viral↗
PubMed1993

The Epstein-Barr virus nuclear antigen 2 interacts with an EBNA2 responsive cis-element of the terminal protein 1 gene promoter.

The Epstein-Barr virus protein EBNA2 acts as a transcriptional activator of cellular and viral genes and plays a crucial role in the immortalization of human primary B-cells by EBV. We have shown previously that EBNA2 transactivates the promoters of the latent membrane antigens LMP, TP1 and TP2. The promoter of the TP1 gene was chosen as a model system to study the molecular mechanism of EBNA2 mediated transactivation. To identify an EBNA2 dependent cis-acting element, various TP1 promoter-reporter gene constructs were transfected in the absence and presence of an EBNA2 expression vector into the established B-cell line BL41-P3HR1. We were able to delineate an 81 bp EBNA2 responsive region between -258 and -177 relative to the TP1 RNA start site. The element worked in either orientation and could mediate EBNA2 dependent transactivation on a heterologous promoter. Electrophoretic mobility shift assays revealed three specific protein-DNA complexes formed with sequences of the EBNA2 responsive element. Two of these were not cell type specific, but the third was detected only in EBNA2 positive cell extracts. Gel-shift analysis in the presence of EBNA2 specific monoclonal antibodies revealed that EBNA2 is a component of the third complex. Thus, these experiments demonstrate that EBNA2 interacts with an EBNA2 responsive cis-element of the TP1 promoter.

Antigens, Surface↗
PubMed1993

[Progressive paralysis: prognostic indications by modern imaging procedures. A case report].

The case of a patient with early diagnosed neurosyphilis (general paresis) is presented. Modern neuroimaging techniques such as single photon emission computed tomography (SPECT) may give clues to the treatment outcome as early as 1 month after antibiotic treatment. Improvement of cognitive functions was accompanied by normalization of the initially altered P300-topography.

Brain Mapping↗
PubMed1992

Short-term assays for detection of conditional cancerogens. I. Construction of DR-CAT Raji cells and some of their characteristics as tester cells.

A number of agents including the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA) (TPA) can induce an abortive virus cycle in the EBV-non-producer Burkitt's-lymphoma line Raji. Two distant regions, DL and DR, of the EBV genome with almost complete homology carry strong promoters which are induced in an abortive or lytic cycle and additionally function as lytic origins of viral DNA replication. To set up a system in which the activity of EBV-inducing agents can be measured in a quantitative and reproducible fashion, we generated a cell line which carries multiple copies of a DR-promoter chloramphenicol-acetyltransferase (CAT) construct on an episomal vector. CAT activity is low in untreated cells, but high upon treatment of the cells with various EBV-inducing agents. Combinations of different agents can produce an over-additive effect. The Raji-DR-CAT cell line may provide a simple quantitative and reproducible test system for EBV-inducing agents, especially for tumor promoters which activate protein kinases C.

Carcinogens↗
PubMed1992

Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses.

To establish normal ranges for assessment of autonomic dysfunction, a battery of cardiovascular reflex tests was performed in 120 healthy subjects aged 15-67 years using a computer-based technique. Tests of heart rate variation (HRV) included 8 measures at rest: coefficient of variation (CV), root mean squared successive difference (RMSSD), spectral analysis of HRV in the low frequency, mid frequency, and high frequency bands in the supine and standing postures; 5 measures during deep breathing: CVb, RMSSDb, Expiration-Inspiration (E-I) difference, E/I ratio, and mean circular resultant of vector analysis; Valsalva ratio, and max/min 30:15 ratio. In addition, the change in systolic and diastolic blood pressure in response to standing and the diastolic blood pressure response to sustained handgrip were determined. The results of all measures, the blood pressure tests excepted, declined significantly with increasing age (r = -0.16 to -0.59; p less than 0.05). Moreover, RMSSD, RMSSDb, and E-I difference decreased considerably with increasing heart rate (r = -0.37 to -0.52; p less than 0.001). The longest and shortest R-R intervals in response to standing were distributed within beats 21-39 and 6-24, respectively. All tests were independent of sex. Log transformation was used to define the age-related lower limits of normal at the 2.3 centile for all tests of HRV, except for the E/I, Valsalva, and max/min 30:15 ratios. The results of these tests had to be analysed using a log(y-1) transformation. The intra-individual reproducibility determined on two consecutive days in 20 healthy subjects and 21 diabetic patients indicated that there were no major differences between the two groups regarding the day-to-day variation of test results, which was highest for the Valsalva ratio. We conclude that: (1) all indices of spectral and vector analyses of HRV are age-dependent and have the advantage of being independent of heart rate; (2) RMSSD, E-I difference, and the 30:15 ratio as it was used previously are not suitable for evaluation of autonomic dysfunction in diabetes; (3) log(y-1) transformation is required to determine age-dependent normal ranges and reproducibility for the three ratios.

Adolescent↗
PubMed1992

[Remission of schizophreniform psychosis after brain tumor surgery].

A 19-year-old female was admitted to hospital due to a schizophrenia-like psychosis of the paranoid type including delusions and various hallucinations. Neurologically she only showed tics of the eyebrows with increased eye blinking. 30 months before an astrocytoma located on the left basal temporal lobe had been resected after the patient suffered from several psychomotor and two grand mal seizures. Following post-operative anticonvulsant therapy seizures had completely disappeared and the patient had been free of symptoms of any kind. After the acute onset of the psychosis another follow-up MRI of the brain using coronary sections revealed a small relapse-tumor. Symptoms disappeared after high-dose neuroleptic therapy. Finally another surgical intervention led to a lasting remission of the psychotic symptomatology (so far 18 months). Postoperatively neuroleptics could be discontinued. Clinical picture and MRI findings will be discussed with a focus on possible etiological factors in schizophrenia.

Adult↗
PubMed1991

[Severe late-onset dystonia while on fluspirilene].

Shooting, tonic cramps of the neck muscles with jolt-like contractions in the mouth and jaw regions and propulsive movements of both arms developed in a 25-year-old woman who, over a period of six months, had been given nine intramuscular injections of the depot neuroleptic fluspirilene, 1.5 mg each, because of apathy and depression. Treatment with biperiden (up to 20 mg daily) and benzodiazepines was unsuccessful, while tiapride (up to 1000 mg daily) brought about slight improvement and 15 mg haloperidol achieved complete remission. However, distinct parkinsonian features developed. Slow gradual reduction of the haloperidol dose again led to extrapyramidal motor symptoms, even when tiapride or bromocriptine was given as well. After six months' administration of clozapine, up to 500 mg daily, and gradual dose reduction all symptoms fully regressed. This case demonstrates that the risk of extrapyramidal motor abnormalities from "neuroleptic anxiolysis" should not be underestimated.

Acute Disease↗
PubMed1991

A double-blind comparative multicentre study of controlled-release remoxipride, immediate-release remoxipride and haloperidol in schizophrenia.

A double-blind multicentre study comparing the efficacy and safety of remoxipride in controlled-release formulation (REM-CR), given once a day, and immediate-release formulation (REM-IR) and haloperidol, given twice daily, was conducted in patients with schizophrenic illness. In total, 150 inpatients were randomized: 49, 51 and 50 in the REM-CR, REM-IR, and haloperidol groups, respectively. The mean daily dose of REM-CR during the last week of treatment was 361 mg, that of REM-IR 332 mg. In the haloperidol group the corresponding dose was 12.5mg per day. The study treatment period was four weeks. The median BPRS total score was 37.5 in the REM-CR group at start of treatment, and 14.5 at last rating (n = 38). For the REM-IR group and the haloperidol group the corresponding figures were 36.0 and 38.0 at start of treatment and 18.0 (n = 43) and 16.5 (n = 40) at last rating. No statistically significant differences were found between the treatments. Therapy-emergent extrapyramidal symptoms (Simpson & Angus rating scale) were significantly (p less than 0.05) more frequent and more severe during haloperidol than during REM-CR and REM-IR treatment, despite significantly higher concurrent use of anticholinergic drugs in the haloperidol group.--REM-CR was comparable in efficacy and tolerability to REM-IR. The tolerability profile favoured both remoxipride formulations over haloperidol. Evaluation of the clinical chemistry, haematology, and cardiovascular data showed no clinically significant deleterious effects on any organ system for either drug.

Adolescent↗
PubMed1991

Epstein-Barr virus nuclear antigen 2 activates transcription of the terminal protein gene.

Transcription of the terminal protein (TP) gene of Epstein-Barr virus (EBV) in Burkitt's lymphoma cells, in EBV-negative Burkitt's lymphoma cells converted with transformation-defective (P3HR1) and transformation-competent (B95-8, AG876) EBV strains, and in EBV-immortalized cell lines was studied. A TP1 cDNA probe spanning the boundary between exons 1 and 2 and discriminating between TP1 and TP2 transcripts was used for S1 analysis. TP RNA expression varied widely in Burkitt's lymphoma cells. TP-specific transcripts were not detectable or only hardly detectable in Burkitt's lymphoma cells with the group I phenotype (CD10+ CD77+ CD21- CD23- CD30- CDw70-) as well as in P3HR1 virus-converted Burkitt's lymphoma lines. TP expression was high in Burkitt's lymphoma lines with the group II and group III phenotypes (CD21+ CD23+ CD30+ CDw70+), in B95-8 and AG876 virus-converted lines, and in EBV-immortalized cells. Detection of TP1 RNA correlated with EBNA2 expression. TP1 transcription was shown to be dependent on EBNA2 expression by stable transfection of an EBNA2 expression vector into P3HR1 virus-converted BL41 cells. EBNA2 is activating the TP1 as well as the TP2 promoter, as shown by the analysis of TP promoter-chloramphenicol acetyltransferase constructs transiently transfected into EBNA2-positive and EBNA2-negative Burkitt's lymphoma cells.

Antigens, Viral↗
PubMed1991

[Psychometric studies of performance deficits in acute schizophrenic patients with special reference to gender].

19 male and 18 female schizophrenic inpatients were examined on cognitive, motor and sensorimotor performance and visual and speech related intellectual ability at the beginning and end of a therapeutic period of 4 weeks on the average. Speed of sensorimotor reaction time revealed a higher performance level with regard to male as compared to female patients. Reverse effects could be demonstrated with respect to precise motor reactions (pegboard). Starting at a higher level of performance female had an important decrease. Considering speed of unprecise movements (tapping) and tremor-parameter (steadiness) impairment of performance occurred in time course for both male and female. Especially simple tasks demanding speed to solve the problem and left-handed requirement are solved in a lower degree indicating impaired reception of information and hemispheric hyperactivation.

Acute Disease↗
PubMed1990

Psychometric alterations in treatment with the MAO-A-inhibitor moclobemide.

Two groups of depressed patients were treated either with a selective MAO-A-inhibitor, moclobemide (n = 13) or a tetracyclic antide-pressant, maprotiline (n = 18), in a 28 days lasting double blind investigation. Before and after treatment psychopathologic symptoms were rated, motor performance was proven, and acoustic and visual sensomotoric performance were investigated. Deterioration of psychomotor performance were seen in patients without amelioration of their psychopathologic symptoms, especially when treated with moclobemide. These findings were regarded as a hint that possibly the therapeutic agent interacts with the wrong transmitter system and perhaps this is the reason for the deterioration of psychomotor functions.

Benzamides↗
PubMed1990

Clinical, biochemical and psychometric findings with the new MAO-A-inhibitors moclobemide and brofaromine in patients with major depressive disorder.

N = 53 inpatients with major depressive disorder have been treated with the reversible, selective MAO-A-inhibitors moclobemide (double-blind versus maprotiline) and brofaromine (open study), respectively. Clinically, significant improvement of depression and an activating profile of action could be observed, typical side effects were sleep disturbances, agitation and weight loss. The neurobiochemical data showed an increase of noradrenaline plasma concentrations under treatment with moclobemide. Visual reaction times improved with antidepressant treatment. MAO-A inhibitors proved to be effective antidepressants in the treatment of hospitalized patients with predominantly endogenous depressions.

Benzamides↗
PubMed1990

Brofaromine (CGP 11 305 A): estimation of plasma concentrations by a biologic technique as compared to liquid chromatography.

In an open clinical trial 13 depressives significantly improved under the reversible and selective type-A monoamine oxidase (MAO) inhibitor brofaromine. The inhibitory potency of deproteinated plasma on a crude MAO preparation from human placenta was measured as a parameter for plasma brofaromine. There were no significant differences in plasma MAO inhibitory potency between responders (improvement greater than 50%; n = 5) and non-responders. 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 biologic assay, however, overestimated brofaromine by a factor of two in acute kinetic experiments with healthy volunteers as compared to a chromatographic technique, although both methods significantly correlated (r = 0.928).

Adult↗
PubMed1990

Alpha 2-adrenoceptor responsivity in depression: effect of chronic treatment with moclobemide, a selective MAO-A-inhibitor, versus maprotiline.

The effect of chronic treatment with the selective and reversible MAO-A-inhibitor moclobemide (MOC) vs. the norepinephrine reuptake inhibitor maprotiline (MAP) on alpha 2-adrenoceptor responsivity was studied by clonidine (CLON)-evoked growth hormone (GH) release in major depressive disorder. Compared to matched controls the depressed patients showed attenuated CLON-induced GH responses before treatment with MOC or MAP. Chronic treatment with both MOC and MAP significantly improved the depressive symptomatology. Although a trend toward increased GH responses to CLON was demonstrated after treatment in both groups, neither MOC nor MAP had a complete effect on restoration of alpha 2-adrenoceptor responsivity. No difference in insulin-like growth factor I (IGF-I) plasma concentrations before and after treatment with MOC or MAP was found. Our results support the view that antidepressants with different mechanisms of action may be capable of restoring alpha 2-adrenoceptor function during recovery from a major depressive episode.

Adult↗