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Biomedical subjects

G Laux

Publications and source records attributed to G Laux.

At least 55 records · Page 3Linked to original sources

[Echocardiography values in the halothane uptake phase--measurement by acoustic quantification and manual evaluation].

In 35 ASA group I and II patients we investigated the influence of haemodynamic changes induced by increasing concentrations of halothane (from 0.0 to 0.6% halothane in 70% N20) on parameters of transesophageal echocardiography (TEE). Measurements by TEE were taken in manual and automatic boundary detection mode. In manual mode the left ventricular endsystolic area (ESA) increased significantly (+16.3%) and the fractional area change (FAC) decreased significantly (-14.9%). There was no significant change of left ventricular end diastolic area (EDA). In the automatic mode there was a significant increase of ESA and EDA (+13.8%; +6.0%) and a significant decrease of FAC (-10.9%). Peak ejection rate (PER) and peak filling rate (PFR) which were also assessed in automated mode decreased significantly (-10.0%; -5.7%) under halothane. No change occurred with manually determined left ventricular endsystolic wall stress (LVEWS). The endsystolic quotient decreased significantly both in manual and automated mode during halothane (-28.3%; -29.9%). No significant difference existed between TEE measurements under apnoea versus under controlled ventilation (except for EDA in automated mode). We conclude that there is no need for apnoea conditions for TEE measurements. In conclusion, TEE proves a useful monitoring system in anesthesia which enables the investigator to assess the negative inotropic effect of halothane. Problems in its practical usage are due to the wide variation of TEE measurements.

Adult↗

[Neuroleptic malignant syndrome from treatment with antidepressives].

The neuroleptic malignant syndrome (NMS) is a rare complication in the treatment of neuroleptics. The pathophysiology is not fully known. A dopaminergic transmission block in the basal ganglia and the hypothalamus is thought to be the pathophysiological mechanism of NMS. There are some findings against the single role of dopamine receptor blockade: NMS is rare under neuroleptic treatment, although a strong dopamine receptor blockade is found even with a low dosis of neuroleptics. NMS can develop even after longterm treatment with neuroleptics and is not improved by dopamine agonists within the expected period. NMS may even develop when neuroleptics are reduced. Several cases have been reported of NMS precipitated by medication without a direct effect on dopaminergic system. Only rare case reports describe NMS under antidepressants. We report on all cases of NMS associated with antidepressants and present the different pathophysiological hypotheses on the precipitation of NMS.

Adult↗

Continuous cardiac output monitoring during adult liver transplantation: thermal filament technique versus bolus thermodilution.

UNLABELLED: Continuous thermodilution (CT) using a pulmonary artery (PA) catheter with a thermal filament has the potential for intraoperative on-line monitoring of cardiac output. Liver transplantation frequently requires rapid fluid administration and often includes the use of an extracorporeal veno-venous bypass. To assess the agreement between CT and bolus thermodilution (BT) in such a setting, we conducted a prospective intraoperative study in 14 liver transplant patients. Throughout the operation, CT cardiac output was recorded and paired with BT measurements taken every 30 min and whenever indicated for clinical reason. Corresponding data were assigned to acquisition periods when patients were on or off veno-venous bypass (flow rate 2.5 +/- 0.2 L/min) and were discriminated by the various range of intravenous infusion rates (< 150 mL/h, 150-1000 mL/h, 1000-2000 mL/h, and 2000-4000 mL/h) and the magnitude of cardiac output (< or = 7.5 L/min, 7.5-10.0 L/min, > 10.0 L/min). A total of 270 data pairs was obtained and examined by analysis of agreement (mean difference +/- SD), variance, error, and weighted regression. Trend analysis was performed for significant CT and BT cardiac output changes, defined as changes greater than 15%. Agreement of both methods was best at peripheral intravenous fluid infusion rates < or = 1000 mL/h and BT cardiac output > 10 L/min (0.0 +/- 0.6 L/min) and was unaffected by veno-venous bypass. Discrepancy was most evident at intravenous fluid infusion rates > 2000 mL/h and BT cardiac output < or = 7.5 L/min (2.1 +/- 1.7 L/min). Correlation of CT and BT cardiac output was excellent (r = 0.95, P < 0.001) for combined data from all patients. Changes in CT cardiac output > 15% (n = 116) correctly indicated the direction in 93% of BT cardiac output changes and were 74% sensitive and 75% specific for significant BT cardiac output changes. The thermal filament technique enhances the usefulness of PA catheterization during liver transplantation but reflects BT cardiac output with clinically acceptable error only at low peripheral intravenous fluid infusion rates. IMPLICATIONS: Cardiac output determines organ perfusion. In clinical practice, it is measured by intermittent thermodilution using right heart catheterization. This intraoperative study compared the intermittent method with a technique based on continuous thermodilution. The new technique provides logistical advantages and challenges the accuracy of the intermittent method during liver transplantation.

Adult↗

[Pharmacotherapy].

The high prevalence of anxiety disorders implies the necessity of adequate treatment by GPs. Regarding psychopharmacological treatment benzodiazepines and antidepressants are the drugs of first choice, low potency neuroleptics, beta-blockers as well as the herbal medicine kava-kava may be indicated in special cases (e.g. low degree of anxiety, abuse or tolerability problems). The separation of generalized anxiety disorder from panic disorder seems to be essential due to treatment implications: antidepressants like Imipramine or SSRIs are the drugs of choice in the latter case. Hints regarding handling as well as possible side-effects of the different psychotropics are given, the combination with psychotherapy (relaxation techniques, behaviour therapy) is recommended being the best way of effective treatment.

Anti-Anxiety Agents↗

[Acoustic hallucinations as a symptom of a REM sleep-associated parasomnia].

This 52-year-old man suffered from auditory hallucinations that occurred during brief episodes of sleep paralysis at the end of REM sleep periods. During these episodes the patient experienced a dissociated state of consciousness with REM sleep intrusions into wakefulness. The occurrence of this mixed state, and of excessive sleep-onset REM periods during daytime polysomnography (MSLT = Multiple Sleep Latency Test), point to a disorder of REM sleep generation. The existence of narcolepsy could be ruled out. The observation of REM sleep-associated hallucinations has been reported earlier. In the presented polysomnographic sleep studies the existence of a REM sleep associated parasomnia characterised by hallucinations and sleep paralysis could be confirmed.

Acoustic Stimulation↗

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↗

Lymphocytopenia and thrombocytopenia during treatment with risperidone or clozapine.

The atypical antipsychotic clozapine is associated with several well-known abnormalities of blood cell count, whereas only rare reports are associated with the neuroleptic risperidone. This report describes lymphocytopenia and thrombocytopenia under treatment with risperidone which continued after changing to clozapine without other clinically significant abnormal hematological parameters. Within one week after discontinuation of both neuroleptics abnormalities of blood cell count reversed to the initial values. Abnormalities of lymphocytes or thrombocytes are rare side-effects under treatment with risperidone or clozapine.

Adult↗

On-line estimation of left ventricular stroke volume using transoesophageal echocardiography and acoustic quantification.

We have examined the usefulness of transoesophageal echocardiography (TOE) and automated endocardium detection for on-line calculation of left ventricular stroke volume. In 12 of 15 patients undergoing abdominal surgery, stroke volume was derived continuously from the multiple discs (MD) and area-length (AL) methods and compared with stroke volume calculated by thermodilution. In 10 patients (80%), more than three manipulations of the ultrasound transducer were required before measurements. Linear regression analysis of automated TOE methods and thermodilution revealed weak correlations (r < 0.75) for stroke volume (114 matched pairs) and its changes (105 matched pairs). Correlation of percentage changes in stroke volume calculated by thermodilution with those derived from MD (r = 0.85) and AL (r = 0.79) was better. Changes in MD (AL) derived stroke volume by more than 20% identified changes in thermodilution-derived stroke volume greater than 20% (n = 57) with a sensitivity of 74% (70%) and a specificity of 82% (79%). Signal instability, lack of accuracy and only a moderate trend capability currently limit the intraoperative usefulness of automated TOE techniques for continuous estimation of stroke volume from a single long-axis plane.

Abdomen↗

The latent membrane protein 2 gene of Epstein-Barr virus is important for efficient B cell immortalization.

The viral latent membrane proteins 2 (LMP2) of Epstein-Barr virus (EBV) were analysed genetically to evaluate their role in B cell immortalization. LMP2 is transcribed as two differently spliced mRNAs which code for the LMP2A and -B proteins, also called terminal protein-1 and -2. LMP2A and -B are found in latently infected, growth-transformed B lymphocytes in vitro, in different human tumours, and in latently infected B cells in vivo. Two different approaches were used to generate EBV mutants in which the second, third and part of the fourth exon of the LMP2 gene were deleted by insertion of a marker gene. Initially, conventional homologous recombination in a Burkitt's lymphoma cell line (P3HR1) between the endogenous EBV genome and an introduced plasmid was used to generate EBV mutants. This experiment identified LMP2 as dispensable for B cell immortalization as has been reported. In a second approach, the same LMP2 mutant gene was analysed in the context of a mini-EBV plasmid. These are E. coli constructs that are sufficient when packaged into an EBV coat both to initiate and to maintain proliferation of infected B cells. In comparison with a fully competent mini-EBV, LMP2- mini-EBVs were found to be greatly reduced in their capacity to yield immortalized B cell clones. This finding confirmed the initially observed bias against LMP2- B cell clones, most of which were found to be coinfected with complementing P3HR1 virus. These results indicate that LMP2 contributes to the efficiency of B cell immortalization and that the LMP2s phenotype is auxiliary in nature.

B-Lymphocytes↗

Antidepressants and drug-metabolizing enzymes--expert group report.

Antidepressant drugs are extensively metabolized. Consequently, the biotransformation pattern of antidepressants has an important influence on their clinical properties, i.e., pharmacokinetics, toxicity, drug-drug interactions, side-effect profile and last but not least therapeutic efficacy. It was against this background that a multidisciplinary group of experts discussed the clinical relevance of the rapidly increasing body of knowledge of antidepressant-metabolizing enzymes. The variability of the response of a given individual to an antidepressant is determined genetically and by the environment. Genetic polymorphism of drug-metabolizing enzymes and inhibition by other substrates may affect the enzymatic biotransformation of antidepressants. In vitro assay techniques allow an estimation of the potential variability in clinical response to antidepressants and a reasonable prediction of the drug-drug interaction patterns. The results of in vitro tests should therefore be considered early in the development of an antidepressant as a background for designing clinical studies (treatment schedules and dosing). Physicians should have an understanding of the relevance of genetic polymorphism for clinical practice. Education is needed in order to fill the existing gaps in knowledge about antidepressant-enzyme interactions and their application in daily treatment practice. The information on potential drug interactions determined by genetic polymorphism and based on studies with enzymes should be increasingly contained in drug compendia.

Antidepressive Agents↗

Identification of latent membrane protein 2A (LMP2A) domains essential for the LMP2A dominant-negative effect on B-lymphocyte surface immunoglobulin signal transduction.

Epstein-Barr virus (EBV) recombinants which carry three different deletion mutations in the LMP2A cytoplasmic amino-terminal domain were constructed. The presence of each mutation, LMP2A delta 21-36, LMP2A delta 21-64, and LMP2A delta 21-85, in EBV-infected transformed lymphoblastoid cell lines was confirmed by PCR analysis and Southern blot hybridization. Confirmation of mutant LMP2A protein expression was by immunofluorescence and immunoblotting with a newly identified rat monoclonal antibody that recognizes each of the LMP2A deletion mutations. Lymphoblastoid cell lines infected with recombinant EBV DNAs containing the mutations were analyzed for loss of LMP2A's dominant-negative effect on surface immunoglobulin signal transduction by monitoring induction of tyrosine phosphorylation, calcium mobilization, and activation of lytic replication following surface immunoglobulin cross-linking. Domains of LMP2A important for induction of tyrosine phosphorylation, calcium mobilization, and activation of lytic replication were identified.

Amino Acid Sequence↗

[Concept for a behavior therapy treatment program in primary insomnia].

The need to find effective non-drug treatments for primary insomnia has lead to the application of a variety of psychological approaches. However, one difficulty in the treatment of insomnia is the variety of types, such as sleep-onset and sleep-maintenance insomnia, as well as individual differences in the specific antecedents and conditions maintaining poor sleep. There is no consensus regarding treatment selection. This paper documents the authors' work in formulating a group intervention approach for patients suffering from primary insomnia. A multiple treatment approach was used to provide flexibility. The group treatment consists of the following elements: (1) stimulus control, (2) restriction of time in bed, (3) general education regarding sleep and sleep hygiene, (4) progressive muscle relaxation and (5) cognitive strategies aimed at reducing stimulating mental activities. A description of the techniques used and the structure and process of the group model used is provided.

Adult↗

Epstein-Barr virus nuclear antigen 2-estrogen receptor fusion proteins transactivate viral and cellular genes and interact with RBP-J kappa in a conditional fashion.

Epstein-Barr virus nuclear antigen 2 (EBNA2) is a transcriptional activator of viral and cellular genes involved in B cell transformation by EBV and is targeted to EBV responsive promoters through interaction with cellular DNA binding proteins such as RBP-J kappa. To develop a conditional system in which the function of EBNA2 can be switched on and off, we have fused the hormone binding domain of the estrogen receptor to the N- or C-terminus of EBNA2. Here we show that after transient or stable transfer of these chimerical EBNA2 genes into human B cell lymphoma lines, transactivation of LMP1, TP1, and TP2 promoter constructs, expression of the cell surface markers CD21 and CD23, and binding of EBNA2 to its cellular partner RBP-J kappa are dependent on the presence of estrogen. The EBNA2 fusion proteins proved to be virtually inactive in the absence of hormone.

Antigens, Viral↗

Clinical characteristics of outpatients with chronic major depression.

A cross-sectional evaluation of 243 unipolar, nonpsychotic outpatients with major depression was conducted. All subjects were diagnosed by RDC with SADS-L structured interviews. Diagnoses included RDC primary/secondary, RDC endogenous/nonendogenous and Winokur's family-history subtypes. Symptom severity was assessed by the 17-item Hamilton Rating Scale for Depression. Chronic depression was defined as the current episode of major depression lasting at least 2 years, corresponding to DSM-III-R and -IV criteria. Patients with chronic depression (n = 64) were compared with those with nonchronic depression (n = 179). Chronicity was not related to gender, symptom severity, prior length of illness, age at onset of illness, RDC endogenous/nonendogenous, RDC primary/secondary or Winokur's family-history subtypes. Those with chronic depression were older and had fewer major depressive episodes than the nonchronic group. That the chronic group had fewer total episodes of depression than the nonchronic group, but a similar age at onset, is consistent with the notion that patients in a current chronic episode have characteristically longer depressive episodes throughout the course of their illness. Those with chronic episodes may be subject to psychological, biological and/or sociocultural factors that preclude an earlier episode remission for these individuals.

Adult↗

[Current status of treatment with benzodiazepines].

Benzodiazepines are the psychotropics most frequently prescribed despite an impressive reduction in use in the last 10 years. Their main pharmacodynamic effects (anxiolytic, sedative, anticonvulsive, muscle-relaxing, amnestic) are the basis for various therapeutic applications and indications. The most important differences among the variety of benzodiazepines are pharmacokinetic ones (elimination half-life, formation of pharmacologically active metabolites). Established indications are anxiety and sleep disorders, seizures, epilepsy, premedication and sedation in emergency medicine. In recent years it has also been proven to be effective in the treatment of panic disorder and catatonia. Among the side effects seen most frequently are impairments of cognitive and psychomotor function as well as rebound phenomena. Discussions have recently focused on the incidence of abuse and dependence as well as case reports on severe amnesia. Alternative medications like neuroleptics in low dosage and antidepressants seem to be predominantly unfavorable due to the fact that they are tolerated less well and sometimes have severe side effects. A clear-cut indication and time-limited prescription can reduce the number of benzodiazepine long-term users, and a comprehensive treatment concept must be the basis of rational prescription of benzodiazepines. The positive benefit-risk ratio as well as research perspectives [identification of receptor subtypes, development of highly selective ligands and partial (inverse) agonists] are reasons for assuming that the era of the benzodiazepines has not come to an end.

Anti-Anxiety Agents↗

The Spi-1/PU.1 and Spi-B ets family transcription factors and the recombination signal binding protein RBP-J kappa interact with an Epstein-Barr virus nuclear antigen 2 responsive cis-element.

Epstein-Barr virus (EBV) immortalizes resting human B cells very efficiently in vitro. The EBV nuclear protein EBNA2 is absolutely required for this process. It also activates transcription of cellular, as well as viral, genes. It is assumed that EBNA2 contributes to B cell immortalization by its transactivating potential, since its transforming and transactivating functions could not be separated. Mutational analysis of the 80 bp EBNA2 responsive cis-element within the viral bidirectional LMP/TP2 promoter region identified two sequence elements, which are both essential for transactivation by EBNA2. These sequences harbour putative consensus binding sites for Spi-1 oncoprotein and recombination signal binding protein RBP-J kappa, the homologue of Drosophila Suppressor of Hairless. Electrophoretic mobility shift assays demonstrated the high affinity binding of Spi-1 and Spi-B, both members of the Ets family of transcription factors, to one sequence element. The other element bound RBP-J kappa with low affinity. In addition, co-transfections showed that the replacement of the Spi-1/Spi-B binding site in the bi-directional LMP/TP2 promoter by the analogous SV40 Spi-1 responsive element did not impair its function on EBNA2-mediated transactivation. It is concluded that the transcriptional regulators Spi-1 and Spi-B as well as RBP-J kappa play an essential role in transactivating the LMP/TP2 promoter by EBNA2 and therefore in the immortalization of B cells by EBV.

Antigens, Viral↗