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S Behrens

Publications and source records attributed to S Behrens.

At least 91 records · Page 5Linked to original sources
PubMed1996

Structure-activity relationship of the ring portion in backbone-cyclic C-terminal hexapeptide analogs of substance P. NMR and molecular dynamics.

The conformations of two backbone-cyclized substance P analogs were derived from homo- and heteronuclear NMR measurements and molecular dynamics simulations carried out in DMSO. The analogs contain subtle variations in the ring chemistry and are compared with biologically active analogs previously examined. The correlation between conformation and activity is used to gain insight into the conformational requirements from the pharmacophore.

Animals↗
PubMed1996

Myocardial vulnerability to T wave shocks: relation to shock strength, shock coupling interval, and dispersion of ventricular repolarization.

INTRODUCTION: Induction of ventricular fibrillation (VF) by T wave shocks is of clinical interest due to the correlation between the upper limit of vulnerability (ULV) and the defibrillation threshold (DFT). However, the ULV has not yet been defined precisely in reference to the entire "area of vulnerability" (AOV), which is defined bifunctionally by both shock strengths and shock coupling intervals, nor has it been related to the dispersion of ventricular repolarization, considered to be an important determinant of vulnerability. METHODS AND RESULTS: In 11 isolated perfused rabbit hearts immersed in a tissue bath containing a 3-lead ECG recording system and two opposite plate electrodes for field shock administration, 7 monophasic action potentials (MAPs) were recorded simultaneously from different epicardial and endocardial regions of the right and left ventricles. An average of 90 +/- 25 monophasic waveform shocks of varying shock strengths and coupling intervals were delivered to each heart to determine the horizontal and vertical boundaries of the AOV. The AOV approximated a rhomboid with homogenous VF inducibility. The ULV and lower limit of vulnerability (LLV) represented discrete corners of the AOV with significant changes in VF inducibility if either shock coupling intervals or shock strength were changed by only 10 msec or 10 V, respectively (P < 0.001). The ULV occurred at 7 +/- 10 msec shorter coupling intervals than the LLV (P < 0.05), and VF-inducing shock strengths at the left corner of the AOV were 50 +/- 67 V higher as compared to the right corner (P < 0.01). The maximal range of VF-inducing coupling intervals coincided (within < 2 msec) with the dispersion of MAPs at 70% repolarization, and the ULV coupling interval coincided (within < 4 msec) with the longest repolarization at 50%. CONCLUSIONS: (1) VF vulnerability to monophasic T wave shocks is defined by an AOV that has the shape of a leftward tilted rhomboid. (2) Both the ULV and LLV are sharply defined upper and lower corners of the AOV rhomboid. (3) The width of the AOV corresponds to the dispersion of ventricular repolarization at the 70% level. (4) Considering the dispersion of ventricular repolarization may yield more precise ULV determinations and a better understanding of the correlation between the ULV and DFT.

Action Potentials↗
PubMed1996

[In vivo registration of monophasic action potentials--new possible applications in clinical electrophysiology].

Monophasic action potential (MAP) recordings have gained a more important role during the recent years. A new application for their use in the clinical laboratory is the precise differentiation between ventricular tachycardias and ventricular fibrillation. A correct diagnosis of the arrhythmic episode may be of relevance for the determination of the defibrillation threshold during implantation and testing of implantable cardioverter defibrillators. Diagnostic studies and ablation procedures of triggered arrhythmias represent another indication for MAP recordings. The focus of enhanced automaticity can be located by the detection of afterdepolarizations which allows a reliable ablation using a MAP-ablation combination catheter. Recently, a new phenomenon has been reported regarding the relationship between ventricular repolarization and excitability during programmed electrical stimulation in humans. Each additional extrastimulus was able to capture the myocardium at a less complete repolarization level than the previous one. This "facilitation of excitability" phenomenon or "encroachment" was correlated with the initiation of ventricular tachyarrhythmias. The involved mechanism can be modulated pharmacologically and might therefore play a role in the antiarrhythmic treatment of patients with ventricular arrhythmias.

Cardiac Pacing, Artificial↗
PubMed1995

Circadian variation of sustained ventricular tachyarrhythmias terminated by appropriate shocks in patients with an implantable cardioverter defibrillator.

To determine the circadian variation of sustained ventricular tachyarrhythmias, 78 consecutive patients with an implanted cardioverter defibrillator were analyzed with regard to the occurrence of spontaneous shock episodes during a mean follow-up period of 18 +/- 12 months. In 39 patients 207 shock episodes that terminated potentially life-threatening ventricular tachyarrhythmias could be related to an exact time of onset. A circadian variation (p < 0.001) of these events was demonstrated, with a primary morning peak between 7 hours and 11 hours and a secondary, much smaller peak between 16 hours and 20 hours. This finding indicates the relevance of endogeneous or exogeneous triggers in the cause of malignant arrhythmias that potentially lead to sudden cardiac death. Subgroup analyses revealed an association of the circadian pattern to the New York Heart Association functional classification, indicating perhaps a different role of triggers in different patient populations.

Aged↗
PubMed1995

Management and prophylaxis of life-threatening arrhythmias--recent achievements.

Patients resuscitated from ventricular fibrillation or haemodynamically compromising ventricular tachycardias have an unfavourable clinical outcome. Moreover, there is no evidence that the prognosis can be improved by empirical use of antiarrhythmic therapy. Therapy guided by electrophysiological stimulation or long-term ECG identifies a subgroup of patients with a better outcome (in whom arrhythmias are suppressed) and a subgroup with a bad prognosis (in whom arrhythmias are not suppressed). However, this does not say that antiarrhythmic drugs actually improve the outcome. It may simply identify patients with an intrinsically good prognosis, regardless of whether they receive drug treatment. Because retrospective trials have reported that empiric administration of amiodarone provides long-term control in two-thirds or more of patients with refractory ventricular tachyarrhythmias, a direct comparison with other drugs guided by electrophysiological testing or long-term ECG was performed (CASCADE-study). Six-years survival was 41% under amiodarone versus 20% with other drugs. Even those conventionally treated patients, whose inducible arrhythmias were suppressed, had a trend toward a worse prognosis compared to those who were inducible and treated empirically with amiodarone. However, the high recurrence rate of arrhythmic events demonstrates the limitation of any antiarrhythmic drug, irrespective of the drug used and irrespective of whether it is given empirically or in a study.

Anti-Arrhythmia Agents↗
PubMed1995

Expression of heat shock genes in Clostridium acetobutylicum.

Characterization of the heat shock response in Clostridium acetobutylicum has indicated that at least 15 proteins are induced by a temperature upshift from 30 to 42 degrees C. These so-called heat shock proteins include DnaK and GroEL, two highly conserved molecular chaperones. Several genes encoding heat shock proteins of C. acetobutylicum have been cloned and analysed. The dnaK operon includes the genes orfA (a heat shock gene with an unknown function), grpE, dnaK, and dnaJ; and the groE operon the genes groES and groEL. The hsp18 gene coding for a member of the small heat shock protein family constitutes a monocistronic operon. Interestingly, the heat shock response in this bacterium is regulated by a mechanism, which is obviously different from that found in Escherichia coli. So far, no evidence for a heat shock-specific sigma factor of the RNA polymerase in C. acetobutylicum has been found. In this bacterium, like in many Gram-positive and several Gram-negative bacteria, a conserved inverted repeat is located upstream of chaperone/chaperonin-encoding stress genes such as dnaK and groEL and may be implicated as a cis-acting regulatory site. The inverted repeat is not present in the promoter region of hsp18. Therefore, in C. acetobutylicum there are at least two classes of heat shock genes with respect to the type of regulation. Evidence has been found that a repressor is involved in the regulation of the heat shock response in C. acetobutylicum. However, this regulation seems to be independent of the inverted repeat motif, and the mechanism by which the inverted repeat motif mediates regulation remains to be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

[Cerebral ischemia during implantation of automatic defibrillators].

In order to study the influence of repetitive episodes of ventricular fibrillation (VF) during defibrillator implantation on the electrical activity of the brain, we performed an electroencephalographic (EEG) monitoring during implantation procedure in 18 patients. For defibrillation threshold testing 62 episodes of VF (1-6 episodes per patient) were induced. The mean duration of VF was 20 +/- 12 s; the mean duration of hypotension during an episode (defined as a mean arterial pressure of 50 mm Hg or less) was 33 +/- 16 s. EEG monitoring was performed using the International 10-20 System. The duration of cardiac arrest-related EEG alteration was assessed by an experienced neurologist and could be determined in 41 test-episodes; in 21 episodes analysis was not possible due to poor recordings. Ischemia-related EEG changes started 7.8 +/- 4.6 s after VF induction and lasted 64 +/- 49 s (range, 12-240). The duration of EEG alteration was significantly (p < .001) correlated with the duration of VF episodes (r = .71) and the associated hypotension (r = .82). With regard to patients the duration of ischemia related EEG changes also correlated significantly (p = .001) with the individual cumulative duration of VF (r = .85) and the associated hypotension (r = .88). In females EEG changes lasted longer than in males (p = .03); this finding, however, was only based on 2 women. Other clinical parameters, such as patient age, degree of congestive heart failure, left ventricular ejection fraction, stroke volume and cardiac index, the order of episodes within the testing sequence, and the time interval between episodes did not correlate with the duration of EEG alteration after VF induction. The duration of ischemia-related EEG alteration during VF episodes depends on the duration of cardiac arrest. In females EEG changes tended to last longer than in males, however, this finding has to be confirmed. An association with other clinical parameters has not been observed. Limitation of VF duration appears to be the most important factor to avoid prolonged cerebral ischemia.

Adult↗
PubMed1994

Mannose transporter of Escherichia coli. Backbone assignments and secondary structure of the IIA domain of the IIABMan subunit.

The mannose transporter of Escherichia coli consists of two transmembrane and one peripheral protein subunit. The complex acts by a mechanism which couples translocation of the substrate with substrate phosphorylation. The peripheral IIABMan is a homodimer. The IIABMan monomer itself contains two domains which are linked by an Ala-Pro-rich hinge and which are both transiently phosphorylated at histidyl residues. The IIA and IIB domains can be separated by limited proteolysis. The IIA domain has a dimer molecular mass of 2 x 14 kDa. Almost complete 1H, 13C, and 15N NMR assignments of the backbone resonances of IIAMan have been achieved using 3D and 4D double-and triple-resonance techniques. Secondary structure elements were derived from NOE data. The IIA domain consists of a central beta-sheet of four parallel and one antiparallel strand (strand order 5 4 3 1 2) with helices on both sides of the sheet. The active-site His-10 is located in a loop at the C-terminus of beta-strand 1. This loop and the loop after strand 3 are at the topological switch point of the sheet.

Amino Acid Sequence↗
PubMed1994

Ventricular fibrillation related to coronary spasm in patients without significant coronary or other structural heart disease.

We present three patients without significant coronary or other structural heart disease who were resuscitated after ventricular fibrillation attributed to coronary spasm. Angina pectoris was present in two of the cases and silent myocardial ischemia in the third. All patients were given calcium antagonists at discharge. A defibrillator was also implanted in the patient with silent myocardial ischemia because further episodes of ischemia would probably have occurred without premonitory symptoms. Coronary spasm might be a mechanism of ventricular fibrillation in patients without significant structural heart disease. Diagnostic tests should therefore be performed to confirm or exclude coronary spasm in such cases. The implantation of an automatic defibrillator seems justified in selected patients with documented coronary spasm, silent myocardial ischemia, and associated sustained ventricular tachyarrhythmia, although prospective studies are not yet available.

Adult↗
PubMed1994

Effects of zotepine, haloperidol and clozapine on MK-801-induced stereotypy and locomotion in rats.

In the present study we compared the effects of the atypical neuroleptic zotepine to haloperidol and clozapine on stereotypies and locomotion induced in rats by the N-methyl-D-aspartate (NMDA) antagonist MK-801. Zotepine caused a dose-dependent reduction of MK-801-induced stereotypies and locomotion. Zotepine at a dosis of 2.5 mg/kg body weight showed a similar effect to 0.25 mg/kg haloperidol in reducing stereotypies and locomotion. Clozapine (5.0 mg/kg) reduced significantly locomotion and non-significantly stereotypies. These results add support to the assumption that MK-801-induced behavior provides an adequate animal model to test the potential efficacy of typical and atypical neuroleptics in the treatment of psychoses.

Animals↗
PubMed1994

The epidemiology of early schizophrenia. Influence of age and gender on onset and early course.

For the investigation of the early course of schizophrenia starting from onset, the standardised Interview for the Retrospective Assessment of the Onset of Schizophrenia was developed and validated. In a representative sample of 267 first-admitted German schizophrenics of a broad diagnosis from a population of 1.5 million, the age at which different diagnostic and onset definitions were satisfied, the symptoms at the time of the interview, and the accumulation of positive and negative symptoms until first admission were assessed. Comparison between the two sexes and three age groups yielded hardly any differences in the accumulation of symptoms and their course until first admission, except for a slightly shorter period of negative symptoms in young males and a slightly longer one in older women--which contradicts prevailing opinion. At the time of the interview, no significant sex differences were found with respect to the core symptoms of schizophrenia (negative and first-rank symptoms), but clear and substantial differences emerged in disease behaviour. The significantly higher age at first onset in women is explained, on the basis of animal experiments and a clinical study, by the neuromodulatory effect of oestrogen on D2 receptors and by a higher vulnerability threshold in women.

Adolescent↗
PubMed1994

[Recurrent ST segment elevations in continuous ECG analysis in the acute phase of myocardial infarct treated with thrombolytic therapy].

Early fluctuations of the ST-segment elevation indicating intermittent opening and reocclusion of the infarct artery has been well documented by angiographic monitoring in individual acute myocardial infarction patients undergoing thrombolytic therapy. However, the frequency of such episodes has not been studied in a consecutive patient group. Furthermore, it is not known what impact this finding has on the reinfarction risk during hospitalization and on left ventricular healing. The present investigation included 79 patients with acute myocardial infarction (pain < or = 6 h). Continuous Holter monitoring of the infarct-related ST elevation was initiated before or directly after starting thrombolytic therapy. During the 24-h observation period, 34 patients (43%) showed episodes of recurrent ST elevation after an initial resolution (group 1). Among those without episodes, ST elevation resolved within 4 h in 34 (43%, group 2) and persisted > or = 4 h in 11 (14%, group 3). Episodes of re-elevation were more frequent during the first 4 h (0.25 episodes per hour) than in the late part of the observation period (0.04 episodes per hour). Most episodes were transient and short lasting; only nine patients showed persistent re-elevations longer than 60 min. During hospitalization, group 1 patients had a higher incidence of reinfarctions and severe ischemic events than those without episodes (group 1 12/34 (35%) vs. group 2 4/34 (12%) vs. group 3 1/11 (9%), p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

[Reproducibility of symptom-limited oxygen consumption and anaerobic threshold within the scope of spiroergometric studies in patients with heart failure].

A prerequisite for the clinical utility of cardiopulmonary exercise testing is high reproducibility of gas-exchange characteristics. Therefore, we studied reproducibility of peak oxygen uptake and anaerobic threshold during bicycle-exercise stress testing in 34 patients with congestive heart failure in NYHA classes II and III. Additionally, we analyzed interobserver variability with regard to anaerobic threshold measured with the V-slope method. Correlations of results between two exercise stress tests were high concerning peak oxygen uptake and anaerobic threshold (r = 0.871 and r = 0.917, respectively). For both measures, however, 90% percentile of the relative difference between tests was 25% and 22%, respectively. Correlation between two observers with regard to the anaerobic threshold was high (r = 0.985). We conclude that reproducible determination of peak oxygen uptake and anaerobic threshold is possible in heart-failure patients. In individual subjects, however, considerable variation of results may occur during serial exercise testing. Interobserver variability with regard to anaerobic threshold is low.

Adult↗
PubMed1993

Cloning, nucleotide sequence and structural analysis of the Clostridium acetobutylicum dnaJ gene.

The complete dnaJ gene of Clostridium acetobutylicum was isolated by chromosome walking using the previously cloned 5' end of the gene as a probe. Nucleotide sequencing of a positively reacting 2.2-kb HincII fragment, contained in the recombinant plasmid pKG4, revealed that the reading frame of the dnaJ gene of C. acetobutylicum consists of 1125 bp, encoding a protein of 374 amino acids with a calculated M(r) of 40376 and an isoelectric point of 9.54. The deduced amino acid sequence showed high similarity to the DnaJ proteins of other bacteria (e.g. Escherichia coli, Bacillus subtilis) as well as of an archaeon (Methanosarcina mazei) and to the corresponding proteins of eukaryotes (Saccharomyces cerevisiae, Homo sapiens). The areas of similarity included a conserved N-terminal domain of about 70 amino acids, a glycine-rich region of about 30 residues, and a central domain containing four repeats of a CXXCXGXG motif, whereas the C-terminal domain was less conserved. Northern (RNA) blot analysis indicated that dnaJ is induced by heat shock and that it is part of the dnaK operon of C. acetobutylicum. The 5' end (901 bp) of another gene (orfB), downstream of dnaJ and not heat-inducible, showed no significant similarity to other sequences available in EMBL and GenBank databases.

Amino Acid Sequence↗
PubMed1993

Vitamin E attenuates the development of haloperidol-induced dopaminergic hypersensitivity in rats: possible implications for tardive dyskinesia.

Chronic haloperidol treatment in rats results in behavioural supersensitivity to dopamine agonists. This mechanism has been suggested as a possible animal model for tardive dyskinesia. In the present study the simultaneous administration of vitamin E to chronic haloperidol treatment in rats prevented the development of behavioural supersensitivity to apomorphine. This finding suggest that the concomitant administration of vitamin E to neuroleptics might prevent the development of tardive dyskinesia in humans.

Animals↗
PubMed1993

Should radiofrequency therapy be performed in every symptomatic patient with supraventricular tachycardia? (Pro drug position).

The indication for treatment of paroxysmal supraventricular tachycardia depends on the frequency and severity of the tachycardia attacks. If the tachycardia attacks are mildly symptomatic and occur only once or twice a year, there is no indication for either continuous drug therapy or radiofrequency ablation. The only therapeutic measure required is termination of each acute event. If symptoms occur frequently, long-term antiarrhythmic drug therapy is then indicated and will be effective for chronic prophylaxis in most individuals with a low risk of proarrhythmic events. Only in patients with severe or life-threatening symptoms or cases refractory to drug therapy would radiofrequency ablation possibly be justified.

Anti-Arrhythmia Agents↗
PubMed1993

[Three-dimensional radiation planning. Studies on clinical integration].

The routine use of three-dimensional treatment planning was evaluated in a clinical project funded by the German Krebshilfe at the Radiological Department of the University of Heidelberg. 166 patients entered the prospective study within 14 months, 155 of them were treated according to the 3D-plans. More than 50% of the patients had thoracic tumors, followed by pelvic tumors. One medicine physicist and one specially trained technician performed the treatment planning. The target volumes were contoured in the CT slices at the planning computer by the responsible radiotherapists. A mean of 6.5 hours per patient was necessary for all planning procedures, however, this time consumption shows a trend toward less time of only four hours including about ten optimization steps. Meanwhile approximately 20 to 30% of all computer assisted planning are performed in 3D, corresponding to about one plan per day. The achieved time consumption is a clinically accepted quantity, that allows the introduction of 3D-planning into clinical routine.

Abdominal Neoplasms↗