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Biomedical subjects

T Seifert

Publications and source records attributed to T Seifert.

36 records · Page 2Linked to original sources
PubMed1997

Beta-blockers inhibit the modification of low-density lipoproteins by sodium hypochlorite in vitro.

The effect of beta-blockers (alprenolol, oxprenolol, atenolol, acebutolol) and the non-steroidal anti-inflammatory drug, diclofenac, on modification of low-density lipoproteins (LDL) by sodium hypochlorite (NaOCl) was investigated in vitro. Beta-blockers and diclofenac inhibit the formation of thiobarbituric acid reactive substances in LDL modified by NaOCl. Beta-blockers, but not diclofenac, inhibit the hypochlorite-induced aggregation of LDL which was determined by photon correlation spectroscopy. The intracellular accumulation of cholesterol esters in J774 macrophages is inhibited by addition of beta-blockers, but not diclofenac, to LDL prior to the addition of NaOCl. The modification inhibiting effect of beta-blockers is inversely correlated to the binding capabilities of these substances to LDL which were assessed by laser electrophoresis. Inhibition of LDL modification in vivo by beta-blockers may reduce the risk of atherosclerosis and, therefore, compensate for the cholesterol-raising effect of these drugs in human plasma.

Acebutolol↗
PubMed1997

[Results of testing defibrillator function of implanted cardioverter/defibrillators].

Postoperative tests of implantable cardioverter defibrillators (ICDs) are routinely performed to ensure appropriate defibrillation by the device. However, efficacy and complications of this procedure are unknown. To scrutinize the currently accepted indications to test the defibrillation function of the ICD we retrospectively analyzed 844 ICD-tests in 439 ICD-systems and 409 patients. 755 ICD-tests (89.4%) were routinely performed (57% before discharge and 43% during follow-up); 58 tests (6.9%) were performed after a change of the antiarrhythmic drug regimen, 24 tests (2.9%) after a revision of a part of the ICD-system, and seven tests (0.8%) because of a suspected dysfunction of the ICD. During routine-tests six ICD-systems (0.8%) failed to defibrillate the patient. However, in all but one test abnormalities of the ICD-system had been observed before the test. After addition of antiarrhythmic drugs, three of 58 ICD-systems (5.2%) failed to defibrillate the patient during the test (amiodarone: n = 2, flecainide: n = 1). Four of seven ICD-systems (57%) tested due to a suspected dysfunction failed to defibrillate the patient. After revisions of parts of the ICD-systems, ICD-tests never revealed a failure of defibrillation. During 16 ICD-tests (1.9%) complications occurred. The most frequent complications was inappropriate shocks (n = 10; 1.2%), the most severe one (transient) neurologic symptoms (n = 4; 0.48%). Our experience demonstrates that postoperative tests of the defibrillation function of ICDs rarely reveal ICD-dysfunction. As testing is unpleasant for the patient and not free of complications, tests might be restricted to those patients in whom an ICD-dysfunction is suspected (based on clinical presentation, results of chest-x-ray, testing of sensing signal and stimulation threshold) or class I or class III antiarrhythmic drugs have been added to the antiarrhythmic drug regimen.

Adolescent↗
PubMed1996

Cardiac output is not affected during intraoperative testing of the automatic implantable cardioverter defibrillator.

INTRODUCTION: Perioperative mortality of patients undergoing implantation of automatic implantable cardioverter defibrillators (ICDs) has been reduced dramatically following the availability of transvenous-subcutaneous defibrillation leads. However, patients with severely reduced left ventricular function show a substantial rate of nonsudden cardiac mortality within the first year. Whether repeated intraoperative inductions of ventricular tachycardia/fibrillation (VT/VF) during implantation lead to hemodynamic deterioration and thus might contribute to development of end-stage heart failure in these patients is unknown. The purpose of the present study was to determine cardiac output and hemodynamic performance during transvenous-subcutaneous ICD implantation in patients with severe left ventricular dysfunction. METHODS AND RESULTS: In 11 patients with a left ventricular ejection fraction (EF) < or = 0.35, cardiac output was measured automatically with a combined continuous cardiac output/mixed venous oxygen saturation pulmonary artery catheter system. ICD implantation was performed during standardized general anesthesia. In the 11 patients (EF = 27 +/- 2% [mean +/- SEM]) a total of 95 episodes of VT/VF followed by defibrillation were induced (episodes per patient = 9 +/- 1; range 6 to 11). Cardiac index was 2.2 +/- 0.2 L.min-1.m-2 after induction of anesthesia (before start of surgery), and 1.9 +/- 0.1 L.min-1.m-2 immediately before first induction of VT/VF. After the last episode of VT/VF, cardiac index was 2.1 +/- 0.2 L.min-1.m-2. Cardiac index measured 1, 2, and 3 minutes after induction of VT/VF was not significantly different when compared to the preinduction value during any episode of VT/VF induction. Similarly, stroke volume index was 39 +/- 5 mL.m-2 immediately before first induction of VT/VF and 36 +/- 3 mL.m-2 after the last episode of VT/VF (NS). At the end of surgery, hemodynamic parameters did not exhibit any significant difference when compared to the data obtained before start of ICD implantation and testing. CONCLUSION: Extensive defibrillation tests during transvenous-subcutaneous ICD implantation in patients with severe left ventricular dysfunction are not associated with acute deterioration of cardiac performance.

Cardiac Output↗
PubMed1995

Method to estimate the rate and extent of intestinal absorption in conscious rats using an absorption probe and portal blood sampling.

PURPOSE: A variety of methods exist which determine the rate and extent of intestinal absorption. The method described here employs an internal absorption reference probe and portal blood sampling in unanesthetized rat. METHODS: Theophylline and tritiated water were selected as absorption reference probes since they are quantitatively absorbed in conscious rat. The fraction of an intestinal dose which reaches portal blood was determined from the resulting portal-systemic blood concentration gradients of the drug relative to the absorption probe. The absorption probes provide a means to calculate the drug mass reaching portal blood without the need of measuring the portal blood flow rate. The technique was evaluated with verapamil and a well-absorbed 5-lipoxygenase inhibitor, A-79035. RESULTS: The fraction of an intrajejunal dose of A-79035 reaching the portal vein (FG) was 0.86 using theophylline as the absorption probe. Verapamil, which is susceptible to extensive hepatic first-pass elimination, was completely absorbed (FG = 0.98) within 1 hour, but was only 21.4% bioavailable. Absorption rate constants, estimated from initial appearance rates in portal blood, were used to monitor factors that affect drug absorption. For example, with a dose solution containing 30% PEG-400, the absorption rate constants of theophylline and A-79035 were significantly reduced. Anesthesia reduced the absorption rate constant for theophylline in rats by 40% compared to conscious animals. CONCLUSIONS: The technique detailed here allows reliable, direct measurement of intestinal absorption which may assist in characterizing oral dosing for novel therapeutic agents.

Animals↗
PubMed1995

Erroneous discharge of an implantable cardioverter defibrillator caused by an electric razor.

We report an unusual case of the erroneous discharge of a third-generation multiprogrammable implantable cardioverter defibrillator in a 64-year-old patient with a history of recurrent ventricular tachycardias caused by electromagnetic interference while shaving with an electric razor. Electromagnetic interference was related to a defect in the electrode's insulation and could not be provoked in an intact electrode.

Defibrillators, Implantable↗
PubMed1995

Internal defibrillation with smaller capacitors: a prospective randomized cross-over comparison of defibrillation efficacy obtained with 90-microF and 125-microF capacitors in humans.

INTRODUCTION: The size of current implantable cardioverter defibrillators (ICD) is still large in comparison to pacemakers and thus not convenient for pectoral implantation. One way to reduce ICD size is to defibrillate with smaller capacitors. A trade-off exists, however, since smaller capacitors may generate a lower maximum energy output. METHODS AND RESULTS: In a prospective randomized cross-over study, the step-down defibrillation threshold (DFT) of an experimental 90-microF biphasic waveform was compared to a standard 125-microF biphasic waveform. The 90-microF capacitor delivered the same energy faster and with a higher peak voltage but provided only a maximum energy output of 20 instead of 34 J. DFTs were determined intraoperatively in 30 patients randomized to receive either an endocardial (n = 15) or an endocardial-subcutaneous array (n = 15) defibrillation lead system. Independent of the lead system used, energy requirements did not differ at DFT for the experimental and the standard waveforms (10.3 +/- 4.1 and 9.5 +/- 4.9 J, respectively), but peak voltages were higher for the experimental waveform than for the standard waveform (411 +/- 80 and 325 +/- 81 V, respectively). For the experimental waveform the DFT w as 10 J or less using an endocardial lead-alone system in 10 (67%) of 15 patients and in 12 (80%) of 15 patients using an endocardial-subcutaneous array lead system. CONCLUSIONS: A shorter duration waveform delivered by smaller capacitors does not increase defibrillation energy requirements and might reduce device size. However, the smaller capacitance reduces the maximum energy output. If a 10-J safety margin between DFT and maximum energy output of the ICD is required, only a subgroup of patients will benefit from 90-microF ICDs with DFTs feasible using current defibrillation lead systems.

Adolescent↗
PubMed1993

The signal-averaged ECG: time-domain analysis.

During the past decade, the high-resolution electrocardiogram as a non-invasive technique for the detection of ventricular late potentials has developed from an experimental method into a routinely applied non-invasive method for risk stratification of patients after myocardial infarction. Meanwhile, several approaches have been developed for the detection of ventricular late potentials including time-domain analysis, frequency-domain analysis and spectrotemporal mapping. Clinical applications are no longer limited to patients after myocardial infarction, but cover a wider spectrum of different cardiac diseases. This review focuses on some methodological aspects as well as on the results and current clinical applications of the analysis of the signal-averaged ECG in the time domain.

Action Potentials↗
PubMed1993

[Reproducibility of the signal-averaged, high-pass filtered electrocardiogram].

In order to test the reproducibility of the signal-averaged electrocardiogram (SAECG) using Simson's method (high-pass filter cutoff frequency 25 Hz, orthogonal leads, recording of 133 s per lead), 121 patients were examined. In all patients, two signal-averaged ECGs were performed on the first day of the study immediately after each other, using identical electrode position. In a subgroup of 47 patients, the same procedure was repeated 3 days later. There was no difference between the mean values of conventionally calculated averaging parameters (heart rate, QRS-duration, root-mean-square voltage in the terminal 40 ms of the highly amplified and filtered QRS-complex [V40], the low amplitude signal duration under 40 microV in the terminal portion of the QRS-complex [LAS], total root-mean-square voltage of the QRS-complex), both with regard to immediate and short-term reproducibility. Thus, conventionally calculated averaging parameters are well reproducible.

Adolescent↗
PubMed1991

Identification of abscess formation in native-valve infective endocarditis using transesophageal echocardiography: implications for surgical treatment.

The object of the study was to follow patients with endocarditis-associated abscesses in order to evaluate the clinical outcome with and without surgical intervention. Transesophageal echocardiography successfully displayed the location and extent of abscess cavities in 14 patients (group A) with aortic valve endocarditis. The infective process was limited to the perivalvular tissue in two, extended into the ascending aorta in six, and included the interventricular septum, the right ventricular outflow tract, interatrial septum, and/or mitral valve annulus in six patients. The complication rate was significantly higher in group A than in group B, which consisted of 27 patients with proven signs of endocarditis but without endocarditis-associated abscesses. The complication rates were embolic events 64.3% in group A vs 29.6% in group B, need for surgery in 64.3% vs 18.5%, and death in 50.0% vs 3.7%, respectively. The duration of fever--as a marker of an active infective process--before diagnosis and the onset of adequate treatment was significantly higher in group A than in group B (46.7 +/- 8.4 days vs 7.7 +/- 2.6 days). Organisms were isolated in 71.4% in group A and in all patients of group B. Streptococcal infections were noted in A in 54.5% vs 44.4% in B., staphylococcal in 27.3% vs 40.7%. Initial surgical repair in 9 of 14 patients in A (64.3%) included nine aortic valve and one mitral valve prosthesis implantations, two aortic valve-annulus reconstructive procedures, one dacron patch closure, and three partial resections of the aorta ascendens with end-to-end anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗
PubMed1989

[Behavior of ventricular late potentials following catheter ablation of ventricular tachycardia].

In 10 patients non-invasively recorded signal-averaged electrocardiograms were obtained before and after direct-current ablation of ventricular tachycardia (right ventricular origin n = 5; left ventricular origin n = 5). The algorithms proposed by Simson and Karbenn et al. were used (modified Frank leads, high-pass filter cut-off frequency 25 Hz). No differences were observed between the mean values of the duration of the QRS-complex, the mean voltage during the last 40 ms of the QRS-complex, the duration of the late potentials and the number of patients having late potentials before and after ablation, respectively. The success of ablation could not be predicted by the signal-averaged ECG. There was no difference between the averaging parameters of those patients without recurrences of ventricular tachycardia during the follow-up period and those with (n = 3). Thus, the signal-averaged ECG did not prove helpful in predicting a successful outcome of direct-current catheter ablation of ventricular tachycardia.

Adult↗
PubMed1986

Findings with cis-Z-clopenthixol in the treatment of acute mania and schizophrenia.

The authors report the results of an open clinical trial with Cis(Z)-Clopenthixol (Cisordinol), the isolated Cis-isomer of the Clopenthixol racemate (Sordinol). The drug was applied to 18 patients with severe forms of manic or schizophrenic disease, diagnosed according to ICD 9. The compound was applied intravenously or orally, daily doses ranging from 10-160 mg. For the duration of the study (6 weeks) the patients were repeatedly rated with the CGI, BPRS or IMPS (abbreviated version), and several hematological and enzyme patterns, cardiac, renal function and electrolytes were monitored, as was the FFA. Due to the relatively small number of patients in relatively heterogeneous diagnostic composition, a number of items rated failed to reach statistical significance. The CGI showed a good therapeutic effect with a minimal incidence or severity of side effects. BPRS and IMPS documented an impressive decline in formal thought-disorders, agitation, logorrhea and tenseness. The sedative effects of the drug were slight and of short duration, anti-Parkinson medication was necessary in more than 50% of the patients studied. The results of the study show a good efficacy of the drug in manic and schizophrenic disorders, Cisordinol being well tolerated intravenously. The range of doses administered is approximately 50% of the dose-range of the parent-drug (Sordinol).

Adult↗
PubMed1985

Influence of cofactor pyridoxal 5'-phosphate on reversible high-pressure denaturation of isolated beta 2 dimer of tryptophan synthase bienzyme complex from Escherichia coli.

High hydrostatic pressure has been shown to cause reversible dissociation of the isolated apo beta 2 dimer of tryptophan synthase from Escherichia coli into enzymatically inactive monomers [Seifert, T., Bartholmes, P., & Jaenicke, R. (1982) Biophys. Chem. 15, 1-8]. Addition of the coenzyme pyridoxal 5'-phosphate affects the structural stability, as well as the kinetics of dissociation and deactivation. The apo beta 2 dimer is deactivated faster than the holoenzyme by a factor of 10. The midpoints of the corresponding equilibrium transition curves are observed at 690 and 870 bar, respectively. As shown by hybridization of native and chemically modified beta chains, the loss of enzymatic activity is accompanied by subunit dissociation. An additional deactivating effect is produced by the pressure-induced release of the cofactor from the holoenzyme. Renaturation after decompression has been monitored by circular dichroism and intrinsic fluorescence emission. Alterations of the dichroic absorption at 222 nm reflect the recovery of the native secondary structure, while tryptophan fluorescence represents a specific probe for the native tertiary structure in the immediate neighborhood of the active center of the enzyme. By application of both methods to monitor the reconstitution of the apo beta 2 dimer, two first-order processes may be separated along the time scale. The faster phase (k1 = 1.2 X 10(-2) s-1) yields a "structured monomer" with 85% native secondary structure and the tryptophan side chain buried in its native hydrophobic environment. As indicated by sodium borohydride reduction, this intermediate is able to interact with the coenzyme pyridoxal 5'-phosphate in the correct way; however, it does not show enzymatic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Apoenzymes↗
PubMed1984

High-pressure dissociation of the beta 2-dimer of tryptophan synthase from Escherichia coli monitored by sucrose gradient centrifugation.

The isolated beta 2-dimer of Escherichia coli tryptophan synthase exhibits reversible high-pressure deactivation and hybridization with an equilibrium transition at 690 and 870 bar for the apoenzyme and holoenzyme, respectively. To investigate the hypothetical dissociation mechanism ultracentrifugal analysis has been applied. In a conventional swing-out rotor (r(max) = 16 cm, fill-height 9 cm) a pressure gradient of 1 less than p less than 1840 bar is formed at maximum speed (40 000 rpm). Using a sucrose gradient to stabilize the particle distribution, pressure-dependent alterations of the state of association of oligomeric systems may be determined. In the present experiments ovalbumin (with a molecular mass close to the beta-monomer) has been used as a reference. The radial sedimentation velocity of the beta 2-dimer (in 5-20% sucrose, 10 degrees C) is found to decrease significantly at p approximately equal to 850 bar. From the slopes in an r-r(degrees) vs t plot the limiting values for the particle weight at the meniscus and the bottom of the tube are found to be the beta 2-dimer (M(r) = 85 800) and the beta-monomer (M(r) = 42 900), thus proving pressure-dependent dissociation. Since sucrose stabilizes the native quaternary structure, the beta 2 leads to 2 beta transition is shifted towards higher pressures compared to the dissociation in standard buffer. Conventional quench experiments in high-pressure cells in the presence of 13% (w/v) sucrose confirm the result of the sucrose gradient centrifugation with respect to the critical pressure where deactivation (and dissociation) occur.

Centrifugation, Density Gradient↗
PubMed1984

High pressure dissociation of lactate dehydrogenase from Bacillus stearothermophilus and reconstitution of the enzyme after denaturation in 6 M guanidine hydrochloride.

Tetrameric lactate dehydrogenase from Bacillus stearothermophilus exhibits unusual stability towards high hydrostatic pressure: In contrast to the mesophilic enzyme, incubation at pressures up to 2.8 kbar does not cause irreversible denaturation. Hybridization under these conditions suggests partial dissociation to the dimer, indicating that reassociation occurs within the dead-time after pressure release (less than 20 s at less than or equal to 40 micrograms/ml, 20 degrees C). Incubation at P less than 2.8 kbar affects neither the native quaternary structure nor the catalytic function of the enzyme. Reconstitution of the unfolded and dissociated subunits after denaturation, e.g., in 6 M guanidine . HC1, is characterized by fast association favouring the native assembled structure. Evidence from spectroscopic measurements shows that reconstitution starts with a fast refolding reaction generating a native-like conformation. The subsequent rate-determining transconformation of the "structured monomers" governs the kinetics of reactivation and reassociation as one single first-order process. Chemical crosslinking with glutaraldehyde proves that the "structured monomers" undergo fast association to form the tetrameric final state of reconstitution, with significant amounts of dimeric intermediates being detectable. The renatured enzyme is indistinguishable from the native enzyme regarding its physicochemical and enzymological properties (e.g., activation by fructose-1,6-bisphosphate, and susceptibility towards proteolytic digestion).

Drug Stability↗
PubMed1982

Reconstitution of the isolated beta2-subunit of tryptophan synthase from Escherichia coli after dissociation induced by high hydrostatic pressure. Equilibrium and kinetic studies.

The isolated beta2-subunit of Escherichia coli tryptophan synthase can be reversibly dissociated into enzymically inactive monomers under high hydrostatic pressure. Deactivation at 1.5 kbar which shows a half-time of 11 min (rate constant k=10 (-3) s (-1) is paralleled by dissociation with a small lag phase of about 5 min. Pressure release leads to 95 +/- 5% recovery of specific activity and complete restoration of the hydrodynamic and spectral properties which specify the native dimer. Over the concentration range 1-100 micrograms/ml (0.02-2.3 micrograms M) the kinetics of reactivation can be fitted by one apparent first-order rate constant (k=6.5 +/- 0.6 X 10 (-4) s (-1), half-time = 17.5 min). The reconstitution of catalytic activity is paralleled by alterations in tryptophan fluorescence at 327 nm, thus presenting direct evidence for conformational changes in the direct vicinity of the active center (k1 = 1.9 X 10 (-3) s(-1), k2 = 6.5 +/- 0.6 X 10(-4) s (-1) ). On the other hand, a definite mechanism of reactivation requires the association of the refolding monomers to be included. The kinetics of dimerization have been followed via hybridization between native and chemically modified beta-chains, yielding an apparent first-order rate constant of 6.3 +/- 0.6 X 10 (-4) s (-1). As a consequence, we propose a sequential uni-uni-bimolecular mechanism, which is characterized by a minimum of two conformational changes in substantially structured monomers followed by a fast dimerization reaction to yield the active beta2-subunit.

Escherichia coli↗
PubMedDate not supplied

[Perioperative cost analysis of cemented versus uncemented total hip endoprostheses for clinical and economic management. Postoperative follow-up study over one year].

QUESTIONS: Are there and what are the differences between in-patient and out-patient costs for cemented or noncemented hip prosthesis? How to make it possible to keep in-patient costs within the limit of the a special global amount ("Fallpauschale")? METHODS: In this study we compared in-patient and out-patient costs of 30 patients with cemented and 30 patients with noncemented hip prosthesis during the first year after surgery. We developed a perioperative management in order to keep the costs in the limits of the "Fallpauschale". RESULTS: The average in-patient cost for the cemented prosthesis group was DM 19.644,89 and for the non-cemented group DM 20.485,33. In both groups these costs went beyond the "Fallpauschale" (DM 18.643,80). Comparing the two groups we found significant differences in costs for the endoprosthesis and for laboratory costs. We discovered a suitable perioperative management to keep costs below the "Fallpauschale". CONCLUSION: Using an appropriate perioperative management it is possible to keep costs in the given limits.

Aged↗
PubMedDate not supplied

Binding of the fluorescent dye 8-anilinonaphthalene 1-sulfonic acid to the native and pressure dissociated beta 2-dimer of tryptophan synthase from Escherichia coli.

The beta 2-dimer of tryptophan synthase from Escherichia coli exhibits weak binding of 8-anilinonaphthalene-1-sulfonic acid (ANS). Titrating the dye at 0.2 mM concentration with the apo-beta 2-dimer at atmospheric pressure causes increased fluorescence emission at 480 nm (lambda exc = 380 nm), corresponding to unspecific binding of the ligand to hydrophobic residues. Increasing hydrostatic pressure affects ANS binding. Up to 700 bar, a sigmoidal increase of ANS fluorescence reflects an increase in hydrophobic surface area, probably caused by subunit dissociation. At approximately 1 kbar, a maximum is reached; beyond this value, pressure competes with ligand binding causing fluorescence emission to be decreased again. Pressure release leads to a drastic fluorescence enhancement, ascribed to ANS binding to the partially and reversibly denatured enzyme. Plotting the total fluorescence enhancement vs. pressure yields a profile which parallels the pressure dependent dimer in equilibrium monomer transition monitored by subunit hybridization (T. Seifert, P. Bartholmes, and R. Jaenicke, Biochemistry, in press).

Anilino Naphthalenesulfonates↗