Biomedical subjects

R Zahn

Publications and source records attributed to R Zahn.

At least 91 records · Page 5Linked to original sources

PubMed1999

Immunogenetic risk factors for anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis.

Wegener's granulomatosis (WG) and microscopic polyangiitis are systemic autoimmune diseases characterized by the presence of ANCA in the sera of patients. Little is known about the aetiologic factors and genetic predisposition as well as the pathogenesis of these disease entities. A slightly decreased representation of HLA-DRB1*13 and HLA-DQB1*0603 individuals was observed in our cohort of ANCA-associated systemic vasculitis (AASV) patients compared with controls. In addition, HLA-DRB1*04 individuals were over-represented in a subgroup of patients with WG in end-stage renal disease as a result of renal vasculitis. In order to identify other genes relevant for these diseases, we investigated highly polymorphic markers in the vicinity of several immunorelevant genes, i.e. tumour necrosis factor (TNF)alpha, IL-2, IL-5 receptor alpha (IL-5RA), in a group of 102 patients with AASV and compared the representation with controls. Furthermore, functional polymorphisms were directly analysed in the promotor region of TNFalpha as well as in the coding region of the FcgammaIIRA genes. Polymorphisms of the TNFalpha promotor (TNF-308) as well as in the FcgammaIIRA gene were excluded as risk factors for the disease in our cohort. No major phenotype distribution differences were observed between patients and controls for the IL-2 and IL-5RA microsatellites. Most importantly, several haplotypes on chromosome 6p appeared strongly associated with proteinase 3 (PR3)-ANCA+ AASV. Thus, as in other autoimmune diseases, different predisposing factors play differential aetiopathogenic roles in various groups of AASV patients.

Adolescent↗

PubMed1999

Spectrum of reperfusion strategies and factors influencing the use of primary angioplasty in patients with acute myocardial infarction admitted to hospitals with the facilities to perform primary angioplasty. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

OBJECTIVE: To determine the frequency of the use of primary angioplasty in patients with acute myocardial infarction and the factors influencing its indications in hospitals with the facilities to perform this treatment. DESIGN: Data from the maximal individual therapy in acute myocardial infarction (MITRA) trial were analysed, concerning the effects of the decisions of individual hospitals, the time of admission of patients, and the effects of patient characteristics on the selection of reperfusion treatment. PATIENTS: Between June 1994 and January 1997 eight hospitals treated 1532 patients with acute myocardial infarction. 418 (27.3%) were treated conservatively, 641 (41.8%) were treated using intravenous thrombolysis, 387 (25.3%) were treated using primary angioplasty, and 86 (5.6%) received a combination of thrombolysis and angioplasty. RESULTS: The proportion of patients treated with primary angioplasty varied from 1.8% to 57.7% among the eight hospitals. The use of primary angioplasty during non-office hours also showed wide variation, ranging from 20% to 54% between centres. The use of thrombolysis was comparatively evenly distributed during the non-office hours, ranging from 50-69%. Four hospitals with a primary angioplasty use rate > 30% showed no difference in the proportion of patients with contraindications for thrombolysis, high risk patients, or a combination of both, when compared with four hospitals with a lower rate of primary angioplasty use (98/322 (30.4%) v 19/65 (29. 2%), respectively, p = 0.847). CONCLUSIONS: In hospitals with the facilities for performing primary angioplasty the most important factors influencing its use were the discretion of the individual hospital and the time of patient admission. Characteristics of patients did not influence the choice of reperfusion treatment

Angioplasty, Balloon, Coronary↗

PubMed1999

Lack of association between HLA-DRB1 alleles of the major histocompatibility complex and p-ANCA status or clinical characteristics in patients with ulcerative colitis.

INTRODUCTION: An association between different HLA-subtypes and ulcerative colitis has been described in various study populations of different ethnic and geographic background. Moreover, a correlation between HLA-DR2 and ulcerative colitis, in particular p-ANCA-positive ulcerative colitis, was reported. Thus, the present study aimed on the correlation of HLA-DRB1* alleles with the presence of p-ANCA and clinical characteristics in individuals of southern german descent. PATIENTS AND METHODS: The study population comprised 56 patients with ulcerative colitis and 177 healthy controls. HLA-DRB1* alleles were assessed by use of the dot blot method. Autoanti-bodies were visualized by indirect immunofluorescence on ethanol-fixed neutrophils. RESULTS: The allele HLA-DRB1*12 was more frequent in patients with ulcerative colitis (p = 0.01). After correction for the number of alleles tested (n = 16) statistical significance was no longer preserved. A weak association between the presence of HLA-DR5 and the detection of p-ANCA in ulcerative colitis was found (p = 0.0375). After correction for the number of comparisons (n = 10) no associations between HLA-DR antigens and the presence of p-ANCA remained. Furthermore, no significant correlations between clinical characteristics of ulcerative colitis and HLA-DR antigens were detected. DISCUSSION: Genes encoding for HLA-DR antigens are unlikely to have an impact on the heredity and the presence of disease phenotypes of ulcerative colitis in a study population of southern german descent.

Adolescent↗

PubMed1999

Primary angioplasty in acute myocardial infarction: differences between referred patients and those treated in hospitals with on-site facilities?

BACKGROUND: Primary angioplasty for acute myocardial infarction (AMI) can only be performed in a limited number of centers. Therefore, some patients will be referred for this procedure. DESIGN: We analyzed the data of the prospective observational MITRA trial, which took place at 54 hospitals in southwest Germany, to describe current practices and outcomes in referred patients compared to patients treated on-site. RESULTS: Out of 491 patients treated with primary angioplasty, 63 (12.8%) were referred. Out of 46 hospitals without facilities to perform primary angioplasty, 29 (63%) never referred patients. Referred patients were less often male (60.3% versus 75.9%; p = 0.013), suffered more often from anterior wall infarction (62.9% versus 45.8%; p = 0.014), and more often had absolute contraindications against thrombolysis (11.1% versus 2.8%; p = 0.006). In-hospital time to treatment was 80 minutes in patients treated on-site compared to 190 minutes in referred patients (p = 0.001). There was a non-significant difference of in-hospital mortality between the two groups (11.1% for referred versus 7.5% on-site; p = 0.319). Referred patients had a higher hospital morbidity as expressed by a higher proportion of post-infarction angina (28.6% versus 4.2%; p = 0.001), a more frequent need for urgent revascularization (43.8% versus 16.4%; p = 0.001) and a higher proportion of advanced heart failure (11.1% versus 4.4%; p = 0.062). CONCLUSIONS: Referral of patients with AMI for primary angioplasty is used only in a minority of hospitals. The referred patients represent a selected, more ill subgroup, resulting in a higher hospital morbidity compared to patients treated on-site. Continuous efforts should be undertaken to decrease the time delay from admission at the initial hospital to the beginning of revascularization.

Acute Disease↗

PubMed1998

Comparison of metoprolol and sotalol in preventing ventricular tachyarrhythmias after the implantation of a cardioverter/defibrillator.

The purpose of this prospective study was to evaluate, on an intention-to-treat basis, the efficacy of d,l-sotalol and metoprolol with regards to the recurrence of arrhythmic events after implantable cardioverter defibrillator (ICD) implantation. After ICD implantation, 70 patients were randomly assigned to treatment with either metoprolol (mean dosage 104+/-37 mg/day in 35 patients) or d,l-sotalol (mean dosage 242+/-109 mg/day in 35 patients). During follow up ventricular tachycardia (VT), fast VT, and ventricular fibrillation (VF) episodes were calculated. Metoprolol treatment led to a marked reduction in the recurrence of arrhythmic events. Actuarial rates for absence of VT recurrence at 1 and 2 years were significantly higher in the metoprolol group compared with the d,l-sotalol group (83% and 80% vs 57% and 51%, respectively, p=0.016). The actuarial rates for absence of fast VT or VF were 80% in the metoprolol group compared with 46% in the d,l-sotalol group (p=0.002). During a follow up of 26+/-16 months, there were 3 deaths in the metoprolol group compared with 6 deaths in the d,l-sotalol group. Actuarial rates of overall survival were not significantly different in the 2 groups (91% vs 83%, p=0.287). In this prospective, randomized, controlled study the recurrence rate of ventricular tachyarrhythmias in patients treated with metoprolol was lower than in patients treated by d,l-sotolol.

Adolescent↗

PubMed1998

Risk of thromboembolic events in patients with atrial flutter.

Based on multiple studies, clear, guided anticoagulation therapy is recommended for patients with atrial fibrillation. The value of anticoagulation therapy in patients with atrial flutter, however, is less well established. Little is known about the incidence of thromboembolism in patients with atrial flutter. We evaluated the risk of thromboembolism in 191 consecutive unselected patients referred for treatment of atrial flutter. A history of embolic events was noted in 11 patients. Acute embolism (<48 hours) occurred in 4 patients (3 after direct current cardioversion, 1 after catheter ablation). During follow-up of 26+/-18 months, 9 patients experienced thromboembolic events. During the follow-up, the overall embolic event rate (including acute embolism and thromboembolic events during follow-up) was 7 % in this patient population. Risk indicators for an embolic event in an univariate analysis were organic heart disease (p = 0.037), depressed left ventricular function (p = 0.02), history of systemic hypertension (p = 0.004), and diabetes mellitus (p = 0.0038). Using multivariate analysis, a history of hypertension was the only independent predictor for elevated embolic risk in this patient population (odds ratio = 6.5; 95% confidence intervals 1.5 to 45). Thus, the thromboembolic risk is higher than previously recognized for patients with atrial flutter. Anticoagulation therapy may decrease this risk.

Aged↗

PubMed1998

The WASp homologue Las17p functions with the WIP homologue End5p/verprolin and is essential for endocytosis in yeast.

Several end mutations that block the internalisation step of endocytosis in Saccharomyces cerevisiae also affect the cortical actin cytoskeleton [1]. END5 encodes a proline-rich protein (End5p or verprolin) required for a polarised cortical actin cytoskeleton and endocytosis [2,3]. End5p interacts with actin [4], but its exact function is not yet known. To help elucidate End5p function, we sought other End5p-interacting proteins and identified the LAS17/BEE1 gene (encoding the yeast homologue of the human Wiskott-Aldrich Syndrome protein, WASp) as a high-copy-number suppressor of the temperature-sensitive growth and endocytic defects of end5-1 cells (carrying a frameshift mutation affecting the last 213 residues of End5p). LAS17 is unable to suppress a full deletion of END5 (end5 delta), however, suggesting that the defective End5-1p in end5-1 mutants may be stabilised by Las17p. The amino terminus of Las17p interacts with the carboxyl terminus of End5p in the yeast two-hybrid system and similar interactions have been shown between WASp and a mammalian End5p homologue, WASp-interacting protein (WIP) [5]. As las17 delta deletion mutants are blocked in endocytosis, we conclude that Las17p and End5p interact and are essential for endocytosis.

Carrier Proteins↗

PubMed1998

Thermodynamic stability and folding of GroEL minichaperones.

The apical domain of GroEL (residues 191 to 376) and its C-terminally truncated fragment GroEL(191-345) are expressed with high yield in Escherichia coli to give functional monomeric minichaperones. Owing to the reversible folding behaviour of the minichaperones we can analyse the folding of the polypeptide binding domain of the multidomain GroEL protein, the folding of which is known to be irreversible. The apical domain shows two reversible temperature transitions with transition midpoints at 35 degrees C and at 67 degrees C that can be attributed to the unfolding of the C-terminal helices and the domain core, respectively. The native state of the domain core is stabilized by 5.5 kcal mol-1 relative to the unfolded state. The rate constant of folding of the apical domain core is independent of the minichaperone concentration and the presence of the C-terminal alpha-helices. A folding intermediate on the folding pathway is destabilized relative to the native state by 1.6 kcal mol-1, which is also detected by equilibrium and kinetic binding of the dye bis-ANS. Reversible folding of the polypeptide domain of GroEL guarantees highly efficient chaperonin activity within the GroEL toroid.

Amino Acid Sequence↗

PubMed1998

[Pseudoaneurysm in the vicinity of the ascending aorta caused by contained disruption at the insertion site of a coronary artery bypass graft. A case report].

In this case report a 65-year-old patient came into the emergency ward with acute chest pain after coronary artery bypass graft operation in 1985. On routine chest X-ray in 1995 a mediastinal widening was diagnosed. The chest X-ray in 1997 (Figure 1) showed an increase of the diameter of the known mediastinal widening. Therefore a CT-scan was performed (Figures 2a and 2b). This showed an enhancement of contrast material in a contained structure, without identifying its origin. Therefore a coronary angiography was done. Here, we diagnosed a contained disruption of the aorta at the insertion site of the bypass graft at the right coronary artery. Figure 3a shows leakage of contrast material out of the aorta into the pseudoaneurysm and in Figure 3b this is demonstrated in a schematic drawing. Figure 4a shows supraselective imaging of the pseudoaneurysm, demonstrated in a schematic drawing in Figure 4b. As the chest pain could only be handled by i.v.-medication, betablocker and bed rest we decided to operate. Intra-operatively the diagnosis was confirmed (Figure 5a and 5b). Postoperatively the patient died due to cerebral ischemia. Despite the lethal outcome an operative revision appears even retrospectively justified because of the increasing size of the pseudoaneurysm in addition to new symptoms that were difficult to treat. On the other hand there are no data available in order to estimate the risk of a spontaneous course.

Aged↗

PubMed1998

[Incidence of atrial fibrillation in relation to atrial catheter site in two-chamber pacemakers].

INTRODUCTION: This study evaluated the impact of the atrial lead implantation site on the subsequent development of atrial arrhythmias. METHOD: Dual chamber pacemakers were implanted in 109 consecutive patients. The indication was AV-block in 51 patients, sick sinus syndrome in 58 patients. No patient had chronic atrial fibrillation, but 12 patients (11%) had paroxysmal atrial fibrillation before implantation. Patients were classified according to the atrial lead implantation site: right atrial appendage and right atrial free wall. RESULTS: Preimplant episodes of atrial fibrillation were similar in patients with lead implantation at the free wall and with implantation in the right atrial appendix (13% vs 7.5%, P=0.53). During a mean follow-up of 24+/-13 months, new paroxysmal atrial fibrillation occurred in 5% after lead implantation in the appendix vs 28% of patients after implantation at the right atrial free wall (P = 0.004). CONCLUSION: The development of atrial arrhythmias in dual chamber pacing is influenced by the implantation site of the atrial lead. The frequency of atrial arrhythmias during follow-up is higher after atrial lead implantation at the right lateral wall than in the appendix.

Adult↗

PubMed1998

Virtual DNA analysis--a new tool for combination and standardised evaluation of SSO, SSP and sequencing-based typing results.

In order to obtain reliable information on HLA types, DNA typing with sequence-specific oligonucleotide/primer (SSO/SSP) typing sets or sequencing-based typing (SBT) is increasingly performed. The quality of the evaluation depends on the presence of a complete listing of all typed alleles as well as on the ability of detecting all corresponding alleles/allele pairs. We have developed the concept of virtual DNA analysis (VDA), which is able to combine all types of SSO/SSP/SBT results and evaluate this typing in combination according to the latest published allele sequence lists. The concept is based on the target DNA recognised by the respective typing techniques. All SSO/SSP or SBT results are transformed to a virtual sample DNA, which subsequently is analysed. Evaluation of generic or allele-specific DNA typing or the combination of both is supported. Due to this flexible approach, all kinds of SSO/SSP sets, as far as the respective SSO/SSP sequences are available, can be entered and evaluated immediately. The combination of collected data of different typing sets and procedures leads to the highest possible typing resolution. If more than one possible allele combination persists, the program reduces the result to the most specific common denominator in a stepwise manner. VDA offers the possibility of re-evaluation of former SSO/SSP/SBT results, alone or in combination. No solutions are omitted. This might be a first step towards standardisation of evaluating DNA-based HLA typing results or transfer of the respective typing data for later evaluation.

Databases, Factual↗

PubMed1998

Is the atrial high rate episode diagnostic feature reliable in detecting paroxysmal episodes of atrial tachyarrhythmias?

The atrial high rate episode diagnostic in the Thera pacemaker reports frequency, duration, and date/time of atrial tachyarrhythmias according to programmed criteria. The aim of the study was to validate the atrial high rate episode diagnostic feature. Episodes of atrial fibrillation recorded by Holter monitoring were compared to episodes detected by the pacemaker. Forty five ambulatory (Holter) recordings were used for evaluation. Thirty of 45 ambulatory (Holter) recordings showed sinus rhythm. On 4 of these 30 ambulatory (Holter) recordings, the Thera detected 12 episodes of atrial tachyarrhythmias as false-positives (sinus rhythm was detected as atrial tachyarrhythmia). The main reason was far-field R and T was oversensing. On 15 of 45 ambulatory (Holter) recordings, 125 episodes of atrial tachyarrhythmias were recorded. Ninety-three of these events also were detected by the pacemaker, while for 32 events the Thera reported sinus rhythm. The main reason was that the episodes were of too short duration. Therefore, the Thera (programmed with detection rate 160 beats/min, detection beats 40, termination beats 10) was unable to detect atrial tachycardias. Software simulation of the diagnostic algorithm under several programming settings using the digitized Holter files demonstrated highly reliable detection of atrial tachyarrhythmias (sensitivity 98%, specificity 100%) when programmed as follows: detection rate 220 beats/min, detection beats 10, termination beats 20. It can be concluded that Thera's high rate episode monitor is a reliable tool for detection of atrial tachyarrhythmias, if programmed as recommended.

Aged↗

PubMed1998

Unexpected complete AV block following transcatheter ablation of a left posteroseptal accessory pathway.

Radiofrequency catheter ablation is the procedure of choice for the nonpharmacological treatment of AV connections that are responsible for debilitating tachycardia. This article describes a patient with a manifest left posteroseptal accessory pathway and recurrent syncopes in whom a transient complete AV block occurred after transcatheter radiofrequency ablation of the left posteroseptal pathway. Three electrical abnormalities were present in this patient: AV infra-Hisian block, a left posteroseptal accessory pathway, and an AV nodal reentry tachycardia. This case report reminds you that one should be prepared for all fall backs during catheter ablation.

Atrioventricular Node↗

PubMed1998

Impact of early risk stratification on the length of hospitalization in patients with acute Q-wave myocardial infarction. 'The 60-minutes myocardial infarction project'.

UNLABELLED: An assessment of individual risk factors may identify a subgroup of postinfarction patients at low risk, i.e. patients appropriate for early discharge. Using a large unselected population of the national registry, 'The 60-Minutes Myocardial Infarction Project', we (1) attempted to provide a retrospective analysis of clinical factors and in-hospital mortality in a population living on the 6th hospital day following admission to define a low-risk patient group with a residual in-hospital mortality of less than 1% eligible for early discharge, and (2) to analyze the current impact of risk stratification based on these clinical factors on the length of hospitalization. The study group consisted of 12,045 survivors on the 6th day after admission out of 14,980 patients of the registry with proven Q-wave myocardial infarction. Risk modeling was performed with multiple logistic regression. RESULTS: A total of 873 patients (7.3%) died after day 6 in hospital. The most important prognostic factors were cardiopulmonary resuscitation prior to admission (odds ratio, OR: 7.2, confidence interval, CI: 5.11-10.22), thrombolysis complicated by severe bleedings (OR: 6.2, CI: 1.2-31. 2) and age >70 years (OR 4.7, CI 3.51-6.39). The other more significant independent predictors of increased mortality were end-stage renal disease, age between 56 and 70 years, systolic blood pressure <95 mm Hg on admission, history of trauma </=2 months, cancer and left-bundle-branch block. Summarizing these nine groups of patients with the strongest association to in-hospital mortality, we defined a high-risk group comprising 79% of the AMI patients with a residual in-hospital mortality of 8.8%. On the other hand, by excluding these nine high-risk patient groups, a low-risk group of 21% of all AMI patients seems to be appropriate for early discharge (residual in-hospital mortality = 1.07%). However, in the current practice, there was no difference regarding the median length of hospital stay between the two risk groups. The low-risk patients were hospitalized 20 days compared to 22 days in the high-risk patients. CONCLUSION: Using a simple logistic regression model, which considers clinical factors of the early hospital phase, one fifth of the infarction patients can be stratified to be at low risk, and might be eligible for early hospital discharge. Currently, an individual risk stratification has no impact on the length of hospital stay in Germany.

Aged↗

PubMed1998

Importance of preimplantation procedures in candidates for an implantable atrial defibrillator.

INTRODUCTION: Due to the limited efficacy of antiarrhythmic drugs for the treatment of atrial fibrillation, several nonpharmacologic therapeutic options have been developed. One of these options is an implantable atrial defibrillator for patients with severe symptoms and infrequent drug-refractory episodes of atrial fibrillation. The purposes of this study were: (1) to evaluate how many patients with atrial fibrillation are possible candidates for an implantable atrial defibrillator; and (2) to report the results and findings of preimplantation testing in a single center. METHODS AND RESULTS: From our atrial fibrillation outpatient clinic, we evaluated the number of possible candidates for an atrial defibrillator using the following criteria: (1) recurrent persistent atrial fibrillation; (2) long-lasting but infrequent episodes; (3) refractory to antiarrhythmic drugs; (4) capability of maintaining normal sinus rhythm; and (5) no factors increasing proarrhythmic risk. In those patients eligible for an atrial defibrillator, a separate preimplantation test was performed to evaluate atrial defibrillation limits and patient acceptance. Thirty-one of 196 patients were possible candidates for an atrial defibrillator. Fourteen of these 31 patients agreed to participate in the METRIX clinical study phase I on atrial defibrillators. Six of these patients met implantation criteria; two patients refused permanent implantation because of intolerable pain. Implantation was performed in four patients; however, one patient could not be cardioverted intraoperatively despite a successful preimplantation test. CONCLUSION: About 16% of selected patients with atrial fibrillation are possible candidates for an atrial defibrillator. However, successful preimplantation testing does not exclude implantation failure.

Aged↗

PubMed1997

Human prion proteins expressed in Escherichia coli and purified by high-affinity column refolding.

An efficient method is presented for the production of intact mammalian prion proteins and partial sequences thereof. As an illustration we describe the production of polypeptides comprising residues 23-231, 81-231, 90-231 and 121-231 of the human prion protein (hPrP). Polypeptides were expressed as histidine tail fusion proteins into inclusion bodies in the cytoplasm of Escherichia coli and refolded and oxidized while N-terminally immobilized on a nickel-NTA agarose resin. This 'high-affinity column refolding' facilitates the preparation of prion proteins by preventing protein aggregation and intermolecular disulfide formation. After elution from the resin the histidine tail can be removed using thrombin without cleaving the prion protein polypeptide chain. The same protocol as used here for hPrP has been successfully applied with bovine and murine prion proteins. The protein preparations are stable for weeks at room temperature in concentrated solution and are thus suitable for detailed structural studies. Preliminary biophysical characterization of hPrP(23-231) suggests that the C-terminal half of the polypeptide chain forms a well-structured globular domain, and that the N-terminal half does not form extensive regular secondary structures.

Amino Acid Sequence↗

PubMed1997

Influence of the global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (GUSTO-1) trial on the use of thrombolytics in Germany. ALKK Study Group. Arbeitsgemeinschaft der Leitenden Kardiologischen Krankenhausärtze.

Our results show significant and independent influence of the GUSTO-1 trial on the use of recombinant tissue plasminogen activator in acute myocardial infarction in Germany. This influence started soon after the publication of the trial and was not restricted to subgroups who benefitted most from recombinant tissue plasminogen activator.

Aged↗

PubMed1997

Importance of electrostatic interactions in the rapid binding of polypeptides to GroEL.

The question of how chaperones rapidly bind non-native proteins of very different sequence and function has been examined by determining the effect of ionic strength on the refolding of barnase on GroEL, and on the thermal denaturation of barnase in the presence of GroEL and SecB. Both chaperones bind the denatured state of barnase, so lowering the T(m) value. The refolding of barnase in the presence of GroEL is multiphasic, the slowest phase corresponding to the refolding of a singly bound molecule of barnase in the complex with GroEL. The fastest phase is related to the association of barnase and GroEL. At high ratios of GroEL to barnase and low ionic strength (less than 200 mM) this fast phase corresponds to the observed rate of binding. The rate of association of barnase and GroEL was found to be highly dependent on ionic strength, and at high ionic strength (greater than 600 mM) the majority of barnase molecules escaped binding and refolded free in solution. The data are consistent with an initial, transient, ionic interaction between barnase and GroEL, before hydrophobic binding occurs, allowing diffusion-controlled association and slow dissociation of unfolded polypeptide.

Bacterial Proteins↗