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Biomedical subjects

R Zahn

Publications and source records attributed to R Zahn.

At least 19 recordsLinked to original sources

Primary percutaneous transluminal coronary angioplasty for acute myocardial infarction in patients not included in randomized studies. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

Patients with acute myocardial infarction included in randomized trials comparing primary percutaneous transluminal coronary angioplasty (pPTCA) with thrombolysis represent a special subgroup of patients with a low event rate. Patients excluded from these trials represent a variety of different subgroups, with different patient characteristics and possibly different clinical event rates. Primary PTCA was performed in 491 consecutive patients with acute myocardial infarction in the prospective multicenter observational Maximal Individual Therapy in Acute Myocardial Infarction trial. They were divided into the following groups: group I, patients fulfilling the inclusion criteria of the randomized trials (284 of 491, 58%); group II, patients not included in these trials (207 of 491, 42%). Of group II the following subgroups were defined: group IIa, patients in cardiogenic shock (20 of 491, 4.1%); group IIb, patients with a left bundle branch block (12 of 491, 2,4%); group IIc, patients with contraindications for thrombolysis (42 of 491, 8.6%); group IId, patients with a nondiagnostic first electrocardiogram (95 of 491, 19.3%); group IIe, patients with a prehospital delay of > 12 hours (72 of 491, 14.7%); group IIf, patients with an unknown prehospital delay (30 of 491, 6.1%). A comparison of groups I and II showed similar baseline characteristics but a higher clinical event rate during hospitalization was seen in group II: combined end point of death, reinfarction, heart failure equal to or greater than NYHA class III, any stroke or postinfarction angina, 26.6% versus 18%; p = 0.022. Hospital deaths were nearly twice as high in these patients, without reaching statistical significance (10.6% vs 6%; p = 0.06). The subgroups of group II showed quite different rates of clinical events. In-hospital death rates were: IIa, 40% (8 of 20); IIb, 8% (1 of 12); IIc, 12% (5 of 42); IId, 5% (5 of 95); IIe, 6% (4 of 72); and IIf, 13% (4 of 30). The incidence of the combined end point was 60% (12 of 20) in IIa, 33% (4 of 12) in IIb, 29% (12 of 42) in IIc, 16% (15 of 95) in IId, 26% (19 of 72) in IIe, and 33% (10 of 30) in IIf. Thus, in clinical practice, about half of the patients treated with pPTCA would not have been included in randomized trials comparing pPTCA with thrombolysis. These patients represent a population at higher risk for in hospital clinical events. However, they do represent very different nonhomogenous subgroups with different clinical event rates.

Aged

Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases.

Bone marrow (BM) is a clinically relevant site of micrometastatic disease in patients with solid epithelial tumors. It is, therefore, important to establish suitable models that allow the in-depth characterization of disseminated tumor cells present at low frequencies of 10(-5)-10(-6) nucleated BM cells. The aim of this study was to assess common phenotypic features of nine tumor cell lines established from BM of patients with cancer of the prostate (four cell lines), breast (two cell lines), lung (two cell lines), and colon (one cell line) using immunocytochemistry, flow cytometry, and reverse transcription-PCR. All cell lines stained positive for both cytokeratins, the epithelial intermediate filaments, and the epithelial cell adhesion molecule E-cadherin, and they lacked markers of BM-derived cells. The tumor origin of the cell lines was supported by the expression of the ErbB2 oncogene (seven of nine) and MAGE mRNA (eight of eight). All cell lines coexpressed cytokeratin and vimentin, the mesenchymal intermediate filament, indicating an epithelial-mesenchymal transition of micrometastatic cells. The invasive phenotype of the immortalized cells was also reflected by the consistent expression of several metastasis-associated adhesion molecules, including alpha5 (eight of nine), alpha6 (five of nine), alphaV (nine of nine), beta1 (nine of nine), and beta3 (nine of nine) integrin subunits and the Mr 67,000 laminin receptor (seven of nine). Contrary to our expectations, metastasis-promoting CD44 variant isoforms were only detected on two lines, whereas all cell lines expressed MUC18/melanoma cell adhesion molecule and intercellular adhesion molecule-1, two members of the immunoglobulin superfamily of adhesion molecules that are not frequently found on primary carcinoma cells. The consistent expression of various epithelial and tumor-associated antigens provides evidence that the established cell lines are derived from disseminated cancer cells present in the BM. The invasive phenotype of the immortalized cells was mirrored by their epithelial-mesenchymal transition and the expression of several metastasis-associated molecules, which might be potential candidates for novel therapeutic targets.

Biomarkers, Tumor

Comparison of primary angioplasty with conservative therapy in patients with acute myocardial infarction and contraindications for thrombolytic therapy. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

The benefit of primary angioplasty in patients with acute myocardial infarction (AMI) and contraindications for thrombolysis compared to a conservative regimen is still unclear. Out of 5,869 patients with AMI registered by the MITRA trial, 337 (5.7%) patients had at least one strong contraindication for thrombolytic therapy. Out of these 337 patients 46 (13.6%) were treated with primary angioplasty and 276 (86.4%) were treated conservatively. Patients treated conservatively were older (70 years vs. 60 years; P=0.001), had a higher rate of a history with chronic heart failure (14.8% vs. 4.4%; P=0.053), a higher heart rate at admission (86 beats/min vs. 74 beats/min; P=0.001), and a higher prevalence of diabetes mellitus (27.1% vs. 12.8%; P=0.056). Patients treated with primary angioplasty received more often aspirin (91.3% vs. 74.6%; P=0.012), beta-blockers (60.9% vs. 46.1%; P = 0.062), angiotensin converting enzyme (ACE) inhibitors (71.7% vs. 44%; P=0.001), and the so-called optimal adjunctive medication (54.4% vs. 32.3%; P=0.004). Hospital mortality was significantly lower in patients who received primary angioplasty (univariate: 2.2% vs. 24.7%; P=0.001; multivariate: OR=0.46; P=0.0230). In patients with AMI and contraindications for thrombolytic therapy, primary angioplasty was associated with a significantly lower mortality compared to conservative treatment. Therefore, hospitals without the facilities to perform primary angioplasty should try to refer such patients to centers with the facilities for such a service, if this is possible in an acceptable time.

Aged

Differences in patients with acute myocardial infarction treated with primary angioplasty or thrombolytic therapy. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

BACKGROUND: Little is known about the differences in patients with acute myocardial infarction (AMI) treated with primary angioplasty or intravenous thrombolysis in clinical practice. METHODS: In all, 5,906 patients with AMI were registered by the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) study. Of these, 491 (8.3%) patients were treated with primary angioplasty and 2,817 (47.7%) with intravenous thrombolysis. RESULTS: There were only minor differences in baseline characteristics between the two groups. Prehospital delay time (median) was longer in the angioplasty group than in the thrombolysis group (161 vs. 120, p = 0.001), as was door-to-treatment time (88 vs. 30 min; p = 0.001). Patients treated with primary angioplasty more often had contraindications for thrombolytic therapy (12.9 vs. 6%, p = 0.001) and received beta blockers (65 vs. 58.1%, p = 0.004), heparin (98.2 vs. 91.6%, p = 0.001), angiotensin-converting enzyme (ACE) inhibitors (64.8 vs. 50%, p = 0.001) and "optimal" concomitant medication (56.4 vs. 42.9%, p = 0.001) more often. Univariate analysis showed a significant lower incidence of heart failure (5.3 vs. 16.5%, p = 0.001), postinfarct angina (7.3 vs. 16.4%, p = 0.001), in-hospital death (7.9 vs. 11.7%, p = 0.015) and the combined end point (21.6 vs. 40.3%, p = 0.001) in these patients. Stepwise logistic regression analysis revealed optimal concomitant medication [odds ratio (OR) = 0.94, 95% confidence interval (CI): 0.89-0.98) and the type of revascularization (OR = 0.65, 95% CI: 0.58-0.73) to be associated with a significant reduction in the incidence of the combined end point. Similar results were obtained in all predefined subgroups. CONCLUSIONS: In clinical practice, patients treated with primary angioplasty are more often treated with beta blockers and ACE inhibitors than patients treated with intravenous thrombolysis. Thus, the selection of patients and the type of revascularization contributes to the reduction in mortality, overt heart failure, and postinfarct angina in these patients.

Angioplasty, Balloon, Coronary

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

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

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

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

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

[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

[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

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

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

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

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

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

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

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