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Biomedical subjects

B Schumacher

Publications and source records attributed to B Schumacher.

At least 19 recordsLinked to original sources

[Catheter ablation as an emergency treatment in Wolff-Parkinson-White syndrome with signs of acute infarct].

A 53-year-old man known to have Wolff-Parkinson-White syndrome suffered an acute posterior-wall myocardial infarction. Despite successful thrombolysis treatment with streptokinase he continued to have attacks of supraventricular tachycardia with angina. The ECG showed a short P-R interval and pre-excitation with positive delta waves in leads V1-6, as well as signs of re-infarction. The tachycardias could not be satisfactorily suppressed by drug treatment. Coronary angiography revealed triple vessel disease. During this investigation ventricular extrasystoles occurred which initiated orthodromic supraventricular tachycardia and angina, as well as monophasic S-T elevations in leads II, III and aVF. This provided the indication for immediate high-frequency catheter ablation left laterally at the mitral anulus after a left-lateral accessory conduction pathway had been identified. Three days later the stenoses of the circumflex and anterior interventricular branches were dilated. The patient has been free of symptoms for 3 months and can exercise up to 150 W. The tachycardias have not recurred.

Angina Pectoris

Vesicular stomatitis virus transcription inhibited by purified MxA protein.

MxA is a GTPase encoded by an interferon-inducible human gene. Its constitutive expression renders transfected mammalian cells resistant to infections with several different RNA viruses, including vesicular stomatitis virus (VSV). Differences in viral RNA levels of VSV-infected cells either expressing or lacking MxA indicated that VSV mRNA synthesis is the principal target of MxA action. We now used purified histidine-tagged MxA (His-MxA) that we produced in Escherichia coli to successfully inhibit VSV in vitro transcription, a reaction catalyzed by VSV ribonucleoprotein complexes isolated from virus-infected cells or from purified virions. MxA was inactive when added to preformed VSV mRNAs, arguing against the possibility that it has a negative effect on viral RNA stability. MxA inhibited both leader RNA and mRNA synthesis of VSV, suggesting that it interfered with transcription initiation. The degree of VSV inhibition correlated directly with the specific GTPase activities of the various wild-type MxA preparations. No inhibition of viral mRNA synthesis was observed when a C-terminally truncated, GTPase-inactive variant of His-MxA was added to the transcription reactions. Purified His-MxA-E645R, a mutant of MxA with normal GTPase activity whose range of antiviral activity in vivo is altered so that it no longer inhibits VSV, showed no inhibitory effect on VSV in vitro transcription. Since MxA inhibited VSV RNA synthesis in the presence of GMP-PNP or GTP gamma S, GTP analogs that are readily accepted by the viral polymerase but cannot be hydrolyzed by MxA, the possibility was excluded that MxA acts by depleting the viral polymerase for its nucleotide substrates. Thus, binding of GTP rather than its hydrolysis seems of importance for the anti-VSV activity of MxA.

Animals

Prospective study of retrograde coronary venography in patients with posteroseptal and left-sided accessory atrioventricular pathways.

The morphologic features of the coronary vein system was prospectively studied with retrograde venography in 117 patients with left-sided (78 patients) and posteroseptal accessory pathway (39). Findings were compared with accessory pathway localization. A mean of 3.3 +/- 1.5 venous branches draining into the coronary sinus or the great cardiac vein could be visualized. The morphologic condition was described and classified. Incidence, morphologic condition, and distribution did not differ between left-sided and posteroseptal accessory pathway. Venous abnormalities including ectasy, diverticulum, narrowing, angulation, and hypoplasia occurred in 22.2%. Diverticulum and narrowing were present in posteroseptal accessory pathway only and always related to the successful ablation site. In patients with left-sided accessory pathway, ectasy, angulation, and hypoplasia were found. Anomalies were less frequent (9% vs 43.6%, p < 0.001) and had no relation to accessory pathway localization. However, the successful ablation site was in 42.3% located < 5 mm to an angiographically visualized venous branch. In conclusion, posteroseptal accessory pathways are often related to coronary sinus abnormalities. In patients with a left-sided accessory pathway venous malformation is uncommon, whereas a close anatomic relation exists between accessory pathway localization and venous ventricular branches.

Adolescent

Intravenous adenosine during atrioventricular reentrant tachycardia: induction of atrial fibrillation with rapid conduction over an accessory pathway.

Adenosine is considered to be a safe agent for termination of orthodromic atrioventricular reentrant tachycardia in patients with accessory pathways. A case with initially successful accessory pathway ablation and without preexcitation during sinus rhythm is presented, in which intravenous adenosine (6 mg) during orthodromic tachycardia was followed by atrial fibrillation and sudden onset of preexcitation with subsequent rapid ventricular response with moderate hemodynamic compromise.

Adenosine

Pacemaker function during radiofrequency ablation.

There are increasing numbers of radiofrequency current ablation procedures being reported. Selected patients have antitachycardia or antibradycardia pacemakers. The pacemaker behavior during and after ablation procedures differs widely. We report on the pacemaker reaction of 25 patients with 13 different devices, most with unipolar electrodes. Sensing failures were observed in 8 (32.0%) and pacing failures in 4 (16.0%) patients. Prolonged pauses and induction of tachyarrhythmias were observed. No pacemaker damage was seen although it is reported by other investigators. We recommend deactivation of implanted generators and an external bipolar pacing electrode. Manufacturers should focus their attention on this problem and protect the generators and their functions for 500 kHz radiofrequency current.

Adult

Echocardiographic imaging of coronary sinus diverticula and middle cardiac veins in patients with preexcitation syndrome: impact on radiofrequency catheter ablation of posteroseptal accessory pathways.

To determine the value of echocardiography for identifying coronary sinus (CS) diverticula and middle cardiac veins (MCVs) in patients with posteroseptal accessory pathways (PAPs), transthoracic (TTE) and transesophageal echocardiography (TEE) were performed in 18 consecutive patients with PAP and in 15 control subjects with left lateral accessory pathway before CS angiography. The size, shape, and location of CS diverticula and MCV were described and compared to angiography. TEE and angiography were concordant for the identification of diverticula (n = 5) and agreed for depicting MCV in 22 of the 27 cases. TTE revealed 4 of 5 diverticula and identified 4 of 27 MCV (P < 0.001). Fourteen MCV but no diverticula were found in the control subject. There was no significant difference between transesophageal and angiographic measurements for the width (23.5 +/- 4.9 vs 26.8 +/- 6.6 mm) and height (13.5 +/- 3.8 vs 15.7 +/- 3.4 mm) of the diverticula, and the width (3.5 +/- 0.7 vs 3.7 +/- 0.6 mm) of MCV. TEE underestimated the length of the MCV (12.0 +/- 1.8 vs 27.2 +/- 6.0, P < 0.001). Delivery of radiofrequency energy within the neck of a diverticulum or within an MCV was successful in 5 of 5, and 6 of 13 cases in patients with PAPs, respectively. In conclusion, echocardiography was as reliable as angiography for detecting and describing CS diverticula and MCV in patients with preexcitation syndrome. Echocardiography is recommended prior to electrophysiological study because it may simplify radiofrequency catheter ablation.

Adult

Impact of the local atrial electrogram in AV nodal reentrant tachycardia: ablation versus modification of the slow pathway.

INTRODUCTION: The purpose of this study was to determine the predictors of successful ablation versus modification sites of the slow pathway in patients with AV nodal reentrant tachycardia. Complete elimination of slow pathway conduction ("ablation") is considered to be an appropriate endpoint during radiofrequency (RF) current delivery, whereas the persistence of residual slow pathway conduction with or without single echo beats ("modification") may be indicative of tachycardia recurrence. METHODS AND RESULTS: Of 131 patients, 71 consecutive patients were followed for 15.1 +/- 7.6 months. After elimination of inducible AV nodal reentrant tachycardia in all patients, residual slow pathway conduction (modification) persisted in 38 patients, whereas complete elimination of slow pathway conduction (ablation) was documented in 33 patients. Including electrophysiologic study after 5 to 7 days and after 3 to 6 months, 6 (8.4%) patients had recurrences: 5 with residual slow pathway conduction after the procedure and 1 with complete elimination of slow pathway conduction (P < 0.05). As compared with modulated sites, ablation sites of the slow pathway were characterized as follows: (1) duration of the local atrial electrogram (AEGM) (66.7 +/- 10.2 vs 54.1 +/- 12.6 msec, P < 0.01); (2) interval from the end of the AEGM to onset of His-bundle deflection (4.4 +/- 8.2 vs 16.1 +/- 9.3 msec, P < 0.01); and (3) number of peaks of the AEGM as an indicator of fractionation (4.1 +/- 0.7 vs 3.0 +/- 0.8, P < 0.01). The rate of junctional tachycardias (103.4 +/- 12.1 vs 102.1 +/- 16.9 per min), the AV ratio (0.4 +/- 0.5 vs 0.5 +/- 0.5), the number of RF current deliveries (4.1 +/- 4.4 vs 4.5 +/- 4.4), the duration of the procedure (124.1 +/- 45.3 vs 125.6 +/- 42.3 min), and the fluoroscopy time (15.5 +/- 10.8 vs 16.6 +/- 9.6 min) as well as power and total energy of RF current deliveries and the anatomically calculated catheter position at the successful site were not statistically different. A subset analysis in patients who received only a single RF application showed the same results for both groups. Patients without recurrence (n = 65) were found to have longer duration of the AEGM (61.9 +/- 14.6 msec) and a shorter interval from the end of AEGM to the onset of His-bundle deflection (10.1 +/- 12.2 msec) than patients with recurrence (n = 6) (47.5 +/- 7.5 msec and 20.8 +/- 12.8 msec, respectively). CONCLUSION: Complete ablation of the slow pathway resulted in a lower recurrence rate. The complete ablation approach is feasible using precisely analyzed local AEGMs to guide RF current in AV nodal reentrant tachycardia in a short procedure time.

Adult

[Prognostic value of signal averaged ECG in dilated cardiomyopathy with spontaneous and induced ventricular tachyarrhythmias].

UNLABELLED: Ventricular late potentials in signal-averaged ECG are a predictor of ventricular tachyarrhythmias in patients with coronary artery disease. The role of signal-average ECG in non-ischemic dilated cardiomyopathy has not been defined yet. We studied the prognostic impact of an abnormal signal-averaged ECG in 31 patients with non-ischemic dilated cardiomyopathy. All signal-averaged ECG recordings were analyzed by time-domain analysis as well as by frequency analysis with spectrotemporal mapping. RESULTS: In 13 (42%) patients time domain analysis and in 9 (29%) patients frequency analysis was found to be abnormal. During follow-up (13 +/- 7 months) seven (23%) patients developed spontaneous ventricular tachyarrhythmias. The mean ejection fraction and the results of programmed ventricular stimulation did not differ significantly between patients with and without clinical episodes. Abnormal time domain analysis was found in five (71%) patients with and in eight (33%) patients without spontaneous tachyarrhythmias (p = 0.07), and abnormal frequency analysis in 3 (43%) patients versus 6 (25%) patients (p = 0.36). The low-amplitude-signal duration was significantly increased in patients with tachyarrhythmias (p = 0.008). Ventricular tachyarrhythmias occurred in 38% of patients with abnormal time domain analysis and in 33% of patients with abnormal frequency analysis. In patients with normal signal-averaged ECG the incidence reached 11% and 18%. For time-domain analysis the sensitivity was 71%, specificity 67%, positive predictive value 38%, and negative predictive value 89%, for spectrotemporal mapping 43%, 75%, 33%, and 82%, respectively. The incidence of electrophysiologically inducible ventricular tachyarrhythmias in patients with abnormal signal-averaged ECG exceeded that in patients with normal findings. CONCLUSION: In patients with non-ischemic dilated cardiomyopathy a normal signal-averaged ECG is associated with a reduced occurrence of ventricular tachyarrhythmic events. Thus, signal-averaged ECG contributes to the evaluation of these patients. The negative predictive value exceeded the positive predictive value.

Adult

The chicken Mx promoter contains an ISRE motif and confers interferon inducibility to a reporter gene in chick and monkey cells.

Genomic DNA containing the first four exons and upstream sequences of the interferon (IFN)-inducible chicken Mx gene was cloned and sequenced. The exon/intron structure of the chicken Mx gene resembles that of the mouse Mx1 gene: exon 1 is very small, the first intron contains a noncoding exon 1' that is alternatively spliced in different chicken breeds and exon 2 harbors the ATG initiation codon. Exons 3 and 4 of the chicken and mouse Mx genes have identical lengths and the encoded polypeptides show a high degree of homology. Sequences upstream of the transcription start site functioned as an IFN-inducible promoter in chick and monkey cells when cloned in front of a promoterless luciferase reporter gene. Deletion analysis suggested that the sequence 5'AGTTTCGTTTCT3' is of critical importance for inducibility. It conforms to the consensus sequence of the IFN-stimulated response element (ISRE) present in Mx and other IFN-alpha/beta-inducible promoters of mammals. These results suggest that the ISRE motif has been conserved and that it regulates expression of IFN-inducible genes in both mammals and birds.

Animals

Predictors of outcome in patients with implantable transvenous cardioverter defibrillators.

The identification of patients who benefit most from implantable cardioverter defibrillator (ICD) therapy is of great interest. To find out if clinical variables, the signal-averaged electrocardiogram, and electrophysiologic study predict occurrence of appropriate ICD discharges and death, we followed-up on 76 patients after implantation of a transvenous ICD. During a mean follow-up period of 18.2 +/- 6.4 months, 29 patients (38.6%) experienced at least one appropriate episode. When these patients were compared with those who had either no therapy or inappropriate episodes, three variables were found to be significant in the identification of patients who experienced appropriate discharges: (1) The mean ejection fraction of patients who received appropriate discharges was 35.4% +/- 13.5% versus 45.1% +/- 15.3% in the other group (p < 0.05); (2) patients with appropriate therapy had sustained monomorphic ventricular tachycardia that was more likely to be inducible (75.9% vs 21.2%, p < 0.01); and (3) in patients with appropriate therapy ventricular fibrillation was less likely to be inducible (10.3% vs 25.5%, p < 0.05). The signal-averaged electrocardiograms were more often abnormal, but the differences were not significant. The total mortality rate in our patient group was 7.8%, with nonsudden cardiac death in four patients, noncardiac death in one patient, and sudden death in one patient. In our patient group a lower ejection fraction and inducible sustained monomorphic ventricular tachycardia were predictors of future ICD discharge after implantation. The survival rate after transvenous ICD implantation is excellent; a longer follow-up period is necessary to further define predictors of total mortality rate.

Cardiac Pacing, Artificial

Loss of late potentials after radiofrequency catheter ablation of recurrent ventricular tachycardia in a patient with right bundle branch block.

The case of a patient with a history of myocardial infarction and recurrent ventricular tachycardia undergoing attempted radiofrequency catheter ablation with loss of late potentials is described. Prior to energy delivery fractionated, late activation could be found using the signal-averaged ECG despite the presence of a right bundle branch block. After successful catheter ablation, the clinical ventricular tachycardia was no longer inducible and the signal-averaged ECG, recorded the next day, showed marked changes indicating loss of late potentials. Our report emphasizes the possibility of late potential recordings despite the presence of bundle branch block.

Aged

Compartmentalized immune response reflects clinical severity of beryllium disease.

Although beryllium disease has been associated with a bronchoalveolar lavage (BAL) lymphocytosis and T cell-mediated immune response, we do not know if either the BAL cellular profile or the compartmentalized pulmonary response to the antigen reflect the severity of the disease. We studied 110 subjects divided into three groups of subjects: beryllium disease patients (n = 55), beryllium-sensitized patients without disease (n = 8), and control subjects (n = 47). Evaluation included completion of a respiratory symptom questionnaire, clinical examination, chest radiograph, spirometry, body plethysmographic lung volumes, and diffusing capacity (DLCO). In the patient groups, we performed maximal exercise testing with an indwelling arterial line. In addition, we examined BAL and performed blood and BAL beryllium lymphocyte transformation tests (BeLT) as measures of the beryllium-specific T cell-mediated response in these two compartments. In beryllium disease patients we correlated the BAL cellular constituents with clinical parameters indicative of disease severity. Beryllium disease patients exhibited elevated numbers of white cells and lymphocytes in BAL compared with both other groups; however, this lymphocytic alveolitis was significantly obscured in smokers. The BAL cellular constituents correlated with BAL BeLT but not with the blood BeLT. BAL cellular constituents also correlated with the radiographic profusion of small opacities, FEV1/FVC, DLCO, maximal achievable work load, VO2max, and measures of gas exchange at rest and at maximum exercise. We conclude that the lymphocyte-predominant pulmonary inflammatory response in beryllium disease is related to the magnitude of the localized response to antigen and that BAL cellularity, differential cell count, and BeLT reflect beryllium disease clinical severity.(ABSTRACT TRUNCATED AT 250 WORDS)

Berylliosis

Alveolar macrophages from patients with beryllium disease and sarcoidosis express increased levels of mRNA for tumor necrosis factor-alpha and interleukin-6 but not interleukin-1 beta.

Recent evidence suggests that the alveolar macrophage-derived cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) play important roles in granulomatous diseases. Our objective was to quantify the mRNA for these cytokines in beryllium disease, a human granulomatous disease of known etiology. We hypothesized that alveolar macrophages and bronchoalveolar lavage fluid from patients with beryllium disease and sarcoidosis would express increased levels of mRNA and proteins, respectively, for TNF-alpha, IL-1 beta, and IL-6 compared with those of normal individuals. We performed bronchoalveolar lavage and used a quantitative polymerase chain reaction to determine alveolar macrophage-derived cytokine gene expression. We determined lavage fluid cytokine levels by enzyme-linked immunosorbent assay. In patients with beryllium disease (n = 23), we observed elevated macrophage mRNA expression for TNF-alpha and IL-6 when compared with that of normal subjects (n = 7). Sarcoidosis patients (n = 6) also had increased expression for TNF-alpha and IL-6 compared with that of normal volunteers. IL-1 beta expression was similar in all three groups. In patients with beryllium disease (n = 39), lavage fluid TNF-alpha concentration was higher than that of 16 normal subjects. Lavage fluid IL-1 beta and IL-6 levels did not differ among the groups. This is the first report of macrophage cytokine expression in beryllium disease. These novel findings suggest that macrophage expression of TNF-alpha and IL-6 may be important in the human granulomatous inflammatory response.

Actins

Distraction effects on muscle. Leg lengthening studied in rabbits.

We investigated changes in the anterior tibial muscle during lengthening of the lower leg in rabbits. In 37 rabbits, an osteotomy of the right middle tibia was performed and was fixed by a unilateral external fixator. The rabbits were randomized into 6 groups. In groups 1, 2, and 3 the tibiae were distracted 0.5 mm/day. In groups 1 and 2, the rabbits were killed after 14 and 28 days of distraction, respectively, and in group 3 after 28 days of distraction, followed by 14 days of rest. Groups 1a, 2a, and 3a served as controls. They were treated similarly as groups 1, 2, and 3, but no distraction was performed. Proliferating cell nuclei were labeled with 5-bromo-2-deoxyuridine and were identified by immunohistochemical staining. The weight of the muscle was measured. During bone lengthening the muscle showed signs of growth, as indicated by increasing weight and number of proliferating cell nuclei. This was observed only during lengthening and it ceased when the lengthening was stopped.

Animals

Experimental use of a modified fibrin glue to induce site-directed angiogenesis from the aorta to the heart.

From 10 cultures of manipulated Escherichia coli bacteria expressing the class I heparin-binding growth factor polypeptide alpha-endothelial cell growth factor, 11.2 +/- 0.7 mg alpha-endothelial cell growth factor was eluted by heparin-sepharose affinity chromatography. Analysis of molecular weight (17,000 kD) was done by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and purification of the growth factor was done by high-performance liquid chromatography. The harvested alpha-endothelial cell growth factor was proved by protein blotting. To assess the growth-promoting activity, we did an endothelial cell growth assay by comparing adult human endothelial cell control cultures, without adding growth factor to the culture medium, with adult human endothelial cell cultures with 0.02 to 20.0 ng/ml alpha-endothelial cell growth factor and 1.0 ng/ml heparin and with adult human endothelial cell cultures with alpha-endothelial cell growth factor but without heparin. Tritiated thymidine counts proved the significant growth-promoting activity of alpha-endothelial cell growth factor. In 10 experimental animals modified fibrin glue containing 1 microgram alpha-endothelial cell growth factor was implanted between the aorta and the myocardium of the left ventricle and results were compared with those in five control animals that received normal fibrin glue without growth factor. After 9 weeks of implantation, angiography and histologic investigation showed newly grown vascular structures between the aorta and the myocardium in all experimental animals, but none in the control animals. Our study proved the feasibility of initiating site-directed formation of new blood vessel structures to the heart by a modified fibrin glue implant containing angiogenic growth factor alpha-endothelial cell growth factor.

Animals