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Biomedical subjects

M B Rosenbaum

Publications and source records attributed to M B Rosenbaum.

At least 19 recordsLinked to original sources
PubMed1995

High prevalence of antibodies against beta 1- and beta 2-adrenoceptors in patients with primary electrical cardiac abnormalities.

OBJECTIVES: This study sought to determine the prevalence of autoantibodies directed against the beta-adrenoceptors in patients with primary electrical cardiac abnormalities, including atrial arrhythmias, ventricular arrhythmias and conduction disturbances, in the absence of any other cardiac abnormality. BACKGROUND: Using synthetic peptides corresponding to the predicted sequences for the second extracellular loop of the human beta 1- and beta 2-adrenoceptors as antigenic targets, autoantibodies directed against the beta-adrenoceptors were recently shown to occur in patients with idiopathic dilated cardiomyopathy and Chagas' heart disease. METHODS: Eighty-six patients (57 with primary electrical abnormalities, 29 with idiopathic dilated cardiomyopathy) and 101 healthy and cardiopathic control subjects were studied. Antibodies against the beta 1- and beta 2-peptides were detected with an enzyme immunoassay performed in blinded manner. In nine selected (seropositive) cases, the immunoglobulin G (IgG) fraction was tested for functional effects on the rate of beating of cultured neonatal rat cardiomyocytes. RESULTS: Antibodies recognizing the beta 1- and beta 2-peptides were found in 11 (52.3%) of 21 patients with ventricular arrhythmias (p < 0.01), 5 (35.7%) of 14 patients with conduction disturbances (p < 0.05), 3 (13.6%) of 22 patients with atrial arrhythmias (p > 0.05) and 11 (37.9%) of 29 patients with dilated cardiomyopathy (p < 0.05) compared with 15 (14.8%) of 101 control subjects. A rapid increase in the rate of beating of the cultured cardiomyocytes was induced by IgG from a selected group of patients, suggesting an agonist-like interaction with a functional epitope. This response was mediated by stimulation of both the beta 1- and beta 2-adrenoceptors in the patients with primary ventricular arrhythmias but only the beta 1-adrenoceptors in the patients with idiopathic dilated cardiomyopathy. CONCLUSIONS: Primary ventricular arrhythmias and conduction disturbances, like idiopathic cardiomyopathy, show a high prevalence of antibodies interacting with functional epitopes of the beta-adrenoceptors, suggesting a common or similar abnormal immunoregulatory process.

Adult↗
PubMed1994

Overdrive prolongation of refractoriness and fatigue in the early stages of human bundle branch disease.

OBJECTIVES: The aim of this study was to assess the response of refractoriness in normal and diseased human bundle branches to changes in cycle length, as well as during a long period of continuous overdrive pacing. BACKGROUND: The anterograde refractory period of the bundle branches in patients with functional bundle branch block shortens as the rate is increased. The rate-dependent response of refractoriness in diseased bundle branches is quite different. However, this difference has not been precisely delineated, and its physiologic meaning is uncertain. METHODS: Refractoriness of the bundle branches was measured by the extrastimulus technique in 16 patients with tachycardia-dependent bundle branch block and 10 patients with functional bundle branch block, both after basic trains of 8 atrial-paced impulses at different cycle lengths and during a 10-min period of continuous overdrive pacing. RESULTS: The baseline refractory period in the bundle branches of patients with functional bundle branch block measured 430 +/- 32 ms (mean +/- SD) and shortened to 368 +/- 30 ms at the shortest cycle length. The maximal effect was reached within the 1st min of overdrive pacing. The baseline refractory period of the bundle branches was significantly longer in patients with tachycardia-dependent bundle branch block (611 +/- 184 ms) and demonstrated a cumulative overdrive prolongation in 15 (83%) of 18 studies with typical manifestations of fatigue. In two other studies, this occurred only after ajmaline administration. CONCLUSIONS: A rate- and time-dependent prolongation of refractoriness frequently occurs in diseased human bundle branches. When absent, this response may be induced under the effects of sodium channel blockers. This would suggest that an abnormality in the recovery from inactivation of the sodium channel might underlie the early stages of bundle branch disease.

Adult↗
PubMed1994

Antibodies to beta-adrenergic receptors disclosing agonist-like properties in idiopathic dilated cardiomyopathy and Chagas' heart disease.

Recent studies confirm the existence of antibodies (Abs) to beta-adrenoceptors in patients with idiopathic dilated cardiomyopathy and Chagas' heart disease. These Abs can be shown to exert both stimulatory and inhibitory effects, which may play a role in the development of the cardiac abnormalities known to occur in these diseases, including advanced heart failure. The hypothesis is advanced that Chagas' heart disease and some forms of idiopathic dilated cardiomyopathy may represent, at least partially, a form of "adrenergic cardiomyopathy."

Animals↗
PubMed1991

Pseudo 2:1 atrioventricular block and T wave alternans in the long QT syndromes.

The extreme prolongation of ventricular action potential duration that occurs in some of the long QT syndromes may result in two forms of alternating activity of the heart: a "pseudo" 2:1 atrioventricular (AV) block and a T wave alternation, both of which are rate dependent. The pseudo 2:1 AV block relates to the extreme prolongation of ventricular refractoriness. The T wave alternation reflects the fact that the rate dependence of action potential duration differs in degree or magnitude in the subendocardial and subepicardial layers of the ventricular wall. Examples of two cases previously reported in the Journal by Weintraub et al. are used to illustrate and discuss these manifestations.

Action Potentials↗
PubMed1990

Contrasting effects of verapamil and procainamide on rate-dependent bundle branch block: pharmacologic evidence for the role of depressed sodium channel responses.

The mechanisms responsible for intermittent bundle branch block are still under debate. The role of the time-dependent behavior of the slow calcium channel has recently been emphasized. To test this hypothesis and ascertain the possible involvement of the fast sodium channel, the effects of the slow calcium channel blocker verapamil and the fast sodium channel blocker procainamide were compared in 10 patients with intermittent bundle branch block. All 10 patients showed bundle branch block during spontaneous sinus rhythm. Maneuvers to slow cardiac rate (that is, carotid sinus massage, Valsalva maneuver) were performed to identify normal conduction as well as phase 4 bundle branch block. Thus, the ranges of diastolic intervals (RR) resulting in phase 3 (tachycardia-dependent) bundle branch block, phase 4 (bradycardia-dependent) bundle branch block and normal conduction were measured in two control studies performed before intravenous administration of verapamil (control 1) and procainamide (control 2) and at the peak effect of both drugs. In the control studies, all 10 patients showed phase 3 bundle branch block, whereas phase 4 bundle branch block occurred in only 4 patients. The ranges of phase 3 bundle branch block, phase 4 bundle branch block and normal conduction were very similar in control studies 1 and 2. The phase 3 bundle branch block range was slightly shortened by verapamil (983 +/- 83.5 ms in control 1; 930 +/- 69.4 ms at the peak effect of verapamil), whereas phase 4 bundle branch block remained unchanged. In contrast, conduction was systematically worsened by procainamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Rate dependence and supernormality in excitability of guinea pig papillary muscle.

It is well known that in most cardiac tissues an increase in rate results in a decrease of excitability and, eventually, conduction block. We used microelectrode techniques to evaluate the rate and time dependence of excitation latency in 27 isolated guinea pig papillary muscles (GPPM). Latency was measured as the interval between the stimulus onset and action potential upstroke. When the intensity of current was just suprathreshold, prolongation of the basic cycle length (BCL) from 300 to 1,000 ms produced an increase in latency or failure of excitation. Such behavior was observed with extracellular as well as intracellular stimulation. Rate-dependent changes in latency were maximal during the first 10-20 s following the rate change and reached a steady state in approximately 200 s. Application of premature beats revealed the presence of a "supernormal phase" in which latency abbreviated. Strength-interval and strength-duration curves demonstrated that changes in excitability accurately paralleled those observed in latency. Hence, supernormal excitability at the end of the phase 3 repolarization was consistently observed in all ventricular muscle experiments. Deceleration-induced decrease of excitability was attended by hyperpolarization, increase of action potential upstroke velocity (Vmax) and action potential amplitude, and decrease in membrane resistance. Our data suggest that paradoxical rate-related changes of excitability in GPPM are the result of changes in the passive membrane properties. Under conditions of depressed conductivity, this particular behavior may account for the occurrence of bradycardia-dependent block.

Animals↗
PubMed1989

Identification of major Trypanosoma cruzi antigenic determinants in chronic Chagas' heart disease.

To identify Trypanosoma cruzi target antigens in overt Chagas' heart disease, a parasite lambda gt11 cDNA library was screened with the serum of a patient with a severe chagasic heart involvement (JL). Using a phage dot array immunoassay, 5 highly antigenic clones, JL1, JL5, JL7, JL8, and JL9, were probed with sera from clinically characterized T. cruzi infected subjects. The correlation of cloned T. cruzi antigen recognition with the clinical status of the subjects led to the identification of a recombinant antigen, JL5, that reacted predominantly with sera from patients with Chagas' heart disease. The antigenic determinant of the JL5 recombinant was a small 35 amino acid peptide. The nucleotide and the deduced amino acid sequence, together with other experimental data, allowed identification as the C-terminal portion of a T. cruzi P ribosomal protein. The C-terminal undecapeptide in JL5, EDDDMGFGLFD, was highly homologous to the same region of the human P protein SD(D/E)DMGFGLFD. The latter sequence has been identified as the P protein epitope in systemic lupus erythematosus (SLE). Positive SLE sera reacted with the JL5 recombinant phage, suggesting that the T. cruzi P protein might induce antibodies with a similar specificity to that of P antibodies in SLE.

Adult↗
PubMed1987

Supernormal conduction in the accessory pathway of patients with overt or concealed ventricular pre-excitation.

It was recently shown that supernormal conduction in the diseased His-Purkinje system is more common than previously thought, and is always associated with prolongation of refractoriness. To assess whether supernormal conduction could also occur in the accessory pathway of patients with ventricular pre-excitation, 21 patients with manifestly prolonged refractoriness in the accessory pathway were studied. Under these conditions, programmed atrial stimulation revealed a phase of supernormal conduction in 16 (76%) of the 21. Therefore, what was believed to be a nonexistent or exceptional physiologic event was shown to be a rather common finding, at least under certain circumstances. Supernormal conduction occurred in all 7 patients with an anterograde refractory period of 480 to 980 ms, and in 5 of 10 patients with a refractory period greater than 1.0 second or with no anterograde conduction. Supernormal conduction could not be demonstrated in four patients with a refractory period less than or equal to 440 ms, but appeared in all four patients after the refractory period was prolonged by a rapid rate of stimulation or administration of ajmaline. The electrophysiologic changes underlying the occurrence of supernormal conduction in the accessory pathway are similar to those previously reported for the bundle branch system. The demonstration of supernormal conduction in the accessory pathway may uncover the presence of concealed ventricular pre-excitation. Supernormal conduction over the accessory pathway may facilitate a rapid ventricular response during atrial fibrillation, even if the refractory period is prolonged.

Heart Conduction System↗
PubMed1987

Chronic idiopathic idioventricular tachycardia caused by slow response automaticity.

A 22-year-old female, asymptomatic and without any evidence of cardiac disease, was found to have a persistent idioventricular tachycardia (IVT). Sinus rhythm and IVT rates were similar and showed parallel changes in successive resting electrocardiograms. Both IVT and sinus rhythm were transiently slowed or suppressed by vagal stimulation and accelerated by sympathetic stimulation. Long periods of atrial overdrive pacing, at a rate 62% faster than the spontaneous rate of IVT, depressed both ectopic and sinus activity. Fast channel blocking agents (lidocaine, disopyramide), and digoxin and amiodarone failed to modify IVT significantly. Verapamil, a calcium channel blocking drug, allowed total control of the arrhythmia. These electrophysiologic and pharmacologic responses suggest that the IVT may relate to the automatic activity of a ventricular focus of the "slow response" type, functionally resembling an "additional" sinus node with preserved innervation. During an 88-month follow-up, the patient continued to be asymptomatic, warning arrhythmias were never found and the features of IVT remained unmodified.

Adult↗
PubMed1986

Comparative antiarrhythmic efficacy of verapamil, 17-monochloracetylajmaline, mexiletine and amiodarone in patients with severe chagasic myocarditis: relation with the underlying arrhythmogenic mechanisms.

The antiarrhythmic effects of verapamil, 17-monochloracetylajmaline, mexiletine and amiodarone were compared in 14 patients with chagasic myocarditis. Drugs and placebo were administered orally in the following order: placebo and verapamil, placebo and 17-monochloracetylajmaline, placebo and mexiletine (1 week each) and placebo and amiodarone (4 weeks each). A 24 hour ambulatory electrocardiographic recording was obtained after administration of each placebo and drug. Verapamil had no effect on the number of ventricular premature complexes, ventricular couplets and runs of ventricular tachycardia. 17-Monochloracetylajmaline did not reduce the number of ventricular premature complexes and ventricular couplets but caused a moderate reduction in runs of ventricular tachycardia. Mexiletine failed to significantly reduce ventricular premature complexes but caused a moderate decrease in both ventricular couplets and runs of ventricular tachycardia. Amiodarone was the only one of the four drugs that caused a substantial reduction of ventricular premature complexes (logarithmic mean 97.8%; p less than 0.001), total suppression of runs of ventricular tachycardia in 11 of 11 patients and suppression of ventricular couplets in 8 of 14 patients and a significant reduction in the remaining 6 patients. The much greater efficacy of amiodarone as compared with the two sodium channel modifiers (17-monochloracetylajmaline and mexiletine) and one calcium channel blocker (verapamil) suggests that its potent antiarrhythmic activity is probably related to other peculiar and still undefined electrophysiologic and pharmacologic properties.

Adult↗
PubMed1986

Liaison consultation psychiatry with patients who have replantation surgery to the upper limb.

Thirty-eight patients who had replantation surgery to the upper limb were studied and findings, case vignettes and specific liaison-consultation issues are presented. The assessment of the patient for pre-existing psychopathology, such as drug and alcohol abuse and personality abnormalities, is emphasised; the possibility of the amputation having been a deliberate, self-inflicted act is noted; and the roles of pre-accident stress and emotional conflict are discussed. Data concerning adverse post-operative emotional reactions are presented and body-image changes, including the disruption to body integrity and the reintegration of the bodily part, are described. The psychological aspects of replantation surgery are compared to other forms of surgery, in particular amputation and renal transplantation.

Accident Proneness↗
PubMed1985

Psychological reactions and processes following replantation surgery: a study of 50 patients.

Fifty consecutive patients admitted for replantation surgery received a psychiatric evaluation. In 28 percent of the patients there was evidence of preaccident psychopathology. Fifty-four percent of the patients reported a recent stressful life event predating the accident. Fifty-four percent of the patients were assessed as having an adverse postoperative emotional reaction. The presence of preaccident psychopathology, evidence of family dysfunction, and a history of a recent stressful life event were positively linked with an adverse postoperative emotional reaction. In addition, patients with hand or arm replants were significantly less likely to require a psychiatric intervention than patients with leg replants. The psychological processes pertaining to the replantation journey are described in five stages: the preaccident period, the initial response, the stage of uncertainty, the recognition of loss, and acceptance and reintegration. Finally, the role of a liaison psychiatrist on a replantation unit is outlined and further research is strongly urged.

Adult↗
PubMed1984

Efficacy of amiodarone during long-term treatment of potentially dangerous ventricular arrhythmias in patients with chronic stable ischemic heart disease.

Amiodarone was administered orally to 30 patients with chronic stable coronary artery disease and severe ventricular arrhythmias. Control studies revealed frequent (more than 30/hr) ventricular premature beats (VPBs) (27 patients), bigeminy (21 patients), couples (29 patients), R-on-T phenomenon (14 patients), ventricular tachycardia (16 patients), and ventricular fibrillation (1 patient). Two 24-hour Holter recordings and stress tests were performed before treatment, and an average of 3.6 per patient were done during treatment. Amiodarone caused suppression of all ventricular arrhythmias in 13 (43%) of the 30 patients and suppression of all complex forms and greater than 90% reduction of VPB number in 14 patients (47%) during a follow-up of 12.4 months. The mean dose was 590 mg/day in the 27 responders and 300 mg/day in the three nonresponders. A similar antiarrhythmic response was observed during stress testing. One of the 30 patients died due to massive pulmonary embolism and no arrhythmias were detected. In addition, amiodarone suppressed the occurrence of anginal pain and effort-induced ST changes in 9 of 10 patients and in 11 of 13 patients, respectively. The rate-pressure product and peak heart rate were significantly reduced in all patients. Our results suggest that amiodarone may be ideally suited for treatment of ventricular arrhythmias and for possible prevention of sudden death in patients with ischemic heart disease.

Adult↗
PubMed1984

Efficacy of amiodarone during long-term treatment of malignant ventricular arrhythmias in patients with chronic chagasic myocarditis.

Oral amiodarone was administered to 24 patients with chronic chagasic myocarditis (CCM) and malignant ventricular arrhythmias. Control 24-hour Holter recordings revealed frequent ventricular premature beats (VPBs) (157 to 2572/hr; mean 714 +/- 125), multiform VPBs, and countless numbers of ventricular couplets in all patients, R-on-T phenomenon in 17 patients, and ventricular tachycardia in 21 patients. Amiodarone caused total and persistent suppression of ventricular couplets and tachycardia and greater than 93% reduction of VPB number in 22 patients, during a follow-up of 26.6 months (range 2 to 55 months). In 1 patient, ventricular couplets and tachycardia persisted despite the fact that a 98.2% reduction of VPB number was achieved. This latter patient was the only one in the whole group who experienced sudden death. The maximal antiarrhythmic effect was attained gradually after 3 to 26 weeks (mean 7.4). In four patients in whom treatment was discontinued after 3 to 12 months, the antiarrhythmic protection lasted 4 to 9 weeks. In nine patients the dose of amiodarone was 600 to 800 mg/day. In 15 patients the dose had to be increased to 800 to 1000 mg/day. Despite the presence of congestive heart failure in seven patients and intraventricular block in 17 patients, no limiting side effects were observed. Amiodarone proved to be extremely effective and safe against the most malignant ventricular arrhythmias of CCM.

Adult↗