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Biomedical subjects

L M Epstein

Publications and source records attributed to L M Epstein.

At least 55 records · Page 3Linked to original sources

Radiofrequency catheter ablation of atrial arrhythmias. Results and mechanisms.

BACKGROUND: Radio frequency catheter ablation is accepted therapy for patients with paroxysmal supraventricular tachycardia and has a low rate of complications. For patients with atrial arrhythmias, catheter ablation of the His bundle has been an option when drugs fail or produce untoward side effects. Although preventing rapid ventricular response, this procedure requires a permanent pacemaker and does not restore the atrium to normal rhythm. Therefore, we evaluated the safety and efficacy of radiofrequency ablation directed at the atrial substrate. METHODS AND RESULTS: Thirty-seven patients with 42 atrial arrhythmias (mean +/- SD age, 41 +/- 24 years) who had failed a median of three drugs were enrolled. Diagnoses were automatic atrial tachycardia in 12, atypical atrial flutter in 1, typical atrial flutter in 18, reentrant atrial tachycardia in 8, and sinus node reentry in 3 patients. Sites for atrial flutter ablation were based on anatomic barriers in the floor of the right atrium. For automatic atrial tachycardia, the site of earliest activation before the P wave was sought. All with reentrant atrial tachycardia had previous surgery for congenital heart disease and reentry around a surgical scar, anatomic defect, or atriotomy incision and our goal was to identify a site of early activation in a zone of slow conduction. At target sites, 20 to 50 W of radiofrequency energy was delivered during tachycardia between the 4- or 5-mm catheter tip and a skin patch, except in 4 patients with atrial flutter, in whom a catheter with a 10-mm thermistor-embedded tip was used. Procedure end point was inability to reinduce tachycardia. Acute success was achieved in 11 of 12 (92%) with automatic atrial tachycardia, 17 of 18 (94%) with typical atrial flutter, 7 of 8 (88%) with reentrant atrial tachycardia, and 3 of 3 (100%) with sinus node reentry but not in the patient with atypical atrial flutter. For tachycardia involving reentry (reentrant atrial tachycardia and atrial flutter), successful ablation required severing an isthmus of slow conduction. For those with atrial flutter, this was between the tricuspid annulus and the coronary sinus os (10) or posterior (4) or posterolateral (3) between the inferior vena cava (2) or an atriotomy scar (1) and the tricuspid annulus. Deep venous thrombosis occurred in 1 patient. At mean follow-up of 290 +/- 40 days, the ablated arrhythmia recurred in 1 (9%) with automatic atrial tachycardia, 5 (29%) with atrial flutter, and 1 (14%) with reentrant atrial tachycardia, all of whom had successful repeat ablation. Previously undetected arrhythmias occurred in 2 patients who are either asymptomatic or controlled with medication. CONCLUSIONS: Ablation of automatic and reentrant atrial tachycardia and atrial flutter had a high success rate and caused no complications from energy application. Repeat procedures may be required for long-term success, especially in patients with atrial flutter. The mechanism by which ablation is successful is similar for atrial flutter and other forms of atrial reentry and involves severing a critical isthmus of slow conduction bounded by anatomic or structural obstacles. Automatic arrhythmias are abolished by directing lesions at the focus of abnormal impulse formation.

Adult↗

Electrophysiological laboratory, electrophysiologist-implanted, nonthoracotomy-implantable cardioverter/defibrillators.

BACKGROUND: Implantable cardioverter/defibrillators (ICDs) have conventionally been implanted in the operating room by surgeons. However, technological developments have reduced size and increased simplicity, bringing the procedure into the realm of the electrophysiologist. The purpose of this study was to evaluate the safety and efficacy of implantation of the entire ICD system by electrophysiologists in an electrophysiology laboratory. METHODS AND RESULTS: Between July 1993 and February 1994, 23 patients (21 men; age, 64 +/- 11 years) underwent transvenous ICD implantation by electrophysiologists working alone, entirely in the electrophysiology laboratory. Indications for ICD were sudden death in 10 patients, uncontrolled life-threatening ventricular tachycardia in 12, and syncope with cardiomyopathy and familial sudden death in 1. Seventeen patients had coronary artery disease and a past history of acute myocardial infarction. Four patients had idiopathic dilated cardiomyopathy, 1 had coronary ectasia and poor left ventricular function, and another had poor left ventricular function related to valvular dysfunction. The mean left ventricular ejection fraction was 34 +/- 10% (range, 20% to 50%). General anesthesia was administered in 22 cases, and deep sedation was used in 1 elderly patient. After positioning of transvenous leads and subcutaneous patch/array lead positioning, defibrillation testing was performed. After transvenous and subcutaneous lead tunneling, all generators were placed subcutaneously in an abdominal pocket. The mean total time in the electrophysiology laboratory was 254 +/- 68 minutes (range, 150 to 375 minutes), with 104 +/- 42 minutes for anesthetic and other preparation, 159 +/- 45 minutes for implantation, and 8.7 +/- 5 minutes (range, 3 to 25 minutes) of fluoroscopy required for positioning of transvenous and subcutaneous lead systems. Implant times showed a significant improvement when the first 10 cases (188 +/- 44 minutes) were compared with the last 10 in the series (124 +/- 44 minutes, P < .01). The mean defibrillation threshold was 17 +/- 5 J (range, 5 to 25 J). There were 5 complications (22%): 1 patch-site hematoma, 1 pneumothorax related to subclavian venous puncture, 1 pulmonary embolism, and 2 patients requiring overnight ventilation after hemodynamic deterioration following defibrillation testing. There were no deaths, and there were no infections. The mean time to hospital discharge after the implant was 5.1 +/- 3.5 days. After 11.6 +/- 9 weeks of follow-up, all devices were functioning satisfactorily, all patients had successfully defibrillated at postimplant predischarge checkup with 29 +/- 5 J, and there had been no late complications. CONCLUSIONS: This is the first report to show that nonthoracotomy ICD implantation may be successfully carried out by electrophysiologists working alone in the electrophysiology laboratory, with a high rate of success and few complications, even in high-risk patients. This high rate of success and safety probably relates to the availability of high-quality fluoroscopy and familiarity with electrophysiology laboratory equipment and personnel.

Adult↗

Radiofrequency catheter ablation of atriofascicular and nodoventricular Mahaim tracts.

BACKGROUND: Several mechanisms have been proposed to explain the pathogenesis of tachycardia in patients with Mahaim tracts. The tachycardia may involve antegrade conduction over an atriofascicular pathway with decremental properties or a nodofascicular pathway. METHODS AND RESULTS: We report six patients with recurrent episodes of preexcited tachycardia with findings consistent with "Mahaim tract" conduction. All patients exhibited decremental antegrade preexcited conduction with atrial pacing and a preexcited tachycardia with initial activation of the proximal right bundle branch. In four patients (group 1), atrial premature complexes (APCs) induced at the tricuspid annulus just after the inscription of the septal atrial electrogram and during left bundle branch block preexcited tachycardia advanced the next preexcited ventricular complex. In these patients, discrete Mahaim potentials were inscribed over the right anterolateral or lateral tricuspid annulus. Two patients (group 2) had evidence of dual atrioventricular nodal conduction. APCs during left bundle branch block tachycardia just after inscription of the septal atrial electrogram failed to advance the next ventricular complex with similar preexcited morphology, and no Mahaim potentials could be recorded from the tricuspid annulus. In group 1 patients, application of radiofrequency energy to sites recording the Mahaim potentials resulted in tachycardia cure. For patients in group 2, selective slow atrioventricular nodal pathway ablation in the midseptal region resulted in complete ablation of both the slow atrioventricular nodal pathway and Mahaim conduction in two patients. CONCLUSIONS: Mahaim tachycardia can be due to atriofascicular pathways, which may be ablated over the right tricuspid annulus, or to septal pathways, which may arise from the slow atrioventricular nodal pathway in patients with dual atrioventricular nodal physiology. In the latter circumstance, successful ablation is achieved by placing the lesion in the midseptal region.

Adult↗

Ventricular septal summit stimulation in atrioventricular nodal reentrant tachycardia.

In all, 18 consecutive patients with atrioventricular nodal reentry tachycardia (AVNRT) underwent right ventricular (RV) stimulation during AVNRT from either the RV apex or summit. Stimulation from the RV apex advanced the tachycardia with the same atrial sequence in 6 of 18 patients (33%), but never conclusively excluded the presence of a low atrial tachycardia. RV summit stimulation resulted in direct stimulation of the low septal right atrium in 6 patients. RV summit stimulation advanced the tachycardia in 4 patients, delayed it in 2 and terminated it in 3 without an atrial electrogram. The latter 2 findings exclude the presence of a low atrial tachycardia. Thus, in patients with AVNRT, application of extrastimuli closer to the putative reentrant site enables greater efficacy in tachycardia resetting and in excluding a low septal atrial tachycardia.

Cardiac Pacing, Artificial↗

Conserved sequence and functional domains in satellite 2 from three families of salamanders.

Thirteen satellite 2 elements from Ambystoma talpoideum and 16 from Amphiuma tridactylum were cloned, sequenced, and compared with the satellite 2 consensus from Notophthalmus viridescens. These elements have maintained a high degree of similarity during the 65-200 Myr that the salamander families, represented by the three species, have been separated. The DNA sequences of the consensus elements from A. talpoideum and A. tridactylum are 81% similar, and both are approximately 65% similar to the N. viridescens consensus. In addition to its DNA sequence, the functional properties of satellite 2 have also been conserved. By selecting and analyzing clones that closely mimicked the consensus of each species, we were able to demonstrate that satellite 2 from each species was capable of promoting transcription after injection into Xenopus laevis oocytes and that synthetic transcripts of satellite 2 from each species were capable of catalyzing their own site-specific cleavage. These properties may be related to the process of retroposition, which was previously proposed to be responsible for the genomic proliferation of satellite 2. Each of these functional properties also has general biological interest.

Ambystoma↗

Tissue-specific permutations of self-cleaving newt satellite-2 transcripts.

Synthetic transcripts of satellite-2 (sat2) DNA from the newt undergo self-catalyzed, site-specific cleavage in vitro using the conserved hammerhead (HH) motif found in a number of infectious plant RNAs. We have analyzed sat2 transcripts from a variety of tissues to obtain evidence for the occurrence of self-cleavage in vivo. We found two distinct types of sat2 transcript populations. Monomeric transcripts in the tests and in somatic tissues such as the liver have ends that map to the in vitro self-cleavage site, and have end groups (5'-hydroxyls and phosphate blocked 3' ends) similar to those produced by self-cleavage. This is the first indication of HH-mediated self-cleavage occurring in animal cells. The monomeric sat2 transcripts found in the newt ovary have a different permutation of the basic DNA repeat sequence. These transcripts begin and end 47 nucleotides upstream from the in vitro self-cleavage site. Despite their apparent lack of utilization of the self-cleavage site, they have end groups which indicate that processing is involved in their formation.

Animals↗

Alternative modes of self-cleavage by newt satellite 2 transcripts.

Synthetic transcripts of satellite 2 DNA from the newt undergo self-catalyzed cleavage in vitro. In this report we present evidence that there are at least two distinct modes of satellite 2 transcript self-cleavage. In one mode, a single cleavage domain folds into a structure which cleaves at a slow rate. This structure may be analogous to, or a variant of, the 'hammerhead' structure believed to be active during the self-cleavage of a number of infectious plant RNAs. In an alternative mode, multiple cleavage domains interact to cleave at an enhanced rate. The permutation of the repeated satellite 2 sequence determines which of these modes of cleavage will predominate, presumably by influencing the overall conformation of the RNA. We present a model for the self-processing of multimeric satellite 2 transcripts which incorporates both of these modes of self-cleavage.

Animals↗

Newt satellite 2 transcripts self-cleave by using an extended hammerhead structure.

Synthetic transcripts of satellite 2 DNA from newts undergo self-catalyzed, site-specific cleavage in vitro. Cleavage occurs within a domain that is similar to the hammerhead domain used by a number of self-cleaving, infectious plant RNAs. The newt hammerhead has a potentially unstable structure due to a stem composed of two base pairs and a 2-nucleotide loop, and unlike other hammerheads that have been studied, it cannot cleave as an isolated unit. Here we show that cleavage by a single newt hammerhead requires additional satellite 2 sequences flanking both ends of the hammerhead domain. We also present a structural model of a truncated satellite 2 transcript which is capable of cleavage. The structure includes an internally looped extension to one of the conserved stems of the hammerhead. By in vitro mutagenesis, the identities of each of the five nucleotides composing one of the internal loops were shown to be critical for cleavage. Additional evidence that the extension stimulates self-cleavage in a manner other than by simply stabilizing the hammerhead is presented.

Animals↗

Modification of the atrioventricular node. A new approach to the treatment of supraventricular tachycardias.

Atrioventricular nodal modification appears to be a relatively safe and effective treatment option for patients with refractory AV nodal reentrant tachycardia. Hopefully, the long-term results will be as encouraging as the initial experience. Newer surgical and catheter techniques, together with a better understanding of the mechanisms underlying AV nodal reentrant tachycardia, may lead to improved efficacy and safety. In the future, AV nodal modification may obviate the need for drug therapy in patients with symptomatic AV nodal reentrant tachycardia and be applied to the treatment of other supraventricular tachycardias.

Anti-Arrhythmia Agents↗

Smoking among medical and engineering students.

A cross-sectional survey, using an anonymous self-administered questionnaire, was conducted among 364 medical and engineering students in their first and later years of study. The study compared knowledge, attitudes towards smoking, and smoking practices between the faculties and between the years. The prevalence of current smoking was 24.1%. It was similar in each faculty and in every year, despite greater knowledge on the adverse health effects of smoking among students in the higher years in the faculty of medicine. Greater knowledge of the risks of smoking is not sufficient to bring about a reduction in smoking habits.

Adult↗

Percutaneous catheter modification of the atrioventricular node. A potential cure for atrioventricular nodal reentrant tachycardia.

Our purpose was to describe a technique of atrioventricular (AV) node modification for patients with drug refractory AV nodal reentrant tachycardia (AVNRT). Nine patients (mean age, 45 +/- 20; range, 14-82) with recurrent drug refractory AVNRT (n = 8) or sudden cardiac death thought to be precipitated by AVNRT (n = 1) underwent a percutaneous catheter procedure to modify AV nodal function. The area between the electrode recording the maximal His-bundle electrogram and the ostium of the coronary sinus was divided into three zones. Perinodal direct current shocks of 100-300 J were delivered to one (n = 2), two (n = 3), or three (n = 4) zones without complications. The procedure endpoints were modification of AV conduction (either first degree AV block or complete retrograde ventriculo-atrial [VA] block) and failure to induce AVNRT before or after isoproterenol and/or atropine administration. Six of nine patients (67%) have had no inducible or spontaneous AVNRT over a mean follow-up of 12.3 +/- 4.1 months (range, 4.5-17). One of the six underwent repeat, successful modification, because AVNRT was inducible at restudy 2 days after the initial procedure. AVNRT recurred in three patients (33%), one early (3 days) and two late (3-4 months). Two of these patients underwent complete ablation of the AV junction and permanent pacemaker placement, whereas one is controlled with drug therapy. Therefore, AV nodal modification resulted in tachycardia control without antiarrhythmic drugs in six of nine (67%) and obviated the need for complete AV junctional ablation in seven of nine patients (78%). Elimination of AVNRT appears to result from either block in the retrograde fast pathway or modification of the antegrade slow pathway, such that AVNRT cannot be sustained. Additional findings suggest that an atrio-Hisian accessory connection may not be involved in AVNRT in some of these patients. Percutaneous catheter AV nodal modification appears to be a promising technique for treatment of refractory AVNRT and may obviate need for complete AV junctional ablation in a substantial number of patients with drug/pacemaker refractory AVNRT.

Adult↗

Unnecessary hospitalization days: rates in two general hospitals in Israel.

The efficient use of hospital resources is an important issue. In order for the hospital management to identify definite areas where and why this use is inefficient, the Appropriateness Evaluation Protocol is used. The rate of unnecessary hospitalization days was thus studied during 1984 in two government general hospitals in Israel. Two simultaneous studies, cross-sectional and longitudinal, were conducted by the same team in the general medicine, surgery and gynecology wards. Unnecessary hospitalizations were found in both hospitals. The rate was particularly high in the surgery departments of the university hospital where there were 2.5-3 times more unnecessary days than in the community hospital. The major reasons for these unnecessary days in the university hospital were internal (problems concerning the use of diagnostic facilities, operating rooms and consultants), whereas in the community hospital they related mainly to discharge planning. The study identified definite areas in which hospital authorities could possibly take action to reduce the wastage.

Adolescent↗

An outbreak of measles among young adults. Clinical and laboratory features in 461 patients.

We report the clinical and laboratory characteristics of measles infection in an unselected group of 461 young adults. Otitis media was diagnosed in 9.8%, sinusitis in 4.1%, pneumonia in 3.7%, and keratitis in 3.3% of the patients. Minor T-wave changes on electrocardiogram were observed in only 0.7% and jaundice in 0.4%. Elevated liver enzymes were found in 51% of the patients. Creatine kinase (CK) MM fraction was high in 44%. Traces of myoglobin were found in the urine of 14% of those with a high CK, and of the 13 patients with the higher CKs, 12 had an abnormal serum aldolase. We emphasize several points of interest in this large and unselected group of young adults. There was 1) possible evidence of rhabdomyolisis in some of our patients; 2) a lower rate of electrocardiogram abnormalities than previously reported; 3) no evident correlation between initial laboratory values and subsequent complications; and 4) lack of a clinical or laboratory difference between patients who had been vaccinated with an attenuated virus during childhood and those who had not.

Adolescent↗

Self-cleaving transcripts of satellite DNA from the newt.

Satellite 2 of the newt, Notophthalmus viridescens, is a 330 bp tandemly repeated sequence scattered throughout the genome. Cytoplasmic transcripts homologous to satellite 2 are found in a variety of tissues. Most of the transcripts correspond precisely in length to the DNA repeat unit or to whole multiples of that repeat. We show here that dimer-sized satellite 2 transcripts, synthesized with SP6 RNA polymerase from a plasmid clone, undergo site-specific, self-catalyzed cleavage in vitro. The reaction proceeds at neutral pH and requires Mg++ but no other cofactor or energy source. The cleavage products have 5'-hydroxyl and 3'-phosphate groups, at least some of which are in the form of 2',3'-cyclic phosphates. In this respect the reaction resembles the self-cleavage of certain small, infectious RNAs found in plants. Furthermore, the in vitro cleavage of satellite 2 transcripts occurs within a sequence that is homologous to the conserved cleavage site of the infectious RNAs. The existence of monomer and multimer transcripts in the cell suggests that the monomer may arise by site-specific cleavage of long primary transcripts. However, the 5' end of the cellular monomer is 46 or 47 bases upstream of the in vitro cleavage site, suggesting that factors in the cell may modify the cleavage reaction.

Animals↗