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Biomedical subjects

M J Frank

Publications and source records attributed to M J Frank.

At least 55 records · Page 3Linked to original sources

Potentially lethal arrhythmias and their management in hypertrophic cardiomyopathy.

The prevalence of potentially lethal arrhythmias (PLA) in groups of patients with hypertrophic cardiomyopathy has been assessed, but the rate at which they develop (their incidence) during long-term follow-up has not been reported. Therefore, conduction system disease (CSD) (sick sinus syndrome and His-ventricular disease), ventricular couplets and ventricular tachycardia (VT) detected by routine electrocardiograms, periodic 24-hour Holter monitoring and periodic exercise stress testing were studied in 50 patients treated with large doses of beta-adrenergic blocking drugs who were followed for 2 to 14 years (mean 5.9). Sixteen PLAs detected at the beginning of observation were excluded from actuarial analysis for new PLAs . Twenty-one patients had 24 new PLAs (7 with CSD, 1 patient with sustained supraventricular tachycardia, 6 with ventricular couplets and 10 with VT); only 43% of these PLAs were heralded by new symptoms. In 6 patients, the arrhythmia caused symptoms and was identified by a routine electrocardiogram. The 3 patients with His-ventricular disease presented with syncope and required electrophysiologic confirmation of this diagnosis. In only 1 patient was a PLA (ventricular couplets) detected only by exercise testing. All other ventricular arrhythmias were detected by Holter monitoring. The incidence of CSD in 47 patients free of this condition at entry was 5% at 5 years and 33% at 10 years. The incidence of ventricular couplets or VT in 39 patients free of these at entry was 26% at 5 years and 75% at 10 years, and the incidence of VT only was 18% at 5 years and 40% at 10 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Kinetics and mechanism of degradation of cefotaxime sodium in aqueous solution.

The degradation kinetics and mechanism of a potent new cephalosporin, cefotaxime sodium, in aqueous solution were investigated at pH 0-10 at 25 degrees and an ionic strength of 0.5. The degradation rates were determined by high-pressure liquid chromatography and were observed to follow pseudo first-order kinetics with respect to cefotaxime sodium concentration. The data suggested that the rate of degradation was influenced significantly by solvolytic, hydrogen ion, and hydroxide ion catalysis. No primary salt effects were observed in the acid or neutral regions; however, a positive salt effect was observed at pH 8.94. Buffer catalysis due to the buffer species employed was not seen during the kinetic studies. The pH-rate profile at 25 degrees indicated that the maximum stability of cefotaxime sodium occurred in the pH 4.5-6.5 region. In aqueous solution, cefotaxime was shown to degrade by two parallel reactions: de-esterification at the C-3 position and beta-lactam cleavage. Good agreement between the theoretical pH-rate profile and the experimental data support the proposed degradation process.

Buffers↗

Current physiologic pacemakers: a serious problem with a new device.

Twenty adults underwent implantation of an automatic (DDD) pacemaker (Medtronic model 7000, Versatrax I) for treatment of symptomatic bradyarrhythmias. Only 9 patients had optimal DDD mode pacing during 78 paced months. In 3 patients, the DDD mode was changed to atrioventricular (AV) sequential (DVI) early because of risk imposed by sustained tachycardia upon underlying myocardial ischemia. The remaining 8 had had tachycardia due to pacemaker reentry, and 7 had neurologic and cardiovascular symptoms. DDD pacing was abandoned in 5 when reentry could not be interrupted by digitalis administration or reprogramming. Three continue to be paced in DDD mode despite intermittent reentrant tachycardias, with digitalis diminishing episodes of reentry in only 1. Mean ventriculoatrial conduction time was 229 +/- 34 ms. Reentrant pacemaker tachycardia developed in 7 of 12 with normal or nearly normal AV conduction, but in only 1 of 5 with complete heart block. Preimplantation electrophysiologic study did not reliably detect and initial postoperative Holter monitoring did not predict reentrant tachycardia. The risk of reentry caused by a short, fixed atrial refractory period combined with the high occurrence of slow retrograde AV conduction, particularly in patients with normal or nearly normal anterograde conduction, renders the Versatrax I and other similar pacemakers unsuitable for DDD mode pacing in many patients.

Bradycardia↗

Value of ventricular premature complex (VPC) morphology in the diagnosis of hypertrophic cardiomyopathy.

Experimental and clinical studies have established the value of ventricular premature complexes (VPC) with a QR pattern in the diagnosis of occult antecedent myocardial infarction. However, the clinical significance of a QR pattern VPC in patients with hypertrophic cardiomyopathy has not been previously evaluated. In order to study this, we examined the ECGs and 24-hour Holter monitor records of 45 consecutive patients with hypertrophic cardiomyopathy and 106 consecutive patients with various other diseases. A QR pattern VPC in the precordial leads with a Q greater than or equal to 40 ms and a Q/R ratio greater than or equal to 0.20 had a specificity of 97%, a sensitivity of 29% and a predictive value of 80% in the diagnosis of hypertrophic cardiomyopathy. We conclude that a QR pattern VPC may be of value in the eclectic diagnosis of hypertrophic cardiomyopathy and that it is not specific for antecedent myocardial infarction as previously reported.

Cardiomyopathy, Hypertrophic↗

Long-term medical management of hypertrophic cardiomyopathy: usefulness of propranolol.

Chronic therapy with propranolol has been shown to reduce the incidence of sudden death in patients with hypertrophic cardiomyopathy (HCM). However, the long-term effect of beta blockade on exercise capacity has not been studied adequately. Therefore, 32 patients with HCM (21 men), mean age of 47 years (range = 14 to 80 years), were evaluated for dyspnea and chest pain and underwent stress testing (ST) prior to therapy. At entry, ST was contraindicated in four patients, because of heart failure (three patients) and sustained supraventricular tachycardia (one patient). The remaining patients completed 4.9 +/- 3.2 min (mean +/- S.D.) of the Bruce protocol with a functional aerobic capacity (FAC) of 51 +/- 28%. All were placed on propranolol, unless a beta blocker with other characteristics was indicated. Dosage was adjusted to achieve a standing heart rate of 60 beats/min unless adverse effects occurred. At last follow-up, 25 patients were receiving 501 +/- 147 mg propranolol/day while the remainder received nadolol or metoprolol. On the most recent ST, patients exercised 6.6 +/- 3.1 min (38% increase), while mean FAC increased by 24% (both P less than 0.05). The FAC improved by more than 15% in 21, by less than 15% in five, was unchanged in five and was worse in only one, a noncompliant patient. The 21 patients with an FAC increment much greater than 15% exercised longer at entry than the remaining 11 (6.6 +/- 3.3 vs 3.9 +/- 2.8 minutes, P less than 0.05). The mean peak ST blood pressure-heart rate product of the group decreased from 26 550 to 17 898 (P less than 0.05), while the symptom scores of dyspnea and chest pain declined from 2.2 +/- 0.8 to 0.8 +/- 0.7 and from 1.4 +/- 1.0 to 0.3 +/- 0.8, respectively (both P less than 0.001). We conclude that beta blockade produces sustained improvement in exercise capacity. Improvement was greatest in those with the least initial impairment, and appears to be related to a reduction in blood pressure-heart rate product.

Adolescent↗

Rhythm disturbances in hypertrophic cardiomyopathies: relationship to symptoms and the effect of 'complete' beta blockade.

Potentially lethal arrhythmias (PLA) are common in hypertrophic cardiomyopathies and are implicated in sudden death. We have demonstrated that propranolol is effective in controlling symptoms, but have not previously evaluated its effect on PLA. Our protocol for long-term management has been applied to 50 patients followed for 2 to 14 years (mean 5.9 years). No patient was excluded because of disease severity or complications. The only reason for exclusion was non-compliance with the protocol. At entry, Holter monitoring revealed 16 PLA in 13 patients (sustained supraventricular tachycardia (SSVT) in two, sinus node dysfunction (SSS) in three, paired beats (PB) in five, and ventricular tachycardia (VT) in six). All patients were initially begun on propranolol, unless a different beta blocker was indicated. Dosage was adjusted to a standing heart rate of 60 beats/min unless adverse drug effects developed. Holter monitoring during follow-up identified 24 new PLA in 21 patients (SSVT = 1, SSS = 4, His-Purkinje disease = 3, VT = 10, and PB = 6). The total number of identified PLA is now 40 in 30 patients. Concurrent symptoms of syncope, presyncope and palpitations were of limited value in identifying PLA because of a lack of predictive accuracy (76%, 64% and 29%, respectively). Invasive electrophysiologic study or dosage adjustment proved that beta blockade was not responsible for the conduction system disorders observed in 10 patients requiring pacemaker insertion. beta-Blockade completely suppressed VT in two patients, PB in five, and SSVT in two.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Classroom use of personal computers in medical education: a practical approach.

Classroom lectures in medical schools have traditionally employed a blackboard and slides. We have developed a compact, durable, and relatively low-priced system for computer-assisted instruction which introduces audiovisual material in a random-access manner. When this system was used in the classroom to provide flexible, clinical simulations, it promoted a high level of audience-instructor interaction and facilitated problem-based learning. The system has been used successfully in lectures in our medical school, at other medical schools, at community hospitals and at national scientific meetings.

Computer-Assisted Instruction↗

Use of a personal computer in the measurement, calculation, and reporting of noninvasive cardiac data.

Echocardiography, phonocardiography, and carotid pulse tracings enable the cardiologist to measure and calculate over 40 different noninvasive parameters including cardiac chamber size, indices of left ventricular performance, and estimates of mean left atrial pressure. However, the entire procedure requires meticulous measurements and time-consuming calculations, particularly when some of the data must be corrected for heart rate or body size. Because of this, many busy noninvasive cardiac laboratories routinely calculate only a few select parameters in most patients. To solve this problem, we used a personal computer system and developed a program that allows rapid, accurate measurement, calculation, display, reporting, magnetic storage, and retrieval of noninvasive cardiac data. The computer is not dedicated to these tasks alone and with appropriate software can also be used for other clinical, educational, office management, and research purposes.

Computers↗

Postextrasystolic changes in systolic time intervals in the assessment of hypertrophic cardiomyopathy.

To determine if postextrasystolic changes in systolic time intervals can be used to estimate the severity of resting or provocable left ventricular outflow pressure gradient, we studied the cardiac catheterisation records of 42 patients with hypertrophic cardiomyopathy looking for instances of a single premature beat preceded by a control sinus beat and followed by a postpremature sinus beat. There were 75 such instances in 25 patients. In comparison to the control beat, the pre-ejection period in the postpremature beat was shorter by deltaPEP = -20 +/- 11 ms in 73 of 75 instances, and remained unchanged in two. The ejection time in the postpremature beat was invariably longer by deltaET = 37 +/- 20 ms (range: 10 to 85 ms) and the pre-ejection period/ejection time ratio lower than control by delta(PEP/ET) = -0 . 10 +/- 0 . 05 (range: -0 . 01 to -0 . 25). Total electromechanical systole in the postpremature beat was shorter (11/75), the same (10/75), or longer (53/75) than in the control beat, the overall change being deltaEMS = -18 +/- 22 ms. Both deltaPEP and delta(PEP/ET) correlated poorly with the systolic peak left ventricular-aortic pressure gradient in either the control beat (Gc) or the postpremature beat (Gx), and also with the change in gradient (delta G) from the control to the postpremature beat. In contrast, significant linear correlations were found between delta EMS and either Gc, Gx, or delta G; and also between deltaET and either Gc, Gx, or deltaG. Since internal and external measurements of ejection time are known to be almost identical, the regression equation (deltaG = 1 . 65 delgaET -9) relating deltaET and deltaG should be useful for the non-invasive assessment of the magnitude of provocable left ventricular outflow pressure gradient in patients with hypertrophic cardiomyopathy with spontaneous or externally-induced premature beats.

Blood Pressure↗

Non-neuronal cells in the spinal cord of nude and heterozygous mice. I. Ventral horn neuroglia.

A quantitative light microscopic analysis of the ventral grey matter in the lumbar spinal cord of homozygous nude (nu/nu) and heterozygous (nu/+) mice was performed to determine the possible contribution of lymphocytes to normal C.N.S. tissue. If lymphocytes were present in the neuropil, they could be mistaken for neuroglial cells. Athymic nude mice offer a good model, since they lack T-lymphocytes and symptoms of neurological involvement. Mean cell counts from 1 micrometer sections were tested by analysis of variance. There were not strain differences for the area and number of neurons. The total neuroglial cell count was also similar, but the number of oligodendrocytes decreased 28%, astrocytes increased 51% and microglia were unchanged in the nude compared with the heterozygous mouse. There were no qualitative differences at the ultrastructural level among the neuroglia of either strain. Either the genetic defect retards and alters neuroglial cell development, or some of the small, round dark nuclei belong to lymphocytes, which have earlier migrated into the C.N.S. parenchyma. Lymphocytes could then participate in a cell-mediated immune response with brain macrophages, which are thought to be primarily derived from mononuclear leukocytes.

Animals↗

Clinical significance and hemodynamic correlates of the third heart sound gallop in aortic regurgitation. A guide to optimal timing of cardiac catheterization.

The hemodynamic and clinical data of 42 patients with chronic significant aortic regurgitation and 31 normal subjects were examined. Of the patients with aortic regurgitation, 28 had a third heart sound (S3) gallop and 14 did not. There was no significant difference in the severity of regurgitation between the patients with or without an S3 gallop. However, all patients with an S3 gallop had an abnormality increased left ventricular residual volume and depressed contractile state. These findings were supported by the hemodynamic data of two patients who underwent cardiac catheterization before and after the development of an S3 gallop. We conclude that the S3 gallop in patients with chronic AR reflects left ventricular dysfunction, rather than more severe degrees of regurgitation per se, and may therefore be useful for selecting patients for cardiac catheterization and consideration for prosthetic aortic valve replacement.

Adolescent↗