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Biomedical subjects

M J Frank

Publications and source records attributed to M J Frank.

At least 37 records · Page 2Linked to original sources

Mexiletine versus quinidine as first-line antiarrhythmia therapy: results from consecutive trials.

The efficacy of mexiletine and quinidine in controlling ventricular couplets (VC) and ventricular tachycardia (VT) was compared in 156 trials (78 for each drug) in 114 consecutive patients. Forty-two patients received both drugs, whereas 36 patients were given mexiletine, and 36 patients received quinidine only. During acute drug testing, mexiletine was more effective than quinidine in controlling VC and VT (54 vs. 32 patients, respectively, P less than .001) and resulted in fewer proarrhythmic events (4 vs. 13, respectively, P less than .05). Mean duration of follow-up for mexiletine (27 +/- 14 mo) and quinidine (21 +/- 14 mo) did not differ. Long-term success was more frequent with mexiletine administration than quinidine administration (33/47 vs. 10/30 patients, respectively, P less than .01). The incidence of sudden death during follow-up with the two drugs did not differ overall, but more patients with ejection fraction greater than or equal to 40% died suddenly while taking quinidine than while receiving mexiletine (4/17 vs. 0/24, P less than .02). Mexiletine is as effective as quinidine for treating VC and VT and appears to be less proarrhythmic. It should be considered as an initial choice in the management of VC and VT.

Aged↗

Relationship of left ventricular mass to impairment of coronary vasodilator reserve in hypertensive heart disease.

An impaired coronary vasodilator reserve has been demonstrated in all stages of hypertensive heart disease but is most likely in the setting of hypertrophy. The decrease in coronary flow reserve has, however, not been predictable previously. We postulated that flow reserve depression might be related to a left ventricular mass threshold. Seventy-two patients (82% with hypertension) with suspected ischemic heart disease who were found to be free of significant coronary artery disease at cardiac catheterization were evaluated utilizing the intracoronary Doppler catheter and two-dimensional directed M-mode echocardiography for determination of coronary flow reserve and left ventricular mass. For left ventricular mass indexed (LVMI) by body surface area (BSA) greater than or equal to 50% above normal using established gender-specific norms, American Society of Echocardiography (ASE) and PENN methods (correction of LV mass by regression equation agreeing with necropsy estimates of mass) predicted impairment of flow reserve (p = 0.005 and 0.009, respectively). Unindexed left ventricular mass and LVMI by height were not helpful in this regard. Using the ASE method for LV mass determination, coronary flow reserve was moderately depressed (2.4 +/- 1.0) for those with LVMI greater than or equal to 50% above normal; in comparison, flow reserve was normal (3.5 +/- 1.3) for those with LVMI less than 50% above normal. A rare patient was able to maintain a normal flow reserve when ASE- and Penn-indexed mass estimates were greater than or equal to 50% above normal, but only in the setting of a markedly elevated mean arterial pressure.

Adult↗

The paradox of 'chronic unstable angina' secondary to an organizing intracoronary thrombus.

We have described a case in which coronary vasospasm and the resultant endothelial shear stresses most likely caused plaque rupture and transient coronary occlusion at the site of a minor atherosclerotic narrowing. Remodeling then led to a long, complex stenotic lesion that included ruptured and dissected endothelium and organized thrombus. This led to severe anginal symptoms over a 3-month period, or the paradox of "chronic unstable angina." Angioplasty was difficult but eventually successful after pulsed high-pressure balloon inflations and intracoronary thrombolytic therapy with streptokinase. This case demonstrates that the clinical course of a patient with minor or insignificant coronary disease may be a dynamic process that cannot be entirely predicted even by recent invasive cardiac studies.

Angina, Unstable↗

Current perspectives in hypertrophic cardiomyopathy: diagnosis, clinical management, and prevention of disability and sudden cardiac death.

Hypertrophic cardiomyopathy is a rare primary myocardial disease known for its dramatic morphologic and clinical manifestations. Sudden cardiac death and functional cardiac symptoms are common. However, differing pathologic mechanisms may be responsible for similar clinical symptoms and make a unified approach to therapy impossible. This review will discuss the genetics, criteria for diagnosis, relationship among pathophysiologic abnormalities and clinical symptoms, and management of hypertrophic cardiomyopathy.

Cardiomyopathy, Hypertrophic↗

Relations among impaired coronary flow reserve, left ventricular hypertrophy and thallium perfusion defects in hypertensive patients without obstructive coronary artery disease.

Invasive Doppler catheter-derived coronary flow reserve, echocardiographic measurements of left ventricular hypertrophy and intravenous dipyridamole-limited stress thallium-201 scintigraphy were compared in 48 patients (40 were hypertensive or diabetic) with clinical ischemic heart disease and no or minor coronary artery disease. Abnormal vasodilator reserve (ratio less than 3:1) occurred in 50% of the study group and markedly abnormal reserve (less than or equal to 2:1) occurred in 27%. Coronary vasodilator reserve was significantly lower (2.2 +/- 0.8 versus 3.5 +/- 1.3, p = 0.003) and indexed left ventricular mass significantly higher (152.6 +/- 42.2 versus 113.6 +/- 24.0 g, p = 0.0007) in patients with a positive (n = 11) versus a negative (n = 32) thallium perfusion scan. Coronary flow reserve was linearly related in coronary basal flow velocity as follows: y = -0.17x + 4.59; r = -0.57; p = 0.00002. The decrement in flow reserve was not linearly related to the degree of left ventricular hypertrophy. Abnormal vasodilator reserve subsets found in hypertensive patients were defined on the basis of basal flow velocity, indexed left ventricular mass and clinical factors. In this series, diabetes did not cause a detectable additional decrement in flow reserve above that found with hypertension alone. These findings demonstrate that thallium perfusion defects are associated with depressed coronary vasodilator reserve in hypertensive patients without obstructive coronary artery disease. Left ventricular hypertrophy by indexed mass criteria is predictive of which hypertensive patients are likely to have thallium defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗

Possible triggering of paroxysmal atrial fibrillation in normal hearts by psychological stressors: a report of two cases.

Paroxysmal atrial fibrillation was triggered by psychological stress in two patients, both of whom had normal echocardiograms and coronary angiography. Neither patient was alcoholic or had ingested ethanol in relation to the onset of atrial fibrillation and both were free of metabolic derangements. Possible mechanisms involved in the triggering of atrial fibrillation are discussed.

Adult↗

Significance of positive or negative thallium-201 scintigraphy in hypertrophic cardiomyopathy.

Myocardial ischemia, fibrosis and infarction may occur in patients with hypertrophic cardiomyopathy (HC) in the absence of epicardial coronary artery disease. To determine their prevalence and relation with common characteristics, stress thallium-201 scintigraphy was performed in 28 patients. Eleven (39%) had positive scans despite normal epicardial coronary arteries (7 patients) or a pretest risk of coronary disease less than or equal to 5% (4 patients). There was no relation between thallium defects and age, sex, chest pain or outflow tract gradients at rest. However, the mean left ventricular ejection fraction was significantly lower in those with perfusion abnormalities compared with those without (64 +/- 15 vs 75 +/- 11%, respectively, p less than 0.05). Also, the mean ventricular septal thickness was greater in patients with positive scans (27 +/- 7 vs 21 +/- 6 mm, p less than 0.05), and there was a nonparametric relation between increasing septal thickness and the frequency of positive scans (p less than 0.025). Seven of 11 patients with positive scans had ventricular tachycardia compared with none among those who had negative scans (p less than 0.001), and 5 of these 11 patients had conduction system disease requiring permanent pacemaker insertion compared with 1 of 17 with negative scans (p less than 0.025). It is concluded that thallium perfusion abnormalities are common in patients with HC in the absence of epicardial coronary disease, and are strongly associated with potentially lethal arrhythmias. Thallium scintigraphy appears to identify a subset of patients with HC at increased risk for sudden death, who therefore require closer follow-up.

Adult↗

Pathophysiology and management of unstable angina.

Significant progress has been made in recent years in unraveling the dynamic mechanisms involved in the production of unstable angina. This knowledge, and advances in medical and interventional therapy allow the formulation of treatment strategies aimed at specific pathogenic mechanisms and promise to reduce mortality and morbidity. This review covers the diagnosis, pathogenesis, risk stratification, and therapy of unstable angina.

Adrenergic beta-Antagonists↗

Myocardial ischemia without atherosclerosis.

Myocardial ischemia in the presence of normal epicardial coronary arteries can be caused by an abnormality in the microcirculation or myocardial cell or by hypertrophy resulting in depressed coronary vasodilator reserve. Newly developed methods of assessing coronary blood flow and velocity make definitive diagnosis possible. Treatment, which may be difficult, includes therapy for the underlying cause, a calcium blocker, and nitrates.

Angina Pectoris↗

Presyncope and syncope. How to find the cause and avoid staggering costs.

Presyncope and syncope are relatively common in the primary care population, but episodes may signal serious metabolic, neurologic, or cardiovascular disease. Accurate diagnosis is important, because treatment must be directed to the underlying cause. The cost of a full evaluation can be staggering; therefore, a goal-oriented approach to diagnosis is most productive and cost-effective.

Age Factors↗

Disappearance of high-grade left anterior descending stenosis after revascularization.

Complete resolution of a high-grade left anterior descending (LAD) stenosis 6 months after revascularization with a left internal mammary artery (IMA) graft and the first reported case of spontaneous IMA graft spasm during repeat cardiac catheterization for continued atypical chest pain in the same patient are reported. Mechanisms involving regression of atherosclerosis and atypical spasm are briefly discussed.

Adult↗

How can we diagnose coronary heart disease in hypertensive patients?

Chest pain is a common complaint among hypertensive patients. Hypertension and coronary heart disease each may present with symptoms and signs that are clinically indistinguishable. Noninvasive testing by routine exercise stress testing and stress radionuclide angiography are not reliably predictive of ischemia resulting from obstructive epicardial coronary artery disease and should be abandoned for that diagnostic purpose. Noninvasive thallium-201 myocardial perfusion imaging for this purpose may prove to be a valuable tool, avoiding the risk and expense of coronary arteriography. However, carefully performed prospective studies are not available. Because of the high prevalence of both diseases, a high priority must be given to obtaining these data and evaluating other noninvasive methods (especially positron emission tomography) if they appear promising.

Cardiomegaly↗

Application of differential scanning calorimetry to the study of solid drug dispersions.

The present study describes the application of differential scanning calorimetry (DSC) to ascertain the crystalline state of a drug with a melting point of approximately 53 degrees C after dispersion on hydrophilic carriers by either simple mixing or by fusion. The carriers examined include polyethylene glycol 6000 and colloidal silicon dioxides. The most interesting of the systems investigated, in which the drug is gradually transformed from the crystalline to the amorphous state at room temperature, are physical mixtures of the drug and colloidal silicon dioxides. The crystalline transformation is manifested by the gradual decrease in the endothermic transition energy of the physical mixture with time. The crystalline transformation is characteristically biphasic with initially fast first-order kinetics, followed by a slow conversion process. The rate of transformation is dependent on the drug-silicon dioxide ratio, temperature, and certain physical properties of the silicon dioxides. An inverse relationship exists between transition energy and the in vitro dissolution rate of the drug in the physical mixtures with silicon dioxide. This suggests that DSC may provide a useful method for evaluating the effects of formulation variables upon dissolution rate.

Calorimetry↗

Nonpolar density gradient ultracentrifugation in the direct determination of myocardial subcellular calcium.

A new method is described for making direct measurements of compartmentalized subcellular stores of calcium in the isolated perfused dog heart. Cellular calcium was immobilized by freezing the myocardium in diastole with an extremely cold fluorocarbon fluid (-125 degrees C). All subsequent procedures were conducted under conditions which prevented ionic diffusion, either at temperatures well below the freezing point of water or in the absence of water. Sarcolemmal and mitochondrial enriched fractions were segregated from dessicated, homogenized, myocardial tissue by ultracentrifugation utilizing density-gradients composed of blends of silicone and halocarbon on fluids within which physiological salts are insoluble. The total calcium content of these isolated fractions were then determined by atomic absorption spectrophotometry. Ouabain and epinephrine were subsequently used to alter the contractility of the perfused hearts and such contractile alterations were then related to changes noted in the calcium activity of the isolated subcellular fractions. In this study the calcium levels of the enriched mitochondrial fractions were elevated by both ouabain and epinephrine, while the calcium levels of the enriched sarcolemmal fractions were elevated only by ouabain. The advantage of this segregative procedure is that it prevents artifactual intercompartmental calcium rearrangement and preserves calcium levels to those initially fixed in situ at the time of freezing.

Animals↗