Left atrial myxoma infected with histoplasma capsulatum

A patient is presented in whom a left atrial myxoma was found to be infected with Histoplasma capsulatum. Histoplasmosis has not been previously associated with this tumor, nor has any fungus without preceding bacterial endocarditis and long-term antibiotic therapy. The clinical course in four previously reported cases of bacterially infected myxoma is reviewed. There have been 18 prior cases of Histoplasma endocarditis and in two the patients have survived. Their clinical presentation and response to therapy are also reviewed, and pertinent therapeutic conclusions drawn. The role of echocardiography in this patient's evaluation and the ultimate successful therapy are discussed.     

Chronic ischemic heart disease: from concept to fact

The development and refinement of techniques relating the determinants of increased myocardial oxygen demand to primary or secondary manifestations of inadequate myocardial blood flow made possible certain major advances in the management of chronic ischemic heart disease over the past 25 years. These include objective and quantitative evaluation of the anatomic basis and the functional consequences of ischemic heart disease, risk stratification for patient subgroups and documentation of the effects of therapy. In addition, studies in which ischemic manifestations were shown to be dissociated from increased myocardial oxygen demand have redirected attention to the supply component of the supply to demand balance for myocardial oxygenation.Diagnostic techniques, management schemata and therapeutic evaluation methods for the electrophysiologic alterations of ischemic heart disease have matured more slowly than those for the ischemic manifestations. While the pathophysiologic concepts underlying knowledge of the ischemic manifestations of coronary artery disease were formulated 25 years ago, in the case of arrhythmias, new concepts needed to be developed to provide the direction for technologic and therapeutic advances. Although the patients at risk for serious arrhythmias and sudden cardiac events are known to be those with severe coronary artery disease, impaired left ventricular function and preexisting electrical instability as manifested by frequent and complex ventricular arrhythmias, the sensitivity and specificity for any single factor as a predictor of risk remain to be established. Similarly, methods to predict efficacy of therapy are still under development. Progress will accelerate when specific factors that predict risk are identified and the methods for measuring those factors are developed and applied to the patient in an organized and systematic manner.The thesis underlying this broad conceptional review is that the fostering of the full-time clinical investigator that occurred during the 1960s and the first half of the 1970s and the consequent systematic development and application of quantitative methods to the study of disease in human beings were major forces for the remarkable progress that has been made in the management of all aspects of cardiovascular disease.     

Cellular immune deficiency with autoimmune hemolytic anemia in purine nucleoside phosphorylase deficiency.

Immunologic and metabolic abnormalities were studied in a five year old boy with 0.07 per cent of normal erythrocyte purine nucleoside phosphorylase activity. The clinical course is characterized by severe autoimmune hemolytic anemia, a transient neurologic disorder with tremor and ataxia, and minor infectious illnesses. There is severe lymphopenia with decreased absolute numbers of T and B lymphocytes. Mitogen-stimulated blastogenesis is reduced, but response to allogeneic lymphocytes is normal. A monoclonal IgG protein is present. There is hypouricemia, elevated plasma inosine level, hypouricosuria and an increase in the urinary concentration of inosine and guanosine. The pattern of heterozygote distribution in the patient's family is compatible with an autosomal recessive trait in which heterozygotes are identifiable. In addition, the unusual laboratory and clinical manifestations of this patient illustrate the heterogeneity of the clinical syndrome associated with purine nucleoside phosphorylase deficiency.     

Pharmacologic treatment of cardiac arrhythmias: 25 years of progress

This review of practical and theoretical advances in antiarrhythmic drug therapy consists of four parts. Part 1, on clinical applications, compares the approaches to treatment 25 years ago with those of today, examines the current status of antiarrhythmic drugs used 25 years ago, reports on drugs approved for clinical use during the past 25 years, reviews new experimental drugs and suggests an approach to classification of antiarrhythmic drugs. Part 2 summarizes the contributions of cellular electrophysiology to the understanding of drug action, with emphasis on the drug-induced block of the voltage- and time-dependent properties of the rapid sodium channel. The subsequent section contains a brief discussion of the impact made by the new knowledge and the new diagnostic technology on the contemporary practices. The main conclusions are 1) that the more rational approach to treatment has benefited proportionately more patients with supraventricular than with ventricular arrhythmias, and 2) that new advances have made it possible to design successful treatments for certain patients with problems that could not be resolved in the past.     

Carcinoid pericarditis

In this case, carcinoid pericarditis with effusion was one of the dominant clinical features. Carcinoid syndrome is considered briefly. The ways in which carcinoid heart disease can manifest itself are reviewed. Finally, it is proposed that carcinoid pericarditis be added to the spectrum of carcinoid heart disease.     

Echocardiography: An overview

In the past 25 to 30 years echocardiography has become a basic examination in clinical cardiology. Thus, it is becoming increasingly necessary for clinicians to be able to utilize it intelligently. Like all medical procedures echocardiography has advantages and limitations, and physicians need to know both. Some of the limitations are being minimized with advances in examination techniques and instrumentation, but many still exist. One limitation is that the ability to satisfactorily educate and train persons in the various ultrasonic techniques has not kept pace with the worldwide popularity of the examination. As a result, quality control will remain a problem at least in the immediate future. New developments in echocardiography as invasive and noninvasive tools are exciting and indicate that ultrasonic examination of the heart should play an increasingly important role in clinical cardiology.     

Comparative studies on fatty acid synthesis, glycogen metabolism, and gluconeogenesis by hepatocytes isolated from lean and obese Zucker rats

Hepatocytes isolated from genetically obese female Zucker rats and lean female Zucker rats were compared. Hepatocytes from fed obese rats exhibited greater rates of fatty acid synthesis, more extensive accumulation of lactate and pyruvate from their glycogen stores, increased rates of net glucose utilization but produced less ketone bodies from exogenous fatty acids and had lower citrate levels than hepatocytes from lean rats. Lipogenesis was not as sensitive to dibutyryl cyclic AMP (DBcAMP) inhibition in hepatocytes from obese rats but glycogenolysis was stimulated to the same extent by this nucleotide in both preparations. Ketogenesis was less sensitive to stimulation by DBcAMP in hepatocytes from obese rats. A difference in sensitivity of lipogenesis to DBcAMP was not found when lactate plus pyruvate was added to the incubation medium, suggesting that a greater rate of glycolysis by hepatocytes from obese rats accounts for their relative insensitivity to DBcAMP. Citrate levels were elevated by DBcAMP to a greater extent in hepatocytes from obese rats. Hepatocytes prepared from lean rats starved for 48 hr were glycogen depleted and lacked significant capacity for lipogenesis and glycogen synthesis. In contrast, hepatocytes isolated from starved obese rats retained considerable amounts of liver glycogen and exhibited detectable rates of lipogenesis and glycogen synthesis. Hepatocytes prepared from starved lean rats gave faster apparent rates of lactate gluconeogenesis than hepatocytes prepared from starved obese rats. Thus, hepatocytes prepared from obese Zucker rats are more glycogenic, glycolytic, and lipogenic but less ketogenic and glucogenic than hepatocytes prepared from lean rats.     

Coronary angiographic, echocardiographic, and electrocardiographic studies on a patient with variant angina due to coronary artery spasm.

A 45-year-old Caucasian female patient with a clinical rehistory and ECG's conforming to the syndrome of variant angina as characterized by Prinzmetal is presented. ECG's recorded during spontaneous pain demonstrated ST-segment elevation and symmetrical peaking of the T-waves in the lateral precordial leads and short runs of ventricular tachycardia. Similar ECG changes were recorded during treadmill exercise- and hand-grip exercise-induced chest pain. An echocardiogram recorded during angina induced by hand-grip exercise demonstrated progressive flattening of septal motion. Multiple views of the coronary system by selective coronary cineangiography were normal with the patient at rest. Angina was then induced by hand-grip exercise and a repeat right anterior oblique view of the left coronary system revealed marked spasm of the left anterior descending artery proximal to the first septal perforator.     

Asymptomatic IgA nephropathy associated with pulmonary hemosiderosis.

A glomerular lesion identical to that of IgA nephropathy was demonstrated unexpectedly in a 17 year old boy who presented with clinical manifestations of pulmonary hemosiderosis and with no evidence of renal disease. This subclinical glomerular lesion would have remained undetected in this patient unless kidney tissue was obtained and examined by immunofluorescence or electron microscopy. It is unknown if the glomerular lesion in this case is causally related to pulmonary hemosiderosis.     

Exercise echocardiography: a clinically practical addition in the evaluation of coronary artery disease

There has been only modest clinical interest in exercise echocardiography because of the technical limitations of the procedure. Recognizing that there have been recent technical advances in the echocardiographic instruments and that echocardiography should, in theory, be an ideal technique for evaluating exercise-induced wall motion abnormalities, a clinically practical method of performing exercise echocardiograms was developed. By obtaining the echocardiograms immediately after treadmill exercise, with the patient sitting at the treadmill, a high percent of studies adequate for interpretation was obtained (92%). The addition of echocardiography to the treadmill exercise test significantly enhanced the diagnostic yield. In addition, in cases of one and three vessel disease, exercise echocardiography identified stenosis in specific coronary arteries. In patients with two vessel disease and left circumflex obstruction, specific vessel identification was less reliable. A high percent of patients with multivessel disease developed wall motion abnormalities with exercise that persisted for at least 30 minutes. It is concluded that echocardiography performed immediately after exercise with the new generation of echocardiographs can be a practical and useful clinical tool.     

The metabolic effects of dichloroacetate

Dichloroacetate activates the pyruvate dehydrogenase complex of many tissues by inhibiting the kinase responsible for phosphorylation and inactivation of the complex. Dichloroacetate also activates the myocardial branched-chain α-keto acid dehydrogenase complex but apparently not by direct inhibition of the analogous kinase. Oxalate and glyoxylate, metabolites of dichloroacetate, are responsible for some in vitro effects of dichloroacetate. Dichloroacetate stimulates leucine oxidation by isolated hepatocytes because glyoxylate transaminates with leucine. Dichloroacetate inhibits lactate gluconeogenesis by hepatocytes incubated in low bicarbonate buffer because oxalate inhibits pyruvate carboxylase under such conditions. In vivo, dichloroacetate decreases blood glucose by limiting the supply of gluconeogenic precursors to the liver. This effect is a consequence of pyruvate dehydrogenase activation in peripheral tissues. Dichloroacetate lowers blood cholesterol in hyperlipidemic patients by uncertain means. Dichloroacetate has been tried experimentally in treatment of diabetes, hypercholesterolemia, and hyperlactatemia, but it has neurotoxicity, can cause cataracts, and may be mutagenic.     

Thallium-201 myocardial scintigraphy: Improved sensitivity,specificity and predictive accuracy by application of a statistical image analysis algorithm

Exercise and 3 hour delayed redistribution thallium-201 myocardial perfusion imaging was performed in 107 patients including 87 patients with documented coronary artery disease and 20 patients with normal coronary arteriograms. A computer algorithm for statistical analysis and redisplay of the analog scintillation data was developed to augment the visual analysis of the standard analog image. The basic algorithm identified the myocardial area (pixel) with the most absolute counts and developed an appropriate standard deviation range from a table. All pixels in the area of the myocardium containing absolute counts below three standard deviation ranges (or approximately 6 standard deviations) were deleted from the final image. The remaining pixels were redisplayed in a digitized bimodal format and the image photographed. Two experienced observers compared visual analysis of the analog image alone and the analog image in conjunction with the computer-analyzed image for sensitivity, specificity and predictive accuracy in the detection of perfusion defects in patients with coronary artery disease and in normal subjects. Sensitivity in patients with coronary artery disease for the analog scintillation image alone was 79 percent (69 of 87) and with computer analysis 95 percent (83 of 87). Specificity in the patients with no coronary disease was 100 percent (20 of 20) for both techniques. The predictive accuracy of the test was 83 percent (89 of 107) for the analog image alone and 96 percent (103 of 107) for the two images combined. It is concluded that use of a computer statistical analysis algorithm of thallium-201 analog myocardial perfusion images improves the accuracy of detection of perfusion defects in patients with coronary artery disease.     

Clinical and electrophysiologic findings in patients with repetitive monomorphic ventricular tachycardia and otherwise normal electrocardiogram

Natural history, structural substrate, electrocardiographic and electrophysiologic characteristics and therapy were evaluated in 18 patients who demonstrated repetitive ventricular tachycardia, defined as repeated episodes of ventricular tachycardia that had a uniform QRS configuration and normal sinus-conducted QRS complexes between the episodes of tachycardia. The patients were young (mean age 37 years) and frequently had a long history of arrhythmia before this evaluation; only two patients had a history of syncope and six were completely asymptomatic. Fourteen patients had no evidence of underlying structural heart disease, three had mitral valve prolapse and one had congestive cardiomyopathy. Episodes of ventricular tachycardia tended to occur in clusters over a 24 hour electrocardiographic recording period.Repetitive ventricular tachycardia was induced in two of nine patients by programmed electrical stimulation, and in seven patients incremental atrial and ventricular pacing suppressed spontaneous arrhythmia. In the one patient whose tachycardia was induced by incremental ventricular pacing there was an inverse relation between pacing cycle length and the interval from the last paced complex to the first complex of ventricular tachycardia, indicating there was overdrive suppression.At a follow-up time of 0.5 to 8 years no patient had died or had worsening of symptoms. Encainide completely eliminated episodes of ventricular tachycardia during acute treatment in five of six patients tested. Seven patients received no antiarrhythmic therapy and the arrhythmia appeared to have spontaneously resolved in four of these patients. Repetitive ventricular tachycardia appears to have distinct clinical and electrophysiologic characteristics. In this series the arrhythmia had a good prognosis and often required no treatment. The electrophysiologic features are consistent with a mechanism of automaticity.     

Calcitonin: a general survey.

Since the initial discovery of calcitonin, a considerable amount of information has been obtained concerning structure, function, secretion, and effects of the hormone from a number of species. The purpose of the present report is to review the studies of structure and function, the factors that influence secretion and synthesis, and the effects and mechanism of action of calcitonin. The clinical uses of the hormone and syndromes of calcitonin excess are discu,sed.     

Amiodarone: electrophysiologic actions, pharmacokinetics and clinical effects

Interest in amiodarone has increased because of its remarkable efficacy as an antiarrhythmic agent. The purpose of this report is to review what is known about the electrophysiologic actions, hemodynamic effects, pharmacokinetics, alterations of thyroid function, response to treatment of supraventricular and ventricular tachyarrhythmias and adverse effects of amiodarone. Understanding the actions of amiodarone and its metabolism will provide more intelligent use of the drug and minimize the development of side effects. The mechanism by which amiodarone suppresses cardiac arrhythmias is not known and may relate to prolongation of refractoriness in all cardiac tissues, suppression of automaticity in some fibers, minimal slowing of conduction in fast channel-dependent tissue, or to interactions with the autonomic nervous system, alterations in thyroid metabolism or other factors. Amiodarone exerts definite but fairly minor negative inotropic effects that may be offset by its vasodilator actions. Amiodarone has a reduced clearance rate, large volume of distribution, low bioavailability and a long half-life that may last 2 months in patients receiving short-term therapy. Therapeutic serum concentrations range between 1.0 and 3.5 micrograms/ml. The drug suppresses recurrences of cardiac tachyarrhythmias in a high percent of patients, in the range of 80% or more for most supraventricular tachycardias and in about 66% of patients with ventricular tachyarrhythmias, sometimes requiring addition of a second antiarrhythmic agent. Side effects, particularly when high doses are used, may limit amiodarone's usefulness and include skin, corneal, thyroid, pulmonary, neurologic, gastrointestinal and hepatic dysfunction. Aggravation of cardiac arrhythmias occurs but serious arrhythmias are caused in less than 5% of patients. Amiodarone affects the metabolism of many other drugs and care must be used to reduce doses of agents combined with amiodarone.     

Role of exercise stress testing in healthy subjects and patients with coronary heart disease. Controversies in cardiology--I.

The value of the exercise stress test in the evaluation of clinically healthy subjects and patients with coronary heart disease is not limited to the isolated interpretation of abnormalities of the S-T segment. Other measurable parameters which are of diagnostic and prognostic importance include: (1) a decrease in systolic blood pressure during exercise; (2) the appearance of complex ventricular arrhythmias of low exercise heart rates; (3) the appearance of inverted U waves during or after exercise; (4) the patient's maximal exercise capacity; and (5) new auscultatory findings postexercise. The reliability of the exercise test as a diagnostic tool is futher enhanced by proper patient selection and careful attention to exercise techniques. Subjects with labile ST-T wave changes during standing hyperventilation, fixed ST-T changes at rest, and intraventricular conduction defects are not ideal candidates for "diagnostic" stress testing and the examining physician must rely more heavily on nonelectrocardiographic findings. The criteria used to define an abnormal S-T response will vary according to the lead system used. However, in both symptomatic and asymptomatic subjects the appearance of marked degrees of S-T depression at low exercise heart rates significantly increases the probability of finding advanced coronary disease, particularly if the S-T depression is seen in multiple monitoring leads and is of prolonged duration postexercise.     

Fulminant soft tissue infection in an elderly man with leukemia

To identify characteristics that may contribute to sodium susceptibility, we conducted studies in normal subjects who are at risk for hypertension, namely, blacks, subjects older than 40 years of age and first-degree relatives of patients with essential hypertension. All three groups exhibited a decreased natriuretic capacity when compared with control subjects. Blacks and older subjects had consistently low renin values, while the plasma renin activity values of the relatives were greater than those in control subjects. Studies in twins showed that natriuretic capacity and several factors influencing sodium excretion are heritable. When blacks were subjected to extremely high sodium intake, a greater increase in blood pressure developed than in whites. These observations are consistent with an intrinsic renal abnormality in blacks and older subjects resulting in modest volume expansion. In the normotensive relatives of hypertensive patients, the renin system may be responsible for the decreased sodium excretory capacity. These alterations are possibly inherited.     

Atrial level right to left intracardiac shunt associated with postoperative hypoxemia: demonstration with contrast two-dimensional echocardiography

Transient hypoxemia is not uncommon after major cardiac or thoracic surgery. The differential diagnosis includes atelectasis, pulmonary embolus, pneumonitis, congestive heart failure and several other diverse cardiovascular and pulmonary problems. Less well recognized is transient right to left intracardiac shunting through a patient foramen ovale or previously unsuspected atrial septal defect. Three cases of clinically important hypoxemia associated with right to left shunting after aortocoronary bypass surgery are presented. The right to left shunting was documented with contrast-enhanced echocardiography, which is a simple, inexpensive and accurate means of screening patients for intracardiac right to left shunts and may play a valuable role in the postoperative management of patients.     

Evaluation of abnormal exercise electrocardiogram in apparently healthy subjects: Labile repolarization (ST-T) abnormalities as a cause of false positive responses

Long-term follow-up studies were carried out in 121 apparently healthy men with an abnormal S-T segment response to exercise—49 Indiana State policemen and 72 subjects from a large occupational health center. The mean follow-up periods were 66 months and 43 months, respectively, for the two groups of subjects. A tendency toward labile S-T or T wave abnormalities were documented during standing rest or with hyperventilation in 61 of these 121 subjects and there was only one new coronary event in this subgroup. The labile ST-T wave changes and the abnormal S-T segment responses to exercise were not consistently reproducible in these subjects, and it was not unusual to see an abnormal S-T segment response at a time when the labile repolarization changes could not be demonstrated. Many of the subjects exhibited labile ST-T wave changes only after oral glucose loading. Significant coronary artery disease was documented in 34 (57 percent) of the remaining 60 subjects during the follow-up period.Coronary cineangiographic studies, obtained in 21 of the 35 subjects from the health center who had had no evidence of labile ST-T wave abnormalities, revealed coronary arterial stenoses of 75 percent or greater in 19. A statistical analysis was carried out in the 35 subjects without labile ST-T abnormalities to determine if there were exercise test variables that would differentiate the true positive from the false positive responses. A set of criteria were identified that yielded a specificity of 92 percent, a sensitivity of 82 percent and a predictive value of 95 percent. The entire group of 72 from the health center subjects had undergone an average of 3.8 exercise tests before their referral to the authors' laboratory. A review of these records revealed that a serial conversion from a normal to an abnormal S-T segment response was not more predictive of underlying coronary artery disease than an initially abnormal test result.