Cellular content and permeability of intraluminal thrombus in abdominal aortic aneurysm.

PURPOSE: A pathologic feature commonly associated with abdominal aortic aneurysms is the presence of variably sized and shaped intraluminal thrombus, which may be fundamental to the disease process. However, the precise role of the intraluminal thrombus in the formation, enlargement, and rupture of abdominal aortic aneurysms is unknown. The hypothesis tested in this study was whether there were structural features of aortic thrombi to suggest that it may be involved in the pathogenesis of abdominal aortic aneurysms. We have investigated this hypothesis using a variety of structural and biochemical techniques. METHODS: Tests performed were light, transmission, and scanning electron microscopy; fluid permeability measurements; and Western blots. RESULTS: Intraluminal thrombus found in abdominal aortic aneurysms is structurally complex and is traversed from the luminal to abluminal surface by a continuous network of interconnected canaliculi. Quantitative microscopic analysis of the thrombus shows cellular penetration for at least 1 cm from the luminal surface of the thrombus. Macro-molecular penetration may be unrestricted throughout the entire thickness of the thrombus. Fibrin deposition occurred throughout the thrombus, whereas fibrin degradation occurred principally at the abluminal surface. CONCLUSIONS: These principally structural studies support the hypothesis that the thrombus is a self-sustaining entity that may have significance in the pathophysiologic mechanism of abdominal aortic aneurysms.

Myocarditis: unresolved issues in diagnosis and treatment.

Myocarditis is an enigmatic disease. Lymphocytic myocarditis is most commonly viral in origin. Considerable evidence suggests that myocardial damage is due to an immune-mediated mechanism rather than to direct effects of the virus itself. The presentation is variable, ranging from a clinically inapparent or relatively benign illness to acute progressive heart failure and death. Although examination of the endomyocardial biopsy specimen is the "gold standard" for the diagnosis of myocarditis there are problems with this technique, relating particularly to sampling error and histologic interpretation. Considerable evidence, both animal and human, suggests that a link between viral myocarditis and dilated cardiomyopathy does exist. There is a rational basis for the use of immunosuppressive therapy in myocarditis. Although many favorable responses have been reported with the use of these agents, the results of more definitive studies are awaited to determine the role of immunosuppressive therapy in myocarditis more clearly. Recommendations for the practical management of patients with myocarditis are made. Whenever possible, patients with this diagnosis should be entered into the ongoing NIH trial.

Metabolic links between the biosynthesis of pyrrolizidine alkaloids and polyamines in root cultures of Senecio vulgaris.

Isotope feeding and inhibitor experiments were performed in order to elucidate the pathway common to polyamine and alkaloid biosynthesis in root cultures of Senecio vulgaris L. α-Difluoromethylarginine, a specific inhibitor of arginine decarboxylase, prevented completely the incorporation of radioactivity from [(14)C]arginine and [(14)C]ornithine into spermidine and the pyrrolizidine alkaloid senecionine N-oxide. In contrast, α-difluoromethylornithine, a specific ornithine-decarboxylase inhibitor, had no effect on the flow of radioactivity from labelled ornithine and arginine into polyamines and alkaloids. Thus, putrescine, the common precursor of polyamines and pyrrolizidine alkaloids, is exclusively derived via the arginine-agmatine route. Ornithine is rapidly transformed into arginine. Recycling of the guanido moiety of agmatine back to ornithine can be excluded. Putrescine and spermidine were found to be reversibly interconvertable and to excist in a highly dynamic state. In contrast, senecionine N-oxide did not show any turnover but accumulated as a stable metabolic product. In-vivo evidence is presented that the carbon flow from arginine into the polyamine/alkaloid pathway may be controlled by spermidine. The possible importance of the metabolic coupling of pyrrolizidine-alkaloid biosynthesis to polyamine metabolism is discussed.

Cost-effectiveness analysis of patient management alternatives after uncomplicated myocardial infarction: a model.

Quantitative decision analyses provide a means whereby the effectiveness, in terms of patient outcome, and costs of diverse clinical approaches to the care of patients with cardiovascular disease can be made explicit and understandable. Increasingly, the profession is being required to justify the costs of clinical care to society, government and third party payers. Such justifications can be effectively presented when structured in decision analytic format. To demonstrate the utility of decision analysis and its extension--cost-effectiveness analysis--as a technique for presenting the rationale for clinical practices and technology utilization, the Cardiovascular Norms Committee of the American College of Cardiology sponsored a model cost-effectiveness analysis. Alternative management options, 6 month mortality and costs for the post-myocardial infarction patient were compared. The options included exercise electrocardiography, exercise thallium scintigraphy and coronary angiography, followed by coronary artery bypass surgery for patients with left main coronary disease only or patients with left main disease, three vessel disease or single or double vessel disease and a significant amount of myocardium in jeopardy. Within the constraints of the model, proceeding directly to angiography for risk stratification was the most effective approach, lowering expected mortality from 8% to approximately 3%. The marginal costs for this strategy, however, were high. The most cost-effective approach was to screen patients initially with exercise electrocardiography.

Nonprogression of coronary artery atherosclerosis in homozygous familial hypercholesterolemia after 31 months of repetitive plasma exchange.

The effects of plasma exchange performed every two weeks for 31 months in combination with diet and drug therapy were studied in a patient with receptor-defective homozygous familial hypercholesterolemia. Coronary angiography performed three years prior to commencing plasma exchange was compared to angiography 31 months after starting the program. Comparison of the angiograms taken six years apart showed no progression of coronary atheroma in the main left coronary artery in which a 30% narrowing was originally seen. An internal mammary artery-coronary artery bypass remained widely patent and showed no development of atherosclerosis. Plasma cholesterol levels were reduced 46% by plasma exchange, diet and drug compared to diet and drug alone. Achilles tendon xanthoma diminished significantly. It appears that plasma exchange combined with diet and drug therapy, while not producing regression of existing atheromatous lesions, does retard or prevent further progression.

Dyslipoproteinemias and manifestations of coronary heart disease. The Lipid Research Clinics Program Prevalence Study.

The Lipid Research Clinics Prevalence Study population underwent a noninvasive evaluation to assess the odds of coronary heart disease (CHD) among individuals with various types of dyslipoproteinemia (DLP) relative to the odds for individuals free of DLP in a nonselected population. The noninvasive evaluation included the Rose questionnaire for angina, a resting electrocardiogram, and a graded treadmill exercise test. The presence of manifestations of CHD was assessed by a combination of these findings. Multiple linear regression and multiple logistic regression analyses were used to evaluate associations between CHD and DLP, with adjustments for the following covariates: age, body mass, systolic blood pressure, alcohol consumption, and cigarette use. There were no consistent associations in women or in men 30 to 49 years old. In men 50 to 69 years old, the mean high-density lipoprotein cholesterol (HDL-C) values and HDL-C/cholesterol ratio were significantly lower in the definite CHD and angina categories, compared with the negative (no evidence of CHD) group. Higher odds ratios for CHD were present in those classified as having type IIa, type IV, and hypoHDL DLPs, relative to those classified as normal by the phenotyping algorithm. These associations were consistent across the several categories of CHD manifestations, but did not reach statistical significance after adjustment for multiple testing. A statistically significant lower odds ratio for CHD was observed in men 50 to 69 classified as having hyperHDL when compared with those without DLPs. The associations between CHD and the various forms of DLP were consistent with those observed between CHD and the plasma lipid and lipoprotein-cholesterol concentrations. The Lipid Research Clinics Prevalence Study confirmed the relationship between elevated low-density lipoprotein cholesterol, decreased HDL-C, and noninvasively determined CHD in a free-living asymptomatic population of older men.