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IV. TOBACCO INDUSTRY INFLUENCE OVER THE RESTATEMENT (THIRD) OF TORTS A. THE RESTATEMENT (THIRD) OF TORTS: PRODUCT LIABILITY In 1991, twenty-six years after Section 402A of the Restatement (Second) of [...]

Protein C activation by thrombin is significantly accelerated by the endothelial cell cofactor, thrombomodulin. In this study, we have developed a radioimmunoassay for thrombomodulin and have measured the cofactor content in several human tissues. The assay method detects as little as 2 ng of thrombomodulin. The highest thrombo-modulin content was found in lung and placenta, but the antigen was also detected in spleen, pancreas, liver, kidney, skin, heart, and aorta. Unexpectedly, thrombomodulin was absent from brain. Extracts from cerebral cortex, cerebellum, centrum semiovale, midbrain, basal ganglia, pons, and medulla were devoid of thrombomodulin. In contrast, thrombomodulin antigen is present in extracerebral intracranial vessels, including basilar and internal carotid arteries and choroid plexus, as well as in endothelium of the pia-arachnoid. ® 1986 by Grune & Stratton. Inc.

Cocaine use has increased in recent years, in part as a result of the increased availability of “crack,” the inexpensive freebase form. Although it is used medicinally and initially was considered a relatively safe street drug, cocaine clearly has addictive potential as well as adverse health consequences even in low doses. Some of its most serious adverse effects involve the cardiovascular system. Understanding the cellular mechanisms of the action of cocaine on the heart allows insight into the pathophysiology of its adverse effects. Blockade of sodium channels accounts for cocaine's anesthetic effects and acts directly on myocytes to impair action potential generation and conduction, predisposing to dysrhythmias. Blockade of neurotransmitter reuptake has many deleterious effects, including dysrhythmogenesis via increased intracellular calcium, myocardial ischemia via vasospasm and increased myocardial oxygen demand, and contraction band necrosis also via increased intracellular calcium. In addition, alterations in platelet-endothelial cell function predispose to coronary artery thrombosis and ischemia. Alterations in immune function of natural killer cells may, among other effects, predispose to the development of myocarditis, the etiology of which is probably multifactoral. Finally, a direct toxic effect of cocaine on myocytes may, in some cases, produce heart muscle dysfunction. These multiple mechanisms of action combined with the deleterious effects of often-present adulterants give rise to an unpredictable, variable, and potentially life-threatening cardiovascular response to cocaine administration.