The evolution of antihypertensive therapy.

Beginning in the early 1950s, when a ganglioplegic agent and a vasodilator were used in combination to provide long-term control of severe hypertension, which neither drug alone could control, much has been learned about the management of hypertension from the use of new antihypertensive agents in man and from clinical trials of antihypertensive regimens. Some of this information includes: the unexpected yet very real hazards as well as benefits associated with the long-term use of powerful drugs, in particular the original description of hydralazine-induced lupus, its relation to genetic markers and its association with control of hypertension; the apparently decreasing need for antihypertensive drugs in subjects with well-controlled severe and moderate hypertension; the identification of risk factors for the complications of hypertension and the quantitation of their effects; the decrease in the incidence of hypertensive complications associated with the pharmacologic treatment of severe, moderate and, at least, the upper ranges of mild hypertension; the possibility of designing a chemical to block a specific reaction and the realization that it would have broader than expected effects; and the primary prevention of myocardial infarction in very high risk subjects.

Heat stroke: a review.

Heat stroke is a complex clinical picture caused by extreme elevation of body temperature and is especially prevalent in hot climates. The danger of heat stroke has apparently always accompanied unacclimatized man on his way through arid zones, and was often the cause of man's fatal adventures in the desert. Large numbers of unacclimatized urban dwellers have suffered when the urban areas have been involved in heat waves. Heat stroke has also been a major problem in hot industrial environments. This paper is a review of pertinent literature on this subject.

Toluene di-isocyanate-induced asthma. I. Reactions to TDI, MDI, HDI and histamine.

A group of twenty four workers handling di-isocyanates and with respiratory disease were investigated by occupational-type bronchial provocation tests for sensitivity to toluene di-isocyanate (TDI), to which all were exposed, and to diphenylmethane di-isocyanate (MDI) and hexamethylene di-isocyanate (HDI). Sixteen gave asthmatic reactions to TDI and eight of these also reacted to MDI. Four of the eight TDI and MDI reactors had histories of exposure only to TDI, and of them two reacted also to HDI. Of nine subjects tested with HDI, three gave asthmatic reactions, and all three also reacted to TDI and MDI. Thus reactions to MDI and HDI were elicited only in the TDI reactors. The possibility of specific sensitivity to these and other di-isocyanates requires tests in subjects exposed to them and not to TDI.

Nicotine and angiogenesis: a new paradigm for tobacco-related diseases.

The pathophysiology of tobacco-related diseases is complex and multifactorial. Among the approximately 4,000 compounds in tobacco smoke are carcinogens such as nitrosamines, irritants such as a variety of phenolic compounds, volatiles such as carbon monoxide, and of course nicotine. Nicotine itself has quite complex actions, mediated in part by nicotinic cholinergic receptors that may have extraneuronal, as well as neuronal distribution. This review discusses the mechanisms by which nicotine contributes to tobacco-related disease, with a focus on the surprising new finding that nicotine is a potent angiogenic agent. Nicotine hijacks an endogenous nicotinic cholinergic pathway present in endothelial cells that is involved in physiological, as well as pathological angiogenesis.

Evaluation of hylan b gel as a soft-tissue augmentation implant material.

BACKGROUND: The ideal soft tissue augmentation material should be an inert, safe, volume-filling material that is easy to use and remains in place over time. Hylan b gel, a cross-linked hyaluronic acid, may have many of these characteristics. OBJECTIVE: We assessed the potential value of hylan b gel as a soft tissue augmentation material. METHODS: A 12-month guinea pig model was used to investigate the tissue effects of hylan b gel versus "collagen" controls. RESULTS: Hylan b gel was found to be biologically compatible and stable in dermal tissues. At 1 year, only hylan b gel implants were evident (12 of 16 test sites). CONCLUSION: In this model hylan b gel performed favorably when compared with the most commonly used soft-tissue augmentation products. The material possesses many desirable implant material characteristics.

Effects of ecarazine, prazosin, phentolamine and hexamethonium on the vasopressor reflexes induced by bilateral carotid artery occlusion and head-up tilting in cats.

In order to examine clinical potential for ecarazine, prazosin, phentolamine and hexamethonium to cause orthostatic hypotension in man, the effects of these drugs on the vasopressor reflexes induced by bilateral carotid artery occlusion (BCO) or head-up tilting (Tilt) have been investigated in gallamine-immobilized cats. Ecarazine at doses of 0.1 to 10 mg/kg i.v. decreased blood pressure in a dose-dependent way whereas at 0.1 to 1 mg/kg it did not affect the pressor response to BCO or Tilt and at 10 mg/kg it suppressed only the response to BCO slightly. On the other hand, prazosin, phentolamine and hexamethonium, at hypotensive doses, not only decreased blood pressure but also inhibited pressor responses to both BCO and Tilt. Because ecarazine lacks in producing orthostatic hypotension, it seems likely that the clinical propensity of drugs to cause such side effect is correlated with the inhibition of Tilt response rather than with that to BCO. The results of comparison of the inhibition by these drugs of Tilt response indicate that ecarazine is the most favorable drug among these four drugs and that phentolamine has the highest incidence of orthostatic hypotension. With respect to the effects of prazosin, phentolamine and hexamethonium, statistically significant correlation between the inhibition of the response to BCO and that to the compensatory reflex to Tilt has been observed. Hence it is suggested that the agents which decrease blood pressure by affecting peripheral sympathetic mechanisms might depress each efferent sympathetic pathway to the same degree.