Excitement of Clinical Investigation

Abstract

E normous personal satisfaction is frequently derived from experiences resulting from systematic clinical investigation. Such are the lessons that have been learned from the tremendous insight that has evolved concerning the careful clinical and fundamental study of new therapeutic agents, events after their release for general clinical use. This has been the case derived from exciting gains into the cardiac and vascular remodeling after introduction of the angiotensinconverting enzyme inhibitors and the statins.According to the editors, an editorial commentary is intended to "highlight, provide a further perspective, and enhance the overall significance of a study that is novel, timely, and contributes to our understanding of the physiology, pathophysiology, clinical treatment or prevention of hypertension." To my way of thinking, there is no better example of such an article to fulfill these criteria than "Modulation of Angiotensin II-Mediated Hypertension and Cardiac Remodeling by Lectin-Like, Oxidized Low-Density Lipoprotein Receptor-1 Deletion" by Hu et al. 1 Inherent in this commentary are its key words: angiotensin II, cardiac remodeling, and lectinlike, oxidized low-density lipoprotein receptor-1 (LOX-1) deletion. Moreover, central to its thesis are the concept and mechanisms of cardiovascular "remodeling."The role of angiotensin in cardiac remodeling was first introduced into pathophysiology, clinical treatment, and prevention by Marc A. and Janice M. Pfeffer in 1988 after a discussion (which I witnessed) with Eugene Braunwald. That conversation concerned submission of an abstract on the benefits of prolonged survival with long-term captopril therapy of rats with myocardial infarction and heart failure for consideration at the forthcoming annual scientific meeting of the American Heart Association. 2 At that time, Braunwald suggested the need for a "hook" so that the article could be accepted on the "main arena" of the program rather than at a smaller session. He thereupon suggested the term "remodeling." That abstract was accepted on that year's "arena session," and I suggest that we have all been hooked on that term ever since. Their laboratory findings were subsequently confirmed clinically in a mechanistic trial of cardiac enlargement after myocardial infarction. 3 The translation of the concept and fundamental work demonstrating inhibition of ventricular remodeling to improve prognosis was then demonstrated in the multicenter clinical Survival and Ventricular Enlargement Trial 4 ; and it was subsequently confirmed by a number of trials bearing a host of acronyms. 5 Each of these trials demonstrated the following: inhibition of the renin-angiotensin system prevented remodeling of the left ventricle, subsequent development of left ventricular failure, a second myocardial infarction, high-grade arrhythmias, and death. I am personally thrilled by this anecdotal story, because the initial experimental investigations were the substance of the late Janice Pfeffer's graduate thesis conducted in my laborato...

The Notion of Secrecy

“…2038 In a similar vein, some German commentators have suggested that the "kleine Münze" doctrine, which affords copyright protection to works of "minor art", could be applied to fragrances. 2039 In this regard, the German Federal Supreme Court has held that works of minor art are simple but nonetheless protectable intellectual creations, such as musical works or non-scientific texts. 2040 Indeed, many have drawn parallels between the processes of composing a musical piece and creating a fragrance.…”