Endocrinology and Metabolism: Progress in Research and Clinical Prac tice is a new series that has been designed to present timely, critical reviews of constantly evolving fields; to provide practical and up-to-date guidance in the solution of pertinent clinical problems; to offer an alterna tive to the laborious search of the literature (and the often frustrating reading of highly technical articles); and to translate the language of the laboratory into that of the practice of medicine. We think that this volume and those to come will prove useful to physi cians (and to physicians in training), as well as to investigators in a wide variety of specialties; in short, to anyone who seeks answers to questions in endocrinology and metabolism. The first chapter of this volume could well serve as a general introduc tion to the entire series. It points out how our growing understanding of the molecular basis of biologic communication has led to the discovery of a growing number of clinical syndromes, as well as to the realization that phenotypically similar diseases may have radically different pathogenetic mechanisms and thus may require radically different therapeutic strata gems."

In the middle of the 17th century, the great French philosopher Rene Descartes wrote (L'Homme, J. Le Gras, Paris, 1669) that a suitable stimulation of the brain results in two types of "movements": exterior movements, designed to seek desirable ends and to avoid undesirable or harmful ones and interior movements or "passions" which through the release of "animal spirits" regulate the heart, the liver, and other organs. When it appears appropriate to meet a threat with force, the passion of rage causes the release of strong spirits, whereas when avoidance appears to be the better choice, the passion of fear causes the brain to release weak spirits. We do not know what influence, if any, Descartes had on the thinking of Walter B. Cannon (Bodily Changes in Pain, Hunger, Fear and Rage, Appleton and Co. , New York, 1920), of Hans Selye (The Story of the Adaptation Syndrome, Acta, Inc. , Montreal, 1952), ofG. W. Harris or of R. Guillemin (Hypothalamic-Hypophysial Interrelationships. A Sym posium. c. c. Thomas, Springfield, 1956), but it is interesting to reflect upon the durable value of great ideas which constantly resurface even if modified by other ideas and by new techniques, as if propelled by a preordained intellectual imperative.

In the last decade, it has become increasingly evident that the clini- cal and morphologic changes underlying many of the complications of diabetes, including cataract formation, retinopathy, nephropathy, neuropathy, and macrovascular disease, are preceded by a variety of disturbances of biochemical and physiologic origin. Dr. Cohen has recently written a superb monograph, entitled Diabetes and Protein Glycosylation: Measurement and Biologic Relevance, in which she thoroughly explores how enhanced nonenzymatic glycosylation in uncontrolled diabetes underscores the pressing need for main- tenance of long-term euglycemia. In the present volume, The Polyol Paradigm and Complications of Diabetes, she reviews, in a most succinct and thorough manner, how another biochemical mechan- ism, involving the polyol pathway, is involved in the pathogenesis of such diabetes complications as retinopathy, neuropathy, nephropa- thy, and cataract formation. Dr. Cohen gives us a clearly written and comprehensive mono- graph, reviewing the chemistry of the polyol pathway and of the aldose reductase inhibitors, and the pathophysiologic significance of increased polyol pathway activity in a variety of tissues affected by Vlll Foreword diabetes mellitus. She insightfully describes the relationship of increased polyol pathway activity to altered metabolism of inositol- containing phospholipids and to changes in various tissue concentra- tions of myo-inositol. Finally, she provides us with a careful review of the existing experimental and clinical studies with a variety of different aldose reductase inhibitors that have been and are being performed in the hope of preventing or reversing long-term compli- cations of diabetes.