This handbook attempts to translate data on various parameters of man's capability in underwater and hyperbaric environments for those without a background in the life sciences. Accomplishing any multifaceted task requires team work, and effective team work depends on facile communication among all participants. To communicate properly, all parties must understand each other's problems and be able to speak a similar language. To this end we believe that this publication will go a long way in furthering the understanding and communication necessary for maximum achievement. The U. S. Navy has a fundamental interest in all types of activities connected with the ocean and is especially interested in the growing field of manned underwater and hyperbaric activities. Thus, the manuscript for this comprehensive book was developed under Office of Naval Research contract N00014-67-A-0214-0013 with The George Washington University. We acknowledge with appreciation the financial support and technical guidance for this undertaking by the Naval Medical Research and Develop ment Command of the Bureau of Medicine and Surgery as well as by the Engineering Psychology Program and the Physiology Program of the Office of Naval Research. JOSEPH P. POLLARD Director Biological and Medical Sciences Division Office of Naval Research vii Preface A need was felt for a book that would document the relationship of the human being to the underwater hyperbaric environment in such a way that the individual unfamiliar with the psychological or biomedical jargon could still understand and appreciate the information."

Science is a force for good in the world-at least usually. But sometimes, when obsession gets the better of scientists, they twist a noble pursuit into something sinister. Under this spell, knowledge isn't everything, it's the only thing-no matter the cost. Bestselling author Sam Kean tells the true story of what happens when unfettered ambition pushes otherwise rational men and women to cross the line in the name of science, trampling ethical boundaries and often committing crimes in the process. The Icepick Surgeon masterfully guides the reader across two thousand years of history, beginning with Cleopatra's dark deeds in ancient Egypt. The book reveals the origins of much of modern science in the transatlantic slave trade of the 1700s, as well as Thomas Edison's mercenary support of the electric chair and the warped logic of the spies who infiltrated the Manhattan Project. But the sins of science aren't all safely buried in the past. Many of them, Kean reminds us, still affect us today. We can draw direct lines from the medical abuses of Tuskegee and Nazi Germany to current vaccine hesitancy, and connect icepick lobotomies from the 1950s to the contemporary failings of mental-health care. Kean even takes us into the future, when advanced computers and genetic engineering could unleash whole new ways to do one another wrong. Unflinching, and exhilarating to the last page, The Icepick Surgeon fuses the drama of scientific discovery with the illicit thrill of a true-crime tale. With his trademark wit and precision, Kean shows that, while science has done more good than harm in the world, rogue scientists do exist, and when we sacrifice morals for progress, we often end up with neither.

This volume represents the first attempt to present in one place the clinical syndromes and the pathophysiologic basis for the "resistance states" to each of the classes of steroid hormones. Glucocorticoids, mineralocorticoids, androgens, estrogens, progesterone and vitamin D have widely diverse roles ranging from the control of homeostasis to reproduction and bone formation. They are similar in that they share a chemical structure and that their action is in the cell nucleus where they induce transcription of specific genes leading to synthesis of function-specific proteins. Clinical syndromes of steroid hormone resistance to androgens (complete and partial testicular feminization), aldosterone (pseudo hypoaldosteronism) and vitamin D (vitamin D-dependent rickets type II) have been known for many years. Progesterone and glucocorticoid resistance syndromes have been described only recently. Resistance to estrogens has not been reported in man or in animals. It is hoped that a detailed reexamination of what is known about each of these conditions at the clinical and molecular levels will enhance our understanding of the function of these hormones and their mechanisms of action. New insight and research initiatives should result. G.P. Chrousos D.L. Loriaus M.B. Lipsett vii ACKNOWLEDGMENTS The contents of this volume are based in part on the proceedings of an International Conference held in Bethesda in the summer of 1984. This conference was sponsored by the National Institute of Child Health and Human Development, Bethesda, Maryland."

This volume contains the proceedings of a conference held at the National Institutes of Health in Bethesda on March 21-23. 1988. jointly sponsored by the International Council for Control of Iodine Deficiency Disorders (ICCIDD) and the Fogarty International Center of the National Institutes of Health. Several themes converged to make this meeting timely. The first is an increasing awareness of iodine deficiency disorders as a world-wide problem of public health and a preventable cause of mental deficiency. and as a subject of scientific effort. Increased interest in these problems owes a great deal to accessibility to remote and under developed areas of the world where iodine deficiency persists. As with any subject. greater scrutiny yields unexpected complexity and interest. It is true that provision of iodine. typically as iodized salt, is the necessary and sufficient preventative for iodine deficiency disorders. without including endemic cretinism. This provision is a governmental, economic and social problem. Apart from this, however, the scientific and medical problem of iodine deficiency and its effect on brain development and function is one of great interest and importance for developmental neurology and psychology. Even though the specific preventative agent is known, we do not totally understand the neurobiological questions raised."

Biophysics is the science of physical principles underlying all processes of life, including the dynamics and kinetics of biological systems. This fully revised 2nd English edition is an introductory text that spans all steps of biological organization, from the molecular, to the organism level, as well as influences of environmental factors. In response to the enormous progress recently made, especially in theoretical and molecular biophysics, the author has updated the text, integrating new results and developments concerning protein folding and dynamics, molecular aspects of membrane assembly and transport, noise-enhanced processes, and photo-biophysics. The advances made in theoretical biology in the last decade call for a fully new conception of the corresponding sections. Thus, the book provides the background needed for fundamental training in biophysics and, in addition, offers a great deal of advanced biophysical knowledge.

This volume contains the text of the presentations delivered at the International Symposium on Rare Diseases "Inherited Neuromuscular Diseases: Translation from Pathomechanisms to Therapies," held in Valencia, Spain, from November 16 to 18, 2008. The symposium represents a part of the continuous efforts on dif- sion of science to the society of the Catedra Santiago Grisolia and the Fundacion Ciudad de las Artes y las Ciencias -Comunitat Valenciana. More than 200 inter- tional scientists from different countries of Europe, the USA, and Australia attended the meeting. The venue was the Auditorium of the Science Museum Principe Felipe. Ten years ago Alan Emery wrote in the preface of Neuromuscular Disorders: Clinical and Molecular Genetics the following comments: "It has been estimated that more than one person in every 3,000 has a serious disabling inherited n- romuscular disorder. The suffering caused by these disorders is considerable, but, until the last decade or so, virtually nothing was known of their pathogenesis. Any rationale approach to treatment was therefore out of the question. However, matters are now changing rapidly. The genes for many of these disorders have been localised and characterised and their gene products identi ed and studied. The detection of preclinical disease, the identi cation of heterozygous carriers and prenatal di- nosis are all becoming possible, and, hopefully, effective treatments may no be too far distant."

This book provides a comprehensive account of the proteins involved in blood coagulation, fibrinolysis and the complement system. A major section of the book is devoted to each of these three systems, with separate chapters dealing in detail with structural aspects and different functional processes. Topics covered in the blood coagulation section include the activation of factors IX and X and prothrombin, and the formation and stabilisation of fibrin. The fibrinolysis section includes the activation of plasminogen, the degradation of fibrin and the regulation of fibrinolysis. The complement system itself is covered in chapters dealing with classical activation, alternative activation, the lytic complex and the regulatory processes involved. In addition, one section deals with special topics, including the kinin system, signal peptides, haemostasis, and the evolution of protein structure. This volume will be of use to researchers and advanced students in the fields of haematology, immunology and clinical chemistry.

Catecholamines are important transmitter substances in the autonomic and central nervous systems. These two volumes provide a comprehensive presentation of the state-of-the-art of catecholamine research and development in the past 15 years. The volumes present in-depth reviews of topical areas of catecholamine research in which substantial progress has been made and which are of current interest to various theoretical and clinical disciplines. Each topic has been dealt with by an established expert. Clinical subjects of relevant importance are included. Catecholamines are of interest in pharmacology, physiology, biochemistry, as well as in neurology, psychiatry, internal medicine (cardiology, hypertension, asthma), ophthalmology and anesthesiology.

Investigation of the mechanisms of cellular response to different mechanical stimuli, as well as mechano-electrical feedback (MEF) in the intact heart is one of the main topics in fundamental and clinical cardiology. The present volume of "Mechanosensitivity in Cells and Tissues: Mechanosensitivity of the Heart" c- bines excellent reviews written by worldwide leaders in this ?eld. The 3rd volume is a great addition to this excellent series of books edited by Andre Kamkin and Irina Kiseleva. This volume successfully combines reviews, aimed at academic, physiology and clinical cardiology communities, devoted to mechanosensitivity of the normal and diseased heart at the ion channel, cell, tissue and organ levels. Kamkin and Kiseleva have made signi?cant contributions to the investigation of mechanosentive ion channels in cardiomyocytes and ?broblasts. Their ba- ground, in addition to extensive collaborations helped them to ?nd and consolidate valuable research ?ndings from prominent specialists in the ?eld of cardiac mechanosensitivity. In the last decade, interest in the role of MEF in the heart has increased sign- cantly. MEF within cardiac tissue is a complex phenomenon in which electroph- iological changes are triggered by myocardial stretch. This phenomenon has been studiedintheclinicalcommunityforoveracenturyandmayhavebothpro-rhythmic and arrhythmogenic consequences. While signi?cant advances have been made in understanding of the effects of mechanical forces on cardiac cells, many questions remain regarding the mechanisms whereby mechanical forces are transduced into changes which alter the behavior of various cardiac cells.

The function of the vestibular system is not as obvious as those of vision, hearing, touch or smell. Vestibular dysfunction, however, is clearly apparent where lesions are present. It is probably for this reason that the vestibular sense was not discovered until the nineteenth century and that clinicians have continued to playa major role in basic vestibular research right up to the present. The relationship between basic and clinical research is certainly stronger in the vesti bular field than in that of tactile sensation, for instance, as testified by the work of clinicians as MENIERE, BREUER, BARANY, DEKLEIJN and FRENZEL. In this respect the situation is similar in vestibular physiology and in endocrinology, and for the same reason. This second part of the vestibular volume of the Handbook of Sensory Physio logy will be of interest to neurologists, otologists, neurosurgeons, ophthalmologists and physiotherapists on the one hand, and psychologists, physiologists, engineers and aviation specialists on the other. For a full understanding of Part 2, it is necessary to have assimilated the basic anatomy, physiology, and biochemistry of Part 1."

Anesthetics produce a reversible state of unconsciousness accompanied by ante- grade amnesia. This remarkable phenomenon brings great relief to surgical patients and wonder to clinicians and scientists. To date, we do not fully understand the mechanisms by which anesthetics ablate conscious sensation and memory. We are, however, making progress. This book presents original results as well as overviews of the current state of knowledge of the problem. It is authored by investigators who know the ?eld well; their research at a number of levels has contributed substantially to our c- rent understanding of anesthetic modulation of memory and consciousness. Most of the contributors were presenters at two workshops organized by Dr. Pearce and Dr. Hudetz at the 40th Annual Winter Conference on Brain Research, held at Snowmass Village, Colorado, from January 27 through February 2, 2007. One workshop focused on anesthetic modulation of consciousness and another on an- thetic modulation of memory. Seven of the chapters are based on material presented at these symposia - appropriately updated with new relevant ?ndings. This infor- tion is supplemented by chapters on anesthesia and sleep, computational analysis of the state of anesthesia, and the clinical phenomenon of "anesthesia awareness," a topic that has recently received much public attention. With these three additional contributions, the book thus includes 10 chapters.

Coronary circulation research is advancing at a rapid rate. Not only are inno vative techniques for studying myocardial perfusion being developed, new mechanisms related to coronary blood flow control and mechanics are also being discovered. The progress in this field justifies an update in the form of this new monograph. The book is divided into the following sections: "Measurement of Coronary Blood Flow and Assessment of Myocardial Per fusion" discusses advances in perfusion measurements in humans as well as nonradioactive microsphere methods. . "Coronary Flow Dynamics" elucidates the effect of heart contraction on coronary flow, perfusion, and reserve distribution as well as systolic-diastolic interaction. Models-a frequent topic of debate-are used to quantify hypotheses. "Models of Coronary Circulation" attempts to elucidate the concept of tissue pressure. "Regulatory Mechanisms of Coronary circulation and its Clinical Relevance" N u.merous mechanisms affecting coronary flow have been defined and studied at the level of isolated vessels and whole organs. The chapters in this section provide an in-depth analysis of a selection of these mechanisms and their inter actions. "Pathophysiology of Coronary Circulation in Ischemic Heart Disease" considers important aspects of factors which restrict perfusion of the myocardium in ischemic heart disease. An understanding these factors is of crucial importance in the management of patients. "Small Vessel Disorder in Coronary Circulation" describes circulatory flow and how it can be influenced by drugs."

This volume contains the manuscripts of the full papers and posters pre- sented at the conference "Dietary Phenylalanine and Brain Function," which took place at the Park Hyatt Hotel, Washington, D.C., on May 8-10, 1987. The conference was organized by a committee that included Drs. Louis Elsas (Emory University, Atlanta), William Pardridge (UCLA), Timothy Maher (Massachusetts College of Pharmacy), Donald Schomer (Harvard), and Richard Wurtman (MIT). It was sponsored by the Center for Brain Sciences and Metabolism Charitable Trust, a foun- dation which, during the past few years, had also organized seven other conferences related to interactions between circulating compounds (drugs, nutrients, hormones, toxins) and brain function. The Center's most recent other conferences were on "Melatonin in Humans" (Vienna, Austria; November 1985) and "The Pharmacology of Memory Disorders Associ- ated with Aging" (Zurich, Switzerland; January 1987). The decision to organize this conference was based on the perception that major changes had recently occurred in society's uses of phenylalanine and phenylalanine-containing products, and on the belief that a meeting of scientists and physicians who work on the amino acid's neurological effects could both catalyze additional research on these effects and assist regula- tory bodies in formulating appropriate public policies relating to the use of these products: phenylalanine, in both its L- and D-forms, has apparently become a popular sales item at "health-food" stores, and thus is now being consumed by a fairly large number of people, in the absence of the other

The recent interest in the pharmacology of the skin and the treatment of its diseases has come about for two reasons. The first is a realisation that many aspects of pharmacology can be studied as easily in human skin as in animal models, where they may be more relevant to human physiology and disease. Examples of this are the action of various vasoactive agents and the isolation of mediators of inflammation after UV irradiation and antigen-induced dermatitis. The second reason is the fortuitous realisation that a pharmacological approach to the treatment of skin disease need not always await the full elucidation of aetiology and mechanism. For example, whilst the argument continued un resolved as to whether the pilo-sebaceous infection which constitutes acne was due to a blocked duct or to a simple increase in sebum production, 13-cis retinoic acid, was found quite by chance totally to ablate the disease; again, whilst cyclosporin, fresh from its triumphs in organ transplantation, has been found able to suppress the rash of psoriasis, it has resuscitated the debate on aetiology. We are therefore entering a new era in which the pharmacology and clinical pharmacology of skin are being studied as a fascinating new way of exploring questions of human physiology and pharmacology as well as for the development and study of new drugs, use of which will improve disease control and at the same time help to define pathological mechanisms.

Plasma proteins are of interest from many points of view. Biochemists have separated and purified numerous plasma proteins and studied their physical properties, amino acid composition and sequence, the carbohydrate com- ponents of some, and binding of metals, hormones, and other materials. Much work has also been carried out on the synthesis, rates of turnoverr, and degradation of plasma proteins. Many plasma proteins show inherited variations, some of which (e.g., those of heptoglobins and transferrins) are common in various human popu- lations while others (e.g., absence of lipoproteins or immunoglobins) are rare but important because of their association with clinical syndromes. Since blood is the most accessible bodily constituent, geneticists have made good use of serum protein differences as genetic markers in family and popula- tion studies. Physiologists have long been interested in plasma proteins in relation to colloid osmotic pressure; transport of lipids, iron, hormones, and other ma- terials; the activities of renal glomeruli and tubules; the function of the liver, and many other bodily activities. Plasma proteins are also widely studied in relation to malnutrition and undernutrition, particularly that associated with defective intake of protein.

This new SpringerBrief in Physiology explores the newest research findings on how exercise influences the fetus in utero and beyond. "Physiology of Prenatal Exercise and Fetal Development" reviews the current findings of how maternal exercise throughout gestation influences fetal development of key organ systems, and also encompasses the relationship between maternal activity level and fetal, birth, and neonatal effects. This information will help researchers and scientists better understand the physiological effects of exercise during pregnancy on offspring development."

Recent publications have addressed specific aspects of the endothelins, such as their roles in disease or the importance of endothelin receptors. However, in this book the entire field of endothelins is covered. This includes the pathways of endothelin production and their regulation, the local and systemic actions of endothelins, receptors for the endothelins and the signalling pathways employed, and the involvement of endothelins in a range of diseases. Attention is also paid to the development through chemistry, pharmacology and toxicology of endothelin antagonists and endothelin-converting enzyme inhibitors, with mention of all the important members of these drug classes. This leads to well-rounded discussions of the potential therapeutic benefit of endothelin inhibitors.

Several methods have been used to demonstrate the vasculature of different organs in man and other species. Many attempts to evaluate the precise microangioarchitecture of organ systems remained unproductive, others were controversial. The development of electron microscope in thirties opend new perspectives in researching microvascular systems. Transmission electron microscopy provided a two-dimensional view on microcirculatory system at higher magnifications, however, its standardization was delayed unnecessarily. The use of methyl methacrylate and related compounds for obtaining replicas of vascular beds, and their study in scanning electron microscope opened a new window in micromorphological research. For the first time, a three-dimensional image analysis of the vascular system was possible. The microvascular corrosion casting method has meanwhile attracted the interest of many contemporary scientists. Its application to medical and biological problems justify it to be used as a routine method for microvascular investigations. The first investigators who used this method, focused either on methodological details or they dealt with the normal microanatomy of organs. The advantages of this method in demonstrating pathological microvascular patterns are also evident.

This volume emphasizes the comparative approach to under standing vertebrate renal function. I am convinced that this approach is of particular value in understanding both the details of renal function at the cellular and subcellular levels and the renal role in regulating fluid volumes and solute concentrations. My exposure to this approach first occurred during a student research experience in the laboratory of Wilbur H. Sawyer, who also provided an introduction to the works of Homer W. Smith and August Krogh. The importance of this approach was reinforced by doctoral and postdoctoral research in the laboratory of Bodil Schmidt-Nielsen. It has been confirmed through years of personal experience since then. My research and my understanding of renal function have been aided through the years by collaboration and discussion with numerous students and associates. Of particular impor tance in developing my views on comparative renal function, and especially on the relationship of structure to function, has been my long association with my colleague and friend, Eldon J. Braun. Donald S. Farner, who suggested the writing of this volume, provided valuable editorial assistance. Much of my personal research in this area has been supported over the years by grants from the United States National Science Foundation and National Institutes of Health. The writing of this volume was completed while I was in Wiirzburg, Federal Republic of Germany, supported by a Senior U.S. Scientist Award from the Alexander von Humboldt Foundation."

This volume arose from the scientific program of the XIIth International Congress of Pharmacology, held in Montreal, Canada, July 24-29, 1994. The scientific program included plenary lectures and symposia, in addition to poster presentations and colloquia. The abstracts of the Congress presentations were published as .supplement 1 of volume 72 by the Cana dian Journal of Physiology & Pharmacology. The Congress organizers sought a more expansive treatment of the Congress proceedings and appointed Dr. A. Claudio Cuello to coordinate preparation of the present volume; Dr. Brian Collier was chair of the scientific program committee and, thus, also collaborated on this work. The objective that we pursued was to produce a volume of reasonable size which would feature all of the plenary lectures and symposia from those authors who agreed to participate. To this end, we solicited mini reviews from plenary lecturers and asked symposia organizers to coordi nate a single short-review covering the individual topics within their event. Those who accepted this challenge are evident in this volume. We express our gratitude to these authors for doing so, and for exercising considerable ingenuity in completing their task within a reasonable time."

"Immunopharmacology" , why not "pharmacoimmunology"? Professor H. O. Schild University College London, 1962 An intact immune response is essential for survival, as is evidenced by the various innate immune deficiency syndromes and by the emergence of the acquired immune deficiency syndrome (AIDS) as a pandemic during the last decade. Substances which stimulate the immune response might contribute to the therapy of AIDS and its precursor, AIDS-related syndrome, as well as of other clinical conditions in which immune responses can be diminished, such as carcinoma and infections. In other circumstances, an intact or heightened immune response may pose clinical problems; hence there is need to suppress, or diminish, components of the immune response. For instance, it is necessary to impair cellular immunity in order to ensure lasting acceptance of heterografts and it is already established that agents effective in transplantation are therapeutically effective in an range of autoimmune diseases. More recently, experimental studies have indicated that aberrant manifestations of humoral immunity, as in allergies, may also be amenable to pharmacological intervention.

Morphology and physiology are two fields which cannot be separated. This statement needs to be amplified: purely factual results of a morphological or physiological nature only have real value when they are gained in the context of certain guiding, embracing questions. By themselves they are mostly of little value, because only a guiding hypothesis or theory is of any importance. Equally, a physiological question will always raise questions as to the morphological substrate, and vice versa. Thus, Wiedemann's discovery, for instance, that the visual cells in each ommatidium of the dipterans have differing fields of vision has revived the question as to what the optical properties of individual visual cells, and the complete ommatidium, might be and how neighboring ommatidia interact. These questions in turn led to that of the morphological, neuronal wiring diagram of the visual cells in the optical ganglia. Within the realm of invertebrates, the morphological and physiological problems of visual perception have been resolved in very different ways on various levels, from the photo receptor to higher centers; despite many investigations, however, there remain unsolved problems. The first chapter of Vol. VII/6B deals with the neuroarchitecture in the visual system of two groups: crustaceans and insects. These systems are best known through recent investigations. The second chapter is devoted to the neural principles in the visual system of insects. It could not have been written without parallel research into morphology."

We are pleased to present to our readers the Proceedings of the Second International Symposium "Proteases: Potential Role in Health and Disease" which was held in Rothenburg ob der Tauber (FRG) during May 17-20, 1987. The topics discussed included those dealing with the physiology and pathophysiology of proteases and their inhibitors, the inter- actions of proteases and hormones, the kallikrein-kinin, com- plement and coagulation system, the function of proteases in arthritis, malignoma, pancreatitis, intestinal tract, lung and kidney disease as well as in hypercatabolic states (acute renal failure, multiple trauma and septicemia). Furthermore some reports dealed with the role of proteases during extracorporeal circulation. The papers presented answered many questions, but raised many more concerning the significance of proteases and their in- hibitors in clinical medicine. It was unfortunately impossible in this volume, to include the extended, lively and stimulating discussions which were enjoyed by the participiants during the conference. The meeting has provided a unique framework for close inter- action between scientists from various disciplines, including molecular biology, biochemistry, physiology, surgery, anaesthe- siology, endocrinology, hematology, pneumatology and nephrology.

Pressure-related chronic wounds are an important health concern that affects millions of patients and accumulates billions in annual costs. These wounds may occur when soft tissues are mechanically compressed between bony prominences and a supporting surface. This book gives a complete and quantitative explanation of the mechanobiology which causes chronic wounds. The reviews give an overall picture on all length scales of the phenomenon, starting from musculoskeletal biomechanics to the modeling of soft tissues and their interaction with bones. At the microscopic levels, it thoroughly reviews experiments and modeling of cellular forces and molecular processes that occur during injury and healing, including the integrity of living cells subjected to sustained mechanical forces and deformations. The results allow a complete picture of the tolerance of human tissues to sustained loads, and an understanding of the risk for onset of chronic wounds. Hence, this book is also valuable for all professionals involved in the prevention and treatment of chronic wounds.

Physical activity and exercise affect many dimensions of health. This book presents a wide-ranging account of the key issues of the biology of physical activity and health. The context is set by considering the comparative and temporal aspects of activity in humans. There follows an examination of the concepts and methodological issues associated with activity, exercise, health and fitness, as well as their interrelationships. Particular attention is given to activity in children, adolescents and the elderly, activity and weight maintenance, and the psychological effects of activity. This topical volume will be of interest to human biologists, biological anthropologists, human physiologists, sports scientists, psychologists, and healthcare professionals involved in preventative medicine, public health, geriatrics, occupational health and community medicine.