This volume is an outgrowth of a symposium held at the University of Michigan, Ann Arbor, Michigan, October 27-29, 1975. This symposium was organized to bring together basic scientists and clinicians for the purpose of exchanging new ideas and the latest information in the area of Steroid Hormone Action and Cancer. The design of the symposium included both formal plenary sessions and informal roundtable discussion groups, the chapters of this volume being drawn primarily from these proceedings. During the last quarter of a century considerable progress has been made toward understanding the molecular mechanisms in volved in steroid hormone action. It now appears that the mechan sim of action of the four major classes of steroid hormones is qualitatively similar. Research during the past decade has demonstrated steroid hormone receptors in a variety of normal and neoplastic tissues. Receptor-containing neoplasms have been shown to be hormone-dependent and undergo regression when treated with hormone antagonists. Natural and synthetic steroids also have been employed for many years to successfully treat various types of cancer, for example: estrogens, androgens and progestagens for breast cancer; estrogens and progestagens for prostatic carcinoma; progestagens for endometrial carcinoma; and corticoids for leu kemias. All of these neoplasms have now been found to possess receptors for the steroids empirically used in their treatment."

As humans ventured into the twentieth century, the industrialized countries were confronted with the scourge of rickets. Although solariums were becoming common in the early 1900s and phototherapy was gaining popularity as a result of the awarding of a Nobel Prize to Finsen in 1903, it wasn't until 1921 when Hess and Unger demonstrated that rickets could be cured by exposure to sunlight that the healthful benefit of sun exposure appreciated. In 1941, Apperly (Cancer Research; 1: 191-195, 1941) noted that the occasional increased risk of skin cancer was associated with a decreased risk of many other more common and serious cancers. The alarming increase in the number of cases of skin cancer, especially melanoma, has caused great concern about the negative role of sunlight in health. The Sixth International Arnold Rikli Symposium on the Biologic Effects of Light was held in Boston, Massachusetts from June 16th - 18th, 2001. The goal of this Symposium was to focus on the very popular practice of tanning either by sunlight or by artificial light sources and the overall impact this practice has on health and disease. The program was organized by members of the Scientific Advisory Committee and my co-chair emeritus, Professor Ernst G. Jung. The Program Committee organized an outstanding state-of-the-art program that was enthusiastically received by the participants.

Evidence accumulated over the past decade show that gonadal steroid hormones participate in an important way in the physiological and pa thophysiological regulation of the cardiovascular system. The hor monal profile appears to put males at a disadvantage biologically in terms of cardiovascular diseases. The incidence of hypertension is higher in men than in pre-monopausal women indicating an influence of gender on the hypertensive disease process. Males and females have equivalent cholesterol levels until puberty but males suffer an ex ponential increase in heart disease in their forties, while the female rise does not start until a decade later, after menopause. Animal and human studies provided ample evidence, that estrogens lower the levels of low density lipoproteins and keep high density lipoproteins elevated. These changes may be advantageous in the prevention of heart diesease. Co ronary artery atherosclerosis has been shown to be more pronounced in ovarectomized female monkeys as in intact females. Androgen, con versely, lowers the high density lipoproteins and elevates low density lipoproteins. Regarding blood pressure, it is well established that hypertension is more severe or develops more rapidly in male than fe male rats in several genetic forms of hypertension, and that gonadal steroid hormones are probably playing an important role in explaining this observation. Risk factors of human hypertension and coronary heart dies ease include menopause and ovarectomy."

Diabetes is a serious illness that can be managed If you're one of the 17 million Americans stricken with diabetes, it's time to strike back. The pH Miracle for Diabetes offers an easy-to-follow program that will help you take control of Type 1 or Type 2 diabetes. Showing you how you can maintain the proper alkaline environment your body needs, this all-natural plan can help you slow, stop, or even reverse the disease and the damage it causes-without the high doses of medication most diabetics use. In just twelve weeks, this groundbreaking program will revitalize your health and renew your spirit. Discover: * Which foods you should eat, which to avoid, and which are best for normalizing blood sugar levels * Dozens of delicious recipes to balance your body's pH * How to replace low-blood sugar quick fixes with healthy, effective alternatives * Guidelines for managing stress and exercising safely * How the "no pain, no gain" approach to fitness leads to overacidity and a rise in blood sugar * Why a cleanse-or "liquid feast"-is the most effective start to the pH eating plan and renewing your energy ...and much more.

Amenorrhea: A Case-Based Clinical Guide is a comprehensive review of the current knowledge regarding normal female reproductive physiology. Replete with interesting case vignettes and providing diagnostic algorithms and therapeutic strategies for amenorrhea, Amenorrhea: A Case-Based Clinical Guide is divided into three sections. The first section is composed of two chapters that provide a thorough review of basic science and clinical knowledge about the organ systems responsible for normal physiology of the menstrual cycle. The second section includes discussion about menstrual cycle disruption as it relates to hypothalamic-pituitary dysfunction, surgical and natural menopause, genetic defects, premature ovarian failure/insufficiency and the effects of caloric excess and restriction. The third section offers an update on the physiological effects of prolonged amenorrhea induced surgically or by hypothalamic dysfunction and also includes an original chapter that focuses solely on the impact of race and ethnicity on the prevalence and diagnosis of amenorrhea. Amenorrhea: A Case-Based Clinical Guide brings together chapters from renowned experts who offer state-of-the-art, clinically useful information in a case-based, reader-friendly fashion. This title will be a welcome addition to the bookshelves of all clinicians who practice in women's health settings.

The human pancreas consists of two organs in one: the exocrine gland made up of pancreatic acinar cells and duct cells that produce digestive enzymes and sodium bicarbonate, respectively; the endocrine gland made up of four islet cells, namely alpha-, beta-, delta- and PP-cells that produce glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. While the physiological role of exocrine p- creas is to secrete digestive enzyme responsible for our normal digestion, absorption and assimilation of nutrients, the endocrine pancreas is to secrete islet peptide h- mones maintaining our glucose homeostasis. The pancreatic functions are nely regulated by neurocrine, endocrine, paracrine and/or intracrine mechanisms. Thus, dysregulation of these pathways should have signi cant impacts on our health and disease. Nevertheless, the underlying mechanisms by which pancreatic functions are regulated remain poorly understood. Recent basic science and clinical studies con rm myriad physiological and pathophysiological roles of the tissue renin-angiotensin systems (RAS). Of parti- lar interest is the recent identi cation of a local and functional RAS in the pancreas, which in uences both its exocrine and endocrine function. Its role in the pat- genesis of pancreatic diseases including diabetes and pancreatitis is increasingly recognized, as is the therapeutic potential of RAS antagonism: RAS blockade l- its disease progression of type 2 diabetes mellitus and impaired glucose tolerance, and may also protect against pancreatic in ammation.

Leading researchers comprehensively translate all the latest scientific information regarding endocrine physiology and development into an understanding of the clinical pathogenesis, diagnosis, and treatment of endocrine disease. Organized by endocrine system, each section of the book concisely describes the chronological development of the human organism, from the fetal/prenatal period through childhood, adolescence, and in some cases, into adulthood. The prenatal sections review recent discoveries concerning transcription factors, homeobox genes, and human molecular mutations-the basic processes governing prenatal development of the individual endocrine organs-and detail the pathophysiology, clinical characteristics, and treatment of pediatric endocrine disorders.

This volume will explore the epidemiology and the basic mechanisms of each of these prenatal phenomena, in an attempt to explain the role of the prenatal environment in promoting postnatal weight gain. This information will contribute to resolving the nature-nurture controversy. This information provides guidance to clinical practitioners involved in both prenatal and postnatal care. This volume further stimulates research into underlying mechanisms and prevention and treatment of this phenomenon.

The volume Appetite Control provides a comprehensive description of the mechanisms controlling food intake, and thereby energy balance, in the mammalian organism. During the last decade, research in this area has produced a remarkable wealth of information and has characterized the function of numerous peptides, transmitters, and receptors in appetite control. Dysfunction of these circuits leads to obesity, a growing health concern. However, the plethora of mechanistic information is in marked contrasts to an almost complete lack of anti-obesity drugs that meet the safety standards required for the chronic therapy of morbid obesity. Consequently, ongoing research aims to identify additional targets and agents for a pharmacological intervention. Thus, the mechanisms of appetite control as well as all agents interfering with its control are of considerable practical interest.

The authors of the volume are distinguished scientists who are leading experts in the field, and who have contributed important, original data to our understanding of the mechanisms of appetite control. They have quite different scientific backgrounds and, together, they represent all relevant disciplines. Thereby, the topics are presented from different points of view, not exclusively from that of pharmacology and neuroendocrinology. Thus, the volume addresses all scientists who are interested in the field of obesity research and the pathophysiology of appetite control."

The discovery of mammalian nitric oxide (NO-) synthesis from I-ar- ginine has led to profound increases in our understanding of basic physiological and pathophysiological processes. This understanding has been achieved by major advances in several areas. Three major ni- tric oxide synthase (NOS) isoforms have been identified at the protein and gene level and their specific tissue localization has been linked to processes subject to regulation by NO-. The molecular basis for the di- verse effects of NO- on cell function has been shown to derive from its chemical reactivity with oxygen-containing species and both heme and non-heme iron-dependent enzymes. The potential regulation of heme- dependent enzymes such as cytochromes P450, guanylate cyclase, cy- clooxygenase, and mitochondrial cytochrome oxidase continues to emerge as a key area in NO- research. In addition, it has become clear that the expression of NOS isoforms and NO- release from cells is subject to regulation by sexual steroids and that, in tum, NO- has the potential to regulate steroid biosynthesis via inhibition of cytochromes P450 involved in steroidogenesis. These recent observations on interactions between the NO-/NOS and cytochrome P450/sexual steroid pathways have important implica- tions for understanding fundamental mechanisms involved in endocri- nological processes. They are also likely to lead to novel insights and novel therapeutic approaches for the management of pathophysiologi- cal conditions associated with alterations in sexual steroid hormones.

Growth Hormone and the Heart endeavors to bring together knowledge that has been accumulated in the area of GH and the heart, from basic to clinical studies, by research groups working on this topic throughout the world. Lessons from different experimental models and from several human diseases (acromegaly, adult GH deficiency, heart failure) suggest to endocrinologists and cardiologists that GH may not only have a role in the physiology and pathophysiology of heart function, but that GH itself may have a place in the treatment of primary heart diseases (such as dilated cardiomyopathy) or of cardiac complications of hypopituitarism. Growth Hormone and the Heart will be a useful update of the research produced in the field of cardiovascular endocrinology. The Editors also hope that this book will serve as the primary step in the recognition of the wide physiological and clinical significance of GH and heart interactions.

Endocrinology, as a discipline, was a late arrival in the corpus of established subjects. Its growth in recent years has been prodigious, extending from mor phology to molecular levels. Most of the major endocrine glands were noted by the early anatomists, although the adrenal glands were not described until 1563 by Bartholomaeus Eustachius (1520-1574). On the other hand, elucidation of the function of these glands was extremely slow. Key work by A. A. Berthold (1849), although overlooked at the time, showed that comb atrophy in castrated fowl was prevented by testis transplantation. The idea that glands produced substances reach ing the bloodstream directly and not via excretory ducts stemmed from Claude Bernard, who first used the term internal secretion in 1855. The clinical observa tions of Thomas Addison at Guy's Hospital-published as a monograph in 1855 entitled The Constitutional and Local Effects of Disease of the Suprarenal Capsules -were seminal. However, the stimulus of this early research did not bring imme diate widespread further investigations. Upon the discovery of secretin in 1902, Bayliss and Starling considered the term "internal secretion" to be clumsy, and the term "hormone" was coined (from OQ UW-1 excite or arouse) and it was first used by Starling in his Croonian of 1905."

The dramatic recent expansion in genomic information has motivated the development of new approaches to characterize gene expression and function. A critical issue for both basic and clinical endocrinologists is the physiological role of genes involved in regulating endocrine functions. Transgenic technologies allow the translation of genotypic information into specific phenotypes by using gene overexpression or loss of specific gene functions. Murine functional genomics is thus of central importance in modem biomedical endocrine research. Although mice are at present, the preferred mammalian species for genetic manipulations because of the availability of pluripotent embryonic. stem cells and inbred strains and the relatively low breeding and maintenance costs, transgenic rats have also been generated and used to study endocrine physiology. The two basic techniques used in the creation of transgenic animal models are integration of foreign DNA into a fertilized oocyte by random chromosomal insertion and homologous recombination in embryonic stem cells that are then introduced into zygotes. Transgenic mice and rats serve as sophisticted tools to probe protein function, as models of human disease, and as hosts for the testing of gene replacement and other therapies. Embryonic stem cell libraries for mouse gene deletion are being developed, which will make it possible to generate knockout mice rapidly and without the need to analyze gene structure, construct targeting vectors, and screen embryonic stem cell clones. A novel approach to transgenesis for the expression of DNA within adult differentiated neuroendocrine cells in vivo is using viral vectors.

The pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) has attracted the interest of our group during the last three decades. As early as 1969, a Nobel Symposium dealing with this topic was organized in Stockholm. This was followed in 1987 by a Nobel Conference devoted to the same subject. The main purpose of these meetings was to bring together the most distinguished scientists from all over the world and present theories on molecular and genetic mechanisms responsible for the development of glucose intolerance in NIDDM. This idea was followed also in the present symposium, "New Concepts in the Pathogenesis of NIDDM," organized with diabetologists from Toronto in Canada. Our purpose is to biannually organize international meetings covering important aspects of dia betes research, hoping that this type of interaction may result in new concepts and treat ment alternatives. For us, participating in this symposium in September 1992, the meeting in Stockholm was very stimulating and innovative. It is a special pleasure that almost all invited lecturers submitted manuscripts. Thus, the publication of the proceedings of the symposium makes it possible for all interested in diabetes research to share new ideas and findings presented at the meeting. Claes-G6ran Ostenson Suad Efendic Mladen V ranic v CONTENTS REGULATION OF INSULIN SECRETION Impaired Glucose-Induced Insulin Secretion: Studies in Animal Models with Spontaneous NIDDM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C. -G. Ostenson, A. Khan, and S. Efendic Perturbation ofIslet Metabolism and Insulin Release in NIDDM. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 WJ. Malaisse 2 Regulation of Cytoplasmic Free Ca+ in Insulin-Secreting Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ."

Dr. Robert L. Jackson, Professor of Child Health at the Uni versity of Missouri-Columbia, decided to retire from clinical practice in 1977 and the Department of Child Health planned a con ference in his honor. The Thirteenth Annual MidweSt Conference on Endocrinology and Metabolism also was in the planning stages and scheduled for two days in the fall. It seemed appropriate to com bine the two into an expanded three-day conference. In view of Dr. Jackson's international reputation in the study and care of children with diabetes mellitus, the conference topic was not dif ficult to find. Experts in this field were delighted to be asked to speak at a conference in Dr. Jackson's honor. We selected a number of excellent speakers to survey the physiology and pathophy siology of pancreatic hormones and their effects in diabetes mel litus, to discuss current knowledge of the microvascular complica tions of the disease, and to put it all into the proper historical perspective of where we have been and where we are going. We think the conference achieved its objective to pay meaningful trib ute to a distinguished member of the scientific community. As with any conference, the conversion of the presentations and discussions to the printed page is a long and arduous process. Many manuscripts were completed well after the conference and references often are more recent than the date of the conference."

It is an authentic privilege to have the opportunity to assemble and edit a new volume on "Prolactin," the first in several decades to be devoted to this fascinating hormone in all its aspects. The obvious clinical rationale for understanding prolactin (PRL) is the frequent occurrence of prolactinomas, the most common type of pituitary tumor. Fortunately, medical management of prolactinomas can be based on our under standing of the physiology of hypothalamic control of the lactotroph. Armed with this knowledge, therapies for proiactinomas are highly successful and well tolerated. Be cause of the historical and practical importance of knowledge regarding the hypothala mus-Iactotroph axis, the first chapters of this volume are dedicated to reviewing the physiology, development, and cell biology of lactotroph regulation. Chapters focusing on prolactinomas and related clinical issues follow these. PRL is the primary hormone that is responsible for "parental care" in many verte brate species. This reproductive strategy is not unique to mammals, but it has devel oped through evolution to be the central distinguishing feature of the mammalian life cycle. Among the mammals, mice have become the most effective research species in recent years. This can be traced to the development of a wide range of methods for manipulating mouse genetics, and thereby influencing development, physiology and behavior. Mice also provide a profound illustration of the physiological challenges faced in maternity. Female mice undergo a post-partum estrous, and often are both pregnant and lactating simultaneously.

Sex-Steroid Interactions with Growth Hormone presents the proceedings of an international symposium held from October 22-25 in Naples, Florida. The proceedings provide new insights and concepts gained by molecular, cellular and neuroendocrine research into mechanistic interactions of the reproductive and somatotrophic axes. Chapters include discussions of the impact of sex steroids on growth hormone secretion in both children and adults; sex steroids, growth hormone releasing factor, and somatostatin; how sex steroids modulate growth hormone action on target issues; and differential effects of growth hormone secretagogues in men and women. This volume is designed for physicians, scientists and other health professionals interested or trained in clinical and basic endocrinology, growth or reproduction.

Since the late 1960s, there has been an acceleration of research focused on understanding how the efferent ducts, the epididymis, and the vas deferens function with respect to the maturation and storage of spermatozoa and as hormone dependent tissues. Another major interest in the epididymis is that it is an attractive target for the development of male contraceptives. There are well over 16,000 peer reviewed articles in the literature on these tissues, their structure, gene expression, protein synthesis and function. Regular international meetings have been initiated that are dedicated to this field. Thus, there is an urgent need for a comprehensive reference volume that spans every facet of epididymal biology, from historical background to the most current results, from basic cell and molecular biology to clinical issues. Well-established experts from every part of the world have contributed to this volume. By necessity, each author was given page limitations so that many topics are not dealt with exhaustively. Whenever possible, references to more comprehensive discussion of specific topics are included.

'Morphological imaging' and 'functional imaging' are current mainstays for the diagnosis, successful treatment and accurate follow-up of patients with endocrine disorders. Functional and Morphological Imaging of the Endocrine System provides the reader with comprehensive but concise insights in the application of cutting edge imaging techniques and updated imaging protocols for the diagnosis and treatment of hypersecretory hormonal syndromes and functional endocrine masses.

Recent Developments in Graves' Ophthalmopathy offers an overview of the pathogenesis, assessment and management of patients with thyroid-associated eye disease. Each chapter is written by an expert and truly represents the current state of the art on the particular topic. This book can therefore almost be considered a textbook on this enigmatic disorder. Recent Developments in Graves' Ophthalmopathy is designed for all those interested in this disease, including basic scientists, clinical endocrinologists, ophthalmologists, radiotherapists, and orbital surgeons. The book gives a comprehensive overview of all aspects of Graves' ophthalmopathy. Subjects covered include the pathology of Graves' eye disease and the controversial views on its autoimmune pathogenesis; assessment of the eye changes using reliable measurements; medical management of Graves' eye disease with an overview of the many treatment options available to the clinician, including orbital radiotherapy and other immunosuppressive treatments; management of the thyroid disease; and finally, the techniques for performing various surgical procedures, which are explained and illustrated.

The purpose of these volumes is to provide a reference work for the methods of purifying many of the receptors we know about. This becomes increasingly important as full-length recep- tors are overexpressed in bacteria or in insect cell systems. A major problem for abundantly expressed proteins will be their purification. In addition to purification protocols, many other de- tails can be found concerning an individual receptor that may not be available in standard texts or monographs. No book of this type is available as a compendium of purification procedures. Receptor Purification provides protocols for the purification of a wide variety of receptors. These include receptors that bind: neurotransmitters, polypeptide hormones, steroid hormones, and ligands for related members of the steroid supergene family and others including receptors involved in bacterial motion. The text of this information is substantial so as to require its publica- tion in two volumes. Consequently, a division was made by grouping receptors depending upon the nature of their ligands. Thus, in volume 1 there are contributions on serotonin receptors, adrenergic receptors, the purification of GTP-binding proteins, opioid receptors, neurotensin receptor, luteinizing hormone re- ceptor, human chorionic gonadotropin receptor, follicle stimulat- ing hormone receptor, thyrotropin receptor, prolactin receptor, epidermal growth factor receptor, platelet derived growth factor receptor, colony stimulating factor receptor, insulinlike growth factor receptors, insulin receptor, fibronectin receptor, interferon receptor, and the cholecystokinin receptor.

"Fertility Preservation in Males: Emerging Technologies and Clinical Applications" contains a selection of the valuable chapters and protocols of Seli and Agarwal s previously published hardcover text "Fertility Preservation: Emerging Technologies and Clinical Applications." Newly available in this convenient and affordable softcover format, this practical reference guide provides an update on options for fertility preservation in men, while also discussing important related epidemiologic, ethical, medico-legal, psychological, and social aspects. Using a format that combines concise scientific background with practical methodological information and easy-to-grasp algorithms, the chapters all conform to a uniform structure, including step by step protocol of laboratory procedures, key issues in commentary and a list of references. The result is a unique resource for reproductive endocrinologists, urologists, embryologists, reproductive scientists, and oncologists."

Leading medical specialists critically review for the general practitioner the latest techniques for the clinical management of diabetic neuropathy. These authoritative contributors focus on the practical aspects of diabetic neuropathy and describe in detail the treatments that are currently available or expected to become available in the near future. They also include concise discussions of the causes of diabetic neuropathy and highlight the relatively unknown features of neuropathy that can significantly impact a patient's life. Comprehensive, up-to-date bibliographies at the end of each chapter provide an opportunity for the interested physician to gain a more detailed picture of a particular topic. This book offers family physicians, internists, endocrinologists, podiatrists, cardiologists, neurologists, and gastroenterologists an authoritative practical guide and a vital day-to-day reference source for the management of their neuropathic diabetic patients.

The purpose of these volumes is to provide a reference work for the methods of purifying many of the receptors we know about. This be comes increasingly important as full-length receptors are overexpressed in bacteria or in insect cell systems. A major problem for abundantly expressed proteins will be their purification. In addition to purification protocols, many other details can be found concerning an individual receptor that may not be available in standard texts or monographs. No book of this type is available as a compendium of purification procedures. Receptor Purification provides protocols for the purification of a wide variety of receptors. These include receptors that bind: neurotransmit ters, polypeptide hormones, steroid hormones, and ligands for related members of the steroid supergene family and others, including receptors involved in bacterial motion. The text of this information is substantial, so as to require its publication in two volumes. Consequently, a division was made by grouping receptors by the nature of their ligands. Thus, in Volume One there are contributions on serotonin receptors, adrenergic receptors, the purification of GTP-binding proteins, opioid receptors, neurotensin receptor, luteinizing hormone receptor, human chorionic gonadotropin receptor, follicle stimulating hormone receptor, thyro tropin receptor, prolactin receptor, epidermal growth factor receptor, platelet derived growth factor receptor, colony stimulating factor recep tor, insulin-like growth factor receptors, insulin receptor, fibronectin receptor, interferon receptor, and the cholecystokinin receptor.

After a decade or longer, approximately one-third of individuals with either type 1 or type 2 diabetes commence a downhill course in which decreasing renal function and failing vision define a Renal-Retinal Syndrome, dominating all aspects of life and presaging early death. Only a generation ago, survival after onset of end-stage renal disease (ESRD) in diabetes was limited because rehabilitation was preempted by blindness, limb amputation, stroke, and heart disease. By 1998, however, team management has improved the outlook, with preserved sight and return to work and home responsibilities, usually for a decade or longer, following kidney transplantation and laser photocoagulation. Recognition of the critical requirement for blood pressure regulation and metabolic control are central themes in management. In this unique book, the accomplishments of ophthalmologists, nephrologists, diabetologists, transplant surgeons, and basic scientists are blended into a strategic approach that may be readily applied by all those caring for diabetic patients. Each of twenty-one presentations suitable for primary care physicians, as well as for subspecialists concerned with macrovascular and microvascular complications of diabetes, is placed in perspective by an introductory editorial analysis. Promising near-term innovative therapies, including insertion of genetically engineered beta cells or polymer-coated islets of Langerhans, interdiction of kinins that promote retinal angiogenesis, and prevention of synthesis of advanced glycosylated endproducts (AGEs), are presented in detail. While comprehensive care of diabetic patients reflects multiple incremental advances that in sum afford major benefit, this text envisions further remarkable changes likely to suppress and possibly entirely prevent the Diabetic Renal-Retinal Syndrome.