Diabetes. Its Medical and Cultural History covers the history of scientific inquiry into this affliction from antiquity to the discovery of insulin (1921) with concurrent consideration of the history of the patient and the cultural historical background. The reprints of medical historical studies discuss general relationships as well as specific details and exceptional research achievements of the past. Included in the bibliography of primary sources are the most important historical contributions in diabetic research and diabetic therapy with the author's name and information on the place of publication. The bibliography of secondary literature consolidates international studies from the past century to the present on the history of the theory of diabetes and therapeutic approaches. Illustrations and literary texts document cultural historical relationships. In index of persons and items facilitates use of this work which is intended to provide a stimulus for the physician, medical historian, medical student, general historian as well as diabetics themselves.

The central nervous system controls vital functions by ef?ciently coordinating peripheral and central cascades of signals and networks in an orchestrated manner. Historically, the brain was considered to be insulin independent. These earlier views have been challenged by ?ndings demonstrating that insulin exerts multiple actions in the brain, regulating vital biological processes such as life span, neuronal survival, cognition, reproduction, feeding behavior, energy balance, and glucose and fat metabolism, and that inef?cient central action of insulin contributes to the development of severe pathologies (Banks et al. 2000; Gerozissis 2003, 2004, 2008; Lustman and Clouse 2005; Okamoto et al. 2001; Park 2002; Perrin et al. 2004; Pocai et al. 2005; Reger et al. 2008; Schwartz and Porte, 2005; Schubert et al. 2004; van der Heide et al. 2005; Woods et al. 1979; Wrighten et al. 2008). Insulin and speci?c insulin receptors are widely distributed in the networks of the central nervous system related mainly to feeding or cognition (Baskin et al. 1983; Bruning et al. 2000; Gerozissis 2003, 2008; Havrankova et al. 1978a, b; Schechter et al. 1996; Schulingkamp et al. 2000; Schwartz et al. 1992; Zhao et al. 2004). Insulin receptors located in the synapses of neurons and in astrocytes are present in high concentrations in the cerebral cortex, olfactory bulb, hippocampus, amygdala, cerebellum and hypothalamus (Abbott et al., 1999; Havrankova et al.

I consider it an honor to have been asked to write the Foreword for The Diabetic Pancreas. Although I have been involved in the study of the pancreas since 1921, my interest goes back even further to the time, in 1918, that my father's sister, a nurse who had trained at the Massachusetts General Hospit.al, devel oped diabetes, lost weight, and died in diabetic coma. This sad event made a deep impression on me and was certainly pardy responsible for my choosing to join the Department of Physiology of the University of Toronto to begin a career in research into diabetes. This is not the place to describe in detail the wide-ranging research and study of the diabetic pancreas in which I have engaged in the past 56 years. Suffice it to say that I am familiar enough with the subject area to be able to predict a great future for this book. The editors have undertaken a very ambitious and worthwhile project, and their efforts have been supported and strengthened by contributors who are respected authorities in their fields, thus ensuring a successful presentation of this major work."

Fundamental to survival of living organisms is their ability to react appropri ately to their environment. Cannon (1929) recognized that "back of internal homeostatic mechanisms are powerful motivating agencies-appetites and hunger and thirst." Almost all observed behavior may be viewed as activity required to meet some physical or emotional need. "The higher in the scale of living things, the more numerous, the more perfect, and the more compli cated do these regulatory agencies become." This statement by Fredricq (1885) regarding internal mechanisms is at least as valid for behavior. Adrenal medullary secretion in preparation of "fight or flight" may be con sidered the first described behavioral neuroendocrine response. The conse quences of more prolonged stress on pituitary-adrenal cortical function and the subsequent unfolding of the means by which the brain controls the secre tion of the anterior and posterior pituitary glands led to the birth of neuroen docrinology. During the last decade, neuroendocrinology has taken a remarkable turn. Peptides which were believed at first to be involved solely in control of the pituitary by the hypothalamus were found in other areas of the brain. Other peptides were encountered in brain by their activity in competing for the high affinity binding of drugs to their receptors, and still others, first found in peripheral organs, were discovered also in brain. Perhaps even more amaz ing was the discovery that one or another of these peptides influence almost every aspect of behavior."

It is curious that research in endocrinology has largely ignored the testis until quite recently. There were two impor tant reasons for this neglect; first, methods of study were difficult, and second, sperinatogenesis was considered to be the concern of the urologist or cell biologist but not the endocrinologist. Since it is now almost an ethical imperative that we develop a male contraceptive, and since a host of new techniques can be brought to bear on problems of testis function, research in male reproductive biology has effloresced. In fact, it has become possible to project aseries of workshops on the testis, each dealing with discrete aspects of biochemistry, physiology and pathology. It is fitting that this first Workshop should be on Binding and Activation, since this area is one of the frontiers in endocrinol ogy. At our present rate of progress it is probable that each of the succeeding workshops will likewise bring together leaders in a rapidly developing area. The National Institute of Child Health and Human Development has the major Federal respon sibility in reproductive biology, and has therefore agreed to sponsor this and succeeding workshops. On behalf of the Institute and for those members of the Committee who have organized this meeting, I welcome you. I am quite sure that this first Workshop on the Testis will initiate aseries of important contributions to scientific thought in male reproduc tive biology. Mortimer B. Lipsett, M. D."

Paget's disease is an old disease historically, but a new disease therapeutic ally. Human remains unearthed in Lancashire, England, dating from ap proximately 900 AD, show clear evidence of the aftliction. However, it was not until the 1800s that physicians rediscovered the condition, and a little more than 100 years ago that Sir James Paget published a perceptive and accurate description of the disease from the clinical and pathologic points of view. He felt the disease represented an inflammatory condition of the skeleton and hence named it osteitis deformans. The condition again lapsed into anonymity for several decades afterwards, and therapeutic approaches did not evolve until after World War II when several groups, located mainly in the Boston area, began using a variety of agents, includ ing corticosteroids for treatment of this condition. These early attempts at therapy were unsuccessful and the condition remained essentially untreat able until the development of the calcitonins and the bisphosphonates in the 1970s. In 1978, the Paget's Disease Foundation, a private nonprofit volun tary health agency, was founded to assist individuals aftlicted by Paget's disease of bone, to provide education regarding this condition to the medical community, and to encourage research efforts to better under stand and treat the condition. An international conference was organized under the aegis of the Paget's Disease Foundation and was held in New York City in October, 1989, ten years after the founding of the Paget's Disease Foundation."

Tumours of the prostate are the commonest types of neoplasm in the male. Whilst the benign form is virtually a universal condition in the ageing male, malignant tumours rank amongst the top causes of cancer death. Despite the fact that the involvement of the testis in the growth of the prostate has been recognised for almost two centuries, it was not until the early 1940s that Charles Huggins' studies on the effect of orchidectomy and oestrogen therapy on prostatic cancer initiated endocrine manipulation in the management of this malignancy. During the 1960s progress in the understanding of the mechanism of hormone action, achieved through advances in molecular biology and the recognition of certain aspects of hormonal control in relation to the genome, introduced a new dimension for approaching endocrine manipulation of prostatic tumours. By the end of that decade a new scientific discipline devoted to prostate research had been born, which brought together investigators in the fields of molecular biology, biochemistry, endocrinology, immunology, urology and pathology to search for the cause and to explore methods for advancing the management of abnormal prostatic growth. Since then a wealth of scientific data has accumulated on the prostate in which endocrinology has manifested itself as the cardinal aspect to which most of the findings can be related.

This volume is devoted to the chemistry, immunology, molecular biology, and physiology of the human chorionic gonadotropin, heG. For this glycoprotein molecule the course from discovery to chemical deciphering covered about fifty years. It was in 1928 that Ascheim and Zondek reported that urine from pregnant women contains something that stimulates the ovaries of mice or rats. This provided the basis for the famous A-Z test for pregnancy and for the "rabbit test" modification introduced by Friedman. As researchers sought to find more sensitive responses to heG, they used a wide variety of species including the South African aquatic toad, Xenopus Zaevis, the terrestrial toad of South America, Bufo arinarus, and the African weaver finch, EupZeetes afra. The weaver finch feather reaction was particularly noteworthy, for it disclosed a non-gonadal response to heG/LH. In retrospect, this may have been an important evolutionary clue to the realization that the designation of the hormone as a "gonadotropin" may have been only partially descriptive of the molecule's physiological function--a concept that is gaining attention, as the papers in this 1980 volume divulge.

This volume contains the papers presented at the Inter- national Symposium on "Cirrhosis, Hepatic Encephalopathy and Ammonium Toxicity", held in Valencia, Spain, November 27-29, 1989. Hepatic cirrhosis as well as other liver failures usual- ly lead to hepatic encephalopathy which is an important cause of death in occidental countries. However the molecular bases of the pathogenesis of hepatic encephalopathy remain unclear and several hypotheses have been proposed. Hyperammonemia is considered one of the main factors responsible for the mediation of hepatic encephalopathy. Therefore, a part of the book is devoted to the effects of hyperammonemia on cerebral function, ammonia and amino acid metabolism, brain microtobules, astrocytes and synaptic trans- mission and their possible role in the pathogenesis of hepatic encephalopathy. Carnitine has a remarkable protective effect against acute ammonium intoxication. Thus some results regarding this effect are also presented, as well as the clinical use of car- nitine. The alterations of the metabolism of ammonia and of seda- tives in liver diseases and their clinical implications are also discussed. The possible role of altered GABA-ergic neurotransmission on the pathogenesis of hepatic encephalopathy has received considerable attention recently. Results of these studies and those on benzodiazepine receptor ligands are presented as well as those on the hypothesis of the role of altered synaptic plasma membrane on the pathogenesis of hepatic encephalopathy.

Diabetes is one of the oldest diseases known to mankind. It was first mentioned in the Ebers Payrus (Egypt 1500 BC) and 'honey urine' was noted by Sushrutha in India in 400 BC. By the first century of the Christian era the disease was well known, both in Roman writings and in Chinese and Japanese writings. The word 'diabetes' was first coined by the Greeks. It means a passing-through of water. They described it as a 'melting of flesh into water', meaning urine. Then in 1674 Doctor Willis discovered by heating, tasting and evaporating urine that a sweet sticky substance was in it, which, of course, was sugar. Rut sugar was not known in England in those days and honey was the only real sweet tasting substance. The Latin word 'mel' which means honey was used and the disease came to be known as diabetes mellitus - that is, the passing of honeyed urine. This is still the full name of the disease.

The elucidation of the structure, function, and clinical significance of the neurohypophysis has been one of the most rewarding chapters in the history of endocrinology. Diabetes insipidus, which can be manifested by passage of 15 liters of urine a day, is one of the most dramatic disorders of the endocrine system, and can readily be managed by replacement therapy with the natural secretions of this gland, or with synthetic analogues that provide a more favorable therapeutic ratio. The neurohypophysis is the archetypical neurosecretory gland. Its secretions arise within well defined nerve cells in the hypothalamus, are transported by axoplasmic flow to nerve endings in the neural lobe, are released in response to propagated action potentials, and are regulated by neurotransmitters and osmotic signals. This gland is a model for homeostatic regulation; functional disorders of this regulation lead to well defined disorders such as the syndrome of inappropriate secretion of antidi uretic hormone (SIADH), which can be mimicked by the ectopic secretion of its hormones by tumor cells. These hormones were the first peptides to be sequenced and synthesized chemically and their structure-function relations have been characterized as well as those of any of the peptide hormones. The concept that peptide hormones generally arise as products of the processing of a larger prohormone precursor was first developed from studies of the neurohypophysis. The concept of stimulus-secretion coupling was first ap plied in neuronal tissue to the neurohypophysis.

During the past several decades, much research effort has gone into the elucidation of the role of neuroendocrine systems as secretory and metabolic regulators of cells of a variety of organs and structures, including the testes, ovaries, adrenals, thyroid, pituitary gland, and mammary glands. However, the role of cells comprising such organs and structures in the modulation of neuroendocrine processes has received considerably less is generally less well appreciated. attention and Nonetheless, it is important that we understand the actions on neuroendocrine systems of substances that reach the brain by way of the vasculature, including hormones, cytokines, toxins, amino acids, drugs, and similar agents. In order to analyze the present state of knowledge on this topic, experimental scientists and clinicians, whose shared interests include actions of circulating agents on the brain, met at a satellite symposium of the XXXI International Congress of Physiological Sciences. This symposium, entitled Circulating Regulatory Factors and Neuroendocrine Function, was held in Smolenice Castle, Czechoslovakia, June 26-July 1, 1989, and reviews delivered at this symposium as invited presentations are published in this volume. Presentations given as free communications have been published separately and are available in Endocrinologia Experimentalis 24: 1-273, 1990.

THE DISCOVERY OF INSULIN, C-PEPTIDE AND PROINSULlN, SPECIES DIFFERENCES Crude insulin was extracted and isolated from dog pancreases removed 7-1 Degrees weeks after ligation of the pancreatic duct for the first time in 1921 by Banting and Best. Its lifesaving properties were subsequently documented in pancreatectomized dogs in 1922. Only about six months elapsed from its discovery until systematic collection of calf and ox pancreases and, later, porcine pancreases was established and the blood glucose lowering effect in diabetics using the crude extract from these glands proven. It was not until 1960, however, that the primary structure of all three species of insulin, lO7 human, porcine and bovine, was elucidated . It then became evident that the differences between bovine, porcine and human insulin amounted to at mosl 3 amino acids. These apparently small differences have a significant impact on the physico-chemical characteristics of the three insulins which again affect, e.g., the rate of absorption of insulin lO9 preparations from the subcutaneous tissue and their immunogenicity, i.e.

Diabetes, particularly type 2, has become increasingly more common around the world. Consequently, the effect of diabetes on the brain has achieved enormous public health importance. A surge in pre-clinical and clinical research on topics ranging from management of hyperglycemia in acute stroke to disturbances in insulin signaling in Alzheimer s disease has led to substantial progress in the field. Written by a panel of international experts, Diabetes and the Brain provides in depth reviews on the cerebral complications of diabetes, and offers introductory chapters on current insights on the pathophysiology and clinical management of diabetes, as well as neuropsychological assessment and dementia. This relevant and easily accessible book explains the cerebral complications of diabetes, with an update on diabetes for neurologists, psychiatrists, and mental health providers and researchers in general, and on stroke and dementia for those involved in research and clinical practice in diabetes."

A. CORBIN Investigations on LHRH and its analogs have just completed their first decade. We have witnessed a veritable explosion of chemical, physiologic and pharmacologic data on this hypothalamic peptide and the approximately 1500 agonist and antagonist analogs that have been synthesized. In order to track this expanding field, I was asked to organize an international symposium on basic and clinical aspects of LHRH analogs as part of the Reproductive Health Care: CDS Symposium held in Maui, Hawaii, in October 1982. This meeting brought together a number of the leading investigators in the field. Much new state-of-the-art information was presented which I and my colleagues felt deserved a wider audience. Drs Vickery, Nestor, and Hafez consented to undertake this task. Upon review of the literature, it was apparent that there was no recent text which fully covered the breadth of developments in the field. Accordingly, the editors decided to use the symposium as a nucleus on which to build a singular, comprehensive state-of-the-art analysis of this rapidly growing discipline, and the application of such knowledge to reproductive medicine. As exemplified by the various areas of expertise provided by the individual contributors, it becomes obvious that the scope of the subject matter, while relating solely to a well-defined chemical class (LHRH analogs) and a circumscribed physiologic and pharmacologic entity (reproduction), has expanded enormously.

The actions of honnones upon systems outside of the usual target sites for such molecules represents an area of increasing interest and growing clinical significance. This volume represents a cross-section of such actions of honnones upon several relevant sites. In the first chapter of this volume Dr. Malick discusses the current status of endorphins as analgesic agents. It is now known that a more primary level of control exists for iJ-endorphin in that a 41-amino acid pep- tide has been isolated from ovine hypothalamus; this peptide stimulates iJ-endorphin release as well as the secretion of corticotropin (Vale et al. , 1981). The analgesic properties of corticotropin and its immunoactive-like analogs are well known. so it does not come as a surprise that these two classes of analgesic peptides are regulated by a common hypothalamic con- trol peptide. It may also be of interest to observe that an increase in iJ-en- dorphin concentration in the pituitary occurs in genetically obese mice and rats, and that such obesity can be attenuated through the administration of nalaxone (Margules et al. , 1978). It has also been determined that genet- ically obese mice have a probable cholecystokinin deficiency in the cerebral cortex in that this peptide is a satiety-inducing agent (Saito, et al. , 1981). The analgesic properties of the latter have also been observed. The extra-pituitary actions of another pituitary peptide, as examined in the second chapter of this volume by Dr.

These Proceedinqs of the Midwest Conference on Endocrinology and Metabolism are being published by Plenum Press for the first time. Earlier Proceedings in the series Vlere published by the University of Missouri at Columbia. The shift to an internationally recognized pub lisher reflects the considerable growth in stature that the Midwest Con ferences have undergone since their inception nine years ago. Originally concerned only with the endocrinology of the thyroid, the Conferences now explore other endocrine areas. Efforts are made to assemble a panel of speakers selected from different sub-disciplines within endocrinology for the purpose of addressing a common problem. The Ninth Conference typifi es til i s approach. The format used in recent Conferences is not unique, but is unfor tunately encountered too rarely. A few prominent scholars are invited to come together to expound their findings and concepts in considerable depth, and to participate in a discussion which, together with the for mal presentation, is published in the Proceedings. The discussion, noted for its unhurried nature, permits wide participation by the audi ence. The subject of the Ninth Conference is one which is basic and im portant not only to endocrinology but also to biology in general. Many, possibly most, life processes change in a rhythmic fashion, with similar states recurring at regular time intervals. This rhythmic property of living systems expresses itself as a recognizable and definable pattern or "time-form" in a manner equivalent to the more customary spatial form."

The Seventh International Congress of Mucosal Immunology held in Prague, the beautiful old capital of The Czech Republic, 16-20 August 1992, was the first to be sponsored by the Society for Mucosal Immunology, and was the largest since their inception 20 years earlier in Birmingham, Alabama. It was attended by 624 participants who gave 538 presentations, more than 10 times the numbers of the first meeting; these proceedings contain 354 papers that were submitted for publication. The political events in Europe that made it possible to hold this Congress in Prague also allowed for the first time the participation of large numbers of scientists from Eastern Europe, as weil as from Asia, and the organizers were truly gratified by this happy circumstance. It is now clear not only that mucosal immunityencompasses the huge area of mucosal surfaces and most physiological organ systems, but also that mucosal immunology extends over the whole global surface and all continents! The sheer size of the Congress and number of manuscripts unfortunately entailed some unexpected problems in editing and assembling the proceedings, partly due to the diversity of linguistic styles not represented at earlier meetings, and we apologize to the authors who have patiently awaited the publication of their contributions.

Endocrinology of Cardiovascular Function is a fitting inauguration to the Endocrine Update Series. The aim of these publications is to provide the clinician with cutting edge, yet succinct, access to the latest advances in endocrinology. Historically, our understanding of hormonal disturbances was restricted to the classical secretory glands and their targets. As Endocrinology of Cardiovascular Function so aptly indicates, endocrinology is no longer constrained by our early physiologic understanding of glandular disorder. Endocrinology of Cardiovascular Function has set the standard of excellence for the future volumes in this series. Shlomo Melmed, M.D. Series Editor, Endocrine Update Growth factors such as IGF-1 play important roles in cardiovascular cell hypertrophy and the response to acute vascular injury. From another perspective, traditional endocrine hormones, such as estrogen, have been found to participate in preventing the development of atherosclerosis in women, acting through novel mechanisms on target vascular cells. Other `endocrine' hormones, such as PTHRP and adrenomedullin, also modulate cardiovascular and renovascular dynamic states, suggesting new roles for these peptides as vasodilators. This multi-authored text is dedicated to highlighting emerging and important new information regarding the endocrinology of the cardiovascular system. Ellis R. Levin, M.D.

The commonest cause of blindness in young and middle-aged people in the Western world is diabetes mellitus. Although the mechanism underlying diabetic retinopathy is still not understood, the technology to reduce its progress exists, provided treatment is given at the appropriate time. Doctors caring for patients with diabetes should be familiar with all aspects of diabetic retinopathy as well as the other ocular complications of diabetes. They also need a basic knowledge of the special techniques used in the diagnosis and treatment of diabetic eye disease (fundus fluorescein angiography, retinal photocoagulation, vitrectomy) and to understand how these procedures affect the diabetic patient in terms of limitation of activities and time off work. To ensure the most efficient use of ophthalmic services a clear plan of referral to ophthalmologists is required. These are the concepts on which this guide is based, compiled by an ophthalmologist involved in the treatment of diabetic eye disease and a physician with a special interest in diabetes. In addition to doctors involved in the management of diabetic patients, this guide may be of value to ophthalmic opticians, medical students and nurses as a self-instruction manual. ' 7 1 Examination of the Eye Testing visual acuity Using the ophthalmoscope The normal fundus The abnormal fundus Recording the findings 9 TESTING VISUAL ACUITY Method Test one eye at a time. Test distant visual acuity. Correct the refractive error if the visual acuity is worse than 6/6.

Diabetes continues to spread across the globe at an alarming rate, with a current count of approximately 386 million worldwide. Physicians and healthcare professionals in all specialties greatly need a concise guide for managing this disease on a daily basis.

"Diabetes Mellitus A Concise Clinical Guide" covers the basics of diagnosis, complications, therapies and prevention. Major developments in understanding diabetes and in therapeutic approaches to this disease are also featured. This book is comprised of sections originally published in the comprehensive textbook, "Principles of Diabetes Mellitus, Second Edition."

Primary care physicians and endocrinologists, as well as medical students, will find this guide an invaluable and practical reference."

Montreal has had a longstanding interest in somatostatin. Two years ago when the final planning began for the International Con gress of Endocrinology in Quebec City in July 1984, we seized the op portunity for having a separate Satellite Symposium on somatostatin here in Montreal. We felt that after a decade of uniformly vigorous growth in somatostatin research, the opportune moment had arrived for a review of the most significant past developments and for setting the directions for the future. Knowing the futility of trying to cover every aspect of the burgeoning somatostatin field in a two day scientific program, we opted for a detailed analysis of selected areas which were reasonably mature and of areas of greatest new activity. To attain these objectives, 27 leading international experts actively involved in their fields were invited to present an indepth review of their work in one of five major categories of somatostatin research. Thirty minutes at the end of each session were assigned for a three way, comprehensive discussion of some of the core concepts between the session moderators, the panellists and the audience. The feedback that we have received from the particip ants leaves little doubt that the meeting was a scientific and social success. This book fulfills our final commitment towards the Meeting which was to record the proceedings in a timely publication.

'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.

This book includes the most significant contributions of the 3rd International Symposium on MULTIPLE RISK FACTORS IN CARDIOVASCULAR DISEASE held in Florence, Italy, July 6-9, 1994. The meeting focused on the risk factors for cardiovascular disease and their interactions. The need for this symposium is based on the epidemiological evidence that individuals from industrialized countries often possess two or more risk factors which synergistically increase the global risk profile. This has become more evident in recent years with the increase in life expectancy of the general population. The evidence that in high risk patients, a combination of risk factors often is detected, is highlighted in these Proceedings. Many recent epidemiological data identifYing the intrinsic and environmental factors contributing to the development of atherosclerosis are discussed. These results, in parallel with basic and clinical research, underline how atherosclerosis is a complex and multifactorial process involving the influences of lipids, including lipoprotein subfractions, blood pressure, rheologic forces, carbohydrate tolerance, and thrombogenic factors. Furthermore, the risk associated with anyone of these risk factors varies widely depending on level of the associated atherogenic risk factors.

The eleventh monograph and meeting of the Foundation on "Hormon al Control of the Hypothalamo-Pituitary-Gonadal Axis" was held in October 1983 at the Weizmann Institute of Science. This monograph honors the memory of Professor Hans R. Lindner, a productive and innovative scientist greatly respected and admired by his col leagues. When addressing the opening session I remarked that my impres sion of the Weizmann Institute was one or two large buildings hous ing the various departments. This was my first visit to Israel and I was overwhelmed by the beautiful semi-tropical gardens of the in stitute, in a setting of shrubs and trees, orange groves and flow ers. Sited among this seventy-five acres are over fifty buildings and residential areas for the staff and visiting scientists. I saw pictures of this area when Dr. Chaim Weizmann founded in 1934, the Daniel Sieff Research Institute, the forerunner of the Weizmann In stitute. The site was sand dunes without a blade of grass. That the desert shall bloom is illustrative of the progress made in Is rael. The topics of the monograph are grouped into twelve sections.