J. Marks – författare

This book makes the case that the plot of the Odyssey is represented within the narrative as a plan of Zeus, Dios boulē, that serves as a guide for the performing poet and as a hermeneutic for the audience. Through occasional participation in events and pervasive influence, the character of Zeus maintains thematic unity as the narrative moves through a mass of potential narrative paths for Odysseus that was already dense and conflicting at the time the Odyssey was taking shape. The “Zeus-centric” reading proposed here offers fresh perspectives on the tenor of interactions among the Odyssey’s characters, on the relationships among traditional accounts of Odysseus’s return, and on long-standing problems of interpretation.

Psychiatry is a discipline that crosses many frontiers, involving a know­ ledge of the anatomy, physiology and biochemistry of the nervous system, of general medicine, of sociology, of psychology, of the law and of all those subjects which comprise the behavioural sciences. Moreover, in the field of psychiatry the explosion of knowledge has led to an increase in special­ ization in sub-disciplines. To all those interested in psychiatry this diversity causes real problems. They may have to consult a wide variety of sources before finding the answer to what may be in fact a relatively simple question. This encyclopaedia aims at providing straightforward answers to the many questions that may arise. The editors wish to stress that this is not intended to be an advanced treatise on the minutiae of the subject. There will be entries with the contents of which some experts may disagree; others which may seem to err on the side of simplicity or of dog­ matism. For whatever imperfections there may be, the editors take full responsibility. They hope that no major topics have been omitted and that the coverage is sufficiently comprehensive as to provide the reader, whether he be directly involved in psychiatry or not, with a useful and practical guide to the subject.

Reproduction and fetal development in humans and experimental animals may be adversely affected by a wide range of drugs and environmental agents. They may be toxic in the parental generation leading to impaired germ cell formation, loss of reproductive poten­ tial and infertility following chronic exposure. Deviant fetal development occurs as a consequence of cellular damage at sensi­ tive stages in development. Changes seen range from intrauterine mortality and structural malformation to growth retardation with physiological and behavioural defects. Concepts on the mechanism of action of teratogens are discussed with reference to some better-known agents. Presently, regulatory authorities prefer whole animal studies in predictive safety evaluation of substances to which a pregnant woman may be exposed. Tests are conducted over one or more generations and are designed to study the influence of test com­ pounds upon general reproductive performance, fertility, fetal development and perinatal and postnatal behaviour. Experiments are designed to permit compounds to be tested under conditions resembling expected human exposure. Small rodents and rabbits are preferred species on account of their convenience as laboratory animals and the available knowledge regarding their reproductive behaviour, fetal development and known sensitivity to human teratogens.

A. N. WORDEN, D. V. PARKE AND J. MARKS THE BACKGROUND There is nothing new about the fact that chemical substances derived either from natural products or by synthetic means .. can give rise to toxicity in animals and human beings, and that they must be subjected to controls. The earliest writings speak of such toxicity and, from the times of ancient Egypt and in the Old Tes­ tament, controls have existed[l]. In the Middle Ages Paracelsus (1493-1541) noted that "All things are poisons, for there is nothing without poisonous qualities. It is only the dose which makes a thing a poison", and hence he stressed the importance of dose relative to toxic reactions [ 2] . Most of the early controls concentrated on substances that were to be deliberately administered to the human subject in the form of medicines. Legislation for many centuries was mainly con­ cerned with regulating the activities of apothecaries and physicians. The Royal College of Physicians, for example, was originally established to control the activities of physicians within London. Among the controls which it exerted was that over the use of medicinal substances. Such controls were, however, poor, based as they were on hearsay evidence of toxicity. For many centuries no means existed for the accurate determination of toxicity.

Reproduction and fetal development in humans and experimental animals may be adversely affected by a wide range of drugs and environmental agents. They may be toxic in the parental generation leading to impaired germ cell formation, loss of reproductive poten­ tial and infertility following chronic exposure. Deviant fetal development occurs as a consequence of cellular damage at sensi­ tive stages in development. Changes seen range from intrauterine mortality and structural malformation to growth retardation with physiological and behavioural defects. Concepts on the mechanism of action of teratogens are discussed with reference to some better-known agents. Presently, regulatory authorities prefer whole animal studies in predictive safety evaluation of substances to which a pregnant woman may be exposed. Tests are conducted over one or more generations and are designed to study the influence of test com­ pounds upon general reproductive performance, fertility, fetal development and perinatal and postnatal behaviour. Experiments are designed to permit compounds to be tested under conditions resembling expected human exposure. Small rodents and rabbits are preferred species on account of their convenience as laboratory animals and the available knowledge regarding their reproductive behaviour, fetal development and known sensitivity to human teratogens.

A. N. WORDEN, D. V. PARKE AND J. MARKS THE BACKGROUND There is nothing new about the fact that chemical substances derived either from natural products or by synthetic means .. can give rise to toxicity in animals and human beings, and that they must be subjected to controls. The earliest writings speak of such toxicity and, from the times of ancient Egypt and in the Old Tes­ tament, controls have existed[l]. In the Middle Ages Paracelsus (1493-1541) noted that "All things are poisons, for there is nothing without poisonous qualities. It is only the dose which makes a thing a poison", and hence he stressed the importance of dose relative to toxic reactions [ 2] . Most of the early controls concentrated on substances that were to be deliberately administered to the human subject in the form of medicines. Legislation for many centuries was mainly con­ cerned with regulating the activities of apothecaries and physicians. The Royal College of Physicians, for example, was originally established to control the activities of physicians within London. Among the controls which it exerted was that over the use of medicinal substances. Such controls were, however, poor, based as they were on hearsay evidence of toxicity. For many centuries no means existed for the accurate determination of toxicity.

Psychiatry is a discipline that crosses many frontiers, involving a know­ ledge of the anatomy, physiology and biochemistry of the nervous system, of general medicine, of sociology, of psychology, of the law and of all those subjects which comprise the behavioural sciences. Moreover, in the field of psychiatry the explosion of knowledge has led to an increase in special­ ization in sub-disciplines. To all those interested in psychiatry this diversity causes real problems. They may have to consult a wide variety of sources before finding the answer to what may be in fact a relatively simple question. This encyclopaedia aims at providing straightforward answers to the many questions that may arise. The editors wish to stress that this is not intended to be an advanced treatise on the minutiae of the subject. There will be entries with the contents of which some experts may disagree; others which may seem to err on the side of simplicity or of dog­ matism. For whatever imperfections there may be, the editors take full responsibility. They hope that no major topics have been omitted and that the coverage is sufficiently comprehensive as to provide the reader, whether he be directly involved in psychiatry or not, with a useful and practical guide to the subject.

The story of the benzodiazepines is a fascinating one: the synthesis of a long series of inert compounds and the abandonment of the project: months later, the renewal of the project and the discovery that this compound R05-0690 (Librium ®) was a sedative and muscle relaxant in laboratory animals: the recognition that its postulated structure was wrong and that it was in fact a member of an entirely new chemical class: the excitement caused by the discovery of the powerful taming effect of the drug in wild animals: the even greater excitement in medical circles when its dramatic anxiety relieving effects were cstablished in humans: the subsequent enormous world­ wide usc of drugs of the benzodiazepine group. I have reason to know the story well for during that period I worked in various capacities in research, marketing and manage­ ment in the British subsidiary of F. Hoffmann-Ia Roche. It was during this period that I became interested in whether dependence on benzodiazepines could occur and if so to what extent, but felt that this could be examined best from outside the concern. Having now retired from Roche back to academic medicine I have taken the opportunity to examine and analyse the evidence.

The story of the benzodiazepines is a fascinating one: the synthesis of a long series of inert compounds and the abandonment of the project: months later, the renewal of the project and the discovery that this compound R05-0690 (Librium ®) was a sedative and muscle relaxant in laboratory animals: the recognition that its postulated structure was wrong and that it was in fact a member of an entirely new chemical class: the excitement caused by the discovery of the powerful taming effect of the drug in wild animals: the even greater excitement in medical circles when its dramatic anxiety relieving effects were cstablished in humans: the subsequent enormous world­ wide usc of drugs of the benzodiazepine group. I have reason to know the story well for during that period I worked in various capacities in research, marketing and manage­ ment in the British subsidiary of F. Hoffmann-Ia Roche. It was during this period that I became interested in whether dependence on benzodiazepines could occur and if so to what extent, but felt that this could be examined best from outside the concern. Having now retired from Roche back to academic medicine I have taken the opportunity to examine and analyse the evidence.

This book has been designed, as its title implies, as a practical book for medical practitioners, although it should be of interest to medical students and nutritionists. It attempts to provide essential information about this important group of substances rather than be an all embracing monograph on the subject. For this reason biochemical and physiological considera­ tions have been kept to a minimum, and aspects of animal disorders and animal husbandry have not been considered. The material is often presented in a rather dogmatic fashion and, with rare exceptions, references are not included since this makes reading more difficult. The exceptions, where references are provided, are the therapeutic claims, and the series of recent studies which have indicated that vitamin deficiencies are still widely present among certain groups of the population of many industrially developed countries. To add to this reference list there is a reading list which has been selected to give key books, reviews with extensive bibliography and important articles over the past 10 years. From this reading list it is possible to trace most of the literature on the vitamins since they were first described over half a century ago.

This book has been designed, as its title implies, as a practical book for medical practitioners, although it should be of interest to medical students and nutritionists. It attempts to provide essential information about this important group of substances rather than be an all embracing monograph on the subject. For this reason biochemical and physiological considera­ tions have been kept to a minimum, and aspects of animal disorders and animal husbandry have not been considered. The material is often presented in a rather dogmatic fashion and, with rare exceptions, references are not included since this makes reading more difficult. The exceptions, where references are provided, are the therapeutic claims, and the series of recent studies which have indicated that vitamin deficiencies are still widely present among certain groups of the population of many industrially developed countries. To add to this reference list there is a reading list which has been selected to give key books, reviews with extensive bibliography and important articles over the past 10 years. From this reading list it is possible to trace most of the literature on the vitamins since they were first described over half a century ago.

Obesity in affluent countries continues to be a serious problem. When one runs an Obesity Clinic there appears to be an unending series of patients who need help. Our understanding of weight control has been advanced not only by the studies of obese patients but also by our investigation of the problems of weight gain in young women with anorexia nervosa. Just as among obese patients there is the group of ''efficient metabolizers'' who can maintain their excessive weight with a calorie intake occasion­ ally as low as 600 kcal per day, so we have demonstrated that among anorexic women there are a few who may fail to gain normal weight with 3500 kcal per day. Some of the latter group may in fact develop T3 (tri-iodothyronine) thyrotoxicosis. One of the major unknown factors is still what determines when patients may be at these extremes. If we knew how to control these extremes we would like, for a time, to switch each to the opposite end of the spectrum. One factor which is becoming apparent from studying people in the machine which continually plots metabolic rate is that the metabolic response to food is a'' major factor in determining a person''s weight. In general terms there is a tendency for those who are below their ideal weight to have an increased metabolic response to food and those who are above ideal weight to have a reduced metabolic response to food.

Obesity in affluent countries continues to be a serious problem. When one runs an Obesity Clinic there appears to be an unending series of patients who need help. Our understanding of weight control has been advanced not only by the studies of obese patients but also by our investigation of the problems of weight gain in young women with anorexia nervosa. Just as among obese patients there is the group of 'efficient metabolizers' who can maintain their excessive weight with a calorie intake occasion­ ally as low as 600 kcal per day, so we have demonstrated that among anorexic women there are a few who may fail to gain normal weight with 3500 kcal per day. Some of the latter group may in fact develop T3 (tri-iodothyronine) thyrotoxicosis. One of the major unknown factors is still what determines when patients may be at these extremes. If we knew how to control these extremes we would like, for a time, to switch each to the opposite end of the spectrum. One factor which is becoming apparent from studying people in the machine which continually plots metabolic rate is that the metabolic response to food is a' major factor in determining a person's weight. In general terms there is a tendency for those who are below their ideal weight to have an increased metabolic response to food and those who are above ideal weight to have a reduced metabolic response to food.

Throughout the history of mankind from primitive man to the present time, vitamin ddiciencies have been a major cause of death and disease. Pellagra, scurvy and beri-beri have decimated armies, ships'' crews and even nations (Figure I). As late as 1925 the disease ''pernicious'' anaemia caused by the ab­ sence of vitamin Bl2 within a person''s body really lived up to its name. Although there were isolated instances of recognition of dietary deficien­ cies even a thousand years ago, the importance of dietary factors in the gene­ sis of these diseases was more widely recognized from the eighteenth century onwards and it was not until this century that the chemical structure of these factors was determined and the substances themselves synthesized. As the science of biochemistry has developed it has been found that the clinical manifestations of vitamin deficiency follow derangement of multiple metabolic functions. The majority of the vitamins in fact form specific co-en­ zymes in various chemical processes but at least one is converted within the body into a hormone. The commercial extraction and synthesis of the vitamins, which began mainly in the 1930S and 1940s, produced adequate quantities for a relief of vitamin detlciency diseases. The use of vitamins then became fashionable and dramatic cures were claimed for an ever increasing number of diseases.