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Pathophysiology of Gestation, Volume II: Fetal-Placental Disorders covers important areas of reproduction such as maternal-fetal interrelationship, biochemistry and physiology of the fetoplacental unit, and use of amniotic fluid constituents as diagnostic tools for fetal well-being. This book is divided into five chapters. Chapter 1 deals with the disorders of placental transfer, clearly illustrating the physical and biochemical processes involved in placental exchanges between mother and fetus. The second chapter is devoted to disorders of placental endocrine functions. The various methods used for studying placental hormone production and the errors in analysis and interpretation of the results are also elaborated. The pathophysiology of amniotic fluid disorders is discussed in Chapter 3, while the genetic factors affecting growth and development from the gamete stage through fertilization and organ formation are described in Chapter 4. The last chapter considers the teratologic impact of the environmental factors on fetal growth and development. This volume is valuable to medical students and individuals concerned with the disorders of the maternal-fetal interrelationship.
Principles of Animal Extrapolation addresses the conceptual basis for animal extrapolation and provides an abundance of documentation that illustrates how these principles may be applied in the selection of the more appropriate models and in the interpretation of toxicological studies. The book analyzes and documents each specific biological cause of interspecies differences in susceptibility to toxic agents, including differences in absorption, gut flora, tissue distribution, metabolism, mechanisms and efficiencies of repair, and excretion. The problem of the heterogenicity of the human population is addressed through several chapters that assess the availability and prospects of developing predictive animal models for normal humans, as well as selected potential high-risk groups. Other topics presented in this book include the biological basis of regulatory actions involving attempts to extrapolate from exceptionally high exposure levels to realistic values, especially carcinogens; an assessment of genotoxicity tests, their ability to predict carcinogenicity in whole animals, and the manner in which they should be used by regulatory agencies; birth defects; and predicting the risk of human teratogenesis. Principle of Animal Extrapolation is essential for environmental toxicologists. It also provides valuable information to biomedical scientists (especially those involved in drug development and testing) and regulatory personnel in agencies such as the EPA, the OSHA, the NIOSH, and the FDA.
The study of birth defects has assumed an importance even greater now than in the past because mortality rates attributed to congenital anomalies have declined far less than those for other causes of death, such as infectious and nutritional diseases. It is estimated that as many as 50% of all pregnancies terminate as miscarriages. In the majority of cases this is the result of faulty development. Major congenital malformations are found in at least 2% of all liveborn infants, and 22% of all stillbirths and infant deaths are associated with severe congenital anomalies. Teratological studies of an experimental nature are neither ethical nor justifiable in humans. Numerous investigations have been carried out in laboratory animals and other experimental models in order to improve our understanding of abnormal intra-uterine development. In less than two decades the field of experimental teratology has advanced phenomenally. As a result of the wide range of information that is now accumulating, it has become possible to obtain an insight into the causes, mechanisms and prevention of birth defects. However, considerable work will be needed before these problems can be resolved. This book brings together some of the more recent and important research findings related to the mechanisms and pathogenesis of abnormal develop ment. It is not only a documentation of the latest experimental work, but it also points out future directions that seem productive and challenging.
In less than 40 years teratology has grown from a little known discipline concerned with studies on the effects of a few physical and chemical stresses on developing fish, amphibians, and birds, to a discipline embracing a vast accumulation of literature on experimental studies in many animal forms and the results of intensive scrutiny of human development under varied conditions, as well. Emphasis has shifted from preoccupation with descrip tions of anatomical defects to concern about subtle and interacting causative factors, to searches for the early reactions to these at the cellular and subcellu lar levels, and to identification of abnormality in the chemical, the functional, and the ultrastructural realms. These changes in orientation have quite naturally made necessary the recruitment of concepts, methods, and expertise from other disciplines. Hence the foundations of teratology, which once were largely morphological, have extended into genetics, biochemistry, molecular biology, reproductive physiology, epidemiology, and several aspects of veteri nary and clinical medicine. It is not surprising that a student or new investigator approaching the field of teratology may feel some dismay when confronted with the confusing array of cross-disciplinary concepts and principles it encompasses today. One of the aims of this work is to introduce what the editors believe is a logical thread of continuity into a field that may be regarded by some as a welter of disordered information.
The study of birth defects has assumed an importance even greater now than in the past because mortality rates attributed to congenital anomalies have declined far less than those for other causes of death, such as infectious and nutritional diseases. It is estimated that as many as 50% of all pregnancies terminate as miscarriages. In the majority of cases this is the result of faulty development. Major congenital malformations are found in at least 2% of all liveborn infants, and 22% of all stillbirths and infant deaths are associated with severe congenital anomalies. Teratological studies of an experimental nature are neither ethical nor justifiable in humans. Numerous investigations have been carried out in laboratory animals and other experimental models in order to improve our understanding of abnormal intrauterine development. In less than two decades the field of experimental teratology has advanced phenomenally. As a result of the wide range of information that is now accumulating, it has become possible to obtain an insight into the causes, mechanisms, and prevention of birth defects. However, considerable work will be needed before these problems can be resolved. The comributions in this volume include some of the more recent and exciting observations on the cellular and molecular aspects of developmental defects. It is not only a documentation of the latest experimental work, but it also indicates new and important areas for future research.
Surprisingly, the beginning of a modern approach This collection of articles and commentaries is an to the problems of birth defects is relatively recent integration of information from many disciplines, and dates from Gregg's classical report in 1941 that and presents a comprehensive survey of both recent mothers who contracted rubella during the first tri and previously reported work related to the major mester of pregnancy gave birth to infants with severe aspects of birth defects. In particular, an attempt multiple anomalies. For the first time, an environ has been made to provide a critical assessment of mental agent was found to be teratogenic in man current concepts and to identify areas in need of and was documented in a thoroughly convincing further investigation. manner. Since then, many important discoveries The scope of this volume and space limitations and significant developments have been made, par precluded discussion of and reference to all papers ticularly in the areas of environmental teratogenesis, of relevance or importance: a work of the present hereditary mechanisms, and prenatal diagnosis. nature must necessarily be selective. Some good In recent years, there has been an impressive papers have been left out or given relatively little surge of interest in the causes and prevention of consideration. It is my hope that the list of Further birth defects. Undoubtedly this resulted not only References will be consulted and should compensate from the thalidomide tragedy, but also from the for this lack of completeness.