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Basic Books
Issues and Reviews in Teratology

Issues and Reviews in Teratology

by Harold Kalter


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Teratology is at once among the oldest and youngest of human preoccupations. Coincident with man's first observations of the stars were his recordings of human and animal deformities. But, such aberrancies must have occurred even earlier, for although it is one of those things-like evolution-that cannot be proven, it is nevertheless indisputable that dysmorphogenesis must have occurred from the time complex forms of life first arose on our planet; and that from the beginnings of human awareness our species was conscious of such happenings. From the earliest recordings of this fascination with the form and meaning of abnormality a tortuous but continuous line extends to modern struggles to understand and control these manifestations. And now, after long occupying an honorable but peripheral place in the halls of philosophical and scientific pursuits, teratology has quite suddenly come to take a prominent position at the hub of a complex crossroads of human concerns. This shift in its fortune has taken several forms. Fetal maldevelopment has become the concern of environmentalists, activists of various persuasions, indus­ trial organizations, government agencies, ethicists, parents-i. e. , individuals and groups whose actions are impelled by apprehension. Such motives are of course not without basis; the trauma of thalidomide left a scar yet raw. For still others­ clinicians, academics, experimentalists-the upsurge in the interest in fetal mal­ development is at a different level, and their pursuits are broad, taking external agents as but one of the causes of defective development.

Product Details

ISBN-13: 9780306412394
Publisher: Basic Books
Publication date: 10/28/1983
Pages: 372

Table of Contents

1. Problems in Human Teratology.- 1. Introductory Remarks.- 2. Advances in Knowledge and Technology during the Past 30 Years.- 2.1. Discovery of Human Chromosomal Aberrations and Advances in Cytogenetics.- 2.2. Documentation of Human Genetic Diseases Caused by Single Defective Mutant Genes.- 2.3. Detection of Human Teratogens.- 3. Clinical Progress through Application of Practical Procedures.- 3.1. Exchange Transfusion.- 3.2. Amniocentesis.- 3.3. Dietary Treatment of Infants with Biochemical Abnormalities.- 3.4. Rubella Vaccination.- 3.5. Screening for Fetal Neural Tube Defects by the Measurement of Alphafetoprotein in the Mother’s Blood.- 3.6. Conclusion.- 4. Present-Day Problems.- 4.1. Is There a Way of Effectively Preventing Spontaneously Occurring Birth Defects of Multifactorial Origin?.- 4.2. Is It Possible to Screen Clinically Malformed Embryos at Early Stages?.- 4.3. Can We Predict the Risk of Teratogenicity of Chemicals in Humans from Available Animal Data?.- 5. Future Perspectives.- 5.1. Certain Types of Birth Defects Will Be Prevented, But There Will Be No Substantial Change in the Overall Rate of Affected Children Born.- 5.2. New Human Teratogens Will Be Discovered, Although They Will Be Few in Number.- 5.3. There Will Be New Methodologies in Teratological Research.- 6. Conclusion.- 7. Summary.- 7.1. Past Progress.- 7.2. Unsolved Problems.- 7.3. The Future.- References.- 2. Teratology: Spectrum of a Science.- 1. Ancient Records.- 2. Portents.- 3. Hybrids.- 4. Teratology and Superstition.- 5. Natural Philosophy.- 6. Anatomy and Pathology.- 7. Embryology and Experimental Teratology.- 8. Genetics.- 9. Surgery.- 10. Obstetrics.- 11. Law.- 12. Prevention.- References.- 3. Cytogenetics of Human Reproductive Wastage.- 1. History and Definition of Abortion.- 2. Historical Aspects of Cytogenetics.- 3. Frequency of Chromosome Anomalies in Miscarriages.- 4. Techniques of Study.- 5. Relative Frequency of Types of Chromosome Anomalies.- 5.1. Trisomy.- 5.2. Sex Chromosome Anomalies.- 5.3. Polyploidy.- 6. Cystic Changes of the Chorionic Villi.- 7. Cytogenetic Studies of Stillbirth and Neonatal Death.- 8. Translocations in Miscarriages.- 9. Chromosome Anomalies and Recurrent Abortion.- 9.1. Introduction.- 9.2. Karyotypes of Multiple Abortions.- 10. Etiology of Chromosome Anomalies.- 10.1. Maternal Age.- 10.2. Radiation Exposure.- 10.3. Hormonal Factors.- 11. Sex Ratio.- 12. Significance of the Cytogenetic Findings in Pregnancy Wastage.- 13. The Future for Cytogenetic Studies of Abortuses.- References.- 4. Twenty Years of Study of the Etiology of Congenital Malformations in Finland.- 1. Introduction.- 2. The Study Population.- 3. The Finnish Register of Congenital Malformations.- 3.1. Notification of Malformations.- 3.2. Matched-Pair Register.- 3.3. Maternal and Child Health Organization.- 3.4. Interview.- 3.5. Controls.- 3.6. Blood Samples.- 3.7. Treatment of Material.- 3.8. Special Studies.- 4. Incidence of Congenital Malformations.- 4.1. Pilot Study.- 4.2. Malformations Registered in 1963–1980.- 4.3. Follow-Up Studies.- 4.4. Failures in Reporting and Detection.- 4.5. Trends and Seasonal Variations.- 4.6. Geographic Distribution.- 5. The Matched-Pair Register.- 5.1. Indicator Defects.- 5.2. Risk Indicators.- 6. Special Studies.- 6.1. Occunational Hazards.- 6.2. Leisure Time.- 6.3. Infectious Diseases.- 7. Limitations and Pitfalls of Epidemiologic Studies.- 7.1. Definitions.- 7.2. Maternal Memory Bias.- 7.3. Confounding Factors.- 7.4. Chance Correlations.- 7.5. Controls.- 8. Concluding Remarks.- References.- 5. Genome and Chromosome Mutations: Balance between Appearance and Elimination.- 1. Introduction.- 2. Numerical Chromosome Anomalies or Genome Mutations.- 2.1. Overall Frequency.- 2.2. Types of Numerical Chromosome Anomalies.- 2.3. Nondisjunction of Chromosomes during Meiosis.- 2.4. Errors of Chromosome Haploid Set.- 2.5. Frequency of Numerical Chromosome Mutations at Fertilization and Natural Selection.- 2.6. Are Genome Mutations Dominant Lethal Mutations?.- 2.7. Are There Genes Favoring Nondisjunctions?.- 3. Chromosome Structural Rearrangements or Chromosome Mutations.- 3.1. Robertsonian Translocations.- 3.2. Reciprocal Translocations.- 3.3. Inversions.- 3.4. Conclusions.- 4. Human Chromosome Heteromorphisms (Variants, Polymorphisms).- 5. Minor Deletions and Mutation.- 6. Chromosomal Mutations and Evolution.- 7. Population Genetics of Structural Chromosome Rearrangements.- 7.1. Notation of Karyotypes and Haplokaryotypes.- 7.2. The Proposed Model.- 7.3. Equilibrium with Polymorphism.- 7.4. Frequency of Balanced Carriers (A1A2) at Equilibrium.- 7.5. Incidence of Unbalanced Individuals at the End of the Third Month of Pregnancy and Its Estimation.- 7.6. Estimation of , the Segregation Distortion, and s, the Reduction of Fertility..- 7.7. Analysis of the Data.- 7.8. Equilibrium Frequencies.- 8. Conclusion.- References.- 6. Developmental Toxicity and Nonhuman Primates: Interspecies Comparisons.- 1. Introduction.- 2. Thalidomide.- 3. Fungicides.- 4. Cytotoxic Agents.- 4.1. Methotrexate.- 4.2. Cyclophosphamide.- 4.3. Hydroxyurea.- 5. X-Irradiation.- 6. Hyperthermia.- 7. Androgens and Progestins.- 8. Glucocorticoids.- 9. Summary.- 10. Experimental Protocols.- 11. Comparative Embryology.- 12. Conclusion.- References.- 7. Teratogenic Risk Assessment: Past, Present, and Future.- 1. Introduction.- 2. Present Testing Strategy: Tolerance Levels/Risk-Benefit Analysis and the Concept of “Thresholds”.- 2.1. The Problem of Variability.- 2.2. The Sensitivity Factor.- 3. The Past in Risk Assessment of Teratogens.- 3.1. Maternal LD50 and Teratogenic Dose Ratios.- 3.2. Teratogenic Dose to Therapeutic Dose Ratios.- 3.3. Structure-Activity Relations.- 3.4. Embryolethal Dose to Teratogenic Dose Ratio.- 4. New Concepts of Toxicity Which May Have Application in Risk Assessment of Potential Teratogens.- 4.1. Surveillance Index.- 4.2. One-Third Maximum Tolerable Dose Rule.- 4.3. Enslein Mathematical Model.- 4.4. Adult Toxic/Developmental Toxic (A/D) Ratio and Relative Teratogenic Index (RTI).- 4.5. Genotoxicity Tier.- 4.6. In Vitro Systems.- 4.7. Animal-to-Animal Extrapolation.- 5. Appropriate Present-Day Approaches to Teratogenic Risk Assessment.- 5.1. Improvements in Existing Screening Methods or Testing Strategy.- 5.2. Surveillance and Epidemiology.- 5.3. Pharmacokinetic Applications.- 5.4. Change in Emphasis in Testing: Developmental Toxicity versus Malformation.- 6. Summary and Conclusions.- References.- 8. Thalidomide and Embryonic Sensory Peripheral Neuropathy: An Appraisal of the Neuropathic Theory of Limb Reduction Defects.- 1. Introduction.- 2. Statement of the Neuropathic Theory of Limb Reduction Defects.- 3. Premises of the Theory.- 4. Analysis of the Premises and Supporting Arguments and Observations.- 4.1. First Premise: Embryonic Limb Development Is Dependent on Neurotrophic Influences.- 4.2. Second Premise: Limb Deformities Produced by Thalidomide Are the Result of Interference with Neurotrophic Influence.- 5. Summary.- 6. Other Theories of the Mechanism of Thalidomide Teratogenicity.- References.- 9. Restorative Growth in Mammalian Embryos.- 1. Introduction.- 2. Embryologic Studies.- 3. Teratologic Studies.- 3.1. Restorative Growth in the Nervous System.- 3.2. Restorative Growth Following Damage by Ionizing Radiation.- 3.3. Restorative Growth Following Damage by Other Agents.- 4. Conclusions and Discussion.- References.- 10. Functional Teratology of the Cardiovascular and Other Organ Systems.- 1. Introduction.- 2. Effects of the Pesticide Mirex on the Fetal Cardiovascular System—A Case Study.- 2.1. Embryonic and Fetal Electrocardiography.- 2.2. Effects of Mirex Exposure on the Fetal Electrocardiogram.- 2.3. Cardiovascular Effects and Postnatal Death.- 2.4. Blood Parameters.- 2.5. The ECG Method and Functional Teratology.- 2.6. Relation to Human Experience.- 3. Functional Teratology of Other Organ Systems.- 3.1. Nervous System.- 3.2. Pulmonary System.- 3.3. Immune System.- 3.4. Renal System.- 4. Concluding Comments.- References.- 11. Searching for the Mechanism of Acetazolamide Teratogenesis.- 1. Acetazolamide Teratology.- 1.1. Species and Strain Susceptibility.- 1.2. Critical Periods.- 2. Carbonic Anhydrase.- 3. Carbonic Anhydrase Inhibition by Acetazolamide.- 4. Carbonic Anhydrase during Development.- 5. Studies of the Mechanism of Acetazolamide Teratogenesis.- 5.1. Earlier Efforts.- 5.2. Other Approaches.- 6. Recent Studies on the Teratogenic Mechanism of Acetazolamide.- 6.1. Teratology.- 6.2. Pharmacokinetics.- 6.3. Histochemical Studies.- 6.4. ImmunodifTusion Analysis.- 6.5. Purification of Carbonic Anhydrase.- 6.6. Immunoprecipitation Analysis.- 7. Comparative Studies in Rats, Rabbits, and Monkeys.- 8. Discussion.- References.

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