The International Life Sciences Institute (ILSI), a nonprofit, public foundation, was established in 1978 to advance the sciences of nutrition, toxicology, and food safety. ILSI promotes the resolution of health and safety issues in these areas by sponsoring research, conferences, publications, and educational programs. Through ILSI's programs, scientists from government, academia, and industry unite their efforts to resolve issues of critical importance to the public. As part of its commitment to understanding and resolving health and safety issues, ILSI is pleased to sponsor this series of monographs that consolidates new scientific knowledge, defines research needs, and provides a background for the effective application of scientific advances in toxicology and food safety. Alex Malaspina President International Life Sciences Institute Contents Series Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi Part I. Approaches to Assessing the Toxicity of Airborne Toxicants Chapter 1. Standard-Setting as an Integrative Exercise: Alchemy, Juggling, or Science? . . . . . . . . . . . . . . . . . . . . . . . 1 D. v. Bates Chapter 2. Species Differences in Inhalation Toxicology: Variations in Exposure-Dose Relationships and Macrophage Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 J. D. Brain Chapter 3. Cell Populations of the Respiratory System: Interspecies Diversity in Composition, Distribution, and Morphology . . . . . . . . . . . . . . . . . . . . . . . . 25 e. G. Plopper, A. Mir, J. St. George, N. Tyler, A. Mariassy, D. Wilson, S. Nishio, D. Cranz, J. Heidsiek, and D. Hyde Chapter 4. Comparative Metabolic Basis for the Disposition and Toxic Effects of Inhaled Materials . . . . . . . . . . . . . . . . . 41 A. R. Dahl Part II. Methodological Issues in Designing and Conducting Studies with Laboratory Animals Chapter 5. Exposure Facilities and Aerosol Generation and Characterization for Inhalation Experiments. . . . . . . . . .

Prostaglandins, Leukotrienes, and Cancer is a multi-volume series which focuses on an emerging area of cancer research. In 1968, R. H. Williams first reported that elevated prostaglandin levels are present in human medullary carcinoma. Since that time, the concept that arachidonic acid metabolites may be involved in cancer has expanded to include every aspect of the disease from cell transformation through metastasis. Prostaglandins and leukotrienes are generic terms used to describe a family ofbioactive lipids produced from unsaturated fatty acids (principally from arachidonic acid) via the cyclooxygenase and lipoxygenase pathways, respectively. Cyclooxygenase products consist of diverse products such as prostaglandin E2 (PGE2), prostacyclin (PGI2) and thromboxane A2 (TXA2), whereas lipoxygenase products consist ofhydroperoxy fatty acids and mono-, di-and tri-hydroxy acids including leukotrienes, lipoxins, and epoxides. The precursor fatty acids for the cyclooxygenase and lipoxygenase pathways are present in cellular phospholipids. This finding established an important control point in their biosynthesis --the release of substrate. This occurs in response to numerous stimuli that act at the cell surface. Dr. Bengt Samuelsson's extensive study ofthe metabolism of prostaglandins indicate that they are rapidly inactivated on a single pass through pulmonary circulation. Thus, they cannot act as circulating hormones and appear to be made on demand in the vicinity oftarget tissues leading to the concept that prostaglandins are local rrormones or autocoids. Altered production, qualitative and/or quantitative, of prostaglandins and leukotrienes has been implicated in the development of a number of disease states (e. g.

This volume represents the formal presentations and discussions which took place during a three-day meeting in March 1988 at The University of Texas M. D. Anderson Cancer Center in Houston. It is" dedicated to my friend of more than thirty years, Prof. Dr. Klaus Joachim Ziilch, who died in Berlin on December 2. 1988 while this volume was still in preparation. Klaus Zulch had devoted a significant portion of his professional life to a better understanding of central nervous tumors. Over the past two decades he served as the Director of the Collaborating Center for CNS Tumors, under the auspices of the World Health Organization (WHO), and it was largely through his efforts that the work of the CelJ. ter in developing criteria for a histologic classification of these neoplasms was kept alive. Without his stimulus this Houston meeting would probably not have taken place. In early 1987 he approached me with the idea of convening, at an early date, a meeting in Houston in collaboration with the Department of Neuro-Oncology of the Cancer Center, of which I was then Chairman. The purpose of this proposed meeting was to discuss recent research developments that might have a profound influence on the classification of brain tumors and ultimately necessitate revision of the "Blue Book" of the WHO on Histological Typing 0/ Tumours 0/ the Central Nervous System.

This volume is a compilation of papers presented at the Tenth International Symposium on Brain Edema held on October 20-23, 1996, in San Diego, California. This follows the sequence of meetings that was initiated 31 years ago in the First International Symposium held in Vienna. Subsequent symposiums were held in Mainz, Montreal, Berlin, Groningen, Tokyo, Baltimore, Bern, and Tokyo CY okohama). A considerable number of papers was chosen from over 100 papers that were received. The organizers wish to thank the Advisory Committee for the excellent work done in selection of the papers. We also wish to thank all the persons who contributed to the success of the Tenth International Symposium, especially the staff who worked behind the scenes. These papers were reviewed, edited, approved or disapproved by the Editorial Board. Those manuscripts that were felt not pertinent to this publication were not accepted by the Editorial Board. Therefore, the excellent quality of those that are in the book are a reflection of the authors' dedication and work and that of those of the Editorial Board in their review process. For the reader's convenience, the papers are structured according to the various disease processes which are associated with the primary topic: hypertension, hydrocephalus, infection, ischemia, tumor, etc. We do hope that the reader will enjoy the articles and that they will provide an impetus and insight for future work.

Human teratocarcinoma has long held a fascination to the pathologist be- cause of the diversity of the seemingly benign differentiated tissues asso- ciated with the tumor. An understanding of this diversity came with the demonstration of the pluripotent nature of the embryonal carcinoma cell, the stem cell of the tumor, in experimental animals. Single cell clones of murine embryonal carcinomas were derived and the resultant cell lines injected into immunosuppressed hosts, where the embryonal carcinoma stem cell itself gave rise to the wealth of differentiated tissues seen in teratocarcinomas. It was also shown that teratocarcinomas could be pro- duced experimentally by transplantation of staged early mouse embryo to extrauterine sites; subsequent experiments suggested that the embryonal carcinoma stem cell was, in fact, comparable to a normal cell of the em- bryonic ectoderm. Many elegant experiments have since been built on this early work; murine embryonal carcinoma cells are providing the ex- perimental material for a first biochemical evaluation of the earliest dif- ferentiation events in mammalian embryogenesis. In this volume, we relate the beginnings of experimental research on human teratoma. The human embryonal carcinoma cells have been char- acterized and established in vitro, providing an experimental model to study the unique biology of these cells. Monoclonal antibodies, estab- lished from work with these in vitro cultures, provide cell surface probes that define populations of embryonal cells and their derivatives in tumor sections.

Many pathologists have little acquaintance with ear, nose concomitant biopsy have become commonplace in the and throat pathology. Some receive few specimens from management of throat disorders. It is hoped that. by ENT tissues; others are deterred from deeper study of the publication of this Atlas, pathologists receiving only material that emanates from regions the normal anatomy occasional specimens will be guided in their provision of of which is so forbidding in its complexity and holds no a report helpful to the clinician and those who are involved familiarity through autopsy investigation, for, apart from with a larger ENT service may be providec with a guide the larynx, there is usually no compelling indication for to the deeper understanding of the subject. examination of the ear, nose or throat at postmortem. Yet. The modern tendency in publication of ristopatholog equally with biopsy specimens from other parts of the ical microphotographs is to omit any statement of their body, the pathologist's report is consequential for the magnification, since it will usually be clear to the reader efficient handling of ear, nose and throat illnesses and what order of enlargement is involved. I n this Atlas, sometimes even for the patient's survival."

Over the last decade, high performance Capillary electrophoresis (HPCE) has emerged as a powerful and versatile separation technique that promises to rival high performance liquid chromatography when applied to the separation of both charged and neutral species. The high speed and high separation efficiency which can be attained using any of the various modes of HPCE has resulted in the increased use of the technique in a range of analytical environments. The procedures are, however, still in the early stages of development and several barriers remain to their adoption as the technique of choice for a range of analytical problems. One such barrier is the selection and optimization of the conditions required to achieve reproducible separations of analytes and it is in this area that this new book seeks to give assistance. The book is written by an international team of authors, drawn from both academic and industrial users, and the manufacturers of instruments. At its heart are a number of tables, divided into specific application areas. These give details of published separations of a wide range of archetypal analytes, the successful separation conditions and the matrix in which they were presented. These tables are based on separations reported since 1992 and are fully referenced to the original literature. The tables are supported by discussions of the problems that a particular area presents and the strategies and solutions adopted to overcome them. The general areas covered are biochemistry, pharmaceutical science, bioscience, ion analysis, food analysis and environmental science.

This volume is the work product of an international group of authors who are experienced in the field of musculoskeletal allografts. The chapters are written by experts in many differing areas of allografting and represents the current knowledge in this rapidly changing dynamic field. The reconstructive community and their patients owe a significant debt of gratitude to Doctors Czitrom and Winkler for this volume. William F. Enneking, M. D. Preface What follows is the result of a timely project bringing together the newest ideas of top experts worldwide in a rapidly growing technology: Orthopaedic Allograft Surgery. The title of the book reflects a method rather than a speciality. It transgresses well established subspecialities of orthopaedic surgery such as joint replacement, oncology, spine, trauma and sports medicine. The technology encompasses knowledge of tissue banking, biology and biomechanics, both in a research and clinical sense. The common denominator for those interested is the need and ability to provide or use allogeneic tissues in orthopaedic applications. Inherent to a multiauthored text based on chapters written by authors from many parts of the world is a variety in format and style. While we tried to some extent reducing large discrepancies, there was no attempt made to eliminate dissimilar ities. We did not aim for a homogeneous textbook. Rather, we asked for originality, novelty, individuality in the presentation of data and concepts. Consequently, chapters vary in format from that seen in a scientific article to that of a descriptive essay."

Pathology of the Stomach and Duodenum comprehensively surveys gastric and duodenal disease, including clinical findings, pathophysiology, and epidemiology, and emphasizing diagnostic gross and microscopic pathology. Topics discussed include anomalies, gastritis, peptic ulceration, hyperplasias and benign epithelial tumors, carcinoma of the stomach and duodenum, carcinoid tumors, reactive and neoplastic lymphoid lesions, gastric smooth muscle and nerve sheath tumors, and miscellaneous lesions and rare conditions reflecting gastroduodenal participation in systemic disease.

The advances in science and medicine we are now experiencing are unprec edented and exciting. Life expectancy is prolonged, and quality of life is much improved. We learn of fabulous new discoveries made at the bench or the bedside every week. Many diseases have been totally eliminated, others can be significantly improved by new therapeutic formulations. Much of the success can be attributed to a better understanding of disease processes and the specific targeting of new and more effective medications. As is the case in many areas of successful human endeavour, there can be a downside. In the case of drugs and chemicals it is their adverse effects which are of concern. Of course, every effort is made to devise medications that are safe, and the need to elucidate and understand mechanisms are crucial, yet adverse effects remain a problem. They can be unpredictable and diverse. Drugs have been shown to induce virtually the whole gamut of human liver pathology from acute fulminant hepatitis to chronic active hepatitis to cirrho sis and even malignancy. Hence the possibility of adverse drug effects must be considered in the differential diagnosis of many patients with liver disease. This is well recognized and is very important; indeed, removal of the offending agent can often lead to reversal of the adverse effect. This is an area of hepatology where we can really make a difference."

In Cellular Cancer Markers leading pathologists and physicians review today's most promising cellular cancer markers, an important emerging class of prognostic markers that can be used in the clinical evaluation of cancer patients. The markers reviewed have been chosen because they are biologically relevant to the growth of cells and possess an accurate and reproducible assay for detection. They also are predictors of tumor behavior, are useful in making clinical decisions, and are cost effective.
Cellular Cancer Markers provides a status report for markers of tumor cell activation, proliferation, and longevity that makes possible an informed judgment regarding the value of many newly proposed tumor markers. It also offers insight into the latest approaches to diagnosing cancer and an appreciation of how these marker-based tests can clarify the prognosis of cancer.

This timely work reflects the growing importance of research into the nature of sleep and its medical aspects. One of the first of its kind, this work on the neuroimmunology of sleep provides an introduction to the interplay between these two key and interlinked areas. Written both from a basic and a clinical perspective, the volume is an invaluable information resource for biomedical professionals and students of the human biology.

Highly practical guide written from both a basic and clinical perspective.

Essentials of Autopsy Practice is dedicated to updating the modern pathologist on the issues related to the autopsy. This first volume contains 12 topical chapters which are not covered in any other text. It comprises the most recent developments in current autopsy and relevant subjects that have not yet been covered in current autopsy textbooks. This is what makes this book exceptional in its field. The book will be of interest to both trainees and consultants in all sub-branches of pathology including forensic pathology. The subject matter will also appeal to other areas of clinical medicine and will make a good reference book.

The pancreas is about the size and shape of the hand; the tail points to the spleen, and the head is nestled in a loop of the duodenum. Loss of the exocrine (digestive) func tions commonly leads to severe gastrointestinal disturbances, malabsorption, a cata bolic state, and weight loss in the face of an adequate diet. Loss of endocrine pancreatic function leads to a large spectrum of disorders associated with the loss of hormone secretions; the most common and most severe is diabetes mellitus. Loss of the entire pancreas owing to trauma, surgery, atherosclerosis, or other medical problems leaves the patient in a digestive and metabolic crisis. The correct diagnosis of pancreatic disorders remains a challenge given the multi faceted function of the pancreas. The clinical laboratory plays an important role, and other tools such as CAT scans, ultrasound, radiographs, biopsies, and even surgery are used to make a diagnosis. The emphasis of Clinical Pathology of Pancreatic Disorders is on the clinical laboratory definition of pancreatic pathology. Disorders of the endocrine pancreas can be highly complex, and sophisticated tests are needed to determine the nature of the disease, its prognosis, and its optimal treat ment. Diabetes is the most common of the endocrine diseases; it presents in many ways, and has varied etiologies. We now know that the diabetes of childhood is usually an autoimmune disease, and this has a major effect on the treatment of these individuals."

General pathologists see many biopsies from transplanted organs but few are in large enough centres so that this forms the bulk of their work. The book describes the changes which can be observed in transplantation in all of the major organ systems that are routinely transplanted and there are accounts of the pathology of infections and of the immunological difficulties that are faced by these patients. The volume will be a valuable guide for those who wish to braoden their knowledge in this field.

Developmental cancer products (oncodevelopmental markers, ODM) not only serve as diagnostic and prognostic indicators but also may be used to study the nature of the carcinogenic process and the biology of tumors. For many years oncologists have searched for markers of cancer cells that would permit unequivocal recognition of cancer in contrast to noncancerous tissue. The earliest and still most widely used method of identification of cancer tissue or cells is the structural resemblance of cancer tissue to fetal or immature tissue. Pathologists not only recognize cancer by its morphologic similarity to fetal tissues, but also in many instances can relate the behavior of a given tumor to the degree of tissue differentiation. Thus, poorly differentiated tumors that resemble fetal tissue generally grow more rapidly and metastasize earlier than do well-differentiated tumors that more closely resemble adult tissue. In recent years the commonality of fetal and cancer tissue has been extended to products of tumor cells that, can be analyzed by biochemical, immunological, or physiological techniques. Increas ingly, products of cancer cells similar to fetal products are being identified and studied. These products range from cell-surface markers (fetal or differentiation antigens), placental proteins, hormones, and isoenzymes to a multitude of products, such as carcinoembryonic antigen (CEA), alphafetoprotein (AFP), lymphocyte markers, and nucleic acids, such as tRNA, that are produced in small amounts by v vi PREFACE continually differentiating cells in the adult but in much greater amounts by tumors."

One would rarely have the opportunity to augment his medical library with a more exhaustive examination of the subject matter than is contained herein. Would only that all areas of one's professional responsibilities be available in such a complete, didactic, written form. Having a decided interest in the subject of head and neck paragangliomas for the past decade, I have had the opportunity to explore the subject through published medical literature and personal investi gation, and feel qualified to commend Doctors Zak and Lawson on their dedica tion, accuracy, and thoroughness in this presentation. One seeking any particular aspect of knowledge from historical to an up-to-date concept on the subject of paragangliomas will find his answer here. Vincent J. Hyams CAPT MC USN Chairman, Otolaryngic Pathology Department Armed Forces Institute of Pathology Washington, D.C. Preface One of us (F.G.Z.) initially became interested in the paraganglionic system when as a resident in pathology at The Mount Sinai Hospital, he performed an autopsy on an elderly woman with an intracranial tumor of the posterior fossa, which extended through the jugular foramen into the neck in a dumbbell fashion."

The field of cellular, molecular, and developmental neuroscience repre sents the interface between the three large, well established fields of neu roscience, cell biology, and molecular biology. In the last 10 to 15 years, this new field has emerged as one of the most rapidly growing and exciting subdisciplines of neuroscience. It is now becoming possible to understand many aspects of nervous system function at the molecular level, and there already are dramatic applications of this information to the treatment of nervous system injury, disease, and genetic disorders. Moreover, there is great optimism that new strategies will emerge soon as a result of the explosion of information. This book was written to introduce students to the major issues, ex perimental strategies, and current knowledge base in cellular, molecular, and developmental neuroscience. The concept for the book arose from a section of an introductory neuroscience course given to first-year medical students at the University of Virginia School of Medicine. The text pre sumes a basic, but not detailed, understanding of nervous system orga nization and function, and a background in biology. It is intended as an appropriate introductory text for first-year medical students or graduate students in neuroscience, neurobiology, psychobiology, or related pro grams;..and for advanced undergraduate students with appropriate back ground in biology and neuroscience. While some of the specific information presented undoubtedly will be outdated rapidly, the "gestalt" of this emerging field of inquiry as presented here should help the beginning stu dent organize new information."

This represents the third volume in a series on cancer markers pub- lished by the Humana Press. The first volume, published in 1980, stressed the relationship of development and cancer as reflected in the production of markers by cancer that are also produced by normal cells during fetal development. The concept that cancer represents a problem of differentiation was introduced by Barry Pierce in describing differenti- ation of teratocarcinomas. Highlighted were lymphocyte markers, alphafetoprotein, carcinoembryonic antigen, ectopic hormones, enzymes and isozymes, pregnancy proteins, and fibronectin. The second volume, published in 1982 and coedited with Britta Wahren, focused on the diagnostic use of oncological markers in human cancers, which were systematically treated on an organ by organ basis. At that time, the application of monoclonal antibodies to the identification of cancer markers was still in a very preliminary stage. A general introduc- tion to monoclonal antibodies to human tumor antigens was given there by William Raschke, and other authors included coverage of those mark- ers then detectable by monoclonal antibodies in their chapters.

A critical phase in coronary heart disease, unstable angina, is thoroughly discussed in contributions by well-known experts. Since myocardial infarction still belongs to the main causes of death, this topic is highly relevant for the present research and possible future treatment of coronary heart disease. The major recent advances made in the pathophysiology, diagnosis and therapy of unstable angina are reported in depth.

Definition of the barrier The interstitial fluid (rSF) of the brain is separated from the blood by the blood-brain barrier (BBB). This barrier must not be thought of as a single entity or as an absolute restriction to all molecules, but as a multiple structure located at several sites within the brain. The first of these interfaces is located at the endothelium of the brain capillaries. Secondly there is a potential site for interchange on the outer linings of the brain between the dura and the arachnoid membranes. Thirdly, there are the choroid plexuses and the cerebrospinal fluid (CSF) which is in contact with the very permeable internal ependymal lining of the brain (Figure 1. 1). Finally there are areas of the brain which lack a blood-brain barrier. These areas constitute the circumventricu lar organs and have leaky capillaries with a barrier at the ependyma which limits the spread of molecules from those regions (Figure 1. 2). Each of these BBB sites has its own characteristic permeability and transport functions. We will now consider the properties of each of these barrier sites between the blood and the brain. THE CEREBRAL CAPILLARY ENDOTHELIUM Morphology This interface has both the largest surface area and the shortest path length between the blood and the brain rSF. The cerebral capillaries, which at first sight seem little different from the rest of the systemic circulation, are in fact unique to the brain."

With the advent of enzyme histochemistry, which this field and simplistic theories will be expanded or revealed hitherto unseen pathological differences discarded. between muscle disorders, muscle biopsy assumed Diseased muscle cells, as any other cell type, show an important diagnostic role. The investigation is easily only limited morphological changes. However bizarre, performed and is being undertaken with increasing very few of these changes, if any, are pathognomonic of frequency. Nevertheless there is still a tendency to a single disease. The exact significance of microscopic regard its interpretation as highly specialized and out findings is to a large extent determined by their clinical side the province of the general histopathologist. In this context. Thus, although this is an atlas, it is definitely atlas I have tried to lift the veil of neuropathological not designed to promote 'spot' histological diagnoses. I mystique and to describe and illustrate the basic have aimed to provide a guide to pathological reactions reactions of muscle cells. of muscle which will be useful to the practising histo Interpretation of the biopsy depends not only upon pathologist and all students of neuro-muscular disease. recognition of morphological abnormalities, but upon I hope that recognition of the lack of specificity of understanding why they occur. Throughout the atlas I individual morphological features will encourage the have attempted to correlate morphological changes . close clinico-pathological correlation which is essential with pathogenetic mechanisms."

It is hoped that this book may serve two purposes. felt that the resulting increase in size and expense of First it is intended for use at the bench. to help solve the book would not be justified. some of the problems of cell identification which The material was collected over many years and puzzle not only beginners. but even experienced we cannot individually acknowledge the great contri observers in the field of cytological diagnosis. Sec bution made by technical staff of the clinical cytology ondly we have reviewed the most significant previous laboratories who assisted the two authors to prepare publications. particularly those of the past 20 years. and stain the sl ides. Most of the electron micrographs so as to provide a source of reference. were made by or with the assistance of the late Denis Cytological diagnosis should not be isolated from W. Jerrome. and we are also grateful to Dr David histopathology. and many readers will regret the lack Ferguson for further help and advice with these. All of the immunocytochemical stains were done by Dr of cyto-histological correlation in our choice of photographs. Cells centrifuged out of suspension in Anna Ghosh. and Drs David Mason and Kevin Gatter pathological fluids bear very little resemblance to kindly commented on that part of the manuscript. their counterparts in tissue sections."

Decoding the significance of proteinuria as an indicator of severity or prognosis in kidney disease is a stimulating challenge to students and practitioners of nephrology. Sir Richard Bright in 1827 associated pro with the disease that bears his name. In the subsequent more teinuria than a century and a half, however, the meaning of the linkage between proteinuria and renal disease remains elusive. Proteinuria is discovered on routine urinalysis in about 10 million Americans, most of whom express no symptoms of kidney disease, each year. From the studies of Robinson (updated in these pages), we know that proteinuria, per se, can be present for 20 years without change in re nal function, as described in orthostatic proteinuria. By contrast, pro teinuria may be the harbinger of swift kidney destruction, rarely cul minating in clinical collapse, a syndrome typifying "malignant proteinuria" as detailed herein by Avram. Although proteinuria is ubiquitous, an orderly management strategy for rational handling of proteinuria of less than nephrotic range is lack ing. Separation of tubular proteinuria and transient proteinuria of fever is now possible routinely. This book provides a record of the contribu tions of investigators and clinicians whose work forms the substrate for production of understanding and, ultimately, marching orders for prac titioners seeking optimized management for their proteinuric patients."

This atlas deals with conditions commonly encountered in the male genital tract. Whilst the majority of illustra tions are photomicrographs, photographs of macro scopic specimens are also used to illustrate important features in distinguishing different pathological con ditions. Special emphasis is placed on the small biopsy specimens obtained from prostate and testis in modern urological practice and the importance of clinico pathological co-operation in pathological practice is stressed. Recent advances in our knowledge of testicu lar tumours are discussed and illustrated. The text is not entirely descriptive and attempts to give an intellectual framework around which histopathological diagnosis in this field can be practised. A modest number of references are included; they have not been singled out as representing milestones in the development of our knowledge of these conditions - the choice has rather more centred upon recent reports from which a litera ture search can be mounted if required. The atlas in no way pretends to be an encyclopaedic reference of con ditions of the male genital tract but attempts to provide an up-to-date comprehensive discussion of the histo pathology of this system. Acknowledgements I am most grateful to Mr Keith Gordon for developing all the photomicrographs and to Mr Geoff Gilbert and his staff in the Audio-Visual Department of the City Hospital who took the majority of the macroscopic illustrations. I must particularly thank my secretary, Mrs Dorothy Clay ton, for typing and retyping my draft chapters and for deciphering my hieroglyphics."