Increasingly, pathologists are being confronted with the effects of a number of complex devices on the body. Cardiac pace-makers are becoming increasingly sophisticated, ventricular support systems for the heart are well established, and vascular and other protheses are being used in increasing numbers. New joint systems, contraceptive devices used as drug delivery systems, and the use of new cement materials all provide challenges in terms of their pathology. The articles in this text collectively form a body of information on these devices not available elsewhere and with an up-to-date bibliography.

This volume forms part of a prestigious series and covers the latest advances in our understanding of the pathophysiology and treatment of asthma. Our understanding of asthma has changed dramatically in recent years, and much of this new information is brought together in this volume written by inter nationally recognised authorities. The aim of the book is to review in depth the changing concepts of inflammatory processes in asthma and to discuss the implications for research of this common chronic disease. Many of the advances in and future therapy our understanding of asthma have originated from a pharmacological approach, and this volume highlights the promising new options for pharma cological intervention. It is hoped this book will be invaluable for research scientists and clinic ians involved in asthma research and will be a major reference resource for chest physicians and those involved in the development of novel pharmaceu tical entities. Each chapter is extensively referenced, generously illustrated with clear diagrams and photographs, and represents a state-of-the-art review of this growing area. c.P. PAGE P.l. BARNES Contents CHAPTER 1 The Pathology of Asthma: An Overview L.A. LAmNEN and A. LAmNEN. With 10 Figures ...................... 1 A. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 1 . . . . . . . . . . . . . . . B. Methods to Investigate the Pathology of Human Asthma ............ 1 C. Bronchial Epithelium and Inflammatory Cells in Asthmatic Patients Between Attacks ........................... 2 I. Mast Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 4 . . . . . . . . . . . . . . II. Eosinophils ............................................... 7 III. Neutrophils.............................................. 10 D. Bronchial Epithelial Inflammation During an Asthma Attack. . . . . .. . 10 E. Epithelial Regeneration .... . . . . . . . . . . . . . . . . . . . . . . .. . . 12 . . . . . . . . ."

Traditions are dangerous; doubly so in science. Traditions are unchanging; science is about change. This was the 4th International Colloquium on Carbohydrate Metabolism in Pregnancy and the Newborn to be held in Aberdeen, and by now the form is set. How much its content has changed is a matter of nice judgement and not under the control of the organizers. It is not within their power to bring news of revolution, if there has been no revolution. Certainly many of the speakers had kent faces from previous Aberdeen meetings, but so they would be at any meeting on diabetes anywhere in the world. The written proceedings of scientific conferences have purposes other than to record changes: sometimes they need to state a consensus. The 3rd Colloquium came to an agreement about the importance of prepregnancy recognition and control of abnormalities of carbohydrate metabolism. The 4th set out to examine what results it had achieved. Much of this book is taken up with follow-up studies of the applications of similar regimes in different parts of the world. Since the first Aberdeen meeting in 1973, progress in the manage ment of diabetic pregnancy has been slow and steady, but the change in the city and the society where the meetings took place has been fast.

Pathology of Multiple Pregnancy collates case material from over 500 autopsies (including embryos) and 1200 placentas from twins, triplets, and higher multiples with selected literature on human multiple reproduction. It emphasizes important new concepts of pathophysiology and interpretation of less than ideal outcomes of multiple conception based on over 30 years experience in the field. Aspects of perinatal pathology unique to twins and higher multiples are emphasized, with practical suggestions for the service pathologist, including items of potential medico-legal significance. Controversial topics, such as the value of studies of concordance for diseases or malformations, and the significance of inter-twin anastomoses, are addressed and suggestions made for further investigation. A close working relationship between pathologists and clinical colleagues is encouraged by discussion of clinico-pathological correlations. And, the most recent discussions on mechanisms of twinning and genetic versus environmental influences on the development of twins are presented.

The subject of the apallic syndrome is one which has long been familiar to me, although I have not personally studied it as deeply as I would have wished. I became acquainted with this syndrome long before the last war, when my neurosurgical colleague Hugh Cairns (1952), made his pioneer contribution under the term "akinetic mutism" . This was an ar- resting title, but it was one which did not altogether satisfy some of his colleagues, includ- ing myself. We found it difficult to suggest an alternative. That is one reason why I wel- come the expression "apallic syndrome" . Forensic practice has forced me from time to time to consider rather more deeply this distressing syndrome, and to try and marshal my ideas in a form which would satisfy my colleagues in the legal profession. More than once I have been instructed to make a medico- legal assessment of these unfortunate patients. The points which have concerned my lawyer friends have not been matters of diagnosis, or of morbid anatomy, or of etiology. The fac- tual problem which has been put before me was to make some approximate assessment as to the expectation of life. Vague guess-work is unacceptable in such circumstances. What the lawyers require is a precise and dogmatic answer.

Progress in science is often promoted by a new method. Diagnostic cytology, however, developed slowly over a whole century, mainly in differentiating malignant from benign cells from various tissues. The decisive step in this development was the intensive investigation of one local ization by Papanicolaou: The application of cytology for screening in the field of gynecologic oncology made it an acknowledged technique. Consequently, materials inves tigated before were tested again on a larger scale and new ones were included into the program. The possibility of a wide-range application of this diag nostic method, which carries a low risk for the patient and is low in cost, attracted the specialists of many fields. One of the problems which has resulted is the coordination of training and quality assurance for a large group of people from different fields and with different interests and whose experience in morphology varies. In this volume general problems of cytology are dis cussed, as is the question "who is a medical cytologist?" Education and training are the topics of the contributions by Coleman, Holzner, Jenny, Koss and Muller, cover ing the situation in the European Community, Germany, Austria, Switzerland, and the USA. A special contribu tion by Lange concerns the situation of cytotechnologists, paramedicals important for cytologic screening programs.

The Leitmotiv of the Second Convention of the Academia Eurasiana Neurochirurgica was "Cerebrum convalescit" - literally "the brain recovers." The focus of the meeting was on plasticity of the central nervous system, one of the most decisive factors in recovery and readaption after cerebral lesions. Distinguished experts from the fields of neurosurgery, neurology, neurophysiology, anatomy, pathology, oncology, and pharmacology discussed the following topics: - Molecular and cellular basis of plasticity - Regeneration and growth in the CNS - Self-organization of neuronal network - Brain oedema - a reparatory process? - Growth factors and carcinogenesis

The tumors of the brain similar to other pathological changes of that particular organ claim for a separate position in scientific medicine regarding biology, morphology, features of clinical manifestation, diagnostics and therapy. During the past years due to rapid progress in basic neurosciences and medical biotechnics the situation of the neuroclinician in front of brain tumors has been dramatically changed. The prerequisites for early and accurate diagnosis as well as for successful treatment also of malignant neoplasms have increased and remarkably improved. At the same time the information necessary for an appropriate pragmatic use of the available cognitive methods and therapeutic means increased along the same scale and is permanently being critically modified or changed due to fundamental new insights which come up in always shorter intervals. These facts necessitate the preparation of publications in which the state of the art is presented in possible completeness, systematic order and proper disposability for rational management and therapeutic strategies.

This Atlas of Oral PathologV is intended primarily as a ances where appropriate and reproduce relevant radio graphs. Every pathologist who deals with bone specimens bench companion for the general diagnostic pathologist. especially the trainee. It has not been designed to cover will know the value of radiographs, and some indeed are the subject fully and in detail, nor does it enter into the reluctantto make a diagnosis in their absence. In addition, radiographs may give a good idea of the extent aFld other more theoretical aspects. Since the book is essentially an atlas the text has been features of a lesion that may be represented in the first kept to a minimum, but in it we have tried to adopt'a instance only by a small biopsy specimen. practical approach, with special regard to differential diag While many of the illustrations have been made from nosis. We have made some remarks about the clinical sections freshly cut and stained for the purpose, others features of the various conditions dealt with, since this have been prepared from stained sections already in our may help the pathologist to appreciate what is in the refer files and since, in addition, the material comes principally ring clinician's mind in an area with which the pathologist from two departments, as well as from outside sources, may not be particularly familiar."

It is a great honor and pleasure for cerebral infarction have been carried me to have Springer-Verlag publish out. Dr. Yoshimoto hoped that the this volume entitled "Treatment of results of research done in our depart Cerebral Infarction." I am much in ment over the last sixteen years con debted to my colleagues for my success cerning cerebral infarction could be in publishing this book. published. Moved by his enthusiasm, I have engaged in clinical work in my colleagues took their share in writ the field of neurosurgery for these few ing each article. I suggested to them decades and I have performed more that this volume should cover primarily than 5,000 major operations of intra the results of our own research, but that cranial surgery. Throughout this time, at the same time it should also include it has been my privilege to conduct a 2- the results of related work done by neurosurgical experts throughout the hour-morning research seminar in our department every Wednesday and to world. Therefore, I hope that this book supervise a great deal of research. At will interest many investigators who these seminars my fellow research have devoted themselves to research in workers and I have exchanged many the field of neuroscience. ideas about the study of neurosurgery My colleagues acknowledge that and we have designed many animal our research has been stimulated and experiments."

Reevaluation of tumor classification, differential diagnosis and differential therapy based on modern knowledge. Revision of all chapters to incorporate new facts based on recent discoveries.

Twenty-five years have passed since J. MILLER'S basic work on the central role of the thymus for the generation of immunological reactivi ty. During this time, the abundance of fascinating literature on the immunological and functional aspects of this organ has been in contrast to the paucity of reports on its role in pathology. The causal or formal pathogenesis even of many of the well-documented pathological fea tures is so far unexplained or at least uncertain. In spite of some concep tual progress related to the work of CASTLEMAN, LEVINE, and ROSAI, we regrettably have to say that in pathology the thymus remains almost as inconspicuous as 25 years ago. Only the new techniques developed in recent years have made it possible to look as closely into the complicated structural organization of the thymus as it appears to be necessary to observe and document abnormalities. Major steps have been taken with the advent of mono clonal antibody immune histochemistry and with detailed ultrastructur al studies in embryology. At this point, pathologists and researchers with a special interest in the thymus were asked to give overviews of their respective fields of interest in light of recent findings in immunology and basic insights into the structural-functional interrelationship of the human thymus. The results of this initiative have been brought together in this volume.

The classification of tumors is important for understanding tumor histogenesis, for predicting prognosis, for differential diagnosis, and for recommending appropriate therapy. Since 1836, when pancreatic cancer was first described, progress has been made in pancreatic cancer morphology, and a number of classifications have been proposed. All of these classifications are mainly based on morphological characteristics. Some are too detailed to be of practical use while others are more pragmatic. Some of the inherent problems in the previous classifications included difficulties in obtaining an adequate number of pan creatic tumors for examination and insufficient clinical data and follow-up. With the increasing incidence of pancreatic cancer in many parts of the world during the past six decades, and with the availability of more tumors to patho logists, advances have been made in pancreatic tumor studies. Classifications by Cubilla and Fitzgerald and by Kloppel, which are generally similar, mostly considered prominent morphological features and their histogenesis. These pathology-oriented classifications, although complete, were not practical from the standpoint of clinicians concerned with the prognosis of individual tumors."

Amyloid-forming proteins are implicated in over 30 human diseases. The proteins involved in each disease have unrelated sequences and dissimilar native structures, but they all undergo conformational alterations to form fibrillar polymers. The fibrillar assemblies accumulate progressively into disease-specific lesions in vivo. Substantial evidence suggests these lesions are the end state of aberrant protein folding whereas the actual disease-causing culprits likely are soluble, non-fibrillar assemblies preceding the aggregates. The non-fibrillar protein assemblies range from small, low-order oligomers to spherical, annular, and protofibrillar species. Oligomeric species are believed to mediate various pathogenic mechanisms that lead to cellular dysfunction, cytotoxicity, and cell loss, eventuating in disease-specific degeneration and systemic morbidity. The particular pathologies thus are determined by the afflicted cell types, organs, systems, and the proteins involved. Evidence suggests that the oligomeric species may share structural features and possibly common mechanisms of action. In many cases, the structure function interrelationships amongst the various protein assemblies described in vitro are still elusive. Deciphering these intricate structure function correlations will help understanding a complex array of pathogenic mechanisms, some of which may be common across different diseases albeit affecting different cell types and systems."

Located at the interface between blood and the brain, the blood-brain barrier is a dynamic permeability barrier formed by a continuous layer of specialized endothelial cells endowed with important permeability, transport, and regulatory functions that both protect the internal milieu of the brain and allow essential nutrients to be transported into the brain. Abnormalities of the blood-brain barrier are increasingly recognized as a key component in the pathogenesis of a range of primary diseases of the brain and the secondary involvement of the brain from pathological processes in other organs. In The Blood-Brain Barrier in Health and Disease, Volume 2, international experts present comprehensive reviews and research accounts on blood-brain barrier dysfunction in infectious and inflammatory diseases, cerebrovascular diseases, stroke, trauma, vitamin deficiency, exposure to neurotoxicants, primary and metastatic brain tumors, and neurodegenerative diseases. This book is intended to serve as a guide and reference to basic and advanced information for researchers, students, and clinicians interested in this fast-expanding field and stimulate further research well into the future.

The purpose of this work is to review the current knowledge of laryngeal pathology in the light of my experience at the Institute of Laryngology and Otology, London. The role of histopathological investigations in the care of patients with diseases of the larynx is given special consideration. Radiologi cal study of the larynx has become more refined in recent years with the introduction of computerised tomography. Microlaryngoscopy with biopsy of the interior of the larynx is now a frequent procedure in the diagnosis of laryngeal disease. In the effort to interpret the findings resulting from these methods, the need for a monograph outlining the pathological basis of laryngeal disorders has arisen. To the best of my knowledge, such a work, devoted to the pathology of the larynx only, has never been written; a modern study in this field is certainly not available. I have aimed the text towards the practising pathologist in order to give it the broadest scope. It was necessary, therefore, to include an account of the basic anatomy of the larynx. For this purpose (and in subsequent descriptions throughout the book) I have not used the formal anatomical terminology for the two folds on either side of the ventricle of the larynx. There is some variation in the use of these terms, and they are not yet completely in general use."

Various textbooks on stereotactic neurosurgery have been published during the last few years (Riechert 1980, Schaltenbrand and Walker 1982, Spiegel 1982), all of them dealing with functional stereo tactics as the major subject in the field. Diagnostic and therapeutic stereotactic interventions are only briefly described, whereas localization techniques are not yet mentioned. Since 1980, however, an increasing number of reports has been published on CT guided and computer monitored stereotactic performances which enable the surgeon to combine diagnostic and therapeutic efforts in one session. With recent progress in scanning techniques, including high resolution CT, NMR, and PET imaging of the brain, it has become possible to study and localize any brain area of interest. With the concomitant advances in computer technology, 3-dimensional reconstruction of deep seated lesions in stereotactic space is possible and the way is open for combined surgery with stereotactic precision and computer guided open resection. This type of open surgery in stereotactic space is already being developed in some centers with the aid of microsurgical, fiberoptic, and laser beam instrumentation. With these advances stereotactic techniques will rapidly become in tegrated into clinical neurosurgery. Stereotactics has become a metho dology which enables the surgeon to attack deep seated and subcortical small tumors. Neurosurgeons may abandon therapeutic nihilism, still frequently seen in glioma treatment, in the near future when stereotactic resection will be feasible and remaining tumor cells may be killed by adjuvant treatment modalities still in development."

MOTOOMI NAKAMURA As we approach the 21st century, ischemic heart disease is the major cause of death in most of the developed nations of the world. Since the 1970s, much effort and expense have led to designs of coronary thrombolytic therapy, percutaneous coronary angioplasty (PTCA), coronary artery bypass grafting, heart transplantation, automatic defibrillators, as well as to the formation of beta blockers and com pounds which block the calcium channel. Socio-educational programs directed at exercise, diet, instruction in the risk factors of smoking, hyperlipidemia and hypertension have contributed to the decrease in the rate of morbidity and mortality of patients with ischemic heart disease. However, the first clinical event of ischemic heart disease, the so-called "heart attack" and sudden cardiac death continues to present problems, as the mechanisms involved in these events are poorly understood. It has long been thought that ischemic heart disease is the sequence of an organic fixed atherosclerotic obstruction of the epicardial coronary arteries and the role of coronary vasomotion has been given much less attention. Recent clinical and laboratory animal studies revealed that increased tonus and spasm of the large epicardial coronary arteries are the cause of various stages of ischemic heart disease. The role of coronary vasospasm in the development of un stable angina, sudden cardiac death and acute myocardial infarction remains open to debate. Pharmacophysiological studies showed that the epicardial large coronary artery contributes only 5% to regulation of normal coronary flow."

Almost all known tumors and tumor-like conditions of the fe- male lower genital tract are classified in this complete mo- nograph on the subject. Clinical features, treatment and prognosis ar included, making this book a practical refe- rence for the busy clinician.

One out of every two men over eigthy suffers from carcinoma of the prostate.It is discovered incidentally in many patients with an alleged benign prostatic hyperplasia. In treating patients, the authors make clear that primary radical prostatectomy is preferred over transurethral resection due to the lower complication rate.

John R. Petersen and Amin A. Mohammad, along with a panel of leading basic and clinical investigators, review those CE methods that are now replacing many routine serum and blood tests in clinical and forensic laboratories. Major areas reviewed include the coating of columns; the analysis of serum, urine, and CSF proteins and paraproteins; abnormal hemoglobins and hemoglobin Alc; peptides, amino and organic acids; therapeutic drugs; drugs of abuse; viral load; and short tandem repeats (STR). The methods discussed include capillary zone, micellar, electrokinetic, capillary gel, and non-aqueous electrophoresis. Innovative and highly practical, Clinical and Forensic Applications of Capillary Electrophoresis demonstrates the power and versatility of CE-not only to develop new assays, but also to markedly simplify today's clinical and forensic laboratory methodology.

The methods of molecular biology, biochemistry, immunocytochem istry, and in-situ hybridization introduce new opportunities for the classification and functional characterization of cell receptors under normal conditions and for a better understanding of pathogenetic mechanisms in human diseases. The cellular localization and trans location of receptor proteins can be identified using morphological methods, and it is apparent that receptors and receptor defects play an important role in pathology, notably in genetic diseases, endocrine disorders, atherosclerosis, infections, and cancer. In this volume in ternational experts give a current review of the morphology and pathological aspects of cell receptors. The complex communication of multicellular organisms is coordi nated by two regulatory systems: neural and humoral. Both systems function via signaling substances (ligands) and signal-recognizing and -transmitting molecules, called receptors. The historical develop ment of the receptor concept is based upon Paul Ehrlich's theory of "receptors in the immune system," Langley's "receptive substances in postssynaptic membranes," and Earl Sutherland's discovery of "sec ond messengers" (cAMP and Ca2])."

Battle is a practical and sometimes lasting way of solving man's problems. It relies on the strength of the combatants and ignores the truth of the dispute. Discussion face to face can dissolve attitudes which have incorrectly determined judgements. The most striking example of this that I know is a Battle in Ireland in the eleventh century, where the king of Leinster fought a Viking prince. The Icelanders had raided Ireland for several generations in search of women, which they lacked since most of the population of Iceland were men who had arrived there by rowing long-boats from Norway. The prince was leading such a raid for the first time. Standing in the prow of the leading boat he saw Irish cavalry galloping along the beach to meet them. As they approached the shore the Irish king rode out of the band to challenge single combat. The Icelander jumped into the surf to meet him. As they raised their swords each realized that the other's face was like his own. When the Irish king spoke the other recognized the language. It had been spoken in Iceland by his grandmother who had been captured and taken there from Ireland. Swords were dropped and replaced by drinking horns. It was soon established that they were cousins. The battle gave way to a life-time of close co-operation.

The decisive factor in trauma is that many processes first occur at the cellular level before they can be determined in laboratory tests, and recognition of them has only recently found its way into intensive care practice. Yet knowledge of the pathophysiology of these processes is essential for an early diagnosis of multiple organ failure and the implementation of adequate therapy, which ultimately make the patient's survival possible. Professor Schlag, an internationally renowned scientist and clinician, has been concerned with the basic pathophysiological principles of shock for many years. In this book he has brought together for the first time an international team of authors primarily from the USA and Europe, who present their collective findings of trauma, shock, development of the organ in shock and early failure and of sepsis-like syndrome, and development of septic multiple organ failure. Patienten mit Multiorganversagen haben immer noch eine schlechte Prognose in der intensivmedizinischen Behandlung, insbesondere wenn sie noch zusatzlich in einen septischen Schock geraten. Hier hilft auch oft eine breite Abdeckung mit modernsten Antibiotika nicht weiter. Neue Ansatze fur eine Therapie dieser problempatienten haben sich in den letzten Jahren durch Erkenntnisse der pathophysiologischeen Vorgange die zum Schock fuhren ergeben. Herr Professor Schlag hat als anerkannte Kapazitat auf dem Gebiet der Traumatologie und Schockforschung fur dieses erste umfassende Werk zu den Grundlagen des Multiorganversagens eine beeindruckende Liste von mehr als 50 international renommierten Autoren zusammenbekommen. Das Buch ist nicht nur eine Aufarbeitung aller Grundlagen des Schocks und Multiorganversagens sondern zudem ein ausgezeichnetes Nachschlagewerk fur jeden intensivmedizinisch tatigen Klinikarzt, egal ob er aus der Anasthesie, der Inneren Medizin oder der Unfallchirurgie kommt."

I was gratified by the most favorable reception and wide usage received by the first edition of this book. A decade seems to be a short period for a book on pathology, and yet it witnessed many important changes of concepts, along with a formidable growth of knowledge. The second edition required extensive reorganization. There are new chapters on mitochondriopathies, on peroxisomal diseases and on spongy myelino pathies. Major revisions and new additions were necessary in many chapters, for instance those on the dysplasias of the cerebral and of the cerebellar hemispheres, which were largely reorganized. The chapters on perinatal pathology were reordered and reorganized to give a more logical sequence of prenatal, perinatal and postnatal lesions. The entire text was worked over for brevity. A wealth of new references was added with the. aim of staying abreast with the literature up to summer 1988. All refer ences were double checked for errors. My gratitude goes to Mrs. Gisela Ropte and Mrs. Cynthia Bunker for their untiring, diligent help. As a result, this second edition is an essentially rewritten text. Advance in the prevention of human suffering is based on a thorough understand ing of the nature of disease. I hope that this text will continue to be of service in this behalf. Perhaps it may also reflect and foster the intellectual curiosity which makes the "reading of brains" so interesting an occupation. Gottingen, 1989 Reinhard L.