Rejection and Tolerance is the latest subject in the Continuing Education series, organized by Fondation Marcel Merieux and Universite Claude Bernard in Lyon. The annual subject is chosen to reflect the status of the topical issues of the year, as taught by leading international experts. The contribution of transplantation and clinical immunology to advanced medicine is considerable and promising. The annual volumes in this series keep the reader abreast of these developments. "

Laryngotracheal Reconstruction: From Lab to Clinic lines for using the technique of tracheal autotra- presents the experimental and clinical aspects of plantation in conservation laryngectomy. The tissue reconstruction of the larynx and trachea. shortcomings and complications of tracheal auto- The book reflects the development and implemen- transplantation encountered in the initial patient tation of a research-based clinical program. The series led to a modification of the technique. The experimental work was started in 1989 with the modified autotransplantation technique proved to aim of improving the reconstructive possibilities be reliable from a reconstructive, functional and in the following two clinical situations: (1) extend- oncological viewpoint. ed hemilaryngectomy defects after tumour In a second part (Chap. VI), healing aspects after removal and (2) tracheal stenoses that are impos- repair of laryngotracheal defects are highlighted. sible to repair by segmental tracheal resection. The The healing mechanisms of the cartilage support, two problems differ in localization (larynx, tra- the mucosal lining and the blood supply were chea), etiology (oncology, traumatic), and treat- studied for each tissue component individually.

The research field of biobanks and tissue research is highly promising. Many projects around the globe are involved in the collection of human tissue and health data for research purposes. These initiatives are driven by the perspective of decisive breakthroughs in the knowledge of the genetic pathways involved in widespread diseases. However, there are considerable ethical and legal challenges to be considered as well. These challenges encompass the use of body material for research purposes, the misuse of genetic and other health data by third parties, trust in science and medicine, concerns regarding privacy, use of genetic data for forensic applications by the state and the police, and regulatory issues. This volume is divided into three parts: the inclusion of the public, the rights of donors and patients, examples and recommendations for the future of tissue research. It presents a comprehensive overview of the most important topics in the field by renowned scholars in medical ethics and biolaw.

Organ transplantation is an essential element of treatment for a wide range of diseases, but despite increasing surgical success rates there remain many other issues affecting selection of patients and clinical outcome with which clinicians and patients themselves must be familiar. Originally published in 2000, this book reviews psychosocial, psychiatric and ethical aspects of organ transplantation in a uniquely authoritative way. Drawing heavily on the pioneering work of the Pittsburgh transplant team, it surveys the essentials of transplantation biology before engaging with a range of topics fundamental to the success of the procedure and the quality of life of recipients and donors alike. The interdisciplinary approach and the authority of the contributors will make this book of value to anyone with an interest in organ transplantation procedures.

The use of cells for the treatment of a variety of diseases is no longer a dream. Today, blood transfusion, bone marrow transplantation, the use of ex vivo cultured skin in wound healing, and peripheral stern cell transplantation, including the ex vivo expansion of hematopoietic stern cells after high-dose chemo/radiation therapy, are routine. This high standard of knowledge and skills in cell transplantation might also re sult in tackling hitherto untreatable diseases. Organ transplantation is presently the only life-saving treatment for a variety of conditions. Important findings in cell and molecular biol ogy, the identification of hematopoietic, mesenchymal and neuronal stern cells, together with breakthroughs in the methodology for isolat ing, purifying, expanding, and storing human cells could make cellular therapy an alternative to organ transplantation in certain diseases within the next decade. Placental blood may be the source of choice in isolating naive progenitor cells for allogeneic transplantation. Immunotherapy is the most hopeful strategy to date for the treat ment of tumors resistant to chemotherapy, radiation therapy, or hor mone therapy. It includes the use of tumor-infiltrating lymphocytes, ex vivo activated memory T lymphocytes, and cell-based vaccines."

Chronic liver failure is a frequent condition in clinical practice that encompasses all manifestations of patients with end-stage liver diseases. Chronic liver failure is a multiorgan syndrome that affects the liver, kidneys, brain, heart, lungs, adrenal glands, and vascular, coagulation, and immune systems. Chronic Liver Failure: Mechanisms and Management covers for the first time all aspects of chronic liver failure in a single book, from pathogenesis to current management. Each chapter is written by a worldwide known expert in their area and all provide the latest state-of-the-art knowledge. This volume is specifically designed to provide answers to clinical questions to all doctors dealing with patients with liver diseases, not only clinical gastroenterologists and hepatologists, but also to internists, nephrologists, intensive care physicians, and transplant surgeons.

With a long practice of organ transplantation, retransplantation has become a major goal in patients with long-term failure of their first transplant (chronic rejection, exhaustion of the transplant, recurrence of the initial disease, etc. ). In addition, retransplantation can be necessary in the initial period, due to severe acute rejection, a non-functioning organ, or surgical complication. Immunological and non-immunological factors affecting the success of a second transplant are described in this volume, together with alternatives to retransplantation. It is hoped that in the future retransplants will be less frequent, as a result of improved prevention of transplant failure. J. L. Torrroine et a/. (ens. ), Retra isplantation, xvii. Q 1997 Kluwer Academic Pirblislters. P . iilted in Great Britain. List of contributors R. ARNOLD Y. W. CHO University of Pittsburgh UCLA School of Medicine Center for Medical Ethics Tissue Typing Laboratory Division of General Internal Medicine 950 Veteran Avenue 200 Lothrop Street - MUH, Suite W-919 Los Angeles, CA 90095-1652 Pittsburgh, PA 15213-2582 USA USA P. COCHAT M. A. BELGER Hopital Edouard Herriot UKTSSA Pavillon S Fox Den Road 5, Place d'Arsonva1 Stoke Gifford F-69437 Lyon Cedex 3 Bristol BS12 5RR France UK B. CUZIN F. BERTHOUX Hopital Edouard Herriot Service de Nephrologie et Pavillon V Transplantation Renale 5, Place d3Arsonval Hopital Nord F-69437 Lyon Cedex 3 F-42055 Saint Etienne Cedex 2 France France J. H. DAUBER C.

Never before has a comprehensive history of the pancreas like History of the Pancreas been published. It not only is a historical review of the science of medicine, it is liberally interspersed with anecdotal vignettes of the researchers who have worked on this organ. Much of it, such as the discovery of the duct of Wirsung, of the islets of Langerhans, of insulin, gastrin and their tumors, reads like the adverture, which it is. This book, divided into 14 chapters, is written in a narrative style and is easily readable, as glimpses of the investigators, those who failed as well as those who succeeded, adds both perspective and human interest. Each chapter is completely referenced, totaling over 1500 references. As a reference book for students, teachers, investigators, writers, its detailed hjistorical documentation is unique. From the pre-Christian era of Asia Minor, to Greece, Rome, Europe and America, to the explosive progress in Japan, the history is there. History of the Pancreas: Mysteries of a Hidden Organ fills a gap.

Progress in the development of surgical implant materials has been hindered by the lack of basic information on the nature of the tissues, organs and systems being repaired or replaced. Materials' properties of living systems, whose study has been conducted largely under the rubric of tissue mechanics, has tended to be more descriptive than quantitative. In the early days of the modern surgical implant era, this deficiency was not critical. However, as implants continue to improve and both longer service life and higher reliability are sought, the inability to predict the behavior of implanted manufactured materials has revealed the relative lack of knowledge of the materials properties of the supporting or host system, either in health or disease. Such a situation is unacceptable in more conventional engineering practice: the success of new designs for aeronautical and marine applications depends exquisitely upon a detailed, disciplined and quantitative knowledge of service environments, including the properties of materials which will be encountered and interacted with. Thus the knowledge of the myriad physical properties of ocean ice makes possible the design and development of icebreakers without the need for trial and error. In contrast, the development period for a new surgical implant, incorporating new materials, may well exceed a decade and even then only short term performance predictions can be made.

Infectious Complications in Transplant Patients has been uniquely designed and formatted to address issues and trends pertaining to pathogens deemed important in critically ill transplant patients. The chapters have been carefully selected so as to direct the focus of the book towards current approaches to controversial, emerging or topical problems in these patients. Each chapter has been authored by a North American and a European specialist. This format serves to impart an added dimension reflective of the diversity of opinions and practices pertaining to unresolved or controversial issues. The authors are recognized experts in their respective fields.

In Drugs and the Liver: High Risk patients and Transplantation, leading physicians, hepatologists, pharmacologists, pathologists and transplant surgeons discuss the most recent advances in the field of liver disease and their treatment. Attention is focused on epidemiology, the diagnosis of disease (clinical chemistry, histopathology, medical imaging analysis), prognosis, prediction, and clinical management. Pathogenesis of diseases such as liver cirrhosis following viral disease or alcohol abuse are discussed at length, and special attention is dedicated to high risk patients (children, fulminant hepatitis). The other major topics include terminal liver failure, for which transplantation is now routine. The latter is discussed in depth, starting from the organ donor management, organ evaluation and preservation, new surgical techniques, post-transplant patient follow-up including side effects of immunosuppression, and reports of the latest drugs used to prevent rejection.

As dogmas in stem cell research are losing their impact and recent findings regarding the use and cultivation of stem cells and tissue transplantation have opened up new therapeutic avenues, this Ernst Schering Research Foundation Workshop was initiated to highlight current and future approaches in this field. The only stem cells that have been used clinically for a long time is the hematopoietic stem cell as a source for bone marrow transplantation. Recent findings now indicate that hematopoietic stem cells, under certain conditions, are able to differentiate into endothelial, neural or muscle cells, providing exciting new therapeutic possibilities. They represent a future source for tissue engineering replacing defective cells or tissues and allowing diseased organs to regain their functions. Both reconstitution techniques are paving the way for the development of new therapeutic strategies, giving hope of being able to cure and not only treat patients.

New Harvest includes contributions from specialists in medical, philosophical, psychological, religious, and legal fields. These essays are not simply a collection, but were developed from a single conception of the four ethical concerns of trans plan tation described in the first chapter. The indi vid ual chapters are all parts of a structure unified by the search for ethical foundations basic to the four concerns. Transplantation is surrounded by a great deal of under standable emotional sensitivi ty. The authors trust that words like "procurement," "harvest," and possibly other expressions found in this book will not offend. We use the current lan but do so with objectivity and respect for those who guage, are personally involved in transplantation. We have made room for, and indeed have invited, different and sometimes conflicting points of view on the complicated ethical ques tions raised by transplant operations. We can not assume that there is one right answer to these questions, at least at our present level of scientific knowledge and ethical wisdom. We do not presume to have identified and analyzed all the ethical questions raised with equal thoroughness. There are four ways in which the scope of the book is limited. Identifying these limitations also helps designate what it is in its own right. First, some questions have been given more attention than others.

Therapeutic immunosuppression has very broad applications in clinical medicine, ranging from prevention and treatment of organ and bone marrow transplant rejection, management of various autoimmune disorders (e.g., rheumatoid arthritis), skin disease, and asthma. Whereas traditionally only a small repertoire of immunosuppressive agents was available for clinical use, recent discoveries have significantly increased the number of approved agents, resulting in numerous trials to further evaluate their potential. In addition, products of the biotechnology industry - monoclonal antibodies, cytokines, cytokine antagonists, and other products of genetic engineering that target key molecular pathways in disease pathogenesis - have either already made, or are on the verge of making an important impact on treatment. There is also considerable interest in the potential of cell-based therapies (particularly hematopoietic stem and dendritic cell therapy) of allo- and autoimmunity. Important recent advances in the immunotherapy of allergic diseases are also covered in this book. Gene therapy offers considerable promise for suppressing pathogenic processes in either transplantation or autoimmune disorders. The possibility of combining these important new advances to maximize benefit to the patient, and to minimize possible untoward effects (which are also given extensive coverage in this book), is one of the most exciting challenges of contemporary medicine. This volume is intended both for practising physicians and surgeons and for biomedical scientists at the graduate/postdoctoral levels, and is designed to provide the theory behind these various approaches to immunosuppression, and to provide state-of-the-art reviews of current developments in each area. Each chapter is contributed by one or more experts in the field. There was a need to bring this information together in a single volume, as much of the key recent developments have been dispersed throughout the biomedical literature, largely in specialized journals. Since, as in the past, important developments in immunosuppressive therapy in one branch of medicine (i.e. transplantation) are likely to benefit another (e.g., dermatology, rheumatology, gastroenterology), cross-disciplinary coverage of the mechanistic basis of the various therapeutic strategies in a single volume is likely to convey the potential of advances in therapy in the most coherent manner possible.

General surgery consists ofa main corpus of propaedeutic elements and clinical problems, which has been modified over the years by the separate development of numerous sub-specialistic branches. Although a common basis on the physiopathology of surgical trauma and post operative complications persists, as a result of general knowledge of surgical diseases, there is no doubt that in the spheres of doctrine and application, both research and clinical medicine have distinguished themselves autonomously in many surgical fields (orthopedics, neurosurgery, cardiovascular surgery, thoracic surgery, urology, etc.). It is therefore difficult to define the present configuration ofgeneral surgery, but without question abdominal surgery occupies a position of pre-eminent importance within the general framework. We are dealing, in fact, with pathological pictures which occur in a section ofthe body ofvast proportions, in which structures, organs, and morphologically complex spaces are arranged to carry out important functions. They are, therefore, subject to considerably complex pathological alterations, such as to establish an interesting field of diagnostic discussion and an exciting training-ground for surgical activity. It can be affirmed that the diagnosis and cures ofabdominal surgical diseases constitute a test ofthe surgeon's experience. Diagnosis is often entrusted to a differential process, the results ofwhich may be confirmed today by complementary diagnostics. This, however, must be guided by predominating clinical considerations, the exaggerated use of diagnostic techniques, detached from clinical examination, being the cause of very serious errors, which can mislead decision making and human contact, which is the basis ofcorrect medical practice.

It has been 15 years since the first report on the isolation of anti-Gal from human serum and the demonstration that this antibody is the most prevalent antibody in humans (Galili et al. , ]. Exp. Med. 160: 1519, 1984). Subsequent interdisciplinary studies in immunology, carbohydrate biochemistry, molecular biology, and evo- lution demonstrated the highly restricted specificity of anti-Gal for the carbohy- drate epitope Gal al-3Galpl-4GIcNAc-R, (termed here the a-gal epitope), the unprecedented evolutionary pattern of distribution of a-gal and anti-Gal in mam- mals, and explained the evolution of this antigen and antibody by analysis of the a 1 ,3galactosyltransferase gene, the gene that encodes the enzyme that synthesizes the a-gal epitope. These studies have suggested that a major selection process that occurred in the course of evolution of ancestral Old World primates resulted in the inactivation of the a1 ,3galactosyltransferase gene and the subsequent appearance of anti-Gal in these primates. Other studies in immunoparasitology have demon- strated the possible physiologic significance of anti-Gal in protection against cer- tain parasitic infections. Major scientific attention was focused on a-gal and anti-Gal with the real- ization in the early nineties that the interaction between this antigen and antibody is the major obstacle to xenotransplantation. The success of immunosuppressive drugs, in the last two decades of the 20th century, in preventing allograft rejection, has raised hopes for cure in many patients in need of organ transplant. Because of limited supply of allografts, only 20% of patients receive the needed organ.

Currently, individuals interested in seeking an in-depth discussion of transplantation immunology must seek individual articles published in several journals, or extrapolate information from various non-transplant immunology textbooks. The purpose of this text is to provide the reader with a single source of information for the basic science of immunobiology of organ transplantation. It is unique that it focuses on immunobiology from the basic research side, with an emphasis on the cellular and molecular levels. The readers will be physicians, scientists, and graduate students interested and engaged in the study of immunology as it relates to allo- and xenotransplantation. This book is designed to be the reference standard for the immunobiology of transplantation.

Neural Stem Cells: Development and Transplantation provides comprehensive, critical and insightful reviews by leading experts in this exciting field of research. This volume will provide the latest data on neural stem cell properties and their therapeutic applications. This volume will be particularly useful for students, basic scientists, and clinicians in the academic or industrial sectors who have an interest in understanding neural development and its application to repairing the nervous system.

Integrated Biomaterials Science provides an intriguing insight into the world of biomaterials. It explores the materials and technology which have brought advances in new biomaterials, highlighting the way in which modern biology and medicine are synergistically linked to other key scientific disciplines-physics, chemistry, and engineering. In doing so, Integrated Biomaterials Science contains chapters on tissue engineering and gene therapy, standards and parameters of biomaterials, applications and interactions within the industrial world, as well as potential aspects of patent regulations. Integrated Biomaterials Science serves as a comprehensive guide to understanding this dynamic field, yet is designed so that chapters may be read and understood independently, depending on the needs of the reader. Integrated Biomaterials Science is attractive to a broad audience interested in a deeper understanding of this evolving field, and serves as a key resource for researchers and students of biomaterials courses, providing all with an opportunity to probe further.

Meniscal transplantation has become an attractive option in selected patients with incapacitating knee pain. This book discusses all aspects of meniscal transplantation, covering the use of both allografts and meniscal substitutes, including collagen and polyurethane implants. Acknowledged experts in the field review the basic science, explain indications, and describe surgical techniques and the results achieved to date. All the material is up to date, with information on new implants, new techniques, and new surgical approaches. Future trends in the treatment of meniscal lesions are also discussed as we move towards the application of regenerative strategies to restore meniscus function. "

In recent years cell-based technologies have gained significant scientific attention, and have become a matter of intense public debate as well. Namely, (i) tissue engineering, the construction of tissues and whole organs using molecularly-designed resorbable biomaterials to create new tissue de novo with or without transplanting cells; (ii) the potential use of human embryonic stem cells for transplantation and regenerative medicine (with similar potential for adult-derived stem cells); (iii) and gene therapy, in relation with cell transplantation, have taken their places as the most discussed biomedical issues of the day. New findings in biomimetic materials, cell signalling pathways, extracellular matrix receptors and ligands, growth factors, and the human genome project are motivating the developments in these challenging research areas. This book includes manuscripts on tissue engineering, stem cells and gene therapies authored by world-renowned scientists of the field. The first section of the volume consists of four chapters giving perspectives for the current status and potential future of tissue engineering and stem cell technologies. The second section of the volume includes five chapters based on experimental and clinical data. In this section, the role of stem cells in liver tissue engineering, cell-based therapies in diabetes mellitus, and chronic degenerative diseases of the central nervous system, and adult-derived stem cell therapies are discussed. The two chapters of the third section focus on the biomarkers for tissue-engineered products, namely for tissue-engineered skin. The eight chapters of the fourth section discuss novel biomaterials developed for neural-, vascular-, aortic-, bone-, cartilage- and endocrine pancreas-tissue engineering applications. The last section of the book includes chapters on practical gene targeting applications, controlled release in gene therapy and tissue engineering, antibodies in cancer, acute-phase genes and phage-displayed peptide libraries. Proceedings of BIOMED 2002 The 9th International Symposium on Biomedical Science and Technology, held September 19-22, 2002, in Antalya, Turkey.

In Japan, cadaveric donor liver transplantation is not common even though cadaveric organ transplantation was legally established in 1998. In contrast, the number of living donor liver transplantations is increasing, with more than 1700 cases at 43 Japanese institutes by November 2001. Indications for and have become living donor liver transplantation are widening in Japan similar to those for cadaveric donor liver transplantation in the United States and Europe. At the same time, split liver transplantation from cadaveric donors shares some technical aspects with living donor liver transplantation. Remarkable progress has been reported recently, and thus it was an auspicious time to hold a symposium on "Current issues in liver/small bowel transplantation" in Japan. We were honored to hold a very fruitful symposium sponsored by the Keio University Medical Science Fund and to bring together top-rank transplant surgeons from Japan and other countries. It was a productive and rewarding time for all participants. We were able to share our experience through excellent presentations followed by active discussions and insightful com ments. At the symposium, we focused on current issues in liver transplanta tion such as widening indications for viral hepatitis and malignant tumors. We also discussed technical aspects and physiological problems in split/iiving donor liver transplant, novel strategies in immunosuppression, and the current status and future prospects in small bowel transplantation. This book contains the papers from all the distinguished guest speakers, focusing on the topics discussed at the symposium."

Clinical lung transplantation has seen an early start within the history of solid organ trans plantation, marked by the 1963 first lung transplant by James D. Hardy. This was prompted by the seemingly easy way of joining the transplanted organ to the recipient by me ans of a few well-defined anastomoses, i.e. bronchus, pulmonary artery and pulmonary vein carry ing left atrial cuff. The following decade thus witnessed a number of such mostly unilateral lung transplants in several centres, in Germany represented by the two only lung transplants performed by E. S. Bucherl, then at the Neukolln City Hospital in Berlin in 1969. As with most other such attempts these two patients suffered early and lethai graft failure. There was only one single lung transplant patient who lived up to ten months after the transplant at Gent, Belgium, having been operated on by Derom in 1969. The alm ost universal failure during this initial phase was attributed to bronchial anasto motic insufficiency, pulmonary infection of either the transplanted lung or the left-in-place contralateral lung and a far-reaching lack of knowledge how to cope with transplant rejec tion. In the early 1970s it had become gene rally accepted that lung transplantation could not be performed successfully."

Liver-Directed Therapy for Primary and Metastatic Liver Tumors is a comprehensive examination of tumors of the liver. It provides a unique multi-modality approach to management of all types of primary and secondary liver tumors. The biology of liver cancers, state of the art radiologic imaging and novel, non-surgical interventional strategies are given. There is an in depth analysis of surgical options including transplantation, resection, interstitial ablation techniques and liver-directed chemotherapy for hepatocellular carcinoma, bile duct cancers, and colorectal and neuroendocrine liver metastases. Because of the unique and comprehensive examination of liver tumors, this work is an excellent resource for surgical, transplant and medical oncologists, surgeons, gastroenterologists, and radiologists.

Organ Shortage: The Solutions is the latest subject in the Continuing Education series, organized by Fondation Marcel Merieux and Universite Claude Bernard in Lyon. The annual subject is chosen to reflect the status of the topical issues of the year, as taught by leading international experts. The contribution of transplantation and clinical immunology to advanced medicine is considerable and promising. The annual volumes in this series keep the reader abreast of these developments. "