Over the past five years, the immense financial pressure on the development and manufacturing of biopharmaceuticals has resulted in the increasing use and acce- ance of disposables, which are discarded after harvest and therefore intended only for single use. In fact, such disposables are implemented in all the main bioprocess production stages today and an even higher growth than those in the biopharmac- tical market is predicted (reaching double figures). Alongside disposable filter capsules, membrane chromatography units, tubing, connectors, flexible containers processing or containing fluids, freezer systems, mixers and pumps, and fully c- trolled disposable bioreactors of up to 2,000 L culture volume are already available on the market. Numerous studies highlight the advantages of disposable bioreactors and reveal their potential for simple, safe and fast seed inoculum production, process devel- ment and small as well as middle volume production (e.g. bioactive substances, viruses for vaccines and gene therapies etc.). They suggest that such disposable bioreactors (typically characterized by the cultivation chamber or bag from plastic materials) may be advantageous for plant, animal and microbial cells. Running industrial activities such as CFD-modelling, development of single-use process monitoring and control technology, and standardized film formulations are attempting to resolve the limitations of the current disposable bioreactors. These achievements, along with substantial improvements in product yield, will reduce the use of stainless steel in the biomanufacturing facilities of the future.

When this book was first conceived as a project the expanding interest in the clinical use of platinum and gold complexes made a survey of the relevant biological properties of metal complexes timely and appropriate. This timeliness has not diminished during the gestation and final publica tion of the manuscript. The introduction contains an explanation of the layout and approach to the book, which I wrote as an overall survey of the wide variety of biological properties of metal complexes. Hopefully, the reader will see the parallels in mechanisms and behavior, even in different organisms. The writing was considerably helped by the enthusiasm and confidence (totally unearned on my part) in the project of Professor Brian James and lowe him my special thanks. I also owe a great debt of gratitude to my colleagues, and especially to Eucler Paniago, of the Universidade Federal de Minas Gerais, for their comprehension and for the initial leave of absence which allowed me to begin the project. To those who read some or all of the manuscript and made suggestions, Bernhard Lippert, Kirsten Skov, and Tom Tritton, as well as the editor's reviewer I am also grateful. As usual, the final responsibility for errors or otherwise rests with the author."

Volume 24 includes six contributions, the author and paper index of volumes 1-24 and the key-word index. Since volume 23 included an index for volumes 16-23 the reader has the possibility to use these monographs as an encyclopedia and is in the position to find references to almost all fields of drug research. The editor hopes that the articles of the present volume will prove interesting and useful to many scientists and would be grateful to receive suggestions and opinions from readers, as in the past case over the 20 years in which this series of monographs has existed. In this respect, thanks are due to all colleagues who have provided helpful criticism of past volumes, thereby helping the editor in his work. Dr. A. Naf again has assisted the editor and has carefully reviewed all manuscripts, formulae and references, and has corrected the proofs. Thanks are due to him for this immense work. At the same time, the editor would like to thank the publishers and printers, Verlag Birkhliu ser, in particular Messrs. Th. Birkhliuser and C. Einsele, for the excellent cooperation and the work they have accomplished."

Wenn uber Fortschritte der Chemie der Gallotannine berichtet werden soll, so muss ein Ausgangspunkt gewahlt werden, von dem aus die neu gewonnenen Erkenntnisse geschildert werden. Das ist in unserem Falle nicht schwer. EMIL FISCHER hatte fur das chinesische Gallotannin (aus den Blattgallen von Rhus semialata) und das turkische Gallotannin (aus den Zweiggallen von Quercus infectoria) das bekannte Bauprinzip der polygalloylierten Glucosen herausgearbeitet. Aber weder ihm noch KARRER (43, 44) ist es moglich gewesen, aus dem Gemisch von Substanzen, die sie untersuchten, einzelne Individuen zu isolieren, deren exakte Konstitution man hatte aufklaren und angeben konnen. Auch mit den modernen Methoden der Gegenstromverteilung und Verteilungschromato graphie ist eine Auf trennung dieser Gemische offenbar bis heute noch nicht gelungen. Ahnlich liegen die Verhaltnisse beim Sumach-Gerbstoff (aus Rhus coriaria), von dem MUNz (58) gezeigt hat, dass der Hauptteil der Substanz aus einer Pentagalloyl-glucose besteht. Erwahnt man noch das Glucogallin und Tetrarin, die GILSON (30, 30a) aus chinesischem Rhabarber isoliert hat, und das Acertannin, ein Digalloyl-anhydrohexit aus koreanischem Acer ginnale, von PERKIN und UYEDA (65), so hat man die im Jahre 1929 bekannten Forschungsergebnisse zusammengestellt, mit Ausnahme des Hamameli-tannins und der Chebulinsaure, die aber im nachstehenden Bericht noch ausfuhrlicher behandelt werden. Somit kann also das Jahr 1929 als Ausgangspunkt fur die vorliegende Berichterstattung gewahlt werden. 11. Gallotannine: Ellagsaure-freie Gerbstoffe. I. Hamameli-tannin."

All the important pharmacological interactions affecting thyroid function are described in this book. The first section is devoted to the physiology and biochemistry of thyroid disease, putting the pharmacological interactions into perspective. The second section reviews all the important pharmacological effects on thyroid function and also deals with the impact of other environmental agents. The chapters are written by internationally recognised experts and extensively referenced to provide an up-to-date review of the pharmacological interactions important to the thyroid and its diseases.

A comprehensive guide to multiple sclerosis, discussing: clinical features, diagnosis, disease-modifying therapy, & symptom & medical management written by world-renowned experts in neurology, specifically MS. Dr Cohen and Dr Rae-Grant who are renowned researchers and physicians in the field of MS and are investigators on several key drug trials.

Extensive use of illustrations and succinct format makes this book an easily accessible and key reference guide.

Reviews cutting-edge agents currently in development, while also discussing the clinical features and standard diagnosing criteria and practices of MS from the clinician s perspective

Designed to include thorough descriptions of standard and novel treatment therapies in MS.

Explains how to most effectively use the top therapies in MS in the context of a clinical practice and based on investigational trials.

Concise but comprehensive

Over the past 30 years, there have been significant advances in our understanding of MS due to the use of MRIs to better visualize the disease and due to the introduction of new ameliorating drugs. However, MS is still an incurable disease and diagnosis remains challenging for many physicians; for instance, symptoms often mimic MS, and there is no specific test for the disease. To ensure optimal patient care, there is a need for physicians to remain up to date with new drugs on the market, disease detection, diagnosis, and latest management options.

The Handbook of Multiple Sclerosis provides a concise, easily accessible guide for all healthcare professionals involved in the diagnosis and management of this condition, including standard therapies, as well as more novel treatments. The book will also include comprehensive evaluations of the pharmacological treatments available, including novel investigational agents currently in development.

"

Volume 41 of "Progress in Orug Research" contains eight reviews and the various indexes which facilitate its use and establish the con nection with the previous volumes. The articles in this volume deal with teratogenesis; nephrotoxicity; bacterial resistance to P. lactam antibiotics; eradication of diseases by vaccination; chirality and drug design; endogenous digitalis-like factors; erythropoietin; and sero tonin (5HT)-antagonists. 3 All these articles give an excellent overview of the respective fields of research. In the 33 years that POR has existed, the Editor has enjoyed the valu able help and advice of many colleagues. Readers, the authors of the reviews, and last but not least, the reviewers have all contributed greatly to the success of this series. Although the comments received so far have generally been favorable, it is nevertheless necessary to analyze and to reassess the current position and the future direction of such a review series. So far, it has been the Editors intention to help disseminate informa tion on the vast domain of drug research, and to provide the reader with a tool with which to keep abreast of the latest developments and trends. The reviews in POR are useful to the non-specialists, who can obtain an overview of a particular field of research in a relatively short time. The specialist readers of POR will appreciate the reviews' comprehensive bibliographies, and, in addition, they may even get fresh impulses for their own research."

Contrast media are drugs by default. Had there been no default, there would be no need for a related pharmacology, and thus no need for this book. Radiographic contrast media (CM) are substances whose primary purpose is to enhance diagnostic information of medical imaging systems. The position of CM in pharmacology is unique. First, there is the unusual requirement of biological inertness. An ideal CM should be completely biologically inert, i.e., stable, not pharmacologically active, and efficiently and innocuously excretable. Because they fail to meet these requirements, CM must be considered drugs. The second unusual aspect of CM is that they are used in large quantities, their annual production being measured in tens of tons. It is not in spite of, but because of, the increased use of new radiographic systems, computed tomography, digital radiography, etc., that consumption is on the rise. And, it is not likely that the other emerging imaging modalities - NMR, ultrasonography, etc. - will displace radiographic CM soon; it is quite probable that these remarkable compounds will continue to play an active role in diagnostic imaging in the foreseeable future.

The 19th volume deals, as did its predecessor, with current problems of tropical medicine. Both volumes are based on various international Symposia which were held in Bombay on the occasion of the 75-year Platinum Jubilee of the Haffkine Institute in the Spring of 1974. The contributions in the 19th volume are based on lectures at thetast three Symposia which dealt with Helminthiasis, Diphtheria, Pertussis, Tetanus and Cholera. The 70 articles provide the reader with an impressive cross-section of the current state of specialized knowledge on the subject and the outstanding problems. Even today, researchers from various disciplines are still confronted with numerous unsolved problems in tropical medicine, and it is to be hoped that the 18th and 19th volumes will provide a stimulus for intensified research in the area of tropical medicine. The editor further hopes that, in the future, a still more fruitful co-operation between developed and developing countries will come about. The editor owes special thanks to Dr. Rafiq Zakaria, Minister, Dr. Gaitonde, as well as Dr. Anand and Dr. Chadha, who were responsible for the organisa tion of the Symposia on which the 19th volume is based. Thanks are also extended to Dr. A. Niif for his conscientious revision of the manuscripts and correction of the galley proofs. In addition, thanks are due to the publishers and the printers, Birkhiiuser, especially to Dr. A. Birkhiiuser, Th. Birkhauser and C. Einsele for their accurate printing and fine presentation of the volume."

Volume 21 of "Progress in Drug Research" contains 5 contributions from various areas of drug research and therapy. As in previous volumes, in the present volume the authors have also tried not only to summarise the current status of particular fields of drug research, but also to provide leads for future research activity. The various contributions in this volume will be of especial value not only to those actively concerned in resolving the diverse problems in drug research, but also to those who wish to keep abreast ofthe latest developments in- fluencing modem therapy. In addition, it is believed that volume 21 and the previous 20 volumes of "Progress in Drug Research" so far published represent a useful reference work of an encyclopaedic character. The editor would also like to take this opportunity of expressing his gratitude to Dr. A. Naffor carefully working over the manuscripts and correcting proofs. Thanks are also due to the publishers and the printers, Druckerei Birkhauser, especially to Dr. A. Birkhauser, Th. Birkhiiuser and C. Einsele, for their painstaking work on the printing and lay-out of the volume. August 1977 Dr. E. JUCKER Sandoz AG, Basel Vorwort Der 21. Band der "F ortschritte der Arzneimittelforschung" umfasst 5 Beitriige aus verschiedenen Gebieten der Arzneimittelforschung> und der Therapie.

One of the most active areas of contemporary organic chemistry involves the search for new catalysts that borrow concepts, strategies and even components from enzymes but yet are not found in nature. Such artificial enzymes not only give enormous insights into the mechanisms of enzyme catalysis but also offer the potential for catalyzing a wide range of chemical reactions with no counterpart in nature. Several approaches have been taken in the deVelopment of new catalysts, some based on biological methods and others on synthetic techniques. Site directed mutagenesis has allowed the direct replacement of amino acids in an enzyme with resulting changes in stability, selectivity and mechanism. Recent developments have shown that even non-natural amino acids can be incorporated into proteins and also that enzymes can function effectively in organic solvents. A different biological route to artificial enzymes has exploited the immune system and its ability to generate millions of antibodies to a given antigen. Novel antigens have been designed to mimic the transition states of chemical reactions. Antibodies elicited against these antigens thus contain an active site that is complementary to transition state structure and can potentially catalyze target reactions. A broad range of reactions can now be 6 catalyzed using the method with rate accelerations reaching 10 compared to the control reactions. Protein engineering and catalytic antibodies represent complex solutions to the problem of artificial enzymes. Their complexity is however their principal limitation.

Volume 36 of "Progress in Drug Research" contains 5 articles and the various indexes which facilitate its use and establish the connec tion with the previous volumes. While all articles deal with some of the topical aspects of drug research, the contribution by Robert R. Ruffolo et al. on "Drug receptors and control of the cardiovas cular system: Recent advances" is indeed in its own right a mono graphic presentation of this important domain. The remaining four reviews provide an overview of the work in volved in the search for new and better medicines, with a focus on chemical, pharmacological, toxicological, biological, biochemical and molecular modeling studies. In the 31 years this series has existed, the Editor has enjoyed the help and advice of many colleagues. Readers, the authors of the in dividual articles, and, last but not least, the reviewers have all con tributed greatly to the success of PDR. Although many comments received have been favorable, it is nevertheless necessary to analyze and to reconsider the current position and the direction of such a series. So far, it has been the Editor's aim to help spread informa tion on the vast domain of drug research, and to provide the reader with a tool helping him or her to keep abreast of the latest develop ments and trends."

Starting in 1986, the European School of Oncology has expanded its activities in post graduate teaching, which consisted mainly of traditional disease-orientated courses, by promoting new educational initiatives. One of these is the cloister seminars, short meet ings intended for highly qualified oncologists and dealing with specific, controversial aspects of clinical practice and research. Another is the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on developments and treatment in specific fields of oncology. This series of ESO Monographs was designed with the specific purpose of disseminat ing the results of the most interesting of the seminars and study groups, and providing concise and updated reviews of the subjects discussed. It was decided to keep the layout very simple in order to keep costs to a minimum and make the monographs available in the shortest possible time, thus overcoming a com mon problem in medical literature: that of the material being outdated even before publication. Umberto Veronesi Chairman, Scientific Committee European School of Oncology Position Paper on the Application of Human Tumour Xenografts as a Model for Preclinical Phase" Studies in the Evaluation of New Anticancer Compounds Outcome of a seminar on Human Tumour Xenografts organised by the European School of Oncology, Milan, 26th-27th May, 1986.

Volume 22 of 'Progress in Drug Research' contains 8 contributions from vari ous areas of drug research and therapy. As in previous volumes, in the present volume the authors have also tried not only to summarize the current status of particular fields of drug research, but also to provide leads for future research activity. The various contributions in this volume will be of especial value not only to those actively concerned in resolving the diverse problems in drug research, but also to those who wish to keep abreast of the latest developments influencing modem therapy. In addition, it is believed that volume 22 and the previous 21 volumes of 'Progress in Drug Research' so far published represent a useful reference work of an encyclopaedic character. The editor would also like to take this opportunity of expressing his gratitude to those who reviewed the previous volumes of this series of monographs and, by doing so gave useful advice for the future volumes. At the same time, thanks are expressed to Dr. A. Naf for carefully working over the manuscripts and correcting proofs. Thanks are also due to the publishers and the printers, Druckerei Birkhauser, especially to Messrs. Th. Birkhauser and C. Einsele. Unfortunately, this is the last volume which went into ptess during Dr. A. Birkhauser's lifetime; he passed away on March 4, 1978 and the editor would like to stress the fact'tl;tat."

Local treatment cures about 30 to 40% of cancers, this proportion depending on the follow-up required to establish it. This means that 60 to 70% of the malignant neoplasias are disseminated either perceptibly (leukemias, visible metas- tases) or imperceptibly, forming a 'minimal imperceptible disease', which local treatment leaves, whether it consists of surgery, radiotherapy, or surgery plus radiotherapy. When the neoplastic tissue is voluminous enough to be per- ceptible, cures can be obtained with chemotherapy or chemo- immunotherapy. When the neoplastic disease is imperceptible, made up of micrometastases, it apparently can be cured by systemic postsurgical chemotherapy, immunotherapy, or chemoimmunotherapy. Hence there is the need for intensive development of these medical therapies which are applied by the medical oncol- ogist and, at present, consist of chemotherapy, immuno- therapy, or chemoimmunotherapy. These medical thera- peutics can only grow with scientific development, the main weapon of which is experimental and clinical pharmacology. These volumes report the communications presented at the 1979 EORTC Annual Plenary Session on Cancer Chemo- and Immunopharmacology.

The author's general aim has been to survey as wide a field of evidence as possible and this had involved excursions into subjects of which he has little first hand knowledge. This width of range also has necessitated a somewhat arbitrary selection of evidence and has prevented full discussion of any indi- vidual problem. The author trusts that he has not misrepresented anyone's results or opinions, and if this has occurred, he can only plead in excuse the peculiar difficulty of giving a brief and yet accurate account of evidence of such a wide variety. The diagrams reproduced in the article have all been redrawn and in many cases the original figures or diagrams have been modified as, for instance, by recalculating dosage on the logarithmic scale. The original authors therefore have no direct responsibility for the diagrams in their present form. The author desires to thank Messrs Arnold and Co. for permitting the repro- duction of Figs. 9 and 23 from similar figures which appeared in his book "The Mode of Action of Drugs on Cells"; portions of other figures from this book also have been reproduced in modified form. The author also desires to thank Dr. J. M. ROBSON for help in correction of the proofs. Edinburgh, July, 1937. A. J. CLARK. Contents.

This book deals with the methods and scientific basis of inhalation toxicology. It describes devices and facilities needed to expose animals to inhaled particles and gases as well as approaches to estimating or measuring the fraction of the inhaled material that is retained in the respiratory tract. The book then reviews the evergrowing repertoire of techniques that can be used to measure the responses elicited by the exposure. Quantitative and qualitative anatomical, physiological, and biochemical strategies are discussed in detail. We believe that the toxicology of inhaled materials is an important and timely topic for several'reasons. During the past decade, morbidity and mortality attributable to cardiovascular disease have significantly decreased. Progress in combatting cancer, the second most important cause of death, has been slower, and lung cancer actually became the leading cause of death in men and the second leading cause of cancer death in women. In addition, the incidence of non-neo plastic respiratory diseases such as emphysema, fibrosis, and chronic bronchitis has increased the past decade. In the United States, the National Institutes of Health (NIH) has recently reported that chronic obstructive pulmonary disease affects nearly 10 miliion persons and accounts for 59,000 deaths yearly; indeed, it ranks as the fifth leading cause of death. Because the incidence is increasing, the NIH estimates that it may become the nation's fourth or even third leading cause of death by the year 2000."

Most drugs, toxins, hormones, and the like bring about their biologic actions by reacting with specific receptors somewhere in the body. Scientists working in all areas of biologic science have shown increasing interest in the analysis of drug-receptor interactions in the broadest sense. Studies of drugs (binding) to receptors in situ and to isolated and partly purified receptors are becoming common practice. The action of a drug in the body is, however, a kinetic event not only with respect to transport of drug molecules to the environment of the receptors, but also with respect to the drug-receptor interaction itself. Kinetics of Drug Action is an integrative approach to drug transport through the body, membrane transport toward the receptors, and the kinetics of drug receptor interaction. This volume is aimed at providing a critical and penetrating study of the problems relevant to the kinetics or drug action from drug dosage to the final response. It is felt that the critical surveys presented in this volume will contribute significantly to receptor study research in various biologic fields and to a better understanding of drug action. I would like to express my gratitude to our secretary Miss MARGOT JANSSEN for the extensive typing of manuscripts and to our laboratory assistant Miss COBY HURKMANS for her dedicated assistance in the correcting some of the manuscripts and preparating the index."

Safety and Efficacy of Radiopharmaceuticals was established as a very important and comprehensive subject at the First Europe an Symposium on Radiopharmacy and Radiopharmaceuticals in Denmark in 1983. The interest in this subject has grown considerably since then due to the growing interest among national authorities to deal with radiopharmaceuticals. The introduction in recent years of nuclear medicine techniques based on radioactive labelled cells and on monoclonal antibodies has stressed the importance of a well functioning approval system for the clinical trial and use of new radiopharmaceuticals. The process of transferring the experience from the non radioactive drug field into the area of radiopharmaceuticals is still ongoing. International organisations such as the World Health Organisa tion is also including this into their quality assurance programme from both the radiopharmaceutical and the radiation hygiene point of view. In order to give an up-to date survey of these areas, experts were invited to prepare review papers under the following headings: Safety and Efficacy of Radiophar maceuticals with Emphasis on Biological Products, Radiophar macy/Radiation Hygiene, Legal Aspects of the Introduction of New Radiopharmaceuticals and some selected aspects of Good Radiopharmacy Practice."

The volumes of this classic series have appeared under the Springer imprint ever since L. Zechmeister founded the series in 1938. The volumes contain contributions on various topics related to the origin, distribution, chemistry, synthesis, biochemistry, function or use of various classes of naturally occurring substances ranging from small molecules to biopolymers. Each contribution is written by a recognized authority in his field and provides a comprehensive and up-to-date review of the topic in question. Addressed to biologists, technologists and chemists alike, the series can be used by the expert as a source of information and literature citations and by the non-expert as a means of orientation in a rapidly developing discipline.

Despite the long association of organohalogen compounds with human activities, nature is the producer of nearly 5,000 halogen-containing chemicals. Once dismissed as accidents of nature or isolation artifacts, organohalogen compounds represent an important and ever growing class of natural products, in many cases exhibiting exceptional biological activity. Since the last comprehensive review in 1996 (Vol. 68, this series), there have been discovered an additional 2,500 organochlorine, organobromine, and other organohalogen compounds. These natural organohalogens are biosynthesized by bacteria, fungi, lichen, plants, marine organisms of all types, insects, and higher animals including humans. These compounds are also formed abiogenically, as in volcanoes, forest fires, and other geothermal events.In some instances, natural organohalogens are precisely the same chemicals that man synthesizes for industrial use, and some of the quantities of these natural chemicals far exceed the quantities emitted by man.

An unprecedented glimpse into the multidimensional learning processes that take place when novice professionals develop the necessary communication skills for effective task accomplishment. This analysis of authentic patient consultations by pharmacy interns is a significant contribution to research on health communication training.