Intensive care is a rapidly changing area of medicine, and after four years from the 2nd edition the volume editors and authors have deemed necessary to update it. In the recent years, in fact, five new randomised controlled trials and five new meta-analyses demonstrate that selective decontamination of the digestive tract [SDD] is an antimicrobial prophylaxis to prevent severe infections of not only lower airways but also of blood. Additionally, SDD has been shown to reduce inflammation including multiple organ failure and mortality. An intriguing observation is the evidence that SDD using parenteral and enteral antimicrobials reduces rather than increases antimicrobial resistance. Moreover, a new chapter on microcirculation had been added. The volume will be an invaluable tool for all those requiring in depth knowledge in the ever expanding field of infection control.

The inspiration for this text was the 1988 volume by Alder and Zbinden, written before the ICH harmonization process for drug safety evaluation (or its ISO analog for device biocompatibility evaluation) had been initiated or come to force. Since then, much has changed in both the world and practice of medicine and the regulation of drugs. The intent of this volume is to provide similar guidance as to what nonclinical safety assessment tests need to be performed to move a drug into man, through development and to market approved (this intent was subsequently extended to cover the closely related medical device biotechnology, and combination product fields) in a concise, abbreviated manner for all the major world market countries.

During its short 20 year history High Performance Liquid Chro matography (HPLC) has won itself a firm place amongst the instrumental methods of analysis. HPLC has caused a revolution in biological and pharmaceutical chemistry. Approximately two thirds of the publications on HPLC are concerned with problems from this area of life science. Biotechnology, where it is necessary to isolate substances from complicated mixtures, is likely to give further impetus to the dissemination of modern liquid chromatog raphy in columns, particularly on the preparative scale. This book presents, by means of examples, the application of HPLC to various fields, as well as fundamental discussions of chromatographic methods. The quality of the analytical result is decisively dependent on the qualities of the equipment employed (by Colin, Guiochon, and Martin). Especially the demands are discussed that are placed on the components of the instrument including those for data acquisition and processing. The section on "quantitative analy sis" (by ABhauer, Ullner) covers besides the principles also the problems of ensuring the quality of the data in detail. The basic problems arising by enlarging the sample size to preparative di mensions and the requirements put on the aparatus are discussed in the section on "preparative applications" (by Wehrli)."

In most natural sciences, modeling is a widespread method of gaining new knowledge about natural and technical systems. This book analyses the concepts of 'model' and 'modeling' in different fields of research. The different methods of modeling as well as the potentials and limits of this concept are reflected and discussed. The book presents a variety of modeling techniques, from mathematical models in climatology, meteorology or oceanography to methods used in morphology, decision-making in ecology and physical modeling in oceanography. In this broad overview regarding modeling, the book is unique.

The Sixth International Conference on Miniaturized Chemical and Biochemical Analysis Systems, known as /JTAS2002, will be fully dedicated to the latest scientific and technological developments in the field of miniaturized devices and systems for realizing not only chemical and biochemical analysis but also synthesis. The first /JTAS meeting was held in Enschede in 1994 with approximately 160 participants, bringing together the scientists with background in analytical and biochemistry with those with Micro Electro Mechanical Systems (MEMS) in one workshop. We are grateful to Piet Bergveld and Albert van den Berg of MESA Research Institute of the University of Twente for their great efforts to arrange this exciting first meeting. The policy of the meeting was succeeded by late Prof. Dr. Michael Widmer in the second meeting, /JTAS'96 held in Basel with 275 participants. The first two meetings were held as informal workshops. From the third workshop, /JTAS'98 (420 participants) held in Banff, the workshop had become a worldwide conference. Participants continued to increase in /JTAS2000 (about 500 participants) held in Enschede and /JTAS2001 (about 700 participants) held in Monterey. The number of submitted papers also dramatically increased in this period from 130 in 1998, 230 in 2000 to nearly 400 in 2001. From 2001, /JTAS became an annual symposium. The steering committee meeting held in Monterey, confrrmed the policy of former /JTAS that quality rather than quantity would be the key-point and that the parallel-session format throughout the 3.

1. 1. General 1. 1. 1. Biaryls-Structural and Biosynthetic Variety The biaryl axis is the joint central structural element of a broad variety of structurally (in particular stereochemically) and biosynthetically inter- esting as well as pharmacologically promising natural products. The increasing importance of this challenging class of secondary metabolites, its widespread occurrence, its pharmacological implications, and, in particular, the phenomenon of axial chirality, have so far been largely underestimated, if not neglected. This is reflected by the fact that there is as yet no true comprehensive review on naturally occurring biaryls in the literature. By this article, we do not intend to provide such a fully comprehensive review, but still want to draw the attention of the scientific community on the manifold rewarding facets of this exciting class of natural products, which is rapidly growing now, with more and more sophisticated analytical and synthetic tools becoming available. Natural biaryls occur far more frequently than initially assumed, among them constitutionally symmetric, simple dimeric monoterpenoid biphenyls like I (I) (see Fig. 1), binaphthalenes like (-)-gossypol (2) (2), bianthraquinones like skyrin (3) (3-7), and biaryls with annelated heterocyclic rings like bismurrayafoline-B (4) (8) and desertorin A (Sa) (9, 10), which is-although built up from a single monomeric precursor -constitutionally unsymmetric.

Volume 23 includes six contributions as well as the Index for volumes 16-23. The key-word Index, like those of volumes II and IS, provides the reader with a simple cross-reference to all fields of possible interest, making this series of monographs even more useful as an encyclopaedic reference work. The scientific articles treat various topical areas of drug research, reviewing developments and indicating unsolved problems. The editor hopes to have provided the reader with a useful orientation and reference work. Experience over the last few years has shown that a more rapid publica- tion of the individual volumes better meets the wishes of readers by keeping pace with the speed of modem research. The present volume, as well as its predecessor, has broken the tradition of 500-600-page volumes in the hope of better satisfying the needs of the readers of this series. Finally, thanks are due to all those who have provided helpful criticism of past volumes, thereby providing valuable advice regarding the form of future volumes, and to Dr. A. Niif for his careful revision of the manu- scripts and correction of the proofs. Thanks are also due to the publish- ers and printers Birkhiiuser, in particular Messrs. Th. Birkhiiuser and C. Einsele. July 1979 Dr. E. Jucker Sandoz Ltd., Basel Vorwort Der 23. Band umfasst sechs Beitrage nebst dem Index der Bande 16-23.

In 1998, we published the data compilation PROTEIN STABILITY AND FOLDING which covered the data from the early beginnings of thermodynamic studies of protein folding until 1996. Since then, the amount of available thermodynamic data has increased nearly twice. The data constitute very important additions to the information on the protein folding problem, the construction of mutant protein, and the practical application of proteins in various fields. The Supplement covers the period 1997-1999 and is designed to make the vast amount of present data accessible to multidisciplinary research where chemistry, physics, biology, and medicine are involved and also biotechnology, pharmaceutical and food research. At the same time the data could be helpful to identify problems unsolved so far, and to avoid unnecessary duplication of scientific work. The structure of the Supplement is the same as in the previous data compilation. However, some additional data characterizing protein-denaturant interaction and protein unfolding by trifluoroethanol have been added. In that context, some previous data have been reconsidered. The author wishes to thank everyone who provided data, ideas, or even unpublished results. Furthermore, support by the Deutsche Forschungsgemeinschaft (INK 16 BI-I) is gratefully acknowledged. Finally, I would like to thank the staff of Springer Verlag for their efforts and for excellent assistance during the production of the data collections.

Since the late 1950's when proton n. m. r. spectroscopy was first used in organic natural products studies the technique has increasingly con of this important area of chemistry. tributed to the rapid advancement Although the potential utility of 13C n. m. r. was recognized very early, essentially no application of 13C n. m. r. appeared in the literature prior to 1966 and 95% of the existing data are less than five years old. The initially slow growth had its cause in inadequate instrumentation, insufficient sensitivity being the main obstacle. This situation drastically changed with the advent and commercial availability of broadband ex citation and Fourier transform methods, giving natural-abundance 13C n. m. r. and its numerous chemical applications a tremendous impetus. Today BC spectra can be recorded on sample quantities down to the submilligram level, which until recently even withstood proton n. m. r. Paralleling the development of experimental techniques considerable progress has also been made on an understanding of spectral parameters, in particular their stereochemical implications on natural products. Although the large majority of data present up to now deals with known structures, an adequate basis now exists which allows the chemist to use the technique for tackling real problems on unknown molecules."

Today's drug research is an extremely complex process which, apart from chemistry, pharmacology, toxicology and preclinical trials, in cludes a variety of sciences such as biotechnology, biochemistry, im munology, physics, biology and even computer sciences. The Table of Contents of the present volume demonstrates this situation and makes it evident that the individual researcher cannot possibly hope to keep abreast of all aspects of modern drug research. In this re spect, the series of monographs "Progress in Drug Research" pro vides valuable help and assistance. Those who simply wish to remain informed of the latest trends and developments in drug research can use the 34 volumes so far available as a source of almost encyclo pedic character. Researchers actively engaged in the various scientific fields forming the entity of drug research can benefit from the wealth of knowledge and experience of the respective authors, and they will be assisted in their endeavour to discover new pharmaceutical agents. Moreover, the extensive bibliographies of the individual reviews provide an invaluable overview of the literature most pertinent to today's drug research. I should like to thank all the authors for their willingness to prepare the reviews and for sharing their insights and experience with the readers. Thanks are also due to Mrs L. Koechlin, H.-P. Thiir and A. Gomm of Birkhauser Publishers for their valuable help in the pre paration of this volume."

Toyiochi Tanaka, Mitsuhiro Shibayama, "Phase Transitions and related Phenomena of Polymer Gels", Akira Onuki "Theory of Phase Transition in Polymer Gels", Alexei Khokhlov, Sergei Starodybtzev, Valentina Vasilevskaya "Conformational Transitions in Polymer Gels: Theory and Experiment", Michal Ilavsky " Effect on Phase Transition on Swellingand Mechanical Behavior of Synthetic Hydrogels", Shozaburo Saito , M. Konno, H. Inomata "Volume Phase Transition of N-Alkylacrylamide Gels", Ronald Siegel "Hydrophobic Weak Polyelectrolyte Gels: Studies of Swelling Equilibria and Kinetics".

The Fifth Chinese Peptide Symposium, hosted by Lanzhou University, was held at Lanzhou, China July 14-17, 1998, with 156 participants, including 30 scientists from abroad, representing nine countries. The four-day conference was both intense and spiritually rewarding. Our goal for CPS-98 was to provide a forum for the exchange of knowledge, cooperation and friendship between the international and Chinese scientific communities, and we believe this goal was met. The symposium consisted of 8 sessions with 42 oral and 90 poster presentations, including synthetic methods, molecular diversity and peptide libraries, structure and conformation of peptides and proteins, bioactive peptides, peptide immunology, De Novo design and synthesis of proteins and peptides, ligand-receptor interactions, the chemistry-biology-interface and challenging problems in peptides. The enthusiastic cooperation and excellent contributions were gratifying and the active response of the invited speakers contributed to the success of the symposium. The presentations were of excellent caliber and represented the most current and significant aspects of peptide science. Dr. Kit Lam of the University of Arizona and Dr. Yun-Hua Ye of Peking University were the recipients of "The Cathay Award" sponsored by the H. H. Liu Education Foundation, offered for their seminal contribution in peptide science and the Chinese Peptide Symposium. Four outstanding young scientists were selected by the organizing committee to receive awards sponsored by Haikou Nanhai Pharmaceutical Industry Co. Ltd. (Zhong He Group).

Shunsuke Hirotsu "Coexistence of Phases and the Nature of First-Order Transition in Poly-N-isopropylacrylamide Gels," Masayuki Tokita "Friction between Polymer Networks of Gels and Solvent," Masahiro Irie "Stimuli-Responsive Poly(N-isopropyl- acrylamide), Photo- and Chemicals-Induced Phases Transitions Edward Cussler, Karen Wang, John Burban"Hydrogels as Separation Agents," Stevin Gehrke "Synthesis, Equilibrium Swelling, Kinetics Permeability and Applications of Environmentally Responsive Gels," Pedro Verdugo "Polymer Gel Phase Transition in Condensation- Decondensation of Secretory Products," Etsuo Kokufuta "Novel Applications for Stimulus-Sensitive Polymer Gels in the Preparation of Functional Immobilized Biocatalysts," Teruo Okano "Molecular Design of Temperature-Responsive Polymers as Intelligent Materials," Atsushi Suzuki "Phase Transition in Gels of Sub-Millimeter Size Induced by Interaction with Stimuli," Makoto Suzuki, O. Hirasa "An Approach to Artificial Muscle by Polymer Gels due to Micro-Phase Separation."

Finally - a book that covers all aspects of the illicit use of cocaine, amphetamines, ecstasy and/or designer drugs such as GHB, written by two experts in their field. The use of these drugs remains a continuous threat in health and medical care delivery, and this book will be an essential asset to the physician who may have to face the evaluation of patients whose use of these drugs compromises an effective treatment plan for other health issues. The book has been conceived to fill the void in existing physician reference materials, and provides a comprehensive review of the theoretical knowledge and scope of pharmacotherapy in individuals who are hooked on a psychoactive substance. While detailed scientific information is obtainable in other major articles, the book's straightforward format and style, along with its illustrations, will make for easy reading as emphasis is put on information specifically related to drugs that occur most abused in today's society. The information provided is based on clinical practice rather than pure experimental data, which will give the physician more effective tools useful in their daily practice. Many mechanisms of action of abuse are described in detail and references are provided to direct the reader to further sources for additional information. As a special feature, the book incorporates uncluttered tables and charts, which result in immediate clarification of the mode of action on the central nervous system and the reason for misuse, thus avoiding usual long and fatiguing text in common reference books. The book aims to give the reader a clear and concise plan on what to do when being faced with an overdose situation. A well-organized Table of Contents rapidly leads the reader from general pharmacological issues to the specific overdose syndrome and its management. Additionally, significant emphasis is placed on the practical do's and don'ts for physicians, with special reference to the predictive signs of aberrant drug-related behavior and the identification of the drug diverter by using urine drug screening.

Established as a classic text on nuclear chemistry and pharmacy, Fundamentals of Nuclear Pharmacy has been thoroughly revised with new information added covering innovations in imaging technology and clinical applications in the field. The Sixth Edition also eliminates outdated information from previous editions on radiopharmaceuticals now discontinued from the market. Dr. Gopal B. Saha's books have continually been praised for their clarity and accuracy while setting new standards for making complex theoretical concepts readily understandable to the reader. Like past editions, this book is intended to be used as a textbook on nuclear chemistry and pharmacy for nuclear medicine residents and students and as a reference book for nuclear medicine physicians and radiologists. New sections in the Sixth Edition include: * PET/CT and SPECT/CT * Digital Imaging * Exploratory IND * Nanoparticle Imaging * Treatment of liver cancer with 90Y-TheraSpheres and 90Y-SIR-Spheres * Treatment of Non-Hodgkin's lymphoma with 131I-Bexxar

Der vorliegende 48. Band der Reihe "Fortschritte der Arzneimittelfor- schung" enthalt acht Beitrage, die wiederum von anerkannten Forschern verfasst wurden. Ausserdem sind auch in diesem Band ein Stichwortver- zeichnis des Bandes sowie ein Autoren-und Titelverzeichnis und ein Titel- verzeichnis aller 48 Bande enthalten. Der Leser hat dadurch die Mog- lichkeit, nicht nur den vorliegenden Band zu konsultieren, sondern auch alle bisher erschienenen Bande quasi als enzyklopadisches N achschla- gewerk zu benutzen. Da alle Beitrage umfangreiche Literaturnachweise enthalten, ist die Moglichkeit des Zugriffes auf Original-Publikationen gegeben, was dem aktiven Forscher besonders wichtig ist und seinen eige- nen Arbeiten Impulse geben kann. Die Artikel des 48. Bandes behandeln neue Entwicklungen der Genetik, der enzymatischen Herstellung von komplexen Peptiden und bringen die neuesten Erkenntnisse der Apoptose unserem Verstandnis naher. Immun- therapie bei Hirnerkrankungen und psychischen Storungen, der Einsatz vonNaturproduktenzur Vorbeugung von Krebserkrankungen, das beun- ruhigende Anwachsen der Arzneimittelresistenz, die Mannigfaltigkeit der Dopamin-Rezeptor-Wirkung und die faszinierende Darstellung einer grosseren Gruppe von neuartigen Nukleosiden als Arzneimittel runden den vorliegenden Band der "Fortschritte der Arzneimittelforschung" ab und bieten dem Leser viel Neuartiges und Interessantes.