Proceedings of a NATO ASI held in Erice, Italy, April 27-May 1, 1995.

This volume is a summary of material presented in the course given in the International School of Phannacology on "Drug Epidemiology and Post-Marketing Surveillance" between September 27 and October 8, 1990, at the "Ettore Majorana Center for Scientific Culture" in Erice, Sicily. The course, which was a NATO Advanced Study Institute, included lectures and workshops presented by experts in the new field of phannacoepidemiology. The material covered includes various approaches to spontaneous reporting of adverse drug reactions, including aggregate approaches, such as those used in France, and detailed analyses of individual reports, such as that done in The Netherlands and in Sweden. Also, included are studies using traditional epidemiology methods. In addition, modern pharmacoepidemiology makes considerable use of automated databases. As such, information is presented on their use as well. Phannacoepidemiology started in hospitals and some of the newest work in the field is returning to the hospital as a site for studies. Material on these topics was presented as well. Finally, selected new methodologic developments were outlined in specific examples presented that were of regulatory and commercial importance. This new field of phannacoepidemiology is exploding in interest internationally. Evidence of this is the increasing development of pharmacoepidemiology programs in industry, medical schools, pharmacy schools, and schools of public health. Also, there is a new International Society ofPhannacoepidemiology. Practitioners in this field tend to specialize in either analyses of spontaneous reporting or the use of formal epidemiologic techniques.

The contents of this book represent papers which were presented at the Third International Meeting on "Side-Effects of Anti-Inflammatory and Analgesic Drugs" which was held under the auspices of the University of Verona, Institute of Pharmacology in Verona on 8-11 May 1991. This meeting was held in conjunction with the 13th European Workshop on Inflammation and although publications from this part of the meeting are not published here (they appear in Agents and Actions), we were fortunate in having a group of people interested in inflammation from varying backgrounds. The success of the third meeting followed previous meetings held in Cambridge and Verona respectively and continue a tradition which has now become well established. The meeting brought together physicians, scientists and those concerned with the production and use of anti-inflammatory drugs to a very stimulating conference to discuss basic issues affecting all aspects of side-effects of anti-inflammatory and analgesic drugs as well as their detection and treatment. The meeting was held in the Auditorium of Glaxo Italy and we are very grateful to that company for use of their facilities as well as to the University of Verona, Institute of Pharmacology, for valuable secretarial and administrative help. The success of the conference would not have been possible without valuable financial assistance of the companies listed separately (under Acknowledgements) as well as to the organizers of the 13th European Workshop on Inflammation who collaborated with us.

Abnormal metabolism and distribution of both copper and zinc occurs in many inflammatory and degenerative diseases. The pattern of these changes varies at different stages of these diseases and with differing types of conditions. The corollary to this situation is the possibility of using drugs or metal complexes to modify both the perturbed status of copper and zinc and thus the disease states. This book comprehensively reviews the clinical and experimental data on the changes in copper and zinc status in different diseases and the use of various complexes of these metals or drugs to treat a diversity of inflammatory and degenerative conditions.

These two volumes contain the proceedings of a 3 day international meeting held at the University of Cambidge and Queens' College Cambridge from 31st July to 2nd August 1985 on the Side-Effects of Anti-Inflammatory Analgesic Drugs. The first meeting was held in Verona, (Italy) in 1982 and the organisers feIt that, with a number of recent developments including the. withdrawal of a num- ber of new anti-inflammatory drugs, and concern being expressed in the lay and specialist medical press and other media about the safety of these drugs, that it was appl'Qpriate to have a second such meeting. The meeting was attended by some 300 delegates and the dis- cussion focussed most intently on the recent issues, . e. g. the value of adverse drug reaction reporting of the non-. steroidal anti- inflammatory (NSAI) drugs, certain side-effects associated with particular NSAI drugs, the predictive value of animal models etc. Organising a meeting de novo without outside help would not have been possible without the immensely valuable help given en- thusiastica1ly by people and financial assistance given most generously by those pharmaceutical companies listed below. These financial contributions were given despite current economic dif- ficulties and moves to restrict the proportion of profits towards educational actlvities.

This report on Future Trends in Inflammation III is the record of what is now firmly established as a series of multidisciplinary meetings organized by the European Biological Research Association. The aim of these meetings is to provide a forum for free exchange of information between basic scien tists of many disciplines and clinicians to provide better understanding of problems of common interest. The next major meeting wi1l be held in 1980.* The European Biological Research Association promotes scientific and clinical collaboration among the member countries ofthe EEe. It encourages exchange of information between scientists and clinicians from centres all over the world. In addition to the major international meetings small work shops are organized on specific problems of common interest. Once again the Editors have attempted to capture the spirit of the meeting by publishing 'verbatim' the discussion. It can be seen that the discussions were exciting and formed an important part of the meeting. It is possible that inaccuracies have crept into the discussions; if so we apologize. It was decided that the proceedings of such a meeting had maximum value with rapid publication. We would like to thank the participants for the enthusiasm and goodwill which persisted throughout the meeting both scientifically and socially. Above all we wish to thank H.R.H. The Duchess of Kent for acting as Patron of this meeting."

These two volumes contain the proceedings of a 3 day international meeting held at the University of Cambidge and Queens' College Cambridge from 31st July to 2nd August 1985 on the Side-Effects of Anti-Inflammatory Analgesic Drugs. The first meeting was held in Verona, (Italy) in 1982 and the organisers felt that, with a number of recent developments including the withdrawal of a num ber of new anti-inflammatory drugs, and concern being expressed in the lay and specialist medical press and other media about the safety of these drugs, that it was appropriate to have a second such meeting. The meeting was attended by some 300 delegates and the dis cussion focussed most intently on the recent issues, e. g. the value of adverse drug reaction reporting of the non-steroidal anti inflammatory (NSAI) drugs, certain side-effects associated with particular NSAI drugs, the predictive value of animal models etc. Organising a meeting de novo without outside help would not have been possible without the immensely valuable help given en thusiastically by people and financial assistance given most generously by those pharmaceutical companies listed below. These financial contributions were given despite current economic dif ficulties and moves to restrict the proportion of profits towards educational activities."

The present volume collects lecture notes from the session of the International School of Mathematical Physics 'Ettore Majorana' on Renormalization Theory that took place in Erice (Sicily), August 17 to August 31, 1975. The School was a NATO Advanced Study Institute sponsored by the Italian Ministry of Public Education, the Italian Minis try of Scientific and Technological Research, and the Regional Sicilian Government. Renormalization theory has, by now, acquired forty years of history. The present volume assumes a general acquaintance with the elementary facts of the subject as they might appear in an introductory course in quantum field theory. For more recent significant developments it provides a systematic intro duction as well as a detailed discussion of the existing state of knowledge. In particular analytic and dimensional renorma lization, normal product technique, and the Bogoliubov-Shirkov Epstein-Glaser method are treated, with applications to physically important gauge theories. All the preceding deals with perturbative renormalization theory. In recent years there has been an interesting development of non-perturbative renormalization theory in models in space-times of two and three dimensions, with the use of the methods of constructive field theory. Despite the simplicity of these models, the results are of significance because they are exact and answer a number of questions of principle. There are parts of renormalization theory which are not well understood, for instance the renormalization theory of non-renormalizable interactions."

The role of trace metals, especially copper and zinc, in the pathogenesis of rheumatic conditions has continued to receive much interest following the initial upsurge of research activity in the 1970s. Meantime also copper and zinc complexes receive continued attention for their potential anti-inflam matory actions. Since the previous major titles were published in this field some years ago (e. g. 1,2) it was considered timely to consider progress which has been made in the interceding period. Thus in this volume aspects are re viewed of the metabolism and biodisposition of copper and zinc, especially as they may be influenced by inflammatory processes, the mode of action of copper and zinc compounds in inflammatory states, and the actions of some newer copper complexes. While we still understand relatively little about how copper and zinc complexes work in inflammation, and indeed what the fate of the ligands and their complexed ions is in inflammation, it is hoped that this volume will be useful for giving a current view of the "state of art" in the field. Special thanks are given to the valued efforts of the contributors, Dr Peter Clarke (Publishing Director, Kluwer Academic Publishers) and Mrs Veronica Rainsford-Koechli for her help in proof-reading the manuscripts. K D Rainsford Hamilton, Ontario, Canada February 1989 References 1. Rainsford, K. D., Brune, K. and Whitehouse, M. W. (eds) (1981). Elements in the pathogenesis a treatment of inflammation."

At present we may be at the cross-roads in the therapeutic approaches we have for the treatment of the 100 or more rheumatic conditions. This is be cause we now recognise that although some advances have been made with the development of a large range of non-steroidal and steroidal drugs during the past two decades or so, we now recognise that many, if not all, of these have rather limited effects on many of the disease processes which underlie the manifestations of the various rheumatic states. Advances in molecular bi- 010gy in the past 5-10 years have enabled these tools to be applied extensive ly for developing further our understanding of the rheumatic disease processes. In some cases these molecular tools (e. g., ), -interferon, interleukin- 2, T-cell antibodies) have been directly employed as therapies themselves. While the outcome from trials with such agents in rheumatoid arthritis in particular has not been as would have been hoped, these results as with cy closporin A and low-dose methotrexate in the therapy of rheumatoid arth ritis have given us important indications for the approach employing what are generally described as "immunomodulators" to control this disease. But this may not be the same type of approach which is desirable for all types of rheumatic conditions. Indeed, even the way which the present range of drugs and other therapies are applied may not be the most effective and safe means of treating different types of arthritic conditions."

Abnormal metabolism and distribution of both copper and zinc occurs in many inflammatory and degenerative diseases. The pattern of these changes varies at different stages of these diseases and with differing types of conditions. The corollary to this situation is the possibility of using drugs or metal complexes to modify both the perturbed status of copper and zinc and thus the disease states.

This book comprehensively reviews the clinical and experimental data on the changes in copper and zinc status in different diseases and the use of various complexes of these metals or drugs to treat a diversity of inflammatory and degenerative conditions.

Proceedings of a NATO ASI held in Erice, Italy, April 27-May 1, 1995.

This volume is a summary of material presented in the course given in the International School of Phannacology on "Drug Epidemiology and Post-Marketing Surveillance" between September 27 and October 8, 1990, at the "Ettore Majorana Center for Scientific Culture" in Erice, Sicily. The course, which was a NATO Advanced Study Institute, included lectures and workshops presented by experts in the new field of phannacoepidemiology. The material covered includes various approaches to spontaneous reporting of adverse drug reactions, including aggregate approaches, such as those used in France, and detailed analyses of individual reports, such as that done in The Netherlands and in Sweden. Also, included are studies using traditional epidemiology methods. In addition, modern pharmacoepidemiology makes considerable use of automated databases. As such, information is presented on their use as well. Phannacoepidemiology started in hospitals and some of the newest work in the field is returning to the hospital as a site for studies. Material on these topics was presented as well. Finally, selected new methodologic developments were outlined in specific examples presented that were of regulatory and commercial importance. This new field of phannacoepidemiology is exploding in interest internationally. Evidence of this is the increasing development of pharmacoepidemiology programs in industry, medical schools, pharmacy schools, and schools of public health. Also, there is a new International Society ofPhannacoepidemiology. Practitioners in this field tend to specialize in either analyses of spontaneous reporting or the use of formal epidemiologic techniques.

The role of trace metals, especially copper and zinc, in the pathogenesis of rheumatic conditions has continued to receive much interest following the initial upsurge of research activity in the 1970s. Meantime also copper and zinc complexes receive continued attention for their potential anti-inflam matory actions. Since the previous major titles were published in this field some years ago (e. g. 1,2) it was considered timely to consider progress which has been made in the interceding period. Thus in this volume aspects are re viewed of the metabolism and biodisposition of copper and zinc, especially as they may be influenced by inflammatory processes, the mode of action of copper and zinc compounds in inflammatory states, and the actions of some newer copper complexes. While we still understand relatively little about how copper and zinc complexes work in inflammation, and indeed what the fate of the ligands and their complexed ions is in inflammation, it is hoped that this volume will be useful for giving a current view of the "state of art" in the field. Special thanks are given to the valued efforts of the contributors, Dr Peter Clarke (Publishing Director, Kluwer Academic Publishers) and Mrs Veronica Rainsford-Koechli for her help in proof-reading the manuscripts. K D Rainsford Hamilton, Ontario, Canada February 1989 References 1. Rainsford, K. D., Brune, K. and Whitehouse, M. W. (eds) (1981). Elements in the pathogenesis a treatment of inflammation."

The present volume collects lecture notes from the session of the International School of Mathematical Physics 'Ettore Majorana' on Renormalization Theory that took place in Erice (Sicily), August 17 to August 31, 1975. The School was a NATO Advanced Study Institute sponsored by the Italian Ministry of Public Education, the Italian Minis try of Scientific and Technological Research, and the Regional Sicilian Government. Renormalization theory has, by now, acquired forty years of history. The present volume assumes a general acquaintance with the elementary facts of the subject as they might appear in an introductory course in quantum field theory. For more recent significant developments it provides a systematic intro duction as well as a detailed discussion of the existing state of knowledge. In particular analytic and dimensional renorma lization, normal product technique, and the Bogoliubov-Shirkov Epstein-Glaser method are treated, with applications to physically important gauge theories. All the preceding deals with perturbative renormalization theory. In recent years there has been an interesting development of non-perturbative renormalization theory in models in space-times of two and three dimensions, with the use of the methods of constructive field theory. Despite the simplicity of these models, the results are of significance because they are exact and answer a number of questions of principle. There are parts of renormalization theory which are not well understood, for instance the renormalization theory of non-renormalizable interactions."

This book brings together physicians, scientists and those concerned with the production and use of anti-inflammatory drugs to discuss basic issues affecting all aspects of side-effects, including their detection and treatment. The chapters cover a wide variety of topics including the epidemiology, clinical and experimental aspects of side-effects in the GI tract, liver, kidney, cartilage, bone and skin as well as the problems associated with the newer range of disease-modifying anti-rheumatic drugs such as methotrexate and cyclosporin. This book should be of interest to all those who develop and use anti-inflammatory analgesic drugs, from basic scientists to clinicians. It contains papers presented at the Third International meeting on "Side-Effects of Anti-inflammatory and Analgesic Drugs" held in Verona, Italy, 8-11 May 1991.