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.

This work on advances in anti-rheumatic therapy covers topics such as: outcome measures in clinical trials of anti-rheumatic drugs; azapropazone (AZP); the mode of action of glucocorticoids; and clinical trials of oral chondroitin sulphate in the treatment of osteoarthritis.

Significant progress has been acquired in the treatment of rheumatic conditions with the introduction of biologic therapies, which has enabled better control of disease activity and improved patients' long-term outcome. Apart from several biologic treatments already licensed for use in autoimmune rheumatic conditions, numerous other agents are currently under investigation. This rapid expansion of the therapeutic armamentarium requires a critical analysis of individual biologic options and their clinical indications, in order to facilitate the optimal use of these new therapies. The authors felt that a comprehensive book revisiting all the evidence available regarding the efficacy, cost-effectiveness and health implications of the use of biologics in rheumatology was needed in order to integrate the clinical, ethical and socio-economic aspects related to their use. This book is aimed at specialist doctors, trainees, nurses and health professionals working in the field of rheumatology. It critically appraises the level of evidence behind the use of biologic agents in diverse autoimmune diseases, comprising separate chapters which focus on rheumatoid arthritis, systemic lupus erythematosus, myositis, systemic sclerosis, Sjogren's syndrome, seronegative spondyloarthropathies, psoriatic arthritis and psoriasis, small, medium and large vessel vasculitis, osteoporosis, and interstitial lung disease associated with rheumatic conditions. In addition, the book explores aspects related to the use of biologic agents, such as ethical considerations of consenting patients to take part in clinical trials with biologics, and adolescent and adult rheumatology nurse perspectives related to patients' benefits of biologic therapies. Particular interest is given to the use of biologics during pregnancy and assessment of their infectious risks. A separate chapter explores the off-target benefits associated with the use of anti-TNF therapies. Several chapters include data about cost-effectiveness, and national and international guidelines for the use of biologic agents in different rheumatic conditions.

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.

Introducing the most recent advances in crystallography, nuclear magnetic resonance, molecular modeling techniques, and computational combinatorial chemistry, this unique, interdisciplinary reference explains the application of three-dimensional structural information in the design of pharmaceutical drugs. Furnishing authoritative analyses by world-renowned experts, Structure-Based Drug Design discusses protein structure-based design in optimizing HIV protease inhibitors and details the biochemical, genetic, and clinical data on HIV-1 reverse transcriptase presents recent results on the high-resolution three-dimensional structure of the catalytic core domain of HIV-1 integrase as a foundation for divergent combination therapy focuses on structure-based design strategies for uncovering receptor antagonists to treat inflammatory diseases demonstrates a systematic approach to the design of inhibitory compounds in cancer treatment reviews current knowledge on the Interleukin-1 (IL-1) system and progress in the development of IL-1 modulators describes the influence of structure-based methods in designing capsid-binding inhibitors for relief of the common cold and much more!

Most studies on autonomic innervation of smooth muscle have focused on the short-term mechanisms involved in neurotransmission in physiological and pathophysiological conditions. However recent obser vations of the long-term plasticity of this system, i. e. its capacity for regeneration and for compensatory change in pattern of innervation and expression of cotransmitters and receptors in ageing, following surgery, trauma or in disease, have indicated that an understanding of the mechanisms involved could influence the design of therapeutic regimes. There is increasing evidence for long-term communication between nerves and smooth muscle cells during development and throughout adult life. To date, the trophic interactions between nerves and airway musculature have attracted little interest, consequently, much of the information presented here is drawn from studies using other smooth muscles. However, the questions posed about trophic interactions dur ing development apply as much to airways smooth muscle neuroeffector systems as to other autonomic neuroeffector systems. These are: i) How do developing nerve fibres know where to go and how do they reach their target sites? ii) What determines the density and pattern of inner vation at reaching the effector? iii) How do the nerves survive and maintain their position once established? iv) What factors influence neurochemical differentiation such that genetically multipotential neu rones are triggered to synthesize one or combinations of neurotransmit ters? v) What influence do nerves have on the structure, function and receptor expression of their effector cells? vi) How do diseases interrupt these processes? - see [1].