Lyme disease is the most common tick-borne illness in the United States, with more than 300,000 cases diagnosed each year. However, doctors are deeply divided on how to diagnose and treat it, giving rise to the controversy known as the "Lyme Wars." Firmly entrenched camps have emerged, causing physicians, patient communities, and insurance providers to be pitted against one another in a struggle to define Lyme disease and its clinical challenges. Health care providers may not be aware of its diverse manifestations or the limitations of diagnostic tests. Meanwhile, patients have felt dismissed by their doctors and confused by the conflicting opinions and dubious self-help information found online. In this authoritative book, the Columbia University Medical Center physicians Brian A. Fallon and Jennifer Sotsky explain that, despite the vexing "Lyme Wars," there is cause for both doctors and patients to be optimistic. The past decade's advances in precision medicine and biotechnology are reshaping our understanding of Lyme disease and accelerating the discovery of new tools to diagnose and treat it, such that the great divide previously separating medical communities is now being bridged. Drawing on both extensive clinical experience and cutting-edge research, Fallon, Sotsky, and their colleagues present these paradigm-shifting breakthroughs in language accessible to both sides. They clearly explain the immunologic, infectious, and neurologic basis of chronic symptoms, the cognitive and psychological impact of the disease, as well as current and emerging diagnostic tests, treatments, and prevention strategies. Written for the educated patient and health care provider seeking to learn more, Conquering Lyme Disease gives an up-to-the-minute overview of the science that is transforming the way we address this complex illness. It argues forcefully that the expanding plague of Lyme and other tick-borne diseases can be confronted successfully and may soon even be reversed.

The papers assembled in this collection comprise a majority of the oral presentations as well as several poster presentations given at the 22nd Annual Symposium arranged by the Bastern Pennsylvania Branch of the American Society for MicrobioloS)'. The symposium would not be possible without the generous support of the many sponsors (see sponsor list) or without the concerted effort of a11 the Committee members. This Symposium series has evolved into an annual Bastern Pennsylvania Branch ASM event that attracts participants from a wide geographie area. It should be noted that one of the hallmarks of these symposia involves interaction between the presenters and those in attendance. Several authors have altered their by the participants. Therefore, the manuscript that manuscripts based on comments fo11ows should be viewed as a group effort of both the participants and presenters. J ames Poupard Lori Walsh Bruee Kleger ix CONTENTS 1 Introduction 1: CURRENT METHODS The Evolution of Antimicrobial Susceptibility Testing Methods . . . . . . . . . . . . . . . 3 James A. Poupard, Stephen F. Rittenhouse, and Lori R. Walsh Antimicrobial Susceptibility Tests: Testing Methods and Interpretive Problems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Patrick R. Murray Clinician Utilization of Rapid Antibiotic Susceptibility Data: A Prospective Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Franklin P. Koontz SESSION 2: CONTEMPORARY ISSUES IN SUSCEPTIBILITY TESTING When We Should Be Testing, How Often and What to Report . . . . . . . . . . . . . . . 35 Raymond C. Bartlett Areas of Recent Emphasis of the National Committee for Clinical Laboratory Standards Subcommittee on Antimicrobial Susceptibility Testing . . . . . . . . . . . . . . . . . . . . . . . 61 James H. Jorgensen Non-Traditional Approaches for Quality Control of Antimicrobial Susceptibility Tests . . . . . . . . . . . . . . . . . . . . . . . . .

The term "autoimmunity" has been used to categorize a number of different diseases of unknown etiology. The term as applied to many of these diseases would probably be interpreted best as "autoreactivity," as the clinical phenotypes are often characterized by an inflammatory-like accumulation of activated cells of the immune system at sites of obvious damage of normal cells and/or tissue. The reasons as to why an immune system should attack itself are far from clear, although the association with specific infectious diseases in genetically susceptible people remains perhaps our best lead. The input of the biotechnological revolution has enabled us to attempt to readdress many of the fundamental questions raised by clinical and serological associations with autoimmune disease. The ability to dissect the immune response to these infectious agents which are associated with autoimmune features (as well as the facility to identify new agents, e. g. HIV), in addition to the ability to clone and sequence immune response genes, has enabled a much better understanding, at least of the complexity of "autoimmunity" to be gleaned. This volume contains the chapters that summarize the plenary presentations given at The Impact of Biotechnology on AUTOIMMUNI1Y meeting in Florence, Italy in June 1993. They cover all aspects from pathogenesis to treatment. The association with infectious diseases and autoimmunity is comprehensively covered by David Isenberg who reviews major issues, such as the association of autoantibodies appearing after infectious disease and antibacterial antibodies associated with autoimmune disease.

The fourth edition of the TNM Classification was published in 1987,1 and a revision in 1992.2 It was the result of efforts by all national TNM Committees towards a worldwide uniform classification. The classifica tion criteria are identical with the fourth edition of the Manual for 3 Staging of Cancer of the American Joint Committee on Cancer (AJCC). Although the classification has found wide acceptance, some workers have pointed out that individual definitions and rules for staging are not sufficiently detailed. This can lead to inconsistent application of the clas sification. the antithesis of standardization. This source of differences in interpretation applies not only to the classification of individual organs but also to the general rules of the system, especially to the definitions of the requirements for the pathological classification (pT, pN). These are specified only for carcinoma of the breast; for other sites, reference must be made back to the general rules. which can lead to variable interpreta tions. The TNM Project Committee of the UICC has addressed this prob lem and collected and considered the criticisms and suggestions from the national TNM Committees as well as from cancer registries, oncolo gical associations and individual users. The result was the decision to complement the 4th edition of the TN M Classification 1.2. 3 with the publi cation of a TNM Supplement containing recommendations for the uni form use of TNM."

The "Europe against Cancer" programme has, from its inception, emphasised the key role which general practitioners must play in the actions necessary to achieve its aim of reducing the incidence and the mortality from cancer in the European Community. General practitioners, because of their day-to-day direct and continuing contact with patients, playa role not only in primary prevention and education of patients, but also in motivating their patients to accept secondary prevention and screening, some of it carried out by general practitioners themselves. These preventive activities are in addi tion to their traditional role in the care and management of patients with cancer at home, and increasingly, their role in active treatment. In view of the importance of the general practitioner in the "Europe against Cancer" programme, the European Commission, with a view to providing general practitioners with up-to-date useful information, has sponsored the production of this series of publi cations on organbased cancers, especially written for general practitioners. Regis Malbois Advisor in charge of the "Europe against Cancer" programme Commission of the European Communities Brussels Preface Colorectal cancer is the second most common cause of death from malignant disease with a high incidence in many European countries. This book is part of a series of pub lications on major cancer diseases designed for the European family doctor. It is pub lished by the Commission of the European Communities within the context of the Eu rope Against Cancer Programme.

Among unconventional agents and unclassified viruses the contributions to this volume focused on prion-related diseases, with special emphasis on bovine spongiform encephalopathy and human spongiform encephalopathies, and Borna disease virus, an agent known since long time to be pathogenic for horses and sheep, which is now discussed as a potential pathogen for humans. Additionally, the volume contains articles about newly discovered viruses like porcine respiratory and reproductive syndrome virus and viruses that are classified only provisionally like African swine fever virus, hepatitis C and E viruses, or the arteriviruses.

The hybridoma technique for producing monoclonal antibodies developed by Drs. Kohler and Millstein in 1975 revolutionized the field of tumor immunology. It is now clear that there are antigens associated with or restricted to human neoplasms that have biologic significance. Monoclonal antibodies have already been demonstrated to have great immunodiagnostic value, and it is anticipated that they will become a component of our therapeutic armamentarium. Most investigators in the field, however, feel the true potential of monoclonal antibodies in cancer therapy remains to be determined. Clearly the most encouraging results have been witnessed in the treatment of hematologic malignancies. This volume of Cancer Treatment and Research explores the current state of the art of immunoconjugate therapy of hematologic malignancies. The first chapter, authored by Drs. Rosen and Kuzel, reviews the current status of radioimmunotherapy of lymphoma. Results of clinical investigations utilizing radiolabeled immunoconjugates in B-cell lymphomas, T-cell lym- phomas, and Hodgkin's disease are discussed. In addition, obstacles to effective antibody therapy are highlighted and toxicities are summarized. Chapter 2, written by Drs. Sgouros and Scheinberg, critiques the treat- ment of leukemia with radiolabeled monoclonal antibodies. In this chapter, the unique features of leukemia that make it particularly suitable for radio- immunotherapy are discussed, an overview of selected clinical trials is presented, and a treatment planning approach to radioimmunotherapy in- corporating biologic and physical parameters is reviewed.

This third edition expands upon the previous edition with current, detailed methods on different aspects, and landmarks advancing knowledge on Salmonella research. With new chapters on molecular assays for detection, identification and serotyping of Salmonella, quantitative proteomic identification of host factors involved in salmonella infection, determination of antimicrobial resistance in salmonella, site-directed mutagenesis, chromosomal gene analysis, various microscopy methods to analyze salmonella interaction with host cells, in vitro modeling of gallbladder-associated salmonella colonization, and analysis of salmonella phages and prophages. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Salmonella: Methods and Protocols, Third Edition aims to provide methods that will have an impacted Salmonella research

Elimination of measles and poliomyelitis diseases from the globe is a priority goal of the World Health Organization. For the first time, in a single volume comprising thirty-one well-documented chapters, internationally recognized experts provide a state-of-the-art treatment of these two important viral diseases. The book offers a wide range of new findings and references on the latest advances regarding the measles and poliomyelitis: * global and molecular genetic epidemiology, characteristics and diseases surveillance * all available vaccines and research to produce more safe and more potent-biotechnology vaccines * immunization programmes, considering the available vaccines and possibility of vaccinal associations in strategy to eliminate/eradicate these diseases * immunity to infections and immunogenicity of vaccines * virus genomes organization and antigenic structures related to vaccine characteristics, stressing their role in immunization strategies * needs of global cooperation, using all available resources, vaccines and strategies to achieve the global control of the diseases. It is addressed to all public health professionals concerned with measles and poliomyelitis control, especially in hospitals, clinics, governmental health services, international health services, centers of infectious diseases, research institutes, medical schools, vaccine producers and experts in immunization strategies and programmes.

This volume is intended to present an eclectic selection of informative reviews on aspects of the malignant lymphomas, including Hodgkin's disease. The choice of suitable review topics in this field is made hazardous by several facts. First, the growth of insight into basic mechanisms of lymphomagenesis is explosive, as is the expansion of our understanding of the need for precise morphologic classification of these diseases. Second, new therapeutic agents, cytotoxic and biologic, as well as new drug delivery strategies, are appearing with remarkable frequency. Finally, old "standard" approaches, such as the staging laparotomy for Hodgkin's disease, are being reconsidered and deserve attention in an up-to-date collection of papers. The 10 reviews presented here fall generally into three categories. First, the optimal diagnostic and therapeutic approaches to Hodgkin's disease are considered by Mark Leibenhaut, who reviews the status of the diagnostic staging laparotomy, and by Philip Bierman, who discusses his thoughts on the timing of high-dose treatment with bone marrow transplantation for this disease. There follow four reviews of current management of specific histologic subtypes of malignant lymphoma. First, Velasquez reviews prognostic factors in both intermediate and high grade lymphomas. Miller and Dahlberg review and update the Southwest Oncology Group experience in developing curative cytotoxic combination therapies for diffuse large-cell lymphomas. Lastly, optimal therapy for two kinds of high grade lymphoma are presented. Butler and Hainsworth describe the Vanderbilt experience with diffuse small noncleaved cell lymphoma and Picozzi reviews lymphoblastic lymphoma.

The previous volume of this series on soft tissue sarcomas highlighted the importance of the multidisciplinary approach to treatment, the focus of which is continued in the present edition. Proper diagnosis and staging remain the cornerstone of the treatment strategy. Sophisticated histopathology techniques and growing consensus on grading systems have further increased the importance of the histopathologist in providing estimates of the prognosis of the patient as well as providing data for the planning of treatment strategy. The use of cytogenetics is relatively new in this field. This might enable the distinction of subgroups in specific histological tumor types. Furthermore, molecular biological studies not only help to reveal inherited predispositions and details in oncogenesis in tumor development, but they may also provide additional predictive factors for tumor behavior. Further data on treatment strategy will be provided by diagnostic imaging, a field in which the role of magnetic resonance imaging is rapidly developing. As far as actual treatment is concerned, surgery still provides the major chance for cure. In view of the endeavor to be as sparing as possible, the addition of radiotherapy to surgery is of utmost importance. Usually radiotherapy is given after surgery, but the optimal sequence of the two modalities still needs to be defined. The combined use of surgery with radiotherapy and/or chemotherapy does have an impact on wound healing.

Colorectal cancer is a collective term for a heterogeneous group of diseases. In a large proportion of cases, the condition is attributable to genetic predisposition. Those directly involved in the treatment of patients with cancer of the large bowel are confronted to an increasing degree with the genetic aspects of the disease. In familial and hereditary forms of the disorder periodic screening of the close relatives of the patients can in principle prevent disease and death from colorectal cancer. Presymptomatic diagnosis by means of DNA technology is now possible in many cases of familial adenomatous polyposis. Genetic diagnosis will be increasingly important for the identification of high-risk groups. This book summarizes those aspects of the genetics of colorectal cancer that are important for clinical pracice. It has been stated that clinicians can contribute to the goal of reducing mortality from cancer by asking each patient about his or her family history of cancer. The aim of this book is to provide a guideline for the management of those situations in which the family history of colorectal cancer is found to be positive.

Although more than 12 years have passed since publication of the first WHO histological classification of central nervous system (CNS) tumours, the changes in this revised edition are not radical. Only one formerly recognized entity has been deleted: the monstrocellular sarcoma, because there is immuno- cytochemical evidence of its astrocytic nature. Several new tumour types have been added: the pleomorphic xanthoastro- cytoma has been generally acknowledged for almost a decade; the neurocytoma has gradually evolved as a clinical-pathological entity; and two new entries, the dysembryoplastic neuroepi- thelial tumour and the desmoplastic infantile ganglioglioma, have only been characterized morphologically during the past few years. We regard the classification as an international standard to facilitate communication and have tried to avoid current con- ceptual controversies. The majority of partiCipants supported inclusion of the term "primitive neuroectodermal tumour" (pNET). However, because of our limited knowledge of the biol- ogy of embryonal CNS tumours, preference was given to use PNET selectively, rather than applying it to all small cell embryo- nal childhood tumours, irrespective of their histological pheno- type. Ependymomas and meningiomas now have new histological SUbtypes. Most of these are not associated with biological behaviour different from the parent tumour type, but their description will aid the practising pathologist to identify and classify these lesions. 2 Introduction Histological Typing Following the philosophy of this WHO series, classification is based primarily on histological assessment of cell types and tis- sue patterns recognized by conventional light microscopy.

In our environmentally conscious society, reports of an increase in the risk of developing several cancers - including melanoma, lymphoma and lung cancer - have excited great controversy. Of these tumors, melanoma has demonstrated the most spectacular increase, generating a considerable body of research. The justification for this volume is found in the need for an up-to-date review of this research. The book represents a comprehensive review of both current research and clinical management of melanoma, arranged in such a way as to be maximally user-friendly to both the basic scientst and the clinician interested in this fascinating disease.

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Scrapie, a naturally occurring neurodegenerative disease of sheep and sometimes goats, is a prototypic disease for the whole group of the subacute spongiform virus encephalopathies. Kuru was the first human disease of this type to be discovered in 1957 by Gajdusek and Zigas, and its discovery opened the whole field in the human biomedical sciences by the very realization of the fact that viruses may induce disease months or even decades after infections, and that these slow virus diseases are more compatible with classical degenerations of the nervous system than with inflammatory disorders of the brain. More than a quarter of a century since discovery of Kuru, and more than half a century following the first transmission of scrapie, the very nature of the infectious virus remains unknown. This comprehensive review covers all aspects of slow unconventional virus infections known today. It includes numerous historical data, biochemistry and molecular biology of the prion protein and its gene, the role of genetics and mutations within PrP gene, spreading and targeting of the virus, biochemistry and neurochemistry of the alterations of different neurotransmitter system and neuropathology. More than 1000 references are listed and critically analyzed; the reader can find references to all experiments and laboratory findings which has ever been done in this field. Furthermore, the book offers different view on the basic problems as for example, the nature of the scrapie agent.

Leukemia continues to offer the scientist a unique opportunity to gain new knowledge about the malignant transformation. As a result, this multi-authored volume, devoted to advances which have occurred over the last seven years, provides the reader with an important new understanding of leukemia, but perhaps even more important, predicts analogous, new developments in the other malignant diagnoses. In this respect, this volume represents the cutting edge of cancer research. This text is unique in that it includes in a single volume the leading contributors to their respective fields covering what the editors feel are the major advances in our knowledge of the biology and therapy of leukemia over the last seven years.

Osteosarcoma in Adolescents and Young Adults: New Developments and Controversies is the fifth volume in the series Cancer Treatment, and Research' devoted to pediatric oncology. Like its immediate predecessor, Hodgkin's Disease in Children: Controversies and Current Practice, this volume also deals with the current state of affairs: where do researchers differ in opinions or firmly held beliefs? What does the future hold for research or for the patients who have benefited from research and are now cured? etc. The first part deals with preclinical and clinical issues that relate to the disease and the second part deals with the results of recent trials and in some cases ongoing trials. It could be argued that section B Pharmacology, Section D Radiotherapy and Section E Surgery of part one belong to part two; however in these sections we have tried to focus on one discipline and in part two, we have tried to focus on the results of multidisciplinary trials. A third part includes a few critiques and editorial comments. This volume was prepared and planned for both basic and clinical oncologists. It is hoped that the basic scientists will gain some insight into the problems of their clinical colleagues and that the clinicians will be willing to read to the more basic articles. It is not a text for students (or for that matter physicians) who want all things to be laid out in black and white'. But it is a text for those students who want to know how vibrant this field of research is and are willing to stand in awe of how much research needs to be done.

The first edition of Oncogenes (1989) focused on several of the better known transforming mechanisms and surveyed a spectrum of solid tumors and hematologic malignancies. Several of the nearly 50 known oncogenes most relevant to human disease were examined. In contrast, this volume presents a very different profile and balance of subject material that reflects the rapidly changing field of molecular oncology and its newly emerging concepts. Among the most important discoveries of the past 4 years are the identification of nearly a dozen different tumor suppressor genes and the finding of an entirely new class of cancer-causing gene (bcl-2) that acts by inhibiting cell death rather than stimulating cell proliferation. This edition begins by reviewing selected malignancies in which our earlier search for clinically relevant oncogenes has led to more focused studies on gain-of-function and loss-of-function genetic abnormalities, as well as autocrine and paracrine growth factor loops known to regulate tumor physiology and malignant cell behavior. Curiously, many of these genetic and functional abnormalities are shared by several different tumor types and are not uniformly present in all tumors of the same type. This observation brings up molecular questions about the tissue-specific determinants that underlie individual cancers and also gives added impetus to the suggestion that molecular abnormalities (referred to as tumor markers) be included among the histopathologic features used for clinical diagnosis and manage ment."

Biomedical scientists widely acknowledge that individuals' immune respon siveness is important in resistance to infections by microorganisms, including fungi. Because of the devastating acquired immunodeficiency syndrome (AIDS) epidemic, caused by the human immunodeficiency retrovirus, it is now accepted that suppressed immune responses, especially cellular immu nity, are important contributors to increased individual susceptibility to opportunistic infections-including infections caused by fungi which were at one time thought to be very lowly or nonpathogenic. Within the last few years, there has been an almost explosive increase in interest and studies concerning the nature and mechanisms of the immune response to fungal infections. Many immunologists who are not well versed in mycology have begun to study the nature and mechanisms of antifungal immunity using a wide variety of newer as well as more conventional immunologic technologies, both in vivo and in vitro. Up to the 1980s, however, there was little interest among basic immunologists concerning fungal immunity. This situation has changed dramatically in the past half decade, mainly because of AIDS."

Present and potential future applications of new diagnostic strategies basedon the direct or indirect detection of cancer genes are delineated in this volume. Among the methodological aspects covered are enzymatic target amplification by the polymerase chain reaction and related techniques, DNA fingerprinting, transfer of putative cancer genes in appropriate receipient cells, and recent developments inthe application of monoclonal antibodies in immunohistochemistry and immunoscintigraphy. The diagnostic and functional implications of mutations in cancer genes such as ras and p53 are described. The characterization of cancer genes and their products is correlated with growth control anddissemination of tumour cells by in vitro or clinical evidence. The contributions in the present volume uptdate the information available on established or newly described cancer genes, and may help manage the transition from basic research to clinical practice.

This monograph gives an excellent review of the issue of antimicrobial prophylaxis in urol ogy and the use of the new fluoroquinolones in urology. The development of the fluoro quinolones has had a profound effect in urology, specifically because of the unique phar macokinetics of the fluoroquinolones with their two or more pK values, making concen tration of these compounds possible in the prostate. Their wide spectra against infecting organisms causing infections in the urinary tract have also made them popular and almost ideal in the treatment of urinary tract infections. This thesis summarizes in an concise way and brings up to date practically all our know ledge concerning the use of fluoroquinolones in urology. The chapter on antimicrobial prophylaxis covers our present knowledge completely, especially concerning the use of these drugs in antimicrobial prophylaxis in transurethral surgery. September 1992 PaulO. Madsen Madison, Wisconsin, USA v Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . V I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1. 1. Author's Publications Referred to in Text . . . . . . . . . . . . . . . . . . . . . . 1 1. 2. Historical Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1. 3. Problems of Antimicrobial Prophylaxis in Urology . . . . . . . . . . . . . . . . 2 D. General Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. 1. Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. 1. 1. Bacteriuria and urinary tract infections . . . . . . . . . . . . . . . . . . . . . . 3 2. 1. 2. Bacteremia and septicemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. 1. 3. Nosocomial infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2. 1. 4. Wound infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2. 2. Pathophysiology of Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2. 3. Specifics of Antimicrobial Agents to be Used in Prophylaxis . . . . . . . . . . 6 2. 4. Role of Quinolones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2. 4. 1. Antimicrobial activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2. 4. 2. Pharmacokinetic properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . ."

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology textbooks are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good in-depth reviews of cancer topics, and published symposium lectures are often the best overviews available. Unfortunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes that aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up to date, and easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion: first, by dividing the oncology literature into specific subdivisions such as lung cancer, genitourinary cancer, pediatric oncology, etc.; and second, by asking eminent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current di agnosis, staging, markers, all forms of treatment modalities, basic biology, and more."

Throughout the world, scientists and the general with environmental illness. Part II presents an over public are concerned about the adverse effects of view of chemical and physical agents commonly toxic agents found in contaminated air, water, food, found in contaminated air, water, food, and soil. and soil. In the past, attention has focused on haz The problem of hazardous wastes is also discussed. ards originating in the workplace. As a consequence, Part III characterizes the body's defense against occupational medicine has become a well-recognized such exposure. Defenses at the portals of entry are and established clinical discipline. Much less atten discussed, with emphasis placed on the role of tion has been paid to nonoccupational hazards. There nutrition. Detoxication and immunologic defense is a growing awareness, however, of the dangers of mechanisms are described. Part IV indicates the exposure to toxic chemical and physical agents in importance of and provides instruction on the the homes, community, and general environment, method of including occupational and environmen especially for the fetus, the infant, the very young, tal factors in the routine medical history. The role of the elderly, and the chronically ill, those most sus enhanced susceptibility as a factor in an individual's ceptible. Environmental medicine, fOCUSing on the response to toxic exposure is discussed."

Biologically active compounds isolated from microorganisms continue to be vital to the development of new drugs and agricultural chemicals. This book was prepared by current and past members of the laboratory of Dr. Satoshi Omura of the Kitasato Institute in Japan. Dr. Omura and his colleagues have discovered and studied a number of important antibiotics, and in their work they have pioneered new methods for screening microbes for interesting and important compounds. This book presents strategies and methods for identifying novel molecules with several types of biological activity. In addition, the book discusses the identification of microbial compounds of agrochemical importance, presents information on chemical screening methods, and concludes with chapters on microbial strain selection, fermentation technology, and genetic engineering of antibiotic-producing microorganisms. This book will be of great interest to scientists working in the very active and competitive fields of antibiotic and agrochemical discovery.