Cytokines And Cell Homeostasis In The Gastroinstestinal Tract

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Cytokines and Cell Homeostasis in the Gastroinstestinal Tract

Author : T. Andus
Publisher : Springer Science & Business Media
ISBN 13 : 9780792387589
Total Pages : 438 pages
Book Rating : 4.3/5 (875 download)

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Book Synopsis Cytokines and Cell Homeostasis in the Gastroinstestinal Tract by : T. Andus

Download or read book Cytokines and Cell Homeostasis in the Gastroinstestinal Tract written by T. Andus and published by Springer Science & Business Media. This book was released on 2000-11-30 with total page 438 pages. Available in PDF, EPUB and Kindle. Book excerpt: The gastrointestinal tract has a number of unique features. Its extensive surface is formed by a single layer of rapidly renewing cells, the intestinal epithelial cells. These cells are in contact with a number of other cell populations, including the largest part of the immune system, and with an excessive luminal antigen load, including vast numbers of bacteria. Furthermore two more organs, namely liver and pancreas, are part of the system. The rapid renewal of the epithelial layer, the interactions of different cell types, and the balance between cell proliferation and death, have been fascinating subjects of studies in recent years. Much has been learned, and cytokines have emerged as important mediators for all these interactions and homeostatic systems. This book, the proceedings of the Falk Symposium 113 on `Cytokines and Cell Homeostasis in the Gastrointestinal Tract', held in Regensburg, Germany, 16-18 September 1999, provides a forum for basic scientists and interested clinicians to exchange ideas, to discuss concepts and to plan further studies.

Intestinal Homeostasis and Disease: A Complex Partnership between Immune Cells, Non-Immune Cells and the Microbiome

Author : Marcela A. Hermoso
Publisher : Frontiers Media SA
ISBN 13 : 2889634353
Total Pages : 222 pages
Book Rating : 4.8/5 (896 download)

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Book Synopsis Intestinal Homeostasis and Disease: A Complex Partnership between Immune Cells, Non-Immune Cells and the Microbiome by : Marcela A. Hermoso

Download or read book Intestinal Homeostasis and Disease: A Complex Partnership between Immune Cells, Non-Immune Cells and the Microbiome written by Marcela A. Hermoso and published by Frontiers Media SA. This book was released on 2020-01-20 with total page 222 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Military Strategies for Sustainment of Nutrition and Immune Function in the Field

Author : Institute of Medicine
Publisher : National Academies Press
ISBN 13 : 0309173183
Total Pages : 722 pages
Book Rating : 4.3/5 (91 download)

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Book Synopsis Military Strategies for Sustainment of Nutrition and Immune Function in the Field by : Institute of Medicine

Download or read book Military Strategies for Sustainment of Nutrition and Immune Function in the Field written by Institute of Medicine and published by National Academies Press. This book was released on 1999-05-13 with total page 722 pages. Available in PDF, EPUB and Kindle. Book excerpt: Every aspect of immune function and host defense is dependent upon a proper supply and balance of nutrients. Severe malnutrition can cause significant alteration in immune response, but even subclinical deficits may be associated with an impaired immune response, and an increased risk of infection. Infectious diseases have accounted for more off-duty days during major wars than combat wounds or nonbattle injuries. Combined stressors may reduce the normal ability of soldiers to resist pathogens, increase their susceptibility to biological warfare agents, and reduce the effectiveness of vaccines intended to protect them. There is also a concern with the inappropriate use of dietary supplements. This book, one of a series, examines the impact of various types of stressors and the role of specific dietary nutrients in maintaining immune function of military personnel in the field. It reviews the impact of compromised nutrition status on immune function; the interaction of health, exercise, and stress (both physical and psychological) in immune function; and the role of nutritional supplements and newer biotechnology methods reported to enhance immune function. The first part of the book contains the committee's workshop summary and evaluation of ongoing research by Army scientists on immune status in special forces troops, responses to the Army's questions, conclusions, and recommendations. The rest of the book contains papers contributed by workshop speakers, grouped under such broad topics as an introduction to what is known about immune function, the assessment of immune function, the effect of nutrition, and the relation between the many and varied stresses encountered by military personnel and their effect on health.

Role of IL-25 in the Maintenance of Intestinal Homeostasis and Host-microbial Interactions

Author : Catherine Heather Plunkett
Publisher :
ISBN 13 :
Total Pages : 319 pages
Book Rating : 4.:/5 (945 download)

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Book Synopsis Role of IL-25 in the Maintenance of Intestinal Homeostasis and Host-microbial Interactions by : Catherine Heather Plunkett

Download or read book Role of IL-25 in the Maintenance of Intestinal Homeostasis and Host-microbial Interactions written by Catherine Heather Plunkett and published by . This book was released on 2013 with total page 319 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Intestinal Stem Cell Niche

Author :
Publisher : Academic Press
ISBN 13 : 9780128134818
Total Pages : 150 pages
Book Rating : 4.1/5 (348 download)

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Book Synopsis Intestinal Stem Cell Niche by :

Download or read book Intestinal Stem Cell Niche written by and published by Academic Press. This book was released on 2018-04-24 with total page 150 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Stem Cells and Their Niches addresses stem cells during development, homeostasis, and disease/injury of the respective organs, presenting new developments in the field, including new data on disease and clinical applications. Video content illustrates such areas as protocols, transplantation techniques, and work with mice. Explores not only reviews of research, but also shares methods, protocols, and transplantation techniques Contains video content to illustrate such areas as protocols, transplantation techniques, and work with mice Each volume concentrates on one organ, making this a unique publication

Regulation of Gastrointestinal Mucosal Growth

Author : Rao N. Jaladanki
Publisher : Biota Publishing
ISBN 13 : 1615047352
Total Pages : 150 pages
Book Rating : 4.6/5 (15 download)

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Book Synopsis Regulation of Gastrointestinal Mucosal Growth by : Rao N. Jaladanki

Download or read book Regulation of Gastrointestinal Mucosal Growth written by Rao N. Jaladanki and published by Biota Publishing. This book was released on 2016-11-30 with total page 150 pages. Available in PDF, EPUB and Kindle. Book excerpt: The mammalian gastrointestinal mucosa is a rapidly self-renewing tissue in the body, and its homeostasis is preserved through the strict regulation of epithelial cell proliferation, growth arrest, and apoptosis. The control of the growth of gastrointestinal mucosa is unique and, compared with most other tissue in the body, complex. Mucosal growth is regulated by the same hormones that alter metabolism in other tissues, but the gastrointestinal mucosa also responds to host events triggered by the ingestion and presence of food within the digestive tract. These gut hormones and peptides regulate the growth of the exocrine pancreas, gallbladder epithelium, and the mucosa of the oxyntic gland region of the stomach and the small and large intestines. Luminal factors, including nutrients or other dietary factors, secretions, and microbes that occur within the lumen and distribute over a proximal-to-distal gradient, are also crucial for maintenance of normal gut mucosal regeneration and could explain the villous-height-crypt-depth gradient and variety of adaptation, since these factors are diluted, absorbed, and destroyed as they pass down the digestive tract. Recently, intestinal stem cells, cellular polyamines, and noncoding RNAs are shown to play an important role in the regulation of gastrointestinal mucosal growth under physiological and various pathological conditions. In this book, we highlight key issues and factors that control gastrointestinal mucosal growth and homeostasis, with special emphasis on the mechanisms through which epithelial renewal and apoptosis are regulated at the cellular and molecular levels.

Molecular Hematology

Author : Drew Provan
Publisher : John Wiley & Sons
ISBN 13 : 1394180470
Total Pages : 452 pages
Book Rating : 4.3/5 (941 download)

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Book Synopsis Molecular Hematology by : Drew Provan

Download or read book Molecular Hematology written by Drew Provan and published by John Wiley & Sons. This book was released on 2024-03-05 with total page 452 pages. Available in PDF, EPUB and Kindle. Book excerpt: Provides a core knowledgebase for those with minimal exposure to hematologic molecular biology, fully revised and updated Molecular Hematology brings together the most up-to-date and reliable information on the molecular basis of major hematologic diseases. Edited and authored by leading experts in the field, this volume demonstrates the clinical relevance of molecular biology in the diagnosis and treatment of blood disorders. Concise, accessible chapters address key topics in modern hematology, such as lymphoma genetics, molecular coagulation, thrombophilia, pharmacogenomics, platelet disorders, hemophilia, anemia, and multiple myeloma. Chapters introduce and summarize specific hematologic diseases, explore the pathogenesis of the disorder, highlight new and emerging molecular strategies, and more. Now in its fifth edition, Molecular Hematology is fully revised to incorporate contemporary hematology research and practice. Entirely new chapters cover topics such as CAR-T cell technology, COVID, cancer cell biology, gene therapy and gene editing in clinical practice, as well as the impact of molecular research on the diagnosis and treatment of various malignant hematologic diseases. This edition includes updated suggested readings and a wealth of new full-color charts, graphs, and illustrations throughout. Covers the molecular biology of different blood diseases, their pathogeneses, and current molecular research and therapies Illustrates the impact of molecular research on hematologic investigations and therapeutics Discusses how progress in basic science and therapeutics has improved the diagnosis and care of patients with various hematologic disorders Surveys recent developments in cancer-cell biology, with an emphasis on leukemia and lymphoma Includes access to a companion Digital Edition providing search across the book, downloadable illustrations, and notation tools Molecular Hematology is a must-have resource for established and trainee clinicians, clinical scientists and researchers, medical students, and upper-level undergraduates in the fields of hematology, oncology, and molecular biology.

Enteric Glia

Author : Brian D. Gulbransen
Publisher : Biota Publishing
ISBN 13 : 1615046615
Total Pages : 72 pages
Book Rating : 4.6/5 (15 download)

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Book Synopsis Enteric Glia by : Brian D. Gulbransen

Download or read book Enteric Glia written by Brian D. Gulbransen and published by Biota Publishing. This book was released on 2014-07-01 with total page 72 pages. Available in PDF, EPUB and Kindle. Book excerpt: The enteric nervous system (ENS) is a complex neural network embedded in the gut wall that orchestrates the reflex behaviors of the intestine. The ENS is often referred to as the “little brain” in the gut because the ENS is more similar in size, complexity and autonomy to the central nervous system (CNS) than other components of the autonomic nervous system. Like the brain, the ENS is composed of neurons that are surrounded by glial cells. Enteric glia are a unique type of peripheral glia that are similar to astrocytes of the CNS. Yet enteric glial cells also differ from astrocytes in many important ways. The roles of enteric glial cell populations in the gut are beginning to come to light and recent evidence implicates enteric glia in almost every aspect of gastrointestinal physiology and pathophysiology. However, elucidating the exact mechanisms by which enteric glia influence gastrointestinal physiology and identifying how those roles are altered during gastrointestinal pathophysiology remain areas of intense research. The purpose of this e-book is to provide an introduction to enteric glial cells and to act as a resource for ongoing studies on this fascinating population of glia. Table of Contents: Introduction / A Historical Perspective on Enteric Glia / Enteric Glia: The Astroglia of the Gut / Molecular Composition of Enteric Glia / Development of Enteric Glia / Functional Roles of Enteric Glia / Enteric Glia and Disease Processes in the Gut / Concluding Remarks / References / Author Biography

Signal Transduction: Pathways, Mechanisms and Diseases

Author : Ari Sitaramayya
Publisher : Springer Science & Business Media
ISBN 13 : 3642021123
Total Pages : 429 pages
Book Rating : 4.6/5 (42 download)

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Book Synopsis Signal Transduction: Pathways, Mechanisms and Diseases by : Ari Sitaramayya

Download or read book Signal Transduction: Pathways, Mechanisms and Diseases written by Ari Sitaramayya and published by Springer Science & Business Media. This book was released on 2009-12-02 with total page 429 pages. Available in PDF, EPUB and Kindle. Book excerpt: Providing an overview of recent developments in the field of signal transduction, this volume emphasizes direct clinical significance. As such, topics like nuclear receptors, apoptosis, growth factors, cell cycles and cancer are examined.

Adenosine Receptors

Author : Gyorgy Hasko
Publisher : CRC Press
ISBN 13 : 1420005774
Total Pages : 377 pages
Book Rating : 4.4/5 (2 download)

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Book Synopsis Adenosine Receptors by : Gyorgy Hasko

Download or read book Adenosine Receptors written by Gyorgy Hasko and published by CRC Press. This book was released on 2006-07-20 with total page 377 pages. Available in PDF, EPUB and Kindle. Book excerpt: After a century of research, several lines of evidence now indicate that the ability of adenosine to directly control inflammatory cells has a major impact on the functions of the inflammatory and immune systems. Consequently, many promising therapeutic approaches are beginning to emerge that focus on the modulation of adenosine, including the deve

Liver Immunology

Author : M. Eric Gershwin
Publisher : Springer Science & Business Media
ISBN 13 : 331902096X
Total Pages : 482 pages
Book Rating : 4.3/5 (19 download)

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Book Synopsis Liver Immunology by : M. Eric Gershwin

Download or read book Liver Immunology written by M. Eric Gershwin and published by Springer Science & Business Media. This book was released on 2013-11-19 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: Liver Immunology: Principles and Practice, Second Edition begins with important information about the epidemiology and mortality of liver disease worldwide. This information is followed by chapters related to basic immunology, application of liver immunology for diagnosis, and several excellent chapters that provide a solid foundation for understanding immune-mediated liver disease, including those associated with the biliary tree. A chapter on non-hepatic manifestations of immune mediated liver disease helps provide context for how these diseases affect the patient overall. In addition, chapters discuss various discrete immunologically-mediated infectious liver disorders including those related to bacteria, parasites, and all of the classic viruses. Chapters on the traditional autoimmune liver diseases -- primary biliary cirrhosis, autoimmune hepatitis, primary sclerosing cholangitis as well as overlap syndrome – are also included. The breadth of this comprehensive second edition is highlighted by chapters on alcoholic liver disease, non-alcoholic fatty liver disease, and drug-induced liver disease, among others. This invaluable new edition ends with a forward-looking view of future directions and how the field might meet the challenge of refractory patients. Developed by a renowned group of authors, Liver Immunology: Principles and Practice, Second Edition will again serve as a comprehensive textbook by providing an excellent overview for this rapidly evolving field. It greatly adds to the understanding of the pathogenesis of these diseases, while also providing novel insights that can be harnessed into helping improve the care of patients afflicted with various immune-mediated diseases. This volume will again be a must-read for clinicians at all levels, investigators and students.

Recent Advances in γδ T Cell Biology: New Ligands, New Functions, and New Translational Perspectives

Author : Dieter Kabelitz
Publisher : Frontiers Media SA
ISBN 13 : 2889197840
Total Pages : 271 pages
Book Rating : 4.8/5 (891 download)

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Book Synopsis Recent Advances in γδ T Cell Biology: New Ligands, New Functions, and New Translational Perspectives by : Dieter Kabelitz

Download or read book Recent Advances in γδ T Cell Biology: New Ligands, New Functions, and New Translational Perspectives written by Dieter Kabelitz and published by Frontiers Media SA. This book was released on 2016-02-16 with total page 271 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gamma/delta (γδ) T-cells are a small subset of T-lymphocytes in the peripheral circulation but constitute a major T-cell population at other anatomical localizations such as the epithelial tissues. In contrast to conventional α/β T-cells, the available number of germline genes coding for T-cell receptor (TCR) variable elements of γδ T-cells is very small. Moreover, there is a prefential localization of γδ T-cells expressing given Vgamma and Vdelta genes in certain tissues. In humans, γδ T-cells expressing the Vg9Vd2-encoded TCR account for anywhere between 50 and >95% of peripheral blood γδ T-cells, whereas cells expressing non-Vd2 genes dominate in mucosal tissues. In mice, there is an ordered appearance of γδ T-cell „waves“ during embryonic development, resulting in preferential localization of γδ T-cells expressing distinct VgammaVdelta genes in the skin, the reproductive organs, or gut epithelia. The major function of γδ T-cells resides in local immunosurveillance and immune defense against infection and malignancy. This is supported by the identification of ligands that are selectively recognized by the γδ TCR. As an example, human Vgamma9Vdelta2 T-cells recognize phosphorylated metabolites („phosphoantigens“) that are secreted by many pathogens but can also be overproduced by tumor cells, providing a basis for a role of these γδ T-cells in both anti-infective and anti-tumor immunity. Similarly, the recognition of endothelial protein C receptor by human non-Vdelta2 γδ T-cells has recently been identified to provide a link for the role for such γδ T-cells in immunity against epithelial tumor cells and cytomegalovirus-infected endothelial cells. In addition to „classical“ functions such as cytokine production and cytotoxicity, recent studies suggest that subsets of γδ T-cells can exert additional functions such as regulatory activity and – quite surpisingly – „professional“ antigen-presenting capacity. It is currently not well known how this tremendous extent of functional plasticity is regulated and what is the extent of γδ TCR ligand diversity. Due to their non-MHC-restricted recognition of unusual stress-associated ligands, γδ T-cells have raised great interest as to their potential translational application in cell-based immunotherapy. Topics of this Research Focus include: Molecular insights into the activation and differentiation requirements of γδ T-cells, role of pyrophosphates and butyrophilin molecules for the activation of human γδ T-cells, role of γδ T-cells in tumor immunity and in other infectious and non-infectious diseases, and many others. We are most grateful to all colleagues who agreed to write a manuscript. Thanks to their contributions, this E-book presents an up-to-date overview on many facets of the still exciting γδ T-cells. Dieter Kabelitz & Julie Déchanet-Merville

The Impact of Food Bioactives on Health

Author : Kitty Verhoeckx
Publisher : Springer
ISBN 13 : 3319161040
Total Pages : 341 pages
Book Rating : 4.3/5 (191 download)

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Book Synopsis The Impact of Food Bioactives on Health by : Kitty Verhoeckx

Download or read book The Impact of Food Bioactives on Health written by Kitty Verhoeckx and published by Springer. This book was released on 2015-04-29 with total page 341 pages. Available in PDF, EPUB and Kindle. Book excerpt: “Infogest” (Improving Health Properties of Food by Sharing our Knowledge on the Digestive Process) is an EU COST action/network in the domain of Food and Agriculture that will last for 4 years from April 4, 2011. Infogest aims at building an open international network of institutes undertaking multidisciplinary basic research on food digestion gathering scientists from different origins (food scientists, gut physiologists, nutritionists...). The network gathers 70 partners from academia, corresponding to a total of 29 countries. The three main scientific goals are: Identify the beneficial food components released in the gut during digestion; Support the effect of beneficial food components on human health; Promote harmonization of currently used digestion models Infogest meetings highlighted the need for a publication that would provide researchers with an insight into the advantages and disadvantages associated with the use of respective in vitro and ex vivo assays to evaluate the effects of foods and food bioactives on health. Such assays are particularly important in situations where a large number of foods/bioactives need to be screened rapidly and in a cost effective manner in order to ultimately identify lead foods/bioactives that can be the subject of in vivo assays. The book is an asset to researchers wishing to study the health benefits of their foods and food bioactives of interest and highlights which in vitro/ex vivo assays are of greatest relevance to their goals, what sort of outputs/data can be generated and, as noted above, highlight the strengths and weaknesses of the various assays. It is also an important resource for undergraduate students in the ‘food and health’ arena.

Nijkamp and Parnham's Principles of Immunopharmacology

Author : Michael J. Parnham
Publisher : Springer Nature
ISBN 13 : 3030108112
Total Pages : 888 pages
Book Rating : 4.0/5 (31 download)

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Book Synopsis Nijkamp and Parnham's Principles of Immunopharmacology by : Michael J. Parnham

Download or read book Nijkamp and Parnham's Principles of Immunopharmacology written by Michael J. Parnham and published by Springer Nature. This book was released on 2019-12-10 with total page 888 pages. Available in PDF, EPUB and Kindle. Book excerpt: Principles of Immunopharmacology provides a unique source of essential knowledge on the immune response, its diagnosis and its modification by drugs and chemicals. The 4th edition of this internationally recognized textbook has been revised to include recent developments, but continues the established format, dealing with four related fields in a single volume, thus obviating the need to refer to several different textbooks. The first section of the book, providing a basic introduction to immunology and its relevance for human disease, has been updated to accommodate new immunological concepts, particularly the role of epigenetics and the latest understanding of cancer immunology. The second section on immunodiagnostics offers a topical description of widely used molecular techniques and a new chapter on imaging techniques. This is followed by a systematic coverage of drugs affecting the immune system, including natural products. This third section contains 15 updated chapters, covering classical immunopharmacological topics such as anti-asthmatic, anti-rheumatic and immunosuppressive drugs, but also deals with antibiotics, plant-derived and dietary agents, with new chapters on monoclonal antibodies, immunotherapy in sepsis and infection, drugs for soft-tissue autoimmunity and cell therapy. The book concludes with a chapter on immunotoxicology and drug safety tests. Aids to the reader include a two-column format, glossaries of technical terms and appendix reference tables. The emphasis on illustrations is maintained from the first three editions. The book is a valuable single reference for undergraduate and graduate medical and biomedical students, postgraduate chemistry and pharmacy students, researchers in chemistry, biochemistry and the pharmaceutical industry and researchers lacking basic immunological knowledge, who want to understand the actions of drugs on the immune system.

Immune Response Activation and Immunomodulation

Author : Rajeev Tyagi
Publisher : BoD – Books on Demand
ISBN 13 : 1789851513
Total Pages : 180 pages
Book Rating : 4.7/5 (898 download)

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Book Synopsis Immune Response Activation and Immunomodulation by : Rajeev Tyagi

Download or read book Immune Response Activation and Immunomodulation written by Rajeev Tyagi and published by BoD – Books on Demand. This book was released on 2019-04-17 with total page 180 pages. Available in PDF, EPUB and Kindle. Book excerpt: Immune Response Activation and Immunomodulation has been written to address the perceived needs of both medical school and undergraduate curricula and to take advantage of new understandings in immunology. We have tried to achieve several goals and present the most important principles governing the function of the immune system. Our fundamental objective has been to synthesize the key concepts from the vast amount of experimental data that have emerged in the rapidly advancing field of immunology. The choice of what is most important is based on what is most clearly established by experimentation, what our students find puzzling, and what explains the wonderful efficiency and economy of the immune system. Inevitably, however, such a choice will have an element of bias, and our bias is toward emphasizing the cellular interactions in immune response by limiting the description of many of the underlying biochemical and molecular mechanisms to the essential facts. This book gives an insight into the role of cytokines in activating immune response during pathogenic invasion. Immunomodulation, aryl hydrocarbons, the role of the protein defensin and nucleated cells in provoking immune response, Bcl protein/gene-based apoptotic pathways, and plant-derived phytochemical-mediated immune response are all central themes of this book.

Immune-deficient Animals in Biomedical Research

Author : Jørgen Rygaard
Publisher : S. Karger AG (Switzerland)
ISBN 13 :
Total Pages : 444 pages
Book Rating : 4.3/5 (91 download)

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Book Synopsis Immune-deficient Animals in Biomedical Research by : Jørgen Rygaard

Download or read book Immune-deficient Animals in Biomedical Research written by Jørgen Rygaard and published by S. Karger AG (Switzerland). This book was released on 1987 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Inflammatory Bowel Disease Nursing Manual

Author : Andreas Sturm
Publisher : Springer
ISBN 13 : 3319750224
Total Pages : 495 pages
Book Rating : 4.3/5 (197 download)

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Book Synopsis Inflammatory Bowel Disease Nursing Manual by : Andreas Sturm

Download or read book Inflammatory Bowel Disease Nursing Manual written by Andreas Sturm and published by Springer. This book was released on 2019-01-24 with total page 495 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive manual discusses the many aspects of inflammatory bowel disease (IBD), providing relevant information along with practical guidance. The reader is also directed to additional resources for extra and current information. This book comes at a time when the number of people suffering from the two major forms of IBD, ulcerative colitis (UC) and Crohn’s disease (CD), is rising around the globe. Despite their huge impact on daily life and health economics, these diseases are not fully understood, and diagnosis and treatment remains a significant challenge. IBD nurses are increasingly recognised as key clinicians within the multidisciplinary team caring for people with IBD. Through experience and specialist knowledge IBD nurses provide timely support, advice, and treatment for people living with this unpredictable condition. IBD nurses are also well placed to liaise with the wider team, developing patient centred services which best fit their local health framework. The combined international expertise and accessible guidance here will equip nurses, or any clinician wanting to increase their competence in IBD management. Thereby this manual aims to contribute to the optimisation of IBD care throughout the world.