This volume, in discussing resistance to ibritumomab, will focus on the mechanism, hematological aspects, radiological and nuclear medicine aspects, and medical physics that deal with radiation dosimetry, and will outline future prospects for overcoming resistance and enhancing efficacy of ibritumomab.

Until recently, endocrinology and critical care medicine were two specialties in medicine that were rather uncomfortable with each other and hence quite i- lated. Fortunately, these two 'alien' disciplines have joined forces in successful attempts to perform high quality research in order to clarify the unknown. By integrating endocrinology in critical care medicine, or vice-versa depending on the specialty of the observer, new experimental and clinical data on the complex endocrine and metabolic derangements accompanying non-endocrine severe i- nesses came available which generated important novel insights with relevant clinical implications. In addition, the state of the art diagnosis and management of primary endocrine diseases that represent life-threatening situations leading to ICU admission has been updated. This issue of Contemporary Endocrinology aims at compiling the new ?ndings. The book indeed covers both areas of 'Acute Endocrinology' that are often taking care of at very distant sites within hospitals. The ?rst part deals with the classical life-threatening illnesses caused by primary endocrine diseases such as thyrotoxicosis, hypothyroidism, acute adrenal crisis, acute calcium disorders, pheochromocytoma, severe hyper- and hypoglycemia . The second part looks at endocrinology from the ICU side, starting with a g- eral overview of the dynamic neuroendocrine and metabolic stress responses in the condition of intensive care-dependent, non-endocrine critical illness.

Information gathered from cell-free systems, cell cultures, animal models, and human studies, together provide important insights to our understanding of hormonal cancer causation, development, and prevention; the primary objective of these Symposia. A special emphasis is placed on the two major endocrine-related cancers, that is, breast and prostate. The emerging fields of colon, lung, and pancreatic cancers in relation to hormones are examined.

Scientific interest in regulatory T cells has revived during the last decade. Initially described in the early seventies as suppressor T cells, the concept of suppressor/regulatory T cells went through turbulent times during the eighties when molecular analysis failed to identify putative suppressor genes. The constructive and elegant cellular experiments on regulatory T cells during the nineties, initiated by Shimon Sakaguchi and co-workers, however have brought these cells back into the limelight. Nowadays, regulatory T cells are regarded as essential components of the immune system, and several different subsets of regulatory T cells have been described. Considerable regulatory function has been attributed to the CD4+CD25+ T cell subset. These cells act by suppressing adaptive and possibly also innate immune responses thereby maintaining or restoring the balance between immunity and tolerance. The suppressive effects of CD4+CD25+ regulatory T cells are cell-contact dependent but a role for soluble factors, particularly in vivo, has been suggested as well.
The aim of this book is to bring together recent developments and viewpoints in the field of CD4+CD25+ regulatory T cells and to discuss the potential use of regulatory T cells in immunotherapy of inflammatory diseases. By linking data on regulatory T cells from experimental models with recent findings from the clinic, this topical book will be of interest to immunologists and other biomedical researchers as well as clinicians that are interested in regulation and manipulation of the immune response during (chronic) inflammatory disease.

Breast and prostate cancers are both hormone-dependent, at least in some stages of their progression. Hormonal manipulation represents an important therapeutic approach. Although most of breast and prostate cancers initially respond to hormone therapy, most tumors reinitiate to growth. Finally, hormone-resistant and metastatic breast and prostate cancers may develop. Thus, the challenge is the dissection of mechanisms by which steroid receptor signaling pathways continue to influence cell growth and invasiveness. Compelling evidence indicates that steroid hormones elicit non-genomic responses in extra-nuclear compartment of target cells. In this cellular location, steroid-coupled receptors rapidly recruit signaling effectors or scaffold proteins and activate multiple pathways leading to proliferation, survival, migration and invasiveness. The immediate challenge is the dissection of key events regulating the steroid response of target tissues to prevent progression and improve treatment of breast and prostate cancers.

This volume of Progress in Molecular Biology and Translational Science focuses on the growth hormone in health and disease.

Most endocrine diseases can be treated successfully, and the patient's state of well-being can usually be improved. Not surprisingly, the earlier the diagnosis is made the more positive the clinical response. Early Diagnosis and Treatment ( f Endocrine Disorders focuses on early signs and symptoms of endocrine disorders and surveys the appropriate tests to document the diseases as well as current recommendations for therapy. Each chapterreviews the pathophysiology of the endocrine disease-important for understanding each disorder as well as the rationale for early therapy-and the basis for the early recognition and treatment of each condition. Although the practicing endocrinologist is likely to be quite knowledgeable regarding many of these diseases, Early Diagnosis and Treatment of Endocrine Disorders includes treatment of those conditions only recently classified as endocrine disorders, such as polycystic ovarian syndrome, obesity, and hypogonadism. The book also provides new approaches that are urgently needed to slow the epidemic of type 2 diabetes, which should be an overriding concern for all clinicians. Until now, no other endocrinology text has focused primarily on the details of early recognition and therapy of endocrine disorders. The information in Early Diagnosis and Treatment of Endocrine Disorders is presented in an orderly and easy-to-follow manner, which should greatly facilitate the early recognition of endocrine diseases by medical students, house staff, primary care physicians, and endocrinologists, the four groups of clinical personnel to which this book is specificall y directed.

Myelodysplastic syndromes are to the bone marrow what pneumonia is to the lungs; the response of an organ to a variety of etiologic insults like aging, toxic exposure, infections and auto-immunity. Among infectious causes alone, pneumonia could be the result of a variety of possible pathogens including bacterial, viral, tuberculous or fungal agents. Similarly, MDS cannot be treated as a single disease. Attempts to harness the inherent complexity of MDS by devising classifications' which group the various syndromes as one disease is as misguided as saying that a pneumonia is not infectious because it did not respond to antibiotics. Progress in the field will occur faster when we re-analyze this premise. Therefore, until a clearer picture of the disease emerges it is best to treat each of the MDS syndromes as a separate entity. Having no classification is better than a misleading one. Cancer research has been notable for its periodic cycles of promise and hope, followed by defeat and disappointments. It is not that there is no solution, but that the problem has not been identified precisely. This book is our attempt to define the most crucial questions related to MDS that need to be addressed immediately through logic, analysis and rigorous experimentation. If the emerging problems appear daunting, then instead of being overwhelmed by them, we should follow the advice of the great 20th century thinker Antonio Gramsci, pessimism of the intellect must be faced with the optimism of will'.

Although phosphorylation of proteins on tyrosine is relatively rare compared to phosphorylation on serine or threonine residues, the past two decades of research into PTP function have led to a great appreciation of the critical role PTPs have in regulating basic cellular processes. Among these important roles is the regulation of cellular signaling pathways related to metabolism. This volume contains chapters which highlight many aspects of PTP function in the context of metabolism. Given the growing obesity and diabetes epidemics in the United States and throughout the world, the desire to identify possible therapeutic targets for treatment of these diseases is a high priority. In many ways, PTPs may be attractive drug targets since they are amenable to targeting with small molecules; however many challenges abound in making PTP inhibitors.

The study of the effects of gonadal hormones in the brain focussed mainly on reproductive actions for a long time. Meanwhile, however, it is well known that gonadal hormones, in particular estrogens, also have neuroprotective and psychoprotective properties. They modulate many brain functions such as cognitive functions, pain regulation, motor coordination, and epilepsy, as well as affective and psychotic disorders, to name just a few. In fact, during the past few years we have experienced a major change in our understanding of the endocrinologic aspects of psychiatric disorders. Endocrinologic irregularities in psychiatric patients are no longer viewed as pure epiphenomena but rather discussed as part of the pathomechanism of the disorders. How exactly estrogens affect various disorders is a fascinating and intriguing aspect of this emerging field of non-reproductive brain actions of gonadal hormones. Among the estrogens, especially estradiol appears to play an important and multimodal role in the brain. Which of estradiol s many membrane, intracellular, and genomic actions matters most in psychiatric disorders, remains to be discovered. The aim of this volume is to summarize the role estrogens play in major psychiatric disorders, such as schizophrenia, depression, and dementia, and to provide a state-of-the-art overview of current knowledge, but also of questions that are still open. It is intended to be a resource for clinicians and readers who are interested in contemporary research developments in this field.

The book aims to review knowledge on the disorders of eating behaviour and body composition in some of the non-primate higher animals and to relate these to similar conditions in humans. With advances in understanding the nature of these disorders and their biological basis, it seems timely to assess what cross-species comparisons can tell us about the general underlying factors at work. This may also help to delineate what may be a general biological basis that humans share with their higher animal comrade species and what may distinguish human from non-human, particularly in a cultural context. This could help in combating better the problems of these conditions in the animal species as well as in man and in suggesting well-based preventive measures. As far as people are concerned the last two decades of the 20th century have shown a significant increase in obesity in the richer countries, particularly the USA (Table 1). Possibly associated with the obesity boom, there is an increasing awareness of other disorders of eating behaviour and body composition. These range from anorexia nervosa, at the other end of body composition to obesity, to others, such as bulimia, with more variable effects on body composition.

Since the first description of Philadelphia chromosome-negative chronic myeloproliferative disorders more than 100 years ago, the diagnosis and therapy of these conditions have been based primarily on clinical experience and judgement. Until recently very little was known about the molecular basis of these diseases. In order to spark research in this area basic scientists and clinicians from various parts of the world have contributed to this volume, the first of its kind to put together the current knowledge. The book deals with the new WHO classification of these disorders, novel aspects of diagnostic pathology, the search for disease-relevant genes utilizing molecular biology and proteomic techniques, the description of the roles of PVR-1 and VHL genes for polycythemias and the discovery of the gene mutation responsible for the idiopathic hypereosinophilic syndrome. A chapter on anagrelide, an important novel drug for the treatment of primary thrombocythemia, is included.

In mammals, a robust physiologic system acts to maintain relative constancy of weight. A key element of this system is leptin. The nature of this "brain-somatic" cross talk is as yet poorly understood, but it is likely to have important implications for the pathophysiology and treatment of obesity, diabetes and other metabolic disorders.  

Amenorrhea: A Case-Based Clinical Guide is a comprehensive review of the current knowledge regarding normal female reproductive physiology. Replete with interesting case vignettes and providing diagnostic algorithms and therapeutic strategies for amenorrhea, Amenorrhea: A Case-Based Clinical Guide is divided into three sections. The first section is composed of two chapters that provide a thorough review of basic science and clinical knowledge about the organ systems responsible for normal physiology of the menstrual cycle. The second section includes discussion about menstrual cycle disruption as it relates to hypothalamic-pituitary dysfunction, surgical and natural menopause, genetic defects, premature ovarian failure/insufficiency and the effects of caloric excess and restriction. The third section offers an update on the physiological effects of prolonged amenorrhea induced surgically or by hypothalamic dysfunction and also includes an original chapter that focuses solely on the impact of race and ethnicity on the prevalence and diagnosis of amenorrhea. Amenorrhea: A Case-Based Clinical Guide brings together chapters from renowned experts who offer state-of-the-art, clinically useful information in a case-based, reader-friendly fashion. This title will be a welcome addition to the bookshelves of all clinicians who practice in women's health settings.

This book reports the text of the lectures of the 6th International Conference on Sodium Calcium Exchange held in Lacco Ameno in the Island of Ischia in the Gulf of Naples, Italy, from October 1 to October 5, 2011. The present book uncovers the most striking new findings on NCX that emerged since the previous Conference on Sodium Calcium Exchange, such as the structural dissection of the molecular determinants of Ca2+ sensitivity of the exchanger, the epigenetic regulation of ncx1 gene, the molecular identification of the mitochondrial Sodium Calcium Exchanger, and the discovery of NCX in unexpected anatomical locations such as the female reproductive tract. The book is organized into 11 parts covering NCX structural aspects, genetic and epigenetic regulation, regulatory mechanisms, subcellular localization in mitochondria, involvement in neurodegenerative diseases and in immune regulation, and the role of the cardiovascular and endocrine systems, as well as diabetes in physiology and pathophysiology. Selected chapters of the book are also devoted to the interaction of NCKX and other ion channels and transporters with NCX, like ASICs, TRPM, and NHE.

Thyroid problems affect an estimated one in three of the adult population, yet they are difficult to diagnose on the basis of blood tests and often go undiagnosed for many year. This is the second, greatly updated and revised, edition of Dr Durrant-Peatfield's practical guide to recognizing the signs and symptoms of thyroid disease and to treating the problem with diet and natural supplements, in conjunction with modern western drugs and surgery when really necessary.

From the perspective of the investigator, Graves' disease is a fascinating disorder with unique features and opportunities for study. The discovery in 1956 that Graves' disease was caused by a humoral factor, later shown to be an antibody to the TSH receptor, was a triumph for modern investigative medicine. Rapid progress is now being made in (i) understanding the molecular interaction between autoantibodies and the TSH receptor, (ii) identifying the genes that contribute to the predisposition to disease, (iii) developing an animal model of Graves' disease, and (iv) identifying the long-sought orbital antigen in ophthalmopathy. From the clinical standpoint, although Graves' disease is eminently treatable, there is no definitive cure. None of the therapeutic options are ideal. It is hoped that rapid progress in understanding the pathogenesis of the disease will lead to the ultimate goal of some form of immunotherapy that will make antithyroid drugs, radioiodine and thyroidectomy obsolete. The chapters in Graves' Disease: Pathogenesis and Treatment represent the viewpoints of many prominent clinicians and investigators working in the field. The editors are grateful for their contributions which cover an unusually comprehensive compendium of subjects relating to the disease.

Based on the most novel approaches and cutting-edge clinical and scientific information regarding radionuclide imaging and therapies for neuroendocrine tumors, this clinical guidebook represents a unique collaborative effort between endocrinologists, nuclear physicians, oncologists, surgeons, physicists, radio-pharmacists and geneticists. It begins with the embryology, classification and molecular genetics of gastroenteropancreatic neuroendocrine tumors and carcinoids, chromaffin cell tumors, and MEN1- and MEN2-related tumors. Following a chapter on radiopharmaceuticals in neuroendocrine imaging, it turns to the physics and technology of current and cutting-edge radiology, including SPECT/CT and PET/CT and PET/MR. Discussing of radionuclide imaging covers the tumors mentioned above, as well as pulmonary and thymic neuroendocrine tumors and medullary thyroid carcinoma. A presentation of radionuclide therapies follows, including 131I-MIBG therapy, somatostatin receptor-based therapy, and alpha radionuclide therapy, as well as the role of nanoparticles. Comprehensive and up-to-date, Diagnostic and Therapeutic Nuclear Medicine for Neuroendocrine Tumors will assist and guide physicians who encounter patients with these conditions, either from a diagnostic or therapeutic standpoint, and particularly emphasizes the current and emerging medical devices and imaging and therapeutic options.