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(Source: Seminars in Hematology)
Source: Seminars in Hematology - September 28, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

Previous IssuesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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Source: Seminars in Hematology - September 28, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

Table of ContentsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Seminars in Hematology)
Source: Seminars in Hematology - September 28, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

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(Source: Seminars in Hematology)
Source: Seminars in Hematology - September 28, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

Iron Sequestration and Anemia of InflammationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Anemia of chronic disease, also called anemia of inflammation, is characterized by hypoferremia due to iron sequestration that eventually results in iron-restricted erythropoiesis. During the last decade, the molecular mechanisms of iron sequestration have been found to center on cytokine-stimulated overproduction of the iron-regulatory hormone hepcidin. The inflammatory cytokine interleukin-6 (IL-6) is a particularly prominent inducer of hepcidin, but other cytokines are likely to contribute as well. Hepcidin excess causes the endocytosis and proteolysis of the sole known cellular iron exporter, ferroportin, trapping iron...
Source: Seminars in Hematology - September 28, 2009 Category: Hematology Authors: Tomas Ganz, Elizabeta Nemeth Source Type: journals

Iron-Refractory Iron Deficiency AnemiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder characterized by iron deficiency anemia unresponsive to oral iron treatment but partially responsive to parenteral iron therapy. IRIDA has recently been shown to be caused by mutations in the gene TMPRSS6, which encodes a transmembrane serine protease (also known as matriptase-2) expressed by the liver. IRIDA patients show inappropriately elevated levels of hepcidin, a circulating hormone produced by the liver that inhibits both iron absorption from the intestine and iron release from macrophage stores. Recent studies suggest that TMPRSS6 nor...
Source: Seminars in Hematology - September 28, 2009 Category: Hematology Authors: Karin E. Finberg Source Type: journals

Hereditary Sideroblastic Anemias: Pathophysiology, Diagnosis, and TreatmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Inherited sideroblastic anemia comprises several rare anemias due to heterogeneous genetic lesions, all characterized by the presence of ringed sideroblasts in the bone marrow. This morphological aspect reflects abnormal mitochondrial iron utilization by the erythroid precursors. The most common X-linked sideroblastic anemia (XLSA), due to mutations of the first enzyme of the heme synthetic pathway, delta-aminolevulinic acid synthase 2 (ALAS2), has linked heme deficiency to mitochondrial iron accumulation. The identification of other genes, such as adenosine triphosphate (ATP) binding cassette B7 (ABCB7) and glutaredoxin 5...
Source: Seminars in Hematology - September 28, 2009 Category: Hematology Authors: Clara Camaschella Source Type: journals

Mutations in the Gene Encoding DMT1: Clinical Presentation and TreatmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Divalent metal transporter 1 (DMT1) is the protein that allows elemental iron entry into the duodenal cell. It is expressed ubiquitously and it also allows the iron exit from the endosomes. This protein plays a central role in iron metabolism and it is strictly regulated. Several animal models elucidate its role in physiology. Recently three patients affected with DMT1 deficiency have been described. This recessively inherited condition appears at birth with severe microcytic anemia. Serum markers could be particularly useful to establish a correct diagnosis: high serum iron, normal total iron-binding capacity (TIBC), incr...
Source: Seminars in Hematology - September 28, 2009 Category: Hematology Authors: Achille Iolascon, Luigia De Falco Source Type: journals

Animal Models of Anemia of InflammationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Anemia of inflammation (AI) is a complex multi-organ response to inflammatory disorders. Because AI can result from many infectious and non-infectious inflammatory diseases, multiple mechanisms may contribute to its pathogenesis, including iron restriction, direct erythropoietic suppression, shortened red blood cell survival, and frank hemolysis. Animal models have been helpful in the study of the mechanisms of AI and its potential treatments, but each model reflects distinct aspects of this heterogeneous syndrome. It is therefore important to study a variety of models of AI. This review focuses on the use of infectious an...
Source: Seminars in Hematology - September 28, 2009 Category: Hematology Authors: Seth Rivera, Tomas Ganz Source Type: journals

Pathogenesis and Management of Iron Deficiency Anemia: Emerging Role of Celiac Disease, Helicobacter pylori, and Autoimmune GastritisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The causes of iron deficiency vary significantly during different stages of life, and according to gender and socioeconomic circumstances. Although dietary iron is important, iron deficiency anemia (IDA) is mostly attributed to blood loss and may be the presenting clinical feature of occult bleeding from the gastrointestinal (GI) tract heralding underlying malignancy. Conventional GI diagnostic workup fails to establish the cause of iron deficiency in about one third of patients. However, abnormal iron absorption caused by hereditary iron-refractory iron deficiency anemia (IRIDA) or acquired disease is increasingly recogni...
Source: Seminars in Hematology - September 28, 2009 Category: Hematology Authors: Chaim Hershko, Barry Skikne Source Type: journals

Recycling Iron in Normal and Pathological StatesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Important advances in our understanding of iron metabolism have been made during the past 10 years, highlighting the mechanisms by which dysregulated iron homeostasis leads to hematologic, metabolic, and neurodegenerative diseases. In particular, the discovery of hepcidin and its fundamental role as the hormonal peptide regulating iron metabolism has delineated the organization of the complex network of proteins that regulates iron metabolism within the body. Maintenance of iron homeostasis is the consequence of tight coordination between iron absorption from the diet by enterocytes, and iron recycling by macrophages follo...
Source: Seminars in Hematology - September 28, 2009 Category: Hematology Authors: Carole Beaumont, Constance Delaby Source Type: journals

The New Age of Iron: Evaluation and Management of Iron-Restricted ErythropoiesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Progress in our understanding of iron metabolism over the last 10 years has been accompanied by important advances in defining the molecular mechanisms of dysregulated iron homeostasis. These advances have been relevant for a range of clinical manifestations, from states of iron deficiency to those of iron overload. (Source: Seminars in Hematology)
Source: Seminars in Hematology - September 28, 2009 Category: Hematology Authors: Lawrence T. Goodnough Source Type: journals

Previous IssuesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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Source: Seminars in Hematology - June 25, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

Forthcoming IssueEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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Source: Seminars in Hematology - June 25, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

Future IssuesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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Source: Seminars in Hematology - June 25, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

Table of ContentsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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Source: Seminars in Hematology - June 25, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

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Source: Seminars in Hematology - June 25, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

Infections in Pediatric Patients With Hematologic MalignanciesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Despite significant advances in supportive care, infection remains second only to malignancy as a cause of death in pediatric oncology patients, and infection accounts for a large fraction of treatment-related costs. Multiple risk factors contribute to infection-related morbidity, chief among them the immunosuppressive effects of leukemia itself and of cytotoxic chemotherapy, prolonged hospitalization and antibiotic use, and loss of barrier integrity associated with mucositis and the need for indwelling central access. While viruses are the most common causes of infection, bacteria are responsible for most life-threatening...
Source: Seminars in Hematology - June 25, 2009 Category: Hematology Authors: L. Charles Bailey, Anne F. Reilly, Susan R. Rheingold Source Type: journals

Management of Infections Complicating Allogeneic Hematopoietic Stem Cell TransplantationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article reviews immune suppression and recovery that occur after allogeneic stem cell transplantation, with changes in the epidemiology, and some of the recent advances that have been made in management of infectious complications. (Source: Seminars in Hematology)
Source: Seminars in Hematology - June 25, 2009 Category: Hematology Authors: John W. Hiemenz Source Type: journals

Infections in Patients With Multiple MyelomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Infectious diseases are the leading causes of death in patients with multiple myeloma (MM). Major changes have occurred in the spectrum of infections paralleling the changes in the treatment of MM. Bacteria (particularly gram-negative organisms) are the most frequent etiologic agents, and invasive fungal infections caused by molds (Aspergillus sp. and Fusarium sp.) have been increasingly reported. New infections have emerged with an increase in the intensity of the treatment of MM. Management of infections in MM patients must include recognition of the likely pathogens. Specific strategies of diagnosis, prophylaxis, and em...
Source: Seminars in Hematology - June 25, 2009 Category: Hematology Authors: Marcio Nucci, Elias Anaissie Source Type: journals

Infections in Patients With Aplastic AnemiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Infection is a major cause of death in patients with aplastic anemia (AA). There are differences between the immunocompromised state of a patient with AA and the patient who is neutropenic due to chemotherapy and this leads to a difference in the infections that they incur. Prolonged neutropenia is one of the largest risk factors for the development of infections with the invasive mycoses and bacteria. Recovery from neutropenia is directly related to survival, and supportive care plays a large role in protection while the patient is in a neutropenic state. The most common invasive mycoses include the Aspergillus species, Z...
Source: Seminars in Hematology - June 25, 2009 Category: Hematology Authors: Jessica M. Valdez, Phillip Scheinberg, Neal S. Young, Thomas J. Walsh Source Type: journals

Neutropenic Fever Syndromes in Patients Undergoing Cytotoxic Therapy for Acute Leukemia and Myelodysplastic SyndromesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fever represents the major surrogate of infection in neutropenic cancer patients. A number of neutropenic fever syndromes have been recognized, the causes and significance of which will vary depending upon the clinical context. First neutropenic fever syndromes are typically of bacterial origin, the character of which may be influenced by whether antibacterial chemoprophylaxis has been administered. Persistent neutropenic fevers are documented during the empirical systemic antibacterial therapy for the first neutropenic fever, the cause of which is likely outside the spectrum of activity of the initial therapy. Recrudescen...
Source: Seminars in Hematology - June 25, 2009 Category: Hematology Authors: E.J. Bow Source Type: journals

Recent Advances in Diagnostic MicrobiologyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The past decade has seen a surge in the development of a variety of molecular diagnostics designed to rapidly identify or characterize medically important microorganisms. We briefly review important advances in molecular microbiology, and then discuss specific assays that have been implemented in clinical microbiology laboratories throughout the country. We also discuss emerging methods and technologies that will soon be more widely used for the prompt and accurate detection of the agents of infectious diseases. (Source: Seminars in Hematology)
Source: Seminars in Hematology - June 25, 2009 Category: Hematology Authors: Lulette Tricia C. Bravo, Gary W. Procop Source Type: journals

Antiviral Therapy in Patients With Hematologic Malignancies, Transplantation, and Aplastic AnemiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Advances in supportive care over the past two decades have decreased the morbidity and mortality attributed to opportunistic infections in immunocompromised patients, including those with hematologic malignancies, hematopoietic stem cell transplantation (HSCT), and aplastic anemia. Despite advances in antiviral therapy, opportunistic viral infections such as influenza, herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) still cause significant morbidity and mortality in patients with compromised host defenses. Antiviral agents are key antimicrobials used for treatment and prophylaxis of vira...
Source: Seminars in Hematology - June 25, 2009 Category: Hematology Authors: Timothy Jancel, Scott R. Penzak Source Type: journals

Recent Advances in Antifungal Prevention and TreatmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article reviews current approaches to prevention and treatment of opportunistic fungal infections in immunocompromised patients with hematological disorders and discusses novel approaches to antifungal chemotherapy and adjunctive treatments. (Source: Seminars in Hematology)
Source: Seminars in Hematology - June 25, 2009 Category: Hematology Authors: Andreas H. Groll, Athanasios Tragiannidis Source Type: journals

Advances in Antibacterial Therapy Against Emerging Bacterial PathogensEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
During the last decade, both gram-positive and gram-negative bacteria that are resistant to most or all available antibacterial classes have become increasingly prevalent nosocomial pathogens, particularly among immunocompromised patients and those hospitalized in intensive care units. Among gram-positive bacteria, increasing concerns are posed for health care– and community-associated methicillin-resistant Staphylococcus aureus (MRSA), S aureus with reduced susceptibility to vancomycin, and vancomycin-resistant enterococci (VRE). A spectrum of newer antibacterial agents has been developed for the treatment of multi-resi...
Source: Seminars in Hematology - June 25, 2009 Category: Hematology Authors: Spyros Pournaras, Elias Iosifidis, Emmanuel Roilides Source Type: journals

Advances and Challenges in Infectious Diseases Supportive Care of Patients With Hematologic Malignancies, Hematopoietic Stem Cell Transplantation, and Severe Aplastic AnemiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Infectious diseases are important causes of morbidity and mortality in immunocompromised patients with hematological malignancies, severe aplastic anemia (SAA), and myelodysplasia. Major advances in infectious diseases supportive care have been critical to improving the outcome of patients suffering from these life-threatening diseases. Advances in diagnosis, treatment, and prevention of life-threatening infections have reduced morbidity and mortality, improved quality of life, and enabled the use of potentially curative chemotherapy, radiation, hematopoietic stem cell transplantation (HSCT), and immunosuppressive therapy ...
Source: Seminars in Hematology - June 25, 2009 Category: Hematology Authors: Thomas J. Walsh Source Type: journals

Forthcoming IssueEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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Source: Seminars in Hematology - April 1, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

Previous IssuesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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Source: Seminars in Hematology - April 1, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

Table of ContentsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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Source: Seminars in Hematology - April 1, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

MastheadEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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Source: Seminars in Hematology - April 1, 2009 Category: Hematology Tags: Frontmatter Source Type: journals

Management of Complications in Multiple MyelomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Multiple myeloma (MM) is characterized by the presence of osteolytic bone disease, renal impairment, anemia, and immune dysfunction. Adequate supportive care is considered an essential part of anti-myeloma therapy. The administration of bisphosphonates has been shown to reduce skeletal related events and hypercalcemia. Bisphosphonates are well tolerated, but preventive steps should be taken to avoid renal impairment and osteonecrosis of the jaw (ONJ). Adequate pain control is of crucial importance for the quality of life of MM patients. Local radiotherapy may rapidly ameliorate symptoms of painful MM bone lesions, and vert...
Source: Seminars in Hematology - April 1, 2009 Category: Hematology Authors: Evangelos Terpos, M. Teresa Cibeira, Joan Blade, Heinz Ludwig Source Type: journals

Emerging Treatments for Multiple Myeloma: Beyond Immunomodulatory Drugs and BortezomibEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The successful clinical development of thalidomide, bortezomib, and lenalidomide not only transformed the therapeutic management of multiple myeloma (MM) but also catalyzed a renewed interest in the development of additional classes of novel agents for this disease. This review focuses on a series of new therapeutics that have shown promising preclinical results, as well as encouraging safety profiles and early evidence of anti-MM activity in clinical studies, either alone or in combination with other, conventional or novel, anti-MM treatments. These agents include second-generation proteasome inhibitors and immunomodulato...
Source: Seminars in Hematology - April 1, 2009 Category: Hematology Authors: Constantine S. Mitsiades, Teru Hideshima, Dharminder Chauhan, Douglas W. McMillin, Steffen Klippel, Jacob P. Laubach, Nikhil C. Munshi, Kenneth C. Anderson, Paul G. Richardson Source Type: journals

Role of Allogeneic Stem Cell Transplantation in Multiple MyelomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
High-dose chemotherapy with autologous stem cell rescue has been regarded as the standard of care for young newly diagnosed myeloma patients. Moreover, the development of new agents with potent anti-tumor activity has further improved survival. However, relapse is a continuous risk primarily due to the inability of current therapies to eradicate all myeloma cells. Allografting is the only potentially curative treatment at least for a subset of multiple myeloma patients due to its well documented graft-versus-myeloma effects. Given the high transplant mortality of the high-dose myeloablative conditionings used until recentl...
Source: Seminars in Hematology - April 1, 2009 Category: Hematology Authors: Benedetto Bruno, Luisa Giaccone, Roberto Sorasio, Mario Boccadoro Source Type: journals

Treatment of Relapsed/Refractory Multiple MyelomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The introduction of several novel and active treatments and improvements in supportive care of myeloma patients has resulted in a prolongation of the survival of these patients. However, myeloma remains an incurable disease and almost all patients will relapse. Effective management of the relapsing/refractory disease incorporates several different strategies, depending on prior treatments, responses, and duration of responses, as well as residual toxicity, age, and physical condition. High-dose dexamethasone still has a role in the management of disease complications such as cytopenias, renal impairment, or spinal cord com...
Source: Seminars in Hematology - April 1, 2009 Category: Hematology Authors: Efstathios Kastritis, Antonio Palumbo, Meletios A. Dimopoulos Source Type: journals

Frontline Treatment in Elderly Patients With Multiple MyelomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Melphalan-prednisone-thalidomide (MPT) and melphalan-prednisone-bortezomib (MPV) currently appear to be the treatments of choice for a large proportion of elderly multiple myeloma (MM) patients ineligible for autologous stem cell transplantation (ASCT). It seems certain that in the near future cyclophosphamide-thalidomide-dexamethasone, with an attenuated dose of dexamethasone (CTDa), and melphalan-prednisone-lenalidomide (MPR) will also be proved superior to MP, thus providing four therapeutic options in this patient group. These options could lead to more personalized treatment approaches, based on patient comorbidities,...
Source: Seminars in Hematology - April 1, 2009 Category: Hematology Authors: Thierry Facon, Jesus San Miguel, Maria Victoria Mateos, Cyrille Hulin Source Type: journals

The Role of High-Dose Therapy With Autologous Stem Cell Support in the Era of Novel AgentsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This review discusses the initial studies concerning the role of high-dose therapy (HDT) in multiple myeloma (MM) and gives the major conclusions drawn from this “historical period.” Later, current studies using new drugs for HDT (induction, conditioning regimen, consolidation, and maintenance) are described and the promising results of this strategy reported. Finally, the issue of HDT in the era of new drug regimens is discussed, as well as the necessity of designing future trials comparing HDT and new drug regimens. (Source: Seminars in Hematology)
Source: Seminars in Hematology - April 1, 2009 Category: Hematology Authors: Michel Attal, Jean-Luc Harousseau Source Type: journals

Front-Line Treatment in Younger Patients With Multiple MyelomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The treatment of newly diagnosed myeloma has evolved rapidly. The choice of initial therapy depends on eligibility for stem cell transplantation, as well as baseline risk factors. Eligibility for transplantation is important since the choice of initial therapy is primarily melphalan-based in patients who are not candidates for transplant, while melphalan-containing regimens are avoided as induction therapy in transplant candidates. An assessment of risk based on independent prognostic markers is important mainly for prognosis but may have some value in choice of initial therapy. For example, bortezomib-based regimens may h...
Source: Seminars in Hematology - April 1, 2009 Category: Hematology Authors: S. Vincent Rajkumar, Pieter Sonneveld Source Type: journals

Staging Systems and Prognostic Factors as a Guide to Therapeutic Decisions in Multiple MyelomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Multiple myeloma (MM) patients have a highly variable disease course and survival varies from a few months to more than 10 years. Numerous prognostic factors have been identified, including age, performance status (PS), serum albumin, β2-microglobulin (β2M), lactate dehydrogenase (LDH), renal function, genetic factors, and serum free light chains (sFLCs) or their ratio (sFLCR). Several models have been built to separate patients into various risk groups with different outcomes. Staging systems need to be simple, accurate, and readily available in order to effectively guide treatment decisions now that effective treatment...
Source: Seminars in Hematology - April 1, 2009 Category: Hematology Authors: Marie-Christine Kyrtsonis, Dimitrios Maltezas, Tatiana Tzenou, Efstathios Koulieris, Arthur R. Bradwell Source Type: journals

Multiple Myeloma in the Era of Novel AgentsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Multiple myeloma (MM) remains an incurable plasma cell disorder, though progress in the understanding of its pathogenesis has identified mechanisms that have recently become targets of new agents with potent anti-myeloma activity such as immunomodulatory drugs (IMiDs) and proteasome inhibitors. These agents have led to a substantial improvement in the management of patients with MM and have increased their overall survival (OS). However, several questions remain unanswered: What is the best first-line regimen for myeloma patients? What is the best combination for relapsed/refractory disease? What is the role of autologous ...
Source: Seminars in Hematology - April 1, 2009 Category: Hematology Authors: Meletios A. Dimopoulos, Michel Attal Source Type: journals