NEJM â Collection Updates for Hematology

CORRESPONDENCE: Transfusion of RhD-Positive Blood in âAsia Typeâ DEL Recipients

Chao-Peng Shao, M.D. — Thu, 04Â FebÂ 2010 00:00:00 -05:00

To the Editor: The RhD status of transfusion recipients and donors is routinely matched for red-cell transfusion. This worldwide practice is due to the potent immunogenicity of RhD. In East...

CLINICAL PROBLEM-SOLVING: Under Pressure

Thu, 04Â FebÂ 2010 00:00:00 -05:00

A 25-year-old woman presented to her local hospital with dyspnea. She described a 2-year history of progressive shortness of breath on exertion. One year earlier she was able to walk...

IMAGES IN CLINICAL MEDICINE: Extramedullary Hematopoiesis Associated with Î²-Thalassemia

Edward Smitaman, M.D. and Ami N. Rubinowitz, M.D. — Thu, 21Â JanÂ 2010 00:00:00 -05:00

A 47-year-old woman of Italian descent with a history of transfusion-dependent Î²-thalassemia intermedia presented to the emergency department with dyspnea that had worsened during the previous several days. The physical...

PERSPECTIVE: Erythropoiesis-Stimulating Agents â Time for a Reevaluation

Thu, 21Â JanÂ 2010 00:00:00 -05:00

Epoetin alfa was approved in 1989 by the Food and Drug Administration (FDA) for the treatment of anemia associated with chronic kidney disease âto elevate or maintain the red blood...

CLINICAL PROBLEM-SOLVING: Painful Purple Toes

Thu, 07Â JanÂ 2010 00:00:00 -05:00

A 57-year-old man presented to the emergency department with painful purple toes. On the day of presentation, he had first been seen in another hospital but left against medical advice...

CLINICAL THERAPEUTICS: Activated Protein C for Sepsis

Susanne Toussaint, M.D., M.A., and Herwig Gerlach, M.D., Ph.D. — Thu, 31Â DecÂ 2009 00:00:00 -05:00

A 55-year-old man is brought to the emergency department with abdominal pain, fever (temperature, 102.9Â°F), and dyspnea. His medical history includes an appendectomy 8 years earlier. Abdominal radiography shows free...

INTERACTIVE MEDICAL CASE: Painful Purple Toes

Thu, 17Â DecÂ 2009 00:00:00 -05:00

A 57-year-old man presented to the emergency department with painful purple toes. He had first noted pain and discoloration in his left great toe 2 weeks earlier. One week before...

EDITORIAL: Anemia and Iron Deficiency â New Therapeutic Targets in Heart Failure?

G. William Dec, M.D. — Thu, 17Â DecÂ 2009 00:00:00 -05:00

Anemia ranges in prevalence from below 10% among patients with mild heart failure symptoms to over 40% for patients with advanced disease.1 Its prevalence is similar among patients who have...

ORIGINAL ARTICLE: Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency

Thu, 17Â DecÂ 2009 00:00:00 -05:00

Background: Iron deficiency may impair aerobic performance. This study aimed to determine whether treatment with intravenous iron (ferric carboxymaltose) would improve symptoms in patients who had heart failure, reduced left...

EDITORIAL: Cangrelor â A Champion Lost in Translation?

Adnan Kastrati, M.D., and Gjin Ndrepepa, M.D. — Thu, 10Â DecÂ 2009 00:00:00 -05:00

Current guidelines recommend the early use of drugs that block platelet adenosine diphosphate (ADP) receptor P2Y12 in patients with acute coronary syndromes in whom percutaneous coronary intervention (PCI) may be...

EDITORIAL: Hematopoietic Stem-Cell Transplantation for Adults with Sickle Cell Disease

Miguel R. Abboud, M.D. — Thu, 10Â DecÂ 2009 00:00:00 -05:00

Sickle cell disease is an inherited hemoglobinopathy that affects over 70,000 persons in the United States. Sickle hemoglobin (hemoglobin S) polymerizes under conditions of hypoxemia and acidosis, thereby perturbing the...

ORIGINAL ARTICLE: Intravenous Platelet Blockade with Cangrelor during PCI

Thu, 10Â DecÂ 2009 00:00:00 -05:00

Background: Intravenous cangrelor, a rapid-acting, reversible adenosine diphosphate (ADP) receptor antagonist, might reduce ischemic events during percutaneous coronary intervention (PCI).

Methods: In this double-blind, placebo-controlled study, we randomly assigned 5362 patients...

ORIGINAL ARTICLE: Platelet Inhibition with Cangrelor in Patients Undergoing PCI

Thu, 10Â DecÂ 2009 00:00:00 -05:00

Background: Cangrelor, a nonthienopyridine adenosine triphosphate analogue, is an intravenous blocker of the adenosine diphosphate receptor P2Y12. This agent might have a role in the treatment of patients who require...

ORIGINAL ARTICLE: Allogeneic Hematopoietic Stem-Cell Transplantation for Sickle Cell Disease

Thu, 10Â DecÂ 2009 00:00:00 -05:00

Background: Myeloablative allogeneic hematopoietic stem-cell transplantation is curative in children with sickle cell disease, but in adults the procedure is unduly toxic. Graft rejection and graft-versus-host disease (GVHD) are additional...

EDITORIAL: Treatment of Anemia in Chronic Kidney Disease â Strategies Based on Evidence

Philip A. Marsden, M.D. — Thu, 19Â NovÂ 2009 00:00:00 -05:00

Anemia associated with chronic kidney disease and end-stage renal disease is due, in large part, to reduced production of renal erythropoietin and abnormalities in extracellular-fluid volume homeostasis.1 Moreover, anemia and...

ORIGINAL ARTICLE: A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease

Thu, 19Â NovÂ 2009 00:00:00 -05:00

Background: Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: The Microcytic Red Cell and the Anemia of Inflammation

SiobÃ¡n B. Keel, M.D., and Janis L. Abkowitz, M.D. — Thu, 05Â NovÂ 2009 00:00:00 -05:00

When evaluating a patient with anemia in whom inflammation is present, the physician typically observes the mean corpuscular volume and then requests biochemical analyses to determine the serum iron and...

EDITORIAL: End Run around Epo

H. Franklin Bunn, M.D. — Thu, 05Â NovÂ 2009 00:00:00 -05:00

Recombinant human erythropoietin is arguably the most successful therapeutic application of recombinant DNA technology to date. Since the initial reports â which appeared 22 and 23 years ago12 â documented...

CLINICAL PROBLEM-SOLVING: A Bloody Mystery

Thu, 05Â NovÂ 2009 00:00:00 -05:00

A 62-year-old woman presented to the urgent care clinic with gingival bleeding after periodontal scaling of her lower-right second molar. She had undergone the procedure 5 hours before arriving at...

REVIEW ARTICLE: Myelodysplastic Syndromes

Ayalew Tefferi, M.D., and James W. Vardiman, M.D. — Thu, 05Â NovÂ 2009 00:00:00 -05:00

According to the 2008 World Health Organization (WHO) classification system for hematologic cancers, the primary myelodysplastic syndromes are one of five major categories of myeloid neoplasms (Table 1).1 The main...

ORIGINAL ARTICLE: A Peptide-Based Erythropoietin-Receptor Agonist for Pure Red-Cell Aplasia

Thu, 05Â NovÂ 2009 00:00:00 -05:00

Background: We investigated whether a novel, synthetic, peptide-based erythropoietin-receptor agonist (Hematide, Affymax) can stimulate erythropoiesis in patients with anemia that is caused by antierythropoietin antibodies.

Methods: In this open-label, single-group trial,...

REVIEW ARTICLE: Atypical HemolyticâUremic Syndrome

Marina Noris, Ph.D., and Giuseppe Remuzzi, M.D. — Thu, 22Â OctÂ 2009 00:00:00 -05:00

The hemolyticâuremic syndrome is characterized by nonimmune hemolytic anemia, thrombocytopenia, and renal impairment.1 The disorder occurs most frequently in children under the age of 5 years, with an annual incidence...

ORIGINAL ARTICLE: X-Linked Thrombophilia with a Mutant Factor IX (Factor IX Padua)

Thu, 22Â OctÂ 2009 00:00:00 -05:00

We report a case of juvenile thrombophilia associated with a substitution of leucine for arginine at position 338 (R338L) in the factor IX gene (factor IXâR338L). The level of the...

INTERACTIVE MEDICAL CASE: A Bloody Mystery

Thu, 15Â OctÂ 2009 00:00:00 -05:00

A 62-year-old woman presented to the urgent care clinic with gingival bleeding after periodontal scaling of her lower right second molar. She had undergone the procedure 5 hours before presentation,...

REVIEW ARTICLE: Cell Death

Thu, 15Â OctÂ 2009 00:00:00 -05:00

All multicellular organisms require apoptosis, the controlled death of cells. Without apoptosis, 2 tons of bone marrow and lymph nodes and a 16-km intestine would probably accumulate in a human...

VIDEOS IN CLINICAL MEDICINE: Bone Marrow Aspiration and Biopsy

Thu, 08Â OctÂ 2009 00:00:00 -05:00

...

CLINICAL PROBLEM-SOLVING: The Writing on the Wall

Thu, 01Â OctÂ 2009 00:00:00 -05:00

A 52-year-old man presented to the emergency department with abdominal discomfort. His symptoms began 5 weeks earlier, when nonradiating discomfort developed in the epigastric region. The pain worsened after eating...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 28-2009 â A 68-Year-Old Man with Fatigue, Cough, and Peripheral-Blood Monocytosis

Thu, 10Â SepÂ 2009 00:00:00 -05:00

Dr. Alfred Ian Lee (Oncology): A 68-year-old man was seen in the cancer center of this hospital because of fatigue, cough, and peripheral-blood monocytosis.

The patient had been well until approximately...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Platelets, Pyrexia, and Plasmodia

Doron C. Greenbaum, Ph.D., and Garret A. FitzGerald, M.D. — Thu, 30Â JulÂ 2009 00:00:00 -05:00

Platelets have long been known to interact cooperatively with erythrocytes in thrombogenesis, both generally and in patients with sickle cell disease.1 Recently, the molecular mechanisms by which neutrophils can bridge...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 23-2009 â A 13-Year-Old Boy with Headache, Nausea, Seizures, and Hypertension

Thu, 23Â JulÂ 2009 00:00:00 -05:00

A 13-year-old boy was admitted to the hospital because of headache, nausea, seizures, renal failure, and hypertension.

The patient had been well until approximately 3 weeks earlier, when intermittent left-sided headaches...

ORIGINAL ARTICLE: Thrombomodulin Mutations in Atypical HemolyticâUremic Syndrome

Thu, 23Â JulÂ 2009 00:00:00 -05:00

Background: The hemolyticâuremic syndrome consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. The common form of the syndrome is triggered by infection with Shiga toxinâproducing bacteria...

BOOK REVIEW:

Thu, 16Â JulÂ 2009 00:00:00 -05:00

Research on umbilical-cord blood has revolutionized the field of hematopoietic stem-cell transplantation, and umbilical-cord blood is now used in about 28% of all bone marrow and stem-cell transplants from unrelated...

CLINICAL THERAPEUTICS: Autologous Hematopoietic Stem-Cell Transplantation for Multiple Myeloma

Jean-Luc Harousseau, M.D., and Philippe Moreau, M.D. — Thu, 18Â JunÂ 2009 00:00:00 -05:00

A previously healthy 59-year-old man presents with persistent pain in his lower back and fatigue. A complete blood count reveals a hemoglobin level of 9.8 g per deciliter. A monoclonal...

IMAGES IN CLINICAL MEDICINE: Tongue Necrosis in a Patient with Essential Thrombocytosis

Alejandro Fernandez-Casado, M.D. and Blanca Sanchez-Gonzalez, Ph.D. — Thu, 28Â MayÂ 2009 00:00:00 -05:00

A 69-year-old woman with complete atrioventricular block was admitted for implantation of a pacemaker. Her medical history included multiple sclerosis with tetraparesis. She had been taking acenocoumarol for the previous...

EDITORIAL: A Common Genetic Mechanism in Malignant Bone Marrow Diseases

Ross L. Levine, M.D., and Martin Carroll, M.D. — Thu, 28Â MayÂ 2009 00:00:00 -05:00

The myelodysplastic syndromes, myeloproliferative disorders, and acute myeloid leukemia (AML) are seemingly unrelated diseases except for their origin in hematopoietic precursor cells in bone marrow. A principal feature of the...

ORIGINAL ARTICLE: Mutation in in Myeloid Cancers

Thu, 28Â MayÂ 2009 00:00:00 -05:00

Background: The myelodysplastic syndromes and myeloproliferative disorders are associated with deregulated production of myeloid cells. The mechanisms underlying these disorders are not well defined.

Methods: We conducted a combination of molecular,...

CORRESPONDENCE: Bevacizumab in Hereditary Hemorrhagic Telangiectasia

Prithviraj Bose, M.D., Jennifer L. Holter, M.D., and George B. Selby, M.D. — Thu, 14Â MayÂ 2009 00:00:00 -05:00

To the Editor: Hereditary hemorrhagic telangiectasia (HHT) (also known as the OslerâWeberâRendu syndrome) is an inherited vascular dysplasia whose main features are mucocutaneous telangiectasias, epistaxis, gastrointestinal bleeding, and iron-deficiency anemia.1...

CLINICAL PROBLEM-SOLVING: A Red Flag

Thu, 07Â MayÂ 2009 00:00:00 -05:00

A 64-year-old man was brought to the emergency department because of sudden-onset blurred vision in both eyes and diplopia, as well as a frontal headache that had begun earlier that...

ORIGINAL ARTICLE: Inhibitors of Factor VIII in Black Patients with Hemophilia

Thu, 16Â AprÂ 2009 00:00:00 -05:00

Background: Black patients with hemophilia A (factor VIII deficiency) are twice as likely as white patients to produce inhibitors against factor VIII proteins given as replacement therapy. There are six...

CLINICAL PRACTICE: Epistaxis

Rodney J. Schlosser, M.D. — Thu, 19Â FebÂ 2009 00:00:00 -05:00

A 61-year-old man presents to the emergency room with left-sided epistaxis that has continued for 1 hour. He estimates having lost approximately 1/2 cup of blood and reports no history...

IMAGES IN CLINICAL MEDICINE: Leukocytosis and Sublingual Microvascular Blood Flow

Arend-Jan Meinders, M.D. and Paul Elbers, M.D. — Thu, 12Â FebÂ 2009 00:00:00 -05:00

A 51-year-old woman presented with a 3-month history of fatigue and a 2-week history of a nonproductive cough and night sweats. Chronic myeloid leukemia was diagnosed, with a leukocyte count...

BOOK REVIEW:

Thu, 12Â FebÂ 2009 00:00:00 -05:00

Since it was first recognized that hepatitis B virus and HIV can be transmitted from donors to recipients by transfusion, physicians and the public alike have been focused on the...

CORRESPONDENCE: An Unusual Outbreak of Hypoglycemia

Thu, 12Â FebÂ 2009 00:00:00 -05:00

To the Editor: The off-label use of drugs for the enhancement of sexual performance in persons without erectile dysfunction is a phenomenon that is increasingly recognized.1 These drugs are available...

EDITORIAL: Not an HIV Cure, but Encouraging New Directions

Jay A. Levy, M.D. — Thu, 12Â FebÂ 2009 00:00:00 -05:00

The history of infectious diseases frequently includes people who were resistant to a pathogen. Such a phenomenon helped the Spanish, who had resistance to smallpox, in their conquest of South...

ORIGINAL ARTICLE: Long-Term Control of HIV by Delta32/Delta32 Stem-Cell Transplantation

Thu, 12Â FebÂ 2009 00:00:00 -05:00

Infection with the human immunodeficiency virus type 1 (HIV-1) requires the presence of a CD4 receptor and a chemokine receptor, principally chemokine receptor 5 (CCR5). Homozygosity for a 32-bp deletion...

IMAGES IN CLINICAL MEDICINE: A Smooth, Shiny Tongue

Hyo Jin Lee, M.D. and Deog Yeon Jo, M.D. — Thu, 05Â FebÂ 2009 00:00:00 -05:00

A 77-year-old woman presented with an insidious onset of fatigue and a burning sensation of the tongue on swallowing food. Six years earlier, she had undergone a total gastrectomy for...

CORRESPONDENCE: Eculizumab for Congenital Atypical HemolyticâUremic Syndrome

Ralph A. Gruppo, M.D. and Russell P. Rother, Ph.D. — Thu, 29Â JanÂ 2009 00:00:00 -05:00

To the Editor: Atypical hemolyticâuremic syndrome of infancy is a rare disorder that is associated with thrombotic microangiopathy and acute renal failure. It often involves complement dysregulation.12 Plasma infusions have...

CORRESPONDENCE: Eculizumab for Atypical HemolyticâUremic Syndrome

Thu, 29Â JanÂ 2009 00:00:00 -05:00

To the Editor: Atypical hemolyticâuremic syndrome is a disease of uncontrolled complement activation associated with a high mortality rate, and most cases progress to end-stage renal disease.1 About 50% of...

ORIGINAL ARTICLE: Arterial Blood Gases and Oxygen Content in Climbers on Mount Everest

Thu, 08Â JanÂ 2009 00:00:00 -05:00

Background: The level of environmental hypobaric hypoxia that affects climbers at the summit of Mount Everest (8848 m [29,029 ft]) is close to the limit of tolerance by humans. We...

ORIGINAL ARTICLE: A Syndrome with Congenital Neutropenia and Mutations in

Thu, 01Â JanÂ 2009 00:00:00 -05:00

Background: The main features of severe congenital neutropenia are the onset of severe bacterial infections early in life, a paucity of mature neutrophils, and an increased risk of leukemia. In...

PERSPECTIVE: The Many Causes of Severe Congenital Neutropenia

Thu, 01Â JanÂ 2009 00:00:00 -05:00

In 1956, Rolf Kostmann, a Swedish pediatrician, described an autosomal recessive disorder that he called infantile genetic agranulocytosis â which is now called severe congenital neutropenia. The Kostmann form of...

CORRESPONDENCE: Prothrombin Time for Detection of Contaminated Heparins

Susanne Alban, Ph.D. and Susanne LÃ¼hn, Pharm.D. — Thu, 18Â DecÂ 2008 00:00:00 -05:00

To the Editor: The recent âheparin scandalâ resulted from the use of contaminated heparin that caused serious adverse events including death.1 The contaminant was identified as synthetically oversulfated chondroitin sulfate...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 39-2008 â A 51-Year-Old Woman with Splenomegaly and Anemia

Jeremy S. Abramson, M.D., Manjil Chatterji, M.D., Aliyah Rahemtullah, M.D. — Thu, 18Â DecÂ 2008 00:00:00 -05:00

Dr. Jeffrey A. Barnes (HematologyâOncology): A 51-year-old woman was admitted to this hospital because of anemia and splenomegaly. The patient was in her usual state of health until approximately 2...

ORIGINAL ARTICLE: Mutation and Congenital Erythrocytosis with Paraganglioma

Thu, 18Â DecÂ 2008 00:00:00 -05:00

Prolyl hydroxylase domain (PHD) proteins play a major role in regulating the hypoxia-inducible factor (HIF) that induces expression of genes involved in angiogenesis, erythropoiesis, and cell metabolism, proliferation, and survival....

ORIGINAL ARTICLE: Outbreak of Adverse Reactions Associated with Contaminated Heparin

Thu, 18Â DecÂ 2008 00:00:00 -05:00

Background: In January 2008, the Centers for Disease Control and Prevention began a nationwide investigation of severe adverse reactions that were first detected in a single hemodialysis facility. Preliminary findings...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 38-2008 â A 58-Year-Old Man with Hemophilia, Hepatocellular Carcinoma, and Intractable Bleeding

Thu, 11Â DecÂ 2008 00:00:00 -05:00

Dr. Abner Louissaint (Pathology): A 58-year-old man with hemophilia was admitted to this hospital because of hepatitis C infection, hepatocellular carcinoma, and recurrent bleeding.

A diagnosis of hemophilia A (factor VIII...

CORRESPONDENCE: Osteosarcoma Derived from Donor Stem Cells Carrying the Norrie's Disease Gene

Thu, 04Â DecÂ 2008 00:00:00 -05:00

To the Editor: There have been few reports of osteosarcoma after allogeneic bone marrow transplantation.1 We report the development of osteosarcoma in a recipient 17 years after stem-cell transplantation.

A 23-month-old...

REVIEW ARTICLE: Pulmonary Complications of Sickle Cell Disease

Mark T. Gladwin, M.D., and Elliott Vichinsky, M.D. — Thu, 20Â NovÂ 2008 00:00:00 -05:00

The inheritance of two copies of a mutant Î²-globin gene, one from each parent, is the underlying cause of sickle cell disease. The mutation, GAGâGTG, substitutes valine for glutamic acid...

IMAGES IN CLINICAL MEDICINE: A Medical Mystery â A 71-Year-Old Man with Pancytopenia

Julia M. Braza, M.D. and Parul Bhargava, M.D. — Thu, 30Â OctÂ 2008 00:00:00 -05:00

A 71-year-old-man presented to the emergency department with dizziness, progressive lethargy, and confusion, which he reported having had for the past 10 days. A complete blood count showed pancytopenia. A...

EDITORIAL: Polymorphisms and the Risk of Invasive Fungal Infections

Eric G. Pamer, M.D. — Thu, 23Â OctÂ 2008 00:00:00 -05:00

Allogeneic hematopoietic stem-cell transplantation is a potentially lifesaving cancer therapy that, at least temporarily, renders patients highly immunocompromised and vulnerable to infection. Aspergillus fumigatus, a common environmental fungus that causes...

ORIGINAL ARTICLE: Toll-like Receptor 4 Polymorphisms and Aspergillosis in Stem-Cell Transplantation

Thu, 23Â OctÂ 2008 00:00:00 -05:00

Background: Toll-like receptors (TLRs) are essential components of the immune response to fungal pathogens. We examined the role of TLR polymorphisms in conferring a risk of invasive aspergillosis among recipients...

IMAGES IN CLINICAL MEDICINE: Gingival Hypertrophy and Leukemia

Eric Tjwa, M.D. and Vera Mattijssen, M.D., Ph.D. — Thu, 16Â OctÂ 2008 00:00:00 -05:00

A 46-year-old woman who was not taking any medications presented with anemia and gingival hypertrophy that had been progressing over a period of 3 months. She was otherwise healthy. Histopathological...

CORRESPONDENCE: Dengue Hemorrhagic Fever Transmitted by Blood Transfusion

Thu, 02Â OctÂ 2008 00:00:00 -05:00

To the Editor: Dengue, the most common vectorborne viral infection worldwide,1 is predominantly transmitted by the Aedes aegypti mosquito. We describe a well-documented cluster of blood transfusionâassociated dengue infections in...

REVIEW ARTICLE: Platelets, Petechiae, and Preservation of the Vascular Wall

Ralph L. Nachman, M.D., and Shahin Rafii, M.D. — Thu, 18Â SepÂ 2008 00:00:00 -05:00

Platelets help to maintain blood circulation by controlling hemorrhage after an injury to the blood-vessel wall that causes physical or biochemical disruption of the endothelium. The development of an activated...

BOOK REVIEW:

Thu, 04Â SepÂ 2008 00:00:00 -05:00

The transfer of blood components, solid tissues, or organs from one person to another is basic to the practice of modern medicine and surgery. Because the only source of blood...

CLINICAL PRACTICE: Hereditary Angioedema

Bruce L. Zuraw, M.D. — Thu, 04Â SepÂ 2008 00:00:00 -05:00

A 19-year-old woman presents to the emergency department with light-headedness, severe abdominal pain, and intractable nausea and vomiting that began 12 hours earlier. The patient reports previous episodes of abdominal...

EDITORIAL: Treatment of Myeloma â Are We Making Progress?

Brian G.M. Durie, M.D. — Thu, 28Â AugÂ 2008 00:00:00 -05:00

In this issue of the Journal, San Miguel et al.1 describe the benefit of combining bortezomib with melphalan plus prednisone, as compared with melphalan plus prednisone alone, as initial therapy...

ORIGINAL ARTICLE: Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma

Thu, 28Â AugÂ 2008 00:00:00 -05:00

Background: The standard treatment for patients with multiple myeloma who are not candidates for high-dose therapy is melphalan and prednisone. This phase 3 study compared the use of melphalan and...

BOOK REVIEW:

Thu, 03Â JulÂ 2008 00:00:00 -05:00

Only 50 years ago, the function of human platelets was barely understood and antiplatelet drugs were unknown â although aspirin had been available since the end of the 19th century....

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Metabolism and Therapeutic Angiogenesis

Peter Carmeliet, M.D., Ph.D., and Myriam Baes, Ph.D. — Thu, 05Â JunÂ 2008 00:00:00 -05:00

Despite great expectations, therapeutic angiogenesis with the vascular endothelial growth factor (VEGF) and related molecules for the treatment of ischemic heart and peripheral arterial occlusive disease has thus far failed...

EDITORIAL: Heparin Comes Clean

Lawrence B. Schwartz, M.D., Ph.D. — Thu, 05Â JunÂ 2008 00:00:00 -05:00

Hypotensive episodes in patients receiving heparin by means of injection, some of which cause death, are voluntarily reported to the Food and Drug Administration (FDA). Many cases occur in medical...

ORIGINAL ARTICLE: Contaminated Heparin Associated with Adverse Clinical Events and Activation of the Contact System

Thu, 05Â JunÂ 2008 00:00:00 -05:00

Background: There is an urgent need to determine whether oversulfated chondroitin sulfate (OSCS), a compound contaminating heparin supplies worldwide, is the cause of the severe anaphylactoid reactions that have occurred...

EDITORIAL: The Aprotinin Story â Is BART the Final Chapter?

Wayne A. Ray, Ph.D., and C. Michael Stein, M.B., Ch.B. — Thu, 29Â MayÂ 2008 00:00:00 -05:00

The aprotinin story began in 1987, when investigators reported that the use of the drug in patients undergoing repeat open-heart surgery decreased the need for blood transfusion by a factor...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 17-2008 â A 63-Year-Old Man with Metastatic Renal-Cell Carcinoma

Thu, 29Â MayÂ 2008 00:00:00 -05:00

A 63-year-old man was admitted to this hospital because of a mass in the left kidney and pulmonary nodules. The patient had been well until approximately 5 months before admission,...

ORIGINAL ARTICLE: A Comparison of Aprotinin and Lysine Analogues in High-Risk Cardiac Surgery

Thu, 29Â MayÂ 2008 00:00:00 -05:00

Background: Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding and to reduce exposure to blood products. We sought to determine whether aprotinin was superior to either tranexamic...

IMAGES IN CLINICAL MEDICINE: Babesiosis

Kyle Noskoviak, M.D. and Elizabeth Broome, M.D. — Thu, 24Â AprÂ 2008 00:00:00 -05:00

A 34-year-old man came to the emergency room with a 3-day history of fevers (peak temperature, 40Â°C), accompanied by shaking chills. Laboratory tests revealed a hemolytic anemia, with a hemoglobin...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 13-2008 â A 46-Year-Old Man with Rheumatoid Arthritis and Lymphadenopathy

Nikhil C. Munshi, M.D., Subba Digumarthy, M.D., and Aliyah Rahemtullah, M.D. — Thu, 24Â AprÂ 2008 00:00:00 -05:00

Viviany Taqueti (Harvard Medical School): A 46-year-old man was seen in the hematologyâoncology clinic of a cancer center affiliated with this hospital because of anorexia and generalized lymphadenopathy.

The patient had...

IMAGES IN CLINICAL MEDICINE: Hemoglobinuria with Malaria

Martin Tombe, M.D. — Thu, 24Â AprÂ 2008 00:00:00 -05:00

An otherwise healthy 30-year-old man had been ill for 2 days when he presented with a temperature of 39Â°C and reported passing dark urine (his case was noted in Bhatt...

ORIGINAL ARTICLE: Pyruvate Kinase Deficiency and Malaria

Thu, 24Â AprÂ 2008 00:00:00 -05:00

Malaria that is caused by Plasmodium falciparum is a significant global health problem. Genetic characteristics of the host influence the severity of disease and the ultimate outcome of infection, and...

CLINICAL THERAPEUTICS: Hydroxyurea for the Treatment of Sickle Cell Anemia

Orah S. Platt, M.D. — Thu, 27Â MarÂ 2008 00:00:00 -05:00

An 18-year-old woman with sickle cell anemia has had increasing symptoms, with painful crises and episodes of the acute chest syndrome. She was hospitalized three times in the past year....

EDITORIAL: New Blood, Old Blood, or No Blood?

John W. Adamson, M.D. — Thu, 20Â MarÂ 2008 00:00:00 -05:00

The use of blood transfusions in medicine is so well established that the procedure is an afterthought to many physicians. Scientific advances have rendered blood and blood products extremely safe...

EDITORIAL: Combating the Eosinophil with AntiâInterleukin-5 Therapy

Michael E. Wechsler, M.D., M.M.Sc. — Thu, 20Â MarÂ 2008 00:00:00 -05:00

The role of eosinophils in common diseases â such as asthma, parasitic disease, or allergic reactions â remains speculative. Even more puzzling is the eclectic group of rare disorders that...

ORIGINAL ARTICLE: Duration of Red-Cell Storage and Complications after Cardiac Surgery

Thu, 20Â MarÂ 2008 00:00:00 -05:00

Background: Stored red cells undergo progressive structural and functional changes over time. We tested the hypothesis that serious complications and mortality after cardiac surgery are increased when transfused red cells...

ORIGINAL ARTICLE: Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumab

Thu, 20Â MarÂ 2008 00:00:00 -05:00

Background: The hypereosinophilic syndrome is a group of diseases characterized by persistent blood eosinophilia, defined as more than 1500 cells per microliter with end-organ involvement and no recognized secondary cause....

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 8-2008 â A 33-Year-Old Man with Fever, Abdominal Pain, and Pancytopenia after Renal Transplantation

Thu, 13Â MarÂ 2008 00:00:00 -05:00

Dr. Robert B. Den (Medicine): A 33-year-old man was admitted to this hospital because of fever, abdominal pain, and pancytopenia.

The patient had received a cadaveric renal allograft 15 years earlier...

ORIGINAL ARTICLE: Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-Î±-1,3-Galactose

Thu, 13Â MarÂ 2008 00:00:00 -05:00

Background: Cetuximab, a chimeric mouseâhuman IgG1 monoclonal antibody against the epidermal growth factor receptor, is approved for use in colorectal cancer and squamous-cell carcinoma of the head and neck. A...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: A New Dawn for Stem-Cell Therapy

Douglas R. Higgs, M.D., D.Sc. — Thu, 28Â FebÂ 2008 00:00:00 -05:00

Recently, the potential use of stem cells for regenerative medicine and for the treatment of genetic disease has rarely been out of the news. Discussion has focused mainly on the...

ORIGINAL ARTICLE: Severe Anemia in Malawian Children

Thu, 28Â FebÂ 2008 00:00:00 -05:00

Background: Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied.

Methods: We conducted a caseâcontrol...

EDITORIAL: Clinical Penetrance of Hereditary Hemochromatosis

Bruce R. Bacon, M.D., and Robert S. Britton, Ph.D. — Thu, 17Â JanÂ 2008 00:00:00 -05:00

In 1996, Feder and colleagues1 showed that homozygosity for a mutation (C282Y) in the HFE gene is responsible for the majority of cases of typical phenotypic hereditary hemochromatosis. At that...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 2-2008 â A 38-Year-Old Woman with Postpartum Visual Loss, Shortness of Breath, and Renal Failure

Thu, 17Â JanÂ 2008 00:00:00 -05:00

Dr. Esperance A. Schaefer (Medicine): A 38-year-old woman was admitted to the hospital, because of blurred vision and shortness of breath, 2 weeks after a cesarean section had been performed...

ORIGINAL ARTICLE: Iron-OverloadâRelated Disease in Hereditary Hemochromatosis

Thu, 17Â JanÂ 2008 00:00:00 -05:00

Background: Most persons who are homozygous for C282Y, the HFE allele most commonly asssociated with hereditary hemochromatosis, have elevated levels of serum ferritin and transferrin saturation. Diseases related to iron...

ORIGINAL ARTICLE: A Gain-of-Function Mutation in the Gene in Familial Erythrocytosis

Thu, 10Â JanÂ 2008 00:00:00 -05:00

Hypoxia-inducible factor (HIF) Î±, which has three isoforms, is central to the continuous balancing of the supply and demand of oxygen throughout the body. HIF-Î± is a transcription factor that...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: B-Cell Identity â Commitment Is Not Forever

Stephen L. Nutt, Ph.D. — Thu, 03Â JanÂ 2008 00:00:00 -05:00

A general rule of cell biology is that once a cell commits to a particular differentiation pathway, there is no turning back. It is thought that the event triggering differentiation...

REVIEW ARTICLE: Platelet Activation and Atherothrombosis

Giovanni DavÃ¬, M.D., and Carlo Patrono, M.D. — Thu, 13Â DecÂ 2007 00:00:00 -05:00

Platelets are essential for primary hemostasis and repair of the endothelium, but they also play a key role in the development of acute coronary syndromes and contribute to cerebrovascular events....

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 33-2007 â A 49-Year-Old HIV-Positive Man with Anemia

Eyal C. Attar, M.D., Suzanne L. Aquino, M.D., and Robert P. Hasserjian, M.D. — Thu, 25Â OctÂ 2007 00:00:00 -05:00

A 49-year-old man infected with the human immunodeficiency virus (HIV) was seen in the hematology clinic at this hospital for evaluation of anemia.

Five weeks earlier (1 week before a routine...

PERSPECTIVE: Hematopoietic-Cell Transplantation at 50

Thu, 11Â OctÂ 2007 00:00:00 -05:00

September 12, 2007, marked the 50th anniversary of E. Donnall (Don) Thomas's initial report of a radical new approach to cancer treatment: radiation and chemotherapy followed by the intravenous infusion...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 30-2007 â A Newborn Girl with Skin Lesions

Mathew M. Avram, M.D., J.D., Verena Gobel, M.D., and Alireza Sepehr, M.D. — Thu, 27Â SepÂ 2007 00:00:00 -05:00

Dr. Elizabeth A. Buzney (Dermatology): A newborn girl was transferred to this hospital because of a rash that had been present at birth. The infant, who weighed 3105 g, was...

ORIGINAL ARTICLE: High-Dose Melphalan versus Melphalan plus Dexamethasone for AL Amyloidosis

Thu, 13Â SepÂ 2007 00:00:00 -05:00

Background: High-dose chemotherapy followed by autologous hematopoietic stem-cell transplantation has been reported to provide higher response rates and better overall survival than standard chemotherapy in immunoglobulin-light-chain (AL) amyloidosis, but these...

ORIGINAL ARTICLE: Efficacy and Safety of Epoetin Alfa in Critically Ill Patients

Thu, 06Â SepÂ 2007 00:00:00 -05:00

Background: Anemia, which is common in the critically ill, is often treated with red-cell transfusions, which are associated with poor clinical outcomes. We hypothesized that therapy with recombinant human erythropoietin...

EDITORIAL: Targeting Anemia with Erythropoietin during Critical Illness

Deborah Cook, M.D., and Mark Crowther, M.D. — Thu, 06Â SepÂ 2007 00:00:00 -05:00

The overall goals of clinical research in the intensive care unit (ICU) are to improve clinical outcomes through enhanced understanding of how critical illness develops and how such illness is...

EDITORIAL: Prophylactic Treatment for Prevention of Joint Disease in Hemophilia â Cost versus Benefit

Goris Roosendaal, M.D., Ph.D., and Floris Lafeber, Ph.D. — Thu, 09Â AugÂ 2007 00:00:00 -05:00

Patients with severe hemophilia number only around 400,000 worldwide, but their lifespan has increased because of improved treatment, and with that the prevalence of the disease is increasing. Despite the...

REVIEW ARTICLE: Drug-Induced Immune Thrombocytopenia

Richard H. Aster, M.D., and Daniel W. Bougie, Ph.D. — Thu, 09Â AugÂ 2007 00:00:00 -05:00

Drug-induced thrombocytopenia can be caused by dozens, perhaps hundreds, of medications. Because thrombocytopenia can have many other causes, the diagnosis of drug-induced thrombocytopenia can easily be overlooked. On occasion, outpatients...

ORIGINAL ARTICLE: Prophylaxis versus Episodic Treatment to Prevent Joint Disease in Boys with Severe Hemophilia

Thu, 09Â AugÂ 2007 00:00:00 -05:00

Background: Effective ways to prevent arthropathy in severe hemophilia are unknown.

Methods: We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to...

ORIGINAL ARTICLE: Clinical Course and Prognosis of Smoldering (Asymptomatic) Multiple Myeloma

Thu, 21Â JunÂ 2007 00:00:00 -05:00

Background: Smoldering (asymptomatic) multiple myeloma is an asymptomatic plasma-cell proliferative disorder associated with a high risk of progression to symptomatic multiple myeloma or amyloidosis. Prognostic factors for the progression and...

PERSPECTIVE: Erythropoietin, the FDA, and Oncology

Thu, 14Â JunÂ 2007 00:00:00 -05:00

As has been the case for patients with chronic renal failure, treatment with erythropoiesis-stimulating agents (ESAs) has substantially raised the hemoglobin concentrations of hundreds of thousands of patients with cancer,...

PERSPECTIVE: Do Cancer Cells Express Functional Erythropoietin Receptors?

Thu, 14Â JunÂ 2007 00:00:00 -05:00

When erythropoietin won market approval in 1988, it was hailed as a wonder drug because of the selectivity of its action and its resulting relative freedom from untoward effects. This...

PERSPECTIVE: Weighing the Hazards of Erythropoiesis Stimulation in Patients with Cancer

Thu, 14Â JunÂ 2007 00:00:00 -05:00

On May 10, 2007, the Food and Drug Administration (FDA) convened a meeting of its Oncology Drug Advisory Committee to discuss concerns about risks associated with the erythropoiesis-stimulating agents (ESAs)...

IMAGES IN CLINICAL MEDICINE: Amyloid Purpura

Lihi Eder, M.D. and Haim Bitterman, M.D. — Thu, 07Â JunÂ 2007 00:00:00 -05:00

A 73-year-old woman presented with new-onset periorbital purpuric, nonblanching, nonpruritic lesions. The lesions appeared spontaneously and were not associated with any recent trauma. She did not take aspirin, nonsteroidal antiinflammatory...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 17-2007 â A 25-Year-Old Woman with Relapsing Fevers and Recent Onset of Dyspnea

Thu, 31Â MayÂ 2007 00:00:00 -05:00

Dr. Surajit Nundy (Department of Medicine): A 25-year-old woman was admitted to this hospital because of a 5-month history of relapsing fevers and a 3-day history of dyspnea. She had...

REVIEW ARTICLE: Prevention and Treatment of Major Blood Loss

Pier Mannuccio Mannucci, M.D., and Marcel Levi, M.D., Ph.D. — Thu, 31Â MayÂ 2007 00:00:00 -05:00

In a medical setting, surgery is the most common cause of major blood loss, defined as a loss of 20% of total blood volume or more. In particular, cardiovascular procedures,...

EDITORIAL: Blood Transfusion â When Is More Really Less?

Howard L. Corwin, M.D., and Jeffrey L. Carson, M.D. — Thu, 19Â AprÂ 2007 00:00:00 -05:00

Blood transfusion has for years been considered to have obvious clinical benefits and to be a relatively low-risk procedure. Not until the early 1980s did transfusion practices begin to come...

ORIGINAL ARTICLE: Transfusion Strategies for Patients in Pediatric Intensive Care Units

Thu, 19Â AprÂ 2007 00:00:00 -05:00

Background: The optimal hemoglobin threshold for erythrocyte transfusions in critically ill children is unknown. We hypothesized that a restrictive transfusion strategy of using packed red cells that were leukocyte-reduced before...

ORIGINAL ARTICLE: A Comparison of Allografting with Autografting for Newly Diagnosed Myeloma

Thu, 15Â MarÂ 2007 00:00:00 -05:00

Background: In this trial of the treatment of newly diagnosed multiple myeloma, we compared a protocol that entailed a hematopoietic stem-cell autograft followed by an allograft from an HLA-identical sibling...

ORIGINAL ARTICLE: Vancomycin-Induced Immune Thrombocytopenia

Thu, 01Â MarÂ 2007 00:00:00 -05:00

Background: Vancomycin has only rarely been implicated as a cause of thrombocytopenia, and there is only limited evidence that this complication is caused by immune mechanisms. We conducted a study...

PERSPECTIVE: Drug-Induced Immune-Mediated Thrombocytopenia â From Purpura to Thrombosis

Thu, 01Â MarÂ 2007 00:00:00 -05:00

In 1949, Ackroyd reported the abrupt onset of severe thrombocytopenia and purpura in patients receiving the sedative allylisopropylacetylcarbamide (Sedormid).1 All the patients had taken Sedormid previously and had become sensitized...

ORIGINAL ARTICLE: GM-CSF Autoantibodies and Neutrophil Dysfunction in Pulmonary Alveolar Proteinosis

Thu, 08Â FebÂ 2007 00:00:00 -05:00

Background: Increased mortality from infection in patients with pulmonary alveolar proteinosis occurs in association with high levels of autoantibodies against granulocyteâmacrophage colony-stimulating factor (GM-CSF). We tested the hypothesis that neutrophil...

PERSPECTIVE: Pulmonary Alveolar Proteinosis â Is Host Defense Awry?

Thu, 08Â FebÂ 2007 00:00:00 -05:00

Pulmonary alveolar proteinosis is a rare disorder caused by abundant accumulation of surfactant-derived components in the lungs. The incidence is estimated to be 0.36 case per million population, and the...

CLINICAL PROBLEM-SOLVING: Anchors Away

Thu, 01Â FebÂ 2007 00:00:00 -05:00

A 50-year-old Asian woman presented with a papulonodular, erythematous rash on her legs below the knees. The skin lesions were nontender and nonpruritic and were accompanied by paresthesias. She had...

ORIGINAL ARTICLE: Exon 12 Mutations in Polycythemia Vera and Idiopathic Erythrocytosis

Thu, 01Â FebÂ 2007 00:00:00 -05:00

Background: The V617F mutation, which causes the substitution of phenylalanine for valine at position 617 of the Janus kinase (JAK) 2 gene (JAK2), is often present in patients with polycythemia...

PERSPECTIVE: Mutations in Polycythemia Vera â Molecular Mechanisms and Clinical Applications

Thu, 01Â FebÂ 2007 00:00:00 -05:00

Janus kinase 2 (JAK2) is a cytoplasmic tyrosine kinase that transduces signals, especially those triggered by hematopoietic growth factors such as erythropoietin, in normal and neoplastic cells. In March and...

EDITORIAL: Prophylaxis and Aspergillosis â Has the Principle Been Proven?

Ben E. De Pauw, M.D., and J. Peter Donnelly, Ph.D. — Thu, 25Â JanÂ 2007 00:00:00 -05:00

Invasive fungal diseases contribute substantially to death and illness associated with the prolonged, profound neutropenia resulting from intensive chemotherapy for hematologic cancers and from myeloablation for allogeneic hematopoietic stem-cell transplantation....

ORIGINAL ARTICLE: Posaconazole vs. Fluconazole or Itraconazole Prophylaxis in Patients with Neutropenia

Thu, 25Â JanÂ 2007 00:00:00 -05:00

Background: Patients with neutropenia resulting from chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome are at high risk for difficult-to-treat and often fatal invasive fungal infections.

Methods: In this randomized,...

IMAGES IN CLINICAL MEDICINE: Livedo Reticularis and Cold Agglutinins

Teresa Kauke, M.D. and Armin J. Reininger, M.D., Ph.D. — Thu, 18Â JanÂ 2007 00:00:00 -05:00

A previously healthy 56-year-old woman had spontaneous eruption of a lacy, net-like erythema of her entire skin, which was especially pronounced on her arms and legs (Panel A). The erythema...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 1-2007 â A 40-Year-Old Woman with Epistaxis, Hematemesis, and Altered Mental Status

Thu, 11Â JanÂ 2007 00:00:00 -05:00

Dr. Amy Jo Chien (Medicine): A 40-year-old woman was admitted to the emergency department of this hospital because of the sudden onset of headache, loss of consciousness, and coagulopathy.

The patient...

PERSPECTIVE: Medicare and Erythropoietin

Thu, 04Â JanÂ 2007 00:00:00 -05:00

Since Medicare coverage of care for end-stage renal disease (ESRD) was implemented in 1973, dialysis treatments paid for by the federal government have extended the lives of hundreds of thousands...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 40-2006 â A 64-Year-Old Man with Anemia and a Low Level of HDL Cholesterol

Thu, 28Â DecÂ 2006 00:00:00 -05:00

A 64-year-old man was seen as an outpatient in the hematology division of this hospital because of anemia and a low serum level of high-density lipoprotein (HDL) cholesterol. A mild...

CLINICAL PRACTICE: Monoclonal Gammopathy of Undetermined Significance

Joan BladÃ©, M.D. — Thu, 28Â DecÂ 2006 00:00:00 -05:00

A 58-year-old man with no significant medical history is found to have an elevated total protein concentration (8.1 g per deciliter) on a routine blood chemical study. He is asymptomatic,...

REVIEW ARTICLE: The Myeloproliferative Disorders

Thu, 07Â DecÂ 2006 00:00:00 -05:00

The myeloproliferative disorders comprise several clonal hematologic diseases that are thought to arise from a transformation in a hematopoietic stem cell. The main clinical features of these diseases are the...

EDITORIAL: Correction of Anemia â Payoffs and Problems

Giuseppe Remuzzi, M.D., and Julie R. Ingelfinger, M.D. — Thu, 16Â NovÂ 2006 00:00:00 -05:00

Anemia develops in most patients with chronic kidney disease, historically often requiring transfusion, with obvious risks. With the advent of recombinant erythropoietin in the late 1980s, it became possible to...

ORIGINAL ARTICLE: Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease

Thu, 16Â NovÂ 2006 00:00:00 -05:00

Background: Anemia, a common complication of chronic kidney disease, usually develops as a consequence of erythropoietin deficiency. Recombinant human erythropoietin (epoetin alfa) is indicated for the correction of anemia associated...

ORIGINAL ARTICLE: Normalization of Hemoglobin Level in Patients with Chronic Kidney Disease and Anemia

Thu, 16Â NovÂ 2006 00:00:00 -05:00

Background: Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established.

Methods: We randomly assigned 603 patients with an estimated glomerular...

EDITORIAL: Retraction: SudbÃ¸ J et al. DNA Content as a Prognostic Marker in Patients with Oral Leukoplakia. N Engl J Med 2001;344:1270-8 and SudbÃ¸ J et al. The Influence of Resection and Aneuploidy on Mortality in Oral Leukoplakia. N Engl J Med 2004;350:1405-13

Gregory D. Curfman, M.D., Stephen Morrissey, Ph.D., and Jeffrey M. Drazen, M.D. — Thu, 02Â NovÂ 2006 00:00:00 -05:00

On February 9, 2006, we published an Expression of Concern1 about two articles we had published by Jon SudbÃ¸ et al.23 In the Expression of Concern, we indicated that we...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 33-2006 â A 43-Year-Old Man with Diabetes, Hypogonadism, Cirrhosis, Arthralgias, and Fatigue

Raymond T. Chung, M.D., Joseph Misdraji, M.D., and Dushyant V. Sahani, M.D. — Thu, 26Â OctÂ 2006 00:00:00 -05:00

A 43-year-old white man was seen at this hospital because of hypogonadism.

The patient had felt well until 6 months earlier, when he noted the gradual onset of fatigue, decreased libido,...

ORIGINAL ARTICLE: The Genotype of the Original Wiskott Phenotype

Thu, 26Â OctÂ 2006 00:00:00 -05:00

The WiskottâAldrich syndrome is an X-linked hereditary disorder associated with combined immunodeficiency, thrombocytopenia, small platelets, eczema, and increased susceptibility to autoimmune disorders and cancers. It is caused by mutations in...

PERSPECTIVE: Lessons from the WiskottâAldrich Syndrome

Thu, 26Â OctÂ 2006 00:00:00 -05:00

The WiskottâAldrich syndrome is a well-recognized triad of eczema, bleeding diathesis, and recurrent infections that occurs in boys. Although it is rare (with an estimated incidence of less than 1...

ORIGINAL ARTICLE: AMG 531, a Thrombopoiesis-Stimulating Protein, for Chronic ITP

Thu, 19Â OctÂ 2006 00:00:00 -05:00

Background: Most current treatments for chronic immune thrombocytopenic purpura (ITP) act by decreasing platelet destruction. In a phase 1â2 study, we administered a thrombopoiesis-stimulating protein, AMG 531, to patients with...

PERSPECTIVE: Immune Thrombocytopenic Purpura â The Changing Therapeutic Landscape

Thu, 19Â OctÂ 2006 00:00:00 -05:00

Immune thrombocytopenic purpura (ITP) in adults is usually a chronic disease in which a low platelet count often causes mucocutaneous bleeding. ITP is a diagnosis of exclusion. Pseudothrombocytopenia and such...

ORIGINAL ARTICLE: Lenalidomide in the Myelodysplastic Syndrome with Chromosome 5q Deletion

Thu, 05Â OctÂ 2006 00:00:00 -05:00

Background: Severe, often refractory anemia is characteristic of the myelodysplastic syndrome associated with chromosome 5q31 deletion. We investigated whether lenalidomide (CC5013) could reduce the transfusion requirement and suppress the abnormal...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 30-2006 â A 41-Year-Old Man with Dyspnea, Fever, and Lymphadenopathy

David T. Scadden, M.D., Victorine V. Muse, M.D., and Robert P. Hasserjian, M.D. — Thu, 28Â SepÂ 2006 00:00:00 -05:00

A 41-year-old man was admitted to the hospital because of shortness of breath and fever. He had been well until 7 months earlier, when a rash and wheezing developed after...

ORIGINAL ARTICLE: Transmission of Human Herpesvirus 8 by Blood Transfusion

Thu, 28Â SepÂ 2006 00:00:00 -05:00

Background: Whether human herpesvirus 8 (HHV-8) is transmissible by blood transfusion remains undetermined. We evaluated the risk of HHV-8 transmission by blood transfusion in Uganda, where HHV-8 is endemic.

Methods: We...

PERSPECTIVE: The Continuing Risk of Transfusion-Transmitted Infections

Thu, 28Â SepÂ 2006 00:00:00 -05:00

In 2002, as mosquitoes carried West Nile virus across the United States, infecting 4200 people, 23 confirmed cases of transfusion-transmitted infection and 7 related deaths were reported.1 This was a...

EDITORIAL: Cardiac Cell Therapy â Mixed Results from Mixed Cells

Anthony Rosenzweig, M.D. — Thu, 21Â SepÂ 2006 00:00:00 -05:00

Despite substantial advances in treatment, ischemic cardiac injury and the ventricular dysfunction it can provoke remain major causes of morbidity and mortality throughout the world. The endogenous regenerative capacity of...

REVIEW ARTICLE: Cancer Stem Cells

Craig T. Jordan, Ph.D., Monica L. Guzman, Ph.D., and Mark Noble, Ph.D. — Thu, 21Â SepÂ 2006 00:00:00 -05:00

The deepening of our understanding of normal biology has made it clear that stem cells have a critical role not only in the generation of complex multicellular organisms, but also...

ORIGINAL ARTICLE: The Complement Inhibitor Eculizumab in Paroxysmal Nocturnal Hemoglobinuria

Thu, 21Â SepÂ 2006 00:00:00 -05:00

Background: We tested the safety and efficacy of eculizumab, a humanized monoclonal antibody against terminal complement protein C5 that inhibits terminal complement activation, in patients with paroxysmal nocturnal hemoglobinuria (PNH).

Methods:...

ORIGINAL ARTICLE: Transcoronary Transplantation of Progenitor Cells after Myocardial Infarction

Thu, 21Â SepÂ 2006 00:00:00 -05:00

Background: Pilot studies suggest that intracoronary transplantation of progenitor cells derived from bone marrow (BMC) or circulating blood (CPC) may improve left ventricular function after acute myocardial infarction. The effects...

ORIGINAL ARTICLE: Intracoronary Bone MarrowâDerived Progenitor Cells in Acute Myocardial Infarction

Thu, 21Â SepÂ 2006 00:00:00 -05:00

Background: Pilot trials suggest that the intracoronary administration of autologous progenitor cells may improve left ventricular function after acute myocardial infarction.

Methods: In a multicenter trial, we randomly assigned 204 patients...

ORIGINAL ARTICLE: Intracoronary Injection of Mononuclear Bone Marrow Cells in Acute Myocardial Infarction

Thu, 21Â SepÂ 2006 00:00:00 -05:00

Background: Previous studies have shown improvement in left ventricular function after intracoronary injection of autologous cells derived from bone marrow (BMC) in the acute phase of myocardial infarction. We designed...

CLINICAL PROBLEM-SOLVING: More Than Meets the Eye

Thu, 07Â SepÂ 2006 00:00:00 -05:00

A 61-year-old woman was hospitalized with a two-day history of palpitations and dyspnea. She was found to be in atrial fibrillation with a rapid ventricular response, and intravenous diltiazem and...

IMAGES IN CLINICAL MEDICINE: Congenital Erythropoietic Porphyria

Pankaj Madan, M.D. and Prem Vardhan, M.D. — Thu, 07Â SepÂ 2006 00:00:00 -05:00

A 32-year-old man presented with severe pain, swelling, and loss of vision in his left eye after excessive exposure to sunlight. He reported multiple, recurrent, discrete blisters developing on sun-exposed...

CLINICAL PRACTICE: Heparin-Induced Thrombocytopenia

Gowthami M. Arepally, M.D., and Thomas L. Ortel, M.D., Ph.D. — Thu, 24Â AugÂ 2006 00:00:00 -05:00

A 63-year-old man with coronary artery disease who has recently undergone bypass surgery presents with dyspnea. Findings on physical examination are unremarkable. Laboratory testing reveals a platelet count of 86,000...

EDITORIAL: Diagnosing Hemolytic Disease of the Fetus â Time to Put the Needles Away?

Kenneth J. Moise, Jr., M.D. — Thu, 13Â JulÂ 2006 00:00:00 -05:00

The RhD (Rh0[D]) antigen is considered the most immunogenic of the antigens found on the surface of the human red cell. In 1941, Levine, Katzin, and Burham1 showed that antibodies...

ORIGINAL ARTICLE: Doppler Ultrasonography versus Amniocentesis to Predict Fetal Anemia

Thu, 13Â JulÂ 2006 00:00:00 -05:00

Background: Pregnancies complicated by Rh alloimmunization have been evaluated with the use of serial invasive amniocentesis to determine bilirubin levels by measuring in the amniotic fluid the change in optical...

CLINICAL PROBLEM-SOLVING: Heading Down the Wrong Path

Thu, 06Â JulÂ 2006 00:00:00 -05:00

A 52-year-old woman who had undergone renal transplantation 13 years earlier was brought by her family to the emergency department of a community hospital. Five days earlier, she had suddenly...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 17-2006 â A 34-Year-Old Man with Cavitary Lung Lesions

Thu, 08Â JunÂ 2006 00:00:00 -05:00

Dr. Anna Kagan (Department of Medicine): A 34-year-old man was admitted to this hospital because of cough, dyspnea, and cavitary lung lesions. Over a period of several days three months...

IMAGES IN CLINICAL MEDICINE: Burton's Line

Santiago NoguÃ©, M.D. and Alex Culla, M.D. — Thu, 18Â MayÂ 2006 00:00:00 -05:00

A 61-year-old man presented for evaluation of increasing abdominal pain of eight months' duration. The patient reported having worked in a lead-smelting company for the past 30 years. The physical...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 15-2006 â A 46-Year-Old Woman with Sudden Onset of Abdominal Distention

Thu, 18Â MayÂ 2006 00:00:00 -05:00

Dr. Patrick S. Yachimski (Gastrointestinal Unit): A 46-year-old woman was admitted to this hospital because of rapidly increasing abdominal girth. She had been well until five weeks earlier, when increasing...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 14-2006 â A 25-Year-Old Woman with Anemia and Iron Overload

Eyal C. Attar, M.D., and Robert P. Hasserjian, M.D. — Thu, 11Â MayÂ 2006 00:00:00 -05:00

A 25-year-old woman was seen in the hematology clinic at this hospital because of anemia and laboratory evidence of increased iron stores.

The patient had been admitted to another hospital one...

REVIEW ARTICLE: Lineage-Specific Hematopoietic Growth Factors

Kenneth Kaushansky, M.D. — Thu, 11Â MayÂ 2006 00:00:00 -05:00

Hematopoiesis is the process that generates blood cells of all lineages. Calculations based on the blood volume and the level and half-life of each type of blood cell in the...

CLINICAL PROBLEM-SOLVING: Ring around the Diagnosis

Thu, 04Â MayÂ 2006 00:00:00 -05:00

A 71-year-old retired schoolteacher from rural Ohio presented to his local hospital with a two-week history of malaise, fever, anorexia, chills, and sweats. He had not had a cough or...

IMAGES IN CLINICAL MEDICINE: Spurious Platelet Count

Michele Siegenthaler, M.D. and Olivier Spertini, M.D. — Thu, 04Â MayÂ 2006 00:00:00 -05:00

A previously healthy 48-year-old man was admitted for severe burns involving his face, thorax, and upper and lower limbs (45 percent of body-surface area) associated with an inhalation injury. The...

CLINICAL PRACTICE: Thrombotic Thrombocytopenic Purpura

James N. George, M.D. — Thu, 04Â MayÂ 2006 00:00:00 -05:00

A 40-year-old obese black woman has had weakness and epigastric pain for several weeks and diarrhea and vomiting for four days. She does not appear acutely ill; physical examination is...

ORIGINAL ARTICLE: Inherited and Somatic Î¶ Mutations in a Patient with T-Cell Deficiency

Thu, 04Â MayÂ 2006 00:00:00 -05:00

A four-month-old boy with primary immunodeficiency was found to have a homozygous germ-line mutation of the gene encoding the CD3Î¶ subunit of the T-cell receptorâCD3 complex. CD3Î¶ is necessary for...

ORIGINAL ARTICLE: An Antibody-Deficiency Syndrome Due to Mutations in the Gene

Thu, 04Â MayÂ 2006 00:00:00 -05:00

Background: The CD19 protein forms a complex with CD21, CD81, and CD225 in the membrane of mature B cells. Together with the B-cell antigen receptor, this complex signals the B...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Disciplining the Stem Cell into Myogenesis

Terry Partridge, Ph.D. — Thu, 27Â AprÂ 2006 00:00:00 -05:00

NaivetÃ© is a much lauded but equivocal virtue of the stem cell that implies both versatility and â if this quality is to be exploited to clinical advantage â the...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 13-2006 â A 50-Year-Old Man with a Painful Bone Mass and Lesions in the Liver

Thu, 27Â AprÂ 2006 00:00:00 -05:00

Dr. Brian M. Wolpin (Hematology and Oncology): A 50-year-old man was referred to the cancer center of this hospital because of a painful lytic bone lesion of the right ulna...

REVIEW ARTICLE: Hematopoietic Stem-Cell Transplantation

Edward A. Copelan, M.D. — Thu, 27Â AprÂ 2006 00:00:00 -05:00

Although hematopoietic stem-cell transplantation was originally conceived more than 50 years ago as a treatment for injury from irradiation and, later, for cancer, associated problems needed to be solved before...

REVIEW ARTICLE: Hereditary Proteinuria Syndromes and Mechanisms of Proteinuria

Thu, 30Â MarÂ 2006 00:00:00 -05:00

The inherited forms of proteinuria comprise a heterogeneous group of rare renal diseases in which glomerular dysfunction and proteinuria are prominent. Despite the rarity of hereditary proteinuria syndromes, genetic, biochemical,...

ORIGINAL ARTICLE: Prevalence of Monoclonal Gammopathy of Undetermined Significance

Thu, 30Â MarÂ 2006 00:00:00 -05:00

Background: The prevalence of monoclonal gammopathy of undetermined significance (MGUS), a premalignant plasma-cell disorder, among persons 50 years of age or older has not been accurately determined. We used sensitive...

ORIGINAL ARTICLE: Discontinuing Prophylactic Transfusions Used to Prevent Stroke in Sickle Cell Disease

Thu, 29Â DecÂ 2005 00:00:00 -05:00

Background: Prophylactic transfusion prevents strokes in children with sickle cell anemia who have abnormalities on transcranial Doppler ultrasonographic examination. However, it is not known how long transfusion should be continued...

PERSPECTIVE: Preventing Stroke in Sickle Cell Anemia

Thu, 29Â DecÂ 2005 00:00:00 -05:00

In the late 1930s, William Bosworth Castle and his colleague Thomas Hale Ham were studying blood samples obtained from patients with sickle cell anemia and found that the viscosity of...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Understanding Heme Transport

Nancy C. Andrews, M.D., Ph.D. — Thu, 08Â DecÂ 2005 00:00:00 -05:00

Iron, the most abundant transition metal in the body, is an essential cofactor for proteins involved in oxygen transport, electron exchange, and the control of toxic free radicals. It is...

IMAGES IN CLINICAL MEDICINE: A Medical Mystery â Extensive Ecchymosis

Denis Mulleman, M.D. and Philippe Goupille, M.D. — Thu, 01Â DecÂ 2005 00:00:00 -05:00

A 71-year-old man was evaluated for severe anemia (hemoglobin level, 7.1 g per deciliter; mean corpuscular volume, 106 Î¼m3), extensive ecchymosis of the lower limbs (Panel A), gingivitis, and hemorrhages...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 33-2005 â A 43-Year-Old Man with Lower Gastrointestinal Bleeding

Thu, 27Â OctÂ 2005 00:00:00 -05:00

Dr. Joshua D. Moss (Department of Medicine): A 43-year-old man was admitted to the hospital because of blood in his stool.

When the patient was a child of about three and...

REVIEW ARTICLE: Î²-Thalassemia

Deborah Rund, M.D., and Eliezer Rachmilewitz, M.D. — Thu, 15Â SepÂ 2005 00:00:00 -05:00

05091528.xml Thalassemia is a hereditary anemia resulting from defects in hemoglobin production.1 Î²-Thalassemia, which is caused by a decrease in the production of Î²-globin chains (Figure 1), affects multiple...

IMAGES IN CLINICAL MEDICINE: in a Peripheral-Blood Smear

Erez Nadir, M.D. and Miriam Kaufshtein, M.Sc. — Thu, 08Â SepÂ 2005 00:00:00 -05:00

A male infant was born at a gestational age of 26 weeks and weighed 830 g. He required intubation and was transferred to the neonatal intensive care unit. His treatment...

ORIGINAL ARTICLE: Levofloxacin to Prevent Bacterial Infection in Patients with Cancer and Neutropenia

Thu, 08Â SepÂ 2005 00:00:00 -05:00

Background: The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention.

Methods: We randomly assigned 760 consecutive adult patients with cancer in...

IMAGES IN CLINICAL MEDICINE: Roth's Spots

Zsolt Varga, M.B., B.Chir. and Jiri Pavlu, M.D. — Thu, 08Â SepÂ 2005 00:00:00 -05:00

A 24-year-old man presented with a three-day history of a blurred patch near the center of his left visual field. He reported no fatigue or weight loss. Ophthalmoscopy showed venous...

REVIEW ARTICLE: Direct Thrombin Inhibitors

Marcello Di Nisio, M.D., Saskia Middeldorp, M.D., and Harry R. BÃ¼ller, M.D. — Thu, 08Â SepÂ 2005 00:00:00 -05:00

Direct thrombin inhibitors (DTIs) are a new class of anticoagulants that bind directly to thrombin and block its interaction with its substrates. Some DTIs â such as recombinant hirudins, bivalirudin,...

EDITORIAL: Problem Solved? West Nile Virus and Transfusion Safety

Lyle R. Petersen, M.D., M.P.H., and Jay S. Epstein, M.D. — Thu, 04Â AugÂ 2005 00:00:00 -05:00

In 2002, just three years after its appearance in the Western Hemisphere, West Nile virus caused the largest outbreak of arboviral encephalitis ever recorded in the United States.1 Epidemiologic investigations...

REVIEW ARTICLE: Diagnosis from the Blood Smear

Barbara J. Bain, F.R.A.C.P., F.R.C.Path. — Thu, 04Â AugÂ 2005 00:00:00 -05:00

An examination of the blood smear (or film) may be requested by physicians or initiated by laboratory staff. With the development of sophisticated automated blood-cell analyzers, the proportion of blood-count...

ORIGINAL ARTICLE: Screening the Blood Supply for West Nile Virus RNA by Nucleic Acid Amplification Testing

Thu, 04Â AugÂ 2005 00:00:00 -05:00

Background: The use of nucleic acid amplification tests of âminipoolsâ of 16 samples to screen blood donors for West Nile virus RNA began in July 2003. We report the yield...

ORIGINAL ARTICLE: West Nile Virus among Blood Donors in the United States, 2003 and 2004

Thu, 04Â AugÂ 2005 00:00:00 -05:00

Background: 05080428.xml West Nile virus first appeared in the United States in 1999 and has since spread throughout the contiguous states, resulting in thousands of cases of disease. By 2002,...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 21-2005 â A Four-Week-Old Male Infant with Jaundice and Thrombocytopenia

Thu, 14Â JulÂ 2005 00:00:00 -05:00

A four-week-old male infant was admitted to this hospital because of jaundice, hyperbilirubinemia, thrombocytopenia, and abdominal distention.

The patient was born at term at another hospital by spontaneous vaginal delivery to...

EDITORIAL: When and How to Treat Essential Thrombocythemia

Tiziano Barbui, M.D., and Guido Finazzi, M.D. — Thu, 07Â JulÂ 2005 00:00:00 -05:00

Essential thrombocythemia is one of the chronic myeloproliferative disorders, a heterogeneous group of diseases involving clonal hematopoietic stem cells that also includes polycythemia vera, idiopathic myelofibrosis, and chronic myelogenous leukemia.1...

ORIGINAL ARTICLE: Hydroxyurea Compared with Anagrelide in High-Risk Essential Thrombocythemia

Thu, 07Â JulÂ 2005 00:00:00 -05:00

Background: We conducted a randomized comparison of hydroxyurea with anagrelide in the treatment of essential thrombocythemia.

Methods: A total of 809 patients with essential thrombocythemia who were at high risk for...

IMAGES IN CLINICAL MEDICINE: Mixed Cryoglobulinemia

Gary Josephsen, M.D. — Thu, 23Â JunÂ 2005 00:00:00 -05:00

A 38-year-old woman presented with increasing abdominal fullness and a new rash on the lower extremities. She had a history of chronic hepatitis C infection, for which she had been...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 17-2005 â A 22-Year-Old Woman with Back and Leg Pain and Respiratory Failure

Thu, 09Â JunÂ 2005 00:00:00 -05:00

A 22-year-old black woman was transferred to this hospital because of respiratory failure.

A diagnosis of sickle cell anemia had been made when the patient was a child, at six years...

CLINICAL PROBLEM-SOLVING: Don't Know Much about History

Thu, 02Â JunÂ 2005 00:00:00 -05:00

A 20-year-old man who had immigrated to the United States from Mexico three months earlier presented to the emergency department, reporting that he had had weight loss and pain in...

EDITORIAL: The Fate of Circulating Osteoblasts

Ernesto Canalis, M.D. — Thu, 12Â MayÂ 2005 00:00:00 -05:00

Bone remodeling is a temporally regulated process resulting in the coordinated resorption and formation of skeletal tissue carried out in basic multicellular units throughout life.1 Signals determining the fate, function,...

ORIGINAL ARTICLE: Circulating Osteoblast-Lineage Cells in Humans

Thu, 12Â MayÂ 2005 00:00:00 -05:00

Background: Although current evidence suggests that only a minuscule number of osteoblast-lineage cells are present in peripheral blood, we hypothesized that such cells circulate but that their concentration has been...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Platelet-Derived Growth Factor CC â A Clinically Useful Angiogenic Factor at Last?

Stefanie Dimmeler, Ph.D. — Thu, 28Â AprÂ 2005 00:00:00 -05:00

Impaired vascularization that limits the supply of oxygen to tissue results in ischemic heart disease or peripheral arterial occlusive disease â potentially fatal conditions. Cardiologists therefore seek strategies to augment...

ORIGINAL ARTICLE: A Gain-of-Function Mutation of in Myeloproliferative Disorders

Thu, 28Â AprÂ 2005 00:00:00 -05:00

Background: Polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis are clonal myeloproliferative disorders arising from a multipotent progenitor. The loss of heterozygosity (LOH) on the short arm of chromosome 9 (9pLOH)...

ORIGINAL ARTICLE: Hemochromatosis and Iron-Overload Screening in a Racially Diverse Population

Thu, 28Â AprÂ 2005 00:00:00 -05:00

Background: Iron overload and hemochromatosis are common, treatable conditions. HFE genotypes, levels of serum ferritin, transferrin saturation values, and self-reported medical history were studied in a multiethnic primary care population.

Methods:...

PERSPECTIVE: A Unifying Mutation in Chronic Myeloproliferative Disorders

John M. Goldman, D.M. — Thu, 28Â AprÂ 2005 00:00:00 -05:00

In 1892, Louis Vaquez of Paris described a patient with cyanotic polycythemia; the autopsy disclosed massive enlargement of the spleen and liver. In 1903, William Osler, then at Johns Hopkins...

PERSPECTIVE: Orchestration of Iron Homeostasis

Robert E. Fleming, M.D., and Bruce R. Bacon, M.D. — Thu, 28Â AprÂ 2005 00:00:00 -05:00

The number of newly identified genes participating in the regulation of iron homeostasis has increased at a remarkable pace. The characterization of these genes has led investigators to challenge previous...

EDITORIAL: Telomerase Mutations in Aplastic Anemia

Willem E. Fibbe, M.D., Ph.D. — Thu, 07Â AprÂ 2005 00:00:00 -05:00

Telomeres are DNAâprotein complexes at the ends of linear eukaryotic chromosomes. They consist of double-stranded, short, repeated sequences of nucleotides, a 3' single-strand overhang of nucleotides, and telomere-binding proteins. Telomeric...

ORIGINAL ARTICLE: Mutations in the Gene for Telomerase Reverse Transcriptase, in Aplastic Anemia

Thu, 07Â AprÂ 2005 00:00:00 -05:00

Background: Mutations in TERC, the gene for the RNA component of telomerase, cause short telomeres in congenital aplastic anemia and in some cases of apparently acquired hematopoietic failure. We investigated...

EDITORIAL: Concurrent Antiplatelet and Fibrinolytic Therapy

Richard A. Lange, M.D., and L. David Hillis, M.D. — Thu, 24Â MarÂ 2005 00:00:00 -05:00

In patients who have myocardial infarction with ST-segment elevation, rupture of an atherosclerotic plaque leads to platelet adhesion, activation, and aggregation, with subsequent vessel occlusion due to thrombus formation. In...

IMAGES IN CLINICAL MEDICINE: Renal Papillary Necrosis Unmasking Sickle Cell Disease

Michalis Voulgarelis, M.D., Ph.D. and Panayiotis D. Ziakas, M.D., Ph.D. — Thu, 24Â MarÂ 2005 00:00:00 -05:00

A 26-year-old healthy Greek woman was evaluated because of new-onset painless hematuria. The physical examination was unremarkable. Laboratory data were notable for a hemoglobin concentration of 7.6 g per deciliter...

ORIGINAL ARTICLE: Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction with ST-Segment Elevation

Thu, 24Â MarÂ 2005 00:00:00 -05:00

Background: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of...

EDITORIAL: COX-2 Inhibitors â Lessons in Drug Safety

Bruce M. Psaty, M.D., Ph.D., and Curt D. Furberg, M.D., Ph.D. — Thu, 17Â MarÂ 2005 00:00:00 -05:00

Approximately six years after the cyclooxygenase-2 (COX-2) inhibitors were approved for use in the United States, the results of three randomized, placebo-controlled trials provide new evidence about the cardiovascular risks...

REVIEW ARTICLE: Anemia of Chronic Disease

Guenter Weiss, M.D., and Lawrence T. Goodnough, M.D. — Thu, 10Â MarÂ 2005 00:00:00 -05:00

Anemia of chronic disease, the anemia that is the second most prevalent after anemia caused by iron deficiency, occurs in patients with acute or chronic immune activation.1234 The condition has...

ORIGINAL ARTICLE: Efficacy of Lenalidomide in Myelodysplastic Syndromes

Thu, 10Â FebÂ 2005 00:00:00 -05:00

Background: Ineffective erythropoiesis is the hallmark of myelodysplastic syndromes. Management of the anemia caused by ineffective erythropoiesis is difficult. In patients with myelodysplastic syndromes and symptomatic anemia, we evaluated the...

PERSPECTIVE: Myelodysplastic Syndromes â Coping with Ineffective Hematopoiesis

Mario Cazzola, M.D., and Luca Malcovati, M.D. — Thu, 10Â FebÂ 2005 00:00:00 -05:00

One of the most challenging problems in hematology is the heterogeneous group of disorders that were formally defined as myelodysplastic syndromes by the FrenchâAmericanâBritish Cooperative Group in 1982. This set...

EDITORIAL: Reducing the Risks of Gastrointestinal Bleeding with Antiplatelet Therapies

Byron Cryer, M.D. — Thu, 20Â JanÂ 2005 00:00:00 -05:00

In the treatment of cardiovascular disease, clinicians commonly are caught between the competing considerations of cardiovascular benefit and gastrointestinal risks. Low-dose aspirin (325 mg or less daily) lowers the risk...

ORIGINAL ARTICLE: Clopidogrel versus Aspirin and Esomeprazole to Prevent Recurrent Ulcer Bleeding

Thu, 20Â JanÂ 2005 00:00:00 -05:00

Background: Concurrent therapy with a proton-pump inhibitor is a standard treatment for patients receiving aspirin who are at risk for ulcer. Current U.S. guidelines also recommend clopidrogel for patients who...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 38-2004 â A 40-Year-Old Man with a Large Tumor of the Skull

Paul G. Richardson, M.D., Ara Kassarjian, M.D., and Wen Jing, M.D. — Thu, 16Â DecÂ 2004 00:00:00 -05:00

Dr. Ronald Takvorian (HematologyâOncology): A 40-year-old man was admitted to this hospital because of a mass of the skull. The patient had been in his usual state of good health...

IMAGES IN CLINICAL MEDICINE: Toxic Neutrophils in Sepsis

Christine L. Hann, M.D., Ph.D. and Eric P. Schmidt, M.D. — Thu, 16Â DecÂ 2004 00:00:00 -05:00

A previously healthy, 37-year-old woman presented to the emergency department obtunded and hypotensive. The previous night, a cough and sore throat had developed, and the patient had awoken with a...

CLINICAL PROBLEM-SOLVING: Why âWhyâ Matters

Thu, 02Â DecÂ 2004 00:00:00 -05:00

A 38-year-old woman presented to the emergency room for evaluation of shortness of breath and jaundice. The previous day, she had attended a wedding, where she felt well. Several hours...

IMAGES IN CLINICAL MEDICINE: Backscatter from Lead

Rutger J. Hassink, M.D., Ph.D. and Pieter A. Doevendans, M.D., Ph.D. — Thu, 04Â NovÂ 2004 00:00:00 -05:00

A 65-year-old man underwent routine chest radiography before undergoing cardiac catheterization. The images (Panels A and B) revealed the presence of many little spheres in the posterior thoracic wall. On...

CLINICAL PROBLEM-SOLVING: Special Cure

Thu, 04Â NovÂ 2004 00:00:00 -05:00

A 42-year-old white man presented with a history of eight months of pain in his low back, hips, ankles, and feet. He had begun experiencing progressively severe pain during a...

IMAGES IN CLINICAL MEDICINE: Getting the Lead Out

Joy Shen, M.D. and Robert Hirschtick, M.D. — Thu, 04Â NovÂ 2004 00:00:00 -05:00

A 32-year-old man reported having had back and abdominal pain, nausea, and constipation for several weeks. The results of laboratory studies were notable for normocytic anemia, a hemoglobin level of...

IMAGES IN CLINICAL MEDICINE: Pathologic Fracture and Lytic Lesions in Multiple Myeloma

Suresh R. Nair, M.D. and Stanley B. Pearson, D.M. — Thu, 28Â OctÂ 2004 00:00:00 -05:00

A 76-year-old woman was admitted with an exacerbation of chronic obstructive pulmonary disease. Her condition improved with bronchodilators, prednisolone, an antibiotic, oxygen, and supportive measures. Two years previously, she had...

REVIEW ARTICLE: Multiple Myeloma

Robert A. Kyle, M.D., and S. Vincent Rajkumar, M.D. — Thu, 28Â OctÂ 2004 00:00:00 -05:00

Multiple myeloma is a plasma-cell neoplasm that is characterized by skeletal destruction, renal failure, anemia, and hypercalcemia.1 Although myeloma remains incurable, recent advances in its treatment, including the use of...

ORIGINAL ARTICLE: Fresh Whole Blood versus Reconstituted Blood for Pump Priming in Heart Surgery in Infants

Thu, 14Â OctÂ 2004 00:00:00 -05:00

Background: In an attempt to reduce the coagulopathic and inflammatory responses seen after cardiopulmonary bypass, the use of fresh whole blood during heart operations has become the standard of care...

PERSPECTIVE: Cardiopulmonary Bypass after 50 Years

L. Henry Edmunds, M.D. — Thu, 14Â OctÂ 2004 00:00:00 -05:00

A little more than 50 years ago, a hole inside a human heart was closed, with a machine maintaining life while the surgery was done. Within the next two years,...

ORIGINAL ARTICLE: Hemoglobin Jamaica Plain â A Sickling Hemoglobin with Reduced Oxygen Affinity

Thu, 07Â OctÂ 2004 00:00:00 -05:00

A baby girl presented with symptomatic sickle cell disease exacerbated by mild hypoxemia, despite a newborn-screening diagnosis of sickle cell trait. DNA sequencing of the Î² globin gene revealed that...

PERSPECTIVE: Genotypes and Phenotypes â Another Lesson from the Hemoglobinopathies

Edward J. Benz, Jr., M.D. — Thu, 07Â OctÂ 2004 00:00:00 -05:00

The human genome project has ignited considerable excitement about the future of medicine by revealing insights into diseases that seemed impossible to unravel only a few years ago. But knowledge...

ORIGINAL ARTICLE: Pure Red-Cell Aplasia and Epoetin Therapy

Thu, 30Â SepÂ 2004 00:00:00 -05:00

Background: Between 1988 and 1998, antibody-associated pure red-cell aplasia was reported in three patients who had undergone treatment with recombinant human erythropoietin (epoetin). Between 1998 and 2000, 13 such cases...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 30-2004 â A 37-Year-Old Woman with Paresthesias of the Arms and Legs

Peter W. Marks, M.D., Ph.D., and Lawrence R. Zukerberg, M.D. — Thu, 23Â SepÂ 2004 00:00:00 -05:00

A 37-year-old woman was seen in the clinic because of numbness in the arms and legs.

Four months earlier, she had noticed tingling and numbness in the fingertips, without weakness, three...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 28-2004 â Newborn Twins with Thrombocytopenia, Coagulation Defects, and Hepatosplenomegaly

Thu, 09Â SepÂ 2004 00:00:00 -05:00

Newborn identical twin male infants were admitted to the neonatal intensive care unit. They were delivered at 32 weeks of gestation by a healthy 27-year-old primipara. The parents were of...

ORIGINAL ARTICLE: Elevated Plasma Factor VIII and D-Dimer Levels as Predictors of Poor Outcomes of Thrombosis in Children

Thu, 09Â SepÂ 2004 00:00:00 -05:00

Background: Elevated levels of plasma factor VIII and D-dimer predict recurrent venous thromboembolism in adults. We sought to determine whether an elevation of factor VIII, D-dimer, or both at diagnosis...

PERSPECTIVE: Factor VIII, D-Dimer, and Thromboembolism in Children

Ulrike Nowak-GÃ¶ttl, M.D., and Andrea Kosch, M.D. — Thu, 09Â SepÂ 2004 00:00:00 -05:00

Symptomatic venous and arterial thromboses are being diagnosed with increasing frequency in neonates, infants, and children. Because of the special properties of the hemostatic system in children, thrombotic manifestations are...

PERSPECTIVE: Tainted Glory â Doping and Athletic Performance

Timothy D. Noakes, M.D., D.Sc. — Thu, 26Â AugÂ 2004 00:00:00 -05:00

Is it possible for the ânaturalâ athlete who competes without chemical assistance to achieve record-breaking performances in sports requiring strength, power, speed, or endurance? Because doping tests are infrequently positive...

EDITORIAL: The Safety and Availability of Blood and Tissues â Progress and Challenges

Jesse L. Goodman, M.D., M.P.H. — Thu, 19Â AugÂ 2004 00:00:00 -05:00

The availability of a safe blood supply is critical for both medical progress and national security. Safety has been increased by nucleic acidâamplification testing, as documented by Stramer et al....

ORIGINAL ARTICLE: Detection of HIV-1 and HCV Infections among Antibody-Negative Blood Donors by Nucleic AcidâAmplification Testing

Thu, 19Â AugÂ 2004 00:00:00 -05:00

Background: Testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNA by means of nucleic acid amplification was introduced in the United States...

REVIEW ARTICLE: Treatment of von Willebrand's Disease

Pier Mannuccio Mannucci, M.D. — Thu, 12Â AugÂ 2004 00:00:00 -05:00

Von Willebrand's disease is an inherited bleeding disorder with a prevalence as high as 1 to 2 percent in the general population, according to screening studies.12 In contrast, estimates based...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 23-2004 â A 50-Year-Old Woman with Low Oxygen Saturation

William E. Hurford, M.D., and Alexander Kratz, M.D., Ph.D. — Thu, 22Â JulÂ 2004 00:00:00 -05:00

A 50-year-old woman was evaluated in the pulmonary clinic because of low oxygen saturation.

Five years earlier, dysfunctional uterine bleeding and dysmenorrhea had developed. A pelvic ultrasonographic examination at that time...

IMAGES IN CLINICAL MEDICINE: Homozygous Hemoglobin C Disease

Rick M. Fairhurst, M.D., Ph.D. and James F. Casella, M.D. — Thu, 24Â JunÂ 2004 00:00:00 -05:00

A Ghanaian child was found on routine screening to have a hemoglobin level of 9.0 g per deciliter, a hematocrit of 24.3 percent, a mean corpuscular volume of 53.8 Î¼m3,...

IMAGES IN CLINICAL MEDICINE: Vitiligo and Pernicious Anemia

Fritz Egli, M.D. and Roland Walter, M.D. — Thu, 24Â JunÂ 2004 00:00:00 -05:00

A 45-year-old woman with a 17-year history of vitiligo (panel A) was evaluated because of persistent fatigue. She was found to have pancytopenia (white-cell count, 3200 per cubic millimeter; hemoglobin...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 19-2004 â A 12-Year-Old Boy with Fatigue and Eosinophilia

Mary S. Huang, M.D., and Robert P. Hasserjian, M.D. — Thu, 17Â JunÂ 2004 00:00:00 -05:00

A 12-year-old boy was evaluated in the hematology clinic of this hospital because of fatigue and peripheral-blood eosinophilia. For one week, he had had fatigue that had caused him to...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 13-2004 â A Newborn Girl with a Large Cutaneous Lesion, Thrombocytopenia, and Anemia

Thu, 22Â AprÂ 2004 00:00:00 -05:00

A newborn girl was transferred to this hospital because of a large cutaneous lesion, thrombocytopenia, and anemia.

The infant had been born at another hospital to a 33-year-old woman (gravida 2,...

REVIEW ARTICLE: Thrombocytosis

Andrew I. Schafer, M.D. — Thu, 18Â MarÂ 2004 00:00:00 -05:00

Thrombocytosis is typically discovered as an incidental laboratory abnormality when the complete blood count is obtained for some unrelated reason. When found, however, it creates an important diagnostic challenge. Thrombocytosis...

PERSPECTIVE: Paul Ehrlich's Magic Bullets

Robert S. Schwartz, M.D. — Thu, 11Â MarÂ 2004 00:00:00 -05:00

March 14, 2004, marks the 150th anniversary of the birth of Paul Ehrlich, one of the generation of pioneers who, during the 50 years that led up to World War...

ORIGINAL ARTICLE: Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Disease

Thu, 26Â FebÂ 2004 00:00:00 -05:00

Background: The prevalence of pulmonary hypertension in adults with sickle cell disease, the mechanism of its development, and its prospective prognostic significance are unknown.

Methods: We performed Doppler echocardiographic assessments of...

PERSPECTIVE: Pulmonary Hypertension in Sickle Cell Disease

Elliott P. Vichinsky, M.D. — Thu, 26Â FebÂ 2004 00:00:00 -05:00

Sickle cell disease was first described in 1910 by Herrick and Irons. The irregularly shaped blood cells observed by Irons were those of Walter Clement Noel, a dental student with...

ORIGINAL ARTICLE: Effect of Eculizumab on Hemolysis and Transfusion Requirements in Patients with Paroxysmal Nocturnal Hemoglobinuria

Thu, 05Â FebÂ 2004 00:00:00 -05:00

Background: Paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation of the PIG-A gene in a hematopoietic stem cell and the subsequent production of blood cells with a deficiency of...

PERSPECTIVE: Black Mornings, Yellow Sunsets â A Day with Paroxysmal Nocturnal Hemoglobinuria

Robert S. Schwartz, M.D. — Thu, 05Â FebÂ 2004 00:00:00 -05:00

The first known description of hemoglobinuria â urine the color of a cola beverage â appears in a 13th-century text, the De Urinis of Johannes Zacharias (Actuarius), physician to the...

PERSPECTIVE: Daily Aspirin â Only Half the Answer

Jerry Spivak, M.D. — Thu, 08Â JanÂ 2004 00:00:00 -05:00

Polycythemia vera is a chronic clonal hematopoieticâstem-cell disorder of unknown cause characterized by autonomous bone marrow function. Among the long-term consequences of this unregulated hematopoiesis are the extramedullary production of...

ORIGINAL ARTICLE: Efficacy and Safety of Low-Dose Aspirin in Polycythemia Vera

Thu, 08Â JanÂ 2004 00:00:00 -05:00

Background: The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial.

Methods: We enrolled 518 patients with polycythemia vera, no clear indication for aspirin treatment, and...

CLINICAL PROBLEM-SOLVING: True, True, and Related

Thu, 01Â JanÂ 2004 00:00:00 -05:00

A 51-year-old woman was admitted to a community hospital with a six-week history of progressive shortness of breath. She had initially noted dyspnea when climbing stairs at work, and by...

EDITORIAL: Multiple Myeloma, 2004 â One or Two Transplants?

Edward A. Stadtmauer, M.D. — Thu, 25Â DecÂ 2003 00:00:00 -05:00

Contrary to a widely held belief, multiple myeloma is not a rare, rapidly fatal disorder that affects only elderly patients. Instead, it is the second most common hematologic cancer after...

ORIGINAL ARTICLE: Single versus Double Autologous Stem-Cell Transplantation for Multiple Myeloma

Thu, 25Â DecÂ 2003 00:00:00 -05:00

Background: We conducted a randomized trial of the treatment of multiple myeloma with high-dose chemotherapy followed by either one or two successive autologous stem-cell transplantations.

Methods: At the time of diagnosis,...

ORIGINAL ARTICLE: The Role of the Wnt-Signaling Antagonist DKK1 in the Development of Osteolytic Lesions in Multiple Myeloma

Thu, 25Â DecÂ 2003 00:00:00 -05:00

Background: Myeloma cells may secrete factors that affect the function of osteoblasts, osteoclasts, or both.

Methods: We subjected purified plasma cells from the bone marrow of patients with newly diagnosed multiple...

PERSPECTIVE: A New Insight into the Formation of Osteolytic Lesions in Multiple Myeloma

Thu, 25Â DecÂ 2003 00:00:00 -05:00

Multiple myeloma is a cancer in which immunoglobulin-producing plasma cells undergo clonal expansion. Its characteristic feature is the monoclonal, or M, spike, usually detectable in serum or urine by protein...

CLINICAL PROBLEM-SOLVING: Step by Step

Thu, 04Â DecÂ 2003 00:00:00 -05:00

A 63-year-old man presented to the emergency department for an evaluation of acute, mild rectal bleeding. He reported a two-week history of exertional dyspnea and generalized weakness, as well as...

ORIGINAL ARTICLE: Relation of an Interleukin-10 Promoter Polymorphism to Graft-versus-Host Disease and Survival after Hematopoietic-Cell Transplantation

Thu, 04Â DecÂ 2003 00:00:00 -05:00

Background: Polymorphisms in cytokine genes can influence immune responses, inflammation, and tissue injury and may affect the outcome of hematopoietic stem-cell transplantation.

Methods: We analyzed single-nucleotide polymorphisms in the genes for...

PERSPECTIVE: A Protective Gene for Graft-versus-Host Disease

Kenneth R. Cooke, M.D., and James L.M. Ferrara, M.D. — Thu, 04Â DecÂ 2003 00:00:00 -05:00

Hematopoietic stem-cell transplantation is an effective but toxic therapy for a number of life-threatening diseases, especially hematologic cancers. The principal complication of allogeneic stem-cell transplantation (the transplantation of grafts from...

IMAGES IN CLINICAL MEDICINE: Giant Hepatic Hemangioma

Toshimi Kaido, M.D. and Masayuki Imamura, M.D. — Thu, 13Â NovÂ 2003 00:00:00 -05:00

A 46-year-old woman had a one-year history of abdominal distention. Physical examination showed an upper-abdominal mass extending from the right hypochondrium to 10 cm below the umbilicus. Laboratory studies disclosed...

ORIGINAL ARTICLE: Transmission of West Nile Virus through Blood Transfusion in the United States in 2002

Thu, 25Â SepÂ 2003 00:00:00 -05:00

Background: During the 2002 West Nile virus epidemic in the United States, patients were identified whose West Nile virus illness was temporally associated with the receipt of transfused blood and...

PERSPECTIVE: Emerging Infections, Transfusion Safety, and Epidemiology

Roger Y. Dodd, Ph.D. — Thu, 25Â SepÂ 2003 00:00:00 -05:00

Over the past few decades, our optimism â or perhaps hubris â that infectious disease had been conquered has been overturned so completely that emerging infections are now a new...

CLINICAL PROBLEM-SOLVING: Anatomy of a Diagnosis

Thu, 04Â SepÂ 2003 00:00:00 -05:00

A 33-year-old man presented for evaluation of hemoptysis. He had been in his usual state of health until the day of presentation, when he had a transient cough productive of...

EDITORIAL: Immune Thrombocytopenic Purpura â Let the Treatment Fit the Patient

James N. George, M.D., and Sara K. Vesely, Ph.D. — Thu, 28Â AugÂ 2003 00:00:00 -05:00

Recognition of immune thrombocytopenic purpura is increasing because of the increasing frequency of routine blood counts that reveal unexpected thrombocytopenia. For patients who may have immune thrombocytopenic purpura, the essential...

ORIGINAL ARTICLE: Initial Treatment of Immune Thrombocytopenic Purpura with High-Dose Dexamethasone

Thu, 28Â AugÂ 2003 00:00:00 -05:00

Background: The role of high-dose dexamethasone in the treatment of immune thrombocytopenic purpura in adults is controversial. We assessed the effectiveness of high-dose dexamethasone as initial treatment in a series...

IMAGES IN CLINICAL MEDICINE: Hyperleukocytosis in Acute Myeloid Leukemia

Michael J. Mauro, M.D. — Thu, 21Â AugÂ 2003 00:00:00 -05:00

A 26-year-old woman was referred for progressive fatigue, dyspnea, blurred vision, and near-syncope. At presentation, she had marked pallor, pyrexia, diffuse nontender lymphadenopathy, and both preretinal and retinal hemorrhages. The...

ORIGINAL ARTICLE: Effect of Priming with Granulocyte Colony-Stimulating Factor on the Outcome of Chemotherapy for Acute Myeloid Leukemia

Thu, 21Â AugÂ 2003 00:00:00 -05:00

Background: Sensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML).

Methods: In a multicenter randomized trial, we assigned patients (age range,...

PERSPECTIVE: Hematopoietic Growth Factors and the Future of Therapeutic Research on Acute Myeloid Leukemia

Charles A. Schiffer, M.D. — Thu, 21Â AugÂ 2003 00:00:00 -05:00

Acute myeloid leukemia (AML) is a malignant disease resulting from acquired mutations that block the differentiation of primitive hematopoietic cells and thereby cause immature myeloid precursors to accumulate. The leukemia...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 25-2003 â A Newborn Boy with Petechiae and Thrombocytopenia

Thu, 14Â AugÂ 2003 00:00:00 -05:00

A newborn boy was admitted to a special-care nursery because of petechiae and thrombocytopenia.

The boy had been delivered at this hospital at 39 weeks' gestation to a 32-year-old woman who...

CLINICAL PRACTICE: Care of Patients Receiving Long-Term Anticoagulant Therapy

Sam Schulman, M.D. — Thu, 14Â AugÂ 2003 00:00:00 -05:00

A 75-year-old man with diabetes mellitus is found to have chronic atrial fibrillation, and warfarin therapy is begun for the prevention of thromboembolic stroke. How should the anticoagulant therapy be...

REVIEW ARTICLE: Adult Stem Cells for Tissue Repair â A New Therapeutic Concept?

Martin KÃ¶rbling, M.D., and Zeev Estrov, M.D. — Thu, 07Â AugÂ 2003 00:00:00 -05:00

Adult human stem cells that are intrinsic to various tissues have been described and characterized, some of them only recently. These cells are capable of maintaining, generating, and replacing terminally...

ORIGINAL ARTICLE: Acquired von Willebrand Syndrome in Aortic Stenosis

Thu, 24Â JulÂ 2003 00:00:00 -05:00

Background: Aortic-valve stenosis can be complicated by bleeding that is associated with acquired type 2A von Willebrand syndrome. However, the prevalence and cause of the hemostatic abnormality in aortic stenosis...

PERSPECTIVE: Aortic Stenosis, von Willebrand Factor, and Bleeding

J. Evan Sadler, M.D., Ph.D. — Thu, 24Â JulÂ 2003 00:00:00 -05:00

Some patients with aortic stenosis have recurrent bleeding into their skin or gastrointestinal tract. Several studies suggest that this bleeding is caused by an acquired defect in von Willebrand factor...

REVIEW ARTICLE: Nuclear Transplantation, Embryonic Stem Cells, and the Potential for Cell Therapy

Konrad Hochedlinger, Ph.D., and Rudolf Jaenisch, M.D. — Thu, 17Â JulÂ 2003 00:00:00 -05:00

Nuclear cloning, also referred to as nuclear transfer or nuclear transplantation, denotes the introduction of a nucleus from an adult donor cell into an enucleated oocyte to generate a cloned...

REVIEW ARTICLE: Prometheus's Vulture and the Stem-Cell Promise

Nadia Rosenthal, Ph.D. — Thu, 17Â JulÂ 2003 00:00:00 -05:00

When Prometheus transgressed the law of the ancient gods and stole fire for humankind, to teach them civilization and the arts, his punishment was typically brutal. Jupiter had the great...

EDITORIAL: Stem-Cell Transplantation for High-Risk Breast Cancer

Gerald J. Elfenbein, M.D. — Thu, 03Â JulÂ 2003 00:00:00 -05:00

The controversy over the question of whether to use high-dose chemotherapy and autologous hematopoietic stem-cell transplantation in women with high-risk breast cancer has persisted for more than a decade.1 It...

ORIGINAL ARTICLE: High-Dose Chemotherapy with Hematopoietic Stem-Cell Rescue for High-Risk Breast Cancer

Thu, 03Â JulÂ 2003 00:00:00 -05:00

Background: The use of high-dose adjuvant chemotherapy for high-risk primary breast cancer is controversial. We studied its efficacy in patients with 4 to 9 or 10 or more tumor-positive axillary...

ORIGINAL ARTICLE: Conventional Adjuvant Chemotherapy with or without High-Dose Chemotherapy and Autologous Stem-Cell Transplantation in High-Risk Breast Cancer

Thu, 03Â JulÂ 2003 00:00:00 -05:00

Background: The prognosis for women with primary breast cancer and 10 or more involved axillary lymph nodes is poor. High-dose chemotherapy with autologous hematopoietic stem-cell transplantation has been reported to...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 19-2003 â A Five-Day-Old Girl with Leukocytosis and a Worsening Rash from Birth

Lawrence C. Wolfe, M.D., Howard J. Weinstein, M.D., and Judith A. Ferry, M.D. — Thu, 19Â JunÂ 2003 00:00:00 -05:00

A five-day-old girl was admitted to the hospital because of a worsening rash from birth and leukocytosis with blasts.

The infant was delivered at 40 weeks' gestation by a 24-year-old woman...

IMAGES IN CLINICAL MEDICINE: Neurologic Manifestations of Vitamin B Deficiency

Katalin Scherer, M.D. — Thu, 29Â MayÂ 2003 00:00:00 -05:00

A 56-year-old woman presented with a four-month history of progressive cognitive decline, weakness, incoordination, and gait disturbance. She had a score of 12 of 28 on the MiniâMental State Examination,...

ORIGINAL ARTICLE: Pernicious Anemia with Neuropsychiatric Dysfunction in a Patient with Sickle Cell Anemia Treated with Folate Supplementation

Meekoo Dhar, M.D., Rita Bellevue, M.D., and Ralph Carmel, M.D. — Thu, 29Â MayÂ 2003 00:00:00 -05:00

03052932.xml The administration of folic acid can mask the megaloblastic anemia caused by cobalamin deficiency.12345 More critically, this masking, although neither complete nor permanent,234 can permit neurologic dysfunction to...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Platelet Storage â Time to Come in from the Cold?

Edward L. Snyder, M.D., and Henry M. Rinder, M.D. — Thu, 15Â MayÂ 2003 00:00:00 -05:00

Refrigerated platelets have better in vitro function than those stored at room temperature,1 but once transfused, they are rapidly cleared from the circulation. Thus, platelets are currently stored at room...

ORIGINAL ARTICLE: High-Dose Chemotherapy with Hematopoietic Stem-Cell Rescue for Multiple Myeloma

Thu, 08Â MayÂ 2003 00:00:00 -05:00

Background: High-dose therapy with supporting autologous stem-cell transplantation remains a controversial treatment for cancer. In multiple myeloma, first-line regimens incorporating high-dose therapy yield higher remission rates than do conventional-dose treatments,...

REVIEW ARTICLE: Molecular Diagnosis of the Hematologic Cancers

Louis M. Staudt, M.D., Ph.D. — Thu, 01Â MayÂ 2003 00:00:00 -05:00

The diagnosis of the hematologic cancers presents a daunting challenge. The many stages of normal hematopoietic differentiation give rise to a number of biologically and clinically distinct cancers. Inherited DNA-sequence...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 13-2003 â A 14-Month-Old Boy with Hepatomegaly, Perianal Lesions, and a Bony Lump on the Forehead

G. Naheed Usmani, M.D., Sjirk J. Westra, M.D., and Souhad Younes, M.D. — Thu, 24Â AprÂ 2003 00:00:00 -05:00

A 14-month-old boy was admitted to the hospital because of hepatomegaly, left-sided ptosis, and a bony lump on the forehead.

The patient had been constipated for several months, passing one hard...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Hemoglobin and the Paracrine and Endocrine Functions of Nitric Oxide

Alan N. Schechter, M.D., and Mark T. Gladwin, M.D. — Thu, 10Â AprÂ 2003 00:00:00 -05:00

Nitric oxide is a highly reactive molecule with many biologic effects. Its function as the âendothelium-derived relaxing factorâ that regulates vascular tone is a central feature of its role as...

IMAGES IN CLINICAL MEDICINE: Hematoma of the Rectus Sheath

David R. Gutknecht, M.D. — Thu, 10Â AprÂ 2003 00:00:00 -05:00

A 79-year-old woman who was taking warfarin and enoxaparin because of deep venous thrombosis reported abdominal pain after coughing. On physical examination, a mass was felt in the left side...

ORIGINAL ARTICLE: A Tyrosine Kinase Created by Fusion of the and Genes as a Therapeutic Target of Imatinib in Idiopathic Hypereosinophilic Syndrome

Thu, 27Â MarÂ 2003 00:00:00 -05:00

Background: Idiopathic hypereosinophilic syndrome involves a prolonged state of eosinophilia associated with organ dysfunction. It is of unknown cause. Recent reports of responses to imatinib in patients with the syndrome...

PERSPECTIVE: The Hypereosinophilic Syndrome and the Biology of Cancer

Robert S. Schwartz, M.D. — Thu, 27Â MarÂ 2003 00:00:00 -05:00

Patients with sustained high-grade eosinophilia without an evident cause usually receive the diagnosis of hypereosinophilic syndrome, a high-sounding term that only masks our ignorance. Apart from the consistent presence of...

CLINICAL PROBLEM-SOLVING: Easy to See but Hard to Find

Brendan M. Reilly, M.D., Peter Clarke, M.D., and Petros Nikolinakos, M.D. — Thu, 02Â JanÂ 2003 00:00:00 -05:00

A 46-year-old woman from the Philippines with no history of serious medical conditions was hospitalized with fatigue, body aches, and a weight loss of 4.5 kg (10 lb) over the...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 33-2002 â A 28-Year-Old Woman with Ocular Inflammation, Fever, and Headache

Stuart B. Mushlin, Jeffrey M. Drazen, Martin A. Samuels, and Eugene J. Mark — Thu, 24Â OctÂ 2002 00:00:00 -05:00

A 28-year-old woman was admitted to the hospital because of ocular inflammation, fever, and headache.

The patient had been well until three weeks earlier, when a cough developed, initially productive of...

EDITORIAL: Effect of Consanguinity on Screening for Thalassemia

Thu, 10Â OctÂ 2002 00:00:00 -05:00

The Î²-thalassemias are among the most common autosomal recessive disorders. They have a remarkably high frequency in the Mediterranean region, the Middle East, the Indian subcontinent, and East Asia. The...

SPECIAL ARTICLE: Screening Extended Families for Genetic Hemoglobin Disorders in Pakistan

Thu, 10Â OctÂ 2002 00:00:00 -05:00

Background: We have investigated a strategy for identifying and counseling carriers of recessively inherited disorders in developing countries where consanguineous marriage is common. In such communities, gene variants are trapped...

ORIGINAL ARTICLE: Salmonella Sepsis Caused by a Platelet Transfusion from a Donor with a Pet Snake

Thu, 03Â OctÂ 2002 00:00:00 -05:00

Platelet transfusions carry a serious risk of bacterial sepsis. Platelets are stored at room temperature for no longer than 120 hours (five days), and a single bacterium of the type...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: COX Inhibitors and Thromboregulation

Thu, 26Â SepÂ 2002 00:00:00 -05:00

From a historical perspective, there is perhaps no more interesting therapeutic saga than that of aspirin, which began as a folk remedy, distilled from willow bark, and became a lifesaving...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 29-2002 â A 17-Year-Old Boy with Acute Mitral Regurgitation and Pulmonary Edema

Bradley J. Bloom and R. Neal Smith — Thu, 19Â SepÂ 2002 00:00:00 -05:00

A 17-year-old boy was admitted to the hospital because of acute mitral regurgitation and pulmonary edema.

The patient had received a diagnosis of juvenile spondyloarthropathy two years earlier. He had intermittent...

REVIEW ARTICLE: Thrombotic Microangiopathies

Joel L. Moake, M.D. — Thu, 22Â AugÂ 2002 00:00:00 -05:00

The thrombotic microangiopathies are microvascular occlusive disorders characterized by systemic or intrarenal aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes. In thrombotic thrombocytopenic purpura, systemic microvascular aggregation of platelets...

IMAGES IN CLINICAL MEDICINE: Malaria and Sickle Cell Disease

Fouad N. Boctor, M.D., Ph.D. and Joan Uehlinger, M.D. — Thu, 04Â JulÂ 2002 00:00:00 -05:00

Figure 1. A 23-year-old man with sickle cell disease was admitted after reporting fever and chills. He had emigrated from West Africa three months earlier. His temperature was 38.2Â°C, and...

CLINICAL PRACTICE: Long-Term Care after Hematopoietic-Cell Transplantation in Adults

Joseph H. Antin, M.D. — Thu, 04Â JulÂ 2002 00:00:00 -05:00

A 35-year-old man who had undergone allogeneic hematopoietic-cell transplantation two years earlier for acute myeloid leukemia recently moved to a new town. He comes in for a general checkup because...

ORIGINAL ARTICLE: Absence of Association of Thrombophilia Polymorphisms with Intrauterine Growth Restriction

Thu, 04Â JulÂ 2002 00:00:00 -05:00

Background: Previous data have demonstrated associations between thrombophilia polymorphisms in pregnant women and an increased risk of intrauterine growth restriction in their offspring, but this finding remains uncertain.

Methods: We performed...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 19-2002 â A 13-Year-Old Girl with a Mass in the Left Parotid Gland and Regional Lymph Nodes

Trevor J.I. McGill and C.-L. Wu — Thu, 20Â JunÂ 2002 00:00:00 -05:00

A 13-year-old girl was admitted to the Massachusetts Eye and Ear Infirmary because of a mass in the left parotid gland.

The patient had been well until four or five months...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 16-2002 â A 41-Year-Old Woman with Global Headache and an Intracranial Mass

David E. Thaler and Matthew P. Frosch — Thu, 23Â MayÂ 2002 00:00:00 -05:00

A 41-year-old woman was admitted to the hospital because of an intracranial mass.

The patient had been in excellent health until one week earlier, when a global headache developed, accompanied by...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 15-2002 â A 53-Year-Old Man with a Myocardial Infarct and Thromboses after Coronary-Artery Bypass Grafting

William C. Aird and Eugene J. Mark — Thu, 16Â MayÂ 2002 00:00:00 -05:00

A 53-year-old man was admitted to the hospital because of a myocardial infarction.

The patient had been well until three months earlier, when he began to have increasingly severe exertional dyspnea,...

REVIEW ARTICLE: Major Radiation Exposure â What to Expect and How to Respond

Fred A. Mettler, Jr., M.D., M.P.H., and George L. Voelz, M.D. — Thu, 16Â MayÂ 2002 00:00:00 -05:00

Uncontrolled, large-scale exposure to radiation has been caused by the detonation of atomic bombs over Japan, fallout from atomic-bomb tests, nuclear-reactor accidents, and the release of material from radiotherapy devices....

EDITORIAL: Can Human Hematopoietic Stem Cells Become Skin, Gut, or Liver Cells?

Thu, 07Â MarÂ 2002 00:00:00 -05:00

Hematopoietic stem cells maintain hematopoiesis and reestablish blood-cell production after bone marrow transplantation. Abnormal clonal expansion of these stem cells may result in chronic myelogenous leukemia, polycythemia vera, and the...

ORIGINAL ARTICLE: Hepatocytes and Epithelial Cells of Donor Origin in Recipients of Peripheral-Blood Stem Cells

Thu, 07Â MarÂ 2002 00:00:00 -05:00

Background: Bone marrow contains stem cells with the potential to differentiate into mature cells of various organs. We determined whether circulating stem cells have a similar potential.

Methods: Biopsy specimens from...

EDITORIAL: Proteolytic Antibodies against Factor VIII in Hemophilia A

Thu, 28Â FebÂ 2002 00:00:00 -05:00

Inhibitory antibodies to factor VIII arise in more than 20 percent of patients with hemophilia A who receive replacement therapy with factor VIII protein.1 Since these antibodies profoundly complicate the...

ORIGINAL ARTICLE: The Prevalence of Proteolytic Antibodies against Factor VIII in Hemophilia A

Thu, 28Â FebÂ 2002 00:00:00 -05:00

Background: Factor VIII inhibitors are IgG alloantibodies that arise during replacement therapy in 25 to 50 percent of patients with severe hemophilia A. The hydrolysis of factor VIII by antiâfactor...

SOUNDING BOARD: Blood and Disaster â Supply and Demand

Thu, 21Â FebÂ 2002 00:00:00 -05:00

The terrorist attacks on September 11, 2001, which resulted in approximately 3000 deaths and more than 4000 injuries, had a predictable effect: people wanted to donate blood. This altruistic and...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 6-2002 â A 54-Year-Old Woman with Left, Then Right, Central-Retinal-Vein Occlusion

Robert Weinstein, M.D., and Mohammad Mahmood, M.D. — Thu, 21Â FebÂ 2002 00:00:00 -05:00

A 54-year-old woman was admitted to the hospital because of occlusion of the central retinal vein in her left eye, followed by occlusion of the central retinal vein in her...

ORIGINAL ARTICLE: A Long-Term Study of Prognosis in Monoclonal Gammopathy of Undetermined Significance

Thu, 21Â FebÂ 2002 00:00:00 -05:00

Background: A monoclonal gammopathy of undetermined significance (MGUS) occurs in up to 2 percent of persons 50 years of age or older. Reliable predictors of progression have not been identified,...

EDITORIAL: Drug-Induced Autoimmune Red-Cell Aplasia

Thu, 14Â FebÂ 2002 00:00:00 -05:00

Whether judged by its therapeutic or economic impact, recombinant human erythropoietin (epoetin) is an extremely successful application of molecular genetic technology to the development of a therapeutic agent. Epoetin is...

ORIGINAL ARTICLE: Pure Red-Cell Aplasia and Antierythropoietin Antibodies in Patients Treated with Recombinant Erythropoietin

Thu, 14Â FebÂ 2002 00:00:00 -05:00

Background: Within a period of three years, we identified 13 patients in whom pure red-cell aplasia developed during treatment with recombinant human erythropoietin (epoetin). We investigated whether there was an...

EDITORIAL: The HemolyticâUremic Syndrome â Toxin, Thrombin, and Thrombosis

Thu, 03Â JanÂ 2002 00:00:00 -05:00

The term âhemolyticâuremic syndromeâ was coined by Gasser et al. in 19551 to describe a devastating illness consisting of acute renal failure accompanied by nonimmune hemolytic anemia and thrombocytopenia. Although...

ORIGINAL ARTICLE: Prothrombotic Coagulation Abnormalities Preceding the HemolyticâUremic Syndrome

Thu, 03Â JanÂ 2002 00:00:00 -05:00

Background: The hemolyticâuremic syndrome is a thrombotic complication of Escherichia coli O157:H7 infection. It is not known whether the coagulation abnormalities precede, and potentially cause, this disorder.

Methods: In 53 children...

ORIGINAL ARTICLE: Cyclooxygenase Inhibitors and the Antiplatelet Effects of Aspirin

Thu, 20Â DecÂ 2001 00:00:00 -05:00

Background: Patients with arthritis and vascular disease may receive both low-dose aspirin and other nonsteroidal antiinflammatory drugs. We therefore investigated potential interactions between aspirin and commonly prescribed arthritis therapies.

Methods: We...

IMAGES IN CLINICAL MEDICINE: Disseminated Intravascular Coagulopathy

Sheldon Bastacky, M.D. and Robert E. Lee, M.D. — Thu, 08Â NovÂ 2001 00:00:00 -05:00

Figure 1. A 34-year-old man with the acquired immunodeficiency syndrome, hemoglobin SC chronic hemolytic anemia, and recurrent episodes of pneumonia due to gram-negative bacteria, cryptococcus, and most recently, aspergillus was...

EDITORIAL: Anemia, Transfusion, and Mortality

Thu, 25Â OctÂ 2001 00:00:00 -05:00

Questions surrounding the risks and costs associated with blood transfusion have led to a reevaluation of clinical transfusion practices during the past 15 years.1 Guidelines for blood transfusion have been...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 27-2001 â A 50-Year-Old Man with Marked Splenomegaly and Anemia

Noopur Raje, M.D., and Judith A. Ferry, M.D. — Thu, 30Â AugÂ 2001 00:00:00 -05:00

A 50-year-old man was admitted to the hospital because of marked splenomegaly and anemia.

The patient had been in good health until three months earlier, when he began to have progressive...

IMAGES IN CLINICAL MEDICINE: A Hair-on-End Skull

Cesar Ramos-Remus, M.D. and Federico Galvan-Villegas, M.D. — Thu, 02Â AugÂ 2001 00:00:00 -05:00

Figure 1. A 24-year-old man with thalassemia major was seen for joint pain without swelling in both ankles and hands. He had received a total of 37 transfusions. He had...

EDITORIAL: Hematopoietic Stem-Cell Transplants Using Umbilical-Cord Blood

Thu, 14Â JunÂ 2001 00:00:00 -05:00

Transplantation of umbilical-cord blood was successfully performed for the first time in 1988 to treat a boy with Fanconi's anemia; the donor, the boy's newborn sister, was a perfect HLA...

ORIGINAL ARTICLE: Hematopoietic Engraftment and Survival in Adult Recipients of Umbilical-Cord Blood from Unrelated Donors

Thu, 14Â JunÂ 2001 00:00:00 -05:00

Background: Umbilical-cord blood from unrelated donors who are not HLA-identical with the recipients can restore hematopoiesis after myeloablative therapy in children. We studied the use of transplantation of umbilical-cord blood...

EDITORIAL: Gene Therapy for Hemophilia

Thu, 07Â JunÂ 2001 00:00:00 -05:00

The current treatment of hemophilia, whether due to a deficiency of factor VIII or factor IX â as reviewed in this issue of the Journal 1 â consists of periodic...

REVIEW ARTICLE: The Hemophilias â From Royal Genes to Gene Therapy

Pier M. Mannucci, M.D., and Edward G.D. Tuddenham, M.D. — Thu, 07Â JunÂ 2001 00:00:00 -05:00

Of the various types of hemophilia, the most common of these lifelong bleeding disorders are due to an inherited deficiency of factor VIII or factor IX (Table 1). The genes...

ORIGINAL ARTICLE: Nonviral Transfer of the Gene Encoding Coagulation Factor VIII in Patients with Severe Hemophilia A

Thu, 07Â JunÂ 2001 00:00:00 -05:00

Background: We tested the safety of a nonviral somatic-cell gene-therapy system in patients with severe hemophilia A.

Methods: An open-label, phase 1 trial was conducted in six patients with severe hemophilia...

IMAGES IN CLINICAL MEDICINE: Erythrophagocytosis

Giambattista Lobreglio, M.D. and Antonio Valacca, M.D. — Thu, 22Â MarÂ 2001 00:00:00 -05:00

Figure 1. A 50-year-old woman presented with fatigue, pallor, and jaundice after taking cefotetan and netilmicin for a respiratory tract infection. The hemoglobin level was 3.1 g per deciliter, the...

ORIGINAL ARTICLE: Treatment of Chronic Granulomatous Disease with Nonmyeloablative Conditioning and a T-CellâDepleted Hematopoietic Allograft

Thu, 22Â MarÂ 2001 00:00:00 -05:00

Background: The treatment of chronic granulomatous disease with conventional allogeneic hematopoietic stem-cell transplantation carries a high risk of serious complications and death. We investigated the feasibility of stem-cell transplantation without...

IMAGES IN CLINICAL MEDICINE: WaldenstrÃ¶m's Macroglobulinemia

Gerburg Wulf, M.D. and Stephen Pool, M.D. — Thu, 15Â MarÂ 2001 00:00:00 -05:00

Figure 1. A 65-year-old man had an 18-month history of slowly progressive swelling and discoloration of both ears, fatigue, night sweats, weight loss, occipital headaches, and photophobia. On examination, his...

ORIGINAL ARTICLE: Transplantation of Bone Marrow as Compared with Peripheral-Blood Cells from HLA-Identical Relatives in Patients with Hematologic Cancers

Thu, 18Â JanÂ 2001 00:00:00 -05:00

Background: In recipients of allogeneic hematopoietic-cell transplants, peripheral-blood cells mobilized with the use of filgrastim (recombinant granulocyte colony-stimulating factor) engraft more rapidly than bone marrow. However, the relative effects of...

ORIGINAL ARTICLE: Disease-Related Conditions in Relatives of Patients with Hemochromatosis

Thu, 23Â NovÂ 2000 00:00:00 -05:00

Background: Hemochromatosis occurs in approximately 5 white people per 1000 and is usually due to homozygosity for mutations in the HLA-linked HFE gene. Although screening has been proposed, the proportion...

ORIGINAL ARTICLE: Bone Marrow Failure Associated with Human Herpesvirus 8 Infection after Transplantation

Thu, 09Â NovÂ 2000 00:00:00 -05:00

Background: Human herpesvirus 8 (HHV-8) infection has been linked to the development of Kaposi's sarcoma and to rare lymphoproliferative disorders.

Methods: We used molecular methods, serologic methods, in situ hybridization, and...

ORIGINAL ARTICLE: Mutations in Coagulation Factors in Women with Unexplained Late Fetal Loss

Thu, 05Â OctÂ 2000 00:00:00 -05:00

Background: The Factor V Leiden and prothrombin-gene mutations are independent risk factors for venous thrombosis; it is debated whether a mutation in the gene encoding methylenetetrahydrofolate reductase, an enzyme involved...

IMAGES IN CLINICAL MEDICINE: Childhood Idiopathic Pulmonary Hemosiderosis

Charles Keller, M.D. and Claire Langston, M.D. — Thu, 14Â SepÂ 2000 00:00:00 -05:00

Figure 1. A three-year-old girl with a declining growth rate and recurrent iron-deficiency anemia presented with a five-day history of nonproductive cough, fever, and anorexia. In association with an upper...

ORIGINAL ARTICLE: Genetic and Clinical Features of Hemoglobin H Disease in Chinese Patients

Thu, 24Â AugÂ 2000 00:00:00 -05:00

Background: Normally, one pair of each of the two Î±-globin genes, Î±1 and Î±2, resides on each copy of chromosome 16. In hemoglobin H disease, three of these four Î±-globin...

ORIGINAL ARTICLE: High Plasma Levels of Factor VIII and the Risk of Recurrent Venous Thromboembolism

Thu, 17Â AugÂ 2000 00:00:00 -05:00

Background: A high plasma level of factor VIII is a risk factor for venous thromboembolism. We evaluated the risk of a recurrence of thrombosis after an initial episode of spontaneous...

IMAGES IN CLINICAL MEDICINE: Methemoglobinemia

Gerard B. Donnelly, M.D. and Diana Randlett, M.S. — Thu, 03Â AugÂ 2000 00:00:00 -05:00

Figure 1. A 39-year-old woman who had a small-bowel obstruction after resection of an appendiceal carcinoid tumor was given benzocaine topical spray for retropharyngeal discomfort from a nasogastric tube. Within...

ORIGINAL ARTICLE: Hepatic Iron Concentration and Total Body Iron Stores in Thalassemia Major

Thu, 03Â AugÂ 2000 00:00:00 -05:00

Background: and Methods: We tested the usefulness of measuring the hepatic iron concentration to evaluate total body iron stores in patients who had been cured of thalassemia major by bone...

ORIGINAL ARTICLE: Incidence of Cancer after Prophylaxis with Warfarin against Recurrent Venous Thromboembolism

Thu, 29Â JunÂ 2000 00:00:00 -05:00

Background: The length of time after an episode of venous thromboembolism during which the risk of newly diagnosed cancer is increased is not known, and whether vitamin K antagonists have...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Blockade of Adhesion of Sickle Cells to Endothelium by Monoclonal Antibodies

Thu, 22Â JunÂ 2000 00:00:00 -05:00

Red cells that contain sickle hemoglobin tend to acquire an abnormal, sickled shape when their mutant hemoglobin polymerizes as a result of low oxygen tension. In the classic view of...

EDITORIAL: The Acute Chest Syndrome of Sickle Cell Disease

Thu, 22Â JunÂ 2000 00:00:00 -05:00

It has become a clichÃ© to say that sickle cell anemia is the first âmolecular disease.â1 The substitution of valine for glycine in Î²-globin has been known as the cause...

ORIGINAL ARTICLE: Causes and Outcomes of the Acute Chest Syndrome in Sickle Cell Disease

Thu, 22Â JunÂ 2000 00:00:00 -05:00

Background: The acute chest syndrome is the leading cause of death among patients with sickle cell disease. Since its cause is largely unknown, therapy is supportive. Pilot studies with improved...

ORIGINAL ARTICLE: Graft-Versus-Host Disease in Children Who Have Received a Cord-Blood or Bone Marrow Transplant from an HLA-Identical Sibling

Thu, 22Â JunÂ 2000 00:00:00 -05:00

Background: Umbilical-cord blood as an alternative to bone marrow for hematopoietic stem-cell transplantation may lower the risk of graft-versus-host disease (GVHD).

Methods: We studied the records of 113 recipients of cord...

EDITORIAL: Thrombotic Thrombocytopenic Purpura and Clopidogrel â A Need for New Approaches to Drug Safety

Thu, 15Â JunÂ 2000 00:00:00 -05:00

In this issue of the Journal, Bennett et al. describe 11 cases of thrombotic thrombocytopenic purpura that occurred in patients during or shortly after they received clopidogrel.1 The evidence linking...

REVIEW ARTICLE: Plasminogen-Activator Inhibitor Type 1 and Coronary Artery Disease

Hans P. Kohler, M.D., and Peter J. Grant, M.D. — Thu, 15Â JunÂ 2000 00:00:00 -05:00

The development of coronary artery disease, and specifically myocardial infarction, involves hyperplasia of arterial smooth muscle, the development of fatty streaks, atheroma formation, plaque rupture, and ultimately thrombus formation and...

ORIGINAL ARTICLE: Thrombotic Thrombocytopenic Purpura Associated with Clopidogrel

Thu, 15Â JunÂ 2000 00:00:00 -05:00

Background: The antiplatelet drug clopidogrel is a new thienopyridine derivative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ticlopidine-associated thrombotic thrombocytopenic...

EDITORIAL: The Prospects for Red-Cell Substitutes

Thu, 01Â JunÂ 2000 00:00:00 -05:00

Blood is still the best thing possible to have in our veins, according to Woody Allen, and that is certainly the case when the blood is our own. We are...

ORIGINAL ARTICLE: Transfusions of Polymerized Bovine Hemoglobin in a Patient with Severe Autoimmune Hemolytic Anemia

Thu, 01Â JunÂ 2000 00:00:00 -05:00

Hemoglobin solutions have several potential advantages as substitutes for erythrocytes for transfusion. Hemoglobin solutions have a prolonged shelf life, are associated with a lower risk of transfusion reactions, and provide...

ORIGINAL ARTICLE: Eosinophilia with Aberrant T Cells and Elevated Serum Levels of Interleukin-2 and Interleukin-15

Thu, 25Â MayÂ 2000 00:00:00 -05:00

The hypereosinophilic syndrome comprises various idiopathic myeloproliferative disorders with sustained eosinophilia and damage to the heart, lungs, skin, and other organs by infiltrating eosinophils.1 A single mechanism for this syndrome...

SOUNDING BOARD: Fortification of Foods with Folic Acid â How Much is Enough?

Thu, 11Â MayÂ 2000 00:00:00 -05:00

In the early 1990s two randomized clinical trials showed that folic acid, or multivitamins containing folic acid, could substantially reduce a woman's risk of bearing a child with a neural-tube...

ORIGINAL ARTICLE: Thymic Function after Hematopoietic Stem-Cell Transplantation for the Treatment of Severe Combined Immunodeficiency

Thu, 04Â MayÂ 2000 00:00:00 -05:00

Background: Immune function can be restored in infants with severe combined immunodeficiency by transplantation of unfractionated bone marrow from HLA-identical donors or T-cellâdepleted marrow stem cells from haploidentical donors, with...

REVIEW ARTICLE: Myelofibrosis with Myeloid Metaplasia

Ayalew Tefferi, M.D. — Thu, 27Â AprÂ 2000 00:00:00 -05:00

Myelofibrosis with myeloid metaplasia is classified broadly as a chronic myeloid disorder and, more specifically, as a chronic myeloproliferative disease1 (Figure 1). The primary pathogenetic mechanism is a clonal stem-cell...

EDITORIAL: High-Dose Chemotherapy plus Autologous Bone Marrow Transplantation for Metastatic Breast Cancer

Thu, 13Â AprÂ 2000 00:00:00 -05:00

In this issue of the Journal, Stadtmauer et al. present the results of a clinical trial in which conventional-dose chemotherapy was compared with high-dose chemotherapy plus autologous bone marrow transplantation...

ORIGINAL ARTICLE: Conventional-Dose Chemotherapy Compared with High-Dose Chemotherapy plus Autologous Hematopoietic Stem-Cell Transplantation for Metastatic Breast Cancer

Thu, 13Â AprÂ 2000 00:00:00 -05:00

Background: We conducted a randomized trial in which we compared high-dose chemotherapy plus hematopoietic stem-cell rescue with a prolonged course of monthly conventional-dose chemotherapy in women with metastatic breast cancer.

Methods:...

IMAGES IN CLINICAL MEDICINE: Ischemic Retinopathy Caused by Severe Megaloblastic Anemia

Kenneth Li, M.B., Ch.B. and Gerald McKay, M.B., Ch.B. — Thu, 23Â MarÂ 2000 00:00:00 -05:00

Figure 1. A 36-year-old woman who had been a vegan for many years presented with a one-week history of decreased visual acuity. She had had megaloblastic anemia six years earlier...

ORIGINAL ARTICLE: High Levels of Coagulation Factor XI as a Risk Factor for Venous Thrombosis

Thu, 09Â MarÂ 2000 00:00:00 -05:00

Background: Factor XI, a component of the intrinsic pathway of coagulation, contributes to the generation of thrombin, which is involved in both the formation of fibrin and protection against fibrinolysis....

EDITORIAL: The Challenge of Thrombophilia in MaternalâFetal Medicine

Thu, 10Â FebÂ 2000 00:00:00 -05:00

Twenty years ago we did not have a problem with thrombophilia as a cause of venous thromboembolism in pregnant and postpartum women, or rather, we did not know we had...

ORIGINAL ARTICLE: Prothrombin and Factor V Mutations in Women with a History of Thrombosis during Pregnancy and the Puerperium

Thu, 10Â FebÂ 2000 00:00:00 -05:00

Background: Venous thromboembolism is a leading cause of morbidity and mortality during pregnancy and the puerperium. However, the role of mutations in the prothrombin and factor V genes and other...

ORIGINAL ARTICLE: Correction of the Hyper-IgM Syndrome after Liver and Bone Marrow Transplantation

Thu, 03Â FebÂ 2000 00:00:00 -05:00

The hyper-IgM syndrome, a rare form of combined primary immunodeficiency, is characterized by neutropenia and defective B-cell isotype switching, which results in elevated or normal levels of serum IgM and...

ORIGINAL ARTICLE: Prediction of Adverse Outcomes in Children with Sickle Cell Disease

Thu, 13Â JanÂ 2000 00:00:00 -05:00

Background: The ability to identify infants with sickle cell anemia who are likely to have severe complications later in life would permit accurate prognostication and tailoring of therapy to match...

ORIGINAL ARTICLE: Noninvasive Diagnosis by Doppler Ultrasonography of Fetal Anemia Due to Maternal Red-Cell Alloimmunization

Thu, 06Â JanÂ 2000 00:00:00 -05:00

Background: Invasive techniques such as amniocentesis and cordocentesis are used for diagnosis and treatment in fetuses at risk for anemia due to maternal red-cell alloimmunization. The purpose of our study...

EDITORIAL: Noninvasive Testing for Fetal Anemia

Thu, 06Â JanÂ 2000 00:00:00 -05:00

Despite the introduction of anti-D immune globulin (Rh immunoglobulin) for the prevention of anti-D red-cell alloimmunization, hemolytic disease of the newborn continues to occur because of the lack or failure...

IMAGES IN CLINICAL MEDICINE: in a Peripheral-Blood Smear

M. Edelman, M.B., B.Ch. and J. Mckitrick, Ph.D. — Thu, 06Â JanÂ 2000 00:00:00 -05:00

Figure 1. A 45-year-old man with the acquired immunodeficiency syndrome presented with night sweats, fatigue, cachexia, and a productive cough. He had a fever (temperature, 40Â°C), tachycardia (heart rate, 136...

REVIEW ARTICLE: Disorders of Iron Metabolism

Nancy C. Andrews, M.D., Ph.D. — Thu, 23Â DecÂ 1999 00:00:00 -05:00

Iron has the capacity to accept and donate electrons readily, interconverting between ferric (Fe2+) and ferrous (Fe3+) forms. This capability makes it a useful component of cytochromes, oxygen-binding molecules (i.e.,...

EDITORIAL: Thalidomide â A Revival Story

Thu, 18Â NovÂ 1999 00:00:00 -05:00

One of the most devastating tragedies of modern medicine was set into motion by the over-the-counter marketing of thalidomide in Europe during the late 1950s for the treatment of morning...

ORIGINAL ARTICLE: Antitumor Activity of Thalidomide in Refractory Multiple Myeloma

Thu, 18Â NovÂ 1999 00:00:00 -05:00

Background: Patients with myeloma who relapse after high-dose chemotherapy have few therapeutic options. Since increased bone marrow vascularity imparts a poor prognosis in myeloma, we evaluated the efficacy of thalidomide,...

ORIGINAL ARTICLE: Alloimmune Thrombocytopenia after Organ Transplantation

Thu, 11Â NovÂ 1999 00:00:00 -05:00

Transplanted organs, particularly livers and kidneys, carry passenger lymphocytes that can transmit autoimmune diseases1 or initiate alloimmune disorders2 in the recipient. We recently treated three unrelated patients who each received...

EDITORIAL: Eosinophilia â Idiopathic or Not?

Thu, 07Â OctÂ 1999 00:00:00 -05:00

In countries where parasitic diseases are prevalent, these infections cause most cases of eosinophilia. Elsewhere, the majority of patients with eosinophilia are found to have atopy or, less often, drug...

ORIGINAL ARTICLE: Abnormal Clones of T Cells Producing Interleukin-5 in Idiopathic Eosinophilia

Thu, 07Â OctÂ 1999 00:00:00 -05:00

Background: The cause of persistent eosinophilia and the hypereosinophilic syndrome is unknown. Recent work suggests that in some patients with the hypereosinophilic syndrome, a clone of abnormal T cells produces...

REVIEW ARTICLE: Fever in Immunocompromised Patients

Philip A. Pizzo, M.D. — Thu, 16Â SepÂ 1999 00:00:00 -05:00

The past two decades have witnessed an increase in the number of patients who are immunocompromised as a consequence of a primary or secondary immunodeficiency disorder or from the use...

ORIGINAL ARTICLE: The Risk of Recurrent Deep Venous Thrombosis among Heterozygous Carriers of Both Factor V Leiden and the G20210A Prothrombin Mutation

Thu, 09Â SepÂ 1999 00:00:00 -05:00

Background: Point mutations in the factor V gene (factor V Leiden) and the prothrombin gene (the substitution of A for G at position 20210) are the most common causes of...

EDITORIAL: Clinical Implications of the Hemochromatosis Gene

Thu, 02Â SepÂ 1999 00:00:00 -05:00

Hereditary hemochromatosis is the most common genetic disorder in whites. The prevalence of this condition (i.e., of homozygosity for the faulty gene) in the white population is approximately 1 in...

ORIGINAL ARTICLE: Hereditary Hemochromatosis in Adults without Pathogenic Mutations in the Hemochromatosis Gene

Thu, 02Â SepÂ 1999 00:00:00 -05:00

Background: and Methods: Hereditary hemochromatosis in adults is usually characterized by mutations in the hemochromatosis (HFE) gene on the short arm of chromosome 6. Most patients have a substitution of...

ORIGINAL ARTICLE: A Population-Based Study of the Clinical Expression of the Hemochromatosis Gene

Thu, 02Â SepÂ 1999 00:00:00 -05:00

Background: and Methods: Hereditary hemochromatosis is associated with homozygosity for the C282Y mutation in the hemochromatosis (HFE) gene on chromosome 6, elevated serum transferrin saturation, and excess iron deposits throughout...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: âTurning Brain into Bloodâ â Clinical Applications of Stem-Cell Research in Neurobiology and Hematology

Thu, 19Â AugÂ 1999 00:00:00 -05:00

A recent report by Bjornson et al.1 of a study entitled, in part, âTurning Brain into Bloodâ challenges much of the dogma in the field of stem-cell research by claiming...

REVIEW ARTICLE: Disseminated Intravascular Coagulation

Marcel Levi, M.D., and Hugo ten Cate, M.D. — Thu, 19Â AugÂ 1999 00:00:00 -05:00

Disseminated intravascular coagulation is characterized by the widespread activation of coagulation, which results in the intravascular formation of fibrin and ultimately thrombotic occlusion of small and midsize vessels.123 Intravascular coagulation...

REVIEW ARTICLE: Drug Treatment of Lipid Disorders

Robert H. Knopp, M.D. — Thu, 12Â AugÂ 1999 00:00:00 -05:00

Arteriosclerosis of the coronary and peripheral vasculature is the leading cause of death among men and women in the United States1 and worldwide.2 In 1992, for example, cardiovascular disease accounted...

EDITORIAL: Fever and Neutropenia â How to Use a New Treatment Strategy

Thu, 29Â JulÂ 1999 00:00:00 -05:00

The treatment of fever and neutropenia has evolved with the development of both new antimicrobial drugs and new strategies for using them. More than three decades ago, Bodey and colleagues...

ORIGINAL ARTICLE: Oral versus Intravenous Empirical Antimicrobial Therapy for Fever in Patients with Granulocytopenia Who Are Receiving Cancer Chemotherapy

Thu, 29Â JulÂ 1999 00:00:00 -05:00

Background: Intravenously administered antimicrobial agents have been the standard choice for the empirical management of fever in patients with cancer and granulocytopenia. If orally administered empirical therapy is as effective...

ORIGINAL ARTICLE: A Double-Blind Comparison of Empirical Oral and Intravenous Antibiotic Therapy for Low-Risk Febrile Patients with Neutropenia during Cancer Chemotherapy

Thu, 29Â JulÂ 1999 00:00:00 -05:00

Background: Among patients with fever and neutropenia during cancer chemotherapy who have a low risk of complications, oral administration of empirical broad-spectrum antibiotics may be an acceptable alternative to intravenous...

REVIEW ARTICLE: The Î²-Thalassemias

Nancy F. Olivieri, M.D. — Thu, 08Â JulÂ 1999 00:00:00 -05:00

In 1925, Thomas Cooley and Pearl Lee described a form of severe anemia, occurring in children of Italian origin and associated with splenomegaly and characteristic bone changes.1 Over the next...

IMAGES IN CLINICAL MEDICINE: Successful Treatment of Severe Thalassemia

Pietro Muretto, M.D. and Emanuele Angelucci, M.D. — Thu, 08Â JulÂ 1999 00:00:00 -05:00

Figure 1. A six-year-old girl underwent successful allogeneic bone marrow transplantation for severe Î²-thalassemia in 1985. Before transplantation, the serum ferritin concentration was 4044 Î¼g per liter and the serum...

EDITORIAL: Does Bone Marrow Transplantation Confer a Normal Life Span?

Thu, 01Â JulÂ 1999 00:00:00 -05:00

In the 1950s and 1960s, many bone marrow transplantations were attempted in terminally ill patients with leukemia or aplastic anemia without success, except in a few patients who had identical-twin...

ORIGINAL ARTICLE: Long-Term Survival and Late Deaths after Allogeneic Bone Marrow Transplantation

Thu, 01Â JulÂ 1999 00:00:00 -05:00

Background: and Methods: It is uncertain whether mortality rates among patients who have undergone bone marrow transplantation return to the level of the mortality rates of the general population. We...

IMAGES IN CLINICAL MEDICINE: Immunologic Crosstalk

Jens Atzpodien, M.D., Ph.D. and Kurt E.J. Dittmar, M.D. — Thu, 03Â JunÂ 1999 00:00:00 -05:00

Figure 1. Initiation of an immune response requires an interaction between antigen-presenting cells, such as dendritic cells, and helper (CD4) T cells. Antigen-presenting cells process antigens and attract helper T...

ORIGINAL ARTICLE: Immunologic and Virologic Status after 14 to 18 Years of Infection with an Attenuated Strain of HIV-1 â A Report from the Sydney Blood Bank Cohort

Thu, 03Â JunÂ 1999 00:00:00 -05:00

Background: and Methods: The Sydney Blood Bank Cohort consists of a blood donor and eight transfusion recipients who were infected before 1985 with a strain of human immunodeficiency virus type...

ORIGINAL ARTICLE: Transplantation of Anergic Histoincompatible Bone Marrow Allografts

Thu, 03Â JunÂ 1999 00:00:00 -05:00

Background: Successful allogeneic bone marrow transplantation relies on global immunosuppression or elimination of T cells. In contrast, the induction of anergy can inactivate specific sets of alloreactive T cells in...

REVIEW ARTICLE: Myelodysplasia

Mark L. Heaney, M.D., Ph.D., and David W. Golde, M.D. — Thu, 27Â MayÂ 1999 00:00:00 -05:00

The myelodysplastic syndromes are clonal hematologic disorders characterized clinically and morphologically by ineffective hematopoiesis. The natural history of these syndromes ranges from a chronic course that may span years to...

IMAGES IN CLINICAL MEDICINE: Apoptosis in Myelodysplastic Syndromes

Giorgio Lambertenghi Deliliers, M.D. and Lorenza Caneva, Ph.D. — Thu, 27Â MayÂ 1999 00:00:00 -05:00

Figure 1. A 45-year-old man presented with pancytopenia due to myelodysplastic syndrome. The bone marrow showed marked trilineage dysplasia. Electron microscopy revealed that the majority of hematopoietic cells in the...

REVIEW ARTICLE: Vascular-BedâSpecific Hemostasis and Hypercoagulable States

Robert D. Rosenberg, M.D., Ph.D., and William C. Aird, M.D. — Thu, 20Â MayÂ 1999 00:00:00 -05:00

Hemostasis is a physiologic mechanism that maintains blood in a fluid state within the circulation. The coagulation of blood is mediated by cellular components and soluble plasma proteins. In response...

LEGAL ISSUES IN MEDICINE: Waste and Longing â The Legal Status of Placental-Blood Banking

George J. Annas, J.D., M.P.H. — Thu, 13Â MayÂ 1999 00:00:00 -05:00

Waste is not always what it seems. In his Cold War novel Underworld, for example, Don DeLillo explores the multifaceted qualities of waste. âWaste,â he notes, âis the secret history,...

IMAGES IN CLINICAL MEDICINE: Madelung's Disease: Inherited from an Ancient Mediterranean Population?

Claudio Feliciani, M.D. and Pierluigi Amerio, M.D. — Thu, 13Â MayÂ 1999 00:00:00 -05:00

Figure 1. A 44-year-old man was evaluated for symmetric deposits of fat on his arms and legs. At the age of 26 years, he had been hospitalized because of axonal...

ORIGINAL ARTICLE: Annexin II and Bleeding in Acute Promyelocytic Leukemia

Thu, 01Â AprÂ 1999 00:00:00 -05:00

Background: Acute promyelocytic leukemia (APL) is associated with a hemorrhagic disorder of unknown cause that responds to treatment with all-trans-retinoic acid.

Methods: We studied a newly described receptor for fibrinolytic proteins,...

REVIEW ARTICLE: Management of Sickle Cell Disease

Martin H. Steinberg, M.D. — Thu, 01Â AprÂ 1999 00:00:00 -05:00

One of every 600 black people in the United States has sickle cell anemia. In addition, sickle cellâhemoglobin C disease and sickle cellâÎ²-thalassemia, which are other common genotypes of sickle...

ORIGINAL ARTICLE: Liposomal Amphotericin B for Empirical Therapy in Patients with Persistent Fever and Neutropenia

Thu, 11Â MarÂ 1999 00:00:00 -05:00

Background: In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, breakthrough fungal infections can...

ORIGINAL ARTICLE: Hematopoietic Stem-Cell Transplantation for the Treatment of Severe Combined Immunodeficiency

Thu, 18Â FebÂ 1999 00:00:00 -05:00

Background: Since 1968 it has been known that bone marrow transplantation can ameliorate severe combined immunodeficiency, but data on the long-term efficacy of this treatment are limited. We prospectively studied...

EDITORIAL: Transfusions in Critically Ill Patients

Thu, 11Â FebÂ 1999 00:00:00 -05:00

The art of fluid administration and hemodynamic support is one of the most challenging aspects of treating critically ill patients. Considering that every year in the United States over 11...

REVIEW ARTICLE: Transfusion Medicine â Blood Transfusion â First of Two Parts

Thu, 11Â FebÂ 1999 00:00:00 -05:00

Blood transfusion and blood conservation (techniques or strategies to avoid the need for blood) are complementary activities that constitute the clinical arena of transfusion medicine. Recent improvements in the safety...

IMAGES IN CLINICAL MEDICINE: An Apoptotic Eosinophil

Ann M. Dvorak, M.D. — Thu, 11Â FebÂ 1999 00:00:00 -05:00

Figure 1. A peripheral-blood eosinophil undergoing apoptosis displays the characteristic condensation of nuclear chromatin into large, electron-dense masses surrounding the central, relatively electron-lucent nuclear matrix. Other changes that are not...

ORIGINAL ARTICLE: A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care

Thu, 11Â FebÂ 1999 00:00:00 -05:00

Background: To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes...

ORIGINAL ARTICLE: Pure Red-Cell Aplasia Associated with Clonal Expansion of Granular Lymphocytes Expressing Killer-Cell Inhibitory Receptors

Thu, 28Â JanÂ 1999 00:00:00 -05:00

Killer-cell inhibitory receptors inhibit cytolysis when natural killer cells encounter cells bearing HLA class I molecules.12 This phenomenon explains the preferential killing by natural killer cells of tumor cells with...

ORIGINAL ARTICLE: Increased Frequency of Genetic Thrombophilia in Women with Complications of Pregnancy

Thu, 07Â JanÂ 1999 00:00:00 -05:00

Background: Obstetrical complications such as severe preeclampsia, abruptio placentae, fetal growth retardation, and stillbirth are associated with intervillous or spiral-artery thrombosis and inadequate placental perfusion. Whether these complications are associated...

EDITORIAL: Thrombophilias and Adverse Outcomes of Pregnancy â What Should a Clinician Do?

Thu, 07Â JanÂ 1999 00:00:00 -05:00

Approximately 1 to 5 percent of pregnant women have serious complications of pregnancy, such as severe preeclampsia, abruptio placentae, intrauterine fetal death, or severe fetal growth retardation. The rates are...

EDITORIAL: Transplantation in First Remission of Acute Myeloid Leukemia

Thu, 03Â DecÂ 1998 00:00:00 -05:00

In patients under the age of 60 who have acute myeloid leukemia, chemotherapy now routinely produces a complete remission in 70 to 80 percent of cases.12 Since it is generally...

ORIGINAL ARTICLE: Therapy with a Purified Plasminogen Concentrate in an Infant with Ligneous Conjunctivitis and Homozygous Plasminogen Deficiency

Thu, 03Â DecÂ 1998 00:00:00 -05:00

Ligneous conjunctivitis is a rare disease characterized by acute or chronic recurrent conjunctivitis in which the conjunctival membranes acquire a wood-like consistency, due primarily to deposits of fibrin.12 Corneal involvement...

ORIGINAL ARTICLE: Chemotherapy Compared with Autologous or Allogeneic Bone Marrow Transplantation in the Management of Acute Myeloid Leukemia in First Remission

Thu, 03Â DecÂ 1998 00:00:00 -05:00

Background: In young adults with acute myeloid leukemia, intensive chemotherapy during the initial remission improves the long-term outcome, but the role of bone marrow transplantation is uncertain. We compared high-dose...

EDITORIAL: Moschcowitz, Multimers, and Metalloprotease

Thu, 26Â NovÂ 1998 00:00:00 -05:00

In 1924, Dr. Eli Moschcowitz described the abrupt onset of petechiae and pallor, followed rapidly by paralysis, coma, and death, in a 16-year-old girl.1 Terminal arterioles and capillaries in the...

EDITORIAL: The Future of Placental-Blood Transplantation

Thu, 26Â NovÂ 1998 00:00:00 -05:00

During the past decade the use of placental blood as a source of transplantable hematopoietic stem cells has been accelerating. Initially, the placental blood was obtained from siblings, but now...

ORIGINAL ARTICLE: Antibodies to von Willebrand FactorâCleaving Protease in Acute Thrombotic Thrombocytopenic Purpura

Han-Mou Tsai, M.D., and Eric Chun-Yet Lian, M.D. — Thu, 26Â NovÂ 1998 00:00:00 -05:00

Background: Thrombotic thrombocytopenic purpura is a potentially fatal disease characterized by widespread platelet thrombi in the microcirculation. In the normal circulation, von Willebrand factor is cleaved by a plasma protease....

ORIGINAL ARTICLE: von Willebrand FactorâCleaving Protease in Thrombotic Thrombocytopenic Purpura and the HemolyticâUremic Syndrome

Thu, 26Â NovÂ 1998 00:00:00 -05:00

Background: Thrombotic thrombocytopenic purpura and the hemolyticâuremic syndrome are severe microvascular disorders of platelet clumping with similar signs and symptoms. Unusually large multimers of von Willebrand factor, capable of agglutinating...

ORIGINAL ARTICLE: Outcomes among 562 Recipients of Placental-Blood Transplants from Unrelated Donors

Thu, 26Â NovÂ 1998 00:00:00 -05:00

Background: A program for banking, characterizing, and distributing placental blood, also called umbilical-cord blood, for transplantation provided grafts for 562 patients between August 24, 1992, and January 30, 1998. We...

EDITORIAL: The Quest for a Bone Marrow Donor â Optimal or Maximal HLA Matching?

Thu, 22Â OctÂ 1998 00:00:00 -05:00

Bone marrow transplantation was first used successfully exactly 30 years ago, in children with congenital immune deficiencies.1 The demonstration that bone marrow transplantation was also effective in treating aplastic anemia...

ORIGINAL ARTICLE: Effect of Matching of Class I HLA Alleles on Clinical Outcome after Transplantation of Hematopoietic Stem Cells from an Unrelated Donor

Thu, 22Â OctÂ 1998 00:00:00 -05:00

Background: The requirements with respect to HLA compatibility and the relative importance of matching for individual class I and class II HLA alleles in the transplantation of hematopoietic stem cells...

REVIEW ARTICLE: Thrombopoietin

Kenneth Kaushansky, M.D. — Thu, 10Â SepÂ 1998 00:00:00 -05:00

Although the cellular physiology of megakaryocyte and platelet production has been understood for nearly a decade, the humoral basis of this process has remained enigmatic until recently. âThrombopoietin â At...

EDITORIAL: Erythropoietin for End-Stage Renal Disease

Thu, 27Â AugÂ 1998 00:00:00 -05:00

Currently, there are approximately 200,000 patients with end-stage renal disease in the United States who require dialysis therapy to stay alive, and dialysis is initiated in nearly 70,000 new patients...

ORIGINAL ARTICLE: The Effects of Normal as Compared with Low Hematocrit Values in Patients with Cardiac Disease Who Are Receiving Hemodialysis and Epoetin

Thu, 27Â AugÂ 1998 00:00:00 -05:00

Background: In patients with end-stage renal disease, anemia develops as a result of erythropoietin deficiency, and recombinant human erythropoietin (epoetin) is prescribed to correct the anemia partially. We examined the...

ORIGINAL ARTICLE: Subcutaneous Compared with Intravenous Epoetin in Patients Receiving Hemodialysis

Thu, 27Â AugÂ 1998 00:00:00 -05:00

Background: Several studies have suggested that if recombinant human erythropoietin (epoetin) is administered subcutaneously rather than intravenously, a lower dose may be sufficient to maintain the hematocrit at a given...

EDITORIAL: Iron-Chelation Therapy with Oral Deferiprone â Toxicity or Lack of Efficacy?

Thu, 13Â AugÂ 1998 00:00:00 -05:00

Red-cell transfusion therapy in patients with homozygous Î²-thalassemia (thalassemia major) decreases the complications of severe anemia and prolongs survival.1 However, the effectiveness of transfusions is limited by the tissue damage...

ORIGINAL ARTICLE: Long-Term Safety and Effectiveness of Iron-Chelation Therapy with Deferiprone for Thalassemia Major

Thu, 13Â AugÂ 1998 00:00:00 -05:00

Background: Deferiprone is an orally active iron-chelation agent that is being evaluated as a treatment for iron overload in thalassemia major. Studies in an animal model showed that prolonged treatment...

REVIEW ARTICLE: Hemostatic Drugs

Pier Mannuccio Mannucci, M.D. — Thu, 23Â JulÂ 1998 00:00:00 -05:00

When bleeding is the consequence of a specific defect of hemostasis, the goal of treatment is to correct the defect. A typical example is the replacement of factor VIII by...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: A Knockout of a Transgenic Mouse â Animal Models of Sickle Cell Anemia

Thu, 16Â JulÂ 1998 00:00:00 -05:00

Animal models of sickle cell anemia can be used to improve understanding of the pathophysiology of the disease, aid in the development of antisickling drugs, and test the feasibility of...

ORIGINAL ARTICLE: Prevention of a First Stroke by Transfusions in Children with Sickle Cell Anemia and Abnormal Results on Transcranial Doppler Ultrasonography

Thu, 02Â JulÂ 1998 00:00:00 -05:00

Background: Blood transfusions prevent recurrent stroke in children with sickle cell anemia, but the value of transfusions in preventing a first stroke is unknown. We used transcranial Doppler ultrasonography to...

EDITORIAL: Sickle Cell Disease â New Treatments, New Questions

Thu, 02Â JulÂ 1998 00:00:00 -05:00

The history of sickle cell disease shows how tortuous the road can be from the discovery of the mechanism of a disease to improvement in the care of affected patients....

EDITORIAL: Venous Thrombosis â The Interaction of Genes and Environment

Thu, 18Â JunÂ 1998 00:00:00 -05:00

Venous thrombosis is the obstruction of the circulation by clots that have been formed locally in the veins or have been released from a thrombus elsewhere. The usual sites of...

ORIGINAL ARTICLE: High Risk of Cerebral-Vein Thrombosis in Carriers of a Prothrombin-Gene Mutation and in Users of Oral Contraceptives

Thu, 18Â JunÂ 1998 00:00:00 -05:00

Background: Idiopathic cerebral-vein thrombosis can cause serious neurologic disability. We evaluated risk factors for this disorder, including genetic risk factors (mutations in the genes encoding factor V and prothrombin) and...

REVIEW ARTICLE: Neuropathies Associated with Paraproteinemia

Allan H. Ropper, M.D., and Kenneth C. Gorson, M.D. — Thu, 28Â MayÂ 1998 00:00:00 -05:00

A number of common disorders of the peripheral nervous system, termed paraproteinemic neuropathies, are closely connected with the presence of excessive amounts of an abnormal immunoglobulin in the blood. These...

REVIEW ARTICLE: Eosinophilia

Marc E. Rothenberg, M.D., Ph.D. — Thu, 28Â MayÂ 1998 00:00:00 -05:00

A marked accumulation of eosinophils occurs in several important disorders, such as allergic diseases, parasitic infections, and cancer.1 The level of eosinophils in the body is normally tightly regulated. In...

ORIGINAL ARTICLE: Genetic Defects and Clinical Characteristics of Patients with a Form of Oculocutaneous Albinism (HermanskyâPudlak Syndrome)

Thu, 30Â AprÂ 1998 00:00:00 -05:00

Background: HermanskyâPudlak syndrome is characterized by oculocutaneous albinism, a storage-pool deficiency, and lysosomal accumulation of ceroid lipofuscin, which causes pulmonary fibrosis and granulomatous colitis in some cases. All identified affected...

ORIGINAL ARTICLE: Bone Marrow Transplants from Unrelated Donors for Patients with Chronic Myeloid Leukemia

Thu, 02Â AprÂ 1998 00:00:00 -05:00

Background: Chronic myeloid leukemia can be cured by marrow transplantation from an HLA-identical sibling donor. The use of transplants from unrelated donors is an option for the 70 percent of...

ORIGINAL ARTICLE: Inhibition of Erythroid Progenitor Cells by Anti-Kell Antibodies in Fetal Alloimmune Anemia

Thu, 19Â MarÂ 1998 00:00:00 -05:00

Background: In alloimmune anemia of the newborn, the level of hemolysis caused by the presence of antibodies to antigens of the Kell blood-group system is less than that caused by...

EDITORIAL: Polycythemia Vera â Chance, Death, and Mutability

Thu, 26Â FebÂ 1998 00:00:00 -05:00

In the course of a day, the bone marrow of an adult produces over 1011 cells â mainly erythrocytes, but also granulocytes, monocytes, lymphocytes, and platelets. This enormous output originates...

IMAGES IN CLINICAL MEDICINE: Platelet Satellitism

Nasir Shahab, M.D. and Maria L. Evans, M.D. — Thu, 26Â FebÂ 1998 00:00:00 -05:00

Figure 1. Platelet satellitism, an in vitro phenomenon of platelet rosetting around polymorphonuclear neutrophils, is observed exclusively in blood treated with EDTA as an anticoagulant at room temperature. Neither heparin...

ORIGINAL ARTICLE: Impaired Expression of the Thrombopoietin Receptor by Platelets from Patients with Polycythemia Vera

Alison R. Moliterno, M.D., W. David Hankins, Ph.D., and Jerry L. Spivak, M.D. — Thu, 26Â FebÂ 1998 00:00:00 -05:00

Background: The cause of polycythemia vera, which originates from a multipotent hematopoietic progenitor cell, is unknown. Thrombopoietin is a hematopoietic growth factor that regulates the production of multipotent hematopoietic progenitor...

ORIGINAL ARTICLE: Expression of Bcl-x in Erythroid Precursors from Patients with Polycythemia Vera

Thu, 26Â FebÂ 1998 00:00:00 -05:00

Background: Deregulating the expression of Bcl-xL, an inhibitor of apoptosis, in an erythropoietin-dependent erythroblast cell line averts apoptosis induced by the withdrawal of erythropoietin. Since in polycythemia vera an abnormal...

ORIGINAL ARTICLE: X-Linked WiskottâAldrich Syndrome in a Girl

Thu, 29Â JanÂ 1998 00:00:00 -05:00

The WiskottâAldrich syndrome is a life-threatening X-linked recessive disorder. Affected males present with recurrent infections, eczema, and thrombocytopenia with small platelets. The immune defect involves both humoral and cellular immunity...

REVIEW ARTICLE: Respiratory Function of Hemoglobin

Connie C.W. Hsia, M.D. — Thu, 22Â JanÂ 1998 00:00:00 -05:00

Hemoglobin is essential for oxygen transport, and the study of its structure and function has led to numerous discoveries that have shaped modern biologic science.1 This review will examine how...

ORIGINAL ARTICLE: Polymorphisms in the Coagulation Factor VII Gene and the Risk of Myocardial Infarction

Thu, 08Â JanÂ 1998 00:00:00 -05:00

Background: High blood levels of coagulation factor VII are associated with a risk of ischemic vascular disease. Although factor VII levels may be genetically determined, the relation between genetic polymorphisms...

EDITORIAL: The Perils of Platelet Transfusions

Thu, 25Â DecÂ 1997 00:00:00 -05:00

The value of platelet transfusions for thrombocytopenia was first reported in 1910, when Duke described three patients with bleeding due to thrombocytopenia, each of whom showed improvement with transfusions of...

ORIGINAL ARTICLE: The Threshold for Prophylactic Platelet Transfusions in Adults with Acute Myeloid Leukemia

Thu, 25Â DecÂ 1997 00:00:00 -05:00

Background: Prophylactic platelet transfusions are usually administered to patients receiving myelotoxic chemotherapy when their platelet count falls below 20,000 per cubic millimeter. Some observations suggest that lower platelet counts can...

ORIGINAL ARTICLE: Leukocyte Reduction and Ultraviolet B Irradiation of Platelets to Prevent Alloimmunization and Refractoriness to Platelet Transfusions

The Trial to Reduce Alloimmunization to Platelets Study Group — Thu, 25Â DecÂ 1997 00:00:00 -05:00

Background: We conducted a multi-institutional, randomized, blinded trial to determine whether the use of platelets from which leukocytes had been removed by a filter or that had been treated with...

EDITORIAL: Sickle Cell Disease and the Endothelium

Thu, 27Â NovÂ 1997 00:00:00 -05:00

The enduring puzzle of sickle cell anemia is how a single deviant base in DNA, which changes a single amino acid in a single protein within a single type of...

ORIGINAL ARTICLE: Circulating Activated Endothelial Cells in Sickle Cell Anemia

Thu, 27Â NovÂ 1997 00:00:00 -05:00

Background: The vascular wall participates in the pathogenesis of sickle cell disease. To determine whether the endothelium is activated in this disease, we studied the number, origin, and surface phenotype...

REVIEW ARTICLE: Pernicious Anemia

Thu, 13Â NovÂ 1997 00:00:00 -05:00

Pernicious anemia is the most common cause of vitamin B12 deficiency. Vitamin B12 deficiency has many causes; the term âpernicious anemiaâ applies only to the condition associated with chronic atrophic...

REVIEW ARTICLE: Pathogenesis and Treatment of Sickle Cell Disease

H. Franklin Bunn, M.D. — Thu, 11Â SepÂ 1997 00:00:00 -05:00

In 1949, the discovery that sickle hemoglobin (Î±2 Î²S2) has an abnormal electrophoretic mobility prompted Linus Pauling and his colleagues to christen sickle cell anemia âa molecular disease.â1 The ensuing...

ORIGINAL ARTICLE: Outcome of Cord-Blood Transplantation from Related and Unrelated Donors

Thu, 07Â AugÂ 1997 00:00:00 -05:00

Background: Cord-blood banks have increased the use of cord-blood transplantation in patients with hematologic disorders. We have established a registry containing information on the outcome of cord-blood transplantation.

Methods: We sent...

ORIGINAL ARTICLE: Fetal Alloimmune Thrombocytopenia

Thu, 03Â JulÂ 1997 00:00:00 -05:00

Background: Alloimmune thrombocytopenia is a serious fetal disorder resulting from platelet-antigen incompatibility between the mother and fetus. The diagnosis is usually made after the discovery of unexpected neonatal thrombocytopenia. Approximately...

EDITORIAL: Hematopoietic Growth Factors â Not Whether, but When and Where

Thu, 19Â JunÂ 1997 00:00:00 -05:00

Many studies have appraised the value of treatment with granulocyte colony-stimulating factor (G-CSF) or granulocyteâmacrophage colony-stimulating factor (GM-CSF) in ameliorating chemotherapy-induced neutropenia. The principal aim of this treatment is to...

ORIGINAL ARTICLE: Granulocyte Colony-Stimulating Factor in Severe Chemotherapy-Induced Afebrile Neutropenia

Thu, 19Â JunÂ 1997 00:00:00 -05:00

Background: Randomized trials of colony-stimulating factors in febrile patients with neutropenia after chemotherapy have not consistently shown clinical benefit. Nevertheless, the use of colony-stimulating factors to treat patients with chemotherapy-induced...

REVIEW ARTICLE: Multiple Myeloma

Multiple myeloma is a disorder in which malignant plasma cells accumulate in the bone marrow and produce an immunoglobulin, usually monoclonal IgG or IgA. Common complications of overt multiple myeloma...

ORIGINAL ARTICLE: High-Dose Intravenous Immune Globulin and the Response to Splenectomy in Patients with Idiopathic Thrombocytopenic Purpura

Thu, 22Â MayÂ 1997 00:00:00 -05:00

Background: High-dose intravenous immune globulin produces a temporary rise in the platelet count in patients with idiopathic thrombocytopenic purpura. Splenectomy may also be effective, but it is not possible to...

REVIEW ARTICLE: The Pathophysiology of Acquired Aplastic Anemia

Neal S. Young, M.D., and Jaroslaw Maciejewski, M.D. — Thu, 08Â MayÂ 1997 00:00:00 -05:00

Plastic anemia, which is pancytopenia with a fatty or âemptyâ bone marrow, is remarkable for the simplicity of its pathologic picture and the direct derivation of its clinical manifestations.1 Although...

IMAGES IN CLINICAL MEDICINE: Myelodysplasia?

E. Wesley Ely, M.D., M.P.H. and Robert O. Rainer, M.D. — Thu, 08Â MayÂ 1997 00:00:00 -05:00

Figure 1. This cell was found in the bone marrow aspirate of a 62-year-old woman with long-standing myelodysplasia, a disorder in which all cell lines of the bone marrow (myeloid,...

ORIGINAL ARTICLE: Prevalence and Genotypes of Î±- and Î²-Thalassemia Carriers in Hong Kong â Implications for Population Screening

Thu, 01Â MayÂ 1997 00:00:00 -05:00

Background: The thalassemias are common in southern China. We determined the prevalence of heterozygous carriers of these genetic disorders in Hong Kong and assessed the feasibility of a community-based screening...

ORIGINAL ARTICLE: Hepatitis-Associated Aplastic Anemia

Thu, 10Â AprÂ 1997 00:00:00 -05:00

Background: Hepatitis-associated aplastic anemia is a variant of aplastic anemia in which aplastic anemia follows an acute attack of hepatitis. The aplastic anemia, however, is often fatal if untreated. To...

REVIEW ARTICLE: Erythropoietin Therapy

Lawrence T. Goodnough, M.D., Terri G. Monk, M.D., and Gerald L. Andriole, M.D. — Thu, 27Â MarÂ 1997 00:00:00 -05:00

Despite impressive advances in the safety of the blood supply,1 the search for therapeutic alternatives to blood continues.23 Erythropoietin (along with iron, vitamin B12, and folic acid) has been recommended...

IMAGES IN CLINICAL MEDICINE: Platelet Aggregate

Dorothea Zucker-Franklin, M.D. — Thu, 27Â MarÂ 1997 00:00:00 -05:00

Figure 1. In this electron micrograph of a platelet aggregate from a normal person, the âeyeâ of the bunny-like figure is a serotonin-containing dense granule; microtubules are seen immediately below...

ORIGINAL ARTICLE: Solid Cancers after Bone Marrow Transplantation

Thu, 27Â MarÂ 1997 00:00:00 -05:00

Background: The late effects of bone marrow transplantation, including cancer, need to be determined in a large population at risk.

Methods: We studied 19,229 patients who received allogeneic transplants (97.2 percent)...

EDITORIAL: Thrombopoietin â Clinically Realized?

Thu, 06Â FebÂ 1997 00:00:00 -05:00

For approximately 30 years, hematologists have sought the humoral regulator of platelet production, thrombopoietin.1 Although a factor with the appropriate physiologic effects was partially purified, the goal continued to evade...

ORIGINAL ARTICLE: Effects of Polyethylene GlycolâConjugated Recombinant Human Megakaryocyte Growth and Development Factor on Platelet Counts after Chemotherapy for Lung Cancer

Thu, 06Â FebÂ 1997 00:00:00 -05:00

Background: Polyethylene glycol (PEG)âconjugated recombinant human megakaryocyte growth and development factor (MGDF, also known as PEG-rHuMGDF), a recombinant molecule related to thrombopoietin, specifically stimulates megakaryopoiesis and platelet production and reduces...

ORIGINAL ARTICLE: Successful Treatment of a Patient with a Thymoma and Pure Red-Cell Aplasia with Octreotide and Prednisone

Thu, 23Â JanÂ 1997 00:00:00 -05:00

Thymomas are rare epithelial neoplasms frequently associated with myasthenia gravis, hypogammaglobulinemia, and pure red-cell aplasia.1234567891011 In pure red-cell aplasia, autoantibodies against early and late erythroid-cell progenitors or erythropoietin, as well...

EDITORIAL: The Therapeutic Potential of Fetal and Neonatal Hematopoietic Stem Cells

Thu, 12Â DecÂ 1996 00:00:00 -05:00

The transplantation of allogeneic hematopoietic stem cells is being used to treat thousands of adults and children with life-threatening hematologic diseases. In the absence of a suitable HLA-identical sibling donor,...

EDITORIAL: Hemochromatosis in Heterozygotes

Thu, 12Â DecÂ 1996 00:00:00 -05:00

Hemochromatosis, first described more than 100 years ago, is a common inherited disorder of iron metabolism in people of European descent.1 Nonetheless, it has been much underdiagnosed and misdiagnosed, in...

ORIGINAL ARTICLE: Bone Marrow Transplantation in Severe Combined Immunodeficiency from a Sibling Who Had Received a Paternal Bone Marrow Transplant

Thu, 12Â DecÂ 1996 00:00:00 -05:00

Bone marrow transplantation to treat autosomal recessive severe combined immunodeficiency was undertaken in a one-month-old girl. The donor was the patient's HLA-mismatched six-year-old sister, who had previously received a marrow...

ORIGINAL ARTICLE: Clinical and Biochemical Abnormalities in People Heterozygous for Hemochromatosis

Thu, 12Â DecÂ 1996 00:00:00 -05:00

Background: Ten percent of whites are heterozygous for the HLA-linked hemochromatosis mutation. We performed a cross-sectional analysis of 1058 genotyped heterozygotes to define the effects of age and sex on...

EDITORIAL: and the HemolyticâUremic Syndrome

Thu, 29Â AugÂ 1996 00:00:00 -05:00

The hemolyticâuremic syndrome is characterized by nonimmune hemolytic anemia, thrombocytopenia, and acute renal failure.1 Extrarenal manifestations, particularly neurologic signs, may be present, indicating that the disease process is not limited...

EDITORIAL: Bone Marrow Transplantation in Sickle Cell Anemia â The Dilemma of Choice

Thu, 08Â AugÂ 1996 00:00:00 -05:00

The clinical complications of sickle cell anemia reflect the vascular damage caused by the abnormal red cells. Filled with hemoglobin S, sickle red cells obstruct and injure vessels when the...

ORIGINAL ARTICLE: Bone Marrow Transplantation for Sickle Cell Disease

Thu, 08Â AugÂ 1996 00:00:00 -05:00

Background: We investigated the risks and benefits of allogeneic bone marrow transplantation in children with complications of sickle cell disease.

Methods: Twenty-two children less than 16 years of age who had...

MOLECULAR MEDICINE: Gene Transfer to Hematopoietic Cells

Malcolm K. Brenner, M.D., Ph.D. — Thu, 01Â AugÂ 1996 00:00:00 -05:00

Although diseases of blood cells constitute a relatively small proportion of clinical disorders, many valuable studies of gene transfer have relied on hematopoietic stem cells or their progeny. What features...

MOLECULAR MEDICINE: Gene Transfer to Hematopoietic Cells

Malcolm K. Brenner, M.D., Ph.D. — Thu, 01Â AugÂ 1996 00:00:00 -05:00

EDITORIAL: Placental-Blood Banking â A New Frontier in Transfusion Medicine

Thu, 18Â JulÂ 1996 00:00:00 -05:00

Bone marrow has for years been the principal source of transplantable hematopoietic stem cells and progenitor cells. For bone marrow transplantation to succeed, it is crucial to find a donor...

ORIGINAL ARTICLE: Cord-Blood Transplantation from an Unrelated Donor in an Adult with Chronic Myelogenous Leukemia

Thu, 18Â JulÂ 1996 00:00:00 -05:00

To circumvent the problems inherent in allogeneic bone marrow transplantation, allogeneic cord blood has been studied as an alternative source of hematopoietic stem cells. Preliminary results with cord blood from...

ORIGINAL ARTICLE: Placental Blood as a Source of Hematopoietic Stem Cells for Transplantation into Unrelated Recipients

Thu, 18Â JulÂ 1996 00:00:00 -05:00

Background: Transplantation of bone marrow from unrelated donors is limited by a lack of HLA-matched donors and the risk of graft-versus-host disease (GVHD). Placental blood from sibling donors can reconstitute...

ORIGINAL ARTICLE: A Prospective, Randomized Trial of Autologous Bone Marrow Transplantation and Chemotherapy in Multiple Myeloma

Thu, 11Â JulÂ 1996 00:00:00 -05:00

Background: The median survival of patients with myeloma after conventional chemotherapy is three years or less. Promising results have been reported with high-dose therapy supported by autologous bone marrow transplantation....

EDITORIAL: Viral Infections and the Blood Supply

Thu, 27Â JunÂ 1996 00:00:00 -05:00

Transfusions are an indispensable part of medical and surgical therapies. Packed red cells, platelets, and plasma infusions allow patients to be treated intensively for cancer, undergo transplantation, survive surgery despite...

ORIGINAL ARTICLE: Routes of Infection, Viremia, and Liver Disease in Blood Donors Found to Have Hepatitis C Virus Infection

Thu, 27Â JunÂ 1996 00:00:00 -05:00

Background: For many people infected with the hepatitis C virus (HCV), the route of exposure, risk of transmission, and severity of associated liver disease are unknown. We studied these variables...

ORIGINAL ARTICLE: The Risk of Transfusion-Transmitted Viral Infections

Thu, 27Â JunÂ 1996 00:00:00 -05:00

Background: Accurate estimates of the risk of transfusion-transmitted infectious disease are essential for monitoring the safety of the blood supply and evaluating the potential effect of new screening tests. We...

EDITORIAL: Platelets and Coronary Artery Disease

Thu, 25Â AprÂ 1996 00:00:00 -05:00

Over a century ago, the German pathologist Rudolf Virchow presented a hypothesis that three factors â vessel injury, altered blood flow, and changes in blood coagulability â were responsible for...

ORIGINAL ARTICLE: Inherited Metabolic Myopathy and Hemolysis Due to a Mutation in Aldolase A

Thu, 25Â AprÂ 1996 00:00:00 -05:00

Glycolysis is the most important source of energy in red cells and working muscles. Inherited defects of glycolysis can cause hemolytic anemia, neurologic abnormalities, and myopathy with exercise intolerance. The...

ORIGINAL ARTICLE: A Polymorphism of a Platelet Glycoprotein Receptor as an Inherited Risk Factor for Coronary Thrombosis

Thu, 25Â AprÂ 1996 00:00:00 -05:00

Background: Platelet glycoprotein IIb/IIIa is a membrane receptor for fibrinogen and von Willebrand factor, and it has an important role in platelet aggregation. It is known to be involved in...

ORIGINAL ARTICLE: Coexistence of Hereditary Homocystinuria and Factor V Leiden â Effect on Thrombosis

Thu, 21Â MarÂ 1996 00:00:00 -05:00

Background: Venous and arterial thromboembolism occurs in only about one third of patients homozygous for homocystinuria, which suggests that other, contributory factors are necessary for the development of thrombosis in...

ORIGINAL ARTICLE: Hyperhomocysteinemia as a Risk Factor for Deep-Vein Thrombosis

Thu, 21Â MarÂ 1996 00:00:00 -05:00

Background: Previous studies have suggested that hyperhomocysteinemia may be a risk factor for venous thrombosis. To assess the risk of venous thrombosis associated with hyperhomocysteinemia, we studied plasma homocysteine levels...

EDITORIAL: Resistance to Erythropoietin

Thu, 07Â MarÂ 1996 00:00:00 -05:00

The main function of red cells is to transport oxygen from the lungs to the peripheral tissues. Erythropoietin controls red-cell production by stimulating the differentiation of erythroid progenitor cells in...

ORIGINAL ARTICLE: Autoantibodies against Erythropoietin in a Patient with Pure Red-Cell Aplasia

Thu, 07Â MarÂ 1996 00:00:00 -05:00

Autoimmunity is often implicated in pure red-cell aplasia. Approximately 10 to 15 percent of patients with pure red-cell aplasia have thymomas,1 and remission of the anemia occurs in 25 to...

ORIGINAL ARTICLE: Recombinant Erythropoietin for the Treatment of Anemia in Inflammatory Bowel Disease

Thu, 07Â MarÂ 1996 00:00:00 -05:00

Background: Some patients with inflammatory bowel disease have anemia that is refractory to treatment with iron and vitamins. We examined whether administering iron and recombinant erythropoietin could raise hemoglobin levels...

ORIGINAL ARTICLE: Anemia, Dialysis, and Dollars

Thu, 15Â FebÂ 1996 00:00:00 -05:00

The association of anemia with renal failure was noted by Richard Bright 160 years ago.1 Anemia develops early in the course of renal failure, becomes prominent as the disease progresses,...

ORIGINAL ARTICLE: The Intensity of Hemodialysis and the Response to Erythropoietin in Patients with End-Stage Renal Disease

Onyekachi Ifudu, M.B., B.S., Joseph Feldman, Dr.P.H., and Eli A. Friedman, M.D. — Thu, 15Â FebÂ 1996 00:00:00 -05:00

Background: Anemia (characterized by a hematocrit of 30 percent or lower) persists in 40 to 60 percent of patients treated for end-stage renal disease with maintenance hemodialysis, despite concomitant erythropoietin...

EDITORIAL: Minor Histocompatibility Antigens and Marrow Transplantation

Thu, 01Â FebÂ 1996 00:00:00 -05:00

Acute graft-versus-host disease (GVHD) and graft rejection are the principal obstacles to successful allogeneic bone marrow transplantation. Even among recipients of transplants from HLA-identical siblings, the incidence of severe acute...

ORIGINAL ARTICLE: Polymorphism of Adhesion Molecule CD31 and Its Role in Acute Graft-Versus-Host Disease

Thu, 01Â FebÂ 1996 00:00:00 -05:00

Background: Graft-versus-host disease (GVHD) caused by poorly defined minor (i.e., other than HLA) histocompatibility antigens remains a serious problem in recipients of bone marrow transplants. We sought to determine whether...

ORIGINAL ARTICLE: Mismatches of Minor Histocompatibility Antigens between HLA-Identical Donors and Recipients and the Development of Graft-Versus-Host Disease after Bone Marrow Transplantation

Thu, 01Â FebÂ 1996 00:00:00 -05:00

Background: Graft-versus-host disease (GVHD) can be a major complication of allogeneic bone marrow transplantation even when the donor and recipient are siblings and share identical major histocompatibility antigens. The explanation...

NEJM â Collection Updates for Hematology

CORRESPONDENCE: Transfusion of RhD-Positive Blood in âAsia Typeâ DEL Recipients

CLINICAL PROBLEM-SOLVING: Under Pressure

IMAGES IN CLINICAL MEDICINE: Extramedullary Hematopoiesis Associated with Î²-Thalassemia

PERSPECTIVE: Erythropoiesis-Stimulating Agents â Time for a Reevaluation

CLINICAL PROBLEM-SOLVING: Painful Purple Toes

CLINICAL THERAPEUTICS: Activated Protein C for Sepsis

INTERACTIVE MEDICAL CASE: Painful Purple Toes

EDITORIAL: Anemia and Iron Deficiency â New Therapeutic Targets in Heart Failure?

ORIGINAL ARTICLE: Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency

EDITORIAL: Cangrelor â A Champion Lost in Translation?

EDITORIAL: Hematopoietic Stem-Cell Transplantation for Adults with Sickle Cell Disease

ORIGINAL ARTICLE: Intravenous Platelet Blockade with Cangrelor during PCI

ORIGINAL ARTICLE: Platelet Inhibition with Cangrelor in Patients Undergoing PCI

ORIGINAL ARTICLE: Allogeneic Hematopoietic Stem-Cell Transplantation for Sickle Cell Disease

EDITORIAL: Treatment of Anemia in Chronic Kidney Disease â Strategies Based on Evidence

ORIGINAL ARTICLE: A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease

CLINICAL IMPLICATIONS OF BASIC RESEARCH: The Microcytic Red Cell and the Anemia of Inflammation

EDITORIAL: End Run around Epo

CLINICAL PROBLEM-SOLVING: A Bloody Mystery

REVIEW ARTICLE: Myelodysplastic Syndromes

ORIGINAL ARTICLE: A Peptide-Based Erythropoietin-Receptor Agonist for Pure Red-Cell Aplasia

REVIEW ARTICLE: Atypical HemolyticâUremic Syndrome

ORIGINAL ARTICLE: X-Linked Thrombophilia with a Mutant Factor IX (Factor IX Padua)

INTERACTIVE MEDICAL CASE: A Bloody Mystery

REVIEW ARTICLE: Cell Death

VIDEOS IN CLINICAL MEDICINE: Bone Marrow Aspiration and Biopsy

CLINICAL PROBLEM-SOLVING: The Writing on the Wall

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 28-2009 â A 68-Year-Old Man with Fatigue, Cough, and Peripheral-Blood Monocytosis

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Platelets, Pyrexia, and Plasmodia

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 23-2009 â A 13-Year-Old Boy with Headache, Nausea, Seizures, and Hypertension

ORIGINAL ARTICLE: Thrombomodulin Mutations in Atypical HemolyticâUremic Syndrome

BOOK REVIEW:

CLINICAL THERAPEUTICS: Autologous Hematopoietic Stem-Cell Transplantation for Multiple Myeloma

IMAGES IN CLINICAL MEDICINE: Tongue Necrosis in a Patient with Essential Thrombocytosis

EDITORIAL: A Common Genetic Mechanism in Malignant Bone Marrow Diseases

ORIGINAL ARTICLE: Mutation in in Myeloid Cancers

CORRESPONDENCE: Bevacizumab in Hereditary Hemorrhagic Telangiectasia

CLINICAL PROBLEM-SOLVING: A Red Flag

ORIGINAL ARTICLE: Inhibitors of Factor VIII in Black Patients with Hemophilia

CLINICAL PRACTICE: Epistaxis

IMAGES IN CLINICAL MEDICINE: Leukocytosis and Sublingual Microvascular Blood Flow

BOOK REVIEW:

CORRESPONDENCE: An Unusual Outbreak of Hypoglycemia

EDITORIAL: Not an HIV Cure, but Encouraging New Directions

ORIGINAL ARTICLE: Long-Term Control of HIV by Delta32/Delta32 Stem-Cell Transplantation

IMAGES IN CLINICAL MEDICINE: A Smooth, Shiny Tongue

CORRESPONDENCE: Eculizumab for Congenital Atypical HemolyticâUremic Syndrome

CORRESPONDENCE: Eculizumab for Atypical HemolyticâUremic Syndrome

ORIGINAL ARTICLE: Arterial Blood Gases and Oxygen Content in Climbers on Mount Everest

ORIGINAL ARTICLE: A Syndrome with Congenital Neutropenia and Mutations in

PERSPECTIVE: The Many Causes of Severe Congenital Neutropenia

CORRESPONDENCE: Prothrombin Time for Detection of Contaminated Heparins

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 39-2008 â A 51-Year-Old Woman with Splenomegaly and Anemia

ORIGINAL ARTICLE: Mutation and Congenital Erythrocytosis with Paraganglioma

ORIGINAL ARTICLE: Outbreak of Adverse Reactions Associated with Contaminated Heparin

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 38-2008 â A 58-Year-Old Man with Hemophilia, Hepatocellular Carcinoma, and Intractable Bleeding

CORRESPONDENCE: Osteosarcoma Derived from Donor Stem Cells Carrying the Norrie's Disease Gene

REVIEW ARTICLE: Pulmonary Complications of Sickle Cell Disease

IMAGES IN CLINICAL MEDICINE: A Medical Mystery â A 71-Year-Old Man with Pancytopenia

EDITORIAL: Polymorphisms and the Risk of Invasive Fungal Infections

ORIGINAL ARTICLE: Toll-like Receptor 4 Polymorphisms and Aspergillosis in Stem-Cell Transplantation

IMAGES IN CLINICAL MEDICINE: Gingival Hypertrophy and Leukemia

CORRESPONDENCE: Dengue Hemorrhagic Fever Transmitted by Blood Transfusion

REVIEW ARTICLE: Platelets, Petechiae, and Preservation of the Vascular Wall

BOOK REVIEW:

CLINICAL PRACTICE: Hereditary Angioedema

EDITORIAL: Treatment of Myeloma â Are We Making Progress?

ORIGINAL ARTICLE: Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma

BOOK REVIEW:

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Metabolism and Therapeutic Angiogenesis

EDITORIAL: Heparin Comes Clean

ORIGINAL ARTICLE: Contaminated Heparin Associated with Adverse Clinical Events and Activation of the Contact System

EDITORIAL: The Aprotinin Story â Is BART the Final Chapter?

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 17-2008 â A 63-Year-Old Man with Metastatic Renal-Cell Carcinoma

ORIGINAL ARTICLE: A Comparison of Aprotinin and Lysine Analogues in High-Risk Cardiac Surgery

IMAGES IN CLINICAL MEDICINE: Babesiosis

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 13-2008 â A 46-Year-Old Man with Rheumatoid Arthritis and Lymphadenopathy

IMAGES IN CLINICAL MEDICINE: Hemoglobinuria with Malaria

ORIGINAL ARTICLE: Pyruvate Kinase Deficiency and Malaria

NEJM â Collection Updates for Hematology

CORRESPONDENCE: Transfusion of RhD-Positive Blood in âAsia Typeâ DEL Recipients

PERSPECTIVE: Erythropoiesis-Stimulating Agents â Time for a Reevaluation

EDITORIAL: Anemia and Iron Deficiency â New Therapeutic Targets in Heart Failure?

EDITORIAL: Cangrelor â A Champion Lost in Translation?

EDITORIAL: Treatment of Anemia in Chronic Kidney Disease â Strategies Based on Evidence

REVIEW ARTICLE: Atypical HemolyticâUremic Syndrome

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 28-2009 â A 68-Year-Old Man with Fatigue, Cough, and Peripheral-Blood Monocytosis

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 23-2009 â A 13-Year-Old Boy with Headache, Nausea, Seizures, and Hypertension

ORIGINAL ARTICLE: Thrombomodulin Mutations in Atypical HemolyticâUremic Syndrome

CORRESPONDENCE: Eculizumab for Congenital Atypical HemolyticâUremic Syndrome

CORRESPONDENCE: Eculizumab for Atypical HemolyticâUremic Syndrome

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 39-2008 â A 51-Year-Old Woman with Splenomegaly and Anemia

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 38-2008 â A 58-Year-Old Man with Hemophilia, Hepatocellular Carcinoma, and Intractable Bleeding

IMAGES IN CLINICAL MEDICINE: A Medical Mystery â A 71-Year-Old Man with Pancytopenia

EDITORIAL: Treatment of Myeloma â Are We Making Progress?

EDITORIAL: The Aprotinin Story â Is BART the Final Chapter?

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 17-2008 â A 63-Year-Old Man with Metastatic Renal-Cell Carcinoma

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 13-2008 â A 46-Year-Old Man with Rheumatoid Arthritis and Lymphadenopathy

EDITORIAL: Combating the Eosinophil with AntiâInterleukin-5 Therapy

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 8-2008 â A 33-Year-Old Man with Fever, Abdominal Pain, and Pancytopenia after Renal Transplantation

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 2-2008 â A 38-Year-Old Woman with Postpartum Visual Loss, Shortness of Breath, and Renal Failure

ORIGINAL ARTICLE: Iron-OverloadâRelated Disease in Hereditary Hemochromatosis

CLINICAL IMPLICATIONS OF BASIC RESEARCH: B-Cell Identity â Commitment Is Not Forever

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 33-2007 â A 49-Year-Old HIV-Positive Man with Anemia

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 30-2007 â A Newborn Girl with Skin Lesions

EDITORIAL: Prophylactic Treatment for Prevention of Joint Disease in Hemophilia â Cost versus Benefit

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 17-2007 â A 25-Year-Old Woman with Relapsing Fevers and Recent Onset of Dyspnea

EDITORIAL: Blood Transfusion â When Is More Really Less?

PERSPECTIVE: Drug-Induced Immune-Mediated Thrombocytopenia â From Purpura to Thrombosis

PERSPECTIVE: Pulmonary Alveolar Proteinosis â Is Host Defense Awry?

PERSPECTIVE: Mutations in Polycythemia Vera â Molecular Mechanisms and Clinical Applications

EDITORIAL: Prophylaxis and Aspergillosis â Has the Principle Been Proven?

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 1-2007 â A 40-Year-Old Woman with Epistaxis, Hematemesis, and Altered Mental Status

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 40-2006 â A 64-Year-Old Man with Anemia and a Low Level of HDL Cholesterol

EDITORIAL: Correction of Anemia â Payoffs and Problems

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 33-2006 â A 43-Year-Old Man with Diabetes, Hypogonadism, Cirrhosis, Arthralgias, and Fatigue

PERSPECTIVE: Lessons from the WiskottâAldrich Syndrome

PERSPECTIVE: Immune Thrombocytopenic Purpura â The Changing Therapeutic Landscape

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 30-2006 â A 41-Year-Old Man with Dyspnea, Fever, and Lymphadenopathy

EDITORIAL: Cardiac Cell Therapy â Mixed Results from Mixed Cells

ORIGINAL ARTICLE: Intracoronary Bone MarrowâDerived Progenitor Cells in Acute Myocardial Infarction