NEJM â Collection Updates for Allergy/Immunology

ORIGINAL ARTICLE: Vaccine-Acquired Rotavirus in Infants with Severe Combined Immunodeficiency

Thu, 28Â JanÂ 2010 00:00:00 -05:00

Live pentavalent humanâbovine reassortant rotavirus vaccine is recommended in the United States for routine immunization of infants. We describe three infants, two with failure to thrive, who had dehydration and...

EDITORIAL: Immune Evasion by Chimeric Trachea

Megan Sykes, M.D. — Thu, 14Â JanÂ 2010 00:00:00 -05:00

The types of allogeneic organs and tissues that can be transplanted have expanded considerably in the past three decades. In addition to organs such as liver, heart, lungs, and pancreas,...

IMAGES IN CLINICAL MEDICINE: Generalized Ostraceous Psoriasis

Salvador Antonio Arias-Santiago, M.D. and RamÃ³n Naranjo-Sintes, Ph.D. — Thu, 14Â JanÂ 2010 00:00:00 -05:00

A 47-year-old woman presented to our hospital with a 2-week history of widespread, painful lesions on her trunk and limbs (Panels A and B). Her medical history included hypercholesterolemia, diabetes,...

ORIGINAL ARTICLE: Tracheal Allotransplantation after Withdrawal of Immunosuppressive Therapy

Thu, 14Â JanÂ 2010 00:00:00 -05:00

Reconstruction of long-segment tracheal defects requires a vascularized allograft. We report successful tracheal allotransplantation after indirect revascularization of the graft in a heterotopic position. Immunosuppressive therapy was administered before the...

ORIGINAL ARTICLE: Comparison of Ustekinumab and Etanercept for Moderate-to-Severe Psoriasis

Thu, 14Â JanÂ 2010 00:00:00 -05:00

Background: Biologic agents offer a range of new therapeutic options for patients with psoriasis; however, the relative benefitârisk profiles of such therapies are not well known. We compared two biologic...

CORRESPONDENCE: Human GM-CSF Autoantibodies and Reproduction of Pulmonary Alveolar Proteinosis

Thu, 31Â DecÂ 2009 00:00:00 -05:00

To the Editor: Idiopathic pulmonary alveolar proteinosis is a rare disease in which surfactant lipids and proteins accumulate in pulmonary alveolar macrophages and alveoli, resulting in respiratory insufficiency and, in...

EDITORIAL: Pandemic Influenza Vaccine Policy â Considering the Early Evidence

Kathleen M. Neuzil, M.D., M.P.H. — Thu, 17Â DecÂ 2009 00:00:00 -05:00

âPolicy decisions regarding influenza rest on judgments about the behavior of the virus, the impact of the disease and our ability to interdict its course. But the virus is capricious,...

ORIGINAL ARTICLE: Trial of 2009 Influenza A (H1N1) Monovalent MF59-Adjuvanted Vaccine

Thu, 17Â DecÂ 2009 00:00:00 -05:00

Background: The 2009 pandemic influenza A (H1N1) virus has emerged to cause the first pandemic of the 21st century. Development of effective vaccines is a public health priority.

Methods: We conducted...

ORIGINAL ARTICLE: A Novel Influenza A (H1N1) Vaccine in Various Age Groups

Thu, 17Â DecÂ 2009 00:00:00 -05:00

Background: There is an urgent need for a vaccine that is effective against the 2009 pandemic influenza A (H1N1) virus.

Methods: A split-virus, inactivated candidate vaccine against the 2009 H1N1 virus...

ORIGINAL ARTICLE: Response to a Monovalent 2009 Influenza A (H1N1) Vaccine

Thu, 17Â DecÂ 2009 00:00:00 -05:00

Background: A novel 2009 influenza A (H1N1) virus is responsible for the first influenza pandemic in 41 years. A safe and effective vaccine is needed. A randomized, observer-blind, parallel-group trial...

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: 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...

CORRESPONDENCE: COX-2 Inhibitors in Patients with Sensitivity to Nonselective NSAIDs

Stefan Cimbollek, M.D., Joaquin Quiralte, M.D., Ph.D., and Robledo Avila, M.D. — Thu, 26Â NovÂ 2009 00:00:00 -05:00

To the Editor: Controlled oral challenge is the only definitive way to detect sensitivity to nonsteroidal antiinflammatory drugs (NSAIDs) in patients with adverse reactions to these agents.1 Patients who have...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 37-2009 â A 46-Year-Old Woman with Chronic Renal Failure, Leg Swelling, and Skin Changes

Daniela Kroshinsky, M.D., Jonathan Kay, M.D., and Rosalynn M. Nazarian, M.D. — Thu, 26Â NovÂ 2009 00:00:00 -05:00

A 46-year-old woman was referred to a rheumatologist at this hospital because of swelling of the legs and skin changes.

The patient had been in her usual state of health until...

ORIGINAL ARTICLE: Rituximab, B-Lymphocyte Depletion, and Preservation of Beta-Cell Function

Thu, 26Â NovÂ 2009 00:00:00 -05:00

Background: The immunopathogenesis of type 1 diabetes mellitus is associated with T-lymphocyte autoimmunity. However, there is growing evidence that B lymphocytes play a role in many T-lymphocyteâmediated diseases. It is...

ORIGINAL ARTICLE: Identification of a Novel Antibody Associated with Autoimmune Pancreatitis

Thu, 26Â NovÂ 2009 00:00:00 -05:00

Background: Autoimmune pancreatitis is characterized by an inflammatory process that leads to organ dysfunction. The cause of the disease is unknown. Its autoimmune origin has been suggested but never proved,...

EDITORIAL: Interleukin-10 in Inflammatory Bowel Disease

Brian Kelsall, M.D. — Thu, 19Â NovÂ 2009 00:00:00 -05:00

In this issue of the Journal, Glocker et al.1 provide the first substantial support for a functional role for the immunosuppressive cytokine interleukin-10 in the pathogenesis of inflammatory bowel disease...

REVIEW ARTICLE: Inflammatory Bowel Disease

Clara Abraham, M.D., and Judy H. Cho, M.D. — Thu, 19Â NovÂ 2009 00:00:00 -05:00

The idiopathic inflammatory bowel diseases comprise two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. Accumulating evidence suggests that inflammatory bowel disease results from an inappropriate inflammatory response...

ORIGINAL ARTICLE: Combined Immunodeficiency Associated with Mutations

Thu, 19Â NovÂ 2009 00:00:00 -05:00

Background: Recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE are features of some variants of combined immunodeficiency. The genetic causes of these variants are unknown.

Methods: We...

ORIGINAL ARTICLE: Inflammatory Bowel Disease and Mutations Affecting the Interleukin-10 Receptor

Thu, 19Â NovÂ 2009 00:00:00 -05:00

Background: The molecular cause of inflammatory bowel disease is largely unknown.

Methods: We performed genetic-linkage analysis and candidate-gene sequencing on samples from two unrelated consanguineous families with children who were affected...

CORRESPONDENCE: Older Age and a Reduced Likelihood of 2009 H1N1 Virus Infection

Thu, 12Â NovÂ 2009 00:00:00 -05:00

To the Editor: Early epidemiologic reports regarding the 2009 pandemic influenza A (H1N1) virus suggest that cases of infection and deaths are concentrated in adults between the ages of 20...

ORIGINAL ARTICLE: Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus

Thu, 12Â NovÂ 2009 00:00:00 -05:00

Background: A new pandemic influenza A (H1N1) virus has emerged, causing illness globally, primarily in younger age groups. To assess the level of preexisting immunity in humans and to evaluate...

EDITORIAL: Yeast Infections â Human Genetics on the Rise

Steven M. Holland, M.D., and Donald C. Vinh, M.D. — Thu, 29Â OctÂ 2009 00:00:00 -05:00

We lead inextricably mycotic lives: yeasts leaven our bread, ferment our wine and beer, and inhabit our skins, mouths, and gastrointestinal tracts; however, not all is harmony. Hippocrates reported aphthous...

ORIGINAL ARTICLE: Human Dectin-1 Deficiency and Mucocutaneous Fungal Infections

Thu, 29Â OctÂ 2009 00:00:00 -05:00

Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family in which four women who were affected by either recurrent vulvovaginal candidiasis...

ORIGINAL ARTICLE: A Homozygous Mutation in a Family with Susceptibility to Fungal Infections

Thu, 29Â OctÂ 2009 00:00:00 -05:00

Background: Chronic mucocutaneous candidiasis may be manifested as a primary immunodeficiency characterized by persistent or recurrent infections of the mucosa or the skin with candida species. Most cases are sporadic,...

CORRESPONDENCE: FOXP3 Forkhead Domain Mutation and Regulatory T Cells in the IPEX Syndrome

Thu, 22Â OctÂ 2009 00:00:00 -05:00

To the Editor: The immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, a rare disorder characterized by multiorgan autoimmunity, often results in death in infancy.1 The IPEX syndrome results from mutations...

ORIGINAL ARTICLE: Osteoporosis Associated with Neutralizing Autoantibodies against Osteoprotegerin

Thu, 08Â OctÂ 2009 00:00:00 -05:00

Autoantibodies against osteoprotegerin, which block the inhibitory effect of osteoprotegerin on signaling by the receptor activator of nuclear factor (NF)-ÎºB (RANK), were identified in a man with celiac disease who...

CORRESPONDENCE: Hypersensitivity to Generic Drugs with Soybean Oil

Thu, 24Â SepÂ 2009 00:00:00 -05:00

To the Editor: The use of generic drugs has increased in the European Union in recent years. The main regulatory requirement for these products is that they be bioequivalent to...

CORRESPONDENCE: Ruptured Abdominal Aortic Aneurysm Related to IgG4 Periaortitis

Qi Qian, M.D., Kianoush B. Kashani, M.D., and Dylan V. Miller, M.D. — Thu, 10Â SepÂ 2009 00:00:00 -05:00

To the Editor: Periaortitis that is associated with immunoglobulin G4 (IgG4) plasma-cell infiltration is a rare condition with undefined incidence and clinical features. In a single-center study in Japan, the...

ORIGINAL ARTICLE: Progressive Multifocal Leukoencephalopathy after Natalizumab Monotherapy

Thu, 10Â SepÂ 2009 00:00:00 -05:00

We describe progressive multifocal leukoencephalopathy (PML) caused by infection with human polyomavirus JC virus in a patient with multiple sclerosis who was treated with natalizumab. The first PML symptoms appeared...

ORIGINAL ARTICLE: Treatment of Progressive Multifocal Leukoencephalopathy Associated with Natalizumab

Thu, 10Â SepÂ 2009 00:00:00 -05:00

We describe the clinical and therapeutic course of a 52-year-old patient with multiple sclerosis in whom progressive multifocal leukoencephalopathy (PML) developed after 12 months of therapy with natalizumab. The patient...

ORIGINAL ARTICLE: Asymptomatic Reactivation of JC Virus in Patients Treated with Natalizumab

Thu, 10Â SepÂ 2009 00:00:00 -05:00

Background: Progressive multifocal leukoencephalopathy (PML) occurs in a fraction of patients with multiple sclerosis who were treated with natalizumab. Most adults who are infected with the JC virus, the etiologic...

PERSPECTIVE: Reemergence of PML in Natalizumab-Treated Patients â New Cases, Same Concerns

Thu, 10Â SepÂ 2009 00:00:00 -05:00

When progressive multifocal leukoencephalopathy (PML), a rare demyelinating disease induced by JC virus, appeared in 2004 as a complication of natalizumab treatment for multiple sclerosis, a more common demyelinating disease,...

REVIEW ARTICLE: Interleukin-17 and Type 17 Helper T Cells

Pierre Miossec, M.D., Ph.D., Thomas Korn, M.D., and Vijay K. Kuchroo, Ph.D. — Thu, 27Â AugÂ 2009 00:00:00 -05:00

In 1986, Mosmann and Coffman introduced the concept of distinct types of helper T cells, which was based on the types of cytokines that T cells produce when they are...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 24-2009 â A 26-Year-Old Woman with Painful Swelling of the Neck

John H. Stone, M.D., M.P.H., Paul A. Caruso, M.D., and Vikram Deshpande, M.D. — Thu, 30Â JulÂ 2009 00:00:00 -05:00

Dr. John H. Stone: A 26-year-old woman was seen in the rheumatology clinic of this hospital because of painful swelling on both sides of the neck.

She had been well until...

IMAGES IN CLINICAL MEDICINE: Lupus-Associated Intestinal Vasculitis

De-Feng Huang, M.D. and Wei-Sheng Chen, M.D. — Thu, 16Â JulÂ 2009 00:00:00 -05:00

A 28-year-old woman presented, and was admitted, to our hospital with a 2-day history of periumbilical postprandial abdominal pain with nausea and vomiting; she was receiving a maintenance regimen of...

BOOK REVIEW:

Thu, 16Â JulÂ 2009 00:00:00 -05:00

This captivating memoir tells the story of an extraordinary life lived against the backdrop of one of the most cataclysmic events of modern times. Leslie Brent, a world-renowned immunologist and...

CORRESPONDENCE: Anti-CTLA4 AntibodyâInduced Lupus Nephritis

Fouad Fadel, M.D., Khalil El Karoui, M.D., and Bertrand Knebelmann, M.D., Ph.D. — Thu, 09Â JulÂ 2009 00:00:00 -05:00

To the Editor: A 64-year-old man with a history of metastatic melanoma was admitted to our hospital for the nephrotic syndrome in 2006. In 2005, subcutaneous metastases had been diagnosed,...

EDITORIAL: Gene Therapy â Still a Work in Clinical and Regulatory Progress

Elizabeth L. Hohmann, M.D. — Thu, 09Â JulÂ 2009 00:00:00 -05:00

In this issue of the Journal, Frank and colleagues present the case history and autopsy results of a widely publicized death in the summer of 2007 of a young woman...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 21-2009 â A 61-Year-Old Woman with Abdominal Pain, Weight Loss, and Renal Failure

Eric G. Neilson, M.D., and Alton B. Farris, M.D. — Thu, 09Â JulÂ 2009 00:00:00 -05:00

Dr. Anna Greka (Renal Unit): A 61-year-old woman was admitted to this hospital because of abdominal pain, weight loss, and an elevated level of serum creatinine. She had been well...

ORIGINAL ARTICLE: Investigation of the Cause of Death in a Gene-Therapy Trial

Thu, 09Â JulÂ 2009 00:00:00 -05:00

We present a case of disseminated histoplasmosis, complicated by retroperitoneal bleeding and leading to death, in a patient who was receiving systemic immunosuppressive therapy for rheumatoid arthritis and who was...

ORIGINAL ARTICLE: Lack of Association between Folate-Receptor Autoantibodies and Neural-Tube Defects

Thu, 09Â JulÂ 2009 00:00:00 -05:00

Background: A previous report described the presence of autoantibodies against folate receptors in 75% of serum samples from women with a history of pregnancy complicated by a neural-tube defect, as...

IMAGES IN CLINICAL MEDICINE: Tattoo Allergy

Joel Cook, M.D. and John Metcalf, M.D. — Thu, 02Â JulÂ 2009 00:00:00 -05:00

A 40-year-old man presented with intractable pruritus within portions of a tattoo imprinted with red ink on the left leg (Panel A). The intense localized itching had begun approximately 4...

EDITORIAL: Human Idiopathic Membranous Nephropathy â A Mystery Solved?

Richard J. Glassock, M.D. — Thu, 02Â JulÂ 2009 00:00:00 -05:00

Just over 50 years ago, the late David Jones1 identified (using the periodic acidâSchiff and methenamine silver stains) the unique glomerular pathologic features of membranous nephropathy, thus distinguishing it from...

ORIGINAL ARTICLE: M-Type Phospholipase A Receptor as Target Antigen in Idiopathic Membranous Nephropathy

Thu, 02Â JulÂ 2009 00:00:00 -05:00

Background: Idiopathic membranous nephropathy, a common form of the nephrotic syndrome, is an antibody-mediated autoimmune glomerular disease. Serologic diagnosis has been elusive because the target antigen is unknown.

Methods: We performed...

BOOK REVIEW:

Thu, 02Â JulÂ 2009 00:00:00 -05:00

Laboratory medicine has no more urgent role than in the diagnosis and management of infections in immunocompromised patients. For this vulnerable population, clinical algorithms are logically rooted in the need...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 20-2009 â A 79-Year-Old Woman with a Blistering Cutaneous Eruption

Mathew M. Avram, M.D., J.D., and Mai Hoang, M.D. — Thu, 25Â JunÂ 2009 00:00:00 -05:00

Dr. Jordan M. Cummins (Dermatology): A 79-year-old woman was admitted to the burn unit of this hospital because of a blistering cutaneous eruption.

Five days before admission, itching on her head...

CORRESPONDENCE: B-CellâDepleting Induction Therapy and Acute Cellular Rejection

Thu, 18Â JunÂ 2009 00:00:00 -05:00

To the Editor: B-cell depletion is an effective treatment for a number of autoimmune diseases in which B cells were not previously considered to be important, such as multiple sclerosis.1...

ORIGINAL ARTICLE: Immunodeficiency Associated with Mutation and Ficolin-3 Deficiency

Thu, 18Â JunÂ 2009 00:00:00 -05:00

Ficolin-3, encoded by the FCN3 gene and expressed in the lung and liver, is a recognition molecule in the lectin pathway of the complement system. Heterozygosity for an FCN3 frameshift...

EDITORIAL: Interleukin-1Î² and the Autoinflammatory Diseases

Charles A. Dinarello, M.D. — Thu, 04Â JunÂ 2009 00:00:00 -05:00

Interleukin-1 is a highly active proinflammatory cytokine that causes not only fever, anorexia, and other constitutional symptoms but also tissue damage and remodeling. All these effects â including joint destruction,...

REVIEW ARTICLE: Immunologic Aspects of Chronic Obstructive Pulmonary Disease

Manuel G. Cosio, M.D., Marina Saetta, M.D., and Alvar Agusti, M.D. — Thu, 04Â JunÂ 2009 00:00:00 -05:00

Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death throughout the world. It affects about 10% of the general population,1 but its prevalence among heavy smokers...

ORIGINAL ARTICLE: An Autoinflammatory Disease Due to Homozygous Deletion of the Locus

Thu, 04Â JunÂ 2009 00:00:00 -05:00

We describe a patient with an autoinflammatory disease in which the main clinical features are pustular rash, marked osteopenia, lytic bone lesions, respiratory insufficiency, and thrombosis. Genetic studies revealed a...

ORIGINAL ARTICLE: An Autoinflammatory Disease with Deficiency of the Interleukin-1âReceptor Antagonist

Thu, 04Â JunÂ 2009 00:00:00 -05:00

Background: Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T cells. We report a disorder caused by mutations of IL1RN, which encodes the interleukin-1âreceptor antagonist, with...

ORIGINAL ARTICLE: Use of Canakinumab in the Cryopyrin-Associated Periodic Syndrome

Thu, 04Â JunÂ 2009 00:00:00 -05:00

Background: The cryopyrin-associated periodic syndrome (CAPS) is a rare inherited inflammatory disease associated with overproduction of interleukin-1. Canakinumab is a human antiâinterleukin-1Î² monoclonal antibody.

Methods: We performed a three-part, 48-week, double-blind,...

CORRESPONDENCE: Nickel Allergy in Danish Women before and after Nickel Regulation

Thu, 21Â MayÂ 2009 00:00:00 -05:00

To the Editor: Over the 20th century, the prevalence of nickel allergy increased in Western Europe and the United States1; this increase has been attributed to increased skin exposure to...

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...

REVIEW ARTICLE: Scleroderma

Armando Gabrielli, M.D., Enrico V. Avvedimento, M.D., and Thomas Krieg, M.D. — Thu, 07Â MayÂ 2009 00:00:00 -05:00

Scleroderma (systemic sclerosis) is a complex disease in which extensive fibrosis, vascular alterations, and autoantibodies against various cellular antigens are among the principal features (Figure 1 and Figure 2).1 There...

ORIGINAL ARTICLE: Mutation Associated with a Syndrome of Immunodeficiency and Autoimmunity

Thu, 07Â MayÂ 2009 00:00:00 -05:00

A mutation in ORAI1, the gene encoding the pore-forming subunit of the Ca2+-releaseâactivated Ca2+ (CRAC) channel, abrogates the store-operated entry of Ca2+ into cells and impairs lymphocyte activation. Stromal interaction...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Crohn's Disease, Autophagy, and the Paneth Cell

Daniel J. Klionsky, Ph.D. — Thu, 23Â AprÂ 2009 00:00:00 -05:00

Because of its very nature, the gastrointestinal tract is potentially subject to inflammation and infection. Much of its surface is designed to be highly exposed and absorptive, yet it faces...

IMAGES IN CLINICAL MEDICINE: Keyhole Pupils

Smita I. Negi, M.D. and Guha Krishnaswamy, M.D. — Thu, 16Â AprÂ 2009 00:00:00 -05:00

A 60-year-old man was evaluated for nasal congestion and ocular itchiness that had been ongoing for several years. Examination was unremarkable, showing normal visual acuity, except for symmetric defects in...

IMAGES IN CLINICAL MEDICINE: Gingival and Periungual Vasculopathy of Juvenile Dermatomyositis

Lisa G. Rider, M.D. and Jane C. Atkinson, D.D.S. — Thu, 09Â AprÂ 2009 00:00:00 -05:00

A 16-year-old girl with long-standing juvenile dermatomyositis had an illness marked by intermittent clinical flares, including increased muscle weakness, joint contractures, photosensitive rashes, and dysphagia, despite treatment with multiple immunosuppressive...

CLINICAL PRACTICE: Graves' Ophthalmopathy

Luigi Bartalena, M.D., and Maria Laura Tanda, M.D. — Thu, 05Â MarÂ 2009 00:00:00 -05:00

A 40-year-old woman who recently received a diagnosis of Graves' disease comes for a follow-up visit. She has been taking methimazole, at a dose of 10 mg daily, and is...

ORIGINAL ARTICLE: Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia

Thu, 05Â MarÂ 2009 00:00:00 -05:00

Background: Eosinophilic inflammation, which may be a consequence of interleukin-5 action, is a characteristic feature of some forms of asthma. However, in three previous clinical trials involving patients with asthma,...

ORIGINAL ARTICLE: Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma

Thu, 05Â MarÂ 2009 00:00:00 -05:00

Background: Exacerbations of asthma are associated with substantial morbidity and mortality and with considerable use of health care resources. Preventing exacerbations remains an important goal of therapy. There is evidence...

CORRESPONDENCE: Rituximab and Omalizumab in Severe, Refractory Insulin Allergy

Thu, 05Â MarÂ 2009 00:00:00 -05:00

To the Editor: We describe the sequential use of two targeted biologic agents to treat a patient with severe systemic insulin allergy accompanied by marked metabolic dysregulation and corticosteroid toxicity.

In...

ORIGINAL ARTICLE: C3 Polymorphisms and Allograft Outcome in Renal Transplantation

Thu, 26Â FebÂ 2009 00:00:00 -05:00

Background: Complement activation plays a role in the development of chronic allograft nephropathy, a common cause of late allograft loss. The role of two complement component 3 (C3) allotypes, called...

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...

EDITORIAL: The Secret Lives of Monoclonal B Cells

Robert F. Vogt, Jr., Ph.D., and Robert A. Kyle, M.D. — Thu, 12Â FebÂ 2009 00:00:00 -05:00

It seems that B cells, the lymphocytes responsible for producing antibodies, are eager to share their secrets. Their revelations were first uncovered indirectly in serum through reactions with microbes, cells,...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 5-2009 â A 47-Year-Old Woman with a Rash and Numbness and Pain in the Legs

Thu, 12Â FebÂ 2009 00:00:00 -05:00

Dr. John H. Stone: A 47-year-old woman was seen in the Rheumatology Clinic of this hospital because of numbness and pain in the legs and a rash.

The patient had been...

ORIGINAL ARTICLE: B-Cell Clones as Early Markers for Chronic Lymphocytic Leukemia

Thu, 12Â FebÂ 2009 00:00:00 -05:00

Background: Otherwise healthy persons with a small number of B-cell clones circulating in the peripheral blood have been designated as having monoclonal B-cell lymphocytosis (MBL). Hospital-based series indicate an excess...

BOOK REVIEW:

Thu, 05Â FebÂ 2009 00:00:00 -05:00

In this latest addition to the Current Directions in Autoimmunity series from Karger, a broad spectrum of immune-mediated cutaneous diseases, including most of the major disorders that are known to...

EDITORIAL: Gene Therapy Fulfilling Its Promise

Donald B. Kohn, M.D., and Fabio Candotti, M.D. — Thu, 29Â JanÂ 2009 00:00:00 -05:00

From its earliest conception, gene therapy held the promise of correcting inherited diseases by inserting a normal copy of the relevant gene into somatic cells.1 Common monogenic diseases of blood...

ORIGINAL ARTICLE: Gene Therapy for Immunodeficiency Due to Adenosine Deaminase Deficiency

Thu, 29Â JanÂ 2009 00:00:00 -05:00

Background: We investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency.

Methods:...

CORRESPONDENCE: Elimination of Antibodies to Recombinant Enzyme in Pompe's Disease

Thu, 08Â JanÂ 2009 00:00:00 -05:00

To the Editor: Infantile Pompe's disease is due to a deficiency of lysosomal acid alpha glucosidase (GAA). In patients in whom GAA is not produced, a status called cross-reacting immunologic...

BOOK REVIEW:

Thu, 01Â JanÂ 2009 00:00:00 -05:00

Millions of children worldwide suffer from allergic diseases such as asthma, atopic dermatitis, allergic rhinitis, or food allergy. The diagnosis and treatment of these children require special attention to the...

CLINICAL PROBLEM-SOLVING: Keeping an Open Mind

Thu, 01Â JanÂ 2009 00:00:00 -05:00

A 67-year-old man presented with a 3-month history of fatigue and fever. He had undergone heart transplantation 6 years earlier for idiopathic cardiomyopathy. He reported no weight loss, night sweats,...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 40-2008 â A 26-Year-Old Man with Blurred Vision

Thu, 25Â DecÂ 2008 00:00:00 -05:00

Dr. Aaron Savar (Neuro-Ophthalmology): A 26-year-old man was seen in the Neuro-Ophthalmology Clinic of the Massachusetts Eye and Ear Infirmary (MEEI) because of blurred vision in the right eye.

Approximately 8...

ORIGINAL ARTICLE: Azathioprine or Methotrexate Maintenance for ANCA-Associated Vasculitis

Thu, 25Â DecÂ 2008 00:00:00 -05:00

Background: Current standard therapy for Wegener's granulomatosis and microscopic polyangiitis combines corticosteroids and cyclophosphamide to induce remission, followed by a less toxic immunosuppressant such as azathioprine or methotrexate for maintenance...

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: 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...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Proteinuria and Immunity â An Overstated Relationship?

Peter W. Mathieson, Ph.D. — Thu, 04Â DecÂ 2008 00:00:00 -05:00

Proteinuria is a cardinal sign of kidney disease, a prognostic marker, and an independent risk factor for cardiovascular disease. It is the earliest sign of renal complications of diabetes, obesity,...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 36-2008 â A 59-Year-Old Man with Chronic Daily Headache

Thu, 20Â NovÂ 2008 00:00:00 -05:00

Dr. Adam B. Cohen (Neurology): A 59-year-old man was admitted to the neurology service of this hospital because of chronic daily headache, fever, and myalgia.

Approximately 6 months earlier, the patient...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Virus Infection, Asthma, and Chronic Obstructive Pulmonary Disease

Ratko DjukanoviÄ, M.D., and Stephan D. Gadola, M.D. — Thu, 06Â NovÂ 2008 00:00:00 -05:00

Both asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic inflammation of the airways. This inflammation is accompanied by increased mucus production and an excessive propensity of the...

EDITORIAL: Immunotherapy on Trial for New-Onset Type 1 Diabetes

Denise L. Faustman, M.D., Ph.D. — Thu, 30Â OctÂ 2008 00:00:00 -05:00

Type 1 diabetes mellitus is an autoimmune disease in which pathologic, autoreactive T cells of the immune system attack the insulin-secreting pancreatic islets of Langerhans. Cytotoxic T cells, which bear...

ORIGINAL ARTICLE: GAD Treatment and Insulin Secretion in Recent-Onset Type 1 Diabetes

Thu, 30Â OctÂ 2008 00:00:00 -05:00

Background: The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to...

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...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 33-2008 â A 63-Year-Old Woman with Dyspnea on Exertion

Charles M. Wiener, M.D., Victorine V. Muse, M.D., and Eugene J. Mark, M.D. — Thu, 23Â OctÂ 2008 00:00:00 -05:00

Dr. Andrew Tinsley (Medicine): A 63-year-old woman was admitted to this hospital because of dyspnea on exertion.

The patient had been in her usual state of health until approximately 3 weeks...

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...

CORRESPONDENCE: Long-Term Results of Rabbit Antithymocyte Globulin and Basiliximab Induction

Daniel C. Brennan, M.D. and Mark A. Schnitzler, Ph.D. — Thu, 16Â OctÂ 2008 00:00:00 -05:00

To the Editor: In our recently reported prospective, randomized, international clinical trial comparing rabbit antithymocyte globulin and basiliximab in renal transplantation (ClinicalTrials.gov number, NCT00235300),1 we observed that induction treatment with...

CORRESPONDENCE: Antigenically Distinct MF59-Adjuvanted Vaccine to Boost Immunity to H5N1

Thu, 09Â OctÂ 2008 00:00:00 -05:00

To the Editor: Antigenically distinct avian influenza A (H5N1) viruses are widely dispersed.1 Clade 1 H5N1 viruses previously predominated in Indochina. Indonesian, Eurasian, and African viruses are clustered in a...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Insights into Inflammation and Influenza

Cameron Simmons, Ph.D., and Jeremy Farrar, M.D., D.Phil. — Thu, 09Â OctÂ 2008 00:00:00 -05:00

The emergence of highly pathogenic avian influenza H5N1 viruses in Asia and their spread globally have delivered a timely reminder of the public health and clinical challenges an influenza pandemic...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 31-2008 â A 39-Year-Old Man with Chest Pain, Arthralgias, and a Mediastinal Mass

Thu, 09Â OctÂ 2008 00:00:00 -05:00

A 39-year-old man was admitted to this hospital because of chest pain, arthralgias, and a mediastinal mass.

Two months before admission, pain in the middle and right chest developed, which radiated...

CORRESPONDENCE: A Case of Conjugal Azathioprine-Induced Contact Hypersensitivity

Thu, 02Â OctÂ 2008 00:00:00 -05:00

To the Editor: A man in his early 30s presented with an intermittent eczematous eruption over the shaft of his penis and scrotum (Figure 1A). His wife was initially concerned...

CLINICAL PRACTICE: Food Allergy

Gideon Lack, M.D. — Thu, 18Â SepÂ 2008 00:00:00 -05:00

A 3-year-old boy with a recent history of hives and wheezing after eating chocolate mousse is evaluated. At 18 months of age, contact urticaria developed after he put his hand...

CORRESPONDENCE: Widespread Amyloid Deposition in Transplanted Human Pancreatic Islets

Thu, 28Â AugÂ 2008 00:00:00 -05:00

To the Editor: We report on a patient with type 1 diabetes mellitus, diagnosed at 16 years of age, in whom widespread amyloid deposits developed many years later in transplanted...

CORRESPONDENCE: AntiâGlomerular Basement Membrane Disease after Alemtuzumab

Thu, 14Â AugÂ 2008 00:00:00 -05:00

To the Editor: Alemtuzumab (Campath-1H) is a humanized anti-CD52 monoclonal antibody, the administration of which causes profound B- and T-lymphocyte depletion. It is licensed for use in the treatment of...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 25-2008 â A 43-Year-Old Man with Fatigue and Lesions in the Pituitary and Cerebellum

John A. Mills, M.D., R. Gilberto Gonzalez, M.D., Ph.D., and Ronald Jaffe, M.D. — Thu, 14Â AugÂ 2008 00:00:00 -05:00

Dr. Flavia V. Castelino (Rheumatology, Allergy, and Immunology): A 43-year-old man was seen in the neuro-oncology clinic of this hospital because of fatigue and lesions in the pituitary and cerebellum...

IMAGES IN CLINICAL MEDICINE: Allergic Bronchopulmonary Aspergillosis

Ting-hsu Chen, M.D. and Helen Hollingsworth, M.D. — Thu, 07Â AugÂ 2008 00:00:00 -05:00

A 26-year-old man who smoked and had a long history of poorly controlled asthma and severe environmental allergies was admitted for an exacerbation of asthma. He reported no recent hospitalizations...

IMAGES IN CLINICAL MEDICINE: Allergic Contact Dermatitis from a Henna Tattoo

Colby C. Evans, M.D. and John D. Fleming, M.B., B.S. — Thu, 07Â AugÂ 2008 00:00:00 -05:00

A 19-year-old otherwise healthy Kuwaiti woman presented 8 days after the brush application of a temporary henna tattoo while in Kuwait for a wedding. Burning and itching at the site...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: The Antiinflammatory IgG

Thu, 17Â JulÂ 2008 00:00:00 -05:00

Intravenous immune globulin is a therapeutic preparation of normal human polyclonal IgG obtained from plasma pooled from several thousand healthy blood donors. Initially used in treating primary and secondary immune...

EDITORIAL: Reducing Antibody Levels in Patients Undergoing Transplantation

Ron Shapiro, M.D. — Thu, 17Â JulÂ 2008 00:00:00 -05:00

The advent of solid-organ transplantation for the treatment of patients with end-stage organ failure has been one of the most exciting medical advances in the late 20th and early 21st...

ORIGINAL ARTICLE: Rituximab and Intravenous Immune Globulin for Desensitization during Renal Transplantation

Thu, 17Â JulÂ 2008 00:00:00 -05:00

Background: Few options for transplantation currently exist for patients highly sensitized to HLA. This exploratory, open-label, phase 1â2, single-center study examined whether intravenous immune globulin plus rituximab could reduce anti-HLA...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 21-2008 â An 11-Month-Old Boy with Fever and Pulmonary Infiltrates

Thu, 10Â JulÂ 2008 00:00:00 -05:00

An 11-month-old boy was admitted to this hospital because of fevers and pulmonary infiltrates. One month before admission, a month after beginning a visit to India with his parents, daily...

REVIEW ARTICLE: Cancer Immunology

Olivera J. Finn, Ph.D. — Thu, 19Â JunÂ 2008 00:00:00 -05:00

Major conceptual and technical advances in immunology over the past 25 years have led to a new understanding of cellular and molecular interplays between the immune system and a tumor....

ORIGINAL ARTICLE: Treatment of Metastatic Melanoma with Autologous CD4+ T Cells against NY-ESO-1

Thu, 19Â JunÂ 2008 00:00:00 -05:00

We developed an in vitro method for isolating and expanding autologous CD4+ T-cell clones with specificity for the melanoma-associated antigen NY-ESO-1. We infused these cells into a patient with refractory...

PERSPECTIVE: Cancer Immunotherapy â The Endgame Begins

Thu, 19Â JunÂ 2008 00:00:00 -05:00

In 1987, an editorial accompanying a report on the use of high-dose interleukin-2 therapy for cancer asked whether the field of immunotherapy was at âthe beginning of the endâ or...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 18-2008 â A 68-Year-Old Man with Headache and Visual Changes after Liver Transplantation

Thu, 12Â JunÂ 2008 00:00:00 -05:00

A 68-year-old man was admitted to the hospital because of headache and loss of vision in the right eye. Orthotopic allogeneic liver transplantation had been performed 3 1/2 months earlier...

CLINICAL PRACTICE: Graves' Disease

Gregory A. Brent, M.D. — Thu, 12Â JunÂ 2008 00:00:00 -05:00

A 23-year-old woman presents with palpitations. Over the past 6 months, she has reported loose stools, a 10-lb (4.5-kg) weight loss despite a good appetite and food intake, and increased...

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...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: How HIV Guts the Immune System

R. Paul Johnson, M.D. — Thu, 22Â MayÂ 2008 00:00:00 -05:00

Although in the absence of treatment, the acquired immunodeficiency syndrome (AIDS) generally develops 8 to 10 years after infection with human immunodeficiency virus (HIV) type 1 (HIV-1), the onslaught on...

CLINICAL THERAPEUTICS: Sublingual Immunotherapy

Anthony J. Frew, M.D. — Thu, 22Â MayÂ 2008 00:00:00 -05:00

A busy 28-year-old professional consults his physician for advice on long-standing hay fever. He reports having itchy eyes and an itchy nose, lacrimation, sneezing, rhinorrhea, and nasal congestion during the...

ORIGINAL ARTICLE: An Immunodeficiency Disease with Mutations and Granulomas

Thu, 08Â MayÂ 2008 00:00:00 -05:00

We describe three unrelated girls who had an immunodeficiency disease with granulomas in the skin, mucous membranes, and internal organs. All three girls had severe complications after viral infections, including...

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...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 11-2008 â A 45-Year-Old Man with Changes in Mental Status after Liver Transplantation

Thu, 10Â AprÂ 2008 00:00:00 -05:00

A 45-year-old man was admitted to this hospital for orthotopic liver transplantation. The patient had been well until the age of 18 years, when a diagnosis of non-A, non-B hepatitis...

REVIEW ARTICLE: Atopic Dermatitis

Thomas Bieber, M.D., Ph.D. — Thu, 03Â AprÂ 2008 00:00:00 -05:00

Atopic dermatitis, or eczema, is a common skin disease that is often associated with other atopic disorders, such as allergic rhinitis and asthma.1 The clinical manifestations of atopic dermatitis (Figure...

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: 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....

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Chemical Immunosuppression in Islet Transplantation â Friend or Foe?

Lucienne Chatenoud, M.D., Ph.D. — Thu, 13Â MarÂ 2008 00:00:00 -05:00

Insulin-dependent (type 1) diabetes mellitus is an autoimmune disease caused by the selective destruction of pancreatic beta cells by CD4+ and CD8+ autoreactive T lymphocytes. The induction of effective and...

REVIEW ARTICLE: EGFR Antagonists in Cancer Treatment

Fortunato Ciardiello, M.D., Ph.D., and Giampaolo Tortora, M.D., Ph.D. — Thu, 13Â MarÂ 2008 00:00:00 -05:00

Cancer cells may acquire the capacity for autonomous and dysregulated proliferation through the uncontrolled production of specific molecules that promote cell growth (growth factors) or through abnormal, enhanced expression of...

ORIGINAL ARTICLE: VEGF Inhibition and Renal Thrombotic Microangiopathy

Thu, 13Â MarÂ 2008 00:00:00 -05:00

The glomerular microvasculature is particularly susceptible to injury in thrombotic microangiopathy, but the mechanisms by which this occurs are unclear. We report the cases of six patients who were treated...

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...

ORIGINAL ARTICLE: Autoimmune Polyendocrine Syndrome Type 1 and NALP5, a Parathyroid Autoantigen

Thu, 06Â MarÂ 2008 00:00:00 -05:00

Background: Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene. Though recent studies concerning AIRE deficiency have begun to...

EDITORIAL: Collaboration, Genetic Associations, and Lupus Erythematosus

Mary K. Crow, M.D. — Thu, 28Â FebÂ 2008 00:00:00 -05:00

Systemic lupus erythematosus (SLE), a disease that preferentially targets women during the reproductive years, is considered by many clinicians and investigators to be the prototypic autoimmune disease. Among clinicians, this...

REVIEW ARTICLE: Systemic Lupus Erythematosus

Anisur Rahman, Ph.D., and David A. Isenberg, M.D. — Thu, 28Â FebÂ 2008 00:00:00 -05:00

To the clinician, systemic lupus erythematosus is important because it is a potentially fatal disease that is easily confused with many other disorders. To the immunologist, lupus is intriguing because...

IMAGES IN CLINICAL MEDICINE: Cold-Induced Urticaria

Aarnoud Huissoon, Ph.D. and Mamidipudi Thirumala Krishna, Ph.D. — Thu, 21Â FebÂ 2008 00:00:00 -05:00

A 43-year-old woman presented with a 10-month history of an urticarial rash induced by cold, particularly when she was swimming. A clinical diagnosis of cold-induced urticaria was made. The diagnosis...

ORIGINAL ARTICLE: Hepatitis E Virus and Chronic Hepatitis in Organ-Transplant Recipients

Thu, 21Â FebÂ 2008 00:00:00 -05:00

Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis that does not progress to chronic hepatitis. We identified 14 cases of acute HEV infection in three patients...

REVIEW ARTICLE: Acute Lower Respiratory Tract Infection

Joseph P. Mizgerd, Sc.D. — Thu, 14Â FebÂ 2008 00:00:00 -05:00

Acute lower respiratory tract infections are a persistent and pervasive public health problem. They cause a greater burden of disease worldwide than human immunodeficiency virus infection, malaria, cancer, or heart...

ORIGINAL ARTICLE: B-Cell Depletion with Rituximab in RelapsingâRemitting Multiple Sclerosis

Thu, 14Â FebÂ 2008 00:00:00 -05:00

Background: There is increasing evidence that B lymphocytes are involved in the pathogenesis of multiple sclerosis, and they may be a therapeutic target. Rituximab, a monoclonal antibody, selectively targets and...

PERSPECTIVE: The B Cell â Old Player, New Position on the Team

Thu, 14Â FebÂ 2008 00:00:00 -05:00

A phase 2 clinical trial of rituximab in the treatment of multiple sclerosis reported by Hauser et al. in this issue of the Journal (pages 676â688) provides important insights into...

IMAGES IN CLINICAL MEDICINE: Blue Hives

Martin J. O'Sullivan, F.R.C.S.I. and Monica Morrow, M.D. — Thu, 07Â FebÂ 2008 00:00:00 -05:00

A 77-year-old woman underwent surgical resection of a 1.5-cm papillary carcinoma of the right breast. Isosulfan blue dye (8 ml) was used intraoperatively to define the associated lymphatic drainage. Three...

EDITORIAL: Pharmacogenomic Biomarkers for Prediction of Severe Adverse Drug Reactions

Magnus Ingelman-Sundberg, Ph.D., B.Sc.Med. — Thu, 07Â FebÂ 2008 00:00:00 -05:00

The accumulating knowledge of human genomic variation is being used for the development of personalized medicine, with the aims of decreasing the number of adverse drug reactions and increasing the...

ORIGINAL ARTICLE: HLA-B*5701 Screening for Hypersensitivity to Abacavir

Thu, 07Â FebÂ 2008 00:00:00 -05:00

Background: Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele. This study was designed to establish the effectiveness of prospective HLA-B*5701 screening to prevent the...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Inflammatory Bowel Disease â Live Transmission

Gail A. Hecht, M.D. — Thu, 31Â JanÂ 2008 00:00:00 -05:00

Inflammatory bowel disease results from a dysregulated immunologic response to commensal microbial flora residing in the intestinal lumen. Although this response is probably due at least in part to a...

EDITORIAL: Immunosuppressive Therapy and Tolerance of Organ Allografts

Thomas E. Starzl, M.D., Ph.D. — Thu, 24Â JanÂ 2008 00:00:00 -05:00

In this issue of the Journal, three articles describe several organ-transplant recipients in whom allografts have maintained good function for up to 5 years without immunosuppressive treatment.123 In two articles...

ORIGINAL ARTICLE: Chimerism and Tolerance in a Recipient of a Deceased-Donor Liver Transplant

Thu, 24Â JanÂ 2008 00:00:00 -05:00

Complete hematopoietic chimerism and tolerance of a liver allograft from a deceased male donor developed in a 9-year-old girl, with no evidence of graft-versus-host disease 17 months after transplantation. The...

ORIGINAL ARTICLE: Tolerance and Chimerism after Renal and Hematopoietic-Cell Transplantation

Thu, 24Â JanÂ 2008 00:00:00 -05:00

We describe a recipient of combined kidney and hematopoietic-cell transplants from an HLA-matched donor. A post-transplantation conditioning regimen of total lymphoid irradiation and antithymocyte globulin allowed engraftment of the donor's...

ORIGINAL ARTICLE: HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression

Thu, 24Â JanÂ 2008 00:00:00 -05:00

08012430.xml 08012430.xml 08012430.xml 08012430.xml Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a...

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...

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...

EDITORIAL: Factoring PAF in Anaphylaxis

A. Wesley Burks, M.D. — Thu, 03Â JanÂ 2008 00:00:00 -05:00

Anaphylaxis has been recognized for more than 100 years, but it remains a condition that is difficult to predict, diagnose, and treat. Generally defined as a serious allergic reaction that...

ORIGINAL ARTICLE: Platelet-Activating Factor, PAF Acetylhydrolase, and Severe Anaphylaxis

Thu, 03Â JanÂ 2008 00:00:00 -05:00

Background: Platelet-activating factor (PAF) is an important mediator of anaphylaxis in animals, and interventions that block PAF prevent fatal anaphylaxis. The roles of PAF and PAF acetylhydrolase, the enzyme that...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Small RNAs and Large DNA Viruses

Jay A. Nelson, Ph.D. — Thu, 20Â DecÂ 2007 00:00:00 -05:00

Although most human cytomegalovirus (CMV) infections are asymptomatic, CMV is a significant pathogen in immunosuppressed patients such as patients with AIDS and those who receive immunosuppressive therapy after solid-organ or...

EDITORIAL: Balancing Efficacy and Toxicity in Kidney-Transplant Immunosuppression

Alan B. Leichtman, M.D. — Thu, 20Â DecÂ 2007 00:00:00 -05:00

Although protocols differ among transplantation centers, most immunosuppressive strategies for kidney-transplant recipients are built on two core practices: delivery of immunosuppression in two phases, usually termed induction and maintenance, and...

REVIEW ARTICLE: Infection in Solid-Organ Transplant Recipients

Jay A. Fishman, M.D. — Thu, 20Â DecÂ 2007 00:00:00 -05:00

Increasingly potent immunosuppressive agents have dramatically reduced the incidence of rejection of transplanted organs while increasing patients' susceptibility to opportunistic infections and cancer.12 At the same time, patterns of opportunistic...

ORIGINAL ARTICLE: Telbivudine versus Lamivudine in Patients with Chronic Hepatitis B

Thu, 20Â DecÂ 2007 00:00:00 -05:00

Background: Reducing hepatitis B virus (HBV) replication to minimal levels is emerging as a key therapeutic goal for chronic hepatitis B.

Methods: In this double-blind, phase 3 trial, 1370 patients with...

ORIGINAL ARTICLE: Reduced Exposure to Calcineurin Inhibitors in Renal Transplantation

Thu, 20Â DecÂ 2007 00:00:00 -05:00

Background: Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens.

Methods: We randomly assigned...

ORIGINAL ARTICLE: Outcomes 18 Months after the First Human Partial Face Transplantation

Thu, 13Â DecÂ 2007 00:00:00 -05:00

Background: We performed the first human partial face allograft on November 27, 2005. Here we report outcomes up to 18 months after transplantation.

Methods: The postsurgical induction immunosuppression protocol included thymoglobulins...

EDITORIAL: Lenalidomide â The Phoenix Rises

Alan F. List, M.D. — Thu, 22Â NovÂ 2007 00:00:00 -05:00

Perhaps the darkest memory in modern pharmaceutical history is that of the devastating effects of thalidomide exposure on fetal development. More than four decades later, thalidomide reemerged from the ashes...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 36-2007 â A 31-Year-Old Woman with Rash, Fever, and Hypotension

Thu, 22Â NovÂ 2007 00:00:00 -05:00

Dr. Jeffrey O. Greenberg (Medicine): A 31-year-old woman was admitted to this hospital because of facial swelling, fever, and hypotension.

The patient had relapsing and remitting multiple sclerosis, associated with severe...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 35-2007 â A 30-Year-Old Man with Inflammatory Bowel Disease and Recent Onset of Fever and Bloody Diarrhea

Thu, 15Â NovÂ 2007 00:00:00 -05:00

Dr. Patrick S. Yachimski (Gastroenterology): A 30-year-old Moroccan man was admitted to this hospital because of fever, abdominal pain, and bloody diarrhea.

The patient had a history of inflammatory bowel disease...

ORIGINAL ARTICLE: Cetuximab for the Treatment of Colorectal Cancer

Thu, 15Â NovÂ 2007 00:00:00 -05:00

Background: Cetuximab, an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor (EGFR), has activity against colorectal cancers that express EGFR.

Methods: From December 2003 to August 2005, 572 patients who...

ORIGINAL ARTICLE: Duration of Humoral Immunity to Common Viral and Vaccine Antigens

Ian J. Amanna, Ph.D., Nichole E. Carlson, Ph.D., and Mark K. Slifka, Ph.D. — Thu, 08Â NovÂ 2007 00:00:00 -05:00

Background: Maintenance of long-term antibody responses is critical for protective immunity against many pathogens. However, the duration of humoral immunity and the role played by memory B cells remain poorly...

REVIEW ARTICLE: Leukotrienes

Marc Peters-Golden, M.D., and William R. Henderson, Jr., M.D. — Thu, 01Â NovÂ 2007 00:00:00 -05:00

Leukotrienes (âleuko,â from white blood cells; and âtrienes,â three conjugated double bonds) comprise a family of products of the 5-lipoxygenase pathway of arachidonic acid metabolism. The cysteinyl leukotrienes C4, D4,...

REVIEW ARTICLE: Celiac Disease

Peter H.R. Green, M.D., and Christophe Cellier, M.D., Ph.D. — Thu, 25Â OctÂ 2007 00:00:00 -05:00

Celiac disease is a unique autoimmune disorder, unique because the environmental precipitant is known. The disorder was previously called celiac sprue, based on the Dutch word sprue, which was used...

ORIGINAL ARTICLE: Hepatitis A Vaccine versus Immune Globulin for Postexposure Prophylaxis

Thu, 25Â OctÂ 2007 00:00:00 -05:00

Background: Hepatitis A vaccine administered to persons after exposure to the hepatitis A virus has not been compared directly with immune globulin, which is known to be highly effective in...

EDITORIAL: STAT3 Signaling and the Hyper-IgE Syndrome

David E. Levy, Ph.D., and Cynthia A. Loomis, M.D., Ph.D. — Thu, 18Â OctÂ 2007 00:00:00 -05:00

The Janus kinase (JAK)âsignal transducer and activator of transcription (STAT) signaling pathway has emerged over the past decade as a major relay between cell-surface receptors and cytokine responses. The human...

ORIGINAL ARTICLE: Mutations in the Hyper-IgE Syndrome

Thu, 18Â OctÂ 2007 00:00:00 -05:00

Background: The hyper-IgE syndrome (or Job's syndrome) is a rare disorder of immunity and connective tissue characterized by dermatitis, boils, cyst-forming pneumonias, elevated serum IgE levels, retained primary dentition, and...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Viral Infections and Nonspecific Protection â Good or Bad?

Emil R. Unanue, M.D. — Thu, 27Â SepÂ 2007 00:00:00 -05:00

Viruses, like many microbes, have complex and diverse relationships with the immune system. We need to kill or control viruses to survive as a species, but under special circumstances, we...

EDITORIAL: Will MICA Glitter for Recipients of Kidney Transplants?

Willy Albert Flegel, M.D. — Thu, 27Â SepÂ 2007 00:00:00 -05:00

Renal transplantation as the treatment of choice for end-stage renal failure is associated with excellent short-term results. The 1-year patient-survival rate is 96%, and the 1-year allograft-survival rate is more...

ORIGINAL ARTICLE: Antibodies against MICA Antigens and Kidney-Transplant Rejection

Thu, 27Â SepÂ 2007 00:00:00 -05:00

Background: Good HLA-A, HLA-B, and HLA-DR matches do not guarantee rejection-free renal transplantation. Some kidney transplants fail despite such matches, suggesting that other antigens might be targets for rejection. Major-histocompatibility-complex...

EDITORIAL: Lessons from a Genomewide Association Study of Rheumatoid Arthritis

Kazuhiko Yamamoto, M.D., Ph.D., and Ryo Yamada, M.D., Ph.D. — Thu, 20Â SepÂ 2007 00:00:00 -05:00

Rheumatoid arthritis is a chronic inflammatory disorder in which the articular joints are gradually destroyed. Occasionally there is systemic involvement, which can include vasculitis in various organs and pulmonary fibrosis....

ORIGINAL ARTICLE: A Polymorphism in the Promoter Region Associated with Systemic Sclerosis

Thu, 20Â SepÂ 2007 00:00:00 -05:00

Background: Systemic sclerosis (scleroderma) is a life-threatening autoimmune disease that is characterized by the presence of specific autoantibodies and fibrosis of the skin and major internal organs.

Methods: We genotyped a...

ORIGINAL ARTICLE: as a Risk Locus for Rheumatoid Arthritis â A Genomewide Study

Thu, 20Â SepÂ 2007 00:00:00 -05:00

Background: Rheumatoid arthritis has a complex mode of inheritance. Although HLA-DRB1 and PTPN22 are well-established susceptibility loci, other genes that confer a modest level of risk have been identified recently....

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: and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus

Thu, 06Â SepÂ 2007 00:00:00 -05:00

Background: Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q.

Methods: We tested single-nucleotide polymorphisms (SNPs)...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Bugging of the Intestinal Mucosa

Clara Abraham, M.D., and Judy H. Cho, M.D. — Thu, 16Â AugÂ 2007 00:00:00 -05:00

An enormous array of adaptive mechanisms on both sides of the hostâmicrobial interface reflects a complex coevolution. Deciphering the cross-talk at this interface may yield new insights into its relevance...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 25-2007 â A 60-Year-Old Man with Fever, Odynophagia, Weight Loss, and Rash

Thu, 16Â AugÂ 2007 00:00:00 -05:00

Dr. Sheila F. Mitsuma (Department of Medicine): A 60-year-old man was admitted to this hospital because of fever, odynophagia, weight loss, and rash.

He had been well until 5 months earlier,...

EDITORIAL: Rituximab and Pemphigus â A Therapeutic Advance

Luis A. Diaz, M.D. — Thu, 09Â AugÂ 2007 00:00:00 -05:00

Pemphigus vulgaris and pemphigus foliaceus are rare autoimmune blistering diseases of obscure causes. The scientific bases for the therapy of these disorders have evolved in the past 60 years. Landmark...

ORIGINAL ARTICLE: A Single Cycle of Rituximab for the Treatment of Severe Pemphigus

Thu, 09Â AugÂ 2007 00:00:00 -05:00

Background: The combination of multiple cycles of rituximab and intravenous immune globulins has been reported to be effective in patients with severe pemphigus. The aim of this study was to...

EDITORIAL: Anti-TNF Antibodies for Crohn's Disease â In Pursuit of the Perfect Clinical Trial

James D. Lewis, M.D., M.S.C.E. — Thu, 19Â JulÂ 2007 00:00:00 -05:00

For decades, many patients with Crohn's disease required prolonged courses of corticosteroids, repeated surgeries, or both, despite treatment with 5-aminosalicylic acid (mesalamine) or immunomodulators such as azathioprine. The introduction of...

ORIGINAL ARTICLE: Maintenance Therapy with Certolizumab Pegol for Crohn's Disease

Thu, 19Â JulÂ 2007 00:00:00 -05:00

Background: Certolizumab pegol is a pegylated humanized Fabâ² fragment with a high binding affinity for tumor necrosis factor Î± that does not induce apoptosis of T cells or monocytes.

Methods: In...

ORIGINAL ARTICLE: Certolizumab Pegol for the Treatment of Crohn's Disease

Thu, 19Â JulÂ 2007 00:00:00 -05:00

Background: Certolizumab pegol is a pegylated humanized Fabâ² fragment that binds tumor necrosis factor Î±.

Methods: In a randomized, double-blind, placebo-controlled trial, we evaluated the efficacy of certolizumab pegol in 662...

IMAGES IN CLINICAL MEDICINE: Phytophotodermatitis and Limes

Miriam Keltz Pomeranz, M.D. and Julie K. Karen, M.D. — Thu, 05Â JulÂ 2007 00:00:00 -05:00

A 23-year-old woman presented to the emergency department with a 3-day history of a painful, erythematous, blistering rash across her sun-exposed skin. Before the onset of the rash, the patient...

ORIGINAL ARTICLE: Allogeneic Bone Marrow Transplantation in Mevalonic Aciduria

Thu, 28Â JunÂ 2007 00:00:00 -05:00

Mevalonic aciduria is a rare, inborn error of isoprene biosynthesis characterized by severe, periodic attacks of fever and inflammation, developmental delay, ataxia, and dysmorphic features. This autosomal recessive disease is...

PERSPECTIVE: Mevalonate Kinase Deficiency and Autoinflammatory Disorders

Thu, 28Â JunÂ 2007 00:00:00 -05:00

A deficiency of mevalonate kinase resulting in mevalonic aciduria was the first inherited defect in cholesterol and nonsterol isoprene biosynthesis to be recognized.1 Nine other enzyme deficiencies have since been...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Why Does Rheumatoid Arthritis Involve the Joints?

Peter E. Lipsky, M.D. — Thu, 07Â JunÂ 2007 00:00:00 -05:00

A long-standing question in rheumatology is why inflammatory arthritides such as rheumatoid arthritis involve the joints. Many studies have addressed this question; a recent article by Lee et al.1 provides...

EDITORIAL: Advances in the Treatment of Amyloidosis

S. Vincent Rajkumar, M.D., and Morie A. Gertz, M.D. — Thu, 07Â JunÂ 2007 00:00:00 -05:00

All forms of amyloidosis are characterized by the deposition of extracellular fibrils in various tissues. These fibrils are the result of the misfolding of a protein from its normal Î±-helical...

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...

ORIGINAL ARTICLE: Natural History and Outcome in Systemic AA Amyloidosis

Thu, 07Â JunÂ 2007 00:00:00 -05:00

Background: Deposition of amyloid fibrils derived from circulating acute-phase reactant serum amyloid A protein (SAA) causes systemic AA amyloidosis, a serious complication of many chronic inflammatory disorders. Little is known...

ORIGINAL ARTICLE: Eprodisate for the Treatment of Renal Disease in AA Amyloidosis

Thu, 07Â JunÂ 2007 00:00:00 -05:00

Background: Amyloid A (AA) amyloidosis is a complication of chronic inflammatory conditions that develops when proteolytic fragments of serum amyloid A protein (SAA) are deposited in tissues as amyloid fibrils....

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 14-2007 â A 59-Year-Old Man with Fever and Pain and Swelling of Both Eyes and the Right Ear

Thu, 10Â MayÂ 2007 00:00:00 -05:00

Dr. David T. Ting (Medicine): A 59-year-old man was admitted to this hospital because of fever as well as pain and swelling of both eyes, which was worse in the...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Tolls and Beyond â Many Roads to Vaccine Immunity

Bali Pulendran, Ph.D. — Thu, 26Â AprÂ 2007 00:00:00 -05:00

Of all the public health measures against infections, vaccination is arguably the most cost-effective. Most successful vaccines can be divided into two types â live attenuated vaccines and nonreplicating vaccines....

ORIGINAL ARTICLE: Interleukin-1âReceptor Antagonist in Type 2 Diabetes Mellitus

Thu, 12Â AprÂ 2007 00:00:00 -05:00

Background: The expression of interleukin-1âreceptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1Î² in human pancreatic...

PERSPECTIVE: Diabetes Treatment â Bridging the Divide

Thu, 12Â AprÂ 2007 00:00:00 -05:00

In the simplest terms, diabetes mellitus results when pancreatic beta cells are unable to maintain adequate insulin secretion to prevent hyperglycemia. A combination of genetic and environmental factors causes the...

EDITORIAL: Natural Killer T Cells in Asthma â Toward Increased Understanding

Ling-Pei Ho, M.D., Ph.D. — Thu, 05Â AprÂ 2007 00:00:00 -05:00

This issue of the Journal contains the second report within about a year on the presence of natural killer T cells in the lungs of patients with asthma. The two...

ORIGINAL ARTICLE: Invariant Natural Killer T Cells in Asthma and Chronic Obstructive Pulmonary Disease

Thu, 05Â AprÂ 2007 00:00:00 -05:00

Background: The number of type 2 helper CD4+ T cells is increased in the airways of persons with asthma. Whether the majority of these cells are class II major-histocompatibility-complexârestricted cells...

EDITORIAL: Modern Genetics, Ancient Defenses, and Potential Therapies

Peter K. Gregersen, M.D. — Thu, 22Â MarÂ 2007 00:00:00 -05:00

Autoimmunity is the reflection of a basic problem confronting all living organisms â how to defend against foreign invasion while maintaining control of the defending forces. The B-cell and T-cell...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 9-2007 â A 27-Year-Old Woman with Pain and Swelling of the Legs

Jean-Michel Vallat, M.D., Didier P. Cros, M.D., and E. Tessa Hedley-Whyte, M.D. — Thu, 22Â MarÂ 2007 00:00:00 -05:00

A 27-year-old woman was seen in the neurology clinic because of pain and swelling in her feet. She had been well until approximately 5 months earlier, when swelling of her...

ORIGINAL ARTICLE: in Vitiligo-Associated Multiple Autoimmune Disease

Thu, 22Â MarÂ 2007 00:00:00 -05:00

Background: Autoimmune and autoinflammatory diseases involve interactions between genetic risk factors and environmental triggers. We searched for a gene on chromosome 17p13 that contributes to a group of epidemiologically associated...

ORIGINAL ARTICLE: Loss of Vaccine-Induced Immunity to Varicella over Time

Thu, 15Â MarÂ 2007 00:00:00 -05:00

Background: The introduction of universal varicella vaccination in 1995 has substantially reduced varicella-related morbidity and mortality in the United States. However, it remains unclear whether vaccine-induced immunity wanes over time,...

CLINICAL PROBLEM-SOLVING: Into the Woods

Nasia Safdar, M.D., Daniel R. Kaul, M.D., and Sanjay Saint, M.D., M.P.H. — Thu, 01Â MarÂ 2007 00:00:00 -05:00

A 79-year-old woman presented with a 1-month history of dyspnea and a cough productive of yellow sputum. She reported no chest pain, hemoptysis, night sweats, or fever. Three months earlier,...

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...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: A Closer Look at Follicular Lymphoma

Louis M. Staudt, M.D., Ph.D. — Thu, 15Â FebÂ 2007 00:00:00 -05:00

A majority of healthy persons have, in their normal B cells, the defining event of follicular lymphoma â a t(14;18) translocation that brings together BCL2 and the gene encoding the...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 4-2007 â A 56-Year-Old Woman with Rapidly Progressive Vertigo and Ataxia

Thu, 08Â FebÂ 2007 00:00:00 -05:00

A 56-year-old woman was admitted to the hospital because of rapidly progressive vertigo and ataxia.

The patient had been well until approximately 10 weeks before admission, when occasional dizziness and nausea...

ORIGINAL ARTICLE: A Human Interleukin-12/23 Monoclonal Antibody for the Treatment of Psoriasis

Thu, 08Â FebÂ 2007 00:00:00 -05:00

Background: Skin-infiltrating lymphocytes expressing type 1 cytokines have been linked to the pathophysiology of psoriasis. We evaluated the safety and efficacy of a human interleukin-12/23 monoclonal antibody in treating psoriasis.

Methods:...

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...

EDITORIAL: Renal-Cell Carcinoma â Molecular Pathways and Therapies

James Brugarolas, M.D., Ph.D. — Thu, 11Â JanÂ 2007 00:00:00 -05:00

Renal-cell carcinoma is among the most resistant of tumors to therapy. Until 2005, only a single treatment, high-dose interleukin-2, had been approved by the Food and Drug Administration (FDA) for...

ORIGINAL ARTICLE: Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma

Thu, 11Â JanÂ 2007 00:00:00 -05:00

Background: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, in patients with advanced clear-cell renal-cell carcinoma.

Methods: From November 2003...

ORIGINAL ARTICLE: Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma

Thu, 11Â JanÂ 2007 00:00:00 -05:00

Background: Since sunitinib malate has shown activity in two uncontrolled studies in patients with metastatic renal-cell carcinoma, a comparison of the drug with interferon alfa in a phase 3 trial...

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...

ORIGINAL ARTICLE: Human Infection Linked to a Lack of Apolipoprotein L-I

Thu, 28Â DecÂ 2006 00:00:00 -05:00

Humans have innate immunity against Trypanosoma brucei brucei that is known to involve apolipoprotein L-I (APOL1). Recently, a case of T. evansi infection in a human was identified in India....

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 39-2006 â A 24-Year-Old Woman with Systemic Lupus Erythematosus, Seizures, and Right Arm Weakness

Thu, 21Â DecÂ 2006 00:00:00 -05:00

Dr. Sherry Chou (Neurology): A 24-year-old woman was transferred to this hospital because of seizures and a lesion in the brain.

A diagnosis of systemic lupus erythematosus (SLE) had been made...

REVIEW ARTICLE: Autoimmune Pancreatitis

Thu, 21Â DecÂ 2006 00:00:00 -05:00

The term âautoimmune pancreatitisâ (or âautoimmune-related pancreatitisâ) was introduced by Yoshida et al. in 1995 to describe the form of chronic pancreatitis that is associated with autoimmune manifestations revealed on...

EDITORIAL: Rabbit Antithymocyte Globulin or Basiliximab for Induction Therapy?

Michelle A. Josephson, M.D. — Thu, 09Â NovÂ 2006 00:00:00 -05:00

In this issue of the Journal, Brennan et al.1 compare the safety and efficacy of two induction therapies commonly used in kidney transplantation: rabbit antithymocyte globulin and basiliximab. Induction refers...

ORIGINAL ARTICLE: Rabbit Antithymocyte Globulin versus Basiliximab in Renal Transplantation

Thu, 09Â NovÂ 2006 00:00:00 -05:00

Background: Induction therapy reduces the frequency of acute rejection and delayed graft function after transplantation. A rabbit antithymocyte polyclonal antibody or basiliximab, an interleukin-2 receptor monoclonal antibody, is most commonly...

REVIEW ARTICLE: Pemphigus, Bullous Impetigo, and the Staphylococcal Scalded-Skin Syndrome

John R. Stanley, M.D., and Masayuki Amagai, M.D., Ph.D. — Thu, 26Â OctÂ 2006 00:00:00 -05:00

Pemphigus, which is caused by autoantibodies, and bullous impetigo (including its generalized form, the staphylococcal scalded-skin syndrome), which is caused by Staphylococcus aureus, are seemingly unrelated diseases. However, 200 years...

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...

ORIGINAL ARTICLE: Treatment of Pemphigus Vulgaris with Rituximab and Intravenous Immune Globulin

Thu, 26Â OctÂ 2006 00:00:00 -05:00

Background: Pemphigus vulgaris is a potentially fatal autoimmune mucocutaneous blistering disease. Conventional therapy consists of high-dose corticosteroids, immunosuppressive agents, and intravenous immune globulin.

Methods: We studied patients with refractory pemphigus vulgaris...

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...

REVIEW ARTICLE: Management of Sepsis

James A. Russell, M.D. — Thu, 19Â OctÂ 2006 00:00:00 -05:00

A better understanding of the inflammatory, procoagulant, and immunosuppressive aspects of sepsis has contributed to rational therapeutic plans from which several important themes emerge.1 First, rapid diagnosis (within the first...

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: Immunotherapy with a RagweedâToll-Like Receptor 9 Agonist Vaccine for Allergic Rhinitis

Thu, 05Â OctÂ 2006 00:00:00 -05:00

Background: Conjugating immunostimulatory sequences of DNA to specific allergens offers a new approach to allergen immunotherapy that reduces acute allergic responses.

Methods: We conducted a randomized, double-blind, placebo-controlled phase 2 trial...

ORIGINAL ARTICLE: Oral Fingolimod (FTY720) for Relapsing Multiple Sclerosis

Thu, 14Â SepÂ 2006 00:00:00 -05:00

Background: Fingolimod (FTY720) is a new oral immunomodulating agent under evaluation for the treatment of relapsing multiple sclerosis.

Methods: We randomly assigned 281 patients to receive oral fingolimod, at a dose...

PERSPECTIVE: Fingolimod and Sphingosine-1-Phosphate â Modifiers of Lymphocyte Migration

Thu, 14Â SepÂ 2006 00:00:00 -05:00

Multiple sclerosis is considered an autoimmune disease in which CD4+ T cells and macrophages destroy oligodendrocytes, which synthesize and maintain axonal myelin sheaths in the central nervous system (CNS). This...

PERSPECTIVE: T-Cell Costimulation â Biology, Therapeutic Potential, and Challenges

Thu, 07Â SepÂ 2006 00:00:00 -05:00

The immune system has the remarkable ability to defend against diverse microbial pathogens and yet not to respond to self. T cells are key mediators of the immune response, and...

EDITORIAL: Volunteers at Risk

Jeffrey M. Drazen, M.D. — Thu, 07Â SepÂ 2006 00:00:00 -05:00

Clinical research can be a risky endeavor. In this issue of the Journal, Suntharalingam et al.1 describe the events that occurred when six healthy volunteers received a dose (0.1 mg...

ORIGINAL ARTICLE: Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412

Thu, 07Â SepÂ 2006 00:00:00 -05:00

Six healthy young male volunteers at a contract research organization were enrolled in the first phase 1 clinical trial of TGN1412, a novel superagonist anti-CD28 monoclonal antibody that directly stimulates...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: The Inflammasome â A Linebacker of Innate Defense

Joost P.H. Drenth, M.D., Ph.D., and Jos W.M. van der Meer, M.D., Ph.D. — Thu, 17Â AugÂ 2006 00:00:00 -05:00

Why study hereditary periodic-fever syndromes, which affect fewer than 500 patients worldwide? The discovery of cryopyrin provides an answer. The story begins in 2001, when investigators showed that mutations in...

CLINICAL THERAPEUTICS: Tumor Necrosis Factor Inhibitors for Rheumatoid Arthritis

D.L. Scott, M.D., and G.H. Kingsley, M.B., Ch.B., Ph.D. — Thu, 17Â AugÂ 2006 00:00:00 -05:00

Rheumatoid arthritis developed in a 25-year-old woman, who was found to have a positive rheumatoid factor (150 IU per milliliter); she had no periarticular radiologic erosions or extraarticular disease. Oral...

ORIGINAL ARTICLE: Neonatal-Onset Multisystem Inflammatory Disease Responsive to Interleukin-1Î² Inhibition

Thu, 10Â AugÂ 2006 00:00:00 -05:00

Background: Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1...

IMAGES IN CLINICAL MEDICINE: Angioedema of the Tongue

Sjoerd W. Westra, M.D. and Cornelis P.C. de Jager, M.D. — Thu, 20Â JulÂ 2006 00:00:00 -05:00

A 75-year-old man presented to the emergency department with diffuse swelling of his tongue that had begun a few hours earlier. He had no known history of allergies. He had...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Reversal of Type 1 Diabetes in Mice

Douglas A. Melton, Ph.D. — Thu, 06Â JulÂ 2006 00:00:00 -05:00

In 2003, the field of diabetes was shaken up by an article published in Science,1 stating that established autoimmune diabetes in mice could be permanently reversed with the injection of...

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...

EDITORIAL: Autoantibodies against PDGF Receptor in Scleroderma

Filemon K. Tan, M.D., Ph.D. — Thu, 22Â JunÂ 2006 00:00:00 -05:00

Scleroderma (systemic sclerosis) is characterized by the deposition and accumulation of excessive amounts of collagen and extracellular-matrix molecules, the dysfunction of microvascular endothelial cells, and altered immune tolerance. These interacting...

CLINICAL THERAPEUTICS: Omalizumab for Asthma

Robert C. Strunk, M.D., and Gordon R. Bloomberg, M.D. — Thu, 22Â JunÂ 2006 00:00:00 -05:00

A 16-year-old boy with a 15-year history of asthma from the age of one year and two visits to the emergency department in the past year presents for evaluation. He...

ORIGINAL ARTICLE: Stimulatory Autoantibodies to the PDGF Receptor in Systemic Sclerosis

Thu, 22Â JunÂ 2006 00:00:00 -05:00

Background: Systemic sclerosis (scleroderma) is characterized by immunologic abnormalities, injury of endothelial cells, and tissue fibrosis. Abnormal oxidative stress has been documented in scleroderma and linked to fibroblast activation. Since...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Imatinib Mesylate â Uncovering a Fast Track to Adaptive Immunity

Mark J. Smyth, Ph.D. — Thu, 25Â MayÂ 2006 00:00:00 -05:00

Tyrosine kinases are major targets of contemporary chemotherapy, and tyrosine kinase inhibitors â such as imatinib mesylate (Gleevec, Novartis; formerly known as STI571) â are approved for the treatment of...

ORIGINAL ARTICLE: Transmission of Lymphocytic Choriomeningitis Virus by Organ Transplantation

Thu, 25Â MayÂ 2006 00:00:00 -05:00

Background: In December 2003 and April 2005, signs and symptoms suggestive of infection developed in two groups of recipients of solid-organ transplants. Each cluster was investigated because diagnostic evaluations were...

PERSPECTIVE: Lymphocytic Choriomeningitis Virus â An Old Enemy up to New Tricks

Thu, 25Â MayÂ 2006 00:00:00 -05:00

Lymphocytic choriomeningitis virus (LCMV) was among the first human pathogenic viruses to be isolated. In the mid-1930s, Armstrong and Lillie obtained a filterable agent thought to be from the brain...

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...

PERSPECTIVE: Disabled Receptor Signaling and New Primary Immunodeficiency Disorders

Thu, 04Â MayÂ 2006 00:00:00 -05:00

During the past decade, we have witnessed major advances in the identification of mutations that cause primary immunodeficiency disorders â exciting results of the successful blending of fundamental and clinical...

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...

CLINICAL PROBLEM-SOLVING: A Jaundiced Eye

Thu, 06Â AprÂ 2006 00:00:00 -05:00

A previously healthy 27-year-old man presented to his primary care physician six days after the onset of a nonproductive cough, sore throat, and a feeling of being ârun down.â During...

EDITORIAL: Vaccines against Avian Influenza â A Race against Time

Gregory A. Poland, M.D. — Thu, 30Â MarÂ 2006 00:00:00 -05:00

Avian influenza A (H5N1) virus poses an important pandemic threat. A study by the Congressional Budget Office estimates that the consequences of a severe pandemic could, in the United States,...

ORIGINAL ARTICLE: Safety and Immunogenicity of an Inactivated Subvirion Influenza A (H5N1) Vaccine

Thu, 30Â MarÂ 2006 00:00:00 -05:00

Background: Influenza A (H5N1) viruses could cause a severe worldwide epidemic, with high attack rates, large numbers of deaths and hospitalizations, and wide disruption. Effective vaccines against these viruses in...

CLINICAL PRACTICE: Optic Neuritis

Laura J. Balcer, M.D., M.S.C.E. — Thu, 23Â MarÂ 2006 00:00:00 -05:00

A 25-year-old woman presents with a one-week history of blurred vision in the left eye. One day before the onset of visual loss, she noted a dull ache in the...

EDITORIAL: Natural Killer T Cells and Asthma

A. Barry Kay, M.D., Ph.D. — Thu, 16Â MarÂ 2006 00:00:00 -05:00

Invariant natural killer T cells, originally characterized in mice and more recently defined in humans, are a unique, conserved T-cell sublineage possessing a rearrangement of the T-cell antigen receptor (VÎ±14JÎ±18...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 8-2006 â A 71-Year-Old Woman with Crohn's Disease and Altered Mental Status

Thu, 16Â MarÂ 2006 00:00:00 -05:00

A 71-year-old woman was admitted to the hospital because of left-sided weakness and a mass in the brain. She had had Crohn's disease for many years but was in her...

REVIEW ARTICLE: Regulation of Immune Responses by T Cells

Hong Jiang, M.D., Ph.D., and Leonard Chess, M.D. — Thu, 16Â MarÂ 2006 00:00:00 -05:00

The T-cell branch of the immune system can respond to a virtually infinite variety of antigens, in part because it includes a very large repertoire of T-cell clones, each with...

EDITORIAL: Autoimmunity and Immunotherapy for Cancer

Henry Koon, M.D., and Michael Atkins, M.D. — Thu, 16Â FebÂ 2006 00:00:00 -05:00

Adjuvant treatment for patients after resection of high-risk and regionally metastatic melanoma remains suboptimal. Despite the Food and Drug Administration's approval of high-dose interferon alfa-2b, the substantial toxicity of the...

EDITORIAL: Inhibition of Tumor Necrosis Factor Î± for Refractory Asthma

Serpil C. Erzurum, M.D. — Thu, 16Â FebÂ 2006 00:00:00 -05:00

Tumor necrosis factor (TNF), originally discovered and named on the basis of its tumor regression activity, is an important cytokine that regulates the pathogenetic mechanisms of chronic inflammatory diseases.12 The...

ORIGINAL ARTICLE: Prognostic Significance of Autoimmunity during Treatment of Melanoma with Interferon

Thu, 16Â FebÂ 2006 00:00:00 -05:00

Background: Immunotherapy for advanced melanoma induces serologic and clinical manifestations of autoimmunity. We assessed the prognostic significance of autoimmunity in patients with stage IIB, IIC, or III melanoma who were...

ORIGINAL ARTICLE: Evidence of a Role of Tumor Necrosis Factor Î± in Refractory Asthma

Thu, 16Â FebÂ 2006 00:00:00 -05:00

Background: The development of tumor necrosis factor Î± (TNF-Î±) antagonists has made it feasible to investigate the role of this cytokine in refractory asthma.

Methods: We measured markers of TNF-Î± activity...

REVIEW ARTICLE: The Many Roles of Chemokines and Chemokine Receptors in Inflammation

Israel F. Charo, M.D., Ph.D., and Richard M. Ransohoff, M.D. — Thu, 09Â FebÂ 2006 00:00:00 -05:00

Chemokines (chemotactic cytokines) are small heparin-binding proteins that direct the movement of circulating leukocytes to sites of inflammation or injury. During the eight years since chemokines and chemokine receptors were...

CLINICAL PRACTICE: Antibiotic Allergy

Rebecca S. Gruchalla, M.D., Ph.D., and Munir Pirmohamed, Ph.D., F.R.C.P. — Thu, 09Â FebÂ 2006 00:00:00 -05:00

A 55-year-old woman presents to the hospital with cellulitis. She reports a history of urticaria 30 years earlier associated with taking penicillin for a respiratory tract infection. Should cephalosporins be...

IMAGES IN CLINICAL MEDICINE: Splenic and Mediastinal Calcifications in Histoplasmosis

Jeremy Topin, M.D. and GÃ¶khan M. Mutlu, M.D. — Thu, 12Â JanÂ 2006 00:00:00 -05:00

A 37-year-old woman from Illinois with a history of an idiopathic T-cell deficiency (CD4 cell count, 249 cells per cubic millimeter, and negative for infection with the human immunodeficiency virus),...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Inhibiting Inflammation in Rheumatoid Arthritis

Gary S. Firestein, M.D. — Thu, 05Â JanÂ 2006 00:00:00 -05:00

Targeting signal-transduction molecules, especially kinases, is a daunting task. First, these enzymes are often widely distributed in many tissues and contribute to a vast array of cellular processes essential for...

REVIEW ARTICLE: Autoimmune Hepatitis

Edward L. Krawitt, M.D. — Thu, 05Â JanÂ 2006 00:00:00 -05:00

Autoimmune hepatitis is a generally progressive, chronic hepatitis of unknown cause that occurs in children and adults of all ages. Occasionally, it has a fluctuating course, with periods of increased...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Immunosuppression, Skin Cancer, and Ultraviolet A Radiation

John A. Parrish, M.D. — Thu, 22Â DecÂ 2005 00:00:00 -05:00

Skin cancer is a serious problem in immunosuppressed patients. In these patients, cutaneous cancers are common in areas of the skin that are exposed to the sun, are more aggressive...

ORIGINAL ARTICLE: Effector Memory T Cells, Early Metastasis, and Survival in Colorectal Cancer

Thu, 22Â DecÂ 2005 00:00:00 -05:00

Background: The role of tumor-infiltrating immune cells in the early metastatic invasion of colorectal cancer is unknown.

Methods: We studied pathological signs of early metastatic invasion (venous emboli and lymphatic and...

PERSPECTIVE: Tumor-Infiltrating T Cells â Friend or Foe of Neoplastic Cells?

Thu, 22Â DecÂ 2005 00:00:00 -05:00

During the past 20 years, there have been many reports of the presence of inflammatory and immune-cell infiltrates in various neoplasms, including colorectal cancer. Initially, these findings were thought to...

EDITORIAL: Mycophenolate Mofetil for Lupus Nephritis

W. Joseph McCune, M.D. — Thu, 24Â NovÂ 2005 00:00:00 -05:00

Systemic lupus erythematosus is a chronic, life-threatening disease that predominantly affects women of childbearing age. Its pathogenesis includes autoantibody-mediated organ damage and antiphospholipid-antibodyâmediated hypercoagulability. Among patients who have lupus the...

ORIGINAL ARTICLE: Mycophenolate Mofetil or Intravenous Cyclophosphamide for Lupus Nephritis

Thu, 24Â NovÂ 2005 00:00:00 -05:00

Background: Since anecdotal series and small, prospective, controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis, larger trials are desirable.

Methods: We conducted a 24-week randomized, open-label,...

IMAGES IN CLINICAL MEDICINE: Lentigo Maligna

Bernard Noel, M.D. and Nathalie Kunzle, M.D. — Thu, 17Â NovÂ 2005 00:00:00 -05:00

An 81-year-old woman was referred for treatment of two asymmetric, poorly circumscribed pigmented macules on the left cheek. The pigmentation was variegated, ranging from light brown to retiform areas of...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: One Commensal Bacterial Molecule â All We Need for Health?

Claudio Fiocchi, M.D. — Thu, 10Â NovÂ 2005 00:00:00 -05:00

Humans are not inherently endowed with a healthy immune system. The fate of the immune system depends on its interaction with a large variety of commensal microorganisms, most of which...

CLINICAL PRACTICE: Allergic Rhinitis

Marshall Plaut, M.D., and Martin D. Valentine, M.D. — Thu, 03Â NovÂ 2005 00:00:00 -05:00

A Baltimore college student has rhinorrhea, sneezing, nasal congestion, and itchy, watery eyes in the spring. He reports having had similar symptoms the previous spring. Over-the-counter allergy pills have failed...

EDITORIAL: Severe Sepsis and Therapy with Activated Protein C

Joseph E. Parrillo, M.D. — Thu, 29Â SepÂ 2005 00:00:00 -05:00

Sepsis, severe sepsis, and septic shock represent a spectrum of increasingly severe diseases that result from serious infection and the body's response to microbiologic invasion. Population data suggest that 750,000...

EDITORIAL: Graft-versus-Host Disease â From the Bench to the Bedside?

GÃ©rard SociÃ©, M.D., Ph.D. — Thu, 29Â SepÂ 2005 00:00:00 -05:00

Myeloablative conditioning with high doses of chemotherapy before transplantation of allogeneic hematopoietic stem cells is a procedure that can cure hematologic malignant diseases, but its wide applicability is limited by...

ORIGINAL ARTICLE: Drotrecogin Alfa (Activated) for Adults with Severe Sepsis and a Low Risk of Death

Thu, 29Â SepÂ 2005 00:00:00 -05:00

Background: In November 2001, the Food and Drug Administration (FDA) approved drotrecogin alfa (activated) (DrotAA) for adults who had severe sepsis and a high risk of death. The FDA required...

ORIGINAL ARTICLE: Protective Conditioning for Acute Graft-versus-Host Disease

Thu, 29Â SepÂ 2005 00:00:00 -05:00

Background: Conditioning with total lymphoid irradiation plus antithymocyte serum protects mice against acute graft-versus-host disease (GVHD) after hematopoietic-cell transplantation. We tested this strategy in humans.

Methods: Thirty-seven patients with lymphoid malignant...

EDITORIAL: Immune Response as a Biomarker for Cancer Detection and a Lot More

Olivera J. Finn, Ph.D. — Thu, 22Â SepÂ 2005 00:00:00 -05:00

In 2000, the American Cancer Society inaugurated a yearly report on guidelines for cancer detection. The latest update, published in 2005,1 is identical to the previous versions in its recommendation...

EDITORIAL: Immunosuppression â The Promise of Specificity

Julie R. Ingelfinger, M.D., and Robert S. Schwartz, M.D. — Thu, 25Â AugÂ 2005 00:00:00 -05:00

The success of organ transplantation owes much to improvements in the immunosuppressive regimens that prevent or suppress allograft rejection. Nevertheless, the potent immunosuppressive drugs that are now in general use...

CLINICAL PROBLEM-SOLVING: A Fractured Diagnosis

Thu, 04Â AugÂ 2005 00:00:00 -05:00

A 44-year-old woman came to the emergency department because of pain in her right thigh shortly after she had a minor fall. A right femoral-neck fracture was diagnosed, and she...

IMAGES IN CLINICAL MEDICINE: Bilateral Pulmonary-Artery Aneurysms in BehÃ§et's Syndrome

Sudhir Lohani, M.D. and Robert Niven, M.D. — Thu, 28Â JulÂ 2005 00:00:00 -05:00

A 28-year-old Asian woman presented with pyrexia of unknown origin, oral and genital ulcers, and hemoptysis. A chest radiograph showed bilateral central hilar opacities (Panel A, arrows). A computed tomographic...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: A New Strategy to Counter Allergy

Jean-Pierre Kinet, M.D. — Thu, 21Â JulÂ 2005 00:00:00 -05:00

Many features of cellular programs are tightly controlled by the balancing actions of activation and inhibitory signals. This principle applies in particular to the cells of the immune system, which...

ORIGINAL ARTICLE: A Relapsing Inflammatory Syndrome and Active Human Herpesvirus 8 Infection

Thu, 14Â JulÂ 2005 00:00:00 -05:00

We describe an immunocompetent 61-year-old woman who was negative for human immunodeficiency virus and who had recurrent human herpesvirus 8 (HHV-8) infection associated with a relapsing systemic inflammatory syndrome characterized...

PERSPECTIVE: Aging, Immunity, and the VaricellaâZoster Virus

Ann Arvin, M.D. — Thu, 02Â JunÂ 2005 00:00:00 -05:00

Older people and their physicians are all too well acquainted with herpes zoster â commonly called shingles, from the Latin cingulum, or âgirdle.â Most recognize that aging creates a special...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 14-2005 â A 38-Year-Old Man with Fever and Blurred Vision

Thu, 12Â MayÂ 2005 00:00:00 -05:00

A 38-year-old man was admitted to this hospital because of blurred vision and fever.

The patient had ulcerative colitis but had been well while receiving treatment with mercaptopurine and balsalazide until...

ORIGINAL ARTICLE: Autoantibodies to Folate Receptors in the Cerebral Folate Deficiency Syndrome

Thu, 12Â MayÂ 2005 00:00:00 -05:00

In infantile-onset cerebral folate deficiency, 5-methyltetrahydrofolate (5MTHF) levels in the cerebrospinal fluid are low, but folate levels in the serum and erythrocytes are normal. We examined serum specimens from 28...

PERSPECTIVE: Autoimmune Folate Deficiency and the Rise and Fall of âHorror Autotoxicusâ

Robert S. Schwartz, M.D. — Thu, 12Â MayÂ 2005 00:00:00 -05:00

In 1904, a little more than a century ago, Julius Donath, a senior physician working in the Vienna Merchants' Hospital, and Karl Landsteiner, the chair of the pathology department at...

EDITORIAL: Agonistic Autoantibodies and Rejection of Renal Allografts

Julie R. Ingelfinger, M.D. — Thu, 10Â FebÂ 2005 00:00:00 -05:00

Allograft rejection remains a major problem in renal transplantation, despite the substantial improvements in post-transplantation management that now result in fewer acute rejection episodes and better overall survival.1 Rejection can...

ORIGINAL ARTICLE: Angiotensin II Type 1âReceptor Activating Antibodies in Renal-Allograft Rejection

Thu, 10Â FebÂ 2005 00:00:00 -05:00

Background: Antibodies against HLA antigens cause refractory allograft rejection with vasculopathy in some, but not all, patients.

Methods: We studied 33 kidney-transplant recipients who had refractory vascular rejection. Thirteen had donor-specific...

IMAGES IN CLINICAL MEDICINE: Destructive Eye Lesions in Wegener's Granulomatosis

Peer Malte Aries, M.D. and Marcus Both, M.D. — Thu, 27Â JanÂ 2005 00:00:00 -05:00

A 33-year-old woman presented with malaise, bloody nasal discharge, nasal crusting, and arthralgia. On examination, disconjugate gaze and protrusion of the right eye with scleritis were found. Serologic evaluation revealed...

ORIGINAL ARTICLE: Etanercept plus Standard Therapy for Wegener's Granulomatosis

The Wegener's Granulomatosis Etanercept Trial (WGET) Research Group — Thu, 27Â JanÂ 2005 00:00:00 -05:00

Background: The majority of patients with Wegener's granulomatosis have disease flares after conventional medications are tapered. There is no consistently safe, effective treatment for the maintenance of remission.

Methods: We conducted...

PERSPECTIVE: The Spectrum of Wegener's Granulomatosis and Disease Relapse

Paul A. Bacon, M.D. — Thu, 27Â JanÂ 2005 00:00:00 -05:00

Wegener's syndrome (Wegener's granulomatosis) is a rare systemic disorder, and because it involves multiple organs, affected patients may seek help from physicians in many specialties. It is classified as a...

CLINICAL PROBLEM-SOLVING: Unfashionably Late

Thu, 06Â JanÂ 2005 00:00:00 -05:00

An 18-year-old man presented with shortness of breath, a cough that was productive of clear sputum, and a two-week history of pleuritic chest pain. He also reported night sweats, fever,...

OCCASIONAL NOTES: Transplantation 50 Years Later â Progress, Challenges, and Promises

Mohamed H. Sayegh, M.D., and Charles B. Carpenter, M.D. — Thu, 23Â DecÂ 2004 00:00:00 -05:00

On December 23, 1954, a surgical team at the Peter Bent Brigham Hospital in Boston, under the direction of Joseph Murray, removed a kidney from a healthy donor and transplanted...

REVIEW ARTICLE: Immunosuppressive Drugs for Kidney Transplantation

Philip F. Halloran, M.D., Ph.D. — Thu, 23Â DecÂ 2004 00:00:00 -05:00

The central issue in organ transplantation remains suppression of allograft rejection. Thus, development of immunosuppressive drugs is the key to successful allograft function. Immunosuppressive agents are used for induction (intense...

PERSPECTIVE: Transplantation â A Medical Miracle of the 20th Century

Peter J. Morris, F.R.S. — Thu, 23Â DecÂ 2004 00:00:00 -05:00

Fifty years ago, on December 23, 1954, a kidney was transplanted from one healthy identical twin to his twin who was dying of renal disease. The surgery was performed at...

IMAGES IN CLINICAL MEDICINE: âShoulder Padâ Sign

Carlos Geraldo Guerreiro de Moura, M.D. and SÃ©rgio Pinto de Souza, M.D. — Thu, 16Â DecÂ 2004 00:00:00 -05:00

A 66-year-old man presented with a two-year history of fatigue, paresthesia of the legs and feet, weight loss, and shoulder enlargement, with limitation of movement. On physical examination, periorbital ecchymoses...

REVIEW ARTICLE: Advances in H-Antihistamines

F. Estelle R. Simons, M.D. — Thu, 18Â NovÂ 2004 00:00:00 -05:00

More than 30,000 peer-reviewed articles on histamine and the H1-antihistamines have been published since this subject was last reviewed in the Journal a decade ago.1 The role of histamine in...

ORIGINAL ARTICLE: Prediction of Survival in Follicular Lymphoma Based on Molecular Features of Tumor-Infiltrating Immune Cells

Thu, 18Â NovÂ 2004 00:00:00 -05:00

Background: Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at...

PERSPECTIVE: Prognosis in Follicular Lymphoma â It's in the Microenvironment

Ralf KÃ¼ppers, Ph.D. — Thu, 18Â NovÂ 2004 00:00:00 -05:00

Considerable clinical heterogeneity and wide variation in survival among patients are characteristic of many B-cell lymphomas. Prognostic markers that predict the clinical behavior of such tumors with greater accuracy than...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Cachexia in Cancer â Zeroing in on Myosin

Jeffrey S. Chamberlain, Ph.D. — Thu, 11Â NovÂ 2004 00:00:00 -05:00

Cachexia is a condition associated with a variety of serious diseases, including cancer, AIDS, and congestive heart failure. It is manifested as weight loss involving both adipose tissue and skeletal...

ORIGINAL ARTICLE: AntiâInterleukin-12 Antibody for Active Crohn's Disease

Thu, 11Â NovÂ 2004 00:00:00 -05:00

Background: Crohn's disease is associated with excess cytokine activity mediated by type 1 helper T (Th1) cells. Interleukin-12 is a key cytokine that initiates Th1-mediated inflammatory responses.

Methods: This double-blind trial...

PERSPECTIVE: Cytokine-Based Therapies for Crohn's Disease â New Paradigms

Fabio Cominelli, M.D., Ph.D. — Thu, 11Â NovÂ 2004 00:00:00 -05:00

Crohn's disease is one of two idiopathic inflammatory bowel diseases that affect approximately 1 million people in North America. Despite important advances in diagnosis and treatment in recent years, the...

CLINICAL PRACTICE: Hypersensitivity to Hymenoptera Stings

Theodore M. Freeman, M.D. — Thu, 04Â NovÂ 2004 00:00:00 -05:00

A 29-year-old man reported that he was stung by a flying hymenopteran â he does not know what type â outside his door, where he had previously noted a nest....

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Chitin Checking â Novel Insights into Asthma

Marsha Wills-Karp, Ph.D., and Christopher L. Karp, M.D. — Thu, 30Â SepÂ 2004 00:00:00 -05:00

Westernized countries are in the midst of an asthma epidemic. Despite much effort, therapeutic advances have not kept pace with the dramatic increases in the incidence, prevalence, and severity of...

ORIGINAL ARTICLE: Inherited Perforin and Mutations in a Patient with Autoimmune Lymphoproliferative Syndrome and Lymphoma

Thu, 30Â SepÂ 2004 00:00:00 -05:00

A 27-year-old man with the autoimmune lymphoproliferative syndrome and a large-B-cell lymphoma had heterozygous mutations in the Fas and perforin (Prf1) genes. The Fas mutation was inherited from his healthy...

ORIGINAL ARTICLE: Autoimmune Lymphoproliferative Syndrome with Somatic Mutations

Thu, 30Â SepÂ 2004 00:00:00 -05:00

Background: Impaired Fas-induced apoptosis of lymphocytes in vitro is a principal feature of the autoimmune lymphoproliferative syndrome (ALPS). We studied six children with ALPS whose lymphocytes had normal sensitivity to...

PERSPECTIVE: Somatic Mutations â Not Just for Cancer Anymore

Jennifer M. Puck, M.D., and Stephen E. Straus, M.D. — Thu, 30Â SepÂ 2004 00:00:00 -05:00

Opportunities for genetic errors during reproduction are so frequent that one wonders how any of us turn out healthy. Although many of these errors are inconsequential, and some can beneficially...

EDITORIAL: Allergen Avoidance to Reduce Asthma-Related Morbidity

Albert L. Sheffer, M.D. — Thu, 09Â SepÂ 2004 00:00:00 -05:00

Central to the reduction of the severity of allergic disease is a decrease in â and preferably the removal of â the offending environmental allergen. Such allergen avoidance is particularly...

ORIGINAL ARTICLE: Results of a Home-Based Environmental Intervention among Urban Children with Asthma

Thu, 09Â SepÂ 2004 00:00:00 -05:00

Background: Children with asthma who live in the inner city are exposed to multiple indoor allergens and environmental tobacco smoke in their homes. Reductions in these triggers of asthma have...

EDITORIAL: Immunotherapy in Allergy to Insect Stings in Children

Rebecca S. Gruchalla, M.D., Ph.D. — Thu, 12Â AugÂ 2004 00:00:00 -05:00

The earliest reported death from an allergic reaction to a stinging insect was that of King Menes of Egypt, who died in 2641 B.C., purportedly as the result of a...

ORIGINAL ARTICLE: Outcomes of Allergy to Insect Stings in Children, with and without Venom Immunotherapy

Thu, 12Â AugÂ 2004 00:00:00 -05:00

Background: Children are thought to âoutgrowâ the allergy to insect stings, but there are no reports documenting the natural history of this reaction. We studied the outcome of allergic reactions...

EDITORIAL: Childhood Leukemia â New Advances and Challenges

Naomi J. Winick, M.D., William L. Carroll, M.D., and Stephen P. Hunger, M.D. — Thu, 05Â AugÂ 2004 00:00:00 -05:00

Since 1970, the rate of cure of acute lymphoblastic leukemia (ALL) in children has increased dramatically, from less than 30 percent to approximately 80 percent. This remarkable improvement has resulted...

ORIGINAL ARTICLE: Loss of Smad3 in Acute T-Cell Lymphoblastic Leukemia

Thu, 05Â AugÂ 2004 00:00:00 -05:00

Background: The receptors for transforming growth factor Î² (TGF-Î²) and their signaling intermediates make up an important tumor-suppressor pathway. The role of one of these intermediates â Smad3 â in...

PERSPECTIVE: TGF-Î² Signaling, Tumor Suppression, and Acute Lymphoblastic Leukemia

James R. Downing, M.D. — Thu, 05Â AugÂ 2004 00:00:00 -05:00

The emergence of a single cancer cell is an extremely complex process that depends not only on the escape of a normal cell from growth-control mechanisms but also on the...

ORIGINAL ARTICLE: Acquired Hypocalciuric Hypercalcemia Due to Autoantibodies against the Calcium-Sensing Receptor

Thu, 22Â JulÂ 2004 00:00:00 -05:00

A complex homeostatic system involving the interplay of the bones, the kidneys, and the intestines has evolved to maintain extracellular calcium concentrations within a relatively narrow range.1 The primary regulator...

PERSPECTIVE: Translational Implications of the Parathyroid Calcium Receptor

Andrew F. Stewart, M.D. — Thu, 22Â JulÂ 2004 00:00:00 -05:00

We live in the era of the Human Genome Project, human and mouse genetics, proteomics, evidence-based medicine, intelligent drug design, and a new âroad mapâ for the National Institutes of...

IMAGES IN CLINICAL MEDICINE: HenochâSchÃ¶nlein Purpura

Mark A. Marinella, M.D. — Thu, 15Â JulÂ 2004 00:00:00 -05:00

A 20-year-old man was admitted to the hospital with a one-day history of fever and acute, painful symmetric polyarthritis that involved the wrists, elbows, and ankles. During the next two...

ORIGINAL ARTICLE: Efficacy of B-CellâTargeted Therapy with Rituximab in Patients with Rheumatoid Arthritis

Thu, 17Â JunÂ 2004 00:00:00 -05:00

Background: An open-label study indicated that selective depletion of B cells with the use of rituximab led to sustained clinical improvements for patients with rheumatoid arthritis. To confirm these observations,...

PERSPECTIVE: B Cells, Be Gone â B-Cell Depletion in the Treatment of Rheumatoid Arthritis

George C. Tsokos, M.D. — Thu, 17Â JunÂ 2004 00:00:00 -05:00

CD20 protein is expressed on the surface membrane of pre-B lymphocytes and mature B lymphocytes. The protein is located in the B-cell membrane, with 44 amino acids exposed in the...

IMAGES IN CLINICAL MEDICINE: Dislocation of the Lenses

Sameer K. Mathur, M.D., Ph.D. and Daniel Grodinsky, M.D. — Thu, 10Â JunÂ 2004 00:00:00 -05:00

A 60-year-old man with a history of frequent falls presented after a fall that resulted in minor trauma to the head. A review of systems was remarkable only for the...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: The Molecular Basis of Streptococcal Toxic Shock Syndrome

Eric J. Brown, M.D. — Thu, 13Â MayÂ 2004 00:00:00 -05:00

Streptococcus pyogenes, also known as group A streptococcus, is the cause of purulent pharyngitis and pyoderma, occasionally complicated by scarlet fever, rheumatic fever, and glomerulonephritis â a scenario familiar to...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 15-2004 â A 31-Year-Old Man with Bilateral Testicular Enlargement

Karen K. Ballen, M.D., and Robert P. Hasserjian, M.D. — Thu, 13Â MayÂ 2004 00:00:00 -05:00

A 31-year-old man was admitted to the hospital because of a testicular mass.

The patient had been well until three months before admission, when he noted bilateral testicular swelling that coincided...

REVIEW ARTICLE: Autoimmune Polyendocrine Syndromes

George S. Eisenbarth, M.D., Ph.D., and Peter A. Gottlieb, M.D. — Thu, 13Â MayÂ 2004 00:00:00 -05:00

The autoimmune polyendocrine syndromes are diverse, and their diversity is a characteristic that is both clinically important and instructive when their basic immunologic features are considered (Table 1).1234 These syndromes...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 11-2004 â A Boy with Rash, Edema, and Hypertension

Michael J. Somers, M.D., Ghaleb H. Daouk, M.D., and Robert T. McCluskey, M.D. — Thu, 08Â AprÂ 2004 00:00:00 -05:00

A 12-year-old boy was admitted to the hospital because of hypertension and edema, and because the results of urinalysis were abnormal.

Fourteen days before admission, cough and nasal congestion, followed by...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Shedding Light on Immunotherapy for Cancer

Steven A. Rosenberg, M.D., Ph.D. — Thu, 01Â AprÂ 2004 00:00:00 -05:00

The realization that human cancers express cancer-associated antigens has stimulated research into the development of immunotherapies to mediate the regression of established tumors. There are three requirements for an effective...

REVIEW ARTICLE: Activation of the T-Cell Oncogene after Gene Therapy for X-Linked Severe Combined Immunodeficiency

Matthew P. McCormack, Ph.D., and Terence H. Rabbitts, Ph.D. — Thu, 26Â FebÂ 2004 00:00:00 -05:00

The emerging field of gene therapy promises to yield exciting new treatments for a range of illnesses. Most forms of gene therapy use viral delivery mechanisms, most commonly retroviruses,1 and...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Getting a Handle on Graft-versus-Host Disease

Robertson Parkman, M.D. — Thu, 05Â FebÂ 2004 00:00:00 -05:00

A central dichotomy of allogeneic hematopoietic stem-cell transplantation for neoplastic diseases is that the immune responses initiated by donor-derived cells provide both the chief benefit and the major limitation of...

ORIGINAL ARTICLE: Effect of Changing the Priority for HLA Matching on the Rates and Outcomes of Kidney Transplantation in Minority Groups

Thu, 05Â FebÂ 2004 00:00:00 -05:00

Background: HLA typing and the time a patient has spent on the waiting list are the primary criteria used to allocate cadaveric kidneys for transplantation in the United States. Candidates...

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: Weighing Optimal Graft Survival through HLA Matching against the Equitable Distribution of Kidney Allografts

Jon J. van Rood, M.D., Ph.D. — Thu, 05Â FebÂ 2004 00:00:00 -05:00

At almost exactly the same time that Dr. David Willard, whose letter to the editor appears in this issue of the Journal (page 624), received three skin grafts in order...

ORIGINAL ARTICLE: Soluble Triggering Receptor Expressed on Myeloid Cells and the Diagnosis of Pneumonia

Thu, 29Â JanÂ 2004 00:00:00 -05:00

Background: The diagnosis and treatment of bacterial pneumonia in patients who are receiving mechanical ventilation remain a difficult challenge. The triggering receptor expressed on myeloid cells (TREM-1) is a member...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: The Danger Within

Keith R. Jerome, M.D., Ph.D., and Lawrence Corey, M.D. — Thu, 22Â JanÂ 2004 00:00:00 -05:00

We come into contact with a vast assortment of external agents every day, and our immune system needs to deal with them. How does the immune system distinguish dangerous from...

ORIGINAL ARTICLE: Immunoproliferative Small Intestinal Disease Associated with

Thu, 15Â JanÂ 2004 00:00:00 -05:00

Background: Immunoproliferative small intestinal disease (also known as alpha chain disease) is a form of lymphoma that arises in small intestinal mucosa-associated lymphoid tissue (MALT) and is associated with the...

PERSPECTIVE: Bacterial Infection and MALT Lymphoma

Julie Parsonnet, M.D., and Peter G. Isaacson, F.R.C.Path. — Thu, 15Â JanÂ 2004 00:00:00 -05:00

Fifty years ago, the idea that infectious agents caused lymphoma would have seemed heretical. Although viruses were known to cause tumors in animals, they were not considered a cause of...

ORIGINAL ARTICLE: Autoantibodies against Folate Receptors in Women with a Pregnancy Complicated by a Neural-Tube Defect

Thu, 08Â JanÂ 2004 00:00:00 -05:00

Background: In the absence of clinical folate deficiency, periconceptional supplementation with folic acid reduces a woman's risk of having an infant with a neural-tube defect. Since antiserum to folate receptors...

REVIEW ARTICLE: Pulmonary Alveolar Proteinosis

Bruce C. Trapnell, M.D., Jeffrey A. Whitsett, M.D., and Koh Nakata, M.D., Ph.D. — Thu, 25Â DecÂ 2003 00:00:00 -05:00

Pulmonary alveolar proteinosis is a rare disorder in which lipoproteinaceous material accumulates within alveoli.1 The clinical course of the disease is variable, ranging from respiratory failure to spontaneous resolution. An...

ORIGINAL ARTICLE: Use of an AntiâInterleukin-5 Antibody in the Hypereosinophilic Syndrome with Eosinophilic Dermatitis

Thu, 11Â DecÂ 2003 00:00:00 -05:00

The hypereosinophilic syndrome comprises a heterogeneous group of conditions characterized by hypereosinophilia and organ dysfunction caused by eosinophil-mediated tissue damage.12 The highly variable response to treatment reflects the heterogeneity of...

PERSPECTIVE: The Discovery of HIV as the Cause of AIDS

Robert C. Gallo, M.D., and Luc Montagnier, M.D. — Thu, 11Â DecÂ 2003 00:00:00 -05:00

Progress in scientific research rarely follows a straight path. Generally, it entails many unexpected meanderings, with a mix of good and bad ideas, good and bad luck. The discovery of...

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...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Shedding Light on Microbial Detection

David A. Relman, M.D. — Thu, 27Â NovÂ 2003 00:00:00 -05:00

The failure to achieve a rapid and reliable means of diagnosing most infectious diseases remains a frustrating testimony to the diversity of pathogens and the complexity of humanâmicrobe interactions. With...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 36-2003 â A 68-Year-Old Woman with Impaired Renal Function

Ajay K. Singh, M.B., B.S., M.R.C.P., and Robert B. Colvin, M.D. — Thu, 20Â NovÂ 2003 00:00:00 -05:00

A 68-year-old woman was admitted to the hospital because of impaired renal function. One month earlier, she had had difficulty breathing and had felt as though she had a fever;...

ORIGINAL ARTICLE: Etanercept as Monotherapy in Patients with Psoriasis

Thu, 20Â NovÂ 2003 00:00:00 -05:00

Background: Inflammatory cytokines such as tumor necrosis factor (TNF) have been implicated in the pathogenesis of psoriasis. We evaluated the safety and efficacy of etanercept, a TNF antagonist, for the...

ORIGINAL ARTICLE: A Novel Targeted T-Cell Modulator, Efalizumab, for Plaque Psoriasis

Thu, 20Â NovÂ 2003 00:00:00 -05:00

Background: Interactions between leukocyte-functionâassociated antigen type 1 (LFA-1) and intercellular adhesion molecules are important in the pathogenesis of psoriasis. Efalizumab, a humanized monoclonal antibody, binds to the Î± subunit (CD11a)...

PERSPECTIVE: Immunologic Targets in Psoriasis

Thomas S. Kupper, M.D. — Thu, 20Â NovÂ 2003 00:00:00 -05:00

In this issue of the Journal, two reports present data on the efficacy of two new biologic drugs for psoriasis. One of these drugs, etanercept, has been used extensively in...

ORIGINAL ARTICLE: Treatment of Rheumatoid Arthritis by Selective Inhibition of T-Cell Activation with Fusion Protein CTLA4Ig

Thu, 13Â NovÂ 2003 00:00:00 -05:00

Background: Effective new therapies are needed for rheumatoid arthritis. Current therapies target the products of activated macrophages; however, T cells also have an important role in rheumatoid arthritis. A fusion...

ORIGINAL ARTICLE: Effect of CD3Î´ Deficiency on Maturation of Î±/Î² and Î³/Î´ T-Cell Lineages in Severe Combined Immunodeficiency

Harjit K. Dadi, Ph.D., Amos J. Simon, Ph.D., and Chaim M. Roifman, M.D. — Thu, 06Â NovÂ 2003 00:00:00 -05:00

The T-cellâreceptor complex consists of the Î± and Î² or Î³ and Î´ variant chains, paired as mutually exclusive heterodimers in association with the invariant chains CD3Î³, Î´, Îµ, and...

PERSPECTIVE: Have We Seen the Last Variant of Severe Combined Immunodeficiency?

Alain Fischer, M.D. — Thu, 06Â NovÂ 2003 00:00:00 -05:00

Over the past 15 years, deciphering of the molecular defects in primary immunodeficiencies has spawned a stream of information on how the immune system works. These advances have been facilitated...

ORIGINAL ARTICLE: Absence of Cross-Reactivity between Sulfonamide Antibiotics and Sulfonamide Nonantibiotics

Thu, 23Â OctÂ 2003 00:00:00 -05:00

Background: The safety of sulfonamide nonantibiotics is unclear in patients with prior allergic reactions to sulfonamide antibiotics.

Methods: We conducted a retrospective cohort study using the General Practice Research Database in...

PERSPECTIVE: Population-Based Studies of Adverse Drug Effects

Wayne A. Ray, Ph.D. — Thu, 23Â OctÂ 2003 00:00:00 -05:00

The prescription of medications has long been the most frequent therapeutic intervention in medicine. In 2000 in the United States, 173 million people filled 2.2 billion outpatient prescriptions, accounting for...

ORIGINAL ARTICLE: Development of Autoantibodies before the Clinical Onset of Systemic Lupus Erythematosus

Thu, 16Â OctÂ 2003 00:00:00 -05:00

Background: Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored....

PERSPECTIVE: Autoantibodies in Systemic Lupus Erythematosus â There before You Know It

Robert H. Shmerling, M.D. — Thu, 16Â OctÂ 2003 00:00:00 -05:00

Autoantibodies are an integral part of the process of classifying, detecting, and, at least in some cases, mediating autoimmune diseases. Since the discovery of the antinuclear antibody more than 40...

EDITORIAL: Toward Asthma Prevention â Does All That Really Matters Happen before We Learn to Read?

Fernando D. Martinez, M.D. — Thu, 09Â OctÂ 2003 00:00:00 -05:00

Patients with asthma and their caregivers are currently faced with a remarkable paradox. Considerable progress has been made during the past 20 years in the pharmacotherapy, educational tools, and environmental...

ORIGINAL ARTICLE: A Longitudinal, Population-Based, Cohort Study of Childhood Asthma Followed to Adulthood

Thu, 09Â OctÂ 2003 00:00:00 -05:00

Background: The outcome of childhood asthma in adults has been described in high-risk cohorts, but few population-based studies have reported the risk factors for persistence and relapse.

Methods: We assessed children...

OCCASIONAL NOTES: The 50th Anniversary of the Discovery of Immunologic Tolerance

Leslie Brent, Ph.D. — Thu, 02Â OctÂ 2003 00:00:00 -05:00

On October 3, 1953 â almost exactly half a century ago â Rupert E. Billingham, Peter B. Medawar, and I published a paper in Nature titled ââActively Acquired Toleranceâ of...

EDITORIAL: Treatment of the Antiphospholipid Syndrome

Michael D. Lockshin, M.D., and Doruk Erkan, M.D. — Thu, 18Â SepÂ 2003 00:00:00 -05:00

Two decades after the presence of anticardiolipin antibodies and a syndrome of spontaneous thrombosis and fetal death were linked,1 and after the publication of approximately 3500 reports in which the...

ORIGINAL ARTICLE: A Comparison of Two Intensities of Warfarin for the Prevention of Recurrent Thrombosis in Patients with the Antiphospholipid Antibody Syndrome

Thu, 18Â SepÂ 2003 00:00:00 -05:00

Background: Many patients with the antiphospholipid antibody syndrome and recurrent thrombosis receive doses of warfarin adjusted to achieve an international normalized ratio (INR) of more than 3.0. However, there are...

IMAGES IN CLINICAL MEDICINE: Uvular Angioedema (Quincke's Disease)

Andrew Kestler, M.D. and Linda Keyes, M.D. — Thu, 28Â AugÂ 2003 00:00:00 -05:00

A 19-year-old man without a history of asthma or allergies presented to the emergency department with difficulty in breathing. He had snorted and smoked cocaine three hours before presentation, after...

IMAGES IN CLINICAL MEDICINE: Systemic Mastocytosis

Arjun Deb, M.D. and Ayalew Tefferi, M.D. — Thu, 14Â AugÂ 2003 00:00:00 -05:00

A 44-year-old woman presented with a one-year history of neck and lower back pain. The neck and back pain had worsened over the previous two months and was associated with...

REVIEW ARTICLE: Molecular Mechanisms of Amyloidosis

Giampaolo Merlini, M.D., and Vittorio Bellotti, M.D., Ph.D. — Thu, 07Â AugÂ 2003 00:00:00 -05:00

The amyloidoses constitute a large group of diseases in which misfolding of extracellular protein has a prominent role. This dynamic process, which occurs in parallel with or as an alternative...

ORIGINAL ARTICLE: Inherited Deficiency of Mannan-Binding LectinâAssociated Serine Protease 2

Thu, 07Â AugÂ 2003 00:00:00 -05:00

The complement system is part of the innate immune system and contributes to the establishment of adaptive immune responses.1 The mannan-binding lectin pathway of the complement system is activated when...

IMAGES IN CLINICAL MEDICINE: Relapsing Polychondritis

David Vroman, M.D. and Kerry D. Solomon, M.D. — Thu, 17Â JulÂ 2003 00:00:00 -05:00

A 64-year-old man was referred to an eye clinic because of recurrent bilateral red eyes and lid swelling, which had started 14 months earlier. One or both eyes would become...

ORIGINAL ARTICLE: Evaluation of Impermeable Covers for Bedding in Patients with Allergic Rhinitis

Thu, 17Â JulÂ 2003 00:00:00 -05:00

Background: Encasing bedding in impermeable covers reduces exposure to house-dust mites, but the clinical benefit of this intervention as part of mite-avoidance measures for patients with allergic rhinitis is not...

ORIGINAL ARTICLE: Control of Exposure to Mite Allergen and Allergen-Impermeable Bed Covers for Adults with Asthma

Thu, 17Â JulÂ 2003 00:00:00 -05:00

Background: The effectiveness of avoidance of house-dust-mite allergen (Dermatophagoides pteronyssinus 1 [Der p1]) in the management of asthma is uncertain.

Methods: We conducted a double-blind, randomized, placebo-controlled study of allergen-impermeable bed...

PERSPECTIVE: Allergen Avoidance in the Treatment of Asthma and Rhinitis

Thomas A.E. Platts-Mills, M.D., Ph.D. — Thu, 17Â JulÂ 2003 00:00:00 -05:00

The evidence that allergens found inside houses are an important cause of perennial rhinitis and asthma comes from three types of studies. In one type, the delivery of allergen in...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Molecular Mimicry in Multiple Sclerosis

Hartmut Wekerle, M.D., and Reinhard Hohlfeld, M.D. — Thu, 10Â JulÂ 2003 00:00:00 -05:00

Most experts believe that multiple sclerosis is an autoimmune disease in which T cells recognize and attack components of the axonal myelin sheath and other features of the central nervous...

REVIEW ARTICLE: Medium- and Large-Vessel Vasculitis

Cornelia M. Weyand, M.D., Ph.D., and JÃ¶rg J. Goronzy, M.D., Ph.D. — Thu, 10Â JulÂ 2003 00:00:00 -05:00

Inflammation of large arteries such as the aorta and its major branches occurs in a number of disorders, including Kawasaki's syndrome, BehÃ§et's syndrome, rheumatoid arthritis, syphilis, and tuberculosis. However, aortitis...

ORIGINAL ARTICLE: Antimyelin Antibodies as a Predictor of Clinically Definite Multiple Sclerosis after a First Demyelinating Event

Thu, 10Â JulÂ 2003 00:00:00 -05:00

Background: Most patients with multiple sclerosis initially present with a clinically isolated syndrome. Despite the fact that clinically definite multiple sclerosis will develop in up to 80 percent of these...

PERSPECTIVE: Do Myelin-Directed Antibodies Predict Multiple Sclerosis?

Jack P. Antel, M.D., and Amit Bar-Or, M.D. — Thu, 10Â JulÂ 2003 00:00:00 -05:00

Multiple sclerosis is characterized by recurrent neurologic events (clinical relapses) that are attributable to multifocal lesions within the central nervous system. Lesions referred to as âactive plaquesâ are characterized by...

ORIGINAL ARTICLE: A Randomized Trial of Maintenance Therapy for Vasculitis Associated with Antineutrophil Cytoplasmic Autoantibodies

Thu, 03Â JulÂ 2003 00:00:00 -05:00

Background: The primary systemic vasculitides usually associated with autoantibodies to neutrophil cytoplasmic antigens include Wegener's granulomatosis and microscopic polyangiitis. We investigated whether exposure to cyclophosphamide in patients with generalized vasculitis...

PERSPECTIVE: Treatment of ANCA-Associated Vasculitis

Carol A. Langford, M.D., M.H.S. — Thu, 03Â JulÂ 2003 00:00:00 -05:00

Vasculitis is defined by inflammation of the blood-vessel wall and forms the pathological foundation of a diverse group of individual disease entities. Among the primary systemic vasculitic diseases, Wegener's granulomatosis...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Celiac Disease â The Villain Unmasked?

Ross McManus, Ph.D., and Dermot Kelleher, M.D. — Thu, 19Â JunÂ 2003 00:00:00 -05:00

Celiac disease (also known as celiac sprue and gluten-sensitive enteropathy) is a common autoimmune condition triggered by ingesting one of several related proteins found in wheat, barley, and rye: the...

EDITORIAL: Celiac Disease â How to Handle a Clinical Chameleon

Alessio Fasano, M.D. — Thu, 19Â JunÂ 2003 00:00:00 -05:00

Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains (including wheat, rye, and barley) in genetically susceptible persons. The disease is associated with HLA-DQ2 in 90...

REVIEW ARTICLE: Alport's Syndrome, Goodpasture's Syndrome, and Type IV Collagen

Thu, 19Â JunÂ 2003 00:00:00 -05:00

Basement membranes form a complex surface on which epithelial cells reside. These membranes provide morphogenic cues that determine the fate of cells, the polarization of subcellular constituents, and the location...

ORIGINAL ARTICLE: Prevalence of Celiac Disease among Children in Finland

Thu, 19Â JunÂ 2003 00:00:00 -05:00

Background: Wheat, rye, and barley proteins induce celiac disease, an autoimmune type of gastrointestinal disorder, in genetically susceptible persons. Because the disease may be underdiagnosed, we estimated the prevalence of...

ORIGINAL ARTICLE: Itraconazole to Prevent Fungal Infections in Chronic Granulomatous Disease

Thu, 12Â JunÂ 2003 00:00:00 -05:00

Background: Chronic granulomatous disease is a rare disorder in which the phagocytes fail to produce hydrogen peroxide. The patients are predisposed to bacterial and fungal infections. Prophylactic antibiotics and interferon...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: The Mast Cell in Inflammatory Arthritis

David E. Woolley, Ph.D., D.Sc. — Thu, 24Â AprÂ 2003 00:00:00 -05:00

Rheumatoid arthritis is a chronic destructive disease of joints, characterized by inflammation, synovial hyperplasia, and abnormal cellular and humoral immune responses. Although several types of cells have been proposed to...

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...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 10-2003 â A 72-Year-Old Man with Rapidly Progressive Leukemia, Rash, and Multiorgan Failure

Francine M. Foss, M.D., Suzanne L. Aquino, M.D., and Judith A. Ferry, M.D. — Thu, 27Â MarÂ 2003 00:00:00 -05:00

A 72-year-old man was transferred to this hospital from another hospital because of rapidly progressive leukemia and multiorgan failure.

The patient had lost an unknown amount of weight during the preceding...

ORIGINAL ARTICLE: Effect of Anti-IgE Therapy in Patients with Peanut Allergy

Thu, 13Â MarÂ 2003 00:00:00 -05:00

Background: Peanut-induced anaphylaxis is an IgE-mediated condition that is estimated to affect 1.5 million people and cause 50 to 100 deaths per year in the United States. TNX-901 is a...

PERSPECTIVE: Studying Peanut Anaphylaxis

Beverly Merz — Thu, 13Â MarÂ 2003 00:00:00 -05:00

In this issue of the Journal, Leung et al. (pages 986â993) report results with a new drug to reduce the risk of anaphylactic reactions to food. In a multicenter, phase...

EDITORIAL: Two Approaches to Peanut Allergy

Henry Metzger, M.D. — Thu, 13Â MarÂ 2003 00:00:00 -05:00

About 80 years ago, Carl Prausnitz injected into his abdominal skin a small amount of serum from his colleague, Heinz KÃ¼stner. When Prausnitz subsequently ate some cooked fish to which...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 8-2003 â A 35-Year-Old Man with Early Dysfunction of a Second Renal Transplant

Mohamed H. Sayegh, M.D., and Robert B. Colvin, M.D. — Thu, 13Â MarÂ 2003 00:00:00 -05:00

A 35-year-old man with end-stage renal disease and a history of failed renal transplantation was admitted to the hospital for another transplantation.

When the patient was 10 years old, diabetes mellitus...

SPECIAL ARTICLE: Diversity of the Immune Repertoire and Immunoregulation

Robert S. Schwartz, M.D. — Thu, 13Â MarÂ 2003 00:00:00 -05:00

Since the midpoint of the 20th century, medical advances in economically developed countries have exceeded all expectations. In 1950, the year I entered medical school, the average life expectancy in...

ORIGINAL ARTICLE: Factors Associated with Progression of Carcinoid Heart Disease

Thu, 13Â MarÂ 2003 00:00:00 -05:00

Background: By releasing vasoactive substances into the circulation, carcinoid tumors can cause right-sided valvular heart disease. Factors associated with the progression of carcinoid heart disease are poorly understood. We conducted...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: In Search of a Better HIV Vaccine â The Heat Is On

Elizabeth G. Phimister, Ph.D. — Thu, 13Â FebÂ 2003 00:00:00 -05:00

Human immunodeficiency virus type 1 (HIV-1) is notorious for its ability to evade the immune system. A recent study by Kwong and colleagues1 has uncovered a new molecular mechanism of...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 5-2003 â A 16-Year-Old Girl with a Rash and Chest Pain

Ivor Caro, M.D., and Artur Zembowicz, M.D. — Thu, 13Â FebÂ 2003 00:00:00 -05:00

A 16-year-old girl was admitted to the hospital because of pleuritic chest pain.

Bilateral imbrication of the hip capsules had been performed 15 months earlier at this hospital because of recurrent...

ORIGINAL ARTICLE: Influence of Immunogenicity on the Long-Term Efficacy of Infliximab in Crohn's Disease

Thu, 13Â FebÂ 2003 00:00:00 -05:00

Background: Treatment with infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor, can result in the formation of antibodies against infliximab. We evaluated the clinical significance of these antibodies...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: A Family of WASPs

Scott B. Snapper, M.D., Ph.D., and Fred S. Rosen, M.D. — Thu, 23Â JanÂ 2003 00:00:00 -05:00

The main clinical features of the WiskottâAldrich syndrome, an X-linked immunodeficiency, are thrombocytopenia with small platelets, eczema, susceptibility to opportunistic and pyogenic infections, and B-cell lymphomas associated with EpsteinâBarr virus....

EDITORIAL: Immunosurveillance against Cancer and Immunotherapy â Synergy or Antagonism?

Thierry Boon, Ph.D., and Nicolas van Baren, M.D. — Thu, 16Â JanÂ 2003 00:00:00 -05:00

Immunologists have long been alert to the possibility that the immune system eliminates many cancers at an early stage and slows down the progress of others.1 In recent years, the...

ORIGINAL ARTICLE: Intratumoral T Cells, Recurrence, and Survival in Epithelial Ovarian Cancer

Thu, 16Â JanÂ 2003 00:00:00 -05:00

Background: Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not been established.

Methods: We performed immunohistochemical analysis of 186 frozen specimens from...

PERSPECTIVE: Risks and Benefits of Gene Therapy

Philip Noguchi, M.D. — Thu, 16Â JanÂ 2003 00:00:00 -05:00

Updated information on this topic from the Food and Drug Administration is available at http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01190.html.

Although most of today's gene-therapy trials are targeted to cancer, there is renewed interest in pursuing...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Complement C5a in the Sepsis Syndrome â Too Much of a Good Thing?

Craig Gerard, Ph.D., M.D. — Thu, 09Â JanÂ 2003 00:00:00 -05:00

In the sepsis syndrome, a âcytokine stormâ unleashes numerous inflammatory mediators that contribute to multiple-organ dysfunction and, frequently, to death. During the past decade, research on how the innate immune...

REVIEW ARTICLE: The Pathophysiology and Treatment of Sepsis

Richard S. Hotchkiss, M.D., and Irene E. Karl, Ph.D. — Thu, 09Â JanÂ 2003 00:00:00 -05:00

Sepsis is the leading cause of death in critically ill patients in the United States. Sepsis develops in 750,000 people annually, and more than 210,000 of them die.12 After numerous...

EDITORIAL: Î± Integrins as Therapeutic Targets in Autoimmune Disease

Ulrich H. von Andrian, M.D., Ph.D., and Britta Engelhardt, Ph.D. — Thu, 02Â JanÂ 2003 00:00:00 -05:00

In this issue of the Journal, two groups of investigators report on clinical trials of natalizumab, a recombinant monoclonal antibody against Î±4 integrins, for the treatment of multiple sclerosis1 and...

ORIGINAL ARTICLE: Natalizumab for Active Crohn's Disease

Thu, 02Â JanÂ 2003 00:00:00 -05:00

Background: In chronic inflammatory conditions such as Crohn's disease, the migration of leukocytes from the circulation into the parenchyma and their activation within inflammatory sites are mediated in part by...

ORIGINAL ARTICLE: A Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis

Thu, 02Â JanÂ 2003 00:00:00 -05:00

Background: In patients with multiple sclerosis, inflammatory brain lesions appear to arise from autoimmune responses involving activated lymphocytes and monocytes. The glycoprotein Î±4 integrin is expressed on the surface of...

EDITORIAL: Kala-Azar â Progress against a Neglected Disease

Thu, 28Â NovÂ 2002 00:00:00 -05:00

Visceral leishmaniasis is a well-recognized disseminated protozoal infection in both children and adults, but it has long been shrouded in mysterious-sounding names such as Dumdum fever and kala-azar (Hindi for...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 36-2002 â A 32-Year-Old Man with Hemoptysis of Nearly Three Decades' Duration

Eric S. Silverman and Eugene J. Mark — Thu, 21Â NovÂ 2002 00:00:00 -05:00

A 32-year-old man was admitted to the hospital because of long-standing hemoptysis and interstitial pulmonary disease.

The patient had been born of a 32-week gestation that was complicated by spotting during...

EDITORIAL: Leukotriene Receptors and Aspirin Sensitivity

Thu, 07Â NovÂ 2002 00:00:00 -05:00

About 15 million people in the United States have asthma. In a small percentage of them, variably estimated at between 3 percent and 10 percent, acute, severe asthma accompanied by...

ORIGINAL ARTICLE: Leukotriene-Receptor Expression on Nasal Mucosal Inflammatory Cells in Aspirin-Sensitive Rhinosinusitis

Thu, 07Â NovÂ 2002 00:00:00 -05:00

Background: Patients with asthma who have aspirin sensitivity have greater cysteinyl leukotriene production and greater airway hyperresponsiveness to the effects of inhaled cysteinyl leukotrienes than their aspirin-tolerant counterparts. We hypothesized...

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...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 32-2002 â A 58-Year-Old Man with Interstitial Pulmonary Disease

Thu, 17Â OctÂ 2002 00:00:00 -05:00

A 58-year-old man was admitted to the hospital because of interstitial pulmonary disease.

The patient had a history of eosinophilic granuloma, which had been confirmed by right-sided open-lung biopsy 25 years...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Defying Death â HIV Mutation to Evade Cytotoxic T Lymphocytes

Thu, 10Â OctÂ 2002 00:00:00 -05:00

Cytotoxic T lymphocytes control viral infections by lysing infected cells and secreting soluble factors (cytokines) that enhance antiviral immunity and suppress infection. The importance of antiviral killer cells in controlling...

EDITORIAL: Antimicrobial Peptides in Health and Disease

Thu, 10Â OctÂ 2002 00:00:00 -05:00

Microbes surround us. However, most of the time we are unaware of them. Our epithelial surfaces, which provide the physical barrier separating us from the environment, are usually free of...

ORIGINAL ARTICLE: Endogenous Antimicrobial Peptides and Skin Infections in Atopic Dermatitis

Thu, 10Â OctÂ 2002 00:00:00 -05:00

Background: The innate immune system of human skin contains antimicrobial peptides known as cathelicidins (LL-37) and Î²-defensins. In normal skin these peptides are negligible, but they accumulate in skin affected...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 30-2002 â An Eight-Year-Old Girl with Fever, Hemoptysis, and Pulmonary Consolidations

Brian P. O'Sullivan, Lori A. Erickson, and John L. Niles — Thu, 26Â SepÂ 2002 00:00:00 -05:00

An eight-year-old girl was admitted to the hospital because of fever, cough, hemoptysis, and pulmonary consolidations.

She had been well until six days before admission, when she was visiting El Salvador....

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Surfaces as an Asthma Gene

Thu, 19Â SepÂ 2002 00:00:00 -05:00

Asthma is thought to result from complex interactions between genes and the environment. Although allergens and endotoxins appear to be environmental modifiers of asthma,12 the genes involved have been harder...

EDITORIAL: Eat Dirt â The Hygiene Hypothesis and Allergic Diseases

Thu, 19Â SepÂ 2002 00:00:00 -05:00

There has been an epidemic of both autoimmune diseases (in which the immune response is dominated by type 1 helper T [Th1] cells, such as type 1 diabetes, Crohn's disease,...

REVIEW ARTICLE: The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases

Jean-FranÃ§ois Bach, M.D., D.Sc. — Thu, 19Â SepÂ 2002 00:00:00 -05:00

Infectious agents can induce autoimmune diseases in several experimental settings, some of which have clinical counterparts. A variety of mechanisms have been invoked to explain these observations, including molecular mimicry...

ORIGINAL ARTICLE: Environmental Exposure to Endotoxin and Its Relation to Asthma in School-Age Children

Thu, 19Â SepÂ 2002 00:00:00 -05:00

Background: In early life, the innate immune system can recognize both viable and nonviable parts of microorganisms. Immune activation may direct the immune response, thus conferring tolerance to allergens such...

REVIEW ARTICLE: IgA Nephropathy

James V. Donadio, M.D., and Joseph P. Grande, M.D., Ph.D. — Thu, 05Â SepÂ 2002 00:00:00 -05:00

IgA nephropathy is a relatively newly recognized disease, first described by Berger and Hinglais in 1968.1 It is now generally known to be the most common form of primary glomerulonephritis...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 23-2002 â A 73-Year-Old Man with Leg Pains, Occipital Headaches, and Night Sweats

William P. Docken and Eugene J. Mark — Thu, 25Â JulÂ 2002 00:00:00 -05:00

A 73-year-old man was admitted to the hospital because of leg pains, occipital headaches, and night sweats.

He had been in good health until two months earlier, when he began to...

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: Antenatal Membranous Glomerulonephritis Due to AntiâNeutral Endopeptidase Antibodies

Thu, 27Â JunÂ 2002 00:00:00 -05:00

Membranous glomerulonephritis, a major cause of the nephrotic syndrome and chronic renal insufficiency, is associated with a wide spectrum of infections, cancers, autoimmune diseases, and drugs. The condition is characterized...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 18-2002 â A 48-Year-Old Man with a Cough and Bloody Sputum

Richard L. Kradin, M.D., and Eugene J. Mark, M.D. — Thu, 13Â JunÂ 2002 00:00:00 -05:00

A 48-year-old man was admitted to the hospital because of bilateral pulmonary infiltrates, bloody sputum, and microhematuria.

The patient was a physician who had been well until about eight years earlier,...

EDITORIAL: Can We Change the Course of Beta-Cell Destruction in Type 1 Diabetes?

Thu, 30Â MayÂ 2002 00:00:00 -05:00

Imagine a nephrologist with no biopsy needle, no imaging techniques, no serum creatinine measurement â a nephrologist whose patients need dialysis when they first present for care. This is the...

ORIGINAL ARTICLE: Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus

Thu, 30Â MayÂ 2002 00:00:00 -05:00

Background: Type 1 diabetes mellitus is a chronic autoimmune disease caused by the pathogenic action of T lymphocytes on insulin-producing beta cells. Previous clinical studies have shown that continuous immune...

EDITORIAL: AntiâTNF-Î± Therapy for Ankylosing Spondylitis â A Specific or Nonspecific Treatment?

Thu, 02Â MayÂ 2002 00:00:00 -05:00

The spondyloarthropathies comprise ankylosing spondylitis, reactive arthritis, arthritis that accompanies inflammatory bowel disease, some forms of psoriatic arthritis, and undifferentiated forms of spondyloarthropathy. The report in this issue of the...

ORIGINAL ARTICLE: Treatment of Ankylosing Spondylitis by Inhibition of Tumor Necrosis Factor Î±

Thu, 02Â MayÂ 2002 00:00:00 -05:00

Background: There are few effective treatments for ankylosing spondylitis, which causes substantial morbidity. Because of the central role of tumor necrosis factor Î± in the spondyloarthritides, we performed a randomized,...

EDITORIAL: The Nuts and Bolts of Peanut Allergy

Thu, 25Â AprÂ 2002 00:00:00 -05:00

In this issue of the Journal, Sampson1 reviews the clinical features of allergy to peanuts. The question is why, in a small but apparently increasing percentage of the population, does...

CLINICAL PRACTICE: Peanut Allergy

Hugh A. Sampson, M.D. — Thu, 25Â AprÂ 2002 00:00:00 -05:00

A 19-year-old woman is brought to the emergency room because of the acute onset of dyspnea, wheezing, vomiting, and generalized flushing. She has well-controlled asthma as well as a history...

EDITORIAL: Continuing Medical Education in the

Thu, 18Â AprÂ 2002 00:00:00 -05:00

In this issue of the Journal, readers will find a quiz based on the article entitled âNonalcoholic Fatty Liver Disease,â by Angulo. This marks the beginning of a new continuing-medical-education...

ORIGINAL ARTICLE: Sustained Correction of X-Linked Severe Combined Immunodeficiency by ex Vivo Gene Therapy

Thu, 18Â AprÂ 2002 00:00:00 -05:00

Background: X-linked severe combined immunodeficiency due to a mutation in the gene encoding the common Î³ (Î³c) chain is a lethal condition that can be cured by allogeneic stem-cell transplantation....

REVIEW ARTICLE: Immune Thrombocytopenic Purpura

Douglas B. Cines, M.D., and Victor S. Blanchette, M.B., B.Chir. — Thu, 28Â MarÂ 2002 00:00:00 -05:00

Immune thrombocytopenic purpura is an autoimmune disorder characterized by a low platelet count and mucocutaneous bleeding. The estimated incidence is 100 cases per 1 million persons per year, and about...

REVIEW ARTICLE: The Antiphospholipid Syndrome

Jerrold S. Levine, M.D., D. Ware Branch, M.D., and Joyce Rauch, Ph.D. — Thu, 07Â MarÂ 2002 00:00:00 -05:00

Antiphospholipid antibodies are a family of autoantibodies that exhibit a broad range of target specificities and affinities, all recognizing various combinations of phospholipids, phospholipid-binding proteins, or both. The term âantiphospholipid...

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...

EDITORIAL: Bullous Pemphigoid Therapy â Think Globally, Act Locally

Thu, 31Â JanÂ 2002 00:00:00 -05:00

Until now, systemic immunosuppressive agents, particularly oral corticosteroids, have been the standard treatment for bullous pemphigoid, which accounts for about 75 percent of cases of autoimmune blistering skin disease.123 Nearly...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 4-2002 â A 75-Year-Old Man with Acute Renal Failure Five Months after Cystoprostatectomy and Urethrectomy for Carcinoma

Hasan Bazari, M.D.,and Shamila Mauiyyedi, M.D. — Thu, 31Â JanÂ 2002 00:00:00 -05:00

A 75-year-old man was admitted to the hospital because of acute renal failure.

He had undergone cystoprostatectomy and urethrectomy with construction of an ileal conduit five months earlier because of prostatic...

CLINICAL PRACTICE: Chronic Urticaria and Angioedema

Allen P. Kaplan, M.D. — Thu, 17Â JanÂ 2002 00:00:00 -05:00

A 35-year-old woman presents with a three-month history of daily generalized hives. The hives are pruritic, red wheals that range from 1.5 to 8.0 cm (0.5 to 3 in.) in...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Locking a Leukocyte Integrin with Statins

Thu, 08Â NovÂ 2001 00:00:00 -05:00

The first of the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (collectively referred to as âstatinsâ) was identified in 1976.1 This enzyme was an ideal target for treating hypercholesterolemia, since it...

EDITORIAL: The Immunology Series Comes to an End

Thu, 01Â NovÂ 2001 00:00:00 -05:00

The thought-provoking article by Zinkernagel in this issue of the Journal1 brings to a close the series of review articles on immunology that have been appearing in these pages during...

REVIEW ARTICLE: Maternal Antibodies, Childhood Infections, and Autoimmune Diseases

Rolf M. Zinkernagel, M.D. — Thu, 01Â NovÂ 2001 00:00:00 -05:00

Recovery from an infectious disease or an encounter with a nonmicrobial antigen is usually followed by the development of resistance to that disease or a rapid and heightened immune response...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 32-2001 â A 77-Year-Old Man with Rheumatoid Arthritis and Acute Dyspnea and Renal Failure

Helen M. Hollingsworth, M.D. and Eugene J. Mark, M.D. — Thu, 18Â OctÂ 2001 00:00:00 -05:00

A 77-year-old man was transferred to this hospital because of worsening bilateral air-space disease and acute renal failure.

He had stopped smoking 30 years before admission. He had mild chronic obstructive...

REVIEW ARTICLE: Vaccines and Vaccination

Gordon Ada, D.Sc. — Thu, 04Â OctÂ 2001 00:00:00 -05:00

More than 70 bacteria, viruses, parasites, and fungi are serious human pathogens.1 Vaccines are available against some of these agents and are being developed against almost all the other bacteria...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 30-2001 â A 22-Year-Old Man with Hyperthyroidism, Fever, Abdominal Pain, and Arthralgia

Mahboob U. Rahman, M.D., Ph.D, Chieh-Min Fan, M.D., and Hyon K. Choi, M.D. — Thu, 27Â SepÂ 2001 00:00:00 -05:00

A 22-year-old man was admitted to the hospital because of fever, abdominal pain, diarrhea, and polyarthralgia.

The patient had been well until two years before admission, when a tremor developed and...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 28-2001 â A 44-Year-Old Woman with Chills, Fever, Jaundice, and Hepatic Abscesses

Raymond T. Chung, M.D., and Eric C. Sheffer, M.D> — Thu, 13Â SepÂ 2001 00:00:00 -05:00

A 44-year-old woman was admitted to this hospital because of abdominal pain, chills, fever, and jaundice.

The patient, a native of southern China, had been treated for intrahepatic stones by lithotripsy...

REVIEW ARTICLE: Cephalosporin Allergy

Pramod S. Kelkar, M.D., and James T.-C. Li, M.D., Ph.D. — Thu, 13Â SepÂ 2001 00:00:00 -05:00

Cephalosporin antibiotics are widely prescribed for common infections such as bronchitis, otitis media, pneumonia, and cellulitis. They are also administered as first-line prophylaxis for many types of surgical procedures. A...

REVIEW ARTICLE: Immunomodulation of Autoimmune and Inflammatory Diseases with Intravenous Immune Globulin

Michel D. Kazatchkine, M.D., and Srini V. Kaveri, D.V.M., Ph.D. — Thu, 06Â SepÂ 2001 00:00:00 -05:00

Intravenous immune globulin has been used in the treatment of primary and secondary antibody deficiencies for more than 25 years. It is a safe preparation with no long-term side effects....

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...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 24-2001 â A 46-Year-Old Woman with Chronic Sinusitis, Pulmonary Nodules, and Hemoptysis

John F. Beamis, M.D., and Eugene J. Mark, M.D. — Thu, 09Â AugÂ 2001 00:00:00 -05:00

A 46-year-old woman was admitted to the hospital because of recurrent hemoptysis.

Eight months earlier, a cough, nonpleuritic left-sided chest pain, and fatigue had developed, with minor episodes of hemoptysis. A...

REVIEW ARTICLE: Autoimmune Diseases

Anne Davidson, M.B., B.S., and Betty Diamond, M.D. — Thu, 02Â AugÂ 2001 00:00:00 -05:00

Autoimmune diseases, with the exception of rheumatoid arthritis and autoimmune thyroiditis, are individually rare, but together they affect approximately 5 percent of the population in Western countries.12 They are a...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 19-2001 â A 50-Year-Old Man with Fever and Joint Pain

Simon M. Helfgott, Alexander Kratz — Thu, 21Â JunÂ 2001 00:00:00 -05:00

A 50-year-old man was admitted to the hospital because of fever and arthralgias.

The patient had been in excellent health until six weeks earlier, when a sore throat, rhinorrhea, headaches, and...

ORIGINAL ARTICLE: Treatment of the Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome (IPEX) by Allogeneic Bone Marrow Transplantation

Thu, 07Â JunÂ 2001 00:00:00 -05:00

The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is a recessive disorder of early childhood.1 Symptoms of the disease generally appear in infancy and include protracted diarrhea, ichthyosiform dermatitis, insulin-dependent...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 17-2001 â A 42-Year-Old Man with Multiple Pulmonary Cysts and Recurrent Respiratory Infections

R. Scott Harris, Eugene J. Mark — Thu, 31Â MayÂ 2001 00:00:00 -05:00

A 42-year-old man was admitted to the hospital because of pulmonary cysts.

The patient had a long history of nasal allergy, with occasional wheezing on exposure to cats; hives after ingestion...

REVIEW ARTICLE: Complement â Second of Two Parts

Mark J. Walport, Ph.D., F.R.C.P. — Thu, 12Â AprÂ 2001 00:00:00 -05:00

The formation of an antibodyâantigen complex (immune complex) is the principal way of activating the classical pathway of the complement system. C1q, an integral part of the first component of...

REVIEW ARTICLE: Complement â First of Two Parts

Mark J. Walport, Ph.D., F.R.C.P. — Thu, 05Â AprÂ 2001 00:00:00 -05:00

Complement is part of the innate immune system and underlies one of the main effector mechanisms of antibody-mediated immunity. It has three overarching physiologic activities (Table 1): defending against pyogenic...

EDITORIAL: Immune Monitoring for Rejection of Kidney Transplants

Thu, 29Â MarÂ 2001 00:00:00 -05:00

Kidney transplantation is the best treatment for patients with end-stage renal disease. The first six months after a technically successful transplantation is, however, often complicated by episodes of renal dysfunction...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 9-2001 â A 64-Year-Old Woman with Peripheral Neuropathy, Paraproteinemia, and Lymphadenopathy

Kenneth C. Gorson, E. Tessa Hedley-Whyte, Martha M. Skinner — Thu, 22Â MarÂ 2001 00:00:00 -05:00

A 64-year-old, right-handed woman was admitted to the hospital because of motor and sensory impairment in her right arm.

Two years before admission, generalized lymphadenopathy had been diagnosed. At that time,...

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...

EDITORIAL: Providing Antiretroviral Therapy for HIV Infection

Thu, 15Â MarÂ 2001 00:00:00 -05:00

Dramatic declines in the incidence of AIDS and the number of deaths from this disease began in the United States in 1996, in association with the widespread use of potent...

ORIGINAL ARTICLE: ABO-Incompatible Heart Transplantation in Infants

Thu, 15Â MarÂ 2001 00:00:00 -05:00

Background: Transplantation of hearts from ABO-incompatible donors is contraindicated because of the risk of hyperacute rejection mediated by preformed antibodies in the recipient to blood-group antigens of the donor. This...

ORIGINAL ARTICLE: Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2

Thu, 15Â MarÂ 2001 00:00:00 -05:00

Background: The HER2 gene, which encodes the growth factor receptor HER2, is amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers, increasing the aggressiveness of the...

REVIEW ARTICLE: Tolerance and Autoimmunity

Thomas Kamradt, M.D., and N. Avrion Mitchison, Ph.D. — Thu, 01Â MarÂ 2001 00:00:00 -05:00

The immunologic specificity of the antigen receptors of T cells and B cells is the result of random shuffling of the many genes that form the DNA code for the...

EDITORIAL: Noninvasive Ventilation for Immunocompromised Patients

Thu, 15Â FebÂ 2001 00:00:00 -05:00

Immunocompromised patients with respiratory failure who require mechanical ventilation have notoriously poor prognoses, with mortality rates ranging from 60 to 100 percent, depending on the underlying diagnosis and factors such...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 5-2001 â A 52-Year-Old Man with Chronic Anemia and Sudden Severe Abdominal Pain

Farhad Navab, Rhonda K. Yantiss — Thu, 15Â FebÂ 2001 00:00:00 -05:00

A 52-year-old man was admitted to the hospital because of an attack of severe abdominal pain.

During the preceding four years, the patient had been evaluated repeatedly for chronic iron-deficiency anemia,...

ORIGINAL ARTICLE: Noninvasive Ventilation in Immunosuppressed Patients with Pulmonary Infiltrates, Fever, and Acute Respiratory Failure

Thu, 15Â FebÂ 2001 00:00:00 -05:00

Background: Avoiding intubation is a major goal in the management of respiratory failure, particularly in immunosuppressed patients. Nevertheless, there are only limited data on the efficacy of noninvasive ventilation in...

ORIGINAL ARTICLE: Virologic and Immunologic Consequences of Discontinuing Combination Antiretroviral-Drug Therapy in HIV-Infected Patients with Detectable Viremia

Thu, 15Â FebÂ 2001 00:00:00 -05:00

Background: In many patients with human immunodeficiency virus (HIV) infection, therapy with potent antiretroviral drugs does not result in complete suppression of HIV replication. The effect of cessation of therapy...

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL: Case 4-2001 â A 26-Year-Old Man with Pain, Erythema, and Swelling of the Legs

Peter W. Bates, Eugene J. Mark — Thu, 08Â FebÂ 2001 00:00:00 -05:00

A 26-year-old man was admitted to the hospital because of pain, erythema, and swelling of the legs.

The patient had been well until two weeks earlier, when he had had occasional...

REVIEW ARTICLE: Asthma

William W. Busse, M.D., and Robert F. Lemanske, Jr., M.D. — Thu, 01Â FebÂ 2001 00:00:00 -05:00

Asthma is a complex syndrome with many clinical phenotypes in both adults and children. Its major characteristics include a variable degree of airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. For...

ORIGINAL ARTICLE: Malabsorption Due to Cholecystokinin Deficiency in a Patient with Autoimmune Polyglandular Syndrome Type I

Thu, 25Â JanÂ 2001 00:00:00 -05:00

Autoimmune polyglandular syndrome type I is an autosomal recessive inherited disease caused by mutations in the autoimmune regulator gene.1 Its hallmarks are the failure of multiple endocrine glands due to...

REVIEW ARTICLE: Allergy and Allergic Diseases â First of Two Parts

A.B. Kay, M.D., Ph.D. — Thu, 04Â JanÂ 2001 00:00:00 -05:00

Allergic rhinitis, asthma, and atopic eczema are among the commonest causes of chronic ill health. These diseases are increasing in prevalence, and they add considerably to the burden of health...

REVIEW ARTICLE: Immunodeficiency Diseases Caused by Defects in Phagocytes

Julie A. Lekstrom-Himes, M.D., and John I. Gallin, M.D. — Thu, 07Â DecÂ 2000 00:00:00 -05:00

Primary phagocytic defects must be included in the differential diagnosis of recurrent infection and fever in a child and occasionally in an adult. Early diagnosis is essential, because manifestations of...

REVIEW ARTICLE: Primary Immunodeficiency Diseases Due to Defects in Lymphocytes

Rebecca H. Buckley, M.D. — Thu, 02Â NovÂ 2000 00:00:00 -05:00

The recognition of impaired immunity in children five decades ago12 spurred an exponential increase in knowledge of the functions of the immune system. More than 95 inherited immunodeficiency disorders have...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Antibodies and Resistance to Natural HIV Infection

Thu, 26Â OctÂ 2000 00:00:00 -05:00

The unprecedented spread of the human immunodeficiency virus (HIV) throughout the world has made the development of an effective AIDS vaccine one of the most urgent challenges facing biomedical science....

REVIEW ARTICLE: T-Cell Function and Migration â Two Sides of the Same Coin

Ulrich H. von Andrian, M.D., Ph.D., and Charles R. Mackay, Ph.D. — Thu, 05Â OctÂ 2000 00:00:00 -05:00

Since the pioneering work of Gowans and colleagues in the 1960s,12 much progress has been made in understanding the pivotal role of cell migration in immunity. We now have considerable...

ORIGINAL ARTICLE: Autoantibodies to Ganglionic Acetylcholine Receptors in Autoimmune Autonomic Neuropathies

Thu, 21Â SepÂ 2000 00:00:00 -05:00

Background: Idiopathic autonomic neuropathy is a severe, subacute disorder with a presumed autoimmune basis. It is indistinguishable from the subacute autonomic neuropathy that may accompany lung cancer or other tumors....

EDITORIAL: Cancer Immunotherapy with Alloreactive Lymphocytes

Thu, 14Â SepÂ 2000 00:00:00 -05:00

In this issue of the Journal, Childs and colleagues present preliminary evidence that in patients with metastatic renal-cell cancer, infusions of allogeneic hematopoietic stem cells after a preparative regimen that...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: The Role of the Interleukin-1âReceptor Antagonist in Blocking Inflammation Mediated by Interleukin-1

Thu, 07Â SepÂ 2000 00:00:00 -05:00

Approaches involving the blockade of inflammatory cytokines such as interleukin-1 and tumor necrosis factor Î± (TNF-Î±) are entering mainstream clinical medicine: antibodies against TNF-Î± and soluble receptors for TNF-Î± are...

REVIEW ARTICLE: The HLA System â First of Two Parts

Jan Klein, Ph.D., and Akie Sato, Ph.D. — Thu, 07Â SepÂ 2000 00:00:00 -05:00

A man dies because his body has rejected a heart transplant; a woman is crippled by rheumatoid arthritis; a child goes into a coma that is brought on by cerebral...

EDITORIAL: Composite-Tissue Transplantation â A New Frontier

Thu, 17Â AugÂ 2000 00:00:00 -05:00

Limb transplantation has long been of interest to surgeons. The legend of the pysician twins Saint Cosmos and Saint Damian, who transplanted a whole leg in a.d. 348, has come...

ORIGINAL ARTICLE: Successful Hand Transplantation â One-Year Follow-up

Thu, 17Â AugÂ 2000 00:00:00 -05:00

Background: On the basis of positive results in studies of the transplantation of pig extremities and the information exchanged at an international symposium on composite-tissue transplantation, we developed a protocol...

REVIEW ARTICLE: Strategies for Making More Organs Available for Transplantation

Bruno Gridelli, M.D., and Giuseppe Remuzzi, M.D. — Thu, 10Â AugÂ 2000 00:00:00 -05:00

Organ transplantation has evolved rapidly from the first early successes1 to the current widespread use of donated organs for the treatment of end-stage kidney, heart, and liver failure. With limited...

REVIEW ARTICLE: Innate Immunity

Ruslan Medzhitov, Ph.D., and Charles Janeway, Jr., M.D. — Thu, 03Â AugÂ 2000 00:00:00 -05:00

The immune system has traditionally been divided into innate and adaptive components, each with a different function and role. The adaptive component is organized around two classes of specialized cells,...

REVIEW ARTICLE: The Immune System â Second of Two Parts

Peter J. Delves, Ph.D., and Ivan M. Roitt, Ph.D. — Thu, 13Â JulÂ 2000 00:00:00 -05:00

The complexity of the cellular interactions that occur during acquired immune responses requires specialized microenvironments in which the relevant cells can collaborate efficiently. Because only a few lymphocytes are specific...

EDITORIAL: Advances in Immunology â A New Series of Review Articles

Thu, 06Â JulÂ 2000 00:00:00 -05:00

In this issue the Journal launches a new series of review articles, Advances in Immunology. The articles will appear monthly, usually in the first issue of the month (some articles...

EDITORIAL: Pemphigus â Decoding the Cellular Language of Cutaneous Autoimmunity

Thu, 06Â JulÂ 2000 00:00:00 -05:00

The primary causes of the most common autoimmune disorders have been elusive. Pemphigus foliaceus has attracted considerable attention, despite its low incidence, because the associated autoantibodies are directly pathogenic, their...

REVIEW ARTICLE: The Immune System â First of Two Parts

Peter J. Delves, Ph.D., and Ivan M. Roitt, D.Sc. — Thu, 06Â JulÂ 2000 00:00:00 -05:00

The immune system is an organization of cells and molecules with specialized roles in defending against infection. There are two fundamentally different types of responses to invading microbes. Innate (natural)...

ORIGINAL ARTICLE: Protection against Pemphigus Foliaceus by Desmoglein 3 in Neonates

Thu, 06Â JulÂ 2000 00:00:00 -05:00

Pemphigus foliaceus is an autoantibody-mediated blistering disease in which antibodies against desmoglein 1 cause loss of adhesion among keratinocytes in the superficial epidermis.1 Desmogleins are transmembrane glycoproteins found in desmosomes,...

ORIGINAL ARTICLE: The Prevalence of Antibodies against Desmoglein 1 in Endemic Pemphigus Foliaceus in Brazil

Thu, 06Â JulÂ 2000 00:00:00 -05:00

Background: Pemphigus foliaceus is an autoimmune skin disease mediated by autoantibodies against desmoglein 1. The endemic form is thought to have an environmental cause. The Terena reservation of LimÃ£o Verde...

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...

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...

REVIEW ARTICLE: Role of Transforming Growth Factor Î² in Human Disease

Thu, 04Â MayÂ 2000 00:00:00 -05:00

In human tissues, normal homeostasis requires intricately balanced interactions between cells and the network of secreted proteins known as the extracellular matrix. These cooperative interactions involve numerous cytokines acting through...

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...

ORIGINAL ARTICLE: C-Reactive Protein and Other Markers of Inflammation in the Prediction of Cardiovascular Disease in Women

Thu, 23Â MarÂ 2000 00:00:00 -05:00

Background: Since inflammation is believed to have a role in the pathogenesis of cardiovascular events, measurement of markers of inflammation has been proposed as a method to improve the prediction...

EDITORIAL: Tumor Necrosis Factor Blockers in Rheumatoid Arthritis

Thu, 16Â MarÂ 2000 00:00:00 -05:00

For patients with rheumatoid arthritis, a new era in treatment has begun. This optimistic view, shared widely by rheumatologists, reflects the introduction in the past two years of novel agents...

ORIGINAL ARTICLE: Meta-Analyses of the Relation between Silicone Breast Implants and the Risk of Connective-Tissue Diseases

Thu, 16Â MarÂ 2000 00:00:00 -05:00

Background: The postulated relation between silicone breast implants and the risk of connective-tissue and autoimmune diseases has generated intense medical and legal interest during the past decade. The salience of...

EDITORIAL: Improving the Success of Organ Transplantation

Thu, 02Â MarÂ 2000 00:00:00 -05:00

The concept of drug-induced immunosuppression arose in the late 1950s with the observation by Schwartz and Dameshek that 6-mercaptopurine, developed as an antileukemic drug, was effective in blocking primary, but...

ORIGINAL ARTICLE: Prevention of Rejection in Cardiac Transplantation by Blockade of the Interleukin-2 Receptor with a Monoclonal Antibody

Thu, 02Â MarÂ 2000 00:00:00 -05:00

Background: Alloantigen-activated T cells express the high-affinity interleukin-2 receptor. Specific blockade of this receptor with the human IgG1 monoclonal antibody daclizumab may prevent rejection of allografts after cardiac transplantation without...

ORIGINAL ARTICLE: Asymptomatic Carriage of and Serum Levels of IgG Antibody against Toxin A

Thu, 10Â FebÂ 2000 00:00:00 -05:00

Background: Clostridium difficile infection can result in asymptomatic carriage, mild diarrhea, or fulminant pseudomembranous colitis. We studied whether antibody responses to C. difficile toxins affect the risks of colonization, diarrhea,...

ORIGINAL ARTICLE: Paraneoplastic Cerebellar Ataxia Due to Autoantibodies against a Glutamate Receptor

Thu, 06Â JanÂ 2000 00:00:00 -05:00

There are many types of cerebellar ataxia, including ataxia due to congenital or metabolic disorders and a paraneoplastic form in patients with gynecologic cancer, breast cancer, lung cancer, or Hodgkin's...

REVIEW ARTICLE: Molecular Mimicry and Autoimmunity

Lori J. Albert, M.D., and Robert D. Inman, M.D. — Thu, 30Â DecÂ 1999 00:00:00 -05:00

Autoimmune disease is the consequence of an immune response against self-antigens that results in the damage and eventual dysfunction of target organs. Although the triggering event in most autoimmune diseases...

EDITORIAL: Anti-IgE Antibody Therapy for Asthma

Thu, 23Â DecÂ 1999 00:00:00 -05:00

Over the past 10 years there have been striking improvements in the treatment of asthma, largely as a result of the earlier and more widespread use of inhaled corticosteroids. The...

ORIGINAL ARTICLE: Treatment of Allergic Asthma with Monoclonal Anti-IgE Antibody

Thu, 23Â DecÂ 1999 00:00:00 -05:00

Background: Immune responses mediated by IgE are important in the pathogenesis of allergic asthma. A recombinant humanized monoclonal antibody (rhuMAb-E25) forms complexes with free IgE and blocks its interaction with...

REVIEW ARTICLE: Inflammatory Skin Diseases, T Cells, and Immune Surveillance

Caroline Robert, M.D., and Thomas S. Kupper, M.D. — Thu, 09Â DecÂ 1999 00:00:00 -05:00

Skin is the primary interface between the body and the environment. The spectrum of insults to which skin is susceptible includes disorders caused by chemical and microbial agents, thermal and...

REVIEW ARTICLE: Inflammatory Skin Diseases, T Cells, and Immune Surveillance

Caroline Robert, M.D., and Thomas S. Kupper, M.D. — Thu, 09Â DecÂ 1999 00:00:00 -05:00

Skin is the primary interface between the body and the environment. The spectrum of insults to which skin is susceptible includes disorders caused by chemical and microbial agents, thermal and...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Immunologic Treatment of Alzheimer's Disease

Thu, 25Â NovÂ 1999 00:00:00 -05:00

The recent report by Schenk et al.1 raises the hope of a vaccine for Alzheimer's disease. This report has justifiably received wide attention in both the scientific and lay media....

EDITORIAL: Interferon Gamma-1b for the Treatment of Idiopathic Pulmonary Fibrosis

Thu, 21Â OctÂ 1999 00:00:00 -05:00

Idiopathic pulmonary fibrosis is a chronic condition of the lung parenchyma involving progressive injury, inflammation, and fibrosis. Data collected from October 1988 through September 1990 in the population-based registry of...

REVIEW ARTICLE: BehÃ§et's Disease

Thu, 21Â OctÂ 1999 00:00:00 -05:00

BehÃet's disease is an inflammatory disorder of unknown cause, characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions.12 All these common manifestations are self-limiting except for the...

ORIGINAL ARTICLE: A Preliminary Study of Long-Term Treatment with Interferon Gamma-1b and Low-Dose Prednisolone in Patients with Idiopathic Pulmonary Fibrosis

Thu, 21Â OctÂ 1999 00:00:00 -05:00

Background: Patients with idiopathic pulmonary fibrosis have progressive scarring of the lung and usually die within four to five years after symptoms develop. Treatment with oral glucocorticoids is often ineffective....

EDITORIAL: Immune Reconstitution

Thu, 14Â OctÂ 1999 00:00:00 -05:00

In this issue of the Journal, Markert et al.1 teach us that transplanting pieces of human thymus can rescue children with the DiGeorge syndrome. Complete DiGeorge syndrome is a rare...

ORIGINAL ARTICLE: Transplantation of Thymus Tissue in Complete DiGeorge Syndrome

Thu, 14Â OctÂ 1999 00:00:00 -05:00

Background: The DiGeorge syndrome is a congenital disorder that affects the heart, parathyroid glands, and thymus. In complete DiGeorge syndrome, patients have severely reduced T-cell function.

Methods: We treated five infants...

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...

EDITORIAL: Immunotherapy for Allergic Rhinitis

Thu, 12Â AugÂ 1999 00:00:00 -05:00

Allergic rhinitis, or hay fever, afflicts 10 to 20 percent of people in the United States and northern Europe. The disease occurs either during the seasons of airborne pollens and...

ORIGINAL ARTICLE: Long-Term Clinical Efficacy of Grass-Pollen Immunotherapy

Thu, 12Â AugÂ 1999 00:00:00 -05:00

Background: Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis, although it is questionable whether there is long-term benefit after the discontinuation of treatment.

Methods: We conducted a...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: DNA Vaccines â Designer Vaccines for the 21st Century

Thu, 22Â JulÂ 1999 00:00:00 -05:00

Over the past 100 years, the development and widespread use of vaccines against infectious agents has been one of the triumphs of medical science. One reason for the success of...

ORIGINAL ARTICLE: Antibodies against Human Herpesvirus 8 in Black South African Patients with Cancer

Thu, 17Â JunÂ 1999 00:00:00 -05:00

Background: Infection with human herpesvirus 8 (HHV-8) has been consistently linked to Kaposi's sarcoma, but its mode of transmission, association with other cancers, and interaction with the human immunodeficiency virus...

EDITORIAL: The Importance of Defining the Paraneoplastic Neurologic Disorders

Thu, 10Â JunÂ 1999 00:00:00 -05:00

The paraneoplastic neurologic disorders are models of the way in which rare diseases can shed light on common clinical problems. Paraneoplastic neurologic disorders, which are neurologic degenerative disorders that occur...

ORIGINAL ARTICLE: A Serologic Marker of Paraneoplastic Limbic and Brain-Stem Encephalitis in Patients with Testicular Cancer

Thu, 10Â JunÂ 1999 00:00:00 -05:00

Background: In patients with cancer, symptoms of limbic and brain-stem dysfunction may result from a paraneoplastic disorder. Paraneoplastic limbic or brain-stem encephalitis occurs more frequently with testicular cancer than with...

EDITORIAL: The New Immunology â The End of Immunosuppressive Drug Therapy?

Thu, 03Â JunÂ 1999 00:00:00 -05:00

In 1970, almost a decade before molecular biology began to make its mark on immunology, Bretscher and Cohn1 advanced a novel theory to explain how the immune system responds to...

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: The Mechanism of Respiratory Failure in Paraneoplastic Pemphigus

Thu, 06Â MayÂ 1999 00:00:00 -05:00

Paraneoplastic pemphigus1 is an autoimmune disease that accompanies an overt or occult neoplasm and causes blisters. It is characterized by the presence of IgG autoantibodies that react against desmosomal and...

ORIGINAL ARTICLE: Infliximab for the Treatment of Fistulas in Patients with Crohn's Disease

Thu, 06Â MayÂ 1999 00:00:00 -05:00

Background: Enterocutaneous fistulas are a serious complication of Crohn's disease and are difficult to treat. Infliximab, a chimeric monoclonal antibody to tumor necrosis factor Î±, has recently been developed as...

ORIGINAL ARTICLE: Hyper-IgE Syndrome with Recurrent Infections â An Autosomal Dominant Multisystem Disorder

Thu, 04Â MarÂ 1999 00:00:00 -05:00

Background: The hyper-IgE syndrome with recurrent infections is a rare immunodeficiency characterized by recurrent skin and pulmonary abscesses and extremely elevated levels of IgE in serum. Associated facial and skeletal...

EDITORIAL: Thirty Years of Bone Marrow Transplantation for Severe Combined Immunodeficiency

Thu, 18Â FebÂ 1999 00:00:00 -05:00

It has been 30 years since the first patient with combined T-cell and B-cell immunodeficiency was successfully treated with transplantation of bone marrow from an HLA-identical sibling.1 Since then, hundreds...

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...

REVIEW ARTICLE: Acute-Phase Proteins and Other Systemic Responses to Inflammation

Cem Gabay, M.D., and Irving Kushner, M.D. — Thu, 11Â FebÂ 1999 00:00:00 -05:00

A large number of changes, distant from the site or sites of inflammation and involving many organ systems, may accompany inflammation. In 1930 interest was focused on these changes by...

EDITORIAL: Does a Low Level of Expression of HLA Molecules Engender Autoimmunity?

Thu, 28Â JanÂ 1999 00:00:00 -05:00

The immune system can summon a variety of defenses against invaders from the outside. Among these deterrents are three types of killer lymphocytes that attack and lyse cellular targets. One...

EDITORIAL: Anticytokine Therapy â A New Era in the Treatment of Rheumatoid Arthritis?

Thu, 28Â JanÂ 1999 00:00:00 -05:00

With the clinical availability of two different approaches to decrease the activity of tumor necrosis factor (TNF), a new era in the treatment of rheumatoid arthritis has begun. In this...

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: A Trial of Etanercept, a Recombinant Tumor Necrosis Factor Receptor:Fc Fusion Protein, in Patients with Rheumatoid Arthritis Receiving Methotrexate

Thu, 28Â JanÂ 1999 00:00:00 -05:00

Background: Patients treated with methotrexate for rheumatoid arthritis often improve but continue to have active disease. This study was undertaken to determine whether the addition of etanercept, a soluble tumor...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Mechanism of Intravenous Immune Globulin Therapy in Antibody-Mediated Autoimmune Diseases

Thu, 21Â JanÂ 1999 00:00:00 -05:00

For more than two decades, the intravenous administration of high doses of IgG pooled from the plasma of healthy donors (immune globulin therapy, also known as âIVIgâ) has benefited patients...

REVIEW ARTICLE: Treatment of Asthma with Drugs Modifying the Leukotriene Pathway

Jeffrey M. Drazen, M.D., Elliot Israel, M.D., and Paul M. O'Byrne, M.B. — Thu, 21Â JanÂ 1999 00:00:00 -05:00

In 1979 and 1980, the chemical structures of the material previously known as slow-reacting substance of anaphylaxis were elucidated as 5(S)- hydroxy- 6(R)-glutathionyl- 7,9-trans-11,14- cis - eico- satetraenoic acid1 and...

REVIEW ARTICLE: Atherosclerosis â An Inflammatory Disease

Russell Ross, Ph.D. — Thu, 14Â JanÂ 1999 00:00:00 -05:00

Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principal risk factors for atherosclerosis,1 the process...

REVIEW ARTICLE: Antigen Localization and Migration in Immunity and Tolerance

Thomas E. Starzl, M.D., Ph.D., and Rolf M. Zinkernagel, M.D. — Thu, 24Â DecÂ 1998 00:00:00 -05:00

Survival in a hostile environment requires the ability to mount a protective immune response while avoiding a reaction of the immune system against the self. We propose that the migration...

ORIGINAL ARTICLE: Photopheresis for the Prevention of Rejection in Cardiac Transplantation

Thu, 10Â DecÂ 1998 00:00:00 -05:00

Background: Photopheresis is an immunoregulatory technique in which lymphocytes are reinfused after exposure to a photoactive compound (methoxsalen) and ultraviolet A light. We performed a preliminary study to assess the...

EDITORIAL: Transplantation Toleranceâ The Search Continues

Thu, 03Â DecÂ 1998 00:00:00 -05:00

The induction in a host of immunologic tolerance to the major histocompatibility complex (MHC) antigens of a donor (in humans, the HLA antigens) is the unquestioned goal of clinical transplantation....

REVIEW ARTICLE: Folding of Secretory and Membrane Proteins

Galina Kuznetsov, Ph.D., and Sanjay K. Nigam, M.D. — Thu, 03Â DecÂ 1998 00:00:00 -05:00

Genetic errors may result in abnormal synthesis of proteins, abnormal folding and processing of proteins after they are synthesized, or changes in the functional properties of proteins. Although the synthesis...

ORIGINAL ARTICLE: The Effect of Tolerance to Noninherited Maternal HLA Antigens on the Survival of Renal Transplants from Sibling Donors

Thu, 03Â DecÂ 1998 00:00:00 -05:00

Background: During pregnancy and nursing, a baby's developing immune system is intimately exposed to the mother's antigens. To determine whether this exposure is of clinical benefit to patients who later...

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...

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....

REVIEW ARTICLE: Pathophysiology of Progressive Nephropathies

Giuseppe Remuzzi, M.D., and Tullio Bertani, M.D. — Thu, 12Â NovÂ 1998 00:00:00 -05:00

In patients with renal diseases characterized by proteinuria, the initial insult to the kidney is usually followed by a progressive decline in the glomerular filtration rate. This decline has been...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Direct Visualization of Antigen-Specific Cytotoxic T Cells â A New Insight into Immune Defenses

Thu, 08Â OctÂ 1998 00:00:00 -05:00

Immunochemists have been making precise measurements of antibodies and antigens for many years, whereas cellular immunologists have had to rely on indirect and often clumsy methods for counting T cells...

REVIEW ARTICLE: Glomerulonephritis

Donald E. Hricik, M.D., Moonja Chung-Park, M.D., and John R. Sedor, M.D. — Thu, 24Â SepÂ 1998 00:00:00 -05:00

Diseases involving the renal glomeruli are encountered frequently in clinical practice and are the most common causes of end-stage renal disease worldwide. In the United States alone, glomerular diseases accounted...

EDITORIAL: Treatment of Crohn's Disease at the Turn of the Century

Thu, 06Â AugÂ 1998 00:00:00 -05:00

Inflammatory bowel diseases are the second most common chronic inflammatory disorder after rheumatoid arthritis. Of these, Crohn's disease afflicts hundreds of thousands of patients, particularly in developed countries, and its...

IMAGES IN CLINICAL MEDICINE: The MangoâPoison Ivy Connection

Mark O. Tucker, M.D. and Chad R. Swan, M.D. — Thu, 23Â JulÂ 1998 00:00:00 -05:00

Figure 1. A 27-year-old man had had a pruritic and eczematous rash for three days. One week earlier, he had peeled a mango, become distracted by a telephone call, and...

ORIGINAL ARTICLE: Vaccination against Lyme Disease with Recombinant Outer-Surface Lipoprotein A with Adjuvant

Thu, 23Â JulÂ 1998 00:00:00 -05:00

Background: The risk of acquiring Lyme disease is high in areas in which the disease is endemic, and the development of a safe and effective vaccine is therefore important.

Methods: We...

REVIEW ARTICLE: The Role of T-Cell Costimulatory Activation Pathways in Transplant Rejection

Mohamed H. Sayegh, M.D., and Laurence A. Turka, M.D. — Thu, 18Â JunÂ 1998 00:00:00 -05:00

Organ transplantation is now common. For patients with end-stage cardiac, hepatic, or pulmonary failure, it can be lifesaving.1 For patients with diabetes mellitus, pancreatic transplantation offers the chance of a...

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...

REVIEW ARTICLE: Antibodies to DNA

Bevra Hannahs Hahn, M.D. — Thu, 07Â MayÂ 1998 00:00:00 -05:00

Antibodies to DNA are of interest to a broad spectrum of physicians and other scientists. The presence of large amounts of serum antibodies to double-stranded DNA is specific for systemic...

ORIGINAL ARTICLE: Recombinant Human Interleukin-2, Recombinant Human Interferon Alfa-2a, or Both in Metastatic Renal-Cell Carcinoma

Thu, 30Â AprÂ 1998 00:00:00 -05:00

Background: Recombinant human interleukin-2 (aldesleukin) and recombinant human interferon alfa can induce notable tumor regression in a limited number of patients with metastatic renal-cell carcinoma. We conducted a multicenter, randomized...

ORIGINAL ARTICLE: Interferon Gamma-1b Compared with Placebo in Metastatic Renal-Cell Carcinoma

Thu, 30Â AprÂ 1998 00:00:00 -05:00

Background: Most trials of immunomodulators in metastatic renal-cell carcinoma have been uncontrolled and subject to selection bias. The objective of this blinded, placebo-controlled study was to compare overall response rates,...

EDITORIAL: Microchimerism and Autoimmune Disease

Thu, 23Â AprÂ 1998 00:00:00 -05:00

The mythological Chimera is described as having the head of a lion, the body of a goat, and the tail of a serpent. In medicine, the term âchimeraâ is used...

EDITORIAL: Hemolytic Disease of the Newborn: Progenitor Cells and Late Effects

Thu, 19Â MarÂ 1998 00:00:00 -05:00

The history of hemolytic disease of the newborn dates to the 1600s, when a French midwife described the birth of twins, one of whom had fatal hydrops fetalis and the...

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...

CLINICAL IMPLICATIONS OF BASIC RESEARCH: Cellular Responses to Interferons and Other Cytokines: The JAKâSTAT Paradigm

Thu, 26Â FebÂ 1998 00:00:00 -05:00

Recently, two rare genetic disorders have been linked to abnormalities in a novel cytokine-signaling mechanism, and the growth of leukemia cells was shown to be inhibited by selective blockade of...

REVIEW ARTICLE: Chemokines â Chemotactic Cytokines That Mediate Inflammation

Andrew D. Luster, M.D., Ph.D. — Thu, 12Â FebÂ 1998 00:00:00 -05:00

The attraction of leukocytes to tissues is essential for inflammation and the host response to infection. The process is controlled by chemokines, which are chemotactic cytokines. This review introduces the...

REVIEW ARTICLE: Protective and Damaging Effects of Stress Mediators

Bruce S. McEwen, Ph.D. — Thu, 15Â JanÂ 1998 00:00:00 -05:00

Over 60 years ago, Selye1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly...

ORIGINAL ARTICLE: Interleukin-2âReceptor Blockade with Daclizumab to Prevent Acute Rejection in Renal Transplantation

Thu, 15Â JanÂ 1998 00:00:00 -05:00

Background: Monoclonal antibodies that block the high-affinity interleukin-2 receptor expressed on alloantigen-reactive T lymphocytes may cause selective immunosuppression. Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically...

EDITORIAL: Interleukin-4 and the Genetics of Atopy

Thu, 11Â DecÂ 1997 00:00:00 -05:00

Interleukin-4 is a critical cytokine in the expression of atopy and allergic diseases. Through its receptor, which consists of a unique Î± chain and the common lymphoid-receptor Î³ chain, it...

ORIGINAL ARTICLE: The Association of Atopy with a Gain-of-Function Mutation in the Î± Subunit of the Interleukin-4 Receptor

Thu, 11Â DecÂ 1997 00:00:00 -05:00

Background: Atopic diseases are very common, and atopy has a strong genetic predisposition.

Methods: Using single-strand conformation polymorphism analysis and DNA sequencing, we searched for mutations in the Î± subunit of...

REVIEW ARTICLE: The Thyrotropin Receptor in Thyroid Diseases

Ralf Paschke, M.D., and Marian Ludgate, Ph.D. — Thu, 04Â DecÂ 1997 00:00:00 -05:00

The growth and function of the thyroid are controlled by thyrotropin1 through the activation of its receptor, which belongs to the large family of G proteinâcoupled receptors. Despite the extreme...

REVIEW ARTICLE: Small-Vessel Vasculitis

J. Charles Jennette, M.D., and Ronald J. Falk, M.D. — Thu, 20Â NovÂ 1997 00:00:00 -05:00

Vasculitis is inflammation of vessel walls. It has many causes, although they result in only a few histologic patterns of vascular inflammation. Vessels of any type in any organ can...

ORIGINAL ARTICLE: Anaphylaxis from the Carboxymethylcellulose Component of Barium Sulfate Suspension

Thu, 30Â OctÂ 1997 00:00:00 -05:00

Although allergic reactions to barium sulfate suspensions are estimated to occur at a rate of less than 2 per million,12 the frequency has been reported to be increasing.34 The cause...

ORIGINAL ARTICLE: Prognostic Value of Immunohistochemically Identifiable Tumor Cells in Lymph Nodes of Patients with Completely Resected Esophageal Cancer

Thu, 23Â OctÂ 1997 00:00:00 -05:00

Background: Current methods of disease staging often fail to detect small numbers of tumor cells in lymph nodes. Metastatic relapse may arise from these few cells.

Methods: We studied 1308 lymph...

ORIGINAL ARTICLE: A Short-Term Study of Chimeric Monoclonal Antibody cA2 to Tumor Necrosis Factor Î± for Crohn's Disease

Thu, 09Â OctÂ 1997 00:00:00 -05:00

Background: Studies in animals and an open-label trial have suggested a role for antibodies to tumor necrosis factor Î±, specifically chimeric monoclonal antibody cA2, in the treatment of Crohn's disease.

Methods:...

REVIEW ARTICLE: The Systemic Amyloidoses

Rodney H. Falk, M.D., Raymond L. Comenzo, M.D., and Martha Skinner, M.D. — Thu, 25Â SepÂ 1997 00:00:00 -05:00

Amyloidosis is not a single disease but a term for diseases that share a common feature: the extracellular deposition of pathologic insoluble fibrillar proteins in organs and tissues. In the...

ORIGINAL ARTICLE: Transfer of Symptomatic Peanut Allergy to the Recipient of a Combined Liver-And-Kidney Transplant

Thu, 18Â SepÂ 1997 00:00:00 -05:00

Peanuts are one of the commonest causes of food allergy in the United States and Europe.123 They are also a leading cause of food-induced anaphylaxis and death, which usually follow...

EDITORIAL: The Case of the Bare Lymphocyte Syndrome â Tracking Down Faulty Transcription Factors

Thu, 11Â SepÂ 1997 00:00:00 -05:00

In this issue of the Journal, Villard and his colleagues in Geneva report a new kind of mutation in children with primary deficiency of major-histocompatibility-complex (MHC) class II molecules (also...

ORIGINAL ARTICLE: Mutation of RFXAP, a Regulator of MHC Class II Genes, in Primary MHC Class II Deficiency

Thu, 11Â SepÂ 1997 00:00:00 -05:00

Background: Major-histocompatibility-complex (MHC) class II deficiency is an autosomal recessive primary immunodeficiency disease in which MHC class II molecules are absent. It is a genetically heterogeneous disease of gene regulation...

REVIEW ARTICLE: Antioxidants and Atherosclerotic Heart Disease

Thu, 07Â AugÂ 1997 00:00:00 -05:00

Epidemiologic studies have demonstrated an association between increased intake of antioxidant vitamins such as vitamin E and vitamin C and reduced morbidity and mortality from coronary artery disease. This association...

EDITORIAL: Autoantibodies and Pregnancy Loss