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* This Week in the Journal
 November 20, 2003
*
Correspondence
* Bisphosphonates in Children with Bone Diseases
* G-CSF Priming in Acute Myelogenous Leukemia
* Maintenance Therapy for Vasculitis Associated with Antineutrophil Cytoplasmic Autoantibodies
* Estimating the Number of Potential Organ Donors in the United States
* Hormone Therapy and Cardiovascular Disease
* The Office for Human Research Protections and the NIH
* Excess Rate of In-Hospital Death in Lyons, France, during the August 2003 Heat Wave
* Treatment of HCV-Related Mantle-Cell Lymphoma with Ribavirin and Pegylated Interferon Alfa
*
Book Reviews
* Familial Breast and Ovarian Cancer: Genetics, Screening and Management
* Hormones, Genes, and Cancer
* Cancer Immune Therapy: Current and Future Strategies
Original Articles
Antiretroviral Therapy and the Risk of Myocardial Infarction

This prospective, observational study assessed the risk of myocardial infarction among 23,468 HIV-1–infected patients in relation to treatment with combination antiviral medications. The incidence of myocardial infarction increased significantly with increasing exposure to combination therapy (adjusted relative rate per year of exposure, 1.26).

Combination antiretroviral therapy is associated with metabolic side effects that increase the risk of myocardial infarction. However, that small risk must be balanced against the substantial benefits of effective treatment of HIV-1 infection.

Related Editorial


Original Articles
A Novel Targeted T-Cell Modulator, Efalizumab, for Plaque Psoriasis

Leukocyte-function–associated antigen type 1 (LFA-1) is involved in the pathogenesis of psoriasis. Efalizumab is a humanized monoclonal antibody that binds to LFA-1 and inhibits T-cell activation. This randomized trial demonstrates the efficacy of efalizumab for moderate-to-severe plaque psoriasis. At 12 weeks, 25 percent of patients who received efalizumab had an improvement in a psoriasis index of at least 75 percent, as compared with 5 percent of those who received placebo.

Studies of longer duration are needed to determine whether efalizumab is a useful therapy for psoriasis.

Related Perspective


Original Articles
Etanercept as Monotherapy in Patients with Psoriasis

Tumor necrosis factor (TNF) is believed to have a role in the pathogenesis of psoriasis. In this 24-week randomized trial involving patients with moderate-to-severe plaque psoriasis, treatment with etanercept, a TNF antagonist, resulted in significant improvement in the psoriasis area-and-severity index. Rates of adverse events were similar in the etanercept and placebo groups.

Antagonism of TNF by the subcutaneous injection of etanercept is an effective treatment for plaque psoriasis. The safety and efficacy of the long-term use of etanercept for psoriasis have not been studied.

Related Perspective


Original Articles
Withdrawal of Cabergoline for Hyperprolactinemia

This study examined withdrawal of cabergoline therapy in patients with nontumoral hyperprolactinemia, microprolactinomas, or macroprolactinomas. Patients in whom prolactin levels remained normal for at least 24 months during treatment with cabergoline underwent withdrawal of the medication. None had recurrent tumors, although in some patients hyperprolactinemia recurred during two or more years of subsequent observation. In 10 female patients (22 percent) and 7 male patients (39 percent) with recurrent hyperprolactinemia, gonadal dysfunction recurred.

Cabergoline withdrawal appears to be safe in patients with normalized prolactin levels and no evidence of tumor, and hyperprolactinemia recurs infrequently after withdrawal.


Review Article
Mechanisms of Disease: Gene Silencing in Cancer

This article reviews the mechanisms of gene silencing in cancer and clinical applications of this phenomenon. The silencing of genes, especially tumor-suppressor genes, is a key event in the development of cancer. The silencing can be effected by a disabling mutation or by a shutting down of the promoter region, the site at which transcription of the gene begins.


Clinical Practice
Prolactinoma

A 22-year-old woman who wants to become pregnant has had no menses since she discontinued the use of an oral contraceptive one year ago, and recently, galactorrhea developed. She takes no medications and has had no headaches, visual loss, dyspareunia, or decreased libido. A test for serum human chorionic gonadotropin is negative, the thyrotropin level is normal, and the serum prolactin level is 95 µg per liter. Magnetic resonance imaging reveals a mass, 3 mm in diameter, in the anterior lobe of the pituitary. How should she be treated?


Case Records of the Massachusetts General Hospital
Case 36-2003

A 68-year old woman was admitted to the hospital because of impaired renal function. The differential diagnosis is discussed by Singh, who presents the diagnostic possibilities according to a paradigm based on prerenal, intrinsic renal, and postrenal factors.


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