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November 20, 2003 Vol. 349 No. 21
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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).
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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.
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.
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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.
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?
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.
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