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July 26, 2001
This Week in the Journal

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Parity, Oral Contraceptives, and the Risk of Ovarian Cancer in Carriers and Noncarriers of a BRCA Mutation
In this study, parity and the use of oral contraceptives were compared in women with ovarian cancer and matched controls. A BRCA1 or BRCA2 mutation was found in 29.0 percent of 840 women with cancer but only in 1.7 percent of 751 controls. Increasing parity was found to be protective against ovarian cancer regardless of the mutation status, but the use of oral contraceptives was protective only in noncarriers.

Increasing parity and oral-contraceptive use have a protective effect against ovarian cancer. The surprise in this study is that oral contraceptives were not protective in carriers of a mutant BRCA1 or BRCA2 ovarian-cancer–susceptibility gene. This finding implies that ovarian cancer develops through different pathways in carriers and noncarriers. It argues against the use of oral contraceptives for the chemoprevention of ovarian cancer in carriers.



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Anti-CD22 Recombinant Immunotoxin BL22 for Chemotherapy-Resistant Hairy-Cell Leukemia
In hairy-cell leukemia, the malignant cells display large amounts of CD22, an adhesion protein restricted to B lymphocytes. A genetically engineered molecule (BL22), consisting of the antigen-binding region of an antibody against CD22 and a portion of the pseudomonas exotoxin, was used to treat hairy-cell leukemia that was resistant to chemotherapy. Of 16 patients given BL22, 11 had a complete remission.

Immunotoxins such as BL22 are novel agents with the ability to target certain neoplasms selectively. They can be highly specific if the malignant cells display a unique or restricted target molecule. In this study, a lethal bacterial toxin entered malignant cells through interactions with CD22.

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Treating Psoriasis by Preventing T-Lymphocyte Activation
T-lymphocyte activation has a role in many chronic autoimmune diseases, including psoriasis. This study evaluated the use of alefacept, a recombinant protein that binds to memory effector T lymphocytes and inhibits their activation, in 229 patients with chronic plaque psoriasis. During the 12-week period of treatment and an additional 12 weeks of follow-up, the patients who received alefacept had significantly greater improvement than did those who received placebo.

The benefit derived from selectively targeting memory effector T lymphocytes in the treatment of psoriasis indicates their critical role as effector cells in this condition. Alefacept may represent an additional treatment option for patients with refractory psoriasis.

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Glanders in a Military Research Microbiologist
After two months of fever, tender adenopathy, and weight loss, a microbiologist was hospitalized with sepsis and acute respiratory failure and was found to have multiple hepatic and splenic abscesses. Cultures demonstrated a gram-negative rod that was eventually identified as Burkholderia mallei, the agent of glanders and an organism that the patient had handled in the laboratory.

Glanders was once a well-recognized disease of horses that was sometimes transmitted to humans. The disease has disappeared from the United States, but B. mallei is highly infectious and is now feared as a potential agent of bioterrorism. This report illustrates the difficulties involved in recognizing a disease and correctly identifying an organism that clinicians have not seen for half a century.

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Clinical Practice: Subclinical Hypothyroidism
A 59-year-old woman is found on routine evaluation to have a serum thyrotropin level of 7 mU per liter. Her only symptoms are mild fatigue and difficulty losing weight. She has a total cholesterol level of 220 mg per deciliter, a low-density lipoprotein cholesterol level of 140 mg per deciliter, and a positive test for antibodies against thyroperoxidase. Should she be treated with thyroxine? This article reviews the implications of subclinical hypothyroidism and recommendations for screening and treatment.

It makes sense to treat asymptomatic persons who have positive antibody tests, pregnant women, women who have ovulatory dysfunction with infertility, and patients who have symptoms consistent with the presence of mild hypothyroidism, hypercholesterolemia, or a goiter.


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Drug Therapy: Treatment of Endometriosis
Women with endometriosis most often have pelvic pain or infertility. This review summarizes the efficacy of the available drugs and surgical treatments for these problems, including the use of assisted reproductive techniques.


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