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Articles 
Daniele Prati, Emanuela Taioli, Alberto Zanella, Emanuela Della Torre, Sonia Butelli, Emanuela Del Vecchio, Luciana Vianello, Francesco Zanuso, Fulvio Mozzi, Silvano Milani, Dario Conte, Massimo Colombo, and Girolamo Sirchia Serum alanine aminotransferase (ALT) activity, the variable most commonly measured to assess hepatic disease, fails to identify many patients with hepatic injury. Current standards for "normal" ALT level were defined by using populations that included persons with subclinical liver disease. In patients with chronic hepatitis C virus infection or nonalcoholic fatty liver disease, revision of normal limits for ALT is advisable.
Cary P. Gross, Raburn Mallory, Asefeh Heiat, and Harlan M. Krumholz Many randomized, controlled trials published in major medical journals do not provide information about the patient recruitment process. As a result, it is difficult for readers to gauge the extent to which participants may represent a highly selected subgroup.
Kirk D. Miller, Henry Masur, Elizabeth C. Jones, Galen O. Joe, Margaret E. Rick, Grace G. Kelly, JoAnn M. Mican, Shuying Liu, Lynn H. Gerber, William C. Blackwelder, Judith Falloon, Richard T. Davey, Jr., Michael A. Polis, Robert E. Walker, H. Clifford Lane, and Joseph A. Kovacs Patients infected with HIV have an unexpectedly high occurrence of osteonecrosis of the hip. Although screening of asymptomatic patients is not warranted, HIV-infected patients with persistent groin or hip pain should be evaluated for this debilitating complication.
Updates
Dmitri Kirpichnikov, Samy I. McFarlane, and James R. Sowers Metformin, the only biguanide available in the United States, is a potent insulin-sensitizing agent that acts primarily on hepatic glucose production and has additional effects on peripheral insulin sensitivity. This update covers many aspects of metformin therapy, including clinical role, combination therapy, mechanisms of antihyperglycemic action, and cardioprotective action. The effects of metformin therapy on the polycystic ovary syndrome, diabetic cardiomyopathy, and vascular reactivity are also discussed.
History of Medicine
Edward J. Huth and Kathleen Case In its first 75 years, Annals of Internal Medicine evolved from being primarily a vehicle for papers presented at the Annual Session of the American College of Physicians to a journal in which all manuscripts are peer reviewed and decisions to publish are based solely on the editors' view of which papers are most important.
Clinical Guidelines
U.S. Preventive Services Task Force* The U.S. Preventive Services Task Force recommends against the routine use of tamoxifen or raloxifene for the primary prevention of breast cancer in women at low or average risk for breast cancer. The Task Force recommends that clinicians discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention. Clinicians should inform patients of the potential benefits and harms of chemoprevention.
Linda S. Kinsinger, Russell Harris, Steven H. Woolf, Harold C. Sox, and Kathleen N. Lohr This systematic review supports the U.S. Preventive Services Task Force's position on chemoprevention of breast cancer.
Editorials
Jerome P. Kassirer As evidenced by Huth and Case's history of Annals in this issue, medical journals have changed in the past 25 years. Molecular medicine, enormous controlled trials, and meta-analyses of dozens of clinical trials have largely replaced case reports, observational studies of a few dozen patients, and physiologic experiments. However, some issues, such as cost containment and ethics, remain vexing. Have medical journals, in fact, improved?
Marshall M. Kaplan In this issue, Prati and colleagues confirm and extend previously reported data demonstrating relations between alanine aminotransferase (ALT) levels, body mass index, and abnormal lipid or carbohydrate metabolism, as well as sex. However, wide adoption of their new, more sensitive values for normal ALT levels would be premature.
Albert G. Mulley, Jr. and Karen Sepucha The U.S. Preventive Services Task Force recommendations on chemoprevention of breast cancer, which appear in this issue with a supporting evidence review by Kinsinger and colleagues, present two serious challenges for clinicians. First, clinicians must respond to misinformed patients and mitigate the worry that may cloud perspective and create demand for chemoprevention when the potential harms far exceed the benefits. Second, clinicians must identify and engage uninformed persons for whom chemoprevention holds potential promise.
Harold C. Sox The beginning of a new volume of Annals is the occasion to tell readers about the changes that we made during the past 6 months.
On Being a Doctor
Eric Michael David Meg was one of the most special people I have ever known, one of those people who watches you grow up just as astutely as you watch them grow up ... a student of all the changes in your life. She died the summer I turned 21.
Letters Adenosine and Aggrenox: A Hazardous Combination
Quality of Care in Patients with Diabetes
Measuring Patient Adherence
Spontaneous Intramural Hematoma of the Esophagus
Severe Rhabdomyolysis Related to Cerivastatin without Gemfibrozil
Gabapentin Toxicity Requiring Intubation in a Patient Receiving Long-Term Hemodialysis
Celecoxib-Induced Cholestatic Hepatotoxicity in a Patient with Cirrhosis
Francis D. Pien
Bryce Templeton
Jordan D. Grumet
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