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September 7, 2006  Vol. 355 No. 10

Audio Summary of this Issue

Perspective
973-975

The pivotal role of costimulation in regulating T-cell activation versus tolerance has stimulated great interest. Drs. Arlene Sharpe and Abul Abbas discuss the manipulation of costimulatory pathways.

976-979

Although physicians learn volumes about treating underlying causes, many receive little training in addressing resultant disability. Dr. Lisa Iezzoni asks, how should doctors be taught to fulfill this role?

979-981

In medical school, students are taught to follow a script: “What brought you to the hospital today?” In this essay, Benjamin Brody, a medical student, discusses the challenge of the conversations that happen after histories are taken, when the patients' ...

Original Articles
983-991

Tumor specimens from patients in a trial of cisplatin-based adjuvant chemotherapy for non–small-cell lung cancer were analyzed for the presence of ERCC1, an enzyme that participates in the repair of DNA damage caused by cisplatin. The absence of ERCC1 in the tumor was associated with a survival benefit from cisplatin-based adjuvant chemotherapy, whereas patients whose tumor expressed the enzyme failed to benefit from the chemotherapy.

992-1005

This nested case–control study of healthy nulliparous women within the Calcium for Preeclampsia Prevention trial shows that the circulating level of soluble endoglin, an antiangiogenic protein, increased markedly 2 to 3 months before the onset of preeclampsia and was generally accompanied by decreased levels of placental growth factor and increased levels of circulating soluble fms-like tyrosine kinase 1. These studies set the stage for a prospective study to determine if measurement of these markers could provide means of identifying women at high risk for preeclampsia.

1006-1017

Unfractionated heparin has been the standard anticoagulant used during percutaneous coronary intervention (PCI). In this trial, adjusted-dose unfractionated heparin was compared with enoxaparin in patients undergoing PCI. Enoxaparin significantly reduced the rate of major bleeding. The effect on prevention of coronary events was not definitively assessed.

1018-1028

In a phase 1 trial, six healthy male volunteers received 0.1 mg per kilogram of body weight of a superagonistic anti-CD28 monoclonal antibody. Unexpectedly, all six volunteers had a transient critical illness characterized by multiorgan failure. These events give a view of a specific form of the cytokine-release syndrome in the absence of underlying medical disease.

Clinical Practice
1029-1036

A 28-year-old man reports feeling anxious and self-conscious around people in school, work, and social situations since his early teens. He appears shy and, on questioning, describes avoidance of speaking up in work meetings, attending social gatherings, and dating. He desperately wants to be more socially active but fears he will appear nervous and embarrass himself. How should he be evaluated and treated?

Review Article
1037-1046

This review of oncogene-induced cell senescence describes a physiological mechanism that provides protection against cancer. The mechanisms underlying the arrest of growth in benign or premalignant neoplasms have considerable clinical implications.

Images in Clinical Medicine
1047
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A 32-year-old man presented with severe pain, swelling, and loss of vision in his left eye after excessive exposure to sunlight. He reported multiple, recurrent, discrete blisters developing on sun-exposed areas that healed with scarring and passing red-...

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This 38-year-old female smoker was admitted because of recurrent right-sided pneumothorax. It was her second day of menstruation; the first episode had also taken place on the second day of her menstrual cycle.

Clinical Problem-Solving
1048-1052
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A 61-year-old woman was hospitalized with a 2-day history of palpitations and dyspnea. She was found to be in atrial fibrillation with a rapid ventricular response, and intravenous diltiazem and a heparin infusion were begun. Her condition improved, but on the third hospital day, she reported feeling weak and nauseated and began passing dark red urine. She did not have a urinary catheter, palpitations, dyspnea, back pain, abdominal pain, dysuria, or dizziness.

Editorials
1054-1055

Clinical oncology has struggled for decades with the predicament of the toxicity of chemotherapy for the treatment of malignant disease. For example, cisplatin and its analogues, carboplatin and oxaliplatin, are commonly used anticancer agents, but they ...

1056-1058

    Preeclampsia, either alone or superimposed on another disorder, is a major cause of maternal and fetal death and the leading cause of premature delivery worldwide.1 Underappreciated is the strain that preeclampsia places on the health care resources of ...

    1058-1060

    About 2.2 million percutaneous coronary interventions (PCIs) were performed worldwide in 2004 (Mead D: personal communication). Success rates of more than 97%, mortality rates of less than 0.5%, and rates of emergency bypass surgery of less than 0.5% can ...

    1060-1061
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    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 per kilogram of body weight) of TGN1412 — a superagonistic humanized ...

    Correspondence
    1062-1064

    To the Editor: According to the findings of Talpaz et al. (June 15 issue),1 the efficacy and safety profile of dasatinib therapy in patients with Philadelphia chromosome–positive leukemias and resistance to or intolerance of imatinib seem promising. ...

    1064-1065

    To the Editor: In the article by Dave et al. (June 8 issue)1 concerning the molecular diagnosis of Burkitt's lymphoma, almost half the patients with Burkitt's lymphoma were children. The data in the companion article by Hummel et al.2 were not stratified ...

    1065-1066

    To the Editor: The report by Rumbold et al. on the Australian Collaborative Trial of Supplements (ACTS) and the accompanying editorial by Jeyabalan and Caritis (April 27 issue)1,2 overlooked a key reason for the lack of effect of vitamin C on the ...

    1067
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    To the Editor: Missing from Katon's review of panic disorder (June 1 issue)1 is the frequent correlation of symptoms with acute respiratory alkalosis resulting from hyperventilation. Table 1 of the article, showing criteria for the diagnosis of panic ...

    1067-1070

    To the Editor: The article by Stevens et al. (June 8 issue)1 on the assessment of kidney function is both helpful and comprehensive. Chronic kidney disease, which poses a public health threat of epidemic proportions, is largely underdiagnosed and often ...

    1070-1071

    To the Editor: Copelan (April 27 issue)1 provides a comprehensive review of hematopoietic stem-cell transplantation, including complications after transplantation. However, the review article does not describe a common complication that causes ...

    1071-1072

    To the Editor: A 26-year-old woman had had abdominal pain since the beginning of her pregnancy. Endoscopy of the esophagus, stomach, and duodenum and abdominal ultrasonography showed only gastroesophageal reflux. Two months later, physical examination ...

    Book Reviews
    1073-1074

    In 1963, Stanford economist Kenneth Arrow, who later shared the Nobel Prize in Economics with John Hicks, wrote a seminal piece in the American Economic Review stating that classic market theory could not be applied to medical services. But that was just ...

    1074-1075

    Improving global health is beneficial to both rich and poor countries. It is vital to economic development, global security against emerging infections, and political stability in countries ravaged by famine and disease. A new generation of economists ...

    1075-1076

    Some years ago, I had the opportunity to visit a leprosy clinic in Boston. It was known as a “Hansen's disease” clinic, a term often preferred by patients. It was held only on Saturday mornings, when the building was otherwise not in use. There was a ...

    Corrections
    1076

    The Silent Epidemic — The Health Effects of Illiteracy Perspective, N Engl J Med 2006:355;339-341.. In the third column of page 340, the second sentence of the second full paragraph should have read, “In one study, more than two thirds of patients with ...

    1076

    Clopidogrel for the Prevention of Atherothrombotic Events Correspondence, N Engl J Med 2006:355;418-421.. On page 420, the second line of the reply letter by Topol should have read, “there was a benefit of dual antiplatelet therapy with respect to the ...