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May 29, 2008  Vol. 358 No. 22

Audio Summary of this Issue

Perspective
2313-2316
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A 20-month-old boy was brought in to the clinic because he was vomiting. Two nights before, the child had fallen down some stairs. Dr. Perri Klass writes about the worry that set in after she saw the boy and about the voices that can echo in your head ...

2316-2317

Paying study subjects is not a new practice, but neither is it uncontroversial. Dr. Carl Elliott and Roberto Abadie ask, is it ethically problematic to pay poor people to test the safety of new drugs?

Original Articles
2319-2331

In this clinical trial involving patients undergoing high-risk cardiac surgery, aprotinin was somewhat more effective than either aminocaproic acid or tranexamic acid in reducing massive perioperative bleeding but at the expense of a higher rate of death, mainly from cardiac causes. Aprotinin cannot be recommended to control blood loss in this clinical setting.

2332-2343

This study investigated the safety and efficacy of subcutaneous methylnaltrexone, a μ-opioid–receptor antagonist, for treating opioid-induced constipation in patients with advanced illness. Methylnaltrexone rapidly induced laxation without affecting central analgesia or precipitating withdrawal.

2344-2354
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In this 12-week randomized trial, prucalopride, a selective 5-HT4 receptor agonist, substantially relieved constipation. Because of cardiac adverse events seen with other 5-HT4 receptor agonists, electrocardiograms were monitored; there was no prolongation of the corrected QT interval. Diarrhea and headache were more common in the prucalopride groups than in the placebo group. This study was not large or long enough to rule out cardiovascular events or other uncommon adverse events.

2355-2365
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This study implicates five genetic loci in bone mineral density. Two of these loci are new; three implicate genes known to be involved in bone remodeling, such as the receptor activator of nuclear factor-κB ligand gene (RANKL). Analyses showed that three of the loci are associated with osteoporotic fracture.

Clinical Practice
2366-2377
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The parents of a 6-year-old girl bring her to a pediatrician because of breast development. Her medical history is unremarkable. The parents are of average height, and the mother reports first menstruating when she was 11 years old. On physical examination, the girl is 125 cm tall (in the 97th percentile for her age), weighs 28 kg, and has a body-mass index of 17.9 (90th percentile for her age). Her breast development is classified as Tanner stage 3, and she has Tanner stage 2 pubic hair. Review of her previous growth data indicates that she has grown 8 cm during the past year. How should her condition be evaluated and managed?

Review Article
2378-2387

The hepatopulmonary syndrome is characterized by defects in oxygenation due to pulmonary abnormalities associated with chronic liver disease. Dyspnea and hypoxemia can be severe and often worsen in the upright position. Gross dilatation of the precapillary and capillary vessels occurs with ventilation–perfusion mismatch. The syndrome usually improves after liver transplantation.

Videos in Clinical Medicine
e25

    Cricothyroidotomy is an emergency procedure performed on patients with severe respiratory distress when orotracheal or nasotracheal intubation has failed or is not feasible. This video shows viewers how to perform an emergency cricothyroidotomy in an adult.

    Images in Clinical Medicine
    2388
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    An 86-year-old woman with severe symptomatic aortic stenosis was referred for routine preoperative cardiac catheterization. During the procedure, pronounced tortuosity of the catheter was noted. Subsequent administration of intravenous contrast material ...

    e26
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    This 46-year-old man with cerebral palsy presented with difficulty in breathing. He was admitted to intensive care with a diagnosis of sepsis.

    Case Records of the Massachusetts General Hospital
    2389-2396

    A 63-year-old man was admitted to this hospital because of a mass in the left kidney, associated with abdominal pain, weight loss of 3.2 kg, and cough. Physical examination disclosed scrotal varicoceles; imaging studies disclosed a mass in the left kidney, a mass in the left adrenal gland, and multiple pulmonary nodules. A diagnostic procedure was performed, and management decisions were made.

    Editorials
    2398-2400

    The aprotinin story began in 1987, when investigators reported that the use of the drug in patients undergoing repeat open-heart surgery decreased the need for blood transfusion by a factor of 8.1 In 1993, the Food and Drug Administration (FDA) approved ...

    2400-2402

    Opioid analgesics generate numerous side effects that complicate their use in postoperative care,1 in the treatment of sickle cell vaso-occlusive episodes, and in the treatment of pain associated with advanced cancer and other life-shortening illnesses.2 ...

    2402-2403

    In this issue of the Journal, Camilleri et al.1 report on their 12-week randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of prucalopride in the treatment of chronic constipation (ClinicalTrials.gov number, NCT00483886)...

    2403-2405

    Osteoporosis is a common skeletal disorder characterized by compromised bone strength and increased bone fragility, affecting up to 40% of postmenopausal women and 15% of men.1 Its clinical significance lies in the occurrence of osteoporotic fractures — ...

    Correspondence
    2406-2407

    To the Editor: With regard to the Local Taxane with Short Exposure for Reduction of Restenosis in Distal Arteries (THUNDER) trial, reported by Tepe et al. (Feb. 14 issue),1 paclitaxel, like endovascular brachytherapy, may postpone rather than inhibit ...

    2408-2409

    To the Editor: The conclusion by Wilbert-Lampen et al. (Jan. 31 issue)1 that World Cup soccer is a risk factor for the occurrence of acute cardiovascular events is weakened considerably by the lack of data on the incidence of such events in the several ...

    2409-2411

    To the Editor: In an otherwise elegant clinical description of the Hutchinson–Gilford progeria syndrome by Merideth and colleagues (Feb. 7 issue),1 we take exception to the authors' suggestion that their findings have overarching significance with ...

    2411-2412

    To the Editor: The study of cost sharing on mammography by Trivedi et al. (Jan. 26 issue)1 and the editorial by Bach2 may lead policymakers to favor value-based insurance over high-deductible health plans. Following the principles of value-based ...

    2412-2413

    To the Editor: In their review article, Rahman and Isenberg (Feb. 28 issue)1 emphasize the role of anti–double-stranded DNA antibodies in the pathogenesis of systemic lupus erythematosus. Such antibodies also occur, however, in 23 to 64% of patients with ...

    2413-2414

    To the Editor: In his review of inflammatory responses in infected lungs, Mizgerd (Feb. 14 issue)1 notes that animal models of influenza A virus pneumonia indicate that neither neutrophil leukocytes nor cytokine signaling seems to be important in the ...

    2414-2415

    To the Editor: Children with nocturnal enuresis are generally believed to be deep sleepers with impaired arousability.1 However, there are conflicting data with regard to sleep patterns in children with enuresis.2,3 Nocturnal enuresis often occurs with ...

    Book Reviews
    2416

    In January, the world lost a visionary in cancer research, M. Judah Folkman. Folkman, who died while traveling to a Keystone symposium to give the keynote address, proposed nearly four decades ago that attacking the tumor vasculature could improve ...

    2416-2417

    This book, written by a Moscow-based journalist, is hard to classify. It is largely a personal and intimate story of the author's struggle to make decisions after she was identified as a carrier of a BRCA mutation — a mutation associated with a high risk ...

    2417-2418

    Now is the perfect time for a book about obesity and genomics. The prevalence of obesity is increasing worldwide, and about two thirds of the population of the United States is obese or overweight. The fields of genetics, genomics, and pharmacogenomics ...

    Correction
    2418

    Gestational Diabetes — Setting Limits, Exploring Treatments Editorial, N Engl J Med 2008:358;2061-2063.. In the paragraph that begins “Also in this issue of the Journal…” (page 2062), the final sentence should have read, “Rates of cesarean delivery and ...