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January 1, 2009  Vol. 360 No. 1

Audio Summary of this Issue

Perspective
1-3

Journalists reporting on health care developments deliver public health messages that can influence the behavior of clinicians and patients. Susan Dentzer argues that when journalists ignore complexities or fail to provide context, the public health ...

3-5

Drs. David Dale and Daniel Link discuss the genetic variants of severe congenital neutropenia. The recent advances in our understanding of the genetic basis of this disorder have important clinical implications.

Original Articles
7-19

In this international randomized, controlled trial, one kidney from each pair from 336 consecutive deceased donors was randomly assigned to machine perfusion and the other to cold storage. All recipients were followed for 1 year. Hypothermic machine perfusion was associated with a reduced risk of the primary end point — delayed graft function — and improved graft survival in the first year after transplantation.

20-31

Infection is a major cause of death in the intensive care unit (ICU). Strategies to reduce rates of infection in ICUs include selective digestive tract decontamination (SDD), in which cefotaxime and topical antimicrobial agents are administered for 4 days, and selective oropharyngeal decontamination (SOD), in which only topical antimicrobial agents are administered. In this cluster-randomization study involving 13 ICUs in the Netherlands, SOD and SDD did not affect crude mortality but did appear to reduce mortality slightly at day 28, with adjustment for covariates.

32-43

Five children from two consanguineous families were born with severe congenital neutropenia, prominent venous angiectasia, and congenital heart defects, urogenital abnormalities, or both. All five children had the same mutation in the gene for glucose-6-phosphatase, catalytic subunit 3 (G6PC3). Their neutrophils had increased susceptibility to apoptosis, and the mutation abolished the enzymatic activity of glucose-6-phosphatase.

44-52

This study shows that the prevalence of hypertension in subjects carrying a loss-of-function mutation in MC4R is less than that in overweight or obese control subjects. Metabolic measurements and results of a clinical trial testing an MC4R agonist suggest that melanocortinergic signaling influences blood pressure through an insulin-independent mechanism.

53-62
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This study examined bone-biopsy specimens obtained after a 3-year, double-blind, randomized, placebo-controlled, dose-ranging trial of oral alendronate to prevent bone resorption in healthy postmenopausal women. Long-term alendronate treatment was associated with an increase in the number of osteoclasts, which include distinctive giant, hypernucleated, detached osteoclasts that undergo protracted apoptosis. The finding of such cells, despite decreased resorption after long-term therapy with oral nitrogen-containing bisphosphonate, may have clinical implications.

Clinical Therapeutics
63-70

A 45-year-old woman is found to have invasive breast cancer and undergoes lumpectomy with dissection of the sentinel lymph nodes. After 6 months of adjuvant chemotherapy, radiation therapy is recommended. Radiation therapy has been shown to reduce the risk of local recurrence after breast-conserving surgery. The most serious complications include lung and heart injury and secondary cancers.

Images in Clinical Medicine
71
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A 50-year-old woman presented with a several-year history of acute and chronic joint pain. Her serum magnesium level was 0.9 mg per deciliter (0.4 mmol per liter) (normal range, 1.6 to 2.5 [0.7 to 1.0]), and the total daily urinary excretion of magnesium ...

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This 44-year-old woman presented with painful diplopia after being struck in the left eye with a bare fist. She had normal muscular balance in primary gaze but could not look up or down with her left eye.

Clinical Problem-Solving
72-76

    A 67-year-old man presented with a 3-month history of fatigue and fever. He had undergone heart transplantation 6 years earlier for idiopathic cardiomyopathy. He reported no weight loss, night sweats, or chills. He also reported no headache, rash, joint swelling, dysuria, or abdominal or respiratory problems.

    Editorials
    78-80

      Organ transplantation is one of the great success stories of modern medicine. Living-donor kidney transplantations between identical twins during the early 1950s first demonstrated the overall feasibility of this procedure and ultimately paved the way to ...

      80-82

      Osteoclasts are multinucleated cells responsible for the resorption of bone matrix. During the development and growth of a human, they ensure proper contouring of the bones and extension of the medullary spaces to provide for hematopoiesis. In the adult ...

      Clinical Implications of Basic Research
      83-84

      Blocking a bacterial sensor that is activated in vivo suppresses the bacterial virulence of Salmonella typhimurium and Francisella tularensis in mice.

      Correspondence
      85-86

      To the Editor: In their article on intensive lipid lowering, Rossebø et al. (Sept. 25 issue)1 report that therapy with simvastatin and ezetimibe did not reduce aortic-valve disease and calcifications in patients with mild-to-moderate asymptomatic aortic ...

      86-87

      To the Editor: The article by Peto et al. (Sept. 25 issue),1 which reports cancer incidence and mortality in three clinical trials of ezetimibe, raises disturbing scientific and ethical questions. Premature unblinding of ongoing trials is not a reliable ...

      87-88
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      To the Editor: In the introductory remarks of their article, Herbst et al. (Sept. 25 issue)1 note, “Smoking causes all types of lung cancer but is most strongly linked with small-cell lung cancer and squamous-cell carcinoma.” In the legend to Figure 1, ...

      88-89

      A 64-year-old man had a dizzy spell lasting several minutes, followed by syncope. A loop recorder showed a sinus-node arrest lasting 25 seconds. A dual-chamber pacemaker was implanted. Despite normal pacemaker function, he had numerous confusional ...

      89-90

      To the Editor: Between the time of the initial marketing of alendronate in October 1995 through mid-May 2008, the Food and Drug Administration (FDA) received reports of 23 patients in the United States receiving a diagnosis of esophageal cancer, with ...

      Book Reviews
      91

      Hope and Suffering is an apt title for this dense, encyclopedic, and riveting book. It includes narratives from patients and their family members that detail the hope, suffering, and despair of the first two decades of cancer therapy, followed by the ...

      91-92

      It is the year 1908. In the United States, more than 150,000 people will die from tuberculosis. If you contract tuberculosis, your best hope is to be shipped off to a sanatorium, where you will live a regimented life and sleep outdoors in subzero ...

      92-93

      Millions of children worldwide suffer from allergic diseases such as asthma, atopic dermatitis, allergic rhinitis, or food allergy. The diagnosis and treatment of these children require special attention to the complexities not only of childhood but also ...