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August 30, 2007  Vol. 357 No. 9

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Perspective
841-843
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The first generation of biopharmaceuticals has begun to lose patent protection. Richard Frank writes that there is concern that without new U.S. regulations, patent expirations may not be accompanied by the introduction of competing, lower-cost biologic ...

844-846

On July 30, the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee of the FDA concluded that the use of rosiglitazone for the treatment of type 2 diabetes was associated with an increased risk ...

846-849
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Drs. Kenneth Baughman and John Jarcho discuss the mechanisms of action of cardiac-support devices and the clinical factors involved in the selection of a ventricular assist device.

Original Articles
851-862
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A large genomewide association study of multiple sclerosis uncovered a number of single-nucleotide polymorphisms that have a strong statistical association with the disease. Of these allelic variants, the three with the strongest association relate to immunologic elements: a gene in the HLA region and alleles of IL2RA and IL7RA. Both IL2RA and IL7RA have been implicated in other autoimmune diseases.

863-873

This study describes 15 men who underwent sustained reversal of idiopathic hypogonadotropic hypogonadism, defined by the attainment of normal adult testosterone levels, after discontinuation of hormonal therapy. Sustained reversal seems to occur in about 10% of patients. Therefore, brief discontinuation of hormonal therapy to assess reversibility of hypogonadotropic hypogonadism is reasonable.

874-884

In this study of 460 patients with traumatic brain injury, a post hoc analysis of a larger randomized trial comparing saline and albumin for fluid resuscitation in patients requiring intensive care, the mortality rate was significantly higher in the albumin group. These findings suggest that albumin should not be used for fluid resuscitation in patients with severe traumatic brain injury.

885-896
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A series of 133 patients with severe heart failure underwent implantation of a continuous-flow left ventricular assist device. At 6 months, 75% of the patients had undergone heart transplantation, had cardiac recovery with device explantation, or continued to receive device support without any contraindication to subsequent transplantation. Important adverse events included postoperative bleeding, stroke, heart failure, and drive-line infection.

897-904

The authors describe three siblings, two men and one woman, with hypogonadism from isolated luteinizing hormone deficiency. They had a newly discovered homozygous 5′-splice-site mutation of the luteinizing hormone beta-subunit gene that leads to aberrant processing and thus abrogates the secretion of luteinizing hormone. This mutation appears to cause familial selective hypogonadotropic hypogonadism in both sexes.

Review Article
905-916

Antiresorptive agents help to restore skeletal balance by reducing bone turnover, primarily at the tissue level. Another therapeutic approach is to enhance bone formation with the use of anabolic agents, which differ fundamentally from antiresorptive drugs in their primary mechanism of action. This article reviews the mechanisms of polypeptide anabolic agents and strontium as potential therapeutic options for osteoporosis.

Images in Clinical Medicine
917
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A 46-year-old woman with metastatic sarcoma who had been treated with five cycles of doxorubicin, ifosfamide, and mesna chemotherapy presented with two symmetrical, horizontal white lines on all of her fingernails but not on her toenails. A diagnosis of ...

e10
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This 44-year-old woman presented with increasing oral papillomatosis, predominantly on the lips and less pronounced on the tongue and buccal mucosa. A biopsy was performed.

Case Records of the Massachusetts General Hospital
918-925

A primigravida delivered a stillborn infant at 39.7 weeks' gestation. Testing was positive for group B streptococcus; she was immune to rubella, and the blood type was B Rh-positive. The pregnancy had been uneventful except for costochondritis 14 weeks before delivery and an oval-shaped red rash with central clearing on the thigh 6 weeks before delivery. On the day of admission, fetal movements ceased and contractions began. An external fetal monitor and ultrasonographic examination confirmed intrauterine fetal death.

Editorials
927-929

High-resolution genomewide association studies using panels of 300,000 to 1 million single-nucleotide polymorphisms (SNPs) aim to define genetic risk profiles of common diseases. These studies herald a fundamentally new opportunity to explore human ...

929-932

In an extraordinary display of nature's myriad intricacies, in higher mammals the gonadotropin-releasing hormone (GnRH) pulse generator, which drives the pulsatile secretion of gonadotropin and sex steroids, is kept in abeyance until the onset of puberty, ...

Clinical Implications of Basic Research
933-935

Diminished levels of the tau protein seem to protect mice from the development of behavioral abnormalities and memory loss that are brought about by mutant amyloid precursor protein.

Correspondence
936-937

To the Editor: A 61-year-old man in cardiogenic shock was recently transferred to our hospital. Angiography revealed total occlusion of the left anterior descending coronary artery and an 80% ostial stenosis of the right coronary artery. Since he had ...

937-940

To the Editor: The study by Nissen and Wolski (June 14 issue)1 shows increased rates of myocardial infarction and death from cardiovascular causes associated with rosiglitazone treatment for type 2 diabetes. The authors' results are intriguing because a ...

941

To the Editor: Ford et al. (June 7 issue)1 have developed a statistical model, called IMPACT, which explains almost 90% of the observed decrease in deaths from coronary heart disease in the United States in the 20 years from 1980 to 2000. This model, ...

941-942

To the Editor: In the article on the syndrome of inappropriate antidiuresis (SIAD), by Ellison and Berl (May 17 issue),1 I disagree with the statement, in the discussion of areas of uncertainty, that “SIAD is characterized by a water excess, rather than ...

943-945

To the Editor: I have three concerns about the description of central venous catheterization in the video by Graham et al. (May 24 issue).1 First, it is misleading to describe the risk of hemothorax as “not applicable” when the internal jugular approach ...

945-946

A 15-year-old girl with rabies encephalitis was treated with a novel therapeutic regimen that included ketamine, ribavirin, and amantadine. The authors report on the favorable outcomes 18 and 27 months after her initial exposure to a rabid bat.

Book Reviews
947-948

This book identifies a central problem that cries out for correction, just when we are awaiting the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V), which has been promised for 2012. As the ...

948-949

This book was written by a sociologist who focuses on a critical but insufficiently studied sociological aspect of residency training programs — why is it that so many residents who start surgical residency programs do not finish them? Getting Cut is ...

949-950

Christopher Columbus returned to Portugal from his epic sea voyage with a cabin full of parrots. Perhaps one of them was infected with the bacterium Chlamydia psittaci and passed it on to Columbus, causing the reactive arthritis that afflicted the ...