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July 22, 2004  Vol. 351 No. 4

Perspective
315-317
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A public data bank of all clinical trials has seemed a quixotic quest. Dr. Robert Steinbrook explains how some recent events have captured wide attention.

317-319

The irinotecan and cetuximab regimen costs approximately $30,790. How should we determine whether these interventions are worth their immense cost? Dr. Deborah Schrag responds.

320-322

Macular degeneration is a class of blinding disorders characterized by changes in the macula, the central area of the neural retina that is responsible for high-acuity vision (see Figure 1). Such disorders are the leading causes of irreversible visual ...

322-323

Dr. Richard T. Johnson relates his experience of a sudden onset of vertigo without hearing loss. Old textbooks incorrectly stated that the symptoms resolve within a few days or weeks.

324-326

We live in the era of the Human Genome Project, human and mouse genetics, proteomics, evidence-based medicine, intelligent drug design, and a new “road map” for the National Institutes of Health (NIH) that relies on multidisciplinary, translationally ...

Original Articles
327-336
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More than 35 years have passed since it was discovered that the application of positive end-expiratory pressure (PEEP) improved arterial oxygenation in patients with certain forms of respiratory failure who were treated with mechanical ventilation. In this study, investigators from an NIH-sponsored consortium compared the effects of higher and lower levels of PEEP on survival after the institution of mechanical ventilation. The trial was terminated early after neither approach proved to have an advantage.

337-345

In this randomized trial, cetuximab, a monoclonal antibody against the epidermal growth factor receptor, was given alone or in combination with irinotecan to patients with advanced colorectal cancer that was refractory to irinotecan therapy. The efficacy of the combination of antibody plus drug was clinically significant and was superior to that of the antibody alone.

346-353

Age-related macular degeneration (AMD) is common, affecting approximately 7 million people in the United States. However, knowledge of its causes is scant. This study builds on studies indicating that fibulin variants may confer susceptibility to AMD. The authors screened five genes encoding members of the fibulin family, extracellular matrix proteins, and found an association between variations in fibulin 5 and AMD.

354-361

Herpes simplex virus has been implicated in the pathophysiology of vestibular neuritis. In this placebo-controlled trial, a course of methylprednisolone initiated within three days after the onset of vestibular neuritis resulted in improved vestibular function at one year, whereas valacyclovir had no effect.

362-369
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A complex homeostatic system involving the interplay of bone, the kidneys, and the intestines maintains extracellular calcium levels within a relatively narrow range. This article describes a patient with autoimmune hyperparathyroidism and hypocalciuric hypercalcemia caused by IgG4 autoantibodies directed against the calcium-sensing receptor. The patient's hypercalcemia and elevated parathyroid hormone levels responded to the administration of glucocorticoids.

Review Article
370-378

West Nile virus is one member of the genus flavivirus, which includes mosquito-borne viruses that cause similar disease patterns in much of the world. The other members of this serogroup include the St. Louis encephalitis virus, the Murray Valley virus, and the Japanese encephalitis virus (which causes thousands of deaths each year in Asia). This review summarizes what is currently known about flavivirus encephalitis, with emphasis on the pathogenesis of West Nile virus infections.

Images in Clinical Medicine
379
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A 37-year-old man presented to the emergency department with a two-day history of crampy abdominal pain, nausea, and vomiting. On physical examination, his temperature was 37.2°C, and his pulse was 110 beats per minute. The examination revealed a markedly ...

e3
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This woman presented with intermittent discomfort in the right upper abdomen and a mass filling the epigastrium.

Case Records of the Massachusetts General Hospital
380-387

A 50-year-old woman was found to have low oxygen saturation by pulse oximetry on preadmission testing for a hysterectomy. She had had an episode of cyanosis after general anesthesia in the past. A physical examination, radiographic studies, pulmonary-function testing, and echocardiography revealed no abnormalities. A diagnostic procedure was performed.

Editorials
389-391

In 1967, Ashbaugh et al.1 introduced the use of positive end-expiratory pressure (PEEP) during mechanical ventilation to treat refractory hypoxemia in patients with the acute respiratory distress syndrome (ARDS). Almost 40 years later, the question of how ...

391-392

    Epidermal growth factor receptor (EGFR) is a member of the HER family of tyrosine kinase cell-surface receptors that are dysregulated in many types of tumor; its expression has been associated with a poor prognosis in colon cancer.1 There are at least two ...

    Clinical Implications of Basic Research
    393-394

    A recent study has uncovered a mechanism through which the proteasome mediates apoptosis. This process may be central to a new treatment for multiple myeloma.

    Correspondence
    395-397

    To the Editor: Hamrahian et al. (April 15 issue)1 describe a technique for measuring free cortisol concentrations that is technically difficult, likely to be expensive, and not widely available. They do not correlate the measured serum free cortisol ...

    397-398

    To the Editor: Our article on clostridium infections associated with musculoskeletal-tissue allografts (June 17 issue)1 describes an epidemiologic investigation that was initiated by the Division of Healthcare Quality Promotion, Centers for Disease ...

    398-399

    To the Editor: Jain et al. (April 15 issue)1 report growing restraint in the practice of transferring numerous embryos after in vitro fertilization. This reassuring news should not, however, distract attention from the fact that other assisted ...

    399-402

    To the Editor: One take-home message from the review article by Burstein et al. on ductal carcinoma in situ of the breast (April 1 issue)1 is that all women who have undergone breast-conserving surgery should receive routine radiotherapy. This is the ...

    402-403
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    To the Editor: Both the Sounding Board article by Osterholm and Norgan and the Perspective article by Thayer (April 29 issue)1,2 call for greatly expanded use of irradiation to prevent foodborne illness. The authors, two of whom receive funding from the ...

    403-404

    To the Editor: In December 1997, many children, and even some adults, in Japan who were watching the television cartoon program “Pocket Monster,” or “Pokemon,” had epileptic seizures.1,2 Because the program was very popular, this incident had a strong ...

    Book Reviews
    405

    The pharmaceutical industry claims that it can continue playing a key role in the development of new weapons against disease only if Americans pay prices for medicines that yield very high profits. It also claims that price controls would cause the stream ...

    405-407

    Each year the Trustees of Medicare report on the current status and projected condition of the Medicare trust funds for the next 75 years. Usually, such events are hardly newsworthy, but this year's report was different. Program outlays rose so ...

    407-408

    The rising cost of health care — and what to do about this problem — is perhaps our nation's most pressing health policy issue. The recent spike in private-insurance premiums has alarmed both employers and employees. More telling is the lack of clear ...

    Corrections
    408

    Pneumocystis Pneumonia Review Article, N Engl J Med 2004:350;2487-2498.. On page 2492, in Table 2, the dose for atovaquone should have read “two times daily,” rather than “three times daily,” as printed. The Web version of the article has been corrected.

    408

    Case 6-2004: A 35-Year-Old Woman with Extensive, Deep Burns from a Nightclub Fire Case Records of the Massachusetts General Hospital, N Engl J Med 2004:350;810-821.. On page 811, in Table 1, the headings of the last two columns should have read “nitric ...

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