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December 26, 2002  Vol. 347 No. 26

Perspective
2094-2095

Inherited disorders of intermediary metabolism are the prototypes for the treatment of genetic disorders. In each condition, accumulation of a metabolite results from a genetically determined abnormality in a metabolic pathway in which there is deficient ...

Original Articles
2097-2103
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In Hong Kong, the seasons for influenza and respiratory syncytial virus (RSV) infection sometimes do not overlap, so that a relatively accurate estimate can be made of the effects of influenza-related acute respiratory disease in children. Using data from a well-defined population, these researchers found high rates of hospitalization attributable to influenza in children: 278.5 per 10,000 children younger than one year of age and 218.4 per 10,000 children one to less than two years of age in 1998.

2104-2110

This randomized, controlled trial compared treatment with celecoxib and treatment with diclofenac plus omeprazole in patients with arthritis and ulcer bleeding. The rates of recurrent ulcer bleeding during six months of follow-up were similar in the two groups (4.9 percent in the celecoxib group and 6.4 percent in the diclofenac-plus-omeprazole group).

2111-2121
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Alkaptonuria is caused by mutations in the HGO gene and a deficiency of homogentisate 1,2-dioxygenase, which lead to an accumulation of homogentisic acid (HGA), ochronosis, and connective-tissue destruction. There is no effective therapy for the disorder. This study of the natural history of alkaptonuria examines findings in 58 patients, 57 of whom had detectable HGO mutations. The data are intended to serve as a base line for future trials of therapy. Nitisinone, which inhibits the enzyme that produces HGA, was administered briefly in two patients; urinary HGA levels decreased and plasma tyrosine levels increased without apparent adverse effects.

2122-2132

Patients with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency require low-phenylalanine diets, even those with mild disease. This study explored the responsiveness of 38 such patients to the cofactor tetrahydrobiopterin. Tetrahydrobiopterin significantly lowered blood phenylalanine concentrations in most of the 10 patients with mild hyperphenylalaninemia and the 21 with mild phenylketonuria, but had no effect in the 7 with classic phenylketonuria. Seven mutations were probably and six were potentially associated with tetrahydrobiopterin responsiveness.

Images in Clinical Medicine
2133
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Figure 1. A 26-year-old man presented with nonproductive cough and exertional dyspnea. Physical examination disclosed acrocyanosis. Chest radiography showed patchy alveolar and interstitial disease in a perihilar “batwing” distribution (Panel A). High-...

Special Article
2134-2140

Phase 1 trials of chemotherapeutic agents have been criticized because it is believed that the consent forms investigators use promise benefits and ignore risks. This study of 272 consent forms obtained from 37 academic cancer centers and six large pharmaceutical companies does not bear out the concern that consent forms for studies of experimental treatments for cancer are inadequate or ethically flawed.

Review Article
2141-2148

Pulmonary surfactants consist of phospholipids and the hydrophobic proteins surfactant protein B and surfactant protein C. These surfactants keep the alveoli in the lung open to the atmosphere. Mutations in the genes encoding these proteins cause a variety of pulmonary syndromes. The pulmonary diseases associated with some of these mutations exemplify the consequences of the accumulation of misfolded proteins in tissue.

Case Records of the Massachusetts General Hospital
2149-2157

Presentation of Case

A 56-year-old man was admitted to the hospital because of rapidly progressive dyspnea and pulmonary abnormalities.

The patient had been well until about two weeks earlier, when he stopped smoking because he “felt like it”; he had a ...

Editorials
2159-2162

Was the disappearance of brooding storks in Germany during the latter half of the last century really responsible for the precipitous decline in the number of newborn babies there? This example illustrates why ecologic studies are considered among the ...

2162-2164

Widespread use of nonsteroidal antiinflammatory drugs (NSAIDs) among the elderly has resulted in a large population of persons at risk for ulcer complications. Selective cyclooxygenase-2 (COX-2) inhibitors were introduced with the hope that they would not ...

Correspondence
2165-2168

To the Editor: In the clinical trial reported by Diegeler et al. (Aug. 22 issue),1 surgery was much more effective than stenting with regard to the prospectively established end point of a major adverse cardiac event (which occured in 31 percent of the ...

2168-2170

To the Editor: The report of Hermine et al. (July 11 issue)1 provides important additional evidence as to the possible role of antiviral therapy for hepatitis C virus (HCV) infection in the treatment of patients with HCV-associated mixed cryoglobulinemia ...

2170-2171

To the Editor: Fisher et al. (Aug. 22 issue)1 report that radical mastectomy and total mastectomy are equally effective in terms of survival (equipotent) and interpret the small differences between the groups in their study as insignificant. We believe, ...

2171-2173

To the Editor: We write to address several statements in Dr. Moake's review of thrombotic microangiopathies (Aug. 22 issue).1 First, assays of the activity of the metalloprotease ADAMTS 13 differ in design; the normal range of activity is assay-specific....

2173

To the Editor: In his provocative article on nonfinancial conflicts of interest in research, Dr. Levinsky (Sept. 5 issue)1 wisely focuses on the ultimate danger of intrinsic conflicts of interest — that of harm to patients or healthy volunteers who ...

2173-2174

To the Editor: Antifungal azoles with activity against aspergillus include itraconazole and three new drugs: voriconazole, posaconazole, and ravuconazole. Voriconazole was recently approved for the treatment of invasive mold infections, and posaconazole ...

Book Reviews
2175

This book is based on interviews with 16 pioneers in cardiac surgery and medical cardiology, almost all of whom are from the United States. Interviews that took place between 1979 and 2000 with Charles Bailey, André Cournand, William Dock, and Willem ...

2175-2176
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Heart Transplantation, a beautifully written, comprehensive monograph, sets new standards. The authors, long-term scientific leaders in the field, are optimally positioned for this task. Their book covers the topic in a consistent and carefully balanced ...

2176-2177

There have been gratifying advances in the treatment of cardiac arrhythmias during the past 20 years. Whereas in the past, pharmacologic therapy was the only real option for most patients with cardiac arrhythmias, the advent of radio-frequency catheter ...

Legal Issues in Medicine
2178-2182

A patient who was denied coverage for a specialized surgical procedure successfully sued her health maintenance organization (HMO). In its appeal to the U.S. Supreme Court, the HMO argued that as an ERISA plan (an employer health plan regulated by the federal Employee Retirement Income Security Act), it was exempt from an Illinois law requiring external review in disputes about the medical necessity of treatment. The Court ruled that the insurance aspects of ERISA plans are not exempt from state laws and that the HMO must offer external review.

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