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August 5, 2004  Vol. 351 No. 6

Perspective
523-526

Dr. Richard P. Wenzel examines the dramatic reduction in the number of pharmaceutical companies engaged in the discovery of antiinfective agents.

524

Although Alexander Fleming discovered penicillin in 1928, the substance was largely ignored until scientists at Oxford University rediscovered it in the early 1940s. Because of World War II, with its air raids and threat of German invasion, the Oxford ...

526-528

After the release of the results of the RALES trial, there was a striking increase in hospital admissions and deaths related to hyerkalemia. Dr. John McMurray and Dr. Eileen O'Meara explain that a number of causes are likely.

528-530

Dr. James R. Downing describes the transforming growth factor β signaling pathway that supresses the early development of cancer cells. There is mounting evidence of a permissive role of TGF-β in the metastatic behavior of established tumors.

531-532

Airway smooth-muscle mass is increased in patients with asthma. This increase in muscle mass is quite marked in lung sections from patients who have died of asthma, but bronchial-biopsy studies indicate that even persons with mild-to-moderate asthma have ...

Original Articles
533-542

In a study of leukemia cells that were resistant or sensitive to prednisolone, vincristine, asparaginase, or daunorubicin — four drugs used in the treatment of childhood acute lymphoblastic leukemia — 124 genes were linked to resistance or sensitivity. The pattern of expression of resistance genes was independently related to the outcome of treatment.

543-551

The Randomized Aldactone Evaluation Study (RALES) showed that spironolactone reduces mortality in patients with severe heart failure; however, the drug can cause hyperkalemia, especially when given with angiotensin-converting–enzyme (ACE) inhibitors. The current study found that, after the publication of RALES, there was an abrupt increase in the rate of prescriptions for spironolactone and in hyperkalemia-associated morbidity and mortality in patients with heart failure who were receiving an ACE inhibitor.

552-559
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Smad3 is a signaling molecule that has a key role in the cascade evoked by the binding of transforming growth factor β, a tumor suppressor, to its receptor on the cell surface. The principal result reported in this study is a lack of Smad3 in malignant cells from children with T-cell acute lymphoblastic leukemia. This novel finding places Smad3 on the list of tumor-suppressing molecules and provides a fresh look at the mechanisms behind childhood leukemia.

560-574

Normally, the growth of airway smooth-muscle cells is kept in check by the antiproliferative effects of glucocorticoids acting in concert with the glucocorticoid receptor and CCAAT/enhancer binding protein α (C/EBPα). These investigators show that airway smooth muscle from patients with asthma has a selective deficiency of C/EBPα, thus obviating the antiproliferative effects of glucocorticoids.

Special Article
575-584
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In this study of Medicare patients and primary care doctors, 22 percent of physicians accounted for 80 percent of visits with black patients. Doctors who treated black patients were less likely to be board certified than those who treated white patients (77 percent vs. 86 percent, P=0.02) and more likely to report an inability to provide high-quality care to all their patients (28 percent vs. 19 percent, P=0.005).

Review Article
585-592

Hyperkalemia can develop as a result of treatment with angiotensin-converting–enzyme inhibitors or angiotensin-receptor blockers. This side effect is most common in patients with risk factors such as diabetes mellitus, heart failure, chronic kidney disease, or advanced age. This review explains the pathophysiology and offers clinical guidance for management.

Images in Clinical Medicine
593

A 38-year-old man presented to the emergency department with nausea, vomiting, and epigastric pain. The patient had type 1 diabetes mellitus and was being treated with insulin. He was also taking lisinopril for the treatment of hypertension.

The initial ...

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Three years earlier, this 27-year-old man had undergone surgery to repair a traumatic rupture of the left side of the diaphragm.

Clinical Problem-Solving
594-599

    A 53-year-old woman presented to an outpatient urgent care clinic with persistent nausea and vomiting. On the previous evening, she had an acute onset of nausea that was followed by vomiting and light-headedness. The patient also reported mild discomfort in the chest and abdomen.

    Editorials
    601-603

      Since 1970, the rate of cure of acute lymphoblastic leukemia (ALL) in children has increased dramatically, from less than 30 percent to approximately 80 percent. This remarkable improvement has resulted from the marriage of laboratory and clinical ...

      603-605

      In the 50 years since the civil-rights movement began we have seen growth in the racial and ethnic diversity of the American people, as well as encouraging evidence that members of racial and ethnic minorities, including black Americans, have increasingly ...

      Clinical Implications of Basic Research
      606-608

      The most common cystic fibrosis mutation prevents the mutant protein (which forms a chloride channel) from reaching its usual destination: the cell surface. A recent study suggests that curcumin, a nutraceutical, may correct the effect of the mutation.

      Correspondence
      609-611

      To the Editor: Yu et al. (April 22 issue)1 report evidence of airborne transmission of the severe acute respiratory syndrome (SARS) virus. In Figure 1 of their article, the Amoy Gardens housing complex appears to be isolated, when in fact, just 20 m east ...

      611-612

      To the Editor: Quill (May 13 issue)1 advocates a “seamless transition into hospice programs if and when palliation becomes the primary objective,” but does not acknowledge a major obstacle to determining that palliation has actually become the primary ...

      612-614

      To the Editor: The Scottish Executive project Have a Heart Paisley was designed to improve the delivery of health care between primary and secondary care providers. Integral to its success is a cardiac-disease registry. European legislation governing the ...

      614-615

      To the Editor: In a section entitled “Procedures for Facial Rejuvenation” in his article on the treatment of photoaging, Stern (April 8 issue)1 briefly mentions blepharoplasty and face-lifts, and he characterizes them as expensive, highly profitable, and ...

      615-616

      To the Editor: Oral et al. reported in 2002 that leptin treatment for a period of four months improved hyperglycemia and hypertriglyceridemia in nine female patients with lipodystrophy.1 We report the efficacy of leptin-replacement therapy given for 12 ...

      Book Reviews
      617-618

      The connection among public health, epidemic disease, and politics can be seen throughout history, from the responses to the Black Death in Italian cities in 1348 to the response — or lack thereof — to the resurgence of tuberculosis on the part of the New ...

      618-619

      The steady and often alarming rate at which new and reemerging pathogens are appearing is well recognized. The past year alone saw a global epidemic caused by a previously unrecognized coronavirus, the first outbreak of monkeypox in the Western Hemisphere,...