New Strains of Bacteria and Exacerbations of Chronic Lung Disease

This prospective study examined the changes in bacterial isolates from sputum samples obtained monthly from 81 outpatients with chronic obstructive pulmonary disease. There were 374 acute exacerbations of lung disease, which were significantly associated with the acquisition of a new strain of Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (relative risk for any new strain, 2.15). An exacerbation was diagnosed at 33 percent of the clinic visits that coincided with the appearance of a new bacterial strain in the sputum.

Earlier studies of chronic lung disease showed no association between clinical exacerbations and the presence of bacterial pathogens in the sputum. With the use of modern techniques to identify specific bacterial strains, this carefully performed study does show a relation between clinical deterioration and the presence of a new bacterial strain.

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Imatinib Mesylate in Advanced Gastrointestinal Stromal Tumors

Unresectable or metastatic gastrointestinal stromal tumors fail to respond to conventional chemotherapy and are usually fatal within 12 to 18 months. Most gastrointestinal stromal tumors have a defect in KIT, a transmembrane tyrosine kinase receptor. The abnormality prevents the death of the cell and forces it to proliferate. The effects of imatinib mesylate, which blocks the abnormal signaling by KIT, was studied in 147 patients with advanced gastrointestinal stromal tumors. There were no complete responses, but about half the patients had a stable partial response.

This study of imatinib in a relatively large number of patients with a rare type of tumor yielded promising results. Longer follow-up will be needed to determine whether the drug really prolongs life. Nevertheless, these results in a disease with a generally hopeless prognosis are encouraging.

Imatinib Mesylate in Chronic Myeloproliferative Diseases

Imatinib mesylate blocks the activity of three protein tyrosine kinases: ABL, KIT, and platelet-derived growth factor receptor (PDGFRB). These kinases have crucial roles in chronic myelogenous leukemia (ABL), gastrointestinal stromal tumors (KIT), and certain myeloproliferative diseases (PDGFRB). The first two types of neoplasms have been shown to respond to imatinib mesylate. This article reports that in four patients, a myeloproliferative disorder involving a rearranged PDGFRB gene also responded to the drug.

These findings fulfill the prediction that a neoplasm that arises from an abnormality of the tyrosine kinase PDGFRB should respond to imatinib. Imatinib is an excellent example of an advance in medicine based on the fusion of molecular biology and molecular pharmacology.

Polyomavirus BK Replication and Allograft Nephropathy

Polyomavirus BK (BKV) nephropathy, an emerging cause of renal-allograft failure, may be linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil. This prospective, single-center study examined urine for cells with viral inclusions, measured BKV DNA in plasma, and evaluated renal-biopsy specimens for evidence of nephropathy in 78 renal-transplant recipients who were being treated with such regimens. Four of five patients in whom BKV nephropathy developed were among the 77 percent of patients who had BKV antibodies before transplantation. The probability of BKV nephropathy was 8 percent (95 percent confidence interval, 1 to 15 percent).

Cytologic analysis of urine and quantitative plasma polymerase-chain-reaction assays may be useful noninvasive methods of monitoring renal-transplant recipients for BKV replication and associated nephropathy.

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Clinical Practice: Obstructive Sleep Apnea

A 43-year-old man presents with heavy snoring; his bed partner reports that he sometimes stops breathing while he sleeps. He has hypertension controlled by medication but is otherwise healthy. He admits to feeling sleepy at times when he drives, although he has not had any motor vehicle accidents. His body-mass index is 33, and he has a large neck circumference (46 cm). How should he be evaluated and treated?

This article discusses the diagnosis and management of obstructive sleep apnea.

Current Concepts: Illness after International Travel

After international travel, up to 5 percent of travelers become ill enough to seek medical attention. This review focuses on the most common and most serious illnesses seen in persons from the industrialized world who have traveled to developing countries. The authors provide practical guidance for the diagnosis and management of fever, persistent diarrhea, and skin lesions in patients who present with these conditions after international travel.

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