American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2000
Polymorphisms of the IL-4, TNF-alpha, and Fcepsilon RIbeta genes and the risk of allergic disorders in at-risk infants.
Polymorphisms in the TNF-alpha (A-308G), IL-4 (C-589T), and Fcalpha RIbeta (E237G) genes have been associated with asthma and related phenotypes. To determine the predictive value of these polymorphisms we have assessed their relative risk (RR) for the development of atopy, asthma, and rhinitis in a high-risk infant population that is being followed longitudinally from birth. DNA was extracted and genotyped for 373 infants and 572 parents for each polymorphism. ⋯ However, we found that the IL4-589*T allele was associated with "probable" asthma (RR = 4.1) and that homozygotes for the IL4-589*T allele had an increased risk for the development of rhinitis (RR = 2.4). Using the transmission disequilibrium test, an association of IL4-589*T with atopy was found. We conclude that IL-4-589*T, but not TNF-alpha-308*2 or Fcalpha RIbeta*G, is a risk factor for the development of atopy, asthma, and rhinitis by 12 mo of age.
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Am. J. Respir. Crit. Care Med. · May 2000
Antituberculosis activity of once-weekly rifapentine-containing regimens in mice. Long-term effectiveness with 6- and 8-month treatment regimens.
The effectiveness of various once-weekly 10 mg/kg rifapentine (P)- containing regimens for treatment of tuberculosis was assessed in mice infected intravenously with 4.3 x 10(6) colony-forming units (cfu) of Mycobacterium tuberculosis H37Rv, and treated 14 d later with various combinations of rifampin (R), P, isoniazid (H), pyrazinamide (Z), ethambutol (E), or streptomycin (S). Control mice treated daily with either 2-mo HRZ + 4-mo HR or 2-mo HRZ + 6-mo HE were rendered spleen and lung culture-negative at 6 mo and 8 mo, respectively. ⋯ When the initial daily phase was reduced to 2 wk, once-weekly PH-containing treatment was successful, at 6 mo, only if it was supplemented with S during the initial daily and the once-weekly phases, and at 8 mo if it was supplemented with daily H during the once-weekly phase. Without these supplements, once-weekly treatment failed in some mice with selection of R-resistant or H-resistant mutants.
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Am. J. Respir. Crit. Care Med. · May 2000
Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease.
Although exacerbations of chronic obstructive pulmonary disease (COPD) are associated with symptomatic and physiological deterioration, little is known of the time course and duration of these changes. We have studied symptoms and lung function changes associated with COPD exacerbations to determine factors affecting recovery from exacerbation. A cohort of 101 patients with moderate to severe COPD (mean FEV(1) 41.9% predicted) were studied over a period of 2.5 yr and regularly followed when stable and during 504 exacerbations. ⋯ In the 404 exacerbations where recovery of PEFR to baseline values was complete at 91 d, increased dyspnea and colds at onset of exacerbation were associated with prolonged recovery times (p < 0.001 in both cases). Symptom changes during exacerbation do not closely reflect those of lung function, but their increase may predict exacerbation, with dyspnea or colds characterizing the more severe. Recovery is incomplete in a significant proportion of COPD exacerbations.