American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 1998
Involvement of alpha-4 integrins in allergic airway responses and mast cell degranulation in vivo.
Antibodies against integrins have been shown to inhibit allergic airway responses. The purpose of this study was to test the hypothesis that the beta1 integrin, very late antigen-4 (VLA-4), is involved in mast cell activation triggered by allergen exposure in sensitized animals. To do this we studied Brown Norway rats that were sensitized to ovalbumin (OA; 1 mg subcutaneously) using Bordetella pertussis as an adjuvant. ⋯ There were significantly lower concentrations of histamine (67.11 +/- 11.90 microgram/ml versus 26.69 +/- 1.84; p < 0.01) and tryptase (0.143 +/- 0. 035 microgram/ml versus 0.053 +/- 0.022 microgram/ml; p < 0.01) in TA-2-treated animals. The increases in the concentrations of biliary N-acetyl-LTE4 after OA challenge were also significantly lower in TA-2-treated animals. These data suggest that a selective anti-VLA-4 monoclonal antibody prevents early responses through inhibition of mast cell activation.
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Am. J. Respir. Crit. Care Med. · Oct 1998
Airspace configuration at different transpulmonary pressures in normal and paraquat-induced lung injury in rats.
The aim of this study is to evaluate histoarchitecture of airspaces at different positive transpulmonary pressures, both during inflation and deflation of excised normal and paraquat-damaged rat lungs. Freshly excised lungs were placed in a plethysmograph connected to a graded pipette. Immediately after the achievement of the desired pressure level (5, 15, 25 cm H2O during inflation, and 15 and 5 cm H2O during deflation), the tracheal cannula was occluded and lungs were quick-frozen by immersion in liquid nitrogen, and fixed using Carnoy's solution. ⋯ Structural unevenness was minimized by massive recruitment followed by alveolar pressurization. In conclusion, this work demonstrates that morphological evidence of uneven distribution of inspired air may be partially reversed by applying larger alveolar pressures. These larger pressures applied at the end-expiration in vivo (positive end-expiratory pressure, PEEP) can minimize the distortion of lung microarchitecture during ventilation.
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Am. J. Respir. Crit. Care Med. · Sep 1998
beta2-Adrenergic receptor haplotypes in mild, moderate and fatal/near fatal asthma.
Excess beta2-agonist use in asthmatics has been associated with increased mortality and morbidity. The mechanisms responsible for these observations are unknown. We hypothesized that polymorphisms of the beta2-adrenergic receptor (beta2AR) at amino acid positions 16, 27, and 164, which are known to alter receptor functions in vitro, may predispose asthmatics to fatal/near-fatal asthma and/or modify asthma severity. ⋯ However, the Gly16/Gln27 haplotype, which undergoes enhanced downregulation in vitro, was substantially more prevalent in moderate asthmatics than in mild asthmatics (p = 0.003, odds ratio = 3.1). We conclude that the beta2AR genotype is not a major determinant of fatal or near-fatal asthma. Furthermore, allele frequency variation among ethnic groups must be considered in clinical studies of beta2AR polymorphisms in asthma.
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Am. J. Respir. Crit. Care Med. · Sep 1998
Randomized Controlled Trial Multicenter Study Clinical TrialEffectiveness and cost of selective decontamination of the digestive tract in critically ill intubated patients. A randomized, double-blind, placebo-controlled, multicenter trial.
We evaluated the effect of selective decontamination of the digestive tract (SDD) on the incidence of ventilator-associated pneumonia (VAP) and its associated morbidity and cost in a mixed population of intubated patients. Two hundred seventy-one consecutive patients admitted to the intensive care units (ICUs) of five teaching hospitals and who had an expected need for intubation exceeding 48 h were enrolled and received topical antibiotics or placebo. Uninfected patients additionally received ceftriaxone or placebo for 3 d. ⋯ In decontaminated patients, the prevalence of gram-negative bacilli fell within 7 d from 47.4% to 13.0% (p < 0.001), whereas colonization with resistant gram-positive strains was higher (p < 0. 05) than in the placebo group. In a mixed population of intubated patients, SDD was associated with a significant reduction of morbidity at a reduced cost. Our findings support the use of SDD in this high-risk group.
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Am. J. Respir. Crit. Care Med. · Sep 1998
Comparative StudyPneumonia in acute respiratory distress syndrome. A prospective evaluation of bilateral bronchoscopic sampling.
We evaluated the diagnostic yield of bilateral bronchoalveolar lavage (BAL) in patients with acute respiratory distress syndrome (ARDS) with suspected ventilator-associated pneumonia (VAP) and compared BAL results from contralateral sites. Ninety-four ARDS patients with suspected VAP underwent 172 bronchoscopies (344 BALs). BAL was processed for quantitative cultures, total cell count and subjected to microscopic analysis for cell differential, presence of intracellular organisms (ICO), and Gram stain. ⋯ Overall, Gram stain had a sensitivity of 54% and a specificity of 87%; and Giemsa stain (> 2% ICO) had a sensitivity of 46% and a specificity of 93%. Antibiotic treatment was modified by the results of BAL cultures in 50 (91%) episodes of pneumonia. In patients with ARDS and suspected VAP, bilateral BAL quantitative bacterial cultures had significant growth on one side only in 19% and in both sides in 13%.