American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 1998
Randomized Controlled Trial Clinical TrialA pilot clinical trial of oral sodium 4-phenylbutyrate (Buphenyl) in deltaF508-homozygous cystic fibrosis patients: partial restoration of nasal epithelial CFTR function.
Sodium 4-phenylbutyrate (Buphenyl, 4PBA) is a new FDA approved drug for management of urea cycle disorders. We have previously presented data suggesting that 4PBA, at clinically achievable concentrations, induces CFTR channel function on the plasma membrane of deltaF508-expressing cystic fibrosis (CF) airway epithelial cells in vitro (Rubenstein, R. C., and P. ⋯ Subjects who had received 4PBA did not demonstrate significantly reduced sweat chloride concentrations or alterations in the amiloride-sensitive NPD. Side effects due to drug therapy were minimal and comparable in the two groups. These data are consistent with 4PBA therapy inducing CFTR function in the nasal epithelia of deltaF508-homozygous CF patients.
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Am. J. Respir. Crit. Care Med. · Feb 1998
Clinical TrialRespective and combined effects of prone position and inhaled nitric oxide in patients with acute respiratory distress syndrome.
Inhaled nitric oxide (NO) and prone position (PP) are two of the new therapeutics proposed in the setting of acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the hemodynamic and respiratory effects of NO and prone position in patients with ARDS. Fourteen patients, sedated, paralyzed, and ventilated using volume-control mode, were prospectively investigated. ⋯ The association of NO with PP (T4) resulted in a significant improvement in PO2/FI(O2) (261 +/- 98 mm Hg) when compared with T0, T1, and T3. Analysis of variance showed a significant and additive effect of NO and PP on both PO2/FI(O2) (p < 0.000) and shunt fraction (QS/QT) (p < 0.01). Since the association of NO with PP presents additive effects on oxygenation, this association can be proposed for the treatment of ARDS.
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Am. J. Respir. Crit. Care Med. · Feb 1998
Analyses of the NRAMP1 and IFN-gammaR1 genes in women with Mycobacterium avium-intracellulare pulmonary disease.
Mycobacterium avium-intracellulare (MAI) pulmonary disease causes substantial morbidity in a population of older, HIV-negative women without preexisting lung disease. The cause for disease susceptibility in these patients is unknown, although their relative phenotypic homogeneity suggests the existence of a common, subtle immune deficiency. An investigation was undertaken to determine if these patients have a defect in their natural resistance-associated macrophage protein (NRAMP1) or interferon gamma receptor 1 (IFN-gammaR1) genes. ⋯ In the NRAMP1 promoter microsatellite, 3 of 8 patients were heterozygous for a dinucleotide sequence insertion, as were 10 of 22 controls. None of the patients had either of the two known IFN-gammaR1 mutations. In conclusion, in women with MAI pulmonary disease, there is no evidence for a genetic defect in NRAMP1 or IFN-gammaR1 to correlate with disease.
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Am. J. Respir. Crit. Care Med. · Feb 1998
Histological indications of a progressive snorers disease in an upper airway muscle.
The etiology of upper airway collapsibility in patients with snoring and obstructive sleep apnea (OSA) remains unclear. Local muscular abnormalities, including neurogenic lesions, could be a contributory factor. The aim of this study was to histologically evaluate the hypothesis of a progressive snorers disease. ⋯ The subjects were also divided into three groups according to their type of nocturnal breathing, i.e., nonsnorers, patients with < 20%, and patients with > or = 45% obstructive breathing. These groups correlated significantly with the degree of abnormality and pathological fiber-size spectra. In conclusion, these results support the hypothesis of a progressive local neurogenic lesion, caused by the trauma of snoring, as a possible contributory factor to upper airway collapsibility.
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Am. J. Respir. Crit. Care Med. · Feb 1998
DNase I acutely increases cystic fibrosis sputum elastase activity and its potential to induce lung hemorrhage in mice.
The potential of DNase I to increase cystic fibrosis sputum elastase activity and lung damage was evaluated. Sputum from CF patients induced little lung hemorrhage when instilled intranasally in C57BL/6 mice. However, sputum treated in vitro by the addition of 1 mg/ml bovine DNase I showed increased neutrophil elastase activity (7.97 +/- 1.56 versus 3.91 +/- 0.62 microM, p < 0.01) and induced marked lung hemorrhage in mice (bronchoalveolar lavage fluid hemoglobin = 192.8 +/- 40.7 versus 44.5 +/- 12.0 microg/ml, p < 0.01). ⋯ Elastase levels returned to pre-rhDNase therapy levels 24 h after aerosol treatment. Sputum collected 1 h after rhDNase on 4 separate days from two of six patients in which elastase levels were highest, induced lung hemorrhage when instilled intranasally in mice. We conclude that DNase I therapy of patients with cystic fibrosis can acutely increase the elastase activity of sputum and also its potential to induce hemorrhage in the murine lung.