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Biomedical subjects

Bernard Maitre

Publications and source records attributed to Bernard Maitre.

9 recordsLinked to original sources
PubMed2007

Decrease in lung nitric oxide production after peritonitis in mice with sickle cell disease.

OBJECTIVE: Nitric oxide bioavailability may limit the occurrence or severity of acute vaso-occlusive episodes in patients with sickle cell disease. Because sepsis is frequently involved in the initiation of vaso-occlusive crisis and acute chest syndrome, we designed the present study in transgenic (SAD) sickle cell mice to investigate whether acute infectious peritonitis affects the enzymatic balance (nitric oxide synthases/arginases) that governs lung nitric oxide production. DESIGN: Controlled animal study. SETTING: Research laboratory of an academic institution. SUBJECTS: Transgenic Hbbsingle/single SAD1 (SAD) mice and nontransgenic wild-type littermates (C57/Black mice, control group). INTERVENTIONS: Cecal ligation and puncture-induced peritonitis. MEASUREMENTS AND MAIN RESULTS: We found that 24 hrs after peritonitis, control littermate mice showed an increase in inducible and endothelial nitric oxide synthase messenger RNA and proteins, together with an increase in exhaled nitric oxide (shift of the balance toward nitric oxide synthesis). In contrast, SAD mice, which showed elevated inducible and endothelial nitric oxide synthase protein expression at baseline, showed a marked decrease in nitric oxide synthase proteins, lung nitric oxide end-products, and exhaled nitric oxide after peritonitis, reflecting a shift of the enzymatic balance toward inhibition of nitric oxide synthesis. Peritonitis increased messenger RNA levels of arginase I and arginase II in controls and SAD mice but with a greater increase in arginase I in SAD than in control mice. Peritonitis was associated with a higher mortality rate at 24 hrs in SAD mice. Inhalation of nitric oxide (40 ppm in air) abolished the mortality rate induced by acute peritonitis in SAD mice. CONCLUSIONS: Acute peritonitis in SAD mice is associated with a defect in lung nitric oxide production and bioavailability that may participate in the acute systemic and lung vaso-occlusive complications of sickle cell disease.

Anemia, Sickle Cell↗
PubMed2006

Angiopoietin/Tie2 pathway influences smooth muscle hyperplasia in idiopathic pulmonary hypertension.

RATIONALE: Angiopoietins are involved in blood vessel maturation and remodeling. OBJECTIVES: One consequence of endothelium-specific tyrosine kinase-2 (Tie2) receptor activation by angiopoietin-1 (Ang1) is the release of endothelium-derived growth factors that recruit vascular wall cells. We investigated this process in idiopathic pulmonary arterial hypertension (iPAH). METHODS: Ang1, Ang2, and total and phosphorylated Tie2 expression (mRNA and protein) was evaluated in human lung specimens and in cultured pulmonary artery smooth muscle cells (PA-SMCs) and pulmonary endothelial cells (P-ECs) isolated from patients with iPAH and control subjects. Media collected from Ang1-treated P-ECs were assessed for their PA-SMC growth-promoting effect. MEASUREMENTS AND MAIN RESULTS: Tie2 receptor was fourfold higher in lungs and P-ECs from patients with iPAH than in those from control subjects, with a parallel increase in phosphorylated lung Tie2 receptor. In contrast, Ang1 and Ang2 expression in lungs, P-ECs, and PA-SMCs did not differ. Incubation of PA-SMCs with medium collected from P-EC cultures induced marked proliferation, and this effect was stronger when using P-ECs from patients with iPAH than from control subjects. Ang1 pretreatment of P-ECs from either patients or control subjects induced a further increase in PA-SMC proliferation. Fluoxetine, an inhibitor of the mitogenic action of serotonin, reduced the growth-promoting effect of P-EC media. Ang1 added to P-ECs from patients with iPAH increased the production of endothelin-1 (ET-1) and serotonin, but not of platelet-derived growth factor-BB or epidermal growth factor, and increased the amount of mRNA encoding tryptophan hydroxylase-1 (the rate-limiting enzyme of serotonin synthesis), preproET-1, and ET-1-converting enzyme. CONCLUSIONS: The Ang1/Tie2 pathway is potentiated in iPAH, contributing to PA-SMC hyperplasia via increased stimulation of endothelium-derived growth factors synthesis by P-ECs.

Angiopoietin-1↗
PubMed2006

Relationship between pressure-volume curve and markers for collagen turn-over in early acute respiratory distress syndrome.

OBJECTIVE: In acute respiratory distress syndrome, the relationships between changes in the elastic behavior of the respiratory system and biological markers of extra-cellular matrix or surfactant turn-over could give some insights into its pathophysiological determinants. DESIGN AND MEASUREMENTS: In 17 patients with acute respiratory distress syndrome, we assessed the relationship between chord compliance measured on pressure-volume curves obtained at two levels of positive end-expiratory pressure (0 and 10[Symbol: see text]cm[Symbol: see text]H(2)O) and biological markers of collagen turn-over or surfactant degradation in bronchoalveolar lavage fluid obtained simultaneously in the early phase of the disease (first 4 days). MAIN RESULTS: The compliance of the respiratory system obtained from the pressure-volume curves was significantly correlated with markers for collagen turn-over (type III procollagen peptide and matrix metalloproteinase 2) and with markers of surfactant degradation (type-IIA secretory phospholipase A2). The correlations were stronger when the curve was traced from positive end-expiratory pressure, suggesting that this condition may improve the assessment of tissue mechanics. A logarithmic relationship best described the correlation between compliance and type III procollagen peptide, in agreement with a collagen-dependent model of maximal distension. The marker for surfactant degradation was associated with ongoing alveolar inflammation (cellularity of bronchoalveolar lavage fluid and tumor necrosis factor-alpha concentration). Interleukin-10, an anti-inflammatory mediator, showed no correlation with compliance. CONCLUSION: These preliminary data suggest that a severe reduction in compliance in the early phase of acute respiratory distress syndrome is associated with both collagen deposition and surfactant degradation.

Adult↗
PubMed2005

Contribution of blinded, protected quantitative specimens to the diagnostic and therapeutic management of ventilator-associated pneumonia.

OBJECTIVE: Sampling techniques for microbiological diagnosis of ventilator-associated pneumonia (VAP) remain debated, and it is unclear to what extent invasive diagnostic techniques impact the management of patients. DESIGN: A prospective observational study of 68 first episodes of suspected pneumonia in which specimens were obtained blindly (endotracheal aspirate [EA] and blinded protected telescoping catheter [PTC]) and via bronchoscopy (directed PTC bronchoscopy and BAL), and in sequence, and the results were provided to the attending physicians in the same order. Therapeutic plans resulting at each step were examined, and their adequacy was assessed using quantitative BAL fluid culture as the diagnostic standard. PARTICIPANTS: Sixty-eight patients with clinically suspected VAP hospitalized in two ICUs in a tertiary care university hospital. RESULTS: There were 35 patients (51%) with VAP confirmed by BAL fluid culture (13 early onset and 22 late onset). EA specimens grew organisms (light growth or more) in all BAL-confirmed VAP cases and 59% of nonconfirmed cases, whereas the sensitivity and specificity of blinded PTC quantitative cultures were 77% and 97%, and did not differ from those of directed PTC cultures (77% and 94%, respectively). Antibiotic therapy based on the clinical severity and likelihood of VAP, Gram stain results, and early blinded PTC culture results was adequate in 54% (19 of 35 VAP patients) within 2 h of sampling and 80% (28 of 35 patients) within 24 h; therapy was revised in only 3 more patients following BAL culture results. New antibiotics were introduced within the first 24 h in 14 of 33 nonconfirmed episodes (42%), and antibiotics were withheld or withdrawn within 48 h in 23 episodes (70%); three of these patients-with both blinded PTC and BAL growing organisms below the threshold-had early subsequently confirmed pneumonia with the same organism. CONCLUSIONS: A therapeutic approach guided by quantitative cultures of blinded specimens helps achieve early adequate management of approximately 90% of patients suspected of having VAP.

Bronchoalveolar Lavage Fluid↗
PubMed2004

Adenovirus-mediated fibroblast growth factor 1 expression in the lung induces epithelial cell proliferation: consequences to hyperoxic lung injury in rats.

High concentrations of oxygen can induce pulmonary toxicity and cause injury to alveolar epithelial and endothelial cells. The present study was performed to determine whether the potent epithelial and endothelial fibroblast growth factor 1 (FGF-1) protected against hyperoxia-induced lung injury. Recombinant adenovirus carrying the gene encoding human secreted FGF-1 (Ad. FGF1) increased the proliferation of lung epithelial cells in vitro. Ad.FGF1 or control vector with an empty expression cassette (Ad.V152) was administered intratracheally to Wistar rats. With Ad.FGF1 (10(9), 5 x 10(9), 10(10), or 5 x 10(10) viral particles [VP]), FGF-1 protein was found in bronchoalveolar lavage fluid 4 days postinfection at levels proportional to the viral dose and was detected in plasma after doses of 10(10) VP or more were administered. Histological examination of the lungs showed intense proliferation and apoptosis of alveolar and bronchial epithelial cells, with few inflammatory cells. The alveolar architecture returned to normal within 17 days. Rats pretreated with Ad.FGF1 (10(9) or 5 x 10(9) VP) 2 days before exposure to hyperoxia (95% O2) survived, whereas rats pretreated with Ad.V152 died within 3 days. In conclusion, adenovirus-mediated FGF-1 overexpression in the lungs causes epithelial cell proliferation and has beneficial effects in hyperoxic lung injury.

Adenoviridae↗
PubMed2003

Induced sputum versus bronchoalveolar lavage during acute chest syndrome in sickle cell disease.

Previous reports have shown that in more than 40% of adults with acute chest syndrome (ACS), fat droplets suggestive of pulmonary fat embolism were present in alveolar macrophages. To determine whether induced sputum (IS) is a reliable test for detecting this embolism, we compared bronchoalveolar lavage and IS results in 20 patients with ACS. We found a correlation between the number of Oil Red O-stained macrophages in sputum and lavage fluid (Spearman's coefficient: rho = 0.657, p < 0.018). Sputum cytology was then studied in another 60 patients who had sickle cell disease with ACS. An elevated percentage of Oil Red O-stained macrophages was found in the sputum of 37/47 patients, but they did not include any of the patients with sickle cell disease but no clinical symptoms. Patients suffering from ACS with Oil Red O-stained macrophages had more extrathoracic concomitant pain than those without (76 vs. 50%, p < 10-8), had more neurologic symptoms (7 vs. 0%, p < 10-8), a lower differential platelet count (-49 +/- 121 vs. +85 +/- 229, p < 0.04), and higher abnormal transaminase values (28 vs. 17%, p < 0.01). We conclude that IS analysis is a safe, noninvasive, and useful test for fat embolism detection in ACS.

Acute Disease↗
PubMed2003

Diagnosing pneumonia during mechanical ventilation: the clinical pulmonary infection score revisited.

The clinical pulmonary infection score-original or modified-has been proposed for the diagnosis and management of ventilator-associated pneumonia. In 79 episodes of suspected pneumonia, we prospectively assessed the diagnostic accuracy of the physicians' clinical assessment of probability and of the modified clinical pulmonary infection score, both measured before (pretest) and after (post-test) incorporating gram stains results, using bronchoalveolar lavage fluid culture as the reference test. The pretest clinical estimate was inaccurate (sensitivity 50%, specificity 58%); the mean clinical pulmonary infection score at baseline was 6.5 +/- 1.3 (range, 3-9) and 5.9 +/- 1.7 (range, 3-9), respectively, for the 40 confirmed and the 39 nonconfirmed episodes (p = 0.07), and only slightly more accurate (sensitivity 60%, specificity 59%) than the clinical prediction. Incorporating the gram stain results of either directed or blind protected sampling increased the diagnostic accuracy (sensitivity and specificity of 85% and 49% and 78% and 56%, respectively) of the clinical score and increased the likelihood ratio for pneumonia of a score of more than six from 1.46 to 1.67 and 1.77. The clinical pulmonary infection score has low diagnostic accuracy; however, incorporating gram stains results into the score may help clinical decision making in patients with clinically suspected pneumonia.

Bronchoalveolar Lavage Fluid↗