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M Aubier

Publications and source records attributed to M Aubier.

At least 91 records · Page 5Linked to original sources
PubMed1996

Role of prostaglandins and nitric oxide on halothane-induced arteriolar dilatation in rat diaphragm.

The effects of anaesthetics on the microcirculation of the diaphragm are incompletely understood. Therefore, we assessed by in vivo intravital microscopy in rats the action of halothane on diaphragmatic arteriolar diameter and the role of nitric oxide and prostaglandins on halothane-induced diaphragmatic arteriolar diameter. We studied 54 rats anaesthetized with thiopentone. Dose-response curves to topically applied Krebs' solution saturated with halothane at increasing concentrations of 0%, 1%, 3% and 5% were carried out in the presence of an inhibitor of nitric oxide synthesis (N omega-nitro-L-arginine (LNA), 300 mumol litre-1) or inhibitors of prostaglandin synthesis (mefenamic acid 20 mumol litre-1 or indomethacin 20 mol litre-1) or in the absence of any inhibitor. We found dose-dependent arteriolar dilatation which was abolished by mefenamic acid and indomethacin. In contrast, the effect of halothane was not modified by LNA. These data demonstrated that halothane-induced arteriolar dilatation in the diaphragm of the rat was mediated by prostaglandins but not by nitric oxide.

Anesthetics, Inhalation↗
PubMed1996

Sparfloxacin for the treatment of community-acquired pneumonia: a pooled data analysis of two studies.

A pooled data analysis of two double-blind studies encompassing 1137 episodes of community-acquired pneumonia in hospitalised adults, of which 560 were treated with sparfloxacin and 577 were randomised to comparator antibacterial agents (amoxycillin/clavulanic acid, erythromycin or amoxycillin administered at reference dosages), was performed. The global efficacy rate at the end of treatment in evaluable patients treated with sparfloxacin was 88.3% compared with 84.1% in those who received comparator antibacterial agents. This analysis verified the efficacy of this new aminofluoroquinolone, given orally once daily, in the treatment of community acquired pneumonia. The overall outcome favoured sparfloxacin for use in the empirical treatment of community-acquired pneumonia.

Adult↗
PubMed1996

Compartmentalized IL-8 and elastase release within the human lung in unilateral pneumonia.

Because interleukin 8 (IL-8) is a potent neutrophil chemotactic and activating cytokine, we investigated IL-8 production in relation to neutrophil migration and elastase release in the human lung during unilateral community-acquired pneumonia (CAP). In 17 patients, the local response in the involved lung was compared with that in the contralateral, noninvolved lung, and with the systemic response. Eight healthy volunteers served as controls. IL-8, total neutrophil elastase (NE), free elastase activity, alpha 1-antitrypsin (alpha 1-AT), and total leukocyte and neutrophil counts were evaluated in bronchoalveolar lavage fluids (BALF). Mean IL-8 concentrations in BALF from the involved lungs of the patients were significantly greater than those in BALF from the noninvolved lung or from controls (p < or = 0.001). By contrast, the serum IL-8 concentration was not different in patients and in controls. Total NE and alpha 1-AT concentrations were increased in BALF from the involved lung as compared with the noninvolved lung or controls (p < or = 0.001). The elastase-inhibitory capacity of alpha 1-AT in BALF was impaired in the involved lung of seven of the 14 patients as compared with the controls, leading to free elastase activity in the involved lung of all patients with CAP. Plasma total NE concentrations were significantly greater in the CAP patients than in the controls. IL-8 concentrations in BALF correlated positively with total leukocyte counts, absolute numbers and percentages of neutrophils, total NE concentrations, and free elastase activity. Our results suggest that during unilateral CAP, locally produced IL-8 may trigger neutrophil accumulation and activation, thus contributing to a local elastase/antielastase imbalance within the site of infection.

Adolescent↗
PubMed1996

Benefits of the low pressure multichannel endotracheal ventilation.

Mechanical ventilation using a modified endotracheal tube, allowing bypass and washout of the endotracheal dead space (McETV), was compared with conventional controlled mechanical ventilation (CMV) in healthy and in surfactant-depleted rabbits. In healthy animals, shifting from CMV to McETV led to an increase in PaO2 (89 +/- 16 versus 104 +/- 13 mm Hg; p < 0.05) and a decrease in PaCO2 (41.5 +/- 3 versus 30 +/- 3 mm Hg; p < 0.05). As a result of reducing the peak inspiratory pressure (PIP) from 21 +/- 2 to 12 +/- 2 cm H2O (p < 0.05), it was possible in McETV mode to maintain comparable ventilation to that achieved by CMV. In surfactant-depleted animals, compared with CMV, McETV produced a rise in PaO2 without change in thoracic volume (from 100 +/- 40 to 150 +/- 60 mm Hg, p < 0.05) and a fall in PaCO2 (from 46 +/- 5 to 37 +/- 4 mm Hg, p < 0.05). After 4 h of ventilation, the surfactant-depleted animals from the CMV group developed thoracic overdistension quicker (at hour 1, p < 0.05) and, consequently, more animals died from pneumothorax compared with the McETV group (five versus two). We concluded that McETV ensured adequate gas exchanges with lower insufflation pressures and could diminish positive pressure ventilation-induced injury.

Animals↗
PubMed1996

[Scleroderma and alveolar inflammation].

Pulmonary fibrosis is a frequent and serious complication of scleroderma whose pathophysiology remains poorly understood. The alveolar structures are infiltrated by activated chronic inflammatory cells, alveolar macrophages and polymorphonuclear neutrophils in particular and these could play a determining role. We have studied the state of activation of alveolar macrophages and monocytes circulating in these patients who presented with scleroderma and interstitial pulmonary involvement and also in healthy subjects. The neutrophil alveolitis observed in the patients is accompanied by a raised level of interleukin-8 secretion by the alveolar macrophages compared to the healthy subjects. Interleukin-8 is an important chemotactic molecule for polymorphonuclear neutrophils in the lung. The neutrophil alveolitis is accompanied by a breakdown in the equilibrium of elastase-antielastase which could participate in the development of alveolar lesions leading to fibrosis. In addition to the activation of macrophages, there is an activation of monocytes marked by the increase in secretion of interleukin-6 and interleukin-8 in vitro during the progression of the disease of scleroderma. Thus, alveolar inflammation is integrated with the overall systemic inflammation whose causes remain unknown.

Case-Control Studies↗
PubMed1996

[Inhaled corticotherapy in asthma: when should it be started and how to stop?].

Bronchial inflammation is an almost constantly encountered feature in asthma, even in early stages. Corticosteroid therapy has been shown to be effective both in reducing bronchial inflammation and improving signs of bronchial hyperreactivity. The possible side effects of prolonged inhaled corticosteroids cannot be ignored. Thus, while the indication for inhaled corticosteroids is severe asthma is clear, many questions are raised in case of intermittent minor asthma. There is still much debate over the correct initial dose (high or low) and the clinical and functional criteria for dose reduction or withdrawal. We discuss here the modalities for starting and stopping inhaled corticosteroids in patients with asthma.

Administration, Inhalation↗
PubMed1996

[Interaction between tumor necrosis factor-alpha and the smooth muscle cells of the airway: implication in the physiopathology of asthma].

Asthma is a disease characterized by a bronchial hyperresponsiveness (BHR). Although the underlying mechanisms that induce this increase in bronchial reactivity remain unknown, evidence suggests that the inflammatory process present in the airways could play an important role in the development of BHR. This latter may result from alterations in the intrinsic properties of airway smooth muscle induced by inflammatory mediators. Tumor necrosis factor alpha (TNF alpha), a pro-inflammatory cytokine, appears to be an interesting candidate considering on one hand that it is able to induce, in human and in animals, a BHR to different inhaled pharmacological agents and on the other hand that high levels of TNF alpha were found in asthmatic airways. Our studies show that TNF alpha induces in a direct manner some modifications of the bronchial smooth muscle which can underly an increased muscle contractility. These modifications include an alteration of the intracellular calcium homeostasis and an increase in the mitogen capacity of the human airway smooth muscle cells. Using antibodies directed against the two existing receptor type of TNF alpha (TNFRp55 and TNFRp75) and TNF alpha-analogs obtained by directed mutagenesis, we showed that these modifications result from the activation of TNFRp55. The implication of this receptor in the other pathophysiologic characteristics of asthma is also discussed in this review.

Antigens, CD↗
PubMed1995

Effects of inhibition of nitric oxide synthesis on TNF alpha serum levels in E. coli endotoxemic rats.

We investigated the effects of nitric oxide (NO) synthesis inhibition on mortality rate and TNF alpha serum levels in rats inoculated with E. Coli endotoxin (30 mg/kg i.v.) Pre-treatment of endotoxemic rats with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis by both the constitutive and the inducible isoforms of the NO synthase, did not change the mortality rate but significantly reduced TNF alpha serum levels. By contrast, administration of aminoguanidine, a more specific inhibitor of the inducible NO synthase, did not modify serum TNF alpha. These results suggest that, in E. Coli endotoxemic rats, NO synthetized by the constitutive isoform of the NO synthase positively modulates TNF alpha synthesis.

Amino Acid Oxidoreductases↗
PubMed1995

Pulmonary MR angiography at 1.0 T: early results with k-space segmented and post-contrast TurboFLASH two-dimensional time-of-flight sequences.

PURPOSE: To evaluate the combined performance of two time-of-flight methods in imaging the pulmonary arteries. MATERIALS AND METHODS: This study was prospectively conducted in 28 patients suspected for pulmonary embolism (PE). Sixteen patients were free of pulmonary vascular disease, and 12 had pulmonary vascular disease as demonstrated by pulmonary angiography. To reduce artifacts caused by cardiac and respiratory motion, MR images were acquired in all subjects using bi-dimensional (2D), gradient-recalled echo (GRE), breath-hold techniques. Sagittal thin (6-mm) sections obtained with ECG gating, k-space segmentation and incremented flip-angles (TONE), and coronal thick (15-mm) sections obtained after a unique injection of Gadolinium chelate were used. RESULTS: High quality images were obtained in all 16 (100%) subjects free of pulmonary disease with both techniques, and in 10 and 12 (87% and 100%) patients suspected for pulmonary artery disease with sagittal and coronal Gd-enhanced MRA, respectively. In patients free of pulmonary disease, TONE images exhibited distal pulmonary arteries with 2.1 subsegmental divisions on average, whereas Gd-enhanced TurboFLASH images were the most accurate to identify proximal pulmonary arteries within the mediastinum, even if only 0.8 subsegmental divisions were seen on average. A correct diagnosis of pulmonary embolism was obtained in all cases but one, with use of both MRA techniques, with an overall accuracy of 86%. CONCLUSION: The association of segmented sagittal GRE images and coronal first-pass Gd-enhanced GRE images can provide information upon normal and diseased pulmonary arteries within the mediastinum until subsegmental pulmonary branches, even in patients with short-breathing. Further studies of patients with various pulmonary artery diseases will confirm whether this technique makes pulmonary MRA feasible in clinical routine situations.

Adult↗
PubMed1995

[Therapeutic management of asthma].

The clinical manifestations of bronchial asthma fall into two categories: acute asthma which consists of asthmatic attacks and their variants, and chronic asthma. The treatment of acute asthma is now well established, while that of chronic asthma, more difficult to organize, is part of a true therapeutic strategy which has two aspects: A more global approach to the treatment must be developed. This means full management of asthmatic patients who must be instructed and considered as active partners in the prevention of acute attacks, the evaluation of the severity of their disease and the application of the treatment prescribed. An asthma severity scale must be devised and a specific therapeutic programme must be offered for each stage of the disease. The general principle, beside treatment of acute asthma, is to pay much attention to the intercritical situation and, in particular, to treat effectively the bronchial inflammation.

Acute Disease↗
PubMed1995

Misuse of pressurized metered dose inhalers by asthmatic patients treated in French private practice.

Although metered dose inhalers (MDIs) are widely used to treat asthma, clinical studies suggest that misuse is frequent. We studied the frequency of, and factors related to, misuse of MDIs in asthmatic patients of French private practice. 264 chest specialists or general practitioners completed questionnaires including characteristics of patients and asthma, technique in using inhalers and previous instruction, for three consecutive asthmatics aged > 6 years and currently using MDIs: 668 adults (mean age 47.8 years +/- 18.5, 51.8% males) and 100 children (mean age 11.5 years +/- 2.1, 72.0% males) were included. Adequate technique (deep inspiration synchronized with inhaler activation, followed by holding breath for 5 seconds) was used by 33.2% of adults and 26.0% of children; optimal technique (same, plus shaking the inhaler before use and activating it only once) was used by 22.1% of adults and 20.0% of children. The main factor related to misuse of MDIs was absence of previous instruction. However only 26.5% of instructed adults and 22.1% of instructed children used the optimal technique. Misuse of MDIs is a public health problem and instruction is unlikely to solve it. The use of different types of devices, like dry powder breath-actuated inhalers should be encouraged.

Adolescent↗
PubMed1994

Secretion of alpha 1-antitrypsin by alveolar epithelial cells.

We have investigated the ability of alveolar epithelial cells (human A549 cell line and rat type-II pneumocytes) to produce alpha 1-antitrypsin (AAT). Northern blot analysis demonstrated the presence of an AAT-specific mRNA transcript in A549 cells. Unstimulated A549 cells secreted immunoreactive AAT at a rate of 0.51 +/- 0.04 ng/10(6) cells/h, with a modified glycosylation compared to serum AAT. AAT formed a complex with neutrophil elastase. Rat type-II pneumocytes secreted immunoreactive AAT. Our results suggest that alveolar epithelial cells could participate in antiprotease defense within the lung through local AAT production.

Amidohydrolases↗
PubMed1994

Concentration of meropenem in serum and in bronchial secretions in patients undergoing fibreoptic bronchoscopy.

The objective of the study was to evaluate the ability of meropenem to reach the bronchial lumen. 24 patients undergoing fibreoptic bronchoscopy for exploratory purposes were given a single dose of meropenem 1 g as an (i.v., infusion over 30 min. Plasma (P) sampling times were: 0, 0.5, 1, 2 and 3 h. Bronchial secretions (BS) were collected by fibreoptic bronchoscopy at the same sampling times (except for 0 and 0.5 h) in three groups of 8 patients. Meropenem was measured by bioassay using E. coli ATCC 39118 as the test-organism. The results showed that meropenem had reached a high plasma concentration at the first sampling time (59.8 mg.l-1) and then the plasma level decreased rapidly to 10.6 mg.l-1 and 2.7 mg.l-1 at 2 and 3 h respectively. The highest concentration achieved in bronchial secretion was 0.53 mg.l-1 in the third hour, ie 20% of the serum level. The data indicate significant penetration of meropenem into bronchial secretions and achievement of a local level sufficiently high to eradicate most respiratory pathogens.

Adolescent↗
PubMed1994

Comparison of enhanced chemiluminescence and colorimetric techniques for the immuno-detection of alpha 1-antitrypsin.

In order to detect, characterize and quantify blotted proteins, such as human alpha 1-antitrypsin (AAT), there is a need for a specific, extremely sensitive, non-radioactive and uniform revelation system applicable to diluted biological fluids and to culture supernatants of cells isolated from such fluids. We compared two immunochemical revelation systems, enhanced chemiluminescence (ECL) and colorimetric procedures, applied to human ATT, after determining their optimal conditions of performance. ECL was the most sensitive method (down to 50 pg blotted AAT), but could not be used to quantify AAT. In contrast, the colorimetric method enables quantification of blotted AAT, either simply dotted or transferred after SDS-polyacrylamide gel electrophoresis, but is not as sensitive as ECL. Using these two complementary procedures, we have been able to detect AAT in the culture supernatant of a monocytic cell line (THP-1), to characterize the different forms of AAT present in the culture supernatant of blood monocytes and to quantify both.

Cell Line↗