[Pirbuterol: a new beta 2-sympathomimetic agent. An open multicenter study].
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Biomedical subjects
Publications and source records attributed to R Pariente.
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Since 1984, the use of the official method for determining the responsibility of drugs in side-effects has been compulsory in France. This method offers, but does not define, different qualificatives for chronological and semeiological criteria. Consensus workshops have been set up to define the undesirable side-effects themselves and the different qualificatives in each of the principal fields of pathology. As regards drug-induced interstitial pneumonia, chest specialists from university hospitals, members of the national system of pharmacovigilance and representatives of the Roussel-Uclaf central department of pharmaco-vigilance have determined: the limits of time elapsed between the beginning and end of drug administration and the occurrence of the adverse reaction; how to interpret various courses of the side-effect with and without temporary discontinuation of the drug, and how to interpret a possible readministration. A list of investigations aimed at excluding the main possible causes of interstitial pneumonia has been drawn up.
We have investigated the morphological effects of an intratracheal challenge with 50 micrograms ovalbumin (OA) on sensitized rat tracheas, in vivo. Female Sprague-Dawley rats were primed ten days before challenge with a single i.t. injection of 100 micrograms OA plus Bordetella pertussis (OA-BP). Two additional groups of animals served as controls: primed animals challenged with saline only and non-primed but OA-challenged animals. Sacrifices--and subsequent morphological studies--were performed prior to and 5, 15 and 60 min after challenge. At each time, the total numbers of epithelial nuclei, subepithelial mast cells (SEMC) and intraepithelial mast cells (IEMC) were scored in six non-adjacent cross sections per trachea. We found that: 1) priming with OA-BP alone did not induce any change in the tracheal mucosa with respect to morphological structure and mast cell counts; 2) no morphological change nor significant modification of the cell counts occurred at any time in tracheas from either of the control groups; 3) in contrast, a luminal heterogeneous exudate and a subepithelial oedema developed in 9 of the 15 tracheas of primed animals within 60 min of OA challenge. In those nine tracheas, the scores of intraepithelial nuclei, of IEMC and of SEMC were found to decrease significantly 15 min after challenge as compared with starting values (p less than 0.05 for each score). The decrease in the number of mucosal mast cells is probably related to the damages of the epithelial cells and to the difficulty with which depleted mast cells can be seen by toluidine blue staining.
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We investigated in the present study the distribution of anti-IgE binding cells in the trachea and in the thoracic lymph nodes of ovalbumin (OA)-sensitized rats. Sensitization of the airways was induced through a single intratracheal injection of the antigen, and was controlled by recording in vitro the antigen-induced contraction of the tracheal muscle: 12 of 15 (80%) OA-injected rats had a demonstrable status of tracheal sensitization. An immunohistochemical method was used for the localization of the anti-IgE binding cells in cryostat and in Carnoy fixed tissue sections. Virtually no cell was found to bind anti-IgE in the tracheas or in the thoracic lymph nodes from control animals. Conversely, we found in OA-sensitized rats that: 1) numerous IgE plasma cells appeared in the medullary cords of the lymph nodes (not in the trachea); 2) in tracheal sections, IgE concentrated in the cytoplasm of subepithelial mast cells and of nonciliated rounded epithelial cells (possibly the so-called globule leukocytes), but few if any mast cells of the connective tissue bound the anti-IgE conjugates.
We investigated in this study the effect of SO2-induced bronchopathy on airway sensitization to ovalbumin in the rat. Sprague-Dawley rats were immunized with a single intratracheal injection of ovalbumin (OA) 100 micrograms in 0.1 ml PBS or 0.1 ml Bordetella pertussis (BP) heat-killed vaccine (6.5 X 10(9) cells X ml-1). The rats were primed immediately after SO2 exposure (60 h, 200 ppm; group I, n = 16) and three months after exposure was achieved (group II, n = 24), then compared to a control group exposed to air (group III, n = 30). Airway sensitization was evaluated by the in vitro contractile response to antigen challenge using paired tracheal rings. Specific IgE level was determined with PCA reactions. No significant difference was found in the maximal contractile responses to carbamyl choline within and between each group. Excepted in animals of group III, OA alone was not found able to sensitize the airways. When OA was used in association with BP, sensitization of the airways occurred, but this occurrence was found to depend upon a previous SO2 exposure: 73.3% in group III, 41.7% in group II and 25% in group I were sensitized. In addition, only five animals (BP + OA injected rats of group III) displayed a PCA positive reaction. It is concluded that: 1) the concomitant intratracheal injection of BP with OA increased the occurrence of specific airway sensitization, 2) a previous chronic exposure to SO2 decreased the specific tracheal smooth muscle sensitization to intratracheal ovalbumin. This decrease persisted, although slighter, when immunization was done three months after the exposure to SO2 was stopped.
Visualization of rat IgA within the tracheal mucosa and the thoracic lymph nodes was achieved using the avidin-biotin-peroxidase complex (ABC) method. This technique was compared to the indirect immunoperoxidase technique and both techniques were applied at the light microscopic level, with various fixing and embedding procedures. The ABC method was found superior to the indirect method with respect to sensitivity, to background staining and to the overall reaction time.
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A longitudinal investigation was conducted simultaneously in Normandy and in the West-Paris region. Based on more than 2000 subjects in Normandy and 1500 in the Paris (St. Lazare) area, the frequency of a bronchial syndrome was established as 21 and 26% respectively; obstructive respiratory failure, 4 and 2% respectively; and restrictive respiratory failure, 1%. The typical elements of risk (tobacco, age, socio-professional sphere) reappear in this study. Alcoholism also seems to be a contributing factor. In a longitudinal investigation, the study of new cases which are in progress will help to identify the onset of the disease and its facilitating circumstances. In the future, the study of the flow-volume curve should be included in epidemiological investigations.
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