Biomedical subjects

R Bégin

Publications and source records attributed to R Bégin.

At least 73 records · Page 4Linked to original sources

PubMed1988

Cyclic nucleotides of lung lavage following acute antigen exposure in chronically exposed sheep.

In the sheep model of chronic allergic airway disease, we measured sequentially for 7 h following antigen exposure (Ascaris suum) histamine and the cyclic nucleotides cAMP and cGMP in bronchoalveolar lavage (BAL) fluids. Results in the six sheep with chronic allergic airway disease (reactive sheep) were compared to those of three sheep chronically exposed to antigen but without acute or chronic airway response (nonreactive sheep). Histamine levels in BAL fluids were not modified after antigen exposure in reactive and nonreactive groups. Before acute challenge, cAMP in BAL was 10.4 +/- 1.0 pmol/ml in reactive sheep and 16.4 +/- 1.0 in nonreactive sheep; cGMP was 0.16 +/- 0.01 pmol/ml in reactive sheep and 0.18 +/- 0.06 in nonreactive sheep. Antigen exposure did not change the lung lavage levels of cAMP or cGMP for up to 7 h in the nonreactive sheep. In the reactive sheep, antigen exposure induced a significant gradual fall in cAMP to 49% of the preexposure level and a rapid and sustained increase of cGMP to 200% of the preexposure level (P less than 0.05). Prechallenge lung resistance was increased in reactive sheep compared to nonreactive sheep. Antigen challenge further increased lung resistance in reactive sheep during the first hour without any change in nonreactive sheep. Reactive sheep BAL eosinophils increased to 900% of the values of nonreactive sheep at 4 and 7 h following challenge. These observations suggest that histamine does not have a major role in allergic response in the chronic sheep asthmatic model; furthermore, cyclic nucleotide modifications could reflect sympathoadrenergic imbalance and/or increase of inflammatory reaction following antigen exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Stiffness of the rib cage in a subset of rheumatoid patients.

In a previous investigation of lung function in patients with rheumatoid arthritis (RA), we observed that some patients had significant dysfunction of their chest wall mechanics without pleural disease that could contribute to their respiratory symptoms. To investigate further the chest wall functions of patients with RA, we selected 10 female lifetime nonsmoking patients with RA and compared them to 10 paid normal volunteers in detailed functional evaluations of lung and chest wall. Patients with significant airflow limitation were excluded from this study. We found a significant 7% reduction in total lung capacity in the RA patients without significant change in lung compliance. However, we found a significant reduction in rib cage compliance in patients with RA (0.044 +/- 0.006 L/cmH2O vs. 0.064 +/- 0.012 in controls), which was associated with a significant 38% reduction in expansion of the rib cage volume during various breathing maneuvers. These changes occurred in the absence of lung or pleural disease. This study documents that patients with RA have limited expansion of rib cage relative to abdomen, thus rib cage restriction and stiffness, which may contribute to reduced lung volume. The shift of thoracoabdominal breathing configuration observed in patients with RA will likely reduce the effectiveness of breathing muscles and thus could contribute to the dyspnea sensation experienced by patients with RA.

Arthritis, Rheumatoid↗

PubMed1988

Imaging the pneumoconioses: a multidisciplinary approach.

The initial early reaction of pulmonary tissue to inorganic dust inhalation is a fibrosing macrophagic alveolitis. This initial pulmonary lesion can be detected by an enhanced gallium 67 pulmonary uptake and analyses of bronchoalveolar lavage. These two techniques can document not only the increased proliferation of macrophages, but also the activation of macrophages to produce excessive amounts of fibronectin and other factors of fibroblastic growth implicated in the pathogenesis of the pneumoconioses. Of equal clinical interest is the development of computed tomography, which has permitted better characterization of the early stages of fibrosis in the pneumoconioses. These refinements in disease recognition will contribute to the earlier detection of pneumoconioses before they become incapacitating. Newer therapeutic methods are also under investigation that could permit inactivation of either the dust itself or the pulmonary macrophage. The coupling of these new diagnostic and therapeutic developments will bring in a new era in occupational pulmonary medicine.

Bronchoalveolar Lavage Fluid↗

PubMed1988

Increased procollagen III aminoterminal peptide-related antigens and fibroblast growth signals in the lungs of patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder characterized by an increased density of inflammatory cells, fibroblasts, and collagen within the lung parenchyma. To gain insights into the mechanisms leading to the increased density of fibroblasts and altered collagen metabolism in the IPF lung, bronchoalveolar lavage fluid from normal subjects and patients with IPF or sarcoidosis was analyzed for (1) the presence of antigenic material related to the aminoterminal propeptide domain of type III procollagen, and (2) fibroblast growth-promoting activity in the extracellular milieu of the lower respiratory tract. Whereas bronchoalveolar lavage fluid (BALF) type III procollagen aminoterminal peptide-related antigen levels in 59 patients with sarcoidosis were similar to the levels of control subjects (p greater than 0.10), 31 patients with IPF had markedly increased levels (12-fold over controls; p less than 0.025, IPF versus controls; p less than 0.01, IPF versus sarcoidosis). Type III procollagen aminoterminal peptide-related antigen levels correlated with an increase in the ability of BALF to stimulate fibroblast proliferation (p less than 0.05). Furthermore, BALF from patients with IPF markedly stimulated human lung fibroblast proliferation in vitro (199% increase, p less than 0.01), whereas lavage fluid from patients with sarcoidosis and from control subjects did not. The enhanced fibroblast proliferation induced by IPF BALF occurred in the absence of serum and exogenous growth factors, suggesting that both competence- and progression-type growth factors were present in the lavage fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Aluminum inhalation reduces silicosis in a sheep model.

In recent studies, we have documented that the biologic activity of quartz can be substantially reduced by surface chemistry modification with aluminum lactate treatment of the particles. In the present study, we evaluated the efficacy of aluminum lactate inhalation to reduce the biologic activity of experimental silicosis in the sheep tracheal lobe model. Four groups of 10 sheep were exposed once to either 100 ml phosphate-buffered saline (PBS) followed by aerosol inhalation of 10 ml PBS at monthly intervals (PBS-PBS group), to 100 ml PBS followed by inhalation of 100 mg aluminum lactate in 10 ml PBS (PBS-Al group), to 100 mg of quartz in 100 ml PBS followed by inhalation of 10 ml PBS (Si-PBS group), or to 100 mg of quartz in 100 ml PBS followed by inhalation of 100 mg aluminum lactate in 10 ml PBS (Si-Al group). Bronchoalveolar lavage (BAL) was repeated at monthly intervals for 6 months from before exposure (Month 0), and all sheep were autopsied at Month 6. All aerosol inhalations were carried out 24 h after BAL starting at Month 1 and monthly thereafter. In the PBS-PBS group and PBS-Al group, all BAL analyses remained at control levels and lung histology remained normal. In the Si-PBS group, BAL analyses documented significant sustained 3- to 10-fold increases in macrophages, lymphocytes, neutrophils, immunoglobulins, lactate dehydrogenase, glycosaminoglycans, lecithin, and phosphatidylglycerol, with histopathologic changes of nodular silicosis (pathologic score, 2.9 +/- 0.9) and mean retention of quartz at 2.83 +/- 0.98 micrograms/mg lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1988

Lung function in silica-exposed workers. A relationship to disease severity assessed by CT scan.

To investigate the relationship of lung function, airflow limitation, and lung injury in silica-exposed workers, we analyzed the clinical, functional, and radiologic data of 94 long-term workers exposed in the granite industry or in foundries. The subjects were divided into four subsets based on chest roentgenogram and CT scan of the thorax: group 1 consisted of 21 subjects with category 0 chest roentgenogram and category 0 CT scan; group 2, 28 subjects with category E 1 on both chest roentgenogram and CT scan; group 3, 18 subjects with category E 1 on chest roentgenogram but with coalescence or conglomeration or both seen only on CT scan; and group 4, 27 subjects with category E 1 and coalescence or conglomeration or both on roentgenogram and CT scan. The groups did not differ in terms of age, height, cigarette smoking, or years of exposure. Lung volumes were significantly reduced only in group 4 (p less than 0.05). Lung compliance, diffusion capacity, and the rest-exercise P(A-a)O2 gradient were reduced in groups 3 and 4 (p less than 0.05). Expiratory flow rates were significantly reduced in groups 2, 3, and 4, with the lowest values in group 4. The expiratory flow rates in group 3 were significantly lower in group 3 than in group 2. These results support the concept that airflow in silica-exposed workers is significantly reduced when the disease is detectable on simple chest roentgenogram; coalescence or conglomeration or both on chest roentgenogram or CT scan is associated with significant loss of lung volumes, gas exchange function, and increased airflow obstruction.

Humans↗

PubMed1988

Effects of cyclophosphamide treatment in experimental asbestosis.

The potential role of immunosuppressive therapy in asbestosis was evaluated in the sheep model of experimental asbestosis. A diffuse peribronchiolar alveolar and interstitial fibrosing alveolitis was developed in 10 animals following 2 years of exposure consisting of slow intratracheal infusion of 100 mg Canadian chrysotile in 100 ml saline every 2 weeks. A control group of 10 sheep concomitantly receiving only 100 ml saline intratracheally was also enrolled in the study. One group of 5 control sheep and one group of 5 asbestosis sheep received 1 mg/kg cyclophosphamide in 10 ml saline iv every 2 weeks, the other 10 sheep receiving only saline. One year after beginning of therapy, survival rates were comparable in the 2 control groups and the asbestosis group without therapy at 80%, whereas it was significantly reduced at 20% in the asbestosis group with therapy. Deaths in the latter were associated with significant increase in peripheral blood and lung lavage neutrophils, increased intensity of fibrosing alveolitis, worsening of lung functions, and worsening in the radiographic diffuse lung opacities. This was documented on histopathology to be associated with more intense fibrotic disease and bacterial pneumonia in the group of sheep with asbestosis receiving the immunosuppressor drug. We conclude that cyclophosphamide therapy in experimental asbestosis accelerated the fibrotic process and reduced significantly the survival rate of the animals.

Animals↗

PubMed1988

[New methods in the early detection of pulmonary fibrosis in asbestosis and silicosis].

Much recent work in thoracic medicine has been slanted towards the early detection of respiratory disease and the prevention of disabling sequelae. In the field of pneumoconioses associated with inhalation of mineral dust the interest of research workers has been largely orientated towards the objectives of early detection and the prevention of fibrotic scarring. To achieve real progress the research workers have used new investigational techniques such as axial tomography of the thorax, quantitative scintigraphy using Gallium-67 and analyses of bronchiolar lavage in parallel with a traditional approach, namely: a clinical examination of the patient, a pulmonary radiograph and respiratory function tests. These studies have enabled further clarification of the specific value of each of these new methods of investigation, whether at the level of early detection, the early recognition of pulmonary fibrosis, the characterisation of the current state of the disease and the prediction of fibrogenic power. Several different forms of intervention on the fibrotic process are currently under trial and may contribute to the prevention of pulmonary fibrosis.

Asbestosis↗

PubMed1988

[Forced oscillation respiratory resistance and MEV in the evaluation of nonspecific bronchial reactivity].

We have evaluated bronchial reactivity to histamine in 64 subjects with various degrees of bronchial obstruction, by the usual method of forced expired volume in one second FEV1 (VEMS) (CP20) and by the measurement of respiratory resistance (Rrs) using the forced oscillation technique. The characteristics of the relation of this histamine dose--spirometric response--Rrs was studied and compared with the usual CP20. We have found a significant linear correlation between the fall of VEMS and the rise in Rrs (R = 0.91, p less than 0.001) and the better concordance between CP20 spirometric and CP40 Rrs (r = 0.90, p less than 0.001). The measurement system for Rrs enables an evaluation of the degree of bronchial obstruction comparable to forced spirometry in bronchial provocation test to histamine and could be used to advantage in those subjects in whom collaboration might be doubtful or inadequate.

Adult↗

PubMed1988

Pathology of silicon carbide pneumoconiosis.

Silicon carbide is a widely used synthetic abrasive manufactured by heating silica and coke in electric furnaces at 2400 degrees C. Until recently it had been considered a relatively inert dust in humans and animals. However, several roentgenologic surveys had revealed lesions similar to low-grade silicosis. A recent epidemiological study has revealed a 35% incidence of pulmonary problems. Tissues from three such workers were available for light microscopy. A mixed pneumoconiosis was found, and lesions can be summarized as follows: (a) abundance of intraalveolar macrophages associated with a mixture of inhaled particles including carbon, silicon, pleomorphic crystals, silicon carbide, and ferruginous bodies showing a thin black central core; (b) nodular fibrosis, generally profuse, containing silica and ferruginous bodies and associated with large amount of carbon pigment; (c) interstitial fibrosis, less prominent than the nodular form; (d) carcinoma in two cases. We believe this pneumoconiosis is sufficiently characteristic to be recognized as a distinct entity. The Stanton hypothesis on fiber properties and carcinogenesis could be applied to silicon carbide dust. At present, it appears that the occupational hazard is limited to the manufacturing process and powdered product used in some industries.

Aged↗

PubMed1987

Asbestos exposure, cigarette smoking, and airflow limitation in long-term Canadian chrysotile miners and millers.

To investigate further the relationships of asbestos exposure, cigarette smoking, and airflow limitation, we have obtained detailed pulmonary function tests (PFT) in 331 long-term Canadian chrysotile workers, 34 of whom were lifetime nonsmokers. Three disease categories were defined on the bases of standard diagnostic criteria, gallium-67 lung uptake, and the lung pressure-volume curve. Category A was composed of workers without changes suggestive of alveolitis or asbestosis. There were eight nonsmokers (ns), among whom we found a statistically significant 30% reduction in airflow conductance (Gus) at low lung volume, which is consistent with the concept of an asbestos airway lesion. The 85 smokers (sm) of category A had reduction of Gus at both high and low lung volumes. Category B was composed of workers without asbestosis but with evidence of asbestos alveolitis. In the six ns, Gus was significantly reduced to 50% normal at low lung volume. The 59 sm had reduction of Gus at both high and low lung volumes but less severely than sm in category A. Category C was composed of workers with asbestosis. The 20 ns had restrictive pattern of lung function, and Gus was decreased to 39% normal at 50% TLC. The 153 sm in C had airflow reduction comparable to sm in B. We concluded that asbestos exposure, which leads to asbestos airway disease, asbestos peribronchiolar alveolitis, and asbestosis, causes airflow limitation at low lung volume but does not reduce the expiratory flow rates on the flow-volume curve in lifetime nonsmokers. In the smoking asbestos workers with alveolitis or asbestosis, the major component of airflow limitation is a smoking effect. In these smoking workers, rigidity of the lung lessens airflow obstruction associated with smoking at the expense of increased work of breathing.

Adult↗

PubMed1987

Airways disease in rheumatoid arthritis patients. One element of a general exocrine dysfunction.

Airflow limitation is a frequent finding in patients with rheumatic diseases. We have previously suggested that it is associated with autoimmune exocrinopathy in Sjögren's syndrome. To compare clinical features of patients with and without airways dysfunction and to further test the hypothesis of a link between airways disease and exocrinopathy, we prospectively studied 2 groups of 15 lifetime nonsmoker female patients with seropositive rheumatoid arthritis (RA). The 2 groups were similar in their clinical and immunologic features, but differed in terms of airways function. Salivary, lacrimal, and sweat gland dysfunction were significantly more prevalent or severe in the group with airways disease. Antinuclear antibodies were also more prominent in the patients with airways disease, but antibodies against RNP, SS-A, SS-B, and double-stranded DNA were not present in these patients. HLA-DR4 was found in 80% of the RA patients with airways disease and in 57% of those without airways disease. HLA-B8 and DR3 were equivalently distributed in both groups. This prospective study further documents the existence of small airways disease in RA and supports the view that autoimmune exocrinopathy predisposes to its expression.

Adult↗

PubMed1987

Late aluminum therapy reduces the cellular activities of simple silicosis in the sheep model.

To evaluate the biological effects of aluminum lactate therapy on nodular silicosis, we exposed the tracheal lobe of three groups of sheep containing eight sheep per group to either 11 mg of Al lactate in 100 ml saline (Al group), 100 mg of Minusil-5 in 100 ml saline (Si group), or 100 mg of Minusil-5 in 100 ml saline followed by 11 mg of Al lactate at monthly intervals 4 months after exposure (Si Al-treated group). The lung biological processes were evaluated by sequential lung lavage analyses of cellularity and biochemistry of supernatant and by autopsy analyses of cellularity and biochemistry of supernatant and by autopsy analyses of lung tissue histopathology and quartz content. Al lactate alone did not have any significant effect. Silica exposure produced the silicotic nodules and significant increases on lung lavage of cellularity, enzyme release, surfactant, and glycosaminoglycan accumulations. Al lactate therapy at month 4 after exposure did not decrease the pathological score of disease, but it significantly reduced all markers of cellular hyperactivity. This therapy was associated with a 65% reduction of the quartz retention in lung tissue and might help to prevent long-term progression of the disease process.

Aluminum↗

PubMed1987

Immunogenetic factors as determinants of asbestosis.

To evaluate the possible role of immunogenetic factors as predisposing determinants of the development of asbestosis in exposed workers, we obtained 53 phenotypes of the human leucocyte antigen (HLA)-A, B, C, and DR antigens in 72 long-term workers of the mines and mills of Quebec and in a reference population of 150 residents. Among the asbestos workers, 32 did not have any abnormality and 40 had asbestosis. The 2 groups did not differ in term of age, exposure, or cigarette smoking habits. In agreement with previous reports, we found no significant change in frequency of the HLA-A, B, or C phenotypes. Furthermore, we did not find any significant change in the frequency of 10 phenotypes of the HLA-DR loci. We conclude that immunogenetic factors are not major predisposing determinants of asbestosis.

Aged↗

PubMed1987

Chronic allergic airway disease in the sheep model: functional and lung-lavage features.

We developed an animal model of chronic allergic airway disease by repeatedly exposing nine sheep to tracheal instillation of ascaris antigen until stable increase in lung resistance at three times control in six reactive sheep (group C) was obtained. They were then compared to the three nonreactive sheep (group B) and a control group of eight sheep exposed to saline only (group A) in terms of pulmonary function tests and bronchoalveolar lavage (BAL) analyses. Lung resistance was 1.5 +/- 0.3 cm H2O/L/sec in group A, 1.8 +/- 0.3 in group B, and 5.9 +/- 1.3 in group C. Trapping volume (functional residual capacity by plethysmography and by helium rebreathing technique) was 0 +/- 0.1 L in group A, 0.05 +/- 0.1 in group B, and 0.51 +/- 0.17 in group C. Upstream resistance at peak flow did not differ between any two groups, but upstream resistance near residual volume was 1.8 +/- 0.3 cm H2O/L/sec in A, 6.2 +/- 1.0 in B, and 28 +/- 6 in C. In BAL, total cells were 25 +/- 5 X 10(4)/ml in A, 35 +/- 8 in B, and 31 +/- 6 in C. Macrophages in BAL were 16 +/- 2 in A, 27 +/- 9 in B, and 24 +/- 4 in C. Neutrophils were 0.5 +/- 0.2 in A, 3.4 +/- 2.5 in B, 2.8 +/- 1.5 in C. Eosinophils were 0.1 +/- 0.1 in A, 0.5 +/- 0.2 in B, and 0.9 +/- 0.3 in C (p less than 0.05 group C versus group A). Total proteins, albumin, alkaline phosphatase, and fibronectin did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

PubMed1987

Quantitative gallium 67 lung scan to assess the inflammatory activity in the pneumoconioses.

Gallium 67 lung scan has recently become increasingly used to evaluate the biological activity of alveolitis of interstitial lung diseases and to stage the disease process. In order to have a more precise and objective indicator of the inflammatory activity in the lung, we and others have developed computer-based quantitative techniques to process the 67Ga scan. In this report, we compare the results of three such computer-based methods of analysis of the scans of 38 normal humans and 60 patients suspected to have pneumoconiosis. Results of previous investigations on the mechanisms of 67Ga uptake in interstitial lung disease are reviewed. These data strengthen the view that quantitative 67Ga lung scan has become a standard technique to assess inflammatory activity in the interstitial lung diseases and that computer-based method of analysis of the scan provides an index of inflammatory activity of the lung disease that correlates with lung lavage and biopsy indices of inflammation in the lung tissue.

Asbestosis↗

PubMed1987

The lung biological activity of American attapulgite.

Attapulgite is a fibrous mineral industrially consumed at the rate of over a million tons per year but the biological activity of the material is not fully known. To evaluate the in vivo toxicity of the fibrous material, we exposed the tracheal lobe of 16 sheep to a single exposure of either 100 ml saline, 100 mg UICC asbestos fibers in 100 ml saline, 100 mg short asbestos fibers in 100 ml saline, or 100 mg attapulgite in 100 ml saline. The animals were studied by bronchoalveolar lavage (BAL) at Days 2, 12, 24, 40, and 60 and by autopsy at Day 60. In the saline-exposed sheep, BAL and lung histology did not change. In the UICC asbestos-exposed animals, we reproduced the BAL changes previously reported (R. Bégin, M. Rola-Pleszczynski, S. Massé, Y. Berthiaume, and G. Drapeau, 1985, Environ. Res. 36, 389-404). In the short asbestos-exposed sheep, there were no significant BAL changes. In the attapulgite sheep, we found significant and sustained increases in total BAL cells (X2, P less than 0.05), macrophages (X2, P less than 0.05), neutrophils (X5, P less than 0.01), fibronectin (X2-3, P less than 0.05), lactate dehydrogenase (X2, P less than 0.05), beta-glucuronidase (X2, P less than 0.05), but BAL cellularity returned to control levels by Day 60 whereas in the UICC asbestos-exposed sheep, it remained significantly above control. Lung histology demonstrated the characteristic peribronchiolar fibrosing alveolitis in the UICC asbestos-exposed sheep, whereas macrophagic alveolitis with minimal airway distortion was seen in the short asbestos-exposed sheep and in all of the attapulgite-exposed sheep but three which had typical peribronchiolar alveolitis quite similar to that observed in UICC-exposed sheep, but of lower intensity. In conclusion, the study documents that attapulgite is not an inert material for lung tissue; it does produce a macrophagic and neutrophilic alveolitis in the early inflammatory phase of lung reaction with peribronchiolar involvement in some sheep. Whether or not this initial attapulgite induced alveolitis leads to lung fibrosis remains to be evaluated in a longer follow-up study of attapulgite-exposed animals.

Animals↗

PubMed1987

CT assessment of silicosis in exposed workers.

For evaluation of the clinical usefulness of CT of the thorax in workers exposed to silica, 58 workers with long-term exposure to silica in the granite and foundry industries of the Eastern Townships of Quebec were examined. CT scans were compared with standard posteroanterior chest radiographs by using the International Labour Office 1980 grading system for silicosis. Six areas of the lung in each patient were assessed by both techniques for profusion (number) of opacities (small nodules), coalescence, and the presence of large opacities. CT scans and chest radiographs yielded similar average scores for detection of opacities. CT identified significantly more coalescence and large opacities in patients with simple silicosis. In patients with complicated silicosis, CT results were comparable with those of chest radiographs. CT of the thorax in workers exposed to silica does not identify more patients with minimal parenchymal disease, but it does detect earlier changes of coalescence.

Humans↗