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Biomedical subjects

R Bégin

Publications and source records attributed to R Bégin.

At least 109 records · Page 6Linked to original sources
PubMed1983

Asbestos-induced lung injury in the sheep model: the initial alveolitis.

In order to study the cellular and biochemical changes in early asbestosis, three groups of sheep were repeatedly exposed to intratracheal instillations of either saline (controls), low doses of UICC chrysotile asbestos (LD), or high doses of the fibers (HD) until an alveolitis was observed in all HD sheep during the twelfth month of exposure. All sheep were studied bimonthly by transbronchial lung biopsy (LB), bronchoalveolar lavage (BAL), pulmonary function tests (PFT), and chest roentgenograms (CXR). While LBs of the HD sheep demonstrated large accumulations of monocyte-macrophages in the alveolar and interstitial spaces, those of controls and LD sheep did not. In BAL, there was no difference in total and differential cell counts between groups, but the BAL lymphocyte proliferative capacity was clearly depressed in all asbestos-exposed sheep. In the BAL supernatant, total proteins (mainly albumin, beta + gamma globulins) and lactate dehydrogenase were significantly elevated in the HD group only. This alveolitis was associated with a fall in vital capacity, lung compliance, diffusing capacity, and arterial PO2. Abnormalities on CXR appeared 3 months later. Thus, the cellular and biochemical features of early asbestosis are clearly distinct from those reported in idiopathic pulmonary fibrosis.

Alveolitis, Extrinsic Allergic↗
PubMed1983

Assessment of progression of asbestosis in the sheep model by bronchoalveolar lavage and pulmonary function tests.

To study the relationship between the results of bronchoalveolar lavage and pulmonary function tests during induction and progression of asbestosis, three groups of six sheep were exposed repeatedly by intratracheal injection to either saline (controls), low doses of Canadian chrysotile UICC asbestos (cumulative exposure 328 mg) (low-dose group), or high doses of the same fibres (cumulative dose 2282 mg) (high-dose group) until there was clear evidence of alveolitis from the lung biopsy specimens of all sheep of the high-dose group. During the course of this induction and for the following eight months lung biopsies, bronchoalveolar lavage and pulmonary function tests were performed at two-month intervals. At the time of initial alveolitis in the high-dose group there was no significant change in the cellularity of the bronchoalveolar lavage fluid, but static lung compliance (Cst), vital capacity (VC), arterial oxygen tension (Pao2), and diffusion capacity (DL/VA) were significantly lower than in the other groups. In the following months, as the alveolitis evolved into a fibrosing process, macrophages and neutrophils from the bronchoalveolar lavage fluid increased significantly and pulmonary function deteriorated. Proteins and enzymes in the bronchoalveolar lavage fluid also increased significantly in the high-dose group. These data show that in the sheep model of asbestosis simple tests of pulmonary function correlate well with histological changes and changes in the bronchoalveolar lavage fluid in the course of the disease and can be used to assess progression of asbestosis.

Animals↗
PubMed1983

Pulmonary uptake of gallium-67 in asbestos-exposed humans and sheep.

To evaluate the 67Ga lung uptake as an indicator of inflammatory activity in asbestosis, we obtained 67Ga lung scans in 58 long-term asbestos workers. The 67Ga localized excessively in the lungs of 17 of the 21 workers with asbestosis. Among workers without sufficient criteria for the diagnosis of asbestosis, the 67Ga scan index was significantly increased in 43% (16 of 37). Among the 16 with positive 67Ga scan, abnormal pressure-volume curve and/or gas exchange data were found in 87%, whereas in the 21 workers with negative 67Ga scan, similar abnormalities were found in only 29%. In the sheep model of the disease, bronchoalveolar analysis after 67Ga scan demonstrated that the excessive uptake of 67Ga in asbestosis is caused by enhanced serum protein leakage and macrophage accumulation in the lung. Thus, 67Ga scanning in asbestos workers may be a useful indicator of early lung damage.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Biochemical components of bronchoalveolar lavage in early experimental asbestosis of the sheep: phospholipase A2 activity, prostaglandin E2 and proteins.

Biochemical analyses of bronchoalveolar lavage (BAL) supernatants of sheep treated with weekly intratracheal instillations (for 6 months) of saline, 2 mg, or 128 mg of asbestos (chrysotile B; UICC) were performed. Our results showed that proteins (either total or its various components) and phospholipase A2 activity were unchanged in the low exposure group as compared to controls. However, in the high exposure group, with histopathological evidence of early asbestosis, there were significant increases in total proteins, albumin, alpha 2-globulin, beta- and gamma-globulins as well as phospholipase A2 activity of BAL fluid. Prostaglandin E2 activity was significantly increased in both low and high dose groups. These changes in protein and lipid components of BAL following asbestos exposure constitute early indices of lung inflammatory reactions which may contribute to the development of asbestosis.

Animals↗
PubMed1983

Heterogeneity of bronchoalveolar lavage cellularity in stage III pulmonary sarcoidosis.

Three cases of stage III pulmonary sarcoidosis are presented. Bronchoalveolar lavage (BAL) revealed normal cell differential counts in the right middle lobe of each patient, but high-intensity lymphocytic alveolitis in the right upper lobe. These findings suggest that BAL should be done in multiple segments of the lung to obtain a truly representative picture of the intensity of the alveolitis in stage III pulmonary sarcoidosis.

Adult↗
PubMed1983

Computer-based quantitative analysis of gallium-67 uptake in normal and diseased lungs.

To study the 67Ga lung uptake as an index of inflammatory activity, we developed a computer-based method to process the data obtained from the 67Ga scan. Background radioactivity below the kidneys was subtracted from counts in all areas and given a score of 0; the maximal liver uptake was scored as 16. Radioactivity over six lung fields was scored by the computer between 0 and 16 and averaged to yield a mean 67Ga lung uptake index. This index of 67Ga lung accumulation correlates with histopathologic scores of inflammation in lung tissue and with bronchoalveolar lavage (BAL) levels of 67Ga radioactivity retrieval. This study reports the quantitative analysis of 67Ga lung uptake in normal subjects and patients with various pulmonary diseases. This method provides an objective index of inflammatory activity in lung tissues, and it is simple, sensitive, and discriminative.

Adult↗
PubMed1983

Asbestos exposure enhances the release of fibroblast growth factor by sheep alveolar macrophages.

Interaction between free airway cells (FAC) and lung fibroblasts was studied in a sheep model of asbestosis. Three groups of six sheep each received, respectively, by repeated intratracheal instillations, saline (control), 328 mg (low dose), and 2282 mg (high dose) of UICC chrysotile B asbestos. Sixteen months after the first instillation, FAC obtained by segmental bronchoalveolar lavage (BAL) of sheep in each group were incubated for various intervals, and the effect of their culture supernatants (FAC-SN) on human embryonic lung fibroblast proliferation was determined. FAC-SN from control animals stimulated thymidine (3H-TdR) incorporation by lung fibroblasts two- to threefold compared to untreated cultures. Maximal stimulation was observed at 48 hr and was correlated with a significant increase of the fibroblast population at 72 hr. FAC population from control sheep consisted primarily of macrophages (79%) and lymphocytes (15%), and separation of these two cell populations indicated that only macrophages produced the fibroblast-stimulating activity. Production occurred within 1 hr of incubation and was maximal between 2 and 4 hr. This activity was nondialyzable and stable at 56 degrees C for 30 min, but was destroyed at 80 degrees C and low pH. Moreover, FAC-SN from sheep exposed to asbestos stimulated 3H-TdR incorporation by fibroblasts five- to sixfold compared to two- to threefold for control FAC-SN. This activity may modulate fibrogenesis and may be involved in the eventual fibrogenic response to asbestos.

Animals↗
PubMed1983

Rapid in vivo assessment of toxicity of respirable particles: a concise report.

To study the in vivo toxicity of respirable particles, bronchoscopic catheterization of the sheep tracheal lobe was used to expose a limited area of the lung. After control studies, 3 groups of 6 sheep received one exposure to either 100 ml saline, 100 mg of latex beads (1.0 mu diam.) in saline or 100 mg of UICC Canadian chrysotile asbestos in saline. The animals were studied at day 1, 8, 15, 22 and 29 by pulmonary function tests (PFT) and bronchoalveolar lavage (BAL). At day 29, the sheep had chest roentgenograms (CR) and were autopsied. In all sheep, PFT did not changed and CR showed minimal infiltrates only in the asbestos-exposed sheep. In the saline sheep, BAL and lung histology did not change. In the latex sheep, at day 1 total BAL cells increased to 370%, macrophages to 215% and neutrophils to 650% (P less than 0.01) without change in BAL proteins or enzymes. These returned to control levels at day 8 and after except for a slight increase in BAL neutrophils. The lung histology showed inflammatory changes without architectural distortion. In the asbestos sheep, the day 1 response was comparable to latex group in terms of BAL cellularity but BAL neutrophils remained significantly elevated at 40% total BAL cells at day 8, 15, 22 and 29. Also lactate dehydrogenase (LDH) and beta-glucuronidase in BAL were significantly elevated from day 1 to day 29. At autopsy, the tracheal lobe of asbestos sheep had pneumonia-like neutrophilic infiltrates in the surroundings of the peripheral airways with early peribronchiolar fibrosis. This new in vivo model can clearly and rapidly differentiate the relative toxicity of respirable particles in the lung tissue and thus should be a useful tool in environmental lung research.

Animals↗
PubMed1982

Perifused alveolar macrophages. A technique to study the effects of toxicants on prostaglandin release.

A technique was developed for perfusing free airway cells (FAC) obtained by guinea-pig bronchoalveolar lavage. 10 x 10(6) FAC (mostly macrophages) were placed on the filter of a Nuclepore chamber perfused with Tyrode's solution or with Eagle's Minimal Essential Medium (MEM); the effluent was collected at intervals and te release of prostaglandin E2 by the perifused cells was used as an index of the inflammatory reaction to toxicants. Zymosan, asbestos fibers and soluble toxic agents stimulated the synthesis of prostaglandins while indomethacin abolished it. Our technique of FAC perifusion allows the sequential study of biochemical events involved in macrophage defense mechanisms as well as providing a simple test for the evaluation of various toxicants.

Animals↗
PubMed1982

Airway disease in a subset of nonsmoking rheumatoid patients. Characterization of the disease and evidence for an autoimmune pathogenesis.

Previous investigations of airway disease in rheumatoid patients have been oriented toward establishing the prevalence of the disease, but the pathogenesis and the time course of the airflow obstruction in rheumatoid disease are still unclear. In this study, we analysed the clinical, serial pulmonary function and histopathologic data of six rheumatoid patients who had never smoked but who had airflow limitations documented repeatedly up to 10 years previously. We have attempted to characterize the site, nature and evolution of the chronic airway disease in this group of patients. Bronchiectasis was excluded in all patients by bilateral bronchography. Clinical and histopathologic evidence of the Sjörgen autoimmune exocrinopathy was documented in five of the patients, and the sixth patient had lymphoplasmocytic infiltrates of the labial glands without obstruction of the lumen or destruction. By pulmonary function tests and histopathologic examination of four open lung biopsies, the airway disease was found to be located predominantly in the peripheral airways of the lung. On each biopsy, the lesions were in different stages of activity, but on all specimens there was a definite predilection for selective bronchiolar injury. Early stage lesions were characterized by mononuclear cell infiltrates of the peribronchiolar tissue which led to deformation of airway lumen, focal mucosal extension and ulceration. Subsequently, the inflammatory reaction was replaced by fibroblastic proliferation, and in the end stage of the disease, there was complete obliteration of many bronchioles by collagenized fibroblastic tissue. From regression analyses of serial pulmonary function tests of these patients, it was concluded that (1) the airway disease in our patients who did not smoke progressed inevitably but not uniformly and (2) deterioration of pulmonary functions was more rapid in our patients than it was in the cigarette smokers who had chronic obstructive lung disease. This study also documents major dysfunctions of the chest wall mechanics which appear to contribute to the restriction of lung volumes in some rheumatoid patients.

Adult↗
PubMed1982

Postnatal maturation of the respiratory response to O2 in awake newborn lambs.

The present study was designed to analyze maturation of the respiratory response to hypoxia and hyperoxia in 41 newborn lambs aged 2-90 days. The O2 respiratory response was tested by progressive isocarbic hypoxia while minute ventilation (VE), tidal volume (VT), respiratory frequency (f), mean inspiratory flow (VT/TI), were measured. The occlusion pressure (P0.1) was also determined as an index of the neuromuscular output of the drive to breathe. The strength of the peripheral chemoreceptors was evaluated by the transient O2 100% inhalation test and by the early change in VE (delta VE) to cyanide (KCN) infusion. In all of the 2-, 10-, 30-, and 90-day groups of lambs, hypoxia induced a significant increase in P0.1 and in delta VE, delta VT, f, and VT/TI. The 2-day-old lambs showed a significantly lower response to hypoxia than did the older groups. Similarly, during the hyperoxia test and KCN infusion. Delta VE was smaller in the 2-day lambs than in the other lambs. We conclude that the postnatal maturation of the ventilatory response to O2 occurs in the first 10 days of life in newborn lambs and it is largely due to an increase in sensitivity of the O2 chemoreceptors.

Animals↗
PubMed1982

Depression of respiration induced by metabolic acidosis in newborn lambs.

The present study evaluates the strength of the drive to breathe and the respiratory response of newborns to metabolic acidosis. The study consisted in a HCl mild and severe acidosis induced in 30 unanesthetized newborn lambs aged from 2 to 90 days. During mild acidosis (pHa = 7.20), all lambs experienced an increase in the minute ventilation (VE) associated with an increase in the neuromuscular drive of breathing which was measured by the occlusion pressure (PO.1). However, with severe acidosis (pHA = 7.10) both VE and PO.1 decreased towards the preacidotic level in the 2- and 10-day-old lambs but continued to increase in older lambs. It is concluded that newborn lambs have an immature drive of breathing and a blunted respiratory output to metabolic acidosis.

Acidosis↗
PubMed1982

Pathogenesis of respiratory insufficiency in myotonic dystrophy: the mechanical factors.

We have previously shown that the chemosensitivity of the respiratory centers is well preserved in myotonic dystrophy but that the ventilatory output is reduced. The present study was designed to determine at which degree of ventilatory performance weakness and fatigability of the respiratory muscles are interfering with ventilation and which mechanical factors contribute to the tachypnea of patients with myotonic dystrophy at rest and during low ventilatory output. We studied 10 patients with the disease and 10 normal control subjects. The strength of respiratory muscles was assessed by measurements of maximal pressure-volume diagrams generated against airway occlusion. Performance was evaluated during 1-min maximal voluntary ventilation (1-min MVV) test, during 7-min 7% CO2 breathing and during quiet breathing. Occlusion pressure (P0.1) in patients at rest was slightly higher than in control subjects, and during CO2 breathing, it was similar to that of control subjects. Maximal static pressure was reduced in patients to an average of 35% of that of control subjects. During the 1-min MVV test, there was a 50% reduction in esophageal and transdiaphragmatic pressure output (Pes, Pdi) in patients, resulting in similar reduction in ventilation (VE) and patients had rapid cycles of alternating dominant thoracic and abdominal volume displacements (Vrc/Vabd) suggesting respiratory muscle fatigue. During the 3- to 4-fold increase in breathing drive induced by hypercapnia, pressure output and the Vrc/Vabd were identical in both groups. However, ventilation was reduced in patients who had tachypneic respiration. In patients, tachypnea was also observed during quiet breathing. This tachypnea was associated with higher impedance of the respiratory system (Zrs) in patients and identical impedance of the lung (ZL) in both groups. In addition, Pdi during tidal volume was significantly higher in patients. These data demonstrate that the ventilatory output in out patients was altered predominantly by weakness and fatigability of the respiratory muscles during high ventilatory performance and by increased impedance of the respiratory system at lower degrees of ventilation.

Adolescent↗
PubMed1982

Morphologic features and function of the airways in early asbestosis in the sheep model.

Previous studies of asbestos exposure in humans and small animals have suggested that air flow limitation associated with small airway disease may be an early manifestation of asbestosis, but the subject is still controversial. In this report, we present the airway morphologic aspects and function of our sheep model of the disease. Three groups of 6 sheep were exposed to repeated intratracheal injections of either saline (control group), 2 mg of UICC Canadian chrysotile asbestos in saline (low exposure group), or 128 mg of the same fibers (high exposure group). At the end of the twelfth month of exposure, an alveolitis had developed in the high exposure group only. Detailed pulmonary function tests were followed within 48 by lung biopsies according to methods described, to which were added air-helium flow-volume curves. Lung biopsies in control and low exposure groups did not demonstrate significant morphologic changes, whereas all biopsies in the high exposure group showed alveolitis characterized by an alveolar and interstitial accumulation of macrophages and mononuclear cells without interstitial fibrosis. On all biopsies, over half of the airways were altered by a similar peribronchiolar process, which at times compressed the peripheral airways. Functionally there was no significant difference between low exposure and control groups. However, compared with the control group, the high exposure group had significantly lower vital capacity (2.0 +/- 0.1 versus 2.9 + 0.1 L, p less than 0.01), lower static lung compliance (91 + 13 versus 132 + 9 ml/cmH2O, p less than 0.05), higher isoflow volume (2.15 + 0.08 versus 1.4 + 0.1 L, p less than 0.01), and higher upstream resistance below the isoflow volume (3.3 + 0.2 versus 1.3 + 0.3 cmH2O L/s, p less than 0.02). These data demonstrate that in the early asbestos-induced peribronchiolar alveolitis of the sheep, which restricts lung volumes, there is a concomitant small airway disease that significantly limits air flow.

Animals↗
PubMed1982

Asbestos related changes in pulmonary and systemic immune responses--early enhancement followed by inhibition.

We recently developed an animal model in order to study the pulmonary and systemic reactions following exposure to environmental pollutants. In this model, conscious sheep received repeated intratracheal instillations of a suspension of 0 (controls), 2mg (low dose) or 128 mg (high dose) of chrysotile asbestos fibres over a 12 month period. A significant dose-dependent enhancement in proliferative responses of pulmonary free airway cells (FAC) to four mitogens was observed after a first instillation. A somewhat weaker stimulation was also observed in peripheral blood mononuclear leucocytes (PBML). At 6 months, the high dose animals no longer displayed the dose-dependent enhancement of FAC responses and manifested actual depression of PBML responses. At 12 months, all asbestos exposed animals showed impaired responses of FAC, whereas only the PBML of high dose animals were showing such an impairment. These data suggest that asbestos exposure has a dose-dependent initial enhancement of local pulmonary as well as systemic responses to mitogens while prolonged exposure and higher doses can subsequently lead to a relative depression of local and systemic cellular immune activity. Although responsive early after asbestos exposure, systemic immunity appears to lag behind local immunity in the late depressive effect of asbestos fibres on mitogen responsiveness. In addition to these cell-directed effects serum factors seem to play an inhibitory role in lymphocyte responses to mitogens in animals repeatedly exposed to asbestos.

Animals↗