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Biomedical subjects

J L Wright

Publications and source records attributed to J L Wright.

At least 145 records · Page 8Linked to original sources

Mineralogic correlates of fibrosis in chrysotile miners and millers.

To determine which mineral parameters relate to the degree of interstitial fibrosis (asbestosis) in the lungs of chrysotile miners and millers, we graded fibrosis histologically and correlated fibrosis grades with fiber concentration and mean size, surface area, and mass, and with total sample fiber length, surface area, and mass in 21 cases. A positive correlation of fibrosis grade with tremolite concentration and a lesser correlation with chrysotile concentration was found for whole lungs, specific sites within lungs, and, for tremolite, single microscopic fields. No correlations were found for measures of chrysotile fiber size, surface area, or mass, but tremolite mean fiber length, aspect ratio, and surface area were, surprisingly, negatively correlated with fibrosis grade. Measures based on total rather than on mean case or site parameters failed to show correlations with fibrosis. We conclude that: (1) degree of pulmonary fibrosis reflects fiber concentration at both a bulk and a microscopic level; (2) mean fiber length and parameters related to mean fiber length also correlate with fibrosis grade, but, contrary to predictions from animal studies, this correlation is negative, suggesting that short fibers may be more important in the genesis of pulmonary fibrosis than is commonly believed; (3) there is no evidence that parameters such as total fiber length, surface area, or mass provide predictors of degree of fibrosis.

Aged↗

Fibre content of lung in amphibole- and chrysotile-induced mesothelioma: implications for environmental exposure.

Using 9 pairs of exposure-period-matched shipyard and insulation workers (amphibole exposure) and chrysotile-industry workers (chrysotile exposure) with mesothelioma, and an additional 9 pairs of workers with asbestosis, we found that the chrysotile workers with mesothelioma had 400 times the median lung fibre burden of the shipyard and insulation workers with mesothelioma. Mesothelioma in the chrysotile workers was associated with a 3 times greater median fibre burden than asbestosis, whereas in the shipyard and insulation workers mesothelioma was associated with only 1/35 the median amphibole burden seen in cases of asbestosis. In the chrysotile workers, the tremolite:chrysotile ratio and the mean fibre sizes were the same for both mesothelioma and asbestosis cases. These data suggest that total fibre load is crucial to the induction of mesothelioma by chrysotile, and that this phenomenon requires, on average, as high a fibre burden as induction of asbestosis by chrysotile. By contrast, for amphibole exposure, mesothelioma appears at a much lower fibre burden than asbestosis. The fibre types appear to differ by at least two orders of magnitude in their potential for inducing mesothelioma. Estimates of risk from environmental exposure must take these differences into account.

Aged↗

The changes in airways structure associated with reduced forced expiratory volume in one second.

We compared the structure of the membranous and respiratory bronchioles of resected lungs from 111 patients with a normal predicted forced expiratory volume in one second (FEV1) to the structure of these airways from 45 patients with an FEV1 reduced below the 95% confidence limits for height and age. Membranous and respiratory bronchioles of less than 2 mm in internal diameter were counted and their diameter and wall thickness were measured. The data show that there were more membranous bronchioles of internal diameter less than 0.4 mm in patients with reduced FEV1. The wall thickness of respiratory bronchioles was increased in the obstructed group and there was also an increase in the ratio of wall thickness to lumen diameter in these airways. The walls of membranous bronchioles were not increased in thickness but there was an increase in the ratio of wall thickness to lumen diameter. Although the data is consistent with the hypothesis that airways obstruction in patients with chronic obstructive pulmonary disease is due to thickening of the airway wall and narrowing of the airway lumen, we cannot rule out distortion of the membranous bronchioles by loss of elastic recoil.

Aging↗

Comparison of inflammatory cells in bronchoalveolar fluid with those in the lumen and tissue peripheral airways and alveolar airspace.

This study compares the inflammatory cell types in the alveolar airspace, peripheral airways, and bronchoalveolar lavage fluid of 65 human lung specimens removed surgically. The data show that the cellular population in the airway tissue is composed of approximately 2-4% neutrophils, and 96-98% mononuclear inflammatory cells. This contrasts with the airway lumen, which contains approximately 5-14% neutrophils, while the alveolar airspace contains 3%, and the lavage fluid contains 4% neutrophils. There is a significant correlation between the percentage of PMN in the walls of the membranous and respiratory bronchioles, as well as between the walls and lumens of respiratory and membranous bronchioles. We conclude that: 1. The lumen of the membranous bronchioles contains a greater percentage of PMN than the lumen of the respiratory bronchiole or of the alveoli. 2. Neutrophils are present in the alveolar airspace. 3. The percentages of PMN present in the lumen of the respiratory bronchiole, alveoli, and lavage fluid are similar. 4. The correlation between percentage of PMN in airway wall and lumen suggests a cellular equilibrium between the 2 sites. 5. In this groups of lungs, there is an apparent stereotypic inflammatory response in that the percentages of PMN in the different anatomical sites are relatively similar from case to case. Various workers have suggested that analysis of the cell types present in bronchopulmonary lavage can be used as a therapeutic index, or as a diagnostic test. Our data suggest that lavage does indeed sample the lower airways and alveolar spaces, and that such usage may well be justified.

Animals↗

Airway inflammation and peribronchiolar attachments in the lungs of nonsmokers, current and ex-smokers.

To determine the effect of smoking cessation on the number and type of inflammatory cells in the walls of the small airways, we examined the lungs of 13 lifetime nonsmokers, 25 patients who had stopped smoking for at least 6 months, and 49 current smokers. We found that, compared to nonsmokers, both ex-smokers and current smokers had significantly increased numbers of total inflammatory cells and polymorphonuclear leukocytes in the walls of the membranous, but not the respiratory bronchioles. These differences were found even when there was no emphysema present in the gross lung specimen, and current and ex-smokers were matched with the nonsmokers for age. The current and ex-smokers had similar numbers and types of inflammatory cells in the airway wall, and in both current and ex-smokers there was no difference in inflammatory cell number or type when the groups were subdivided based on emphysema score less than or greater than 5. Analysis of peribronchiolar alveolar attachments showed an increase in percentage of alveoli destroyed associated with an increased interalveolar distance in both the current and ex-smokers, which did not change with the presence of emphysema. Pulmonary function was similar in the current and ex-smokers, and the group with emphysema showed greater functional abnormalities compared to the group with little or no emphysema. We conclude that the cigarette smoking habit induces a stereotypical inflammatory response in the small airways. This inflammatory response does not abate after smoking cessation, and in this cross-sectional study, appears to be independent of the presence or absence of emphysema, but related to destruction of the peribronchiolar alveolar attachments.

Aged↗

Airway inflammatory cells in upper and lower lobes in lungs of patients with and without emphysema.

Tissue destruction seen in emphysema is thought to be due to the proteolytic enzymes released by inflammatory cells. Since centriacinar emphysema is worse in upper lobes, it has been suggested that inflammation should be more marked in the upper lobes. To ascertain whether the inflammatory cell population in the walls and lumens of airways is similar in the upper and lower lobes and whether this distribution is altered by the presence of emphysema, we examined the number and types of airway inflammatory cells in 10 surgical pneumonectomy specimens. We found that there was no difference between the upper and lower lobes in the numbers and types of inflammatory cells in the airway walls and lumens. This was true whether or not emphysema was present. We conclude that, in this cross-sectional study, the presence of emphysema in the upper lobes of lung is not associated with an increased number of acute inflammatory cells.

Aged↗

Grommets and cholesteatoma in children.

Cholesteatoma in children may be a sequel to chronic exudative otitis media with tympanic membrane retraction but the role of grommets in the possible facilitation of squamous epithelial invasion into the middle ear is not yet clear. A retrospective study was made of the history and prior treatment in 25 children who underwent mastoidectomy for cholesteatoma at St. Mary's Hospital between 1975 and 1986. Thirteen patients had undergone previous middle ear aeration procedures which included myringotomy, cortical mastoidectomy and grommets. There was no difference in the site or severity of cholesteatoma in the operated and non-operated cases. Of the seven patients with a history of multiple grommets three had primarily attic, and three had primarily mesotympanic disease. The latter had greater ossicular erosion. One patient with an intact tympanic membrane had grommet insertion subsequently developed a cholesteatoma. While cholesteatoma due directly to the presence of grommets is rare, it appears that children who require multiple grommet insertions constitute a high risk group and should be very closely monitored.

Adolescent↗

Pulmonary vascular structure and function in chronic obstructive pulmonary disease.

Cardiac catheterization data from eight patients with severe chronic obstructive lung disease and pulmonary hypertension at rest (greater than 25 mm Hg) were compared with those obtained from 14 patients with mild to moderate disease whose pulmonary artery pressure was within the normal range at rest (mean 15 (SEM 1) mm Hg), but increased with exercise (30 (2) mm Hg). We obtained lung sections from necropsy material from the group with severe disease, and from surgical specimens in the group with mild to moderate disease, and compared the structure of the vasculature in these groups with that obtained from surgical specimens in a non-smoking control group of seven patients. Oxygen administration either at rest or during exercise did not greatly affect the pulmonary arterial pressures. When cardiac index was plotted against pulmonary artery pressure at rest and during exercise and extrapolated to the axis there was no evidence for a critical closing pressure in either group. The vessels in the groups with mild to moderate and severe chronic obstructive lung disease showed intimal thickening (each 19% (SD 0.5%)) by comparison with the non-smoking group (16% (0.5%]. The group with severe disease, in addition, had medial hypertrophy (27% (0.5%) versus 24% (SD 1%) in the non-smoking group). These data are consistent with the idea that the diseased vessels are distorted and rigid. The lack of effect of breathing oxygen on the vascular response at rest and during exercise suggests that hypoxic vasoconstriction has a minimal role in the pulmonary hypertension of chronic obstructive lung disease. The data suggest that the intimal changes could narrow the vessel calibre in those patients with mild to moderate disease, and that the thickened media present in the vessels from patients with severe disease may act in concert with the enlarged intima to produce more severe vascular obstruction.

Blood Pressure↗

Exponential analysis of the pressure-volume curve. Correlation with mean linear intercept and emphysema in human lungs.

We investigated the effect of obvious emphysematous lesions and the mean airspace size in the lung surrounding these lesions on the exponential constant K of the lung pressure-volume curve. The severity of the centrilobular emphysematous (CLE) lesions was determined in resected lung specimens, and the mean linear intercept (Lm) was measured on random histologic sections taken from regions without obvious emphysema. The exponential constant K was determined by fitting lung pressure-volume data obtained from the patient just prior to resection to the equation V = A - Be-KP. This allowed us to compare patients with little or no emphysema that had either normal (0.16 +/- 0.03 SD; n = 12) or increased (0.27 +/- 0.04 SD; n = 12) K to other patients that had severe emphysema but either normal (0.17 +/- 0.01 SD; n = 10) or increased (0.25 +/- 0.03 SD; n = 10) K. In subjects without emphysema, K was significantly related to Lm, suggesting that K is a measure of mean alveolar size. In the subjects with emphysema, a lower value for K was associated with more severe airway dysfunction and gas trapping. We conclude that K reflects airspace size except when airway closure subtracts the contribution of lung units from the deflation pressure-volume curve.

Aged↗

Quartz but not iron oxide causes air-flow obstruction, emphysema, and small airways lesions in the rat.

Recent epidemiologic studies have suggested that some workers exposed to inorganic dusts develop air-flow obstruction independent of or greater than that produced by cigarette smoke; the morphologic basis of this effect is unknown. To investigate this problem, we administered saline alone, 10 mg iron oxide (an inert dust), or 10 or 30 mg of quartz to rats by intratracheal instillation. Animals were killed after 30 days, and pulmonary function and morphologic changes were examined. The iron oxide group was similar to the saline control group in all functional and morphometric parameters. However, both quartz-exposed groups showed evidence of air-flow obstruction, with more severe abnormalities in the high dose group. These findings correlated with morphometric observations of emphysema and thickened airway walls, with changes again more severe in the high dose group. Early silicotic nodules were also present in the latter animals. We conclude that in addition to the classic lesions of nodular silicosis, quartz can produce morphologic and functional changes of air-flow obstruction; no such changes are seen with iron oxide. These observations may explain the air-flow obstruction seen in workers exposed to mineral dusts.

Airway Obstruction↗

Cigarette smoke potentiates asbestos-induced airflow abnormalities.

It has been suggested that exposure to both asbestos and cigarette smoke can produce worse parenchymal lung disease than exposure to asbestos alone. Using a guinea pig model of asbestos administration that produces primarily airway disease and associated airflow abnormalities, we showed previously that the combination of asbestos and smoke acts synergistically to produce more marked increases in tissue collagen, fibrosis of airway walls, and early interstitial fibrosis than are seen with asbestos alone. To investigate the functional effects of these morphological and biochemical abnormalities, pulmonary function tests for volumes and flows, including lung volumes, pressure-volume curves, and flow-volume curves, were performed. By themselves, both smoke and asbestos produced increases in total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC); the two agents together made all these changes worse than either one alone. Both smoking and asbestos moved the pressure-volume curve upward, and the effects of the two agents together were again greater than either alone. Similarly, both smoke and asbestos decreased flows, and the two agents produced more severe impairment than either one by itself. The changes in volumes, pressure-volume curve, and flows correlated with both increased thickness of small airway walls and increases in airspace size. These observations indicate that, at least in this guinea pig model, cigarette smoke can potentiate the functional consequences of asbestos exposure.

Asbestos↗

Inflation of lung biopsies for frozen section.

It is widely accepted that fixation inflation of lung surgical specimens, including open lung biopsies, greatly aids histologic examination and diagnosis. This method is not, however, appropriate for frozen section material. To obviate this problem, we have inflated the specimen with the embedding medium used for frozen section. This procedure provides inflation of the lung sample, increases the ease with which the biopsy is sectioned in the cryostat, and also reduces the shattering commonly seen in standard frozen sections of lung.

Biopsy↗

A new quantitative method for the analysis of monoacylglycerol isomers using 13C nuclear magnetic resonance spectroscopy.

Current methods for determining the regiochemistry of monoacylglycerols are lengthy, tedious and aggravated by the ready isomerization of 2-acyl-sn-glycerols. A new method employs a very rapid adsorption chromatography step in which isomerization is kept to a minimum, followed by formation of the isopropylidene derivatives using mild procedures. These cyclic derivatives of 1- and 3-acyl-sn-glycerols and 2-acyl-sn-glycerols are stable thermally and display certain characteristic 13C NMR resonances. Integration of these resonances yields directly the proportion of monoacylglycerol isomers in the mixture. The method was applied to the analysis of monoacylglycerols produced by enzymatic hydrolysis of synthetic and naturally occurring triacylglycerols.

Glycerides↗

Structure of central airways in current smokers and ex-smokers with and without mucus hypersecretion: relationship to lung function.

Forty-five patients who underwent thoracotomy and lung resection for tumour were studied to compare the structure of the central airways in current smokers and ex-smokers. The patients were divided into four groups: current smokers with mucus hypersecretion (n = 15), current smokers without mucus hypersecretion (n = 14), ex-smokers with mucus hypersecretion (n = 5), and ex-smokers without mucus hypersecretion (n = 11). Quantitative histological studies of the airway wall showed no difference in gland size, smooth muscle, connective tissue, or Reid index between the groups. The central airways of patients with mucus hypersecretion showed increased mucosal inflammation. The five ex-smokers in whom mucus hypersecretion persisted after they had stopped smoking had both central and peripheral airways affected by the inflammatory response, and these patients also had an abnormal result in the nitrogen washout test.

Humans↗

Differential diagnosis of bronchiolitis obliterans with organizing pneumonia and usual interstitial pneumonia: clinical, functional, and radiologic findings.

To assess the role of chest radiography in the differential diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP) and usual interstitial pneumonia (UIP), records of 34 patients with biopsy-proved BOOP (16 patients) or UIP (18 patients) were reviewed. Chest radiographs taken before biopsy were available in 26 patients, clinical information in 33, and pulmonary function data in 22. These data were reviewed independently, without knowledge of the pathologic diagnosis. The clinical symptoms of BOOP were similar to those of UIP, although the duration of symptoms was longer in UIP (P less than .05), and the prevalence of systemic symptoms was higher in BOOP (P less than .025). The physical findings were similar except that finger clubbing was more common in patients with UIP than in those with BOOP (P less than .01). There was no significant difference in lung volumes, flows, or diffusing capacity between BOOP and UIP. The chest radiograph showed distinguishing features between UIP and BOOP in 23 of 26 patients. The most characteristic radiologic finding in BOOP was the presence of patchy areas of air-space consolidation (eight of 11 patients).

Adult↗