Biomedical subjects

B Wiggs

Publications and source records attributed to B Wiggs.

At least 37 records · Page 2Linked to original sources

PubMed1990

Inhibition of antigen-induced airway hyperresponsiveness, but not acute hypoxia nor airway eosinophilia, by an antagonist of platelet-activating factor.

The role of platelet-activating factor (PAF) in Ag-induced airway hyperresponsiveness was evaluated in a guinea pig model using the PAF antagonist SDZ 64-412. Repeated OVA challenge by aerosol (twice weekly x 4 wk) of previously sensitized guinea pigs produced striking airway hyperresponsiveness as determined by pulmonary resistance changes to increasing doses of inhaled acetylcholine given 3 days after the last OVA challenge. Each OVA challenge produced significant hypoxia that was unaffected by oral pretreatment with 20 mg/kg SDZ 64-412, 2 h before each challenge (pO2 = 35 +/- 2 mm Hg for OVA alone vs 40 +/- 6 mm Hg for SDZ and OVA groups, respectively). SDZ 64-412 pretreatment abolished the airway hyperresponsiveness resulting from repeated Ag challenge. Morphometric analysis revealed that SDZ 64-412 treatment had no effect on the increased numbers of eosinophils that infiltrated the airways of OVA-challenged guinea pigs. These results suggest that PAF may be a primary mediator of airway hyperresponsiveness, but not acute bronchoconstriction, induced by repeated Ag challenge. This activity of PAF appears independent of eosinophil recruitment to airways.

Acetylcholine↗

PubMed1990

Mineralogic parameters related to amosite asbestos-induced fibrosis in humans.

We have previously shown that in the lungs of a group of chrysotile miners and millers, grade of interstitial fibrosis (asbestosis) is directly proportional to tremolite fiber or chrysotile fiber concentration but is inversely proportional to mean fiber length and length-related parameters. To compare the effects of the commercial amphibole asbestos amosite on parenchymal fibrosis, we histologically graded fibrosis in four different sites in the lungs of 20 shipyard and insulation workers with heavy amosite exposure and measured by analytic electron microscopy fiber concentration and size in corresponding portions of lung tissue. Fibrosis grade was found to be strongly positively correlated with amosite concentration and negatively correlated with mean fiber size parameters, including fiber length, width, surface area, and mass. A comparison of our present results with our data on the chrysotile miners and millers showed that the regression lines of fibrosis grade versus concentration for amosite, chrysotile, and tremolite were statistically different. These findings indicate that amosite concentration, like chrysotile and tremolite concentration, is closely and directly related to fibrosis at the local lung level. Furthermore, these observations again raise the possibility that short fibers may be more important than is commonly believed in the genesis of fibrosis in man. Last, the concentration comparison data indicate that, fiber for fiber, amosite is more fibrogenic than is chrysotile or tremolite, and indirectly suggest that tremolite is more fibrogenic than is chrysotile.

Aged↗

PubMed1989

The effect of cigarette smoking on neutrophil kinetics in human lungs.

Neutrophils may play a part in the pathogenesis of the centrilobular emphysema associated with cigarette smoking. The capillary bed of the lungs concentrates neutrophils approximately 100-fold with respect to erythrocytes, producing a large pool of marginated cells. We examined the effect of cigarette smoking on the kinetics of this pool of cells, using 99mTc-labeled erythrocytes to measure regional blood velocity and 111In-labeled neutrophils to measure the removal of neutrophils during the first passage through the pulmonary circulation, their subsequent washout from the lungs, and the effect of local blood velocity on the number of neutrophils retained in each lung region. We observed no difference in these measurements between subjects who had never smoked (n = 6) and smokers who did not smoke during the study (n = 12). However, subjects who did smoke during the study (n = 12) had a significantly slower rate of washout of radiolabeled neutrophils from the lung (0.08 +/- 0.04 of the total per minute, as compared with 0.13 +/- 0.06 in smokers who did not smoke during the experiment and 0.14 +/- 0.08 in non-smokers) (P = 0.02). We also observed an increase in the regional retention of labeled neutrophils with respect to blood velocity in 5 of the 12 subjects who smoked during the study, but in none of the other subjects. We conclude that the presence of cigarette smoke in the lungs of some subjects increases the local concentration of neutrophils, and suggest that the lesions that characterize emphysema may be a result of the destruction of lung tissue by neutrophils that remain within pulmonary microvessels.

Adult↗

PubMed1989

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↗

PubMed1989

The distribution of amosite asbestos fibers in the lungs of workers with mesothelioma or carcinoma.

We have previously shown that there are differences in the sizes of fibers of amosite asbestos in different parts of the lung in workers with relatively high asbestos exposure and malignant pleural mesothelioma. To determine whether this distribution pattern is specific to cases of mesothelioma, we compared the fiber distribution in the lungs of 20 cases of mesothelioma and 10 cases of carcinoma of the lung. The two test groups were statistically identical in terms of age, and exposure period, and overall both groups had very similar mean fiber concentrations and mean fiber sizes. When individual sampling sites within the lung were considered, neither group showed preferential fiber concentration in any area. However, there were definite differences in the intrapulmonary fiber size distribution both within and between the two groups: Cases of mesothelioma showed accumulation of lung fibers in the peripheral upper lobe with shorter central upper lobe fibers. The lung cancer cases demonstrated a reverse pattern, with shorter fibers in the peripheral compared to central upper lobe, but accumulations of long fibers in the peripheral lower lobe. Fiber surfaces and masses showed similar differences among sample sites. We conclude that (1) there is no evidence for fiber concentration variations in different portions of the lung; (2) there is strong evidence for variations in fiber sizes in different portions of the lung, and these differences are most clearly related to fiber length, surface area, and mass; (3) contrary to data from experimental animals, there are no clear gravitational effects on fiber distribution in humans; and (4) there are reproducible differences in intrapulmonary fiber size distribution between mesothelioma and lung cancer cases. These differences may be a manifestation of individual handling of mineral particles because of structural variations in individual lungs.

Aged↗

PubMed1988

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↗

PubMed1988

Erythrocyte transit and neutrophil concentration in the dog lung.

We subdivided regional erythrocyte (RBC) transit time into the fraction spent in the large (greater than 50 microns), small (20-50 microns), and capillary (less than 20 microns) vessels of canine lungs. Using a combination of physiological and morphological techniques, the number of RBC and granulocytes in each vessel size was obtained by dividing the aggregate volume of the cell by the calculated volume of a single cell. The data show that the average transit time was 0.60 s in large vessels, 0.10 s in small vessels, and 1.37 s in capillary vessels and was longer (P less than 0.05) in the upper lung regions for small vessels and capillaries. RBCs pass through approximately 60 capillary segments at an average velocity of approximately 550 micron/s. Pulmonary hematocrit averaged 0.95 of the systemic hematocrit and was lower in capillaries than small vessels. PMN's were concentrated approximately 10-fold in the small vessels and 100-fold in the capillaries compared with peripheral blood. The multisegmented nature of the capillary bed allows this concentration because RBCs find pathways to stream around the slower moving PMNs.

Animals↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1987

Accumulation of long asbestos fibers in the peripheral upper lobe in cases of malignant mesothelioma.

Animal studies suggest that mesothelioma is most effectively induced by fibers longer than 8 mu. However, studies of asbestos fibers recovered from human lungs in cases of mesothelioma indicate that, at least in large-scale samples, relatively few fibers meet this size criterion, perhaps implying that the animal data do not apply to man. Since asbestos concentration in lung is known to be extremely inhomogeneous, it is also possible that long fibers may selectively accumulate in specific sites, such as under the pleura. To examine this possibility, we selected ten cases of mesothelioma that contained relatively large amounts of amosite asbestos and extracted fibers from an 0.5-cm-thick strip of subpleural tissue and an area 3-cm deep to the subpleural sample for upper and lower lobes. Amosite fibers were identified and sized by electron microscopic techniques. Fibers in the peripheral upper lobe were significantly longer, broader, and of higher aspect ratio than those in the central upper lobe. The lower lobe showed a reverse pattern, with longer fibers and broader fibers in the central sample. These data indicate that the two lobes behave differently in regard to fiber size, with selective accumulation of long fibers in the peripheral upper lobe, but not in the peripheral lower lobe. Whether these differences reflect differences in initial deposition of fibers within the lung, or, more likely, specific redistribution of fibers, is unclear, but in either case, accumulation of long fibers immediately under the upper lobe pleura may be important in the genesis of mesothelioma.

Asbestos↗

PubMed1987

Types, numbers, sizes, and distribution of mineral particles in the lungs of urban male cigarette smokers.

We analyzed the exogenous mineral particle concentration, size, type, and distribution for particles larger than 0.1 micron in the left lungs of 10 long-term male cigarette smokers. The mean number of particles found was 465 +/- 295 X 10(6)/g dry lung, of which 80% were kaolinite, micas, feldspars, free silica, and talc. Lead particles were extremely rare, despite their ubiquity in urban air. Overall there were no differences in particle concentration in upper vs lower lobes or central vs peripheral sampling sites. However, a significant correlation was found for upper lobe (r = 0.68), but not lower lobe (r = 0.08), particle concentration and amount of cigarette smoking. Overall, the geometric mean particle size was 0.6 +/- 2.1 microns; 56% of the particles in the upper lobes were larger than 0.75 micron in diameter, compared to 17% in the lower lobes, and the mean upper lobe particle size was greater than the mean lower lobe particle size for all individual mineral types. There was a remarkable homogeneity of mean particle size from patient to patient (mean intercase arithmetic particle size +/- SD of 0.8 +/- 0.1 micron). Particle size was not affected by the amount of smoking. We conclude that contrary to some published acute deposition data, there are no long-term differences in upper vs lower lobe particle concentration; total upper lobe particle retention is influenced by the amount of smoking as measured by pack-years, whereas total lower lobe particle retention appears to be independent by the amount of smoking; particles retained in the upper lobe are somewhat larger than those retained in the lower lobe, but the amount of smoking does not appear to influence retained particle size; the size of long-term retained particles most likely reflects largely atmospheric particle burden; and in the absence of overwhelming dust loads, the lung is able to regulate retained particle concentration and size in a fairly narrow range.

Health↗

PubMed1987

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↗

PubMed1987

Cigarette smoke makes airway and early parenchymal asbestos-induced lung disease worse in the guinea pig.

In order to assess the effects of cigarette smoke and asbestos exposure, we divided guinea pigs into 4 groups: smoking or nonsmoking, and asbestos-exposed or not asbestos-exposed groups. Asbestos-exposed animals were given a single intratracheal instillation of 5 mg UICC amosite, a dose and method of administration that we have previously shown produces morphologic changes in the small airways as well as minimal interstitial fibrosis. Animals were smoked 5 days per week for 6 months. By itself, smoking did not affect lung collagen content, small airways wall thickness, or the volume fraction of tissue surrounding airways, but it did cause a significant increase in alveolar mean linear intercept (Lm). Asbestos alone increased collagen content, airway wall thickness, and tissue volume fraction surrounding airways, the latter measure used to assess interstitial fibrosis. An unexpected finding was that asbestos also increased Lm. The two agents administered together caused more severe changes of all types than were produced by either agent alone, and the interaction between the 2 was generally synergistic. Smoke-exposed animals retained 3 times the asbestos fiber burden of those not smoke-exposed; the increase in retention was greater for short than for long fibers. We conclude that cigarette smoke can potentiate the fibrosis induced by asbestos, possibly because of increased fiber retention. As well, in this model, asbestos or asbestos plus cigarette smoke produces increases in alveolar size.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

A comparison of bronchiolitis obliterans with organizing pneumonia, usual interstitial pneumonia, and small airways disease.

This report is based on 43 cases where a diagnosis of either bronchiolitis obliterans with organizing pneumonia (BOOP), usual interstitial pneumonia (UIP), or small airways disease (SAD) was established by lung biopsy. The severity of histologic abnormalities in the peripheral airways and interstitial spaces were measured on these biopsies using semiquantitative techniques and compared with the clinical data available in 42 of 43 cases, preoperative chest radiographs in 31 of 43, and preoperative pulmonary function tests in 29 of 43. The data show that when a diagnosis of BOOP was made, there was a higher total pathologic score for membraneous bronchiolitis (MB) and respiratory bronchiolitis (RB) than for UIP and SAD (p less than 0.005). This was due to peribronchiolar inflammation and the presence of loose connective tissue in the RB lumen. The pathologic changes in the interstitial space were less severe in SAD than in BOOP or UIP (p less than 0.005). Clubbing was more frequent in UIP (p less than 0.01), and symptoms were of shorter duration in BOOP (p less than 0.05). The radiographic assessment showed that the characteristic finding in BOOP was patchy air-space consolidation, a finding that was not present in UIP or SAD.

Bronchial Diseases↗

PubMed1986

Diagnostic utility of lymphocyte subset analysis in AIDS case finding.

Abnormalities of lymphocyte subsets, especially low absolute number of helper T cells, are characteristically present in acquired immune deficiency syndrome (AIDS). Similar abnormalities can be found in patients with persistent generalized lymphadenopathy (PGL) or AIDS-related complex (ARC) and, to a lesser degree, in asymptomatic people who have been exposed to human T-lymphotropic virus type III (HTLV-III). Nevertheless, there appears to be a widespread perception that lymphocyte subset analysis may be useful in AIDS case finding within high-risk groups. We evaluated the diagnostic utility of absolute number of helper T cells and ratio of helper to suppressor T cells in 33 patients with AIDS, 43 patients with PGL who had been referred for lymph node biopsy, 90 patients with PGL and 195 male homosexual controls. At conventional cutoff levels the tests did not appear to revise the probability of AIDS upward to any clinically significant degree when the pretest probability of AIDS was low. Lymphocyte subset analysis does not appear to be a cost-effective method of AIDS case finding in identified groups at risk in which the prevalence of AIDS is low.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Fiber size and number in workers exposed to processed chrysotile asbestos, chrysotile miners, and the general population.

We analyzed chrysotile and chrysotile-associated amphibole (largely tremolite) asbestos fibers in 21 workers exposed to various types of processed (milled) chrysotile ore, 20 long-term chrysotile miners, and 20 members of the general population (controls). Significantly greater amounts of both chrysotile and tremolite were found in processed-ore workers and miners than in controls. On average, the mean fiber lengths and aspect ratios for the mining and processed-ore-exposed workers were similar and were significantly greater than the values seen in the controls; within the processed-ore group, there was a marked variation in these parameters, and some workers appeared to be exposed to fairly long, thin fibers. It was found empirically that the fiber size data, and to a lesser extent the concentration data, could be used to classify workers accurately into those with processed-ore exposure and controls. We conclude that fiber sizes in the lungs of processed-ore-exposed workers are similar to those of chrysotile miners and are considerably longer than those found in the general population; some processed-ore workers have longer fibers which might be responsible for higher disease incidences in certain working groups; tremolite accompanies chrysotile in a variable proportion of workers exposed to processed chrysotile products and might be important in the genesis of mesothelioma in such workers; and mineralogic analysis will usually detect exposure even when chrysotile has largely disappeared from lung tissue.

Air Pollutants, Occupational↗

PubMed1986

Smoking inhibits asbestos clearance.

To determine whether smoking affects the clearance of asbestos fibers, guinea pigs were given amosite asbestos by intratracheal instillation and divided into 3 groups: (1) nonsmokers, (2) animals exposed to smoke only after asbestos instillation, and (3) animals exposed to smoke both before and after asbestos instillation. Asbestos fiber concentrations and sizes were measured at 1 wk and 1 month after exposure. Between 1 wk and 1 month the asbestos burden in nonsmokers decreased on average 6-fold, whereas both smoking groups failed to show a significant decrease. Over this time period, the mean length of retained fibers increased in the nonsmokers but decreased in both smoking groups. This phenomenon was seen in tissue samples and lavage samples, although lavaged fibers were consistently shorter than tissue fibers. We conclude that in this model, cigarette smoking impedes asbestos clearance, largely by increasing retention of short fibers. This increased pulmonary fiber burden may be important in the increased disease rate seen in asbestos workers who smoke.

Animals↗

PubMed1986

In vivo human tracheal pressure-area curves using computerized tomographic scans. Correlation with maximal expiratory flow rates.

In order to develop a simple technique to measure in vivo pressure-area (P-A) curves of the extrathoracic trachea in humans, we studied 14 normal male subjects. Valsalva and Mueller maneuvers were performed at FRC, and tracheal cross-sectional area (TXSA) was measured using computed tomography. Extrathoracic tracheal transmural pressure (TMP) was obtained as airway opening minus atmospheric pressure (Pat). Tracheal "compliance" (TC) was measured on the "inflation" limb of the P-A curve. Tracheal compliance was not a significant predictor of maximal expiratory flow rates, and TXSA at zero TMP was a significant predictor of peak expiratory flow rate but not of FEV1 or Vmax50. P-A curves showed an unexpected configuration characterized by a plateau or an increase in TXSA with TMP lower than -15 cm H2O. P-A curves obtained in 5 subjects using extrathoracic esophageal pressure as tracheal external pressure instead of atmospheric pressure did not show a plateau or an increase in TXSA with Mueller maneuvers. In these 5 subjects, TC using esophageal pressure rather than Pat did not aid in the prediction of flow. We conclude that extrathoracic tracheal external pressure is not Pat because this pressure is probably affected by transmission of pleural pressure to the cervical interstitial tissue as well as by the contraction of cervical accessory inspiratory muscles. Therefore, true tracheal compliance cannot be simply measured since it requires placement of an esophageal balloon.

Adult↗