Asbestos exposure, asbestosis, and lung cancer.
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Asbestosis↗
Biomedical subjects
D E Banks
Publications and source records attributed to D E Banks.
Respiratory health effects of opencast coalmining: a cross sectional study of current workers.
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Coal Mining↗
Immunodominance of a low-affinity major histocompatibility complex-binding myelin basic protein epitope (residues 111-129) in HLA-DR4 (B1*0401) subjects is associated with a restricted T cell receptor repertoire.
The pathogenesis of multiple sclerosis (MS) is currently ascribed in part to a T cell-mediated process targeting myelin components. The T cell response to one candidate autoantigen, myelin basic protein (MBP), in the context of HLA-DR15Dw2, has been previously studied in detail. However, the characteristics of cellular immunity in the context of other MS-associated HLA-DR haplotypes are scarcely known. MBP-specific T cell lines (TCL) were generated from HLA-DR4 (B1*0401)-positive MS subjects. Out of 275 MBP-specific TCL, 178 (64. 7%) specifically recognized region MBP(111-129), predominantly in the context of DRB1*0401. The major T cell epitope for MBP recognition corresponded to residues MBP(116-123). These TCL expressed disparate profiles of cytokine secretion and cytotoxicity. T cell receptor analysis, on the other hand, revealed a strikingly limited heterogeneity of rearrangements. In contrast to MBP(81-99), which binds with high affinity to HLA-DR15 and is recognized by a diverse T cell repertoire, MBP(111-129) binds weakly to DRB1*0401, suggesting that only high affinity T cell receptors might be able to efficiently engage such unstable MHC/peptide complexes, thus accounting for the T cell receptor restriction we observed. This study provides new insight about MBP recognition and proposes an alternative mechanism for immunodominance of self-antigen T cell epitopes in humans.
Adult↗
Assessment of the relationship between isocyanate exposure levels and occupational asthma.
As part of a previous study, we identified Ontario cases of isocyanate-induced occupational asthma (OA) and the companies at which they worked. The Ontario Ministry of Labour maintained a computerized database including isocyanate air sampling determinations conducted by the Ministry. Within this database, we compared levels of isocyanate concentrations measured at 20 case companies [with compensated isocyanate asthma (OA) claims] with 203 noncase companies, based on air samples collected during the same 4-year period during which the OA claims arose. The proportion of case companies that were ever recorded as having a measured ambient isocyanate concentration of > or = 0.005 ppm was greater than that for noncase companies, for TDI users (43% vs 22%), and for MDI users (40% vs 27%). This reached conventional significance when combined across companies and isocyanate types (50% vs 25%; P < 0.05). This provides some evidence that facilities having OA claims have higher isocyanate exposures than do those without claims.
Air Pollutants↗
Clinical perspective of inorganic dusts, metals, and fumes exposures.
Although the clinical presentations of illnesses associated with dusts, metals, and fumes exposures remain unchanged, there is increasing insight into the mechanisms of these diseases, how these illnesses occur, and what might be necessary to alter their natural history. It is discouraging to note that despite aggressive measures designed to make workplace environments safe, workers continue to develop these preventable illnesses.
Air Pollutants, Occupational↗
Silicosis in the 1990s, revisited.
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Animals↗
Weight gain and longitudinal changes in lung function in steel workers.
Associations among dust exposure, smoking habits, and demographic factors and longitudinal changes of lung function were assessed among male steel workers. Cohort descriptive data analysis was conducted in 541 steel workers who had performed spirometry at least twice between 1982 and 1991 (mean follow-up, 6.1 years). The annual change (slope) in FVC, FEV1, FEV1/FVC%, and in body weight was determined by simple linear regression. The Pearson correlation coefficient between weight change and spirometry changes was calculated. Comparisons were also done in 75 pairs of steel workers matched by age, height, initial FEV1, and smoking status, but whose FEV1 declines differed by > or = 60 mL/yr. The FEV1 and FVC declined an average of 44 and 50 mL/yr, respectively, for the cohort as a whole. The FEV1 and FVC declined 52 and 54 mL/yr for current smokers, 43 and 53 mL/yr for ex-smokers, and 36 and 43 mL/yr for nonsmokers, respectively. Increasing weight was highly correlated with accelerated decline in lung function (p<0.0001). In the matched pairs, mean slopes for FVC, FEV1, and FEV1/FVC ratio were -96 mL/yr, -95 mL/yr, and -0.40%/yr for the rapid decliners; and +5 mL/yr, +10 mL/yr, and +0.10%/yr for their partners (p<0.0001). Matched pair comparisons showed that the rapid decliners averaged a 4.313 kg weight gain, while their partners gained 1.044 kg during the follow-up period. The slope of weight gain was 0.708 kg/yr for rapid decliners and 0.191 kg/yr for comparison workers (p<0.0036). Weight gain, in addition to aging and cigarette smoking, was found to be associated with the longitudinal rate of decline in FVC, FEV1, and FEV1/FVC ratio.
Adult↗
The relationship between latex skin prick test responses and clinical allergic responses.
BACKGROUND: Allergic responses to latex have been reported more frequently in the past 5 years. Although commercial skin prick test solutions are available and can be used in the diagnosis of latex allergy in some countries, the characteristics of patients sensitized to latex relative to their skin test responses have not been reported. OBJECTIVE: The purpose of this study is to relate the clinical characteristics of patients with latex sensitivity to the size of their latex skin prick test response. METHODS: A retrospective review of patients who were attending a hospital-based allergy and asthma clinic and who had positive skin test responses to a commercial latex skin test solution was undertaken. RESULTS: Of 47 patients who had skin test responses to latex, 36 had a mean wheal diameter at least 3 mm greater than the negative control (diluent). Sixty-eight percent were health care workers. There was a positive association between the size of skin test response and severity of latex-induced symptoms (p < 0.001). A history of banana sensitivity was also associated with larger skin test responses (p < 0.05). CONCLUSION: The size of the skin prick test response to latex solution that is commercially available in Canada reflects the severity of latex-induced clinical allergic responses.
Adult↗
Improvement in lung function measurements using a flow spirometer that emphasizes computer assessment of test quality.
We compared retrospective measurements of lung function from 101 steel workers using a commercially available spirometer to prospective lung function measurements performed, on average, 1.3 years later, with a newly developed spirometer. This spirometer was designed and developed to incorporate technology that provides immediate feedback on the quantitative and qualitative aspects of each forced expiratory effort. Of the 101 workers, 82 who had spirometry performed with each spirometer had at least two acceptable curves, and 51 workers tested with each spirometer had curves that met all American Thoracic Society (ATS) criteria for spirometry. No group showed the anticipated decline in forced expiratory volume in 1 second (FEV1) over time. The results showed an increased number of curves meeting ATS acceptability and reproducibility criteria, and a statistically significant increase in the FVC in all groups, and an increase in the FEV1 in the group encompassing all workers. Use of technology that strengthens the interaction between the spirometry technician, the data available to the technician on the computer, and the participant appears to represent true underlying lung function more accurately. Such an approach to the collection of lung function data should be considered by those evaluating spirometers for implementation in the workplace or pulmonary function laboratory as well as by those planning future spirometer development.
Humans↗
Reduction of lung dust burden in pneumoconiosis by whole-lung lavage.
Pneumoconioses are characterized as irreversible, progressive respiratory diseases. No effective therapy exists to prevent progression of these diseases. Whole-lung lavage (WLL) might limit the rate of disease progression through the removal of dust, inflammatory cells, and cytokines. We performed WLL on a 54-year-old underground miner employed as a motorman and roof bolter and a 55-year-old driller at a surface coal mine. Both demonstrated normal lung function and chest radiographs showing ILO profusion category 2 nodular interstitial changes. From Subject 1, we recovered 5.24 x 10(8) cells (90% macrophages) from the right lung and 3.45 x 10(8) cells (94% macrophages) from the left lung. WLL removed 1.82 g of mineral dust (non-coal) on the right and 1.64 g on the left. From Subject 2, we recovered 7.49 x 10(8) cells (46% macrophages) from the right and 9.78 x 10(8) cells (69% macrophages) from the left lung. WLL removed 0.40 g of mineral dust on the right and 0.53 g on the left. Proinflammatory cytokines, growth factors, and cellular enzymes were also recovered. In cases of pneumoconiosis, WLL is capable of removing relatively large quantities of dust, cells, and soluble materials from the lungs. Only long-term follow-ups of individuals with progressive dust-induced disease who receive WLL therapy in the context of a clinical trial will provide information regarding the importance of removing mineral dust and inflammatory cells from the lung.
Bronchoalveolar Lavage↗
Longitudinal and cross-sectional analyses of lung function in steelworkers.
We evaluated associations between dust exposure, demographic factors, and lung function by longitudinal and cross-sectional analyses in 475 steelworkers who participated in at least three spirometry tests over 5 yr between 1982 and 1991. Baseline and follow-up spirometry and changes between baseline and final follow-up assessment attributable to age, height, weight, weight gain, smoking status, pack-years, and years worked in dusty areas were examined using stepwise multiple linear regression techniques. Smoking, aging, being overweight, excessive weight gain, and dust exposure were related to a lower level and a steeper slope of decline of pulmonary function. Cigarette smoking was also an important risk factor. Dust exposure was related to the level of lung function, with a stronger effect at baseline than at follow-up. Estimated loss at baseline of FEV1, FVC, and FEV1/FVC% was 9.3, 6.4 ml, and 0.1 % per year of employment in a dusty area, respectively, whereas the association between dust exposure and longitudinal decline of lung function was weak. However, a strong relationship between weight gain and longitudinal decline of FEV1 and FVC was found. Estimated decreases in FEV1 and FVC attributable to weight gain were 4.7 and 6.3 ml per lb/yr, respectively. This work suggests that weight gain is an important determinant for longitudinal lung function decline. This large impact of weight gain in the decline of lung function in a middle-age and relatively overweight working population has not been previously reported. Additional work needs to be undertaken to show the strength of this relationship in other populations.
Adult↗
Bronchoprovocation tests in the diagnosis of isocyanate-induced asthma.
Over the past 25 years, investigators have continued to improve on the approach to providing nonirritant exposures for the accurate diagnosis of isocyanate-induced asthma. Although the technology used in testing has become more sophisticated and may be fairly considered the domain of the bioengineer, the chemist, and the industrial hygienist, the requirements of the physician have remained unchanged. The physician must observe the level of exposure closely and monitor the worker's symptoms and lung function. Direct physician involvement in the testing procedure remains critical to the worker's safety and for the accurate diagnosis of isocyanate-induced asthma.
Asthma↗
Pulmonary response to hyperoxia: effects of magnesium.
Animals and humans rapidly develop respiratory failure and die within a few days when exposed to 100% oxygen. Postmortem examination of the lungs shows histopathologic features characteristic of diffuse alveolar damage, clinically recognized as adult respiratory distress syndrome (ARDS). At the present time, there is no effective therapy available to alter outcomes in ARDS. Importantly, hypomagnesemia also is frequently observed in critically ill patients at risk of developing ARDS. In a model of hyperoxic lung injury, rats were exposed to 100% oxygen for 48, 64, and 96 hr and several experiments were performed. First, changes in the features of bronchoalveolar lavage and in alveolar macrophage function were compared in rats exposed to room air and those exposed to hyperoxia. Second, we studied the effect of hypomagnesemia on the severity of hyperoxic lung injury. Third, we evaluated the pulmonary responses to high-dose and normal-dose Mg therapy in rats exposed to hyperoxia. In all groups, hyperoxia induced significant changes in the total and differential cell counts with increased lipid peroxidation of lavaged cells, enhanced chemiluminescence from alveolar macrophages, and protein leakage into the alveolar spaces. After 48 hr of hyperoxia, oxygen-free radical formation and hydrogen peroxide production by the alveolar macrophage were diminished compared to baseline, implying a toxic effect of hyperoxia on the alveolar macrophages. Overall, hypomagnesemia tended to magnify the degree of hyperoxic lung injury, while high-dose Mg therapy tended to attenuate the effects of hyperoxia. In conclusion, in this animal model of diffuse alveolar damage, alterations in host serum magnesium levels may modulate the degree of lung damage.
Animals↗
Fluoromicroscopic studies of bleomycin-induced intracellular oxidation in alveolar macrophages and its inhibition by taurine.
The mechanism of bleomycin-induced pulmonary fibrosis is not yet clear. Recent studies have shown that alveolar macrophages (AM) can be stimulated by bleomycin in vitro releasing inflammatory cytokines, suggesting that the interaction of bleomycin with AM is an important step in the drug-induced fibrotic process. Bleomycin is known to bind DNA and generate oxygen radicals through complexation with Fe2+ and oxygen. To provide more insight into the cellular oxidative property of bleomycin, we have developed a fluoromicroscopic method using 2',7'-dichlorofluorescin diacetate (DCFHDA) as an oxidative fluorescence probe to study the bleomycin-induced intracellular oxidation in rat AM and the inhibition of the oxidation by taurine, a compound known to inhibit the bleomycin-induced fibrosis. Bleomycin at 5 to 20 micrograms/ml has a moderate stimulatory effect (1.87- to 2.66-fold) on the secretion of superoxide anion. A high concentration of bleomycin (20 micrograms/ml), however, inhibits cell response to zymosan-induced secretion of superoxide anion. At 4 micrograms/ml, bleomycin has no effect on cell membrane integrity or morphology but results in a significant increase in intracellular oxidation. This oxidative process is Fe(2+)-dependent and is accompanied by an increase in intracellular calcium (35 nM). Both the intracellular oxidation and calcium rise induced by internalized bleomycin are inhibited by pretreatment of cells with varying concentrations of taurine (25, 125, and 187.5 microM). The inhibitory effect on intracellular oxidation was found to be 36, 57, and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Altered calcium homeostasis and cell injury in silica-exposed alveolar macrophages.
There is evidence to suggest that cell injury induced in alveolar macrophages (AM) following phagocytic activation by silica particles may be mediated through changes in intracellular free calcium [Ca2+]i. However, the mechanism of silica-induced cytotoxicity relative to [Ca2+]i overloading is not yet clear. To provide a better insight into this mechanism, isolated rat AMs were exposed to varying concentrations of crystalline silica (particle size < 5 microns in diameter) and the fluctuation in their [Ca2+]i and cell integrity were quantitatively monitored with the fluorescent calcium probe, Fura-2 AM, and the membrane integrity indicator, propidium iodide (PI). Results from this study indicate that silica can rapidly increase [Ca2+]i in a dose-dependent manner with a characteristic transient calcium rise at low doses (< 0.1 mg/ml) and an elevated and sustained rise at high doses (> 0.1 mg/ml). Depletion of extracellular calcium [Ca2+]o markedly inhibited the [Ca2+]i rise (approximately 90%), suggesting that Ca2+ influx from extracellular source is a major mechanism for silica-induced [Ca2+]i rise. When used at low doses but sufficient to cause a transient [Ca2+]i rise, silica did not cause significant increase in cellular PI uptake during the time of study, suggesting the preservation of membrane integrity of AMs under these conditions. At high doses of silica, however, a marked increase in PI nuclear fluorescence was observed. Depletion of [Ca2+]o greatly inhibited cellular PI uptake, induced by 0.1 mg/ml or higher doses of silica. This suggests that Ca2+ influx, as a result of silica activation, is associated with cell injury. Indeed, our results further demonstrated that the low dose effect of silica on Ca2+ influx is inhibited by the Ca2+ channel blocker nifedipine. At high doses of silica (> 0.1 mg/ml), cell injury was not prevented by nifedipine or extracellular Ca2+ depletion, suggesting that other cytotoxic mechanisms, i.e., nonspecific membrane damage due to lipid peroxidation, are also responsible for the silica-induced cell injury. Silica had no significant effect on cellular ATP content during the time course of the study, indicating that the observed silica-induced [Ca2+]i rise was not due to the impairment of Ca(2+)-ATPase pumps, which restricts Ca2+ efflux. Pretreatment of the cells with cytochalasin B to block phagocytosis failed to prevent the effect of silica on [Ca2+]i rise. Taken together, these results suggest that the elevation of [Ca2+]i caused by silica is due mainly to Ca2+ influx through plasma membrane Ca2+ channels and nonspecific membrane damage (at high doses).(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Intraocular pressure during mechanical ventilation with different levels of positive end-expiratory pressure.
OBJECTIVE: To determine the effect of positive end-expiratory pressure (PEEP) on intraocular pressure. DESIGN: Prospective, controlled, longitudinal, dual center study. In one group, patients served as their own control. In the second group, isolated determinations of intraocular pressure were made in mechanically ventilated patients receiving PEEP. SETTING: Adult intensive care units of two university hospitals. PATIENTS: Intraocular pressures were measured serially in eight patients during the recovery phase of different clinical conditions and in 22 patients receiving mechanical ventilation with PEEP > or = 10 cm H2O for > 24 hrs. INTERVENTIONS: Group A) In eight patients, a PEEP dose-response curve was established (PEEP 0, 5, 10, 15, and 0 cm H2O every 15 mins). Intraocular pressures were measured at the end of each period. Group B) In 22 patients, measurement of intraocular pressures were done while the patients received mechanical ventilation with PEEP > or = 10 cm H2O for at least > 24 hrs. MEASUREMENTS AND MAIN RESULTS: In both groups, there was a positive correlation between the PEEP level and the central venous pressure (p < .05 in group A, and p < .03 in group B). No relationships between intraocular pressure and PEEP or central venous pressure were observed. However, there was a correlation between intraocular pressure and length of PEEP therapy (p < .03). We found ocular hypertension in only one patient (right eye intraocular pressure = 26 mm Hg; left eye intraocular pressure = 24 mm Hg). CONCLUSIONS: Short-term therapy with PEEP of < or = 15 cm H2O does not present a clinically important significant risk for intraocular pressure increase in a population with normal basal ocular tonometry. During prolonged mechanical ventilation with PEEP, increments in intraocular pressure may occur, but these increments appear to not be of a clinically relevant magnitude.
Adult↗
Mechanisms of hydroxyl free radical-induced cellular injury and calcium overloading in alveolar macrophages.
Excessive production of reactive oxygen radicals by alveolar macrophages is proposed to play an important role in oxidative lung injury. A major product oxygen radical formation is the highly reactive hydroxyl radical (.OH) generated via a biologic Fenton reaction. In addition to its known ability to induce lipid peroxidation, recent studies have suggested that the .OH may exert its cytotoxic effect through the alteration of [Ca2+]i homeostasis. To test this potential mechanism as well as to investigate the relationship between .OH and Ca2+ overloading in cytotoxic injury, isolated rat alveolar macrophages were exposed to externally generated radical system, H2O2 (0.01 to 1 mM) and Fe2+ (1 mM) and their [Ca2+]i levels and cell injury were monitored using quantitative fluorescence microscopy with the aid of the specific Ca2+ indicator, Fura-2, and membrane integrity indicator, propidium iodide. Electron spin resonance measurements using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) confirmed the production of the .OH radical by this system. Upon the addition of the radicals, the macrophages displayed a rapid initial rise in [Ca2+]i which was followed by a slower but more pronounced [Ca2+]i elevation that reached a level 3 to 5 times higher than the basal level. This process preceded cell death as evident by nuclear propidium iodide fluorescence. Depletion of extracellular Ca2+ inhibited both the [Ca2+]i response and cell injury. Preincubation of the cells with the Ca2+ channel blocker verapamil or .OH radical scavenger mannitol similarly inhibited the [Ca2+]i rise and loss of viability. Firefly luciferase assay of cellular ATP content demonstrated that the alterations in [Ca2+]i following .OH treatment preceded the depletion of ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Understanding circulatory shock. Is it hypovolemic, cardiogenic, or vasogenic?
Circulatory shock comprises a group of complex circulatory syndromes that result from a variety of conditions. It alters the function of most organ systems and has very high mortality. Identification of the type of shock (hypovolemic, cardiogenic, vasogenic, or a combination) and optimal treatment are aided by hemodynamic monitoring, including determination of preload, cardiac output, and systemic vascular resistance. Experimental studies and isolation of bioactive substances have improved understanding of the mechanisms involved in shock. Restoration of intravascular volume, cardiac contractility, and vascular tone and control of the underlying septic process when applicable are the basis of current therapy. Close monitoring and support of the affected organ systems in an intensive care environment facilitate recovery. Encouraging results with new treatments indicate improved chances for a satisfactory outcome in patients with circulatory shock.
Humans↗