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Biomedical subjects

I A Greaves

Publications and source records attributed to I A Greaves.

At least 19 recordsLinked to original sources

Environmental endotoxin measurement: the Kinetic Limulus Assay with Resistant-parallel-line Estimation.

A Limulus assay method was specifically designed for environmental endotoxin aerosols. Application of new statistical and sample preparation methods strengthened the validity and precision of the Limulus test. Statistically, the Kinetic Limulus Assay with Resistant-parallel-line Estimation (KLARE) differed from conventional analytic methods (as used in chromogenic assays and other kinetic methods) by routinely using a dilution series of the unknown sample as well as the standard to compute potency and an estimate of variance for each sample. Analysis of dose-response slopes for the standard and unknowns detected inhibition and enhancement effects--without multiple assay. Concentration-dependent interference and a more complex, concentration-independent interference with the Limulus assay were detected. Resistant regression and a standardized data analysis corrected for concentration-dependent interference. Sample preparation in a buffer eliminated concentration-independent interference and, thus, improved both the validity and the precision of potency measurements. The utility of a sample buffer and of parallel-line analysis, with both turbidimetric and chromogenic lysates, was demonstrated by assay of three control standard LPS and reference LPS (EC5). The limit of detection for endotoxin was less than 1 pg/ml in buffer. Samples containing greater than or equal to 10 pg/ml were measured with a coefficient of variation of approximately 6% in a single assay. Reproducibility of potency estimates for four samples over 3 days was compared on the basis of standard errors of the mean. The conventional method gave on average a CV of 65% while the resistant-parallel-line method gave, on average, a CV of 6%. Also, the conventional method failed to detect interference and, thus, included data from invalid assays. Conventional analysis of environmental aerosol samples was highly sensitive to the choice of dilution factor causing as much as 1000% variation in the result. By contrast, KLARE results changed by at most 30% with similar changes in initial dilution because KLARE was able to detect, and correct for, the influence of interferant compounds.

Aerosols

Investigation of reports of sexual dysfunction among male chemical workers manufacturing stilbene derivatives.

A Health Hazard Evaluation was conducted by the National Institute for Occupational Safety and Health in an area of a large chemical plant that manufactured the stilbene derivative 4,4'-diaminostilbene-2,2'-disulfonic acid, an intermediate used for the production of optical brightening agents. Men employed in the area reported problems with impotence. The study population consisted of 44 men aged 20-57 years (mean age 37) employed in the area at the time of the evaluation. An industrial hygiene investigation, health and work history questionnaire survey, physical examinations, and blood chemistry and serum hormone evaluation were conducted. Fourteen percent of the men reported symptoms of impotence over the preceding 6 or more months, 7% had potency problems of shorter duration, and 7% were not currently impotent but had experienced impotence for 6 or more months in the past; 36% experienced decreased libido, all since beginning work in the production area. Low levels of serum testosterone (less than 350 ng/dl) were observed in 37% of the men. The low serum testosterone concentrations were not accounted for fully by diurnal variation or an effect of rotating shift work. It is suggested that exposures to chemicals possessing estrogenic activity may be related to the observed health effects in these workers.

Adult

Endotoxin measurement: aerosol sampling and application of a new Limulus method.

A new Limulus test was designed specifically for measuring endotoxin in environmental aerosols. The new Limulus method has a detection limit for airborne endotoxin of 2.2 pg (NP-1 activity)/m3 and can precisely quantitate aerosols containing 14 or more pg/m3 from samples representing 6.5 m3 of air. Aerosols in the range 100 to 500 pg/m3 were measured with 95% confidence of +/- 32% and an aerosol of 10 pg/m3 with 95% confidence of +/- 50%. Qualitative information about airborne endotoxin was also obtained from the assay. A wide variety of filter media were found to inactivate lipopolysaccharide in solution. This implies that airborne endotoxin can be measured only relative to the conditions of a particular study and that comparison of endotoxin aerosol measurements made under different circumstances are invalid. The research and policy implications of this observation are discussed. The need for improved collection and extraction methods notwithstanding, it was proposed that a buffered, parallel-line Limulus assay method be adopted as the standard method for measuring environmental endotoxin. The kinetic-turbidimetric Limulus assay with resistant-parallel-line estimates (KLARE), rate response method, should be considered a prime candidate for the standard method because of its precision, sensitivity, resistance to interference by pH, internal validation of estimates, and ability to provide qualitative as well as quantitative information about airborne endotoxin.

Aerosols

Toxicity of intratracheally instilled cotton dust, cellulose, and endotoxin.

Cotton dust includes respirable particles containing endotoxin and elastase, agents associated with emphysema. To examine whether a respirable fraction of cotton dust could produce emphysema in an animal model, we intratracheally instilled hamsters with respirable cotton dust particles (0.75 mg/100-g animal), mass median aerodynamic diameter less than or equal to 4.8 microns, twice weekly for 6 wk. We also examined whether instilled endotoxin (255 micrograms/100-g animal) could produce emphysema in hamsters and whether cellulose (0.75 mg/100-g animal) is an appropriate inert comparison dust. A saline-instilled group was the control. Hamsters were killed 8 wk after the last instillation. Static pressure-volume deflation curves of air-filled excised lungs were analyzed to measure lung distensibility. Lungs were fixed in inflation using glutaraldehyde and were examined morphometrically to obtain surface area and numbers of granulomata. Endotoxin-treated animals had increased distensibility, reduced surface-to-volume (S/V) ratio, and morphologically apparent mild centrilobular emphysema. Cellulose-treated animals had decreased distensibility, normal S/V ratio, and significant numbers of granulomata with patchy areas of thickened interalveolar septa. Cotton-dust-instilled animals had normal distensibility, reduced S/V ratio, significant numbers of granulomata, and mild centrilobular emphysema. These data suggest that cotton dust produces a significant parenchymal lesion with elements similar to both the emphysematous response to endotoxin and the fibrotic nodular response to cellulose.

Animals

Acute pulmonary responses among automobile workers exposed to aerosols of machining fluids.

Previous investigations of workers exposed to machining fluids have shown increased rates of cough and phlegm and have shown that these exposures may cause occupational asthma. To examine acute responses to these agents, cross-shift lung function changes related to machining fluid aerosols among 89 machine operators at two factories producing automobile parts were measured and compared with the findings for 42 unexposed assembly workers studied similarly at the same factories. Workers wore a personal air-sampling device on a Monday and Friday of a working week, and spirometry was performed before and after the work shifts on both days. On Mondays, a 5% or greater decrease in the forced expiratory volume in 1-second (FEV1), regarded as an "FEV1-response," occurred in 23.6% of the machinists and in only 9.5% of the assembly workers (relative risk = 2.5, p less than .05). After adjusting statistically for a history of childhood asthma, for smoking prior to lung function testing, and for race, odds ratios for an FEV1-response of 4.4 among workers exposed to aerosols of straight mineral oils, 5.8 for oil emulsions, and 6.9 for synthetic fluids were found. The FEV1-responses on Fridays were similar to those on Mondays. There was no progressive decline in FEV1 over the work week. Personal air samples, collected with a two-stage impactor, allowed aerosol masses to be measured in three size fractions: less than 3.5 microns, 3.5-9.8 microns, and greater than 9.8 microns aerodynamic diameter. Exposure levels to each type of machining fluid were remarkably similar within each size fraction and for total aerosol levels. Total aerosol concentrations for assembly workers ranged from 0.07 to 0.44 mg/M3, and for machinists from 0.16 to 2.03 mg/m3. Inhalable particle (less than or equal to 9.8 microns) levels were derived from the sum of the air concentrations in the two smallest-size fractions, and significant cross-shift decrements in FEV1 on Mondays and Fridays were associated with inhalable aerosol levels greater than 0.20 mg/m3. These findings show that acute airflow obstruction is associated with exposures to aerosols of various machining fluids and that airway responses occur well below current recommended exposure limits.

Aerosols

Work related decrement in pulmonary function in silicon carbide production workers.

The relation between pulmonary function, cigarette smoking, and exposure to mixed respirable dust containing silicon carbide (SiC), hydrocarbons, and small quantities of quartz, cristobalite, and graphite was evaluated in 156SiC production workers using linear regression models on the difference between measured and predicted FEV1 and FVC. Workers had an average of 16 (range 2-41) years of employment and 9.5 (range 0.6-39.7) mg-year/m3 cumulative respirable dust exposure; average dust exposure while employed was 0.63 (range 0.18-1.42) mg/m3. Occasional, low level (less than or equal to 1.5 ppm) sulphur dioxide (SO2) exposure also occurred. Significant decrements in FEV1 (8.2 ml; p less than 0.03) and FVC (9.4 ml; p less than 0.01) were related to each year of employment for the entire group. Never smokers lost 17.8 ml (p less than 0.02) of FEV1 and 17.0 (p less than 0.05) of FVC a year, whereas corresponding decrements of 9.1 ml (p = 0.12) in FEV1 and 14.4 ml (p less than 0.02) in FVC were found in current smokers. Similar losses in FEV1 and FVC were related to each mg-year/m3 of cumulative dust exposure for 138 workers with complete exposure information; these findings, however, were generally not significant owing to the smaller cohort and greater variability in this exposure measure. Never smokers had large decrements in FEV1 (40.7 ml; p less than 0.02) and FVC (32.9 ml; p = 0.08) per mg-year/m3 of cumulative dust exposure and non-significant decrements were found in current smokers (FEV1: -7.1 ml; FVC: -11.7 ml). A non-significant decrement in lung function was also related to average dust exposure while employed. No changes were associated with SO(2) exposure or and SO(2) dust interaction. These findings suggest that employment in SiC production is associated with an excessive decrement in pulmonary function and that current permissible exposure limits for dusts occurring in this industry may not adequately protect workers from developing chronic pulmonary disease.

Adult

Respiratory symptoms associated with low level sulphur dioxide exposure in silicon carbide production workers.

Relations between pulmonary symptoms and exposure to respirable dust and sulphur dioxide (SO2) were evaluated for 145 silicon carbide (SiC) production workers with an average of 13.9 (range 3-41) years of experience in this industry. Eight hour time weighted average exposures to SO2 were 1.5 ppm or less with momentary peaks up to 4 ppm. Cumulative SO2 exposure averaged 1.94 (range 0.02-19.5) ppm-years. Low level respirable dust exposures also occurred (0.63 +/- 0.26 mg/m3). After adjusting for age and current smoking status in multiple logistic regression models, highly significant, positive, dose dependent relations were found between cumulative and average exposure to SO2, and symptoms of usual and chronic phlegm, usual and chronic wheeze, and mild exertional dyspnoea. Mild and moderate dyspnoea were also associated with most recent exposure to SO2. Cough was not associated with SO2. No pulmonary symptoms were associated with exposure to respirable dust nor were any symptoms attributable to an interaction between dust and SO2. Cigarette smoking was strongly associated with cough, phlegm, and wheezing, but not dyspnoea. A greater than additive (synergistic) effect between smoking and exposure to SO2 was present for most symptoms. These findings suggest that long term, variable exposure to SO2 at 1.5 ppm or less was associated with significantly raised rates of phlegm, wheezing, and mild dyspnoea in SiC production workers, and that current threshold limits for SO2 may not adequately protect workers in this industry.

Adult

Pulmonary function in beryllium workers: assessment of exposure.

The inhalation of beryllium causes a serious lung disease characterised by pronounced radiographic and functional impairments and occurs in workers engaged in the extraction and manufacture of the metal. This paper describes the beryllium exposure levels and refining processes in a large beryllium factory operating since the 1930s. Lifetime beryllium exposure histories were estimated for the 309 workers present at a health survey conducted in 1977. Beryllium exposure levels in the plant were high for many years, with some estimated exposure levels in excess of 100 micrograms/m3. As late as 1975, there were exposures to beryllium above 10 micrograms/m3 in some jobs. After about 1977, the plant was in compliance with the permissible exposure limit of 2.0 micrograms/m3. The median cumulative exposure in this cohort was 65 micrograms/m3-years and the median duration of exposure was 17 years. From these data a series of exposure parameters, functions of the exposure histories that characterise biologically important dimensions of exposure were calculated for each worker.

Beryllium

Beryllium exposure and pulmonary function: a cross sectional study of beryllium workers.

A cross sectional study of 297 white male workers employed in a large beryllium plant was conducted to test the hypothesis that long term exposure to beryllium is associated with decrements in pulmonary function. Spirometric measurement of pulmonary function, chest radiographs, and arterial blood gas measurements were collected. After controlling for age, height, and smoking in multivariate regression models, decrements in FVC and FEV1 were found to be associated with cumulative exposure to beryllium in the period up until 20 years before the health survey. These decrements were observed in workers who had no radiographic abnormalities. The alveolar-arterial oxygen difference was associated with cumulative exposure in the 10 years immediately before survey, after controlling for age and smoking. These findings suggest that beryllium may have both short and long term pulmonary effects that are distinct from the classic forms of acute and chronic beryllium disease.

Adult

Cotton dust and endotoxin exposure-response relationships in cotton textile workers.

Endotoxin exposure has been implicated in the etiology of lung disease in cotton workers. We investigated this potential relationship in 443 cotton workers from 2 factories in Shanghai and 439 control subjects from a nearby silk mill. A respiratory questionnaire was administered and pre- and postshift forced expiratory volume (FVC) and flow in one second (FEV1) were determined for each worker. Multiple area air samples were analyzed for total elutriated dust concentration (range: 0.15 to 2.5 mg/m3) and endotoxin (range: 0.002 to 0.55 microgram U.S. Reference Endotoxin/m3). The cotton worker population was stratified by current and cumulative dust or endotoxin exposure. Groups were compared for FEV1, FVC, FEV1/FVC%, % change in FEV1 over the shift (delta FEV1%), and prevalences of chronic bronchitis and byssinosis, and linear and logistic regression models were constructed. No dose-response relationships were demonstrated comparing dust concentration to any pulmonary function or symptom variable. A dose-response trend was seen with the current endotoxin level and FEV1, delta FEV1%, and the prevalence of byssinosis and chronic bronchitis, except for the highest exposure level group in which a reversal of the trend was seen. The regression coefficients for current endotoxin exposure were significant (p less than 0.05) in the models for FEV1 and chronic bronchitis but not in the models for delta FEV1% (i.e., acute change in FEV1) or byssinosis prevalence. The coefficient for dust level was never significant in the models.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants, Occupational

Respiratory effects of work in retail food stores. III. Pulmonary function findings.

Findings are reported from a prospective morbidity study which examined the effects on pulmonary function associated with the particulate and gaseous air contaminants to which retail food store workers are exposed. A total of 685 supermarket employees (including meat wrappers, meat cutters and store clerks) performed standard ventilatory function tests [forced expiratory volume in 1 s (FEV1.0) and forced vital capacity (FVC)] during a base-line survey. Those available four years later (305) were resurveyed in a similar manner. A suggestive chronic effect on pulmonary function was shown in those with high cumulative exposures and allergic history. Among those workers who had continuous exposure to air contaminants in settings with "hot-wire" plastic wrap film cutters the annual rates of change in FEV1.0 and FVC were twice as great as the changes found among comparable workers who were not exposed to fumes from wrapping film. Those who switched from the "hot-wire" to the "cool-rod" cutters during the course of the follow-up had intermediate rates of change in lung function.

Adult

Respiratory effects of work in retail food stores. II. Respiratory symptoms.

This study examined the relationships between the prevalence of respiratory tract symptoms and estimates of environmental exposures in retail food stores, in particular exposures to emissions from the cutting of polyvinyl chloride wrap. When respiratory symptoms were compared with a measure of cumulative exposure, there was evidence that the prevalence of symptoms of episodic airway narrowing was higher for workers who had been exposed directly or indirectly to meat wrapping operations independent of a significant association of these symptoms with allergic or asthmatic history. Whether this finding reflects a nonspecific irritant effect or allergic sensitization cannot be determined from these data. No single substance present in the work environment studied has, as yet, been identified as associated with these effects.

Adult

Respiratory effects of work in retail food stores. I. Methodology and exposure assignments.

This study was designed to examine whether retail food store employees have an unusual prevalence or incidence of respiratory symptoms or pulmonary function abnormalities attributable to their work environment. The methodology and development of exposure assignments are presented. Employees from 75 supermarkets (a total of 685 meat cutters, wrappers and store clerks) were tested in a base-line survey, and those still available (305) were resurveyed four years later. Each subject completed a standard questionnaire on job history, health history, cigarette smoking, and respiratory symptoms and also performed five forced expiratory efforts on a standardized spirometer. The major air contaminants were identified including the composition and levels of exposures associated with the different ways of cutting plastic film wrap. A cumulative exposure estimate for each subject was made. Parts II and III of this study present the association of these work environment factors with respiratory symptoms and ventilatory function.

Adult

Estimates of ventilation from body surface measurements in unrestrained subjects.

To make estimates of ventilation from measurements of body surface movements in unrestrained subjects, we measured changes in linear dimensions and cross-sectional areas of the rib cage (RC) and abdomen (AB) of six healthy unrestrained subjects during a variety of maneuvers. RC and AB anteroposterior diameters and abdominal length in the cephalocaudal axis (axial displacement) were measured with magnetometers, and RC and AB cross-sectional areas were measured with a respiratory inductance plethysmograph. Flow was measured at the mouth with a pneumotachograph and integrated electrically to give volume. Volume and body surface measurements were analyzed by multiple linear regression. Addition of the axial measurements to either the anteroposterior dimensions or cross-sectional areas of RC and AB improved estimates of tidal volume in all subjects (P less than 0.01). With measurements of axial displacement and cross-sectional area of the RC and AB, tidal volume could be reliably estimated to within 20% of actual ventilation. We conclude that measurement of axial displacements improves estimates of ventilation in unrestrained subjects.

Abdomen

Chronic airflow obstruction. Evolution of disordered function in cigarette smokers.

Measurements of the mechanical behaviour of the lung, which reflect lung structure, have been used to elucidate the evolution of chronic airflow obstruction in male cigarette smokers and subjects with pulmonary emphysema. The exponent K, from a single exponential function fitted to static pressure-volume data, is an index of lung distensibility directly related to the size of peripheral airspaces. Elastic recoil pressure is inversely related to K. Conductance measured during forced and interrupted deflations of the lungs reflects the dimensions of airways. K increased abnormally with age in smokers suggesting an increase in the airspace size caused by the effects of cigarette smoke which probably acts by intensifying elastase activity in lung tissue. Decreased conductance implying narrowing of airways is found in young smokers, but conductance rises and airways become more distensible in older smokers. A progressive increase in K (with decrease in recoil pressure) and a decrease in conductance are responsible for the advancement of severe airflow obstruction in cigarette smokers.

Adolescent

Large lungs after childhood asthma: a consequence of enlarged airspaces.

The long-term effects of asthma on lung volume were investigated in 18 asthmatic patients during periods of remission from airway obstruction; ten had developed asthma in childhood (before 8 years of age) and eight after the age of 18 years. Subjects whose asthma began in childhood had an increased total lung capacity (TLC) on average; adult-onset asthmatics had normal mean lung volumes. Exponential analysis of static pressure-volume curves in these subjects showed that the childhood-onset asthmatics had lungs of increased distensibility, while adult-onset asthmatics had lungs of normal distensibility. In a further ten adults selected for having had asthma in the past and an increased vital capacity, all had developed asthma in childhood, had lungs of increased distensibility and an increased TLC. Increased distensibility and an increased TLC were closely associated within individuals. The close relationship between distensibility and the size of peripheral air spaces demonstrated in mammalian lungs, suggests that asthma in childhood may increase TLC and distensibility because of an increase in the size of peripheral airspaces.

Adolescent