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Biomedical subjects

M R Cullen

Publications and source records attributed to M R Cullen.

At least 19 recordsLinked to original sources
PubMed1992

Morphologic, biochemical, and cytogenetic studies of bone marrow and circulating blood cells in painters exposed to ethylene glycol ethers.

In a previous cross-sectional survey, up to 15% of shipyard painters were found to have mild anemia or granulocytopenia, mostly acquired since employment. Environmental studies had suggested a possible etiologic role for ethylene glycol ethers, solvents to which the men were heavily exposed and which have established myelotoxic potential. To exclude alternative hypotheses, examine possible common patterns of injury, and identify potential risk factors and markers for such an effect, the affected painters were further studied. The painters were matched with two groups of controls: exposed painters without evidence of hematologic abnormality on the previous survey and unexposed controls. Altogether 25 subjects were studied by histopathologic examination of bone marrow, cytogenetic studies of marrow cells, and peripheral lymphocytes and peripheral red cell studies of membrane and metabolic function. Except for an unexpected finding of a race-associated effect on marrow histology, insignificant differences were seen among the groups in terms of marrow morphology and cellularity, stem cell growth kinetics, and marrow or peripheral cytogenetics. Two metabolic abnormalities of peripheral red cells related to exposure or clinical status of the subjects were found. Pyruvate kinase, an established marker of acquired myelodysplasia, was significantly depressed in the subjects with previously abnormal counts. Although reduced glutathione levels and holoenzyme activities of glutathione reductase (GSHR) did not differ among groups, exposed subjects had decreased saturation of GSHR with flavin adenine dinucleotide which could be restored in vitro, suggesting riboflavin deficiency or impaired riboflavin metabolism. Thus, although a unique pattern of bone marrow injury by histologic or genetic assay attributable to ethylene glycol ethers was not defined, biochemical effects of possible mechanistic importance were identified. The relevance of these findings as subclinical disease markers remains to be established.

Adult↗
PubMed1992

The relationship between large airway and alveolar space inflammation and airway metaplasia.

Bronchoscopy and bronchoalveolar lavage (BAL) yield important information about the lower respiratory tract of subjects who have been exposed to asbestos. Evidence of metaplasia is easily detected with random biopsies in large airways and a relationship with smoking status can be found. A significant finding, however, is that inflammatory cells recovered by late BAL aliquots which presumably reflect alveolar space inflammation are also importantly associated with the presence of metaplasia. Asbestos provides an important stimulus for recruitment of inflammatory cells. These cells release oxidants which can be responsible for direct or indirect mutagenesis. Our data suggest that this inflammatory cell recruitment may be an important additional factor predictive of airway metaplasia and perhaps subsequent carcinogenesis.

Asbestosis↗
PubMed1992

Association between neutrophil concentration in bronchoalveolar lavage fluid and recent losses in diffusing capacity in men formerly exposed to asbestos.

It has been observed widely that some individuals exposed to asbestos will experience continued losses of lung function after asbestos exposure ceases. Unfortunately, there are few data on factors that determine clinical course, limiting the clinician's ability to determine prognosis in an individual case and restricting the possibility for testing or targeting any potential intervention to alter the course among the millions at risk. In an attempt to address this question, we studied a volunteer population of 50 such men from among a stable, heterogeneous population of asbestos-exposed workers who had been continuously followed in our occupational medicine clinics for up to 12 years (mean, 6.3 years); most had some clinical or roentgenographic sign of asbestos effect, pleural or parenchymal. Each subject was reexamined clinically, functionally, and roentgenographically. Asbestos and tobacco exposure histories were carefully reviewed with the subjects and quantified based on these reports and available data regarding the various work environments from which they came. Subsequently, each underwent a bronchoalveolar lavage to assess cellularity and levels of various proteins. The levels of risk factors, clinical findings, and biologic parameters from lavage were examined for their relationship to serial changes in lung function during the period over which they had been previously followed. Results of the study demonstrate that serial changes in lung function were not closely related to level or length of prior exposure, smoking behavior, chest roentgenographic findings, or lung volumes. Progressive loss of diffusing capacity for carbon monoxide (Dco) was significantly associated with two factors: level of neutrophil concentration in lavage fluid (0.043 +/- 0.016 ml/min/mm Hg/yr drop for each 0.1 x 10(4) neutrophils per milliliter, p = 0.02) and the level of Dco itself (0.17 +/- 0.07 ml/min/mm Hg/yr drop for each 10 percent decrease in percent Dco predicted, p = 0.01). The relationship with neutrophil concentration was statistically independent of the association with Dco itself and stronger; it persisted when loss of Dco was adjusted for baseline value. Lung volume changes were not associated with any predictor variables, alone or in combination. We conclude that the presence of neutrophils in bronchoalveolar lavage fluid is associated with recent disease progression that may have implications in studies of the mechanisms of asbestos-associated disease and in clinical treatment of patients at risk.

Asbestosis↗
PubMed1992

Association between acute inflammatory cells in lavage fluid and bronchial metaplasia.

In epidemiologic studies, airway disease and parenchymal injury are known morbid outcomes of occupational exposure to asbestos. However, the relationship of inflammatory events considered to be responsible for parenchymal injury to the subsequent development of airway injury is unknown. To assess this we performed bronchoalveolar lavage (BAL) and airway biopsies on a population of subjects with exposure to asbestos in the workplace. As an index of airway injury, we employed histologic metaplasia seen in mucosal biopsy specimens. Lung BAL fluid was analyzed for two potentially relevant protein markers and for inflammatory cells recovered from the lower respiratory tract. We related metaplasia to demographic features of this study population (eg, smoking history and asbestos exposure data) and also to the protein and cellular markers recovered by BAL. We studied 50 workers and detected keratinizing metaplasia in 15 and varying lesser abnormalities in the other 28. Cigarette smoking was not associated with the presence of metaplasia (p less than 0.2). Smoking status was associated with an increase in BAL cells (p less than 0.02); however, neither the percent nor concentration of acute inflammatory cells was significantly increased. Acute inflammatory cells (percent and cells per milliliter of BAL fluid) were significantly increased among the subjects with severe metaplasia compared with other study subjects. This increase was true of both neutrophils and eosinophils and the sum of these two (p less than 0.02). Stratification of subjects by smoking status demonstrated a persistent association of inflammatory cells with metaplasia. By logistic regression analysis, polymorphonuclear leukocytes per milliliter and eosinophils per milliliter were significantly related to the presence of metaplasia in two independent models (odds ratios, 9.9 and 7.6, respectively). Cigarette smoking and other demographic or BAL variables were not significantly associated with metaplasia in these models.

Asbestosis↗
PubMed1992

Automated integration of external databases: a knowledge-based approach to enhancing rule-based expert systems.

Expert system applications in the biomedical domain have long been hampered by the difficulty inherent in maintaining and extending large knowledge bases. We have developed a knowledge-based method for automatically augmenting such knowledge bases. The method consists of automatically integrating data contained in commercially available, external, on-line databases with data contained in an expert system's knowledge base. We have built a prototype system, named DBX, using this technique to augment an expert system's knowledge base as a decision support aid and as a bibliographic retrieval tool. In this paper, we describe this prototype system in detail, illustrate its use and discuss the lessons we have learned in its implementation.

Asthma↗
PubMed1991

Chrysotile asbestos and health in Zimbabwe: I. Analysis of miners and millers compensated for asbestos-related diseases since independence (1980).

Data on the health effects caused by locally mined chrysotile asbestos in Zimbabwe have been very limited. The prevailing local view has been that risk is minimal. In this report we critically reassess the cases of 51 individuals with asbestos exposure who have been compensated by the Central Pneumoconiosis Bureau since independence in 1980. Results demonstrate that the major health risks of exposure reported elsewhere--morbid asbestosis, nonmalignant pleural disease, malignant mesothelioma, and lung cancer--all occur in Zimbabwe, at least among workers in the asbestos mines and mills. It is concluded that further investigation and control measures in the industry are warranted.

Asbestos↗
PubMed1991

Chrysotile asbestos and health in Zimbabwe: II. Health status survey of active miners and millers.

As part of the effort to establish industrial practice and public policy regarding asbestos in Zimbabwe, we have conducted a cross-sectional study of the chrysotile mines and mills. A stratified random sample of workers with greater than 10 years of exposure has been evaluated by spirometry, chest radiographs, and employment history. The latter was converted to quantitative estimates of exposure dose, using a matrix based on measured and reconstructed fiber levels for each job and facility during the years of work. Based on these data, a clear dose-response between asbestos exposure and functional loss has been demonstrated, with mean losses from predicted of about 400-600 cc in vital capacity in the 10% of the population with heaviest exposures. Low-grade parenchymal radiographic abnormalities (ILO grade greater than or equal to 1/0) were evident in 8.7% of the total study group and were almost 10 times more common in those with more than 100 fibers/cc.years cumulative exposure than in those with 16 fibers/cc.years or less. Pleural disease was relatively rare, occurring in just under 10% of the study group, and was unrelated to exposure dose. Overall, these findings are compatible with results of similar studies in Quebec and Swaziland and suggest that similar control strategies are probably indicated.

Asbestos↗
PubMed1991

The relationship between large airway inflammation and airway metaplasia.

To assess the role of acute inflammatory cells in large airways in the pathogenesis of metaplasia, we performed BAL (divided into aliquots) and mucosal biopsies on asbestos workers. They had evidence of asbestos-related lung injury. We found that acute inflammatory cells were significantly increased in the first aliquot. Ex-smokers had a greater percentage of PMN compared with nonsmokers and current smokers. The subjects were subgrouped with respect to biopsy-detected metaplasia. There was no difference between these groups for percentage or total number of PMN in the first aliquot. However, subjects with metaplasia had significant reduction in FEV1/FVC compared with those without. We conclude that there are significant differences in cells between the first and subsequent aliquots. Although inflammatory stimuli may be important in the pathogenesis of metaplasia, PMN present in the first aliquot could not be related to the severity of the metaplastic changes in these workers.

Animals↗
PubMed1991

The effect of chloroquine prophylaxis on yellow fever vaccine antibody response: comparison of plaque reduction neutralization test and enzyme-linked immunosorbent assay.

Weekly oral chloroquine prophylaxis for malaria has been associated with impaired antibody response to intradermal rabies vaccination. Experimental data indicate that chloroquine may inhibit yellow fever virus in vitro, yet there has been no clinical evidence to suggest that antibody response to yellow fever vaccine is impaired by concomitant oral administration of chloroquine. A prospective trial was undertaken to evaluate the antibody response to yellow fever 17D vaccine (Connaught Laboratories) of volunteers who were randomized to taking either chloroquine or no drug. Of fifty subjects, 28 were randomized to taking chloroquine, 22 were randomized to taking no drug. Yellow fever 17D vaccine was administered on day 0 and blood sampled on days 0, 14, 35 and 210. Chloroquine was administered weekly for four weeks. There was no significant difference in peak antibody titer by plaque reduction neutralization testing (PRNT) between the group that took chloroquine (mean log peak of reciprocal titer 1.43 +/- SD 0.60) with vaccine subcutaneously compared to vaccine-only group (mean log peak of reciprocal titer = 1.21 +/- 0.55). All fifty subjects seroconverted to yellow fever vaccine by day 210. ELISA testing was also performed on all subjects. The two tests showed good correlation (Spearman r = 0.675), although ELISA readings were positive by day 14 in significantly more subjects (p = .01). We conclude that routine anti-malarial doses of chloroquine do not affect antibody response to yellow fever 17D vaccine. ELISA testing, a less complex and less time-consuming test, correlates well with PRNT and is proposed for additional trials to measure yellow fever 17D vaccine response in flavivirus non-immune subjects.

Administration, Oral↗
PubMed1990

Methyl bromide intoxication in four field-workers during removal of soil fumigation sheets.

Methyl bromide is a highly toxic and penetrating compound used extensively as an insecticide for dry foodstuffs and as a soil fumigant (in greenhouses and fields) for the control of nematodes, fungi, and weeds. More than 300 cases of systemic poisoning and 60 fatalities attributable to methyl bromide have been reported [Alexeeff and Kilgore, 1983], resulting in substantial regulations concerning its handling, storage, application, and disposal. A recent exposure incident at a Connecticut nursery represents to our knowledge the first report of toxicity stemming from exposures in the field during removal of plastic sheets days after injection of methyl bromide into soil. Following removal of polyethylene sheets covering soil fumigated with methyl bromide, four field-workers developed fatigue and light-headedness and 3 workers noted progressive respiratory, gastrointestinal (GI), and neurologic symptoms. The acute systemic symptoms improved over several days, but later-onset neuropsychiatric symptoms persisted for several weeks. This incident stresses the need for improved worker education and strict adherence to safety precautions during all stages of methyl bromide fumigation and raises the possibility of an increased risk of toxicity associated with methyl bromide fumigation during a cool season.

Adult↗
PubMed1990

Prevalence of pneumonoconiosis among coal and heavy metal miners in Zimbabwe.

No prevalence data on pneumonoconiosis among Zimbabwe's 30,000 miners have been available. Passage of a 1984 law requiring examination of all miners has provided a data base to assess this, but the records had not been previously evaluated or stored in a manner to facilitate this. In 1988 we developed a strategy to utilize the existing records to estimate cross-sectional rates rapidly. In this report, we describe the approach and demonstrate high rates of simple pneumonoconiosis among long-term workers in the coal, nickel, copper, and gold mines. These data, though limited, provide a rationale for more detailed investigations in these workforces and an impetus to establish an ongoing surveillance plan for the nation's miners.

Analysis of Variance↗
PubMed1990

Clinical and pathological characteristics of hepatotoxicity associated with occupational exposure to dimethylformamide.

The clinical characteristics, laboratory results, and liver biopsy findings of seven workers with toxic liver injury associated with exposure to several solvents, including substantial levels of the widely used solvent dimethylformamide, are presented. Three patients had short exposure (less than 3 months), four long exposure (greater than 1 year). Among those with brief exposure, symptoms included anorexia, abdominal pain, and disulfiram-type reaction. Aminotransferases were markedly elevated with the ratio of alanine aminotransferase to aspartate aminotransferase always greater than 1. Liver biopsy showed focal hepatocellular necrosis and microvesicular steatosis with prominence of smooth endoplasmic reticulum, complex lysosomes, and pleomorphic mitochondria with crystalline inclusions. Among workers with long exposure, symptoms were minimal and enzyme elevations modest. Biopsies showed macrovesicular steatosis, pleomorphic mitochondria without crystalloids, and prominent smooth endoplasmic reticulum, but no evidence of persisting acute injury or fibrosis. Abnormal aminotransferases in both groups may persist for months after removal from exposure, but progression to cirrhosis in continually exposed workers was not observed. We conclude that exposure of these workers to solvents, chiefly dimethylformamide, may result in two variants of toxic liver injury with subtle clinical, laboratory, and morphological features. This may be readily overlooked if occupational history and biopsy histology are not carefully evaluated.

Adult↗
PubMed1990

Incorporating environmental medicine into training programs in occupational medicine.

Demand is increasing rapidly for medical evaluation and management of individuals and groups exposed to chemical, physical, and biologic hazards in the non-workplace environment. Because general physicians are ill prepared to respond and no existing specialty has obvious expertise, occupational physicians who have some relevant background could have a central role to play in filling these perceived needs. However, incorporation of environmental medicine into the specialty will require reexamination of our skills and training. The focus of this essay is to explore aspects of environmental medicine practice that demand expansion of the current repertoire of skills. Based on these, we propose modifications of training that could facilitate such expansion without sacrifice of the core principles of traditional occupational medicine.

Curriculum↗