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Biomedical subjects

H W Davies

Publications and source records attributed to H W Davies.

At least 19 recordsLinked to original sources
PubMed2005

Predicting historical dust and wood dust exposure in sawmills: model development and validation.

Nonspecific dust measurements are used as a surrogate for wood dust exposure in sawmills. However, the wood dust component of dust has been found to vary by job and work area. Thus, the use of nonspecific dust exposure levels in epidemiologic studies may introduce exposure misclassification when assessing wood-related health effects. To improve exposure assessment in a retrospective cohort of 28,000 sawmill workers, we developed and evaluated the validity of two empirical models of exposure: one for nonspecific dust and one for wood dust. The dust model was constructed using 1,395 dust measurements collected in 13 sawmills for research or regulatory purposes from 1981 to 1997. Inter-sampler conversion factors were used to obtain inhalable dust equivalents if necessary. The wood dust model was constructed after applying adjustment factors to subtract nonwood components of the dust from the original measurements. The validity of the two models was tested against measurements (n = 213) from a technologically similar mill that was not part of the cohort study. The proportions of variability explained by the dust and wood dust models were 35% and 54%, respectively. When tested against the validation mill, the biases in the dust model were -33% for outdoor jobs and 2% for indoor jobs. The biases in the wood dust model were 2% for outdoor jobs and -3% for indoor jobs. Strong correlations were observed between the predicted and observed geometric means of jobs (0.79 and 0.70 for the dust model and wood dust model, respectively). Testing the validity of predictive models examines the generalizability of the models. The low overall bias, especially in the wood-specific model, increases our confidence in the use of these models for all sawmills to assess both nonspecific particulate and wood-related health effects in the historical cohort study.

Cohort Studies↗
PubMed1999

Determinants of exposure to inhalable particulate, wood dust, resin acids, and monoterpenes in a lumber mill environment.

In a lumber mill in the northern inland region of British Columbia, Canada, we measured inhalable particulate, resin acid, and monoterpene exposures, and estimated wood dust exposures. Potential determinants of exposure were documented concurrently, including weather conditions, tree species, wood conditions, jobs, tasks, equipment used, and certain control measures. Over 220 personal samples were taken for each contaminant. Geometric mean concentrations were 0.98 mg/m3 for inhalable particulate, 0.49 mg/m3 for estimated wood dust, 8.04 micrograms/m3 for total resin acids, and 1.11 mg/m3 for total monoterpenes. Multiple regression models for all contaminants indicated that spruce and pine produced higher exposures than alpine fir or mixed tree species, cleaning up sawdust increased exposures, and personnel enclosure was an effective means of reducing exposures. Sawing wood in the primary breakdown areas of the mill was the main contributor to monoterpene exposures, so exposures were highest for the barker operator, the head rig operator, the canter operator, the board edgers, and a roving utility worker in the sawmill, and lowest in the planer mills (after kiln drying of the lumber) and yard. Cleaning up sawdust, planing kiln-dried lumber, and driving mobile equipment in the yard substantially increased exposures to both inhalable particulate and estimated wood dust. Jobs at the front end of the sawmill where primary breakdown of the logs takes place had lower exposures. Resin acid exposures followed a similar pattern, except that yard driving jobs did not increase exposures.

Air Pollutants, Occupational↗
PubMed1999

A field comparison of inhalable and thoracic size selective sampling techniques.

We measured inhalable, thoracic, and so-called "total" wood dust exposure in British Columbia lumber mill workers. Particle-size selective sampling was conducted using the GSP and Seven hole inhalable samplers, the PEM thoracic sampler and the 37-mm closed-face cassette "total" sampler. All measurements were full-shift personal samples, obtained from randomly selected workers. We obtained intersampler comparison data for the following pairs of instruments: GSP and 37-mm sampler; GSP and seven-hole sampler (SHS); and PEM and 37-mm sampler. The intersampler measurement ratios were estimated as: GSP/37-mm sampler = 4.2; GSP/SHS = 1.7; and PEM/37-mm sampler = 1.6. The GSP/37-mm sampler ratio is consistent with previously reported findings, while PEM/37-mm sampler and GSP/SHS ratios were both larger than expected. We found that in all comparisons, the measurement ratio had significant variability that was greatest at low ambient dust concentrations. Although it was not possible to attribute the source of the variability to specific sampler types, we concluded that the GSP sampler might be susceptible to "projectile" particles not normally aspirated, and may be vulnerable to direct aspiration of dust from accidentally contacted surfaces. The PEM was designed for environmental monitoring, and it is possible that it is unsuited to the higher particulate concentrations found in some occupational settings. Disparities among inhalable sampling techniques such as that between GSP and SHS should be investigated further in light of the proposed adoption of the inhalable method as an industrial standard.

Air Pollutants, Occupational↗
PubMed1998

Cytogenetic analysis of South Asian berry pickers in British Columbia using the micronucleus assay in peripheral lymphocytes.

Micronuclei in peripheral blood lymphocytes from British Columbia seasonal farmworkers and controls were evaluated using the cytokinesis-block technique. The farmworkers harvested berry crops and were likely occupationally exposed to pesticides. Subjects were 39 female subjects of South Asian descent; 18 farmworkers employed during 1993 and 21 age-matched controls. The mean age was 55.9 years. Micronuceli were also scored for the presence of kinetochores. No significant difference was found between the frequency of micronucleated binucleates in the farmworkers group (19.20/1000 binucleates), and the control group (21.76/1000 binucleates). However, among the farmworkers employed in 1993, there was a positive, but not statistically significant, association between micronucleated cell frequency and weeks worked: 16.44/1000 binucleates in those working less than 20 weeks; 23.78/1000 binucleates in those working 20 to 23 weeks; and 25.43/1000 binucleates in those working more than 23 weeks. In those who had ever been employed as farmworkers, there was an elevated frequency of micronucleated cells in the group with the longest history of employment as a farmworker (25.28/1000 binucleates) compared to those with the shortest employment history (16.48/1000 binucleates). This trend remained evident after adjusting for age, red blood cell folate, meat consumption, coffee consumption and recent vaccination. A positive association between the consumption of meat and micronucleus frequency was also observed. Non-meat eaters were likely life-long vegetarians. Micronuclei in farmworkers had a lower frequency of kinetochore positive micronuclei than controls. This study indicates that South Asian berry pickers in British Columbia may be at risk for genetic damage. More studies in other ethnic groups and in males are needed to generalize the findings of this study. More direct measures of exposure are needed to elucidate the sources of genotoxicity.

Adult↗
PubMed1995

Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate whether concurrent administration of misoprostol reduces the occurrence of serious upper gastrointestinal complications, such as perforation, gastric outlet obstruction, or bleeding, in patients with rheumatoid arthritis who are receiving nonsteroidal anti-inflammatory drugs (NSAIDs). DESIGN: 6-month randomized, double-blind, placebo-controlled trial. SETTING: 664 clinical practices of family medicine, internal medicine, or rheumatology in the United States and Canada. PATIENTS: 8843 men and women (mean age, 68 years) receiving continuous therapy with any of 10 specified NSAIDs for control of symptoms of rheumatoid arthritis. Patients were enrolled between July 1991 and August 1993. INTERVENTION: Patients were randomly assigned to receive 200 micrograms of misoprostol or placebo four times a day. MEASUREMENTS: Development of serious upper gastrointestinal complications detected by clinical symptoms or findings (not by scheduled endoscopy). RESULTS: Serious upper gastrointestinal complications were reduced by 40% (odds ratio, 0.598 [95% CI, 0.364 to 0.982; P = 0.049]) among patients receiving misoprostol (25 of 4404 patients) compared with those receiving placebo (42 of 4439 patients). During the first month, more patients receiving misoprostol (20%) than placebo (15%) withdrew from the study, primarily because of diarrhea and related problems (P < 0.001). Risk factors for serious upper gastrointestinal complications were increasing age, history of peptic ulcer or bleeding, and cardiovascular disease. Patients with all four risk factors would have a 9% risk for a major complication in 6 months. CONCLUSIONS: In older patients with rheumatoid arthritis, misoprostol reduced serious NSAID-induced upper gastrointestinal complications by 40% compared with placebo.

Aged↗
PubMed1986

Carbon tetrachloride and 2-isopropyl-4-pentenamide-induced inactivation of cytochrome P-450 leads to heme-derived protein adducts.

When CCl4 was incubated with rat liver microsomes from phenobarbital-treated rats in an aerobic or anaerobic atmosphere, over 69% of the heme moiety of cytochrome P-450 was destroyed. At least 45% of the degraded heme under both reaction conditions was accounted for as heme-derived products irreversibly bound to microsomal proteins. Furthermore, 33% of the irreversibly bound products were bound specifically to a 54-kDa form of cytochrome P-450. A structurally different compound, 2-isopropyl-4-pentenamide, also destroyed the heme moiety of cytochrome P-450 and produced heme-derived adducts of microsomal proteins that accounted for 28% of the destroyed heme. These results represent a novel mechanism for the destruction of cytochromes P-450 by xenobiotics.

Acetamides↗
PubMed1986

Inactivation of cytochrome P-450 by 2-isopropyl-4-pentenamide and other xenobiotics leads to heme-derived protein adducts.

When cytochrome P-450 in phenobarbital-induced rat liver microsomes was destroyed by 2-isopropyl-4-pentenamide (AIA) in vitro, 50% of the degraded heme was recovered as heme-derived products irreversibly bound to microsomal proteins. In contrast, less than 50% of the degraded heme was accounted for as N-alkylated porphyrins. Furthermore, 64% of the irreversibly bound products was bound specifically to a 54-kD form of cytochrome P-450. Several other compounds which have been reported to destroy cytochrome P-450 by forming N-alkylated porphyrins also produced heme-derived protein adducts. These findings indicate that the formation of heme-derived protein adducts may represent an important pathway for the irreversible degradation of cytochrome P-450 by many xenobiotics.

Acetamides↗
PubMed1986

Inhibition of overall protein and RNA synthesis as a mechanism for the tunicamycin induced decrease in cytochrome P-450 in rat hepatocytes.

In rat hepatocytes maintained in culture, cytochrome P-450 and NADPH cytochrome c reductase activities were decreased by tunicamycin in a dose and time dependent fashion. The effect of tunicamycin was mainly due to inhibition of protein synthesis. Tunicamycin decreased L-[35S] methionine incorporation into many proteins, including a 52 kDa cytochrome P-450 isozyme. Tunicamycin also reduced RNA synthesis. These results indicate that tunicamycin decreased cytochrome P-450 levels in hepatocytes by inhibiting protein and RNA synthesis.

Animals↗
PubMed1985

Immunochemical evidence of trifluoroacetylated cytochrome P-450 in the liver of halothane-treated rats.

Four hours after the administration of halothane to phenobarbital-pretreated rats, subcellular fractions of liver were isolated and the proteins in the fractions were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, transferred to nitrocellulose sheets, and immunochemically stained with anti-trifluoroacetylated antibodies. The microsomal fraction contained the highest level of trifluoroacetylated adducts. Its major trifluoroacetylated component was immunochemically identified as a phenobarbital-inducible form of cytochrome P-450 (54 kDa), whereas the other observed trifluoroacetylated protein fraction (59 kDa) was not identified. The plasma membrane fraction also contained a 54-kDa trifluoroacetylated adduct, which was immunochemically related to the 54-kDa cytochrome P-450. Microsomes from untreated rats that were administered halothane contained only the 59-kDa trifluoroacetylated protein fraction. The specificity of the immunochemical staining for the bound oxidative metabolite of halothane was confirmed by the finding that rats treated with deuterated halothane had considerably less stained liver proteins than did those treated with halothane. These results suggest that the CF3COX oxidative metabolite of halothane is so reactive that it binds predominantly to the cytochrome P-450 that produced it.

Acetylation↗
PubMed1984

Pharmacokinetics of intranasally applied medication during a cold.

The rate at which interferon is cleared from the nose after local administration was measured in volunteers both before and after challenge with virulent strains of human rhinovirus. Interferon was not cleared more rapidly after virus challenge, and there was no relationship between the amount of nasal secretion produced after challenge, and the rate of interferon clearance. These findings suggest that an inverse relationship between the quantity of a locally applied antirhinovirus drug which is recovered in nasal wash, and clinical and laboratory evidence of rhinovirus infection may be taken as evidence for a beneficial effect of the drug.

Administration, Intranasal↗
PubMed1983

Comparative intranasal pharmacokinetics of interferon using two spray systems.

Physician-administered and self-administered interferon (IFN) nasal sprays were compared by measuring residual IFN recovered from the nose at intervals following single doses. Amounts of IFN recovered five minutes after administration and the decay curves of recoverable antiviral and immunoreactive IFN with time were variable between volunteers but similar for both methods. It follows that a self-administered IFN spray would be suitable for future trials of IFN in upper respiratory infections. It was also confirmed that IFN persists in the nose for at least 24 h and is not all recovered by nasal washing, suggesting that it may be bound to, then slowly released from, nasal mucosal cells.

Administration, Intranasal↗
PubMed1981

Synthesis and turnover of membrane glycoconjugates in monolayer culture of pig and human epidermal cells.

The regression and turnover of the surface glycoconjugates of trypsin-prepared pig and human cultured epidermal cells have been determined using the glycoprotein precursors N-acetyl-D-(I-3H) glucosamine (3H-NAG) and N-(3H)-acetyl-D-mannosamine (3H-NAM). Sialic acid assays have been performed on similar unlabelled cells. The major points which emerged from this study were: (1) Trypsin-damaged cell surfaces are rapidly repaired, probably by normal membrane turnover. There was a 12% regeneration of sialic acid within 2 h and total resynthesis occurred within 24 h. (2) The presence of an internal membrane system, part of which also demonstrates turnover, probably contributed to the speed of surface membrane repair. Some of the glycoprotein/sialic acid of this internal membrane system (30%) remains bound for a considerable length of time. (3) The membrane turnover maintains the cell in equilibrium so that total loss equals the synthesis of glycoprotein. (4) The equilibration of 3H-NAG or 3H-NAM uptake between 24 and 48 h is limited by the relative concentrations of glucose and labelled sugar in the medium at this time. (5) 3H-NAm was a more specific marker of glycoprotein than 2H-NAG. (6) The results for human epidermal cells closely matched those for pig epidermal cells, indicating that pig cells can be used as a model for human cells.

Acetylglucosamine↗
PubMed1978

The use of a continuous cell line for the isolation of influenza viruses.

Cultures of MDCK cells exposed to trypsin were as efficient as cultures of rhesus monkey kidney cells for detecting influenza virus, both in dilutions of infected allantoic fluids and in nose and throat swabs. We suggest that the MDCK cell/trypsin system provides a satisfactory alternative to monkey kidney cultures for the isolation of influenza viruses from clinical specimens.

Cell Line↗