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Biomedical subjects

A Salvan

Publications and source records attributed to A Salvan.

At least 19 recordsLinked to original sources
PubMed2005

Evaluation of skin and respiratory doses and urinary excretion of alkylphosphates in workers exposed to dimethoate during treatment of olive trees.

This article describes a study of exposure to dimethoate during spraying of olive trees in Viterbo province in central Italy. Airborne concentrations of dimethoate were in the range 1.5 to 56.7 nmol/m(3). Total skin contamination was in the range 228.4 to 3200.7 nmol/d and averaged 96.0% +/- 3.6% of the total potential dose. Cotton garments afforded less skin protection than waterproof ones, which were in turn associated with higher skin contamination than disposable Tyvek overalls. Total potential doses and estimated absorbed doses, including their maxima, were below the acceptable daily intake of dimethoate, which is 43.6 nmol/kg body weight (b.w.). Urinary excretion of alkylphosphates was significantly higher than in the general population, increasing with exposure and usually showing a peak in the urine sample collected after treatment. Metabolite concentrations were influenced by the type of individual protection used: minimum levels were associated with the closed cabin and maximum levels with absence of any respiratory or hand protection. Urinary alkylphosphates showed a good correlation with estimated absorbed doses and are confirmed as sensitive biologic indicators of exposure to phosphoric esters.

Adult↗
PubMed2001

Use of a toxicokinetic model in the analysis of cancer mortality in relation to the estimated absorbed dose of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD).

We performed an analysis of All cancer and Lung cancer mortality in relation to estimated absorbed dose of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) in the cohort of chemical workers at 12 US plants assembled by the US National Institute for Occupational Safety and Health (NIOSH) (n = 5172). Estimates of cumulative exposure to TCDD were based on a minimal physiologic toxicokinetic model (MPTK) that accounts for inter- and intra-individual variations in body mass index (BMI) over time. Population-level parameters related to liver elimination and background (input or concentration) of TCDD were estimated from separate data with repeated measures of serum TCDD (US Air Force Health Study). An occupational TCDD input parameter was estimated based on one-point-in-time TCDD data available for a subset (n = 253) of the NIOSH cohort. Model-based time-dependent cumulative dose estimates (area under the curve (AUC) of the lipid-adjusted serum TCDD concentration over time) were obtained for members of the full cohort with recorded body height and weight (n = 4049), as this information is required by the MPTK model to compute dose. Missing-value problems arose in the estimation of the occupational input parameter (n = 42) and in TCDD-dose calculation in the full cohort (n = 886) and they were handled with multiple imputation methods. Risk-regression analyses were based on Cox log-linear models including age at entry, year of entry and duration of employment as categorical covariates in addition to the logarithm of cumulative TCDD dose in ppt-years. Risk sets were stratified on birth cohort. Estimates of the unlagged exposure coefficient in these models were 0.1249 [95% confidence interval (CI) 0.0144, 0.2354] for All cancer and 0.2158 (95% CI 0.02376, 0.4078) for lung cancer. A 10-year lag produced an increase in the estimate for all cancer (0.1539, 95% CI 0.0387, 0.2691), whereas, the estimate for lung cancer was not affected much (0.2125, 95% CI 0.0138, 0.4112). At a dose level of 100 times the background the estimates obtained with a 10-year lag translate into a relative risk of 2.03 (95% CI 1.19-3.45) for all cancer and of 2.66 (95% CI 1.07-6.64) for lung cancer. Higher estimates of the exposure coefficients were obtained after imputation of missing values. This increase in risk seemed due to the inclusion of short-term workers, who may exhibit a higher mortality for reasons other than dioxin exposure.

Body Mass Index↗
PubMed2001

[Infantile leukemia and exposure to 50/60 Hz magnetic fields: review of epidemiologic evidence in 2000].

We review the epidemiological evidence on childhood leukemia and residential exposure to 50/60 Hz magnetic fields. The possibility of carcinogenic effects of power frequency magnetic fields (ELF-EMF), at levels below units of micro tesla (microT), was first raised in 1979 by a case-control study on childhood cancer carried out in Denver, USA. In that study, excess risks of total cancer and leukemia were observed among children living in homes with "high or very high current configuration", as categorised on the basis of proximity to electric lines and transformers. Many other epidemiological studies have been published since then, characterised by improved--although still not optimal--methods of exposure assessment. At the end of 2000, the epidemiological evidence to support the association between exposure to extremely-low-frequency magnetic fields and the risk of childhood leukemia is less consistent than what was observed in the mid 90s. At the same time, a growing body of experimental evidence has accumulated against both a direct and a promoting carcinogenic effect of ELF-EMF. Such "negative" experimental evidence hampers a causal interpretation of the "positive" epidemiological studies.

Child↗
PubMed2000

Mortality among rubber chemical manufacturing workers.

BACKGROUND: A retrospective cohort mortality study evaluated ischemic heart disease (IHD) among workers in the "rubber chemicals" manufacturing department of a Western New York plant. A previous study at the plant found elevated chest pain and angina among workers in this department. METHODS: Mortality experience of workers employed from 1946-1988 was followed through December 31, 1994. Mortality was compared to U.S. population rates and to local Niagara county rates by using the NIOSH life table analysis system. Poisson regression was used to examine patterns of IHD within the cohort. RESULTS: The standardized mortality ratio (SMR) for IHD among workers in the rubber chemicals department was 1.51 (U.S. rates) and 1.19 (Niagara county rates). Increased mortality from IHD in the rubber chemicals department was most pronounced at younger ages (< 50, SMR = 2.4); workers in a second chemical production department also had an elevated (but not statistically significant) SMR of 1.5 for IHD. CONCLUSIONS: IHD mortality among workers in the rubber chemicals department was elevated, particularly among those under 50 years of age. Potential occupational risk factors for IHD include the rotating shift pattern for employees assigned to two chemical production departments and chemical exposures present in the rubber chemicals department.

Adolescent↗
PubMed1999

Uncertainty in estimating exposure using a toxicokinetic model. The example of 2,3,7,8-tetrachlorodibenzo-p-dioxin.

This paper deals with sources of uncertainty in the use of a minimal physiological toxicokinetic model to obtain dose estimates for a dose-response analysis of cancer in an occupational cohort. Toxicokinetic models make it possible to construct exposure parameters that are more closely related to the individual dose than traditional measures of exposures to toxic agents. However, the process introduces a wide array of sources of uncertainty. Selecting a model structure to describe the kinetics of a toxic agent implies necessarily making simplifications and assumptions that influence the range of applicability of the model. Once a model has been selected, the value of certain model parameters (constants) must be assigned, for example, from anthropometric data. The question then arises of how sensitive the model predictions are to variations in the values of these constants. Other model parameters, typically those describing the kinetics of the agent, are next estimated from actual data. There may be limitations in the data concerning, for example, sparseness (too few observations per subject) or missing values. The methods used for parameter estimation carry their own set of assumptions that need to be appropriate to the situation at hand. In summary, the dioxin example is used to characterize the sources of uncertainty at different levels, such as model structure, methods and data used for parameter estimation, estimation of occupational exposure, and imputation of missing values in exposure indices derived from the kinetic model.

Environmental Exposure↗
PubMed1998

Brain metabolic profiles obtained by proton MRS in two forms of mitochondriopathies: Leber's hereditary optic neuropathy and chronic progressive external ophthalmoplegia.

The status of brain metabolism has been evaluated using monovoxel short echo time (20 ms) 1H magnetic resonance spectroscopy in 6 patients with two forms of mitochondrial disorders without clinical cerebral involvement: 2 patients with Leber's hereditary optic neuropathy (LHON) and 4 patients with chronic progressive external ophthalmoplegia (CPEO). Patients with LHON displayed normal spectra. In all patients with CPEO, the brain metabolic profiles were abnormal, with no single uniform pattern. No typical cerebral metabolic profile was found even when these disorders were classified either by syndrome or by biochemical defect. No lactate signal was detected. The metabolic alterations observed in CPEO patients contrasted with the absence of clinical signs of encephalopathy. The absence of a typical metabolic profile reflects the large variability in the clinical expression of biochemical defects in mitochondriopathies, and the lack of convergence between genetic deletions, biochemical anomalies and clinical syndromes.

Adult↗
PubMed1998

Estimation of occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin using a minimal physiologic toxicokinetic model.

In this study we investigated estimation of occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on a minimal physiologic toxicokinetic model in humans. Our purpose was to obtain a mathematical tool for dose-response studies based on human data. We first simplified an existing model of TCDD kinetics in humans and estimated its parameters (i.e., liver elimination and background input of TCDD) using repeated measures of serum dioxin taken in Vietnam veterans (Ranch Hand data and data from an unexposed reference group). We carried out computer simulation and estimation of the model parameters both under a nonlinear weighted least-squares model (naive pooled data approach) and under a nonlinear mixed-effects model. The best parameter estimates were obtained with log-transformed data under a mixed-effects model: liver elimination parameter kf = 0.022 days-1 (95% confidence interval [CI] = 0.020, 0.024), and background input rate input = 0.1251 pg/kg/day (95% CI = 0.071, 0.179). The dioxin kinetic model and its estimated parameters were then used to provide dose estimates for a cohort of workers with exposure to TCDD at chemical plants in the United States. First, the model was used to estimate the rate of occupational intake of TCDD in a subset of the cohort consisting of 253 subjects for whom one measure of serum TCDD was available. A model of change in body-mass index over time was also identified for this subsample. The occupational exposure rate was estimated by linear regression using the above values of kinetic parameters and assuming an initial condition for serum TCDD of 7 ppt, i.e., the average level found in unexposed workers. The estimate of the occupational exposure parameter was 232.7 pg/kg/day (95% CI 192, 273). This value can be applied to the full cohort to obtain for each cohort member the time course of serum dioxin concentration from which exposure indices can be derived. Sensitivity coefficients to model parameters (background input, kf, occupational exposure, and the assumed TCDD concentration at hire) allow for a convenient recalculation of the serum TCDD curve and of the derived exposure indices for different assumed values of the model parameters.

Humans↗
PubMed1997

Work with video display terminals and the risk of reduced birthweight and preterm birth.

To determine whether the use of video display terminals (VDTs) is associated with an increased risk of reduced birthweight (RBW) and preterm birth, a cohort of telephone operators who used VDTs at work was compared to a cohort of non-VDT-users. Among 2,430 women interviewed, 713 eligible singleton live births were reported. Exposure was estimated from company records and a representative sample of electromagnetic fields was measured at the VDT workstations. For RBW (< or = 2,800 g), we found no excess risk associated with any VDT use during pregnancy (odds ratio [OR] = 0.9; 95% confidence interval [CI] = 0.5-1.7). For preterm birth (< or = 37 weeks), we similarly found no excess risk (OR = 0.7; 95% CI = 0.4-1.1). The risks estimated did not change substantially when hours working with VDTs were used as exposure variables. By contrast, increased risks were found for several known risk factors for LBW and preterm birth. We conclude that occupational VDT use does not increase the risk of RBW and preterm birth.

Adult↗
PubMed1996

Negative bias in exposure-response trends in occupational studies: modeling the healthy workers survivor effect.

Many occupational studies analyze trends between cumulative exposure and mortality. The authors show that such trends are, in general, negatively confounded by employment status. Mortality rates for workers who leave work ("inactive" workers) are higher than for active workers because some workers leave because they are ill. The percentage of inactive relative to active person-time is higher in low categories of cumulative exposure, causing employment status to act as a negative confounder of exposure-response trends (the opposite occurs for time-since-hire). We illustrate these phenomena using 10 "negative" mortality studies, in which adjustment for employment status removes false trends. However, adjustment for employment status will lead to biased estimates when it acts as an intermediate variable between cumulative exposure and death, as occurs directly when exposure causes a disabling disease that, in turn, causes death or indirectly when exposure causes workers to leave work. The authors illustrate this problem using simulated follow-up data for leaving, disease incidence, and mortality. In the null case in which cumulative exposure affects neither disease incidence (or mortality) nor leaving rates, employment status indeed acts as a negative confounder of exposure-response trends, and traditional adjustment eliminates this confounding. However, when cumulative exposure affects disease incidence or rates of leaving, adjustment for employment status will not be adequate. Employment status falls under the general rubric of variables that are simultaneously confounders and intermediate variables.

Bias↗
PubMed1995

Selecting an exposure lag period.

In epidemiology, there is an inclination to consider more credible the larger estimates of exposure effect. For example, higher relative risks or rate ratios are often emphasized as a criterion for choosing among various hypothesized exposure-lag values. An alternative criterion for this choice might be based on a goodness-of-fit measure. We present examples, based on hypothetical data, in which an exposure-lag parameter is estimated by trial and error fitting: we compare the behavior of the likelihood-ratio goodness-of-fit statistic obtained over the assigned values of the parameter with that of the relative risk. We show that there can be inconsistencies between the highest-estimate and likelihood-based goodness-of-fit criteria. Concern about the validity of the highest-estimate criterion prompts us to recommend that this criterion not be used for the estimation of exposure-weighting parameters, which should preferably be based on a priori biological knowledge or on goodness-of-fit criteria.

Case-Control Studies↗
PubMed1995

Mortality among Navajo uranium miners.

OBJECTIVES: To update mortality risks for Navajo uranium miners, a retrospective cohort mortality study was conducted of 757 Navajos from the cohort of Colorado Plateau uranium miners. METHODS: Vital status was followed from 1960 to 1990. Standardized mortality ratios were estimated, with combined New Mexico and Arizona non-White mortality rates used for comparison. Cox regression models were used to evaluate exposure-response relationships. RESULTS: Elevated standardized mortality ratios were found for lung cancer (3.3), tuberculosis (2.6), and pneumoconioses and other respiratory diseases (2.6). Lowered ratios were found for heart disease (0.6), circulatory disease (0.4), and liver cirrhosis (0.5). The estimated relative risk for a 5-year duration of exposure vs none was 3.7 for lung cancer, 2.1 for pneumoconioses and other respiratory diseases, and 2.0 for tuberculosis. The relative risk for lung cancer was 6.9 for the midrange of cumulative exposure to radon progeny compared with the least exposed. CONCLUSIONS: Findings were consistent with those from previous studies. Twenty-three years after their last exposure to radon progeny, these light-smoking Navajo miners continue to face excess mortality risks from lung cancer and pneumoconioses and other respiratory diseases.

Adult↗
PubMed1994

A case-control study of cancer mortality at a transformer-assembly facility.

To address earlier reports of excess cancer mortality associated with employment at a large transformer manufacturing plant, each plant operation was rated for seven exposures: Pyranol (a mixture of polychlorinated biphenyls and trichlorobenzene), trichloroethylene, benzene, mixed solvents, asbestos, synthetic resins, and machining fluids. Site-specific cancer deaths among active or retired employees were cases; controls were selected from deaths (primarily cardiovascular deaths) presumed to be unassociated with any of the study exposures. Using job records, we then computed person-years of exposure for each subject. All subjects were white males. The only unequivocal association was that of resin systems with lung cancer (odds ratio = 2.2 at 16.6 years of exposure, P = 0.001, in a multiple logistic regression including asbestos, age, year of death, and year of hire). Certain other odds ratios appeared larger, but no other association was so robust and remained as distinct after considering the multiplicity of comparisons. Study power was very limited for most associations, and several biases may have affected our results. Nevertheless, further investigation of synthetic resin systems of the type used in the study plant appears warranted.

Adult↗
PubMed1990

Bias in the one-step method for pooling study results.

The one-step (Peto) method for obtaining pooled effect estimates can yield extremely biased results when applied to unbalanced data. Even for balanced studies, the one-step estimate may incorporate an unacceptable degree of bias. In place of the one-step estimate, we recommend use of ordinary Mantel-Haenszel, weighted least squares, or maximum likelihood estimates whenever the total number of events is adequate for such methods. If the total number of events is small, we recommend exact methods.

Data Interpretation, Statistical↗
PubMed1981

A modeling study of the effect of fasting on bilirubin kinetics in Gilbert's syndrome.

The mechanism of fasting hyperbilirubinemia (FH) is not fully understood. We investigated basal bilirubin kinetics in 20 Gilbert's patients and in 7 healthy volunteers. The study was repeated in seven of these Gilbert's patients after 48-h fasting. A two-compartment model proved to be adequate for interpreting crystalline bilirubin kinetics in these individuals. The parameters of bilirubin kinetics were estimated by employing a maximum likelihood parameter estimation technique. Consistency of the model and uniqueness of the estimated parameter values (from the covariance matrix) were shown. Our results confirmed previous observations regarding impaired bilirubin kinetics in Gilbert's patients as compared to controls. The main results obtained from kinetic studies in Gilbert's patients after fasting were i) no modification in the bilirubin clearance, and ii) a more than twice increase of bilirubin turnover. These data indicate that FH is related to an increased bilirubin production (mainly intrahepatic). Furthermore, evidence arises from this study that the bilirubin tolerance test is a useful diagnostic test for Gilbert's syndrome.

Adolescent↗