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J M Samet

Publications and source records attributed to J M Samet.

At least 109 records · Page 6Linked to original sources
PubMed1995

What can we expect from epidemiologic studies of chemical mixtures?

Determining the health risks of complex mixtures is equally daunting to toxicologists using experimental approaches and to epidemiologists using observational approaches. Accurate exposure estimation is essential in investigating the health consequences of exposures to chemical mixtures; random and non-random errors in exposure estimation typically blunt the sensitivity of epidemiologic studies and constrain interpretation of findings. On the other hand, epidemiologic data have the implicit strength of directly addressing risks of exposures in human populations and, for this reason, the findings of epidemiologic research have received prominence in the development of regulations. Epidemiologic studies have proved informative about many complex mixtures including cigarette smoke, diesel exhaust, and even the human diet, perhaps one of the most complex mixtures to which we are exposed. The continued interest in studying complex chemical mixtures is emphasized by this and other recent meetings directed at the topic. The variety of approaches used by epidemiologists in approaching complex mixtures reflects the difficulty of exposure estimation. Five general strategies can be identified, each with differing underlying assumptions and yielding results with distinct implications from biological and public health perspectives. These include treating the mixture as though it were a single agent, using a single component as a surrogate for the mixture, creating a summary index involving multiple components, attempting to estimate independent effects of individual components, and characterizing the independent and joint effects of key components of the mixture. These approaches have proved successful in establishing the adverse effects of a number of complex chemical mixtures including mainstream and environmental tobacco smoke and outdoor air pollution. New approaches for exposure assessment, including personal monitoring and biomarkers, should strengthen future epidemiologic investigations of complex chemical mixtures.

Air Pollutants↗
PubMed1995

Lung cancer in radon-exposed miners and estimation of risk from indoor exposure.

BACKGROUND: Radioactive radon is an inert gas that can migrate from soils and rocks and accumulate in enclosed areas, such as homes and underground mines. Studies of miners show that exposure to radon decay products causes lung cancer. Consequently, it is of public health interest to estimate accurately the consequences of daily, low-level exposure in homes to this known carcinogen. Epidemiologic studies of residential radon exposure are burdened by an inability to estimate exposure accurately, low total exposure, and subsequent small excess risks. As a result, the studies have been inconclusive to date. Estimates of the hazard posed by residential radon have been based on analyses of data on miners, with recent estimates based on a pooling of four occupational cohort studies of miners, including 360 lung cancer deaths. PURPOSE: To more fully describe the lung cancer risk in radon-exposed miners, we pooled original data from 11 studies of radon-exposed underground miners, conducted a comprehensive analysis, and developed models for estimating radon-associated lung cancer risk. METHODS: We pooled original data from 11 cohort studies of radon-exposed underground miners, including 65,000 men and more than 2700 lung cancer deaths, and fit various relative risk (RR) regression models. RESULTS: The RR relationship for cumulative radon progeny exposure was consistently linear in the range of miner exposures, suggesting that exposures at lower levels, such as in homes, would carry some risk. The exposure-response trend for never-smokers was threefold the trend for smokers, indicating a greater RR for exposure in never-smokers. The RR from exposure diminished with time since the exposure occurred. For equal total exposure, exposures of long duration (and low rate) were more harmful than exposures of short duration (and high rate). CONCLUSIONS: In the miners, about 40% of all lung cancer deaths may be due to radon progeny exposure, 70% of lung cancer deaths in never-smokers, and 39% of lung cancer deaths in smokers. In the United States, 10% of all lung cancer deaths might be due to indoor radon exposure, 11% of lung cancer deaths in smokers, and 30% of lung cancer deaths in never-smokers. This risk model estimates that reducing radon in all homes exceeding the U. S. Environmental Protection Agency's recommended action level may reduce lung cancer deaths about 2%-4%. These estimates should be interpreted with caution, because concomitant exposures of miners to agents such as arsenic or diesel exhaust may modify the radon effect and, when considered together with other differences between homes and mines, might reduce the generalizability of findings in miners.

Adult↗
PubMed1995

Selective induction of prostaglandin G/H synthase I by stem cell factor and dexamethasone in mast cells.

This study examines the regulatory effects of two cytokines, stem cell factor (SCF) and interleukin-3, and a glucocorticoid, dexamethasone, on lipid mediator generation in mouse bone marrow-derived mast cells (BMMC). Treatment of BMMC with SCF induced a modest, dose-dependent increase in three eicosanoids, thromboxane B2, prostaglandin D2, and leukotriene B4. These increases were accompanied by a marked elevation in cytosolic PLA2 (cPLA2). Dexamethasone blocked the induction of cPLA2 levels and the elevation in leukotriene B4 induced by SCF. By contrast, the combination of SCF and dexamethasone dramatically increased (5-8-fold) the capacity by BMMC to produce prostanoid products. This increase in prostanoid products was mirrored by an increase in prostaglandin G/H synthase I (PGHS-I) levels. Dexamethasone, alone, had no effect on PGHS-I, cPLA2, or prostanoid levels. Moreover, neither SCF or dexamethasone, alone or in combination, influenced prostaglandin G/H synthase II (PGHS-II) levels. In contrast to SCF, interleukin-3 alone or in combination with dexamethasone had no effect on prostanoid synthesis or PGHS-I or II levels. To better understand the SCF and dexamethasone effect, PGHS-I and PGHS-II mRNA expression were examined by Northern analysis. PGHS-I mRNA was markedly induced (maximal levels at 5 h) by the combination of SCF and dexamethasone. PGHS-II mRNA was undetectable in either control or SCF/dexamethasone-treated BMMC. Neither SCF or dexamethasone, alone, altered mRNA for either PGHS isotype. Taken together, these studies reveal that PGHS-I may be critical to prostanoid formation in mast cells exposed to cytokines and glucocorticoids. Moreover, they suggest that synergistic induction of PGHS-I could represent a novel mechanism for the anti-inflammatory action of glucocorticoids.

Animals↗
PubMed1995

Asthma and the environment: do environmental factors affect the incidence and prognosis of asthma?

Rising mortality and prevalence rates for asthma in the United States and other countries have again raised concern that environmental agents, particularly air pollutants, may be responsible. While asthma has been linked to environmental causes and triggers, we still have not found specific agents underlying the increasing morbidity and mortality from the disease. Research may be strengthened by the identification of genes for asthma, leading to improved characterization of gene-environment interactions and by more accurate methods for exposure assessment.

Air Pollution↗
PubMed1995

Biased comparisons of lung cancer survival across geographic areas: effects of stage bias.

This report illustrates bias that may affect comparative analyses of cancer survival across geographic areas and describes how it limits the conclusions that can be drawn from such data. Despite the application of a standardized procedure for assigning tumor stage, patients from different areas who are assigned the same stage category may not be homogeneous with respect to extent of disease, if staging is accomplished more aggressively in one group than in another. Stage-specific comparisons of survival may be biased as a result. Cancer sites for which a large majority of patients are treated surgically may be less susceptible to stage bias.

Aged↗
PubMed1995

Radon-exposed underground miners and inverse dose-rate (protraction enhancement) effects.

Recent models for radon-induced lung cancer assume that at high levels of cumulative exposure, as experienced historically by many underground miners of uranium and other ores, the risk of lung cancer follows an inverse dose-rate (protraction enhancement) pattern. That is, for equal total dose, a greater risk is incurred by those whose total dose is accumulated at a lower rate over a longer duration than at a higher rate over a shorter duration. This inverse dose-rate effect is hypothesized to be the consequence of multiple traversals of the nucleus of a target cell by alpha particles. It has recently been concluded, however, that for low total doses, as in most residential settings, the inverse dose-rate effect should diminish and perhaps even disappear, since at very low doses the probability that more than one alpha particle would traverse a cell is small and there would be no possibility for interactions from multiple hits. Pooling original data from 11 cohort studies of underground miners, including nearly 1.2 million person-y of observation and 2,701 lung cancer deaths, we evaluate the presence of an inverse dose-rate effect and its modification by total dose. An inverse dose-rate effect was confirmed in each cohort, except one, and overall in the pooled data. There also appears to be a diminution of the inverse dose-rate effect below 50 Working Level Months (WLM), although analyses were necessarily hampered by a limited range of exposure rates at low total WLM. These data support both the presence of an inverse dose-rate effect, as well as its diminution at low total dose. As a consequence, assessment of risks of radon progeny exposure in homes (on average 15-20 WLM for a lifetime) using miner-based models should not assume an ever-increasing risk per unit dose. Rather, it is more appropriate to apply risk models that take into account protraction enhancement and its diminution.

Humans↗
PubMed1995

Trends in alcohol-related mortality among New Mexico's American Indians, Hispanics, and non-Hispanic whites.

Reduction of alcohol-related mortality is a national goal for health promotion and disease prevention. We conducted this analysis to determine whether trends in New Mexico's Hispanics, non-Hispanic Whites, and American Indians were consistent with national trends in alcohol-related mortality, and whether differences in drinking patterns could account for racial and ethnic differences in rates. Age-adjusted, race-specific, and ethnic-specific alcohol-related mortality rates and 95% confidence intervals were calculated for 5-year periods for 1958-1991 using New Mexico vital statistics data. We estimated the prevalence of acute and chronic at-risk drinking behaviors and abstinence from data collected by the Behavioral Risk Factor Surveillance System (BRFSS) for the period 1986-1992. We found that alcohol-related mortality rates varied substantially by race, ethnicity, sex, age, and calendar period. American Indians had the highest rates for both sexes. Rates increased sharply from the period 1958-1962 until the late 1970s and the early 1980s, and then began to decrease rapidly. However, during the most recent decade, the rates have followed contrasting trends in the three ethnic and racial groups. Although rates have continued to decline among non-Hispanic Whites, rates for Hispanics and American Indians have not declined, and still remain substantially higher than rates during the 1958-1962 period. Differences in at-risk drinking behaviors reported to the BRFSS do not explain the contrast in race-specific and ethnic-specific mortality rates. Although progress has been made in reducing national per capita alcohol consumption and alcohol-related mortality, certain high-risk racial and ethnic groups may not be sharing in the progress.

Adult↗
PubMed1995

Asthma in Jemez Pueblo schoolchildren.

Asthma, a major chronic health problem of children, has received little investigation in Native Americans. We conducted a survey of asthma in children of Jemez Pueblo, Jemez, New Mexico, in response to concerns of the community and health care providers about the frequency of asthma. In collaboration with Jemez Pueblo, we developed a standardized questionnaire and administered it to parents of 318 children aged 3 to 13 years. Parents reported that 12.3% had been diagnosed as having asthma or reactive airway disease by a physician or other health care practitioner. Asthma was reported as still active at the time of the interview for 55% of those subjects. The study showed that asthma was not uncommon among the Jemez Pueblo children and, in fact, was more common than in recent nationwide surveys.

Adolescent↗
PubMed1995

Regulation of arachidonic acid, eicosanoid, and phospholipase A2 levels in murine mast cells by recombinant stem cell factor.

The current study evaluates the capacity of recombinant rat stem cell factor (rrSCF) to regulate enzymes that control AA release and eicosanoid generation in mouse bone marrow-derived mast cells (BMMCs). Initial studies indicated that rrSCF provided for 24 h inhibited the release of AA into supernatant fluids of antigen- and ionophore A23187-stimulated BMMCs. Agonist-induced increases in cellular levels of AA were also inhibited, albeit to a lesser degree by rrSCF. To determine the inhibitory mechanism, several steps (e.g., mobilization of cytosolic calcium, release of BMMC granules, and regulation of phospholipase A2 [PLA2] activity) that could influence AA release were measured in rrSCF-treated cells. rrSCF did not alter the capacity of BMMCs to mobilize cytosolic calcium or release histamine in response to antigen and ionophore. BMMCs released large amounts of PLA2 with characteristics of the group II family in response to antigen and ionophore A23187. rrSCF treatment of BMMCs reduced the secretion of this PLA2 activity by BMMCs. Partial purification of acid-extractable PLA2 from rrSCF-treated and untreated BMMCs suggested that rrSCF decreased the quantity of acid-stable PLA2 within the cells. In contrast to group II PLA2, the quantity of cPLA2 (as determined by Western blot analysis) increased in response to rrSCF. To assess the ramifications of rrSCF-induced reductions in AA and group II PLA2, eicosanoid formation was measured in antigen- and ionophore-stimulated BMMCs, rrSCF-inhibited (100 ng/ml, 24 h) prostaglandin D2 (PGD2), thromboxane B2, and leukotriene B4 by 48.4 +/- 7.7%, 61.1 +/- 10.0% AND 38.1 +/- 3.6%, respectively, in antigen-stimulated cells. Similar patterns of inhibition were observed in ionophore-stimulated BMMCs. The addition of a group I PLA2 or exogenous AA to BMMCs reversed the inhibition of eicosanoid generation induced by rrSCF. Together, these data indicate that rrSCF differentially regulates group II and cytosolic PLA2 activities in BMMCs. The resultant reductions in eicosanoid generation suggest that group II PLA2 provides a portion of AA that is used for eicosanoid biosynthesis by BMMCs.

Animals↗
PubMed1995

Controlling the avoidable causes of cancer: needs and opportunities for etiologic research.

This meeting of the President's Cancer Panel was designed to provide an overview of known and suspect causes of cancer and to indicate those that might be considered avoidable. Two complex concepts are inherent in this charge: cause and avoidability. Risk factors for cancer are designated as causal when the evidence from observational and laboratory research is judged sufficient in relation to criteria for causality; the extent to which cancers of specific sites can be avoided is best estimated by the attributable risk statistic, which incorporates both the exposure pattern and the relative risk for the cancer-causing agent. A research agenda on avoidable causes of cancer should then address both the risks associated with the agents that cause cancer and the pattern of exposure to the agents. Presentations at the meeting highlighted gaps in the evidence on the risks associated with various known and potential causes of cancer and on the patterns of exposure across the diverse groups within the population. In spite of these gaps, presenters emphasized that the evidence is already sufficient to justify intervention for many agents and that action need not be delayed for the well-characterized causes of cancer. In addition to research recommendations offered by presenters for specific causal agents, the scientific basis for cancer prevention might be generally strengthened by new research strategies directed at developing new tools for exposure assessment, for investigating the risks of mixtures, and for population surveillance.

Humans↗
PubMed1995

Errors in exposure assessment, statistical power and the interpretation of residential radon studies.

To date, epidemiological studies of risk from residential radon have not convincingly demonstrated an association with lung cancer. These case-control studies, however, have inherent limitations due to errors in estimates of exposure to indoor radon. These errors take on special significance because the level of residential risk predicted from studies of underground miners is relatively low and possibly at the limit detectable by current epidemiological methods. To illustrate the problem caused by errors in exposure assessment, a series of case-control studies were simulated and resulting dose-response relationships evaluated. For each of four assumed error distributions for exposure to radon progeny, 10 indoor radon studies of 700 cases and 700 controls were generated randomly from a population with a risk of radon-induced lung cancer based on extrapolations from studies of underground miners. When exposures were assumed as known without error, 6 of 10 studies failed to find a significant dose response, in accord with the theoretical power of the study of 0.47. For simulations in which exposures were measured with error, the situation was worse, as the power of the study was reduced further and it was even less likely that a single study would result in a significant finding. For each error scenario, combining data from the 10 simulated studies did result in a significant dose response. However, the pooled results are somewhat misleading, because the effects of mobility, missing radon measurements, residential occupancy and potential confounding variables such as cigarette smoking were not taken into account. Empirical estimates of power were computed using 1,000 simulated case-control studies. When mobility and missing radon measurements in prior homes were incorporated into the design, the power of the study decreased, reducing the chance of detecting a significant effect of exposure. Enlarging study size to 2,000 cases and 2,000 controls increased the power of the study to 0.90 when exposure error was absent and subjects lived in one home only, but power was below 0.40 under realistic conditions for exposure error and mobility. When studies were generated under an assumption that exposure does not increase risk, up to 15% of simulated studies with 700 cases and 700 controls resulted in an estimated dose-response parameter in excess of the dose response from studies of miners. With increasing mobility and exposure error, it became virtually impossible to distinguish between the distributions of risk estimates from simulated studies based on an underlying excess relative risk of 0.015/working level month from estimates based on no risk from exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Case-Control Studies↗
PubMed1994

Evidence that secretory phospholipase A2 plays a role in arachidonic acid release and eicosanoid biosynthesis by mast cells.

This study investigated the role of secretory PLA2 (sPLA2) in arachidonic acid (AA) release and lipid mediator generation in mouse bone marrow-derived mast cells. Initial studies indicated that mast cells contain multiple PLA2 activities and secreted PLA2 activity upon Ag stimulation. The secreted PLA2 activity is blocked by DTT and by a group II PLA2-neutralizing Ab. Mast cells incubated with groups I or II PLA2 selectively release polyunsaturated fatty acids, such as AA, into supernatant fluids. The bulk of AA released by sPLA2 is derived from phosphatidylethanolamine. The fatty acids released by extracellular PLA2 mimic those found in supernatant fluids after Ag stimulation of mast cells. Incubation of mast cells with PLA2 generates cyclooxygenase (CO) products but no 5-lipoxygenase (5-LO) products. Ag, but not PLA2, induces the translocation of 5-LO to cellular membranes and the formation of 5-LO products. The addition of sPLA2 to Ag-stimulated mast cells increases the synthesis of 5-LO products. Octadeuterated AA (2H8AA) added to the outside of cells to trace extracellular AA metabolism is rapidly converted to CO products. Addition of sPLA2, or Ag in combination with 2H8AA reduces the quantity of 2H8AA converted to deuterated CO products, when compared with adding 2H8AA alone. The reduction of deuterated CO products can be accounted for with increases in nondeuterated CO products. 2H8AA is only converted to 5-LO produces when mast cells are activated with Ag. The amount of 2H8AA converted to deuterated 5-LO products is reduced by the addition of PLA2 to Ag-stimulated cells. The competitive formation of deuterated and nondeuterated products observed when mast cells are incubated with 2H8AA, indicates that extracellular AA released by sPLA2 is used for both CO and 5-LO product formation. Taken together, these data reveal a role for sPLA2 in the release of AA and demonstrate that AA released by this mechanism is used for eicosanoid generation.

Animals↗
PubMed1994

Determinants of receiving breast-conserving surgery. The Surveillance, Epidemiology, and End Results Program, 1983-1986.

BACKGROUND: Although breast-conserving surgery was used with increasing frequency during the 1980s for management of breast cancer, most women still undergo mastectomy, and a substantial variation has been documented in the proportion of women receiving breast-conserving surgery across regions of the country. Using data from the Surveillance, Epidemiology, and End Results (SEER) Program for 1983-1986, we assessed characteristics of the county of residence as predictors of receipt of breast-conserving surgery and determined whether regional variation persisted after considering these characteristics. METHODS: The data used involved all 19,661 non-Hispanic white women with localized breast cancer diagnosed in 1983 through 1986 in the nine SEER regions. Information on county characteristics was obtained from standard sources and merged with the SEER data. Univariate multivariate statistical methods were used to assess the effects of county characteristics on type of surgery for breast cancer. RESULTS: As anticipated, age was a strong predictor of type of surgery. In analyses that controlled for age, county characteristics that significantly predicted receipt of breast-conserving surgery included physician-to-population ratio, education and income levels, the presence of cancer center, and the presence of a city of at least 100,000. After controlling for these factors using multiple logistic regression, substantial regional variation persisted. CONCLUSIONS: Regional variation in treatment of localized breast cancer across the SEER regions is not explained by patient's age or county characteristics. Research is needed to address the decision making of individual patients and their physicians regarding type of surgery.

Aged↗
PubMed1994

Contrasting trends of prostate cancer incidence and mortality in New Mexico's Hispanics, non-Hispanic whites, American Indians, and blacks.

BACKGROUND: Prostate cancer has increased in epidemic proportions during the 1980s. Although marked differences in ethnic and racial temporal trends for prostate cancer have been observed both in the United States and internationally, the trends in Hispanics and American Indians have not been described extensively. METHODS: To characterize the occurrence of prostate cancer among non-Hispanic whites, Hispanics, American Indians, and blacks in New Mexico, the authors examined cancer incidence data collected by the New Mexico Tumor Registry for the period 1969-1991 and mortality data collected by the New Mexico Bureau of Vital Statistics for the period 1958-1991. RESULTS: From 1969 to 1991, age-adjusted incidence rates increased from 74.4 to 139.1 per 100,000 (87%) among non-Hispanic whites and from 54.0 to 94.7 (75%) among Hispanics. American Indians had the lowest incidence rates of all groups. Over the same period, incidence rates for local-stage cancers increased by 93% and 81% among non-Hispanic whites and Hispanics, respectively, but were stable for American Indians and blacks, whereas rates for regional-stage cancers increased sharply. Incidence rates of distant-stage disease decreased among non-Hispanic whites from 1969 through 1991. In contrast, incidence rates of distant-stage disease among Hispanics increased through 1982. From 1983 to date, age-adjusted mortality rates of prostate cancer decreased among all groups except Hispanics. CONCLUSION: The patterns of incidence and mortality are consistent with a stage migration. The recent decrease in age-adjusted prostate cancer mortality rates for non-Hispanic whites is consistent with that expected following the decrease in distant-stage disease incidence. Differential access to medical care and prostate cancer screening may account for these trends.

Black or African American↗
PubMed1994

Assessment of ecologic regression in the study of lung cancer and indoor radon.

Ecologic regression studies conducted to assess the cancer risk of indoor radon to the general population are subject to methodological limitations, and they have given seemingly contradictory results. The authors use simulations to examine the effects of two major methodological problems that affect these studies: measurement error and misspecification of the risk model. In a simulation study of the effect of measurement error caused by the sampling process used to estimate radon exposure for a geographic unit, both the effect of radon and the standard error of the effect estimate were underestimated, with greater bias for smaller sample sizes. In another simulation study, which addressed the consequences of uncontrolled confounding by cigarette smoking, even small negative correlations between county geometric mean annual radon exposure and the proportion of smokers resulted in negative average estimates of the radon effect. A third study considered consequences of using simple linear ecologic models when the true underlying model relation between lung cancer and radon exposure is nonlinear. These examples quantify potential biases and demonstrate the limitations of estimating risks from ecologic studies of lung cancer and indoor radon.

Bias↗