A case-control study in North Carolina involving 255 women with oral and pharyngeal cancer and 502 controls revealed that the exceptionally high mortality from this cancer among white women in the South is primarily related to chronic use of snuff. The relative risk associated with snuff dipping among white nonsmokers was 4.2 (95 per cent confidence limits, 2.6 to 6.7), and among chronic users the risk approached 50-fold for cancers of the gum and buccal mucosa--tissues that come in direct contact with the tobacco powder. In the absence of snuff dipping, oral and pharyngeal cancer resulted mainly from the combined effects of cigarette smoking and alcohol consumption. The carcinogenic hazard of oral snuff is of special concern in view of the recent upswing in consumption of smokeless tobacco in the United States.
examined the cardiac autonomic response to daily variations in PM in 26 elderly (mean age 81) individuals for 3 consecutive weeks. Several standardized methods were used to measure 24-hr average PM concentrations prior to the clinical test inside (indoor PM2.5) and immediately outside (outdoor PM2.5 and PM2.5-10) of participants' residences. Resting, supine, 6-min R wave to R wave (R-R) interval data were collected to estimate high frequency (0.15-0.40 Hz) and low frequency (0.04-0.15 Hz) powers and standard deviation of normal R-R intervals (SDNN) as cardiac autonomic control indices. Participant-specific lower heart rate variability days were defined as days for which the high-frequency indices fell below the first tertile of the individual's high-frequency distribution over the study period. Indoor PM2.5 > 15 microg/m3 was used to define high pollution days. Results show that the odds ratio (95% confidence interval) of low heart rate variability high frequency for high (vs. not high) pollution days was 3.08 (1.43, 6.59). The ss-coefficients (standard error) from mixed models to assess the quantitative relationship between variations in indoor PM2.5 and the log-transformed high frequency, low frequency, and SDNN were: -0.029 (0.010), -0.027 (0.009), and -0.004 (0.003), respectively. This first study of cardiac autonomic control response to daily variations of PM2.5 indicates that increased levels of PM2.5 are associated with lower cardiac autonomic control, suggesting a possible mechanistic link between PM and cardiovascular disease mortality.ImagesFigure 1
A revised protocol for the exfoliated cell micronucleus assay was field-tested in a population exposed to a genotoxic agent, snuff, at levels associated with a significant increase in cancer risk. The standard assay involves examination of epithelial smears to determine the prevalence of micronucleated cells, an indication of chromosome breakage or mitotic interference. The assay was revised to increase specificity and to include separate scoring of other nuclear anomalies associated with cytotoxicity and genotoxicity. The modified assay was applied to buccal smears of 38 female snuff users and 15 female nonusers recruited from a North Carolina clinic in 1987. The prevalence of micronucleation was elevated in the snuff users as compared with the nonusers (prevalence ratio = 2.4, 95% confidence interval 1.1-5.2) and, to a lesser extent, at the usual contact site as compared with a distal buccal site in the snuff users (prevalence ratio = 1.5, 95% confidence interval 0.9-2.5). The pattern of relative frequencies of several nuclear anomalies provided strong evidence of a cytotoxic effect, the prevalence ratios ranging from 2 to 13. Nuclear degenerative phenomena can be difficult to distinguish from classical micronuclei; thus, the observed association of indicators of cytotoxicity with exposure introduces the possibility of bias away from the null in micronucleus findings due to differential misclassification. Until methods to better distinguish extranuclear bodies of different origins become available, investigators should use the revised protocol and should focus on agents not thought to be cytotoxic.
This study investigates the relationship between ambient fine particle pollution and impaired cardiac autonomic control in the elderly. Heart rate variability ( HRV ) among 56 elderly ( mean age 82 ) nonsmoking residents of a retirement center in Baltimore County, Maryland, was monitored for 4 weeks, from July 27 through August 22, 1998. The weather was seasonally mild ( 63 ± 848F mean daily temperature ) with low to moderate levels of fine particles ( PM 2.5 < 50 g / m 3 ) . Two groups of approximately 30 subjects were examined on alternate days. A spline mixed -effects model revealed a negative relationship between outdoor 24 -h average fine particulate matter ( PM 2.5 ) and high -frequency ( HF ) HRV that was consistent with our earlier Baltimore study for all but 2 days. These 2 days were the only days with significant precipitation in combination with elevated PM 2.5 . They were also unusual in that back -trajectory of their air masses was distinctly different from those on the other study days, emanating from the direction of rural Pennsylvania. Mixed -effects analysis for all 24 study days showed a small negative association of outdoor PM 2.5 with HF HRV ( À 0.03 change in log [ HF HRV ] for a 10 g / m 3 increment in PM 2.5 ) after adjustment for age, sex, cardiovascular status, trend, maximum temperature, average dew point temperature, random subject intercepts, and autocorrelated residuals. After excluding study days 4 and 5, this association was strengthened ( À 0.07 change in log [ HF HRV ] for 10 g / m 3 PM 2.5 , 95% CI À 0.13 to À 0.02 ) and was similar to that obtained in an earlier study ( À 0.12 change in log [ HF HRV ] for a 10 g / m 3 increment in outdoor PM 2.5 , 95% CI À 0.24 to À 0.00 ) [ Liao D., Cai J., Rosamond W.D., Barnes R.W., Hutchinson R.G., Whitsel E.A., Rautaharju P., and Heiss G. Cardiac autonomic function and incident coronary heart disease: a population -based case -cohort study. The ARIC Study. Atherosclerosis Risk in Communities Study. Am J Epidemiol 1997: 145 ( 8 ) : 696 ± 706 ] . Acute ( 1 to 4 h ) previous PM 2.5 exposure did not have a stronger impact than the 24 -h measure. A distributed lag model incorporating the six preceding 4 -h means also did not indicate any effect greater than that observed in the 24 -h measure. This study is consistent with earlier findings that exposures to PM 2.5 are associated with decreased HRV in the elderly.
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