Proposed PCB congener groupings for epidemiological studies.

Polychlorinated biphenyls (PCBs) have been the target of many epidemiological studies because of their toxic potential and widespread prevalence in the environment. Advances in analytic techniques have made it possible to distinguish routinely among the 209 different congeners, which vary widely in their biological properties. We propose here a classification system for the most commonly detected congeners. Group 1 (potentially estrogenic, weak phenobarbital inducers); Group 2 (potentially antiestrogenic and immunotoxic, dioxinlike); and Group 3 (phenobarbital, CYP1A and CYP2B inducers, biologically persistent). Group 2 is further subdivided according to non- and mono-ortho substituted vs. di-ortho substituted, in analogy with toxicity of dioxin congeners

Time to First Cigarette after Waking Predicts Cotinine Levels

There is wide variability in cotinine levels per cigarette smoked. We hypothesized that in addition to smoking frequency, other behavioral measures of nicotine dependence, such as the time to first cigarette after waking, are associated with cotinine levels. To test this hypothesis, we measured plasma and urinary cotinine in a community-based study of 252 black and white daily cigarette smokers. Among one pack per day smokers, plasma cotinine levels varied from 16 to 1,180 ng/mL, a 74-fold difference. Two nicotine dependence phenotypes were discerned by time after waking. Subjects in the “low” dependent phenotype smoked > 30 minutes after waking and nearly all smoked ≤20 cigarettes per day. Cotinine levels increased linearly with cigarette consumption in this group. Subjects in the “high” dependent phenotype smoked ≤30 minutes after waking but had a wide range in the frequency of daily cigarettes (6-70). Compared with the low dependent phenotype, there were relatively small differences in cotinine by cigarette frequency with evidence of a plateau effect in heavy smokers (∼30). After adjusting for cigarette frequency, the levels of cotinine by time to first cigarette were as follows: ≤5 minutes, 437 [95% confidence limits (CL), 380-494]; 6 to 30 minutes, 352 (95% CL, 291-413), 31 to 60 minutes, 229 (95% CL, 140-317), and > 60 minutes, 215 (95% CL, 110-321). Similar findings were observed for urinary cotinine. These findings suggest that the time to first cigarette is a strong predictor of nicotine uptake and should be considered in the design of smoking interventions. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3415–20

Conformation of Guanosine Cytidine 3',5'-Monophosphate (GpC)

A brief communication of preliminary results of solution of dinucleoside phosphate GpC

Structure of guanosine-3′,5′-cytidine monophosphate. I. Semi-empirical potential energy calculations and model-building

The conformation and packing scheme for guanosine-3’,5’-cytidine monophosphate, GpC, were computed by minimizing the classical potential energy. The lowest energy conformation of the isolated molecule had dihedral angles in the range of helical RNA’s, and the sugar pucker was C3‘ endo. This was used as the starting conformation in a packing search over orientation space, the dihedral angles being flexible in this step also. The packing search was restricted by constraints from our x-ray data, namely, (1) the dimensions of the monoclinic unit cell and its pseudo-C2 symmetry (the real space group is P21), (2) t,he location of the phosphorous atom, and (3) the orientation of the bases. In addition, a geometric function was devised to impose Watson-Crick base pairing. Thus, a trial structure could be sought without explicit inclusion of intermolecular potentials. An interactive computer graphics system was used for visualizing the calculated structures. The packing searches yielded two lowest energy schemes in which the molecules had the same conformation (similar to double-helical RNA) but different orientations within the unit cell. One of these was refined by standard x-ray methods to a discrepancy index of 14.4% in the C2 pseudocell. This served as the starting structure for the subsequent refinement in the real P21 cell

Respiratory Health of 985 Children Exposed to the World Trade Center Disaster: Report on World Trade Center Health Registry Wave 2 Follow-up, 2007–2008

Background. The World Trade Center (WTC) disaster of September 11, 2001, has been associated with early respiratory problems including asthma in workers, residents, and children. Studies on adults have documented persistence of longer term, 9/11-related respiratory symptoms. There are no comparable reports on children. Methods. We surveyed 985 children aged 5–17 years who enrolled in the WTC Health Registry in 2003–04, and who were re-surveyed in 2007–08. Health data were provided by parents in both surveys and focused on respiratory symptoms suggestive of reactive airway impairment (wheezing or the combination of cough and shortness of breath) in the preceding 12 months. At follow-up, adolescents aged 11–17 years completed separate surveys that screened for post-traumatic stress symptoms and behavior problems (Strengths and Difficulties Questionnaire, SDQ). Associations between respiratory symptoms in the prior 12 months with 9/11 exposures and behavioral outcomes were evaluated with univariate and multivariate methods. Results. Of the 985 children, 142 (14.4%) children reported respiratory symptoms in the prior 12 months; 105 (73.9%) children with respiratory symptoms had previously been diagnosed with asthma. Among children aged 5–10 years, respiratory symptoms were significantly elevated among African-Americans (adjusted odds ratio, (aOR) 3.8; 95% confidence interval (CI) 1.2–11.5) and those with household income below $75,000 (aOR 1.9; CI 1.0–3.7), and was more than twice as great in children with dust cloud exposure (aOR 2.2; CI 1.2–3.9). Among adolescents aged 11–17 years, respiratory symptoms were significantly associated with household income below$75,000 (aOR 2.4; CI 1.2–4.6), and with a borderline or abnormal SDQ score (aOR 2.7, 95% CI 1.4–5.2). Symptoms were reported more than twice as often by adolescents with vs. without dust cloud exposure (24.8% vs. 11.5%) but the adjusted odds ratio was not statistically significant (aOR 1.7; CI 0.9–3.2). Conclusions. Most Registry children exposed to the 9/11 disaster in New York City reported few respiratory problems. Respiratory symptoms were associated with 9/11 exposures in younger children and with behavioral difficulties in adolescents. Our findings support the need for continued surveillance of 9/11 affected children as they reach adolescence and young adulthood, and for awareness of both physical and behavioral difficulties by treating clinicians

Sarcoidosis Diagnosed After September 11, 2001, Among Adults Exposed to the World Trade Center Disaster

Objective: Explore relationships between World Trade Center (WTC) exposures and sarcoidosis. Methods: Sarcoidosis has been reported after exposure to the WTC disaster. We ascertained biopsy-proven post-9/11 sarcoidosis among WTC Health Registry enrollees. Cases diagnosed after Registry enrollment were included in a nested case–control study. Controls were matched to cases on age, sex, race or ethnicity, and eligibility group (eg, rescue or recovery worker). Results: We identified 43 cases of post-9/11 sarcoidosis. Twenty-eight incident cases and 109 controls were included in the case–control analysis. Working on the WTC debris pile was associated with sarcoidosis (odds ratio 9.1, 95% confidence interval 1.1 to 74.0), but WTC dust cloud exposure was not (odds ratio 1.0, 95% confidence interval 0.4 to 2.8). Conclusions: Working on the WTC debris pile was associated with an elevated risk of post-9/11 sarcoidosis. Occupationally exposed workers may be at increased risk

Exposure to fogger trucks and breast cancer incidence in the Long Island Breast Cancer Study Project: a case-control study

Background: Few studies have supported an association between breast cancer and DDT, usually assessed with biomarkers that cannot discern timing of exposure, or differentiate between the accumulation of chronic low-dose versus acute high-dose exposures in the past. Previous studies suggest that an association may be evident only among women exposed to DDT during biologically susceptible windows, or among those diagnosed with estrogen receptor/progesterone receptor-positive (ER+PR+) breast cancer subtypes. Self-reported acute exposure to a fogger truck, which sprayed DDT prior to 1972, was hypothesized to increase the risk of breast cancer, particularly among women exposed at a young age or diagnosed with ER+PR+ breast cancer. Methods: We examined these possibilities in the Long Island Breast Cancer Study Project (LIBCSP) (1,508 cases, 1,556 controls), which included exposure assessment by structured questionnaire and serum samples collected between 1996–1998, using adjusted logistic and polytomous regression to estimate ORs and 95% CIs. Results: Women with ER+PR+ breast cancer had a 44% increased odds of ever seeing a pre-1972 fogger truck compared to other subtypes (OR = 1.44; 95% CI 1.08-1.93). However, there was little variation in the observed increase in breast cancer risk when considering all women who reported seeing a pre-1972 fogger truck at their residence (OR = 1.16; 95% CI 0.98, 1.37), or during hypothesized susceptible windows. Self-reported acute exposure was not correlated with serum concentrations, a biomarker of long-term exposure. Conclusions: These findings support the hypothesis that seeing a fogger truck, a proxy measure for acute DDT exposure, may be associated with ER+PR+ tumors, the most commonly diagnosed breast cancer subtype among American women

Handheld cellular telephones and risk of acoustic neuroma

The hypothesis that intracranial energy deposition from handheld cellular telephones causes acoustic neuroma was tested in an epidemiologic study of 90 patients and 86 control subjects. The relative risk was 0.9 (p _ 0.07) and did not vary significantly by the frequency, duration, and lifetime hours of use. In patients who used cellular telephones, the tumor occurred more often on the contralateral than ipsilateral side of the head. Further efforts should focus on potentially longer induction periods

Influence of Type of Cigarette on Peripheral versus Central Lung Cancer

Objectives: Adenocarcinoma has replaced squamous cell carcinoma as the most common cell type of lung cancer in the United States. It has been proposed that this shift is due to the increased use of filter and lower-tar cigarettes, resulting in increased delivery of smoke to peripheral regions of the lungs, where adenocarcinoma usually occurs. We reviewed radiologic data to evaluate the hypothesis that tumors in smokers of cigarettes with lower-tar yield are more likely to occur peripherally than tumors in smokers of higher-yield cigarettes. Methods: At two urban academic medical centers, we reviewed computed tomographic scans, chest radiographs, and medical records to assign tumor location (peripheral or central) for 330 smokers diagnosed with carcinoma of the lung between 1993 and 1999. We compared the proportion of tumors in a peripheral versus central location by lifetime filter use and average lifetime tar rating (<21 and ≥21 mg). Results: Tumor location (69% peripheral and 31% central) was unrelated to cigarette filter use. Smokers of cigarettes with lower-tar ratings were more likely than those with higher ratings to have peripheral rather than central tumors (odds ratio, 1.76; 95% confidence interval, 0.89-3.47). When restricted to subjects with adenocarcinoma or squamous cell carcinoma, the odds ratio (95% confidence interval) was 2.31 (1.05-5.08). Conclusions: Among cigarette smokers with lung cancer, use of cigarettes with lower-tar yield was associated with preferential occurrence of tumors in peripheral sites. Our findings support the hypothesis that changes in smoking associated with lower-tar cigarettes have led to a shift in the location of smoking-related lung cancer

Comparison of Serum Cotinine Concentration within and across Smokers of Menthol and Nonmenthol Cigarette Brands among Non-Hispanic Black and Non-Hispanic White U.S. Adult Smokers, 2001–2006

Background: The Food and Drug Administration (FDA) is examining options for regulating menthol content in cigarettes. There are many pharmacologic properties of menthol that may facilitate exposure to tobacco smoke, and it has been suggested that the preference for menthol cigarettes in black smokers accounts for their higher cotinine levels. Objective: To assess cigarettes smoked per day–adjusted cotinine levels in relation to smoking a menthol or nonmenthol cigarette brand among non-Hispanic black and white U.S. adult smokers under natural smoking conditions. Method: Serum cotinine concentrations were measured in 1,943 smokers participating in the 2001 to 2006 National Health and Nutrition Examination Surveys (NHANES). The effect of smoking a menthol brand on cigarettes smoked per day–adjusted serum cotinine levels in these two populations was modeled by adjusting for sex, age, number of smokers living in the home, body weight, time since last smoked, and FTC (Federal Trade Commission)-measured nicotine levels. The 8- or 12-digit Universal Product Code (UPC) on the cigarette label was used to determine the cigarette brand and whether it was menthol. Results: Smoking a menthol cigarette brand versus smoking a nonmenthol cigarette brand was not associated (P≥ 0.05) with mean serum cotinine concentration in either black or white smokers. Conclusions: The higher levels of cotinine observed in black smokers compared with white smokers are not explained by their higher preference for menthol cigarette brands. Impact: Further studies like ours are needed to improve our ability to understand health consequences of future changes in tobacco product design