Cancer risk due to occupational exposure to polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) demonstrate carcinogenic activity in animal models. Although some epidemiologic studies have implicated PAHs as risk factors for human cancer, the evidence reported to date has not been consistent. The purpose of this report is to describe the associations between occupational exposure to PAHs in the workplace and each of 14 types of cancer. A population-based, case-control study was carried out in Montreal to investigate associations between a large variety of environmental and occupational exposures on the one hand, and several types of cancer on the other. A detailed job history was obtained from each subject along with information on a number of potential confounders. Each job history was reviewed by a team of experts, who used this information to construct a corresponding history of occupational exposures. Among the PAH exposures considered were benzo(a)pyrene (B(a)P) and five categories of PAHs defined on the basis of the source material, namely, wood, petroleum, coal, other sources, and any source. Altogether, 3,730 cancer patients and 533 population controls were interviewed and their job exposure histories coded. For each of 14 types of cancer analyzed, three control groups were available: other cancer patients, population controls, and the pooled set of cancer and population controls. The associations between 14 cancer types and 6 PAH exposures were analyzed using logistic regression methods. For most types of cancer evaluated, there was no evidence of excess risk due to PAHs at the levels encountered in the occupations in which PAH exposure has been prevalent in the Montreal area. For a few cancer sites–the esophagus, the pancreas, and the prostate gland–there were suggestions of excess risk; these observations are noteworthy hypotheses for further investigation. For lung cancer, there appeared to be an increased risk due to PAHs among nonsmokers and light smokers, but not among heavy smokers.     

Reduced Serum Theophylline Concentrations after Discontinuation of Azithromycin: Evidence for an Unusual Interaction

A 68-year-old man receiving long-term therapy with oral sustained-release theophylline 450 mg twice/day was admitted to the hospital after failing treatment with azithromycin for an acute exacerbation of obstructive lung disease. Peak serum theophylline concentration was 20 μg/ml (normal 10–20 μg/ml). Azithromycin was discontinued and the theophylline dosage reduced by 33%. The subsequent 80% decrease in serum theophylline to 4.6 μg/ml was unexpectedly large. Two rechallenges produced similar transient depressions of serum theophylline concentrations after withdrawal of azithromycin, suggesting an interaction. Withdrawal of azithromycin may leave an increased number of active enzyme sites available as the drug is cleared from the system. In some circumstances, it may be useful for pharmacokinetic interaction studies to continue measuring concentrations after the suspected interacting agent is stopped.     

Cerebral vascular effects of angiotensin II: new insights from genetic models.

Very little is known regarding the mechanisms of action of angiotensin II (Ang II) or the consequences of Ang II-dependent hypertension in the cerebral circulation. We tested the hypothesis that Ang II produces constriction of cerebral arteries that is mediated by activation of AT1A receptors and Rho-kinase. Basilar arteries (baseline diameter approximately 130 microm) from mice were isolated, cannulated and pressurized to measure the vessel diameter. Angiotensin II was a potent constrictor in arteries from male, but not female, mice. Vasoconstriction in response to Ang II was prevented by an inhibitor of Rho-kinase (Y-27632) in control mice, and was reduced by approximately 85% in mice deficient in expression of AT1A receptors. We also examined the chronic effects of Ang II using a model of Ang II-dependent hypertension, mice which overexpress human renin (R+) and angiotensinogen (A+). Responses to the endothelium-dependent agonist acetylcholine were markedly impaired in R+A+ mice (P<0.01) compared with controls, but were restored to normal by a superoxide scavenger (PEG-SOD). A-23187 (another endothelium-dependent agonist) produced vasodilation in control mice, but no response or vasoconstriction in R+A+ mice. In contrast, dilation of the basilar artery in response to a NO donor (NONOate) was similar in R+A+ mice and controls. Thus, Ang II produces potent constriction of cerebral arteries via activation of AT1A receptors and Rho-kinase. There are marked gender differences in cerebral vascular responses to Ang II. Endothelial function is greatly impaired in a genetic model of Ang II-dependent hypertension via a mechanism that involves superoxide.     

Surfer's ear: external auditory exostoses are more prevalent in cold water surfers.

OBJECTIVE: The study goal was to demonstrate the prevalence and severity of external auditory exostoses (EAEs) in a population of surfers and to examine the relationship between these lesions and the length of time surfed as well as water temperature in which the swimmers surfed. It was hypothesized that subjects who predominantly surfed in colder waters had more frequent and more severe exostoses. METHODS: Two hundred two avid surfers (91% male and 9% female, median age 17 years) were included in the study. EAEs were graded based on the extent of external auditory canal patency; grades of normal (100% patency), mild (66% to 99% patency), and moderate-severe (<66% patency) were assigned. Otoscopic findings were correlated with data collected via questionnaires that detailed surfing habits. RESULTS: There was a 38% overall prevalence of EAEs, with 69% of lesions graded as mild and 31% graded as moderate-severe. Professional surfers (odds ratio 3.8) and those subjects who surfed predominantly in colder waters (odds ratio 5.8) were found to be at a significantly increased risk for the development of EAEs. The number of years surfed was also found to be significant, increasing one's risk for developing an exostosis by 12% per year and for developing more severe lesions by 10% per year. Individuals who had moderate-severe EAEs were significantly more likely to be willing to surf in colder waters than were those who had mild EAEs (odds ratio 4.3). CONCLUSIONS: EAEs are more prevalent in cold water surfers, and additional years surfing increase one's risk not only for developing an EAE but also for developing more severe lesions.     

Primary care referrals for lumbar spine radiography: diagnostic yield and clinical guidelines.

BACKGROUND: Primary care requests for radiographs of the lumbar spine have come under increasing scrutiny. Guidelines aiming to reduce unnecessary radiographs by limiting referrals to patients at high risk of serious disease have been widely distributed. Trial evidence suggests that guidelines can reduce radiography referrals. It is not clear whether this reduction has been achieved in routine practice. AIM: This study, using routine data, was conducted to measure trends in pnmary care referrals for lumbar spine radiography at two hospitals between 1994 and 1999. DESIGN OF STUDY: Analysis of primary care requests for lumbar spine radiography from computerised records. SETTING: Addenbrooke's Hospital, Cambridge (1 July 1994 to 30 June 1999), and Ipswich General Hospital (1 July 1995 to 30 June 1999), United Kingdom. METHOD: All primary care requests for lumbar radiography were identified electronically from computerised information systems. A random sample of 2100 radiography reports were classified according to clinical importance. These classifications were used to examine whether the proportion of radiographs demonstrating potentially more serious findings had increased between 1994 and 1999. RESULTS: There was no evidence that primary care referrals for radiography of the lumbar spine had decreased between 1994 and 1999 at either hospital. General practitioners did not progressively refer more high-risk patients for lumbar radiography. Only a small proportion of patients had important radiographic findings that might warrant specialist referral or specific therapy. CONCLUSION: The implementation of diagnostic guidelines offers much to the NHS. However in these two hospitals, the reduction in radiograph utilisation evident in trials was not achieved. Guideline development is a resource intensive process; distribution must be supported by more effective implementation strategies.     

Tissue collection for correlative studies in childhood cancer clinical trials: ethical considerations and special imperatives.

Federal regulations prescribe distinct protections for children participating in research studies. Procedures for collecting tissue specimens from children solely for research purposes must pose no more than a minor increase over minimum risk, thereby limiting the approvable correlative biologic studies to evaluate molecularly targeted agents in children with cancer. Ethical issues arise when approvable correlative studies are a mandatory component of an early-phase pediatric clinical trial of new anticancer agents. The National Cancer Institute Cancer Therapy Evaluation Program sponsored a workshop in 2002 to discuss tissue collection for correlative biologic studies in early-phase childhood cancer clinical studies of molecularly targeted agents. Workshop participants recommended the following: (1) tissue specimens for correlative studies should provide vital clinical and scientific results to qualify for early-phase pediatric study consideration; (2) parents should receive a realistic appraisal of the risks, requirements, and potential for benefit of phase I protocol participation; (3) investigators should clearly distinguish clinically necessary procedures from research procedures of no benefit to the child to improve correlative study informed consent; and (4) participation in correlative research studies included in clinical trials generally should be voluntary. The need to acquire important biologic data regarding new molecular agents will challenge the ingenuity of pediatric cancer researchers, necessitating the application of highly sensitive laboratory assay methods, new imaging procedures, and preclinical models of childhood cancer. Such innovative methods can allow necessary scientific information to be obtained while simultaneously respecting the protections appropriately afforded to children participating in research studies and minimizing the burden of research participation for children with cancer and their families.     

Heightened vulnerability and increased risk-taking among adolescent chat room users: results from a statewide school survey.

PURPOSE: To profile adolescent Internet chat room users in terms of demographic characteristics, psychological and environmental factors, and behavioral risk factors. METHODS: The study sample was drawn from respondents to an anonymous statewide survey of 50,168 9th-grade public school students and included 40,376 students who reported Internet access at home and 19,511 who accessed chat rooms. Data were collected by the Minnesota Student Survey (MSS), a survey that has been administered triennially by the state's education department to public school students in grades 6, 9, and 12 since 1989. The MSS includes more than 117 questions (300 variables) addressing attitudinal, behavioral, and environmental issues. Data analysis consisted of comparing the odds of a particular characteristic or behavior for chat room users with that of nonusers. Analyses were run separately for boys and girls. The homogeneity of odd ratios was tested with the Breslow-Day statistic using SPSS for Windows. RESULTS: For boys and girls, use of Internet chat rooms was associated with psychological distress, a difficult living environment, and a higher likelihood of risky behaviors. Although most chat room users did not report serious problems, this group included a disproportionate number of troubled individuals. CONCLUSIONS: Because chat room use serves as an indicator of heightened vulnerability and risk-taking, parents and others need to be aware of potential dangers posed by online contact between strangers and youth.     

Estradiol and tryptophan depletion interact to modulate cognition in menopausal women.

Despite an abundance of data in animals, there is little research in humans regarding how estrogen and serotonin (5-HT) may interact to influence cognition. Through the use of estrogen treatment (ET) and tryptophan depletion (TRP-D) in a within-subject design involving healthy menopausal women, we have manipulated both estrogen and 5-HT in order to evaluate their individual and joint effects. Although neither manipulation influenced visuospatial learning, a significant interaction suggested that estrogen exerted a protective effect on verbal memory, such that TRP-D impaired performance to a greater extent before the administration of ET. In consonance with this finding, ET was associated with a small, but positive mood effect on the day following active TRP-D. In addition, ET significantly improved letter-cued verbal fluency with and without TRP-D. Finally, time since last menstrual period was significantly associated with verbal memory scores, such that longer length of hypogonadism resulted in decreased verbal memory performance. These data support the interaction of estrogen and 5-HT in nonreproductive behavior in humans as well as highlight the role of ovarian steroids in cognition.     

Healthy choices: motivational enhancement therapy for health risk behaviors in HIV-positive youth.

This study piloted a brief individual motivational intervention targeting multiple health risk behaviors in HIV-positive youth aged 16-25. Interviews about sexual behavior and substance use and viral load testing were obtained from 51 HIV-positive youth at baseline and post intervention. Youth were randomized to receive a four-session motivational enhancement intervention (N = 25) or to a wait-list control (N = 26). Of the eligible youth approached, 88% agreed to participate, and 80% percent of participants completed at least three of four sessions. The treatment group showed significantly greater reductions in unprotected sex acts and in viral load compared with controls. Although change scores for substance use were not significantly different between the two groups, paired t tests demonstrated that reductions in alcohol use and marijuana use were significant for the treatment group at the trend level. There were no significant differences in substance use from baseline to posttest for the control group. Findings demonstrate the potential of a brief motivational enhancement intervention to improve health risk behaviors in HIV-positive youth. Larger randomized clinical trials are warranted. Resources required for retention should not be underestimated.