Residential proximity to agricultural pesticide use and incidence of breast cancer in the California Teachers Study cohort

We examined the association between residential proximity to agricultural pesticide use and breast cancer incidence among members of the California Teachers Study cohort, a large study of professional school employees with extensive information on breast cancer risk factors, followed for cancer incidence since 1995. We identified 1552 invasive breast cancer cases, diagnosed between 1996 and 1999, among 114,835 cohort members. We used California Pesticide Use Reporting data to select pesticides for analysis based on use volume, carcinogenic potential, and exposure potential; a Geographic Information System was used to estimate pesticide applications within a half-mile radius of subjects' residences. We applied Cox proportional hazard models to estimate hazard rate ratios (HR) for selected pesticides, adjusting for age, race, and socioeconomic status. We saw no association between residential proximity to recent agricultural pesticide use and invasive breast cancer incidence. HR estimates for the highest compared to the lowest exposure categories for groups of agents were as follows: probable or likely carcinogens (1.07, 95% confidence interval (CI): 0.86-1.32), possible or suggestive carcinogens (1.06, 95% CI: 0.87-1.29), mammary carcinogens (1.15, 95% CI: 0.90-1.48), and endocrine disruptors (1.03, 95% CI: 0.86-1.25). HR estimates for other groups and individual pesticides did not differ from unity, nor was there a trend for any groupings of or individual pesticides examined. Stratifying by menopausal status or family history of breast cancer did not substantially affect our results. Our analyses suggest that breast cancer incidence is not elevated in areas of recent, high agricultural pesticide use in California.     

Maintenance treatment with interferon for advanced ovarian cancer: results of the Northern and Yorkshire gynaecology group randomised phase III study

A randomised phase III trial was conducted to assess the role of interferon-alpha (INFalpha) 2a as maintenance therapy following surgery and/or chemotherapy in patients with epithelial ovarian carcinoma. Patients were randomised following initial surgery/chemotherapy to interferon-alpha 2a as 4.5 mega-units subcutaneously 3 days per week or to no further treatment. A total of 300 patients were randomised within the study between February 1990 and July 1997. No benefit for interferon maintenance was seen in terms of either overall or clinical event-free survival. We conclude that INF-alpha is not effective as a maintenance therapy in the management of women with ovarian cancer. The need for novel therapeutics or strategies to prevent the almost inevitable relapse of patients despite increasingly effective surgery and chemotherapy remains.     

Tau phosphorylation in Alzheimer’s disease

The two predominant pathological concomitants of Alzheimer’s disease (AD) are senile plaques and neurofibrillary tangles. Although many biochemical studies have addressed the composition and formation of these AD hallmarks, very little is known about the interrelationship between the two. Here we present evidence that the tau phosphorylation characteristic of neurofibrillary tangles may be mediated by a physical association of MKK6 (mitogen-associated protein kinase kinase 6) with tau and subsequent phosphorylation of tau by the MKK6 substrate, p38 MAPK; and that APP (β-amyloid precursor protein) may be co-immunoprecipitated both with MKK6 and its upstream MAPKKK, ASK1. Taken together with recent data demonstrating APP dimerization by β-amyloid peptide (Aβ) (Lu et al., 2003), and the possible activation of ASK1 via APP dimerization (Hashimoto et al., 2003), these results suggest a model of AD in which Aβ peptide dimerizes APP directly, leading to the activation of ASK1, MKK6, and p38, with subsequent phosphorylation of tau at sites characteristic of AD.     

Health literacy and knowledge of chronic disease

We sought to examine the relationship between health literacy and knowledge of disease among patients with a chronic disease. A total of 653 new Medicare enrollees aged 65 years or older who had at least one chronic disease (115 asthma, 266 diabetes, 166 congestive heart failure, 214 hypertension), completed both the in-person and telephone survey. Health literacy measured by the short test of functional health literacy in adults (S-TOFHLA) and demographic information were collected during the in-person survey. Knowledge of disease was assessed by questions based on key elements in educational materials during a telephone survey. Overall, 24% of patients had inadequate and 12% had marginal health literacy skills. Respondents with inadequate health literacy knew significantly less about their disease than those with adequate literacy. Multivariate analysis indicated that health literacy was independently related to disease knowledge. There are many opportunities to improve patients' knowledge of their chronic disease(s), and efforts need to consider their health literacy skills.     

Do we practise what we preach?

There are recommendations regarding many facets of lifestyle. We proposed to look at hospital doctors' habits in East Yorkshire. METHOD: A simple questionnaire was sent out to 574 doctors in the Hull and East Yorkshire Hospitals NHS Trust. Non-responders were re-mailed. Age, sex, grade, specialty, number of portions of fruit and vegetable per day, alcohol intake, smoking, exercise and hours worked. RESULTS: 301 doctors (238 males, 60 females) responded (response rate 58%). Approximately half of doctors who responded were consultants. Few respondents smoked (6.6%), and the mean alcohol consumption, 8.35 units per week (SE 0.54), was less than the recommended limits for men and women. Most doctors fell short of the "recommended" 5 portions of fruit and vegetables per day (median 3 per day) and nearly half worked more than 56 hours per week. Most respondents took at least the recommended amount of exercise per week (112 SE25 minutes) although 26% of doctors took no exercise at all.     

Postinflammatory hyperpigmentation following torture

Hyperpigmentation after torture in darker skinned patients has regularly been noted, although its pathophysiology, and thus its forensic importance, has not previously been documented. Hyperpigmentation is not well described in the dermatological literature. It is the result of inflammation. Any inflammation can cause hyperpigmentation, and the shape of the resulting lesion can closely follow the contours of the site of original inflammatory response. This can be important in correlating the lesion with the alleged cause. It also helps to establish the differential diagnosis of the lesion, which also assists in assessing the degree of consistency between the lesion and the alleged cause. Patterns of hyperpigmentation can therefore, be helpful in assessing allegations of torture months or years after the event.     

Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum

Pathological processes, including cerebral ischemia, can enhance neurogenesis in the adult brain, but the fate of the newborn neurons that are produced and their role in brain repair are obscure. To determine if ischemia-induced neuronal proliferation is associated with migration of nascent neurons toward ischemic lesions, we mapped the migration of cells labeled by cell proliferation markers and antibodies against neuronal marker proteins, for up to 2 weeks after a 90-min episode of focal cerebral ischemia caused by occlusion of the middle cerebral artery. Doublecortin-immunoreactive cells in the rostral subventricular zone, but not the dentate gyrus, migrated into the ischemic penumbra of the adjacent striatum and, via the rostral migratory stream and lateral cortical stream, into the penumbra of ischemic cortex. These results indicate that after cerebral ischemia, new neurons are directed toward sites of brain injury, where they might be in a position to participate in brain repair and functional recovery.     

Gene-environment interactions in renal cell carcinoma

The majority of renal cell carcinomas (RCCs) are sporadic, and increasing incidence rates suggest that such environmental risk factors as smoking play a role in the etiology of the disease. Cases with RCC were selected from the population-based cancer registry of Orange County, California, between 1994 and 1997; controls were recruited by telephone using random digit dialing. A total of 115 case and 259 control subjects were genotyped for N-acetyltransferase 2 (NAT2), which codes for a polymorphic enzyme involved in tobacco-carcinogen metabolism. Subjects with slow acetylator genotypes were found to be at twofold increased risk (odds ratio (OR) = 1.8; 95 percent confidence interval (CI): 1.1, 2.9) of RCC. Although cancer risk doubled among smokers (OR = 2.2; 95 percent CI: 1.3, 3.7), stratified analysis revealed gene-environment interaction among slow acetylators that smoked (OR = 3.2; 95 percent CI: 1.7, 6.1) compared with rapid acetylators that smoked (OR = 1.4; 95 percent CI: 0.7, 2.9). A dose response was found for pack-years among slow acetylators (p < 0.01) but not among rapid acetylators (p = 0.06). Although smoking is a well-established risk factor of RCC, our data suggest that the risk is pronounced among slow rather than rapid acetylators.     

New aspects in genotoxic risk assessment of styrene exposure--a working hypothesis

Styrene is one of the most important plastic monomers worldwide. Styrene-7,8-oxide (SO), the major in-vivo metabolite of styrene, is classified as probably carcinogenic to humans and carcinogenic in rodents. Biological monitoring of exposure to styrene is usually carried out by determination of mandelic acid and phenylglyoxylic acid, the two main styrene metabolites in urine. SO binds covalently to human plasma protein and haemoglobin. The ability of SO to induce DNA adducts and DNA strand-breaks has been well documented. Recently in-vitro results showed that SO may disrupt the pre-existing oxidative status in white blood cells. This disruption would alter the balance between oxidants and antioxidants in cells. Styrene exposure can also result in oxidative DNA damage. A significant increase of 8-hydroxy-2;-deoxyguanosine (8-OHdG) has been found in white blood cells of styrene-exposed workers. According to these findings we propose a new hypothesis for the genotoxic risk assessment of styrene. Depletion of glutathione and increase in lipid peroxidation, similarity in the decrease of high molecular weight (HMW) DNA fragments after SO exposure compared to hydrogen peroxide (H(2)O(2)) exposure, oxidative DNA damage (increased amounts of 8-OHdG and an increased level of DNA strand-breaks) following styrene or SO exposure are due to oxidative stress which can be a result of the imbalance between oxidants and antioxidants. Formation of protein-, RNA- and DNA-adducts, changes in DNA repair capacity and styrene metabolism following styrene exposure could cause this imbalance between oxidants and antioxidants. Oxidative stress seems to be the basis for genotoxic risk assessment of styrene.