Janice Harper

In a case-control study we assessed whether exposure to high job strain during the first 20 weeks of pregnancy increases the risk of preeclampsia and gestational hypertension. Cases (128 with preeclampsia and 201 with gestational hypertension) and controls (N = 401) were primiparous women who had a paid occupation for at least 1 week during the first 20 weeks of their pregnancy and who delivered between 1984 and 1986 in 10 hospitals of Quebec, Canada. Based on their job title, we assigned women scores of psychological demand and decision latitude derived from the National Population Health Survey and classified these women as exposed to high (high demand, low latitude) versus low (low demand, high latitude) job strain. Women exposed to high job strain were more likely to develop preeclampsia [adjusted odds ratio (aOR) = 2.1; 95% confidence interval (CI) = 1.1-4.1] than women exposed to low job strain. The risk was quite similar for women exposed to a full-time, high strain job (> or =35 hours per week) (aOR = 2.0) than in a part-time, high strain job (aOR = 1.8). High job strain increased the risk of gestational hypertension slightly (aOR = 1.3; 95% CI = 0.8-2.2). These results indicate that women exposed to high job strain are at higher risk of developing preeclampsia and, to a lesser extent, gestational hypertension.

Vitamin D has recently emerged as a potentially protective agent against colorectal neoplasia. We assessed the associations between dietary vitamin D, plasma 25-hydroxyvitamin D [25(OH)D], dietary calcium, and colorectal adenomas in a large screening sigmoidoscopy-based case-control study in Southern California. Because conversion of serum 25(OH)D to serum 1,25-vitamin D is highly regulated by serum calcium, we also assessed modification of the 25(OH)D-adenoma association by calcium intake. Cases were 473 subjects with a primary adenoma, and controls were 507 subjects who had no adenomas at sigmoidoscopy and no history of adenomas. Compared with those in the lowest quartile of intake, those in the highest quartile of dietary vitamin D had an adjusted odds ratio (OR) of 0.83 [95% confidence interval (CI) = 0.49-1.41] and those in the highest quartile of dietary calcium had an OR of 0.82 (95% CI = 0.49-1.25). There was a suggestion that plasma 25(OH)D may be protective in this population (OR for highest vs. lowest quartile = 0.74, 95% CI = 0.51-1.09). A significant protective effect of 25(OH)D was clearly evident only in those with calcium intakes below (OR = 0.40 for highest vs. lowest quartile, 95% CI = 0.22-0.71, p for trend = 0.005) and above (OR = 1.17, 95% CI = 0.69-1.99, p for trend = 0.94) the median calcium intake.

Cigarette smoking has been associated with adenomatous polyps of the large bowel but not with increased risk of colorectal cancer. Giovannucci et al recently proposed a hypothesis to explain this inconsistency. A key testable aspect of the hypothesis is that smoking in the distant past increases the risk of large polyps. Questions also remain about the association between colorectal polyps and consumption of alcohol. To address these issues, we examined data from 488 cases with adenomatous polyps and 488 controls. Subjects were members of a prepaid health plan in Los Angeles who had a sigmoidoscopy in 1991-1993. As expected, the adjusted odds of polyps in current smokers compared with never-smokers was increased [odds ratio = 2.43; 95% confidence interval (CI) = 1.56-3.79]. For those who had smoked in the distant past (for example, 30 or more pack-years before 20 years ago), the adjusted odds of an adenoma > or = 1 cm, relative to nonsmokers, was 0.88 (95% CI = 0.23-3.42). The adjusted odds of polyps in those consuming > or = 46 gm per day of alcohol compared with nondrinkers was 1.50 (95% CI = 0.72-3.13). Although imprecise, these data do not support the hypothesis that past smoking increases the risk of large polyps, but our results indicate a weak association between alcohol use and risk of adenomatous polyps.

Anti-neutrophil cytoplasm antibodies (ANCA) with specificity for myeloperoxidase (MPO) occur in the sera of patients with microscopic angiitis, an autoimmune disease characterized by necrotizing vasculitis and crescentic glomerulonephritis. These autoantibodies have been shown to stimulate neutrophil degranulation and are believed to participate in pathogenesis. A neutrophilic vasculitis has been reported in MRL-lpr mice which has histological appearances similar to microscopic angiitis. In the present study we show that 22% of female MRL-lpr mice develop MPO autoantibodies. These animals develop a clinical syndrome of vasculitis and glomerulonephritis that is distinct from immune complex disease. Anti-MPO monoclonal antibodies derived from these mice are polyreactive and react with double-stranded DNA. They bind a conformational epitope on human MPO which is also expressed by activated human neutrophils. The results suggest that a subset of MRL-lpr mice develop ANCA-related vasculitis rather than systemic lupus erythematosus and may be used as a model for human microscopic angiitis.

We conducted a large, sigmoidoscopy-based case-control study to examine the relation of intake of macronutrients, meat, and fiber to occurrence of adenomas of the large bowel. Cases were subjects diagnosed for the first time with one or more histologically confirmed adenomas. Controls had no polyps of any type at sigmoidoscopy, had no history of polyps, and were individually matched to cases by gender, age, date of sigmoidoscopy, and Kaiser Center. The response rate was 84% for cases and 82% for controls. Complete dietary data for 488 matched pairs were available. All odds ratios are from matched analyses adjusted for energy. We observed positive associations with risk of adenomas for calories, animal fat, saturated fat, red meat, and the ratio of red meat to poultry and fish. Protective effects were observed for vegetable protein, carbohydrates, and dietary fiber. The fiber effects diminished after adjusting for fruits and vegetables. Results after mutually adjusting for the effects of saturated fat, fiber and the ratio of red meat to chicken and fish suggest that each of these variables has an effect on risk of adenomas that is independent of the other 2 exposures.