Birth weight,weight over the adult life course and risk of breast cancer

Breast cancer has been suggested to potentially have prenatal origins. We examined associations between birth weight, body mass index (BMI) at four-time points over 25 years of adulthood, and risk of postmenopausal breast cancer, with emphasis on whether the association between birth weight and risk of breast cancer was mediated by weight and height changes over the adult life course. Postmenopausal women (n = 70,397) aged 50–79 years without breast cancer at enrollment (1993–1998) were followed up to 25 years. Weight and height were measured at baseline. Birth weight, and weights at ages 18, 35 and 50 were self-reported. Breast cancer cases were centrally adjudicated. Compared to women with birth weight of 6–8 pounds, women with birth weight of <6 pounds had lower risk of breast cancer (HR = 0.88 95% CI: 0.79–0.99). 44% and 21% of the relationship between birth weight and breast cancer risk was mediated by adult height and weight at baseline, respectively. Birth weight of 8 pounds or more was not associated with risk of postmenopausal breast cancer. Weight gain in adulthood was associated with increased risk of breast cancer regardless of time periods. In conclusion, lower birthweight was associated with lower risk of postmenopausal breast cancer, and this reduction in risk was significantly mediated by childhood or adolescent growth, especially by adult height. Our data suggest that reaching and maintaining a healthy weight during adulthood is key in the prevention of breast cancer.     

An Early Study on the Mechanisms that Allow Tissue-Engineered Vascular Grafts to Resist Intimal Hyperplasia

Intimal hyperplasia is one of the prominent failure mechanisms for arteriovenous fistulas and arteriovenous access grafts. Human tissue-engineered vascular grafts (TEVGs) were implanted as arteriovenous grafts in a novel baboon model. Ultrasound was used to monitor flow rates and vascular diameters throughout the study. Intimal hyperplasia in the outflow vein of TEVGs was assessed at the anastomosis and at juxta-anastomotic regions via histological analysis, and was compared to intimal hyperplasia with polytetrafluoroethylene (PTFE) grafts in the baboon model and in literature reports from other animal models. Less venous intimal hyperplasia was observed in histological sections with arteriovenous TEVGs than with arteriovenous PTFE grafts. TEVGs were associated with a mild, noninflammatory intimal hyperplasia. The extent of intimal tissue that formed with TEVG placement correlated with the rate of blood flow through tissue engineered vascular grafts at 2 weeks postimplant. Outflow vein dilatation was observed with increased flow rate. Both mid-graft flow rates and outflow vein diameters reached a plateau by week 4, which suggested that venous remodeling and intimal hyperplasia largely occurred within the first 4 weeks of implant in the baboon model. Given their compliant and noninflammatory nature, TEVGs appear resistant to triggers for venous intimal hyperplasia that are common for PTFE arteriovenous grafts, including (1) abundant proinflammatory macrophage populations that are associated with PTFE grafts and (2) compliance mismatch between PTFE grafts and the outflow vein. Our findings suggest that arteriovenous TEVGs develop only a mild form of venous intimal hyperplasia, which results from the typical hemodynamic changes that are associated with arteriovenous settings.     

C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus

CONTEXT: Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus (DM); however, clinical data addressing this issue are limited. OBJECTIVE: To determine whether elevated levels of the inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) are associated with development of type 2 DM in healthy middle-aged women. DESIGN: Prospective, nested case-control study. SETTING: The Women's Health Study, an ongoing US primary prevention, randomized clinical trial initiated in 1992. PARTICIPANTS: From a nationwide cohort of 27 628 women free of diagnosed DM, cardiovascular disease, and cancer at baseline, 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls. MAIN OUTCOME MEASURES: Incidence of confirmed clinically diagnosed type 2 DM by baseline levels of IL-6 and CRP. RESULTS: Baseline levels of IL-6 (P<.001) and CRP (P<.001) were significantly higher among cases than among controls. The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 (95% confidence interval [CI], 3.7-15.4) and 15.7 for CRP (95% CI, 6.5-37.9). Positive associations persisted after adjustment for body mass index, family history of diabetes, smoking, exercise, use of alcohol, and hormone replacement therapy; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 (95% CI, 0.9-5.6; P for trend =.07) and 4.2 for CRP (95% CI, 1.5-12.0; P for trend =.001). Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c) of 6.0% or less and after adjustment for fasting insulin level. CONCLUSIONS: Elevated levels of CRP and IL-6 predict the development of type 2 DM. These data support a possible role for inflammation in diabetogenesis.     

Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus

Context  Endothelial dysfunction occurs in diagnosed type 2 diabetes mellitus but may also precede development of diabetes. Objective  To determine whether elevated plasma levels of biomarkers reflecting endothelial dysfunction (E-selectin; intercellular adhesion molecule 1 [ICAM-1]; and vascular cell adhesion molecule 1 [VCAM-1]) predict development of type 2 diabetes in initially nondiabetic women. Design and Setting  Prospective, nested case-control study within the Nurses' Health Study, an ongoing US study initiated in 1976. Participants  Of 121 700 women initially enrolled, 32 826 provided blood samples in 1989-1990; of those free of diabetes, cardiovascular disease, or cancer at baseline, 737 developed incident diabetes by 2000. Controls (n = 785) were selected according to matched age, fasting status, and race. Main Outcome Measure  Risk of confirmed clinically diagnosed type 2 diabetes by baseline levels of E-selectin, ICAM-1, and VCAM-1. Results  Baseline median levels of the biomarkers were significantly higher among cases than among controls (E-selectin, 61.2 vs 45.4 ng/mL; ICAM-1, 264.9 vs 247.0 ng/mL; VCAM-1, 545.4 vs 526.0 ng/mL [all P values .004]). Elevated E-selectin and ICAM-1 levels predicted incident diabetes in logistic regression models conditioned on matching criteria and adjusted for body mass index (BMI), family history of diabetes, smoking, diet score, alcohol intake, activity index, and postmenopausal hormone use. The adjusted relative risks for incident diabetes in the top quintile vs the bottom quintiles were 5.43 for E-selectin (95% confidence interval [CI], 3.47-8.50), 3.56 for ICAM-1 (95% CI, 2.28-5.58), and 1.12 for VCAM-1 (95% CI, 0.76-1.66). Adjustment for waist circumference instead of BMI or further adjustment for baseline levels of C-reactive protein, fasting insulin, and hemoglobin A_1c or exclusion of cases diagnosed during the first 4 years of follow-up did not alter these associations. Conclusion  Endothelial dysfunction predicts type 2 diabetes in women independent of other known risk factors, including obesity and subclinical inflammation.      

Body mass index, migraine, migraine frequency and migraine features in women

We evaluated the association of body mass index (BMI) with migraine and migraine specifics in a cross-sectional study of 63 467 women aged ≥ 45 years, of whom 12 613 (19.9%) reported any history of migraine and 9195 had active migraine. Compared with women without migraine and a BMI < 23 kg/m², women with a BMI ≥ 35 kg/m² had adjusted odds ratios (ORs) (95% confidence intervals) of 1.03 (0.95, 1.12) for any history of migraine. Findings were similar for active migraineurs. Women with a BMI of ≥ 35 kg/m² had increased risk for low and high migraine frequency, with the highest estimate for women who reported daily migraine. Compared with women with the lowest associated risk (migraine frequency < 6 times/year; BMI between 27.0 and 29.9 kg/m²), women with a BMI ≥ 35 kg/m² had an OR of daily migraine of 3.11 (1.12, 8.67). Among the women with active migraine, a BMI ≥ 35 kg/m² was associated with increased risk of phonophobia and photophobia and decreased risk of a unilateral pain characteristic and migraine aura. Our data confirm previous findings that the association between BMI with migraine is limited to migraine frequency and specific migraine features.     

Triggering of sudden death from cardiac causes by vigorous exertion

BACKGROUND: Retrospective and cross-sectional data suggest that vigorous exertion can trigger cardiac arrest or sudden death and that habitual exercise may diminish this risk. However, the role of physical activity in precipitating or preventing sudden death has not been assessed prospectively in a large number of subjects. METHODS: We used a prospective, nested case-crossover design within the Physicians' Health Study to compare the risk of sudden death during and up to 30 minutes after an episode of vigorous exertion with that during periods of lighter exertion or none. We then evaluated whether habitual vigorous exercise modified the risk of sudden death that was associated with vigorous exertion. In addition, the relation of vigorous exercise to the overall risk of sudden death and nonsudden death from coronary heart disease was assessed. RESULTS: During 12 years of follow-up, 122 sudden deaths were confirmed among the 21,481 male physicians who were initially free of self-reported cardiovascular disease and who provided information on their habitual level of exercise at base line. The relative risk of-sudden death during and up to 30 minutes after vigorous exertion was 16.9 (95 percent confidence interval, 10.5 to 27.0; P<0.001). However, the absolute risk of sudden death during any particular episode of vigorous exertion was extremely low (1 sudden death per 1.51 million episodes of exertion). Habitual vigorous exercise attenuated the relative risk of sudden death that was associated with an episode of vigorous exertion (P value for trend=0.006). The base-line level of exercise was not associated with the overall risk of subsequent sudden death. CONCLUSIONS: These prospective data from a study of U.S. male physicians suggest that habitual vigorous exercise diminishes the risk of sudden death during vigorous exertion.     

Self-selected posttrial aspirin use and subsequent cardiovascular disease and mortality in the physicians' health study

BACKGROUND: The randomized aspirin component of the Physicians' Health Study (PHS) was terminated early, after 5 years, primarily because of the emergence of a statistically extreme (P<.00001) 44% reduction of first myocardial infarction (MI) among those assigned to aspirin. As a result, there were insufficient numbers of strokes or cardiovascular disease (CVD)-related deaths to evaluate these end points definitively. METHODS: Data on self-selected aspirin use were collected until the beta carotene component ended as scheduled after 12 years. Posttrial use of aspirin was assessed at the 7-year follow-up among 18 496 participants with no previous reported CVD. Randomized and posttrial observational results in the PHS were compared, and differences between those self-selecting aspirin and those not were examined. RESULTS: At 7 years, 59.5% of participants without CVD reported self-selected aspirin use for at least 180 d/y, and 20.8% for 0 to 13 d/y. Use was significantly associated with family history of MI, hypertension, elevated cholesterol levels, body mass index, alcohol consumption, exercise, and use of vitamin E supplements. In multivariate analyses, self-selected aspirin use for at least 180 vs 0 to 13 d/y was associated with lower risk for subsequent MI (relative risk [RR], 0.72; 95% confidence interval [CI], 0.55-0.95), no relation with stroke (RR, 1.02; 95% CI, 0.74-1.39), and significant reductions in CVD-related (RR, 0.65; CI, 0.47-0.89) and total mortality (RR, 0.64; CI, 0.54-0.77). CONCLUSION: These associations between self-selected aspirin use and CVD risk factors increase the likelihood of residual confounding and emphasize the need for large-scale randomized trials, such as the ongoing Women's Health Study, to detect reliably the most plausible small to moderate effects of aspirin in the primary prevention of stroke and CVD-related death.     

Splenic necrosis in Wegener's granulomatosis

The CT appearance of asymptomatic splenic necrosis in a 11-year-old girl with Wegener's granulomatosis is presented. Sonography showed splenic inhomogeneity with patency of the splenic artery and vein. Follow-up CT showed lobulation and shrinkage of the spleen with return to a normal attenuation.     

Wegener's granulomatosis in childhood

The authors reviewed the medical histories and radiological examinations of five pediatric patients with a histologic diagnosis of Wegener's granulomatosis (WG) seen over a six year period in whom a total of 22 thoracic CT scans were performed. Involvement of both the upper and lower respiratory tracts was seen in all patients at presentation. One patient had subglottic stenosis necessitating tracheotomy. Pulmonary hemorrhage occurred in three patients at initial diagnosis. Classic cavitary lung nodules were seen in two patients — one at initial presentation, the other at relapse. The plain radiographic lower respiratory tract manifestations of pediatric WG were protean both at initial presentation and during follow up. Similarly, disease expression was highly variable on thoracic CT examinations but, overall, multifocal parenchymal infiltrates with or without small peripheral nodules were the commonest thoracic CT manifestations. As a consequence of cytotoxic and corticosteroid therapy the long-term prognosis of WG has improved considerably in recent years. Knowledge of the varied patterns of the primary disease and potential for iatrogenic complications are necessary for successful radiologic assessment of pediatric patients with WG.