Emory University

About: Emory University is a education organization based out in Atlanta, Georgia, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 51959 authors who have published 122469 publications receiving 6010698 citations.

Menarche, menopause, and breast cancer risk: Individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies

Abstract: BACKGROUND:Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.METHODS:Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.FINDINGS:Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons).INTERPRETATION:The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.

Oxidative Stress and Cardiovascular Injury: Part II: Animal and Human Studies

Abstract: This review so far has considered the role of vascular cells in the generation of reactive oxygen species (ROS) and novel approaches to their detection in integrated systems such as animal models of vascular disease and humans. We now turn attention to evidence consistent with a role for ROS in models of human disease and in discrete patient populations. We also briefly comment on the outcomes of clinical trials of antioxidants. Mainly, these have been disappointing. However, it is premature to conclude that the oxidation hypothesis of disease causality has been adequately tested. Animal studies, for the most part, support a fundamental role for ROS in cardiovascular disease. Any controversy could in part reflect the use of ineffective antioxidants and the selection of models in which ROS generation is of marginal relevance to the measured outcome. Both of these issues require a quantitatively accurate measurement of drug effect (ie, antioxidant capacity) before hypotheses relating to the role of oxidant stress can be addressed rationally. These issues pertain to clinical trials also, as we will discuss. However, animal studies permit administration of much more powerful antioxidants (eg, rate constant for interaction of superoxide dismutase (SOD) with O2·− ≈1.6×109 · mol/L−1 · s−1) than is possible in humans (eg, rate constant for vitamin E ≈0.59 mol/L−1 · s−1) or, like in the case of vitamin E, doses of the antioxidant in excess of those usually applied in clinical research. ### Atherosclerosis Animal models of atherosclerosis have documented that all the constituents of the plaque produce and use ROS. Lesion formation is associated with the accumulation of lipid peroxidation products1,2 and induction of inflammatory genes,3 inactivation of NO·resulting in endothelial dysfunction, 4,5 activation of matrix metalloproteinases,6 and increased smooth muscle cell growth.7 …

Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid.

Abstract: Neuroendocrine tumors of the lung embrace a spectrum from low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), and high-grade categories of large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCLC). We studied 200 neuroendocrine lung tumors to critically evaluate the Arrigoni histologic criteria for AC using statistical analysis to delimit more rigorously an intermediate survival for AC between TC and the high-grade tumors of LCNEC and SCLC. Histologic features that might predict prognosis were used for Kaplan-Meier and Cox proportional hazards survival analysis, and an optimal mitotic range for AC was calculated. The optimal mitotic range for AC was 2 to 10 mitoses per 2 mm2 of viable tumor (10 high-power fields). Based on this finding, we collapsed mitoses into three categories ( or = 11) and performed Cox multivariate analysis for all 200 neuroendocrine tumors. Mitotic counts were the only independent predictor of prognosis. Based on this analysis, we propose that AC be defined as a tumor with neuroendocrine morphology, mitotic counts between 2-10 per 2 mm2 of viable tumor (10 high-power fields), or coagulative necrosis. Using these criteria, the 200 neuroendocrine tumors were classified as 51 TC, 62 AC, 37 LCNEC, and 50 SCLC. The 5- and 10-year survival was 87% and 87% for TC, 56% and 35% for AC, 27% and 9% for LCNEC, and 9% and 5% for SCLC, respectively. After stratification for stage, survival for AC was significantly worse than for TC (p < 0.001); for LCNEC and SCLC it was significantly worse than for AC; but the survival for LCNEC was no different than that for SCLC.

A Standardized Method for Measuring Intracranial Arterial Stenosis

Abstract: BACKGROUND AND PURPOSE: Atherosclerosis of the major intracranial arteries is an important cause of ischemic stroke. We established measurement criteria to assess percent stenosis of a major intracranial artery (carotid, middle cerebral, vertebral, basilar) and determined the interobserver/intraobserver agreements and interclass/intraclass correlations of these measurements. METHODS: We defined percent stenosis of an intracranial artery as follows: percent stenosis = [(1 − (D stenosis /D normal ))] × 100, where D stenosis = the diameter of the artery at the site of the most severe stenosis and D normal = the diameter of the proximal normal artery. If the proximal segment was diseased, contingency sites were chosen to measure D normal : distal artery (second choice), feeding artery (third choice). Using a hand-held digital caliper, three neuroradiologists independently measured D stenosis and D normal of 24 stenotic intracranial arteries. Each observer repeated the readings 4 weeks later. We determined how frequently two observers9 measurements of percent stenosis of each of the 24 diseased arteries differed by 10% or less. RESULTS: Among the three pairs of observers, interobserver agreements were 88% (observer 1 versus observer 2), 79% (observer 1 versus observer 3), 75% (observer 2 versus observer 3) for the first reading and were 75% (observer 1 versus observer 2), 100% (observer 1 versus observer 3), and 71% (observer 2 versus observer 3) for the second reading. Intraobserver agreement for each of the observers was 88%, 83%, and 100%. Interclass correlation was 85% (first reading) and 87% (second reading). Intraclass correlation was 92% (first and second readings combined). CONCLUSION: This method shows good interobserver and intraobserver agreements for the measurement of intracranial stenosis of a major artery. If validated in subsequent studies, this method may serve as a standard for the measurement of percent stenosis of an intracranial artery.