We conclude that chronic alcohol abuse is an independent risk factor for acute respiratory distress syndrome and increases the severity of nonpulmonary organ dysfunction in patients with septic shock.

Objective-Stroke risk due to intracranial atherosclerosis increases with degree of arterial stenosis. We evaluated the previously unexplored role of collaterals in modifying stroke risk in intracranial atherosclerosis and impact on subsequent stroke characteristics.Methods-Collateral flow was graded in blind fashion on 287/569 baseline angiograms (stenoses of 50-99% and adequate collateral views) in the WASID trial. Statistical models predicted stroke in the symptomatic arterial territory based on collateral flow grade, percentage of stenosis, and previously demonstrated independent covariates.Results-Across all stenoses, extent of collaterals was a predictor for subsequent stroke in the symptomatic arterial territory (HR none vs. good: 1.14, 95% CI 0.39 to 3.30, poor vs good: 4.36, 95% CI 1.46 to 13.07, p<0.0001). For 70-99% stenoses, more extensive collaterals diminished risk of subsequent territorial stroke (HR none vs. good: 4.60, 95% CI 1.03 to 20.56, poor vs good: 5.90, 95% CI 1.25 to 27.81, p=0.0427). At milder degrees of stenoses (50-69%), presence of collaterals was associated with greater likelihood of subsequent stroke (HR none vs. good: 0.18, 95% CI 0.04 to 0.82, poor vs good: 1.78, 95% CI 0.37 to 8.57, p<0.0001). In multivariate analyses, extent of collaterals was an independent predictor for subsequent stroke in the symptomatic arterial territory (HR none vs. good: 1.62, 95% CI 0.52 to 5.11, poor vs good: 4.78, 95% CI 1.55 to 14.7, p=0.0019).Address correspondence to: David S. Liebeskind, M.D., UCLA Stroke Center, 710 Westwood Plaza, Los Angeles, CA 90095, (310) 794-6379, (310) 267-2063 fax, davidliebeskind@yahoo.com. Disclosures Dr. Liebeskind reports having received grant funding from NINDS and consulting fees from Concentric Medical, Inc., and CoAxia, Inc. Dr. Saver reports having received grant funding from NINDS and consulting fees from AGA Medical, Boehringer Ingelheim, Bristol Myers Squibb, CoAxia, Concentric Medical, Ev3, FibroGen, ImaRx, Sanofi Aventis, and Talecris. He receives support for editorial work in MedReviews. Dr. Chimowitz is the recipient of a research grant (U01 NS058728) from the US Public Health Service National Institute of Neurological Disorders and Stroke (NINDS) to fund SAMMPRIS trial. He has also been supported by grants 1 K24 NS050307 and 1 R01 NS051688-01 from the NIH/NINDS. He reports being paid fees by the Bristol-Myers Squibb / Sanofi Pharmaceuticals Partnership, Astra-Zeneca, and the Sankyo Lilly Partnership for consulting on antithrombotic agents that were not evaluated in the WASID trial, and from Guidant Corporation for consulting on a medical device (an intracranial stent) that was not evaluated in this trial. Interpretation-Collateral circulation is a potent determinant of stroke risk in intracranial atherosclerosis, demonstrating a protective role with severe stenoses and identifying more unstable milder stenoses. NIH Public Access

Angiogenesis and lymphangiogenesis are essential for breast cancer progression and are regulated by vascular endothelial growth factors (VEGF). To determine clinical and molecular correlates of these processes, we measured blood and lymphatic vascular microvessel density in 29 invasive carcinomas (22 ductal, six lobular, one papillary), using the vascular marker CD31 and the novel lymphatic marker D2-40. Microvessel density was assessed microscopically and by image cytometry, and was compared with tumor histology, grade, stage, lymph node metastasis, hormone receptors, HER2/neu status, and expression of VEGF, VEGF-C and VEGF-D by immunohistochemistry or quantitative RT-PCR. Strong correlation was observed between visual and image cytometric microvessel density using D2-40 but not CD31 (P ¼ 0.016 and 0.1521, respectively). Image cytometric CD31 microvessel density correlated with tumor size, grade, stage and lymph node metastasis (P ¼ 0.0001, 0.0107, 0.0035 and 0.0395, respectively). D2-40 microvessel density correlated with tumor stage (P ¼ 0.0123 by image cytometry) and lymph node metastasis (P ¼ 0.0558 by microscopy). Immunohistochemical VEGF signal in peritumoral blood vessels correlated with image cytometric CD31 and D2-40 microvessel density (P ¼ 0.022 and 0.0012, respectively), consistent with the role of VEGF in blood and lymphatic vascular growth. Intratumoral VEGF-C and VEGF-D expression by quantitative RT-PCR correlated with D2-40 (P ¼ 0.0291 by image cytometry) but not with CD31 microvessel density, which could suggest a selective role of VEGF-C and VEGF-D in lymphangiogenesis. CD31 and D2-40 microvessel density correlated significantly with several prognostic factors, including lymph node metastasis. Thus, measurements of angiogenesis and lymphangiogenesis may have utility for breast cancer pathology, particularly for estimation of metastatic risk. Angiogenesis (blood vessel growth) and lymphangiogenesis (lymph vessel growth) are critical processes for tumor growth, invasion and metastasis.

Cys/CySS and GSH/GSSG redox states in human plasma undergo diurnal variation with an increased magnitude of variation in Cys/CySS redox state in older persons. This variation could alter sensitivity to oxidative stress over a course of hours.