Objective-Our preliminary data suggested that angiotensin II (Ang II)-induced reactive oxygen species are involved in intercellular adhesion molecule-1 (ICAM-1) expression and leukocyte infiltration in the rat thoracic aorta. Other reports demonstrating reactive oxygen species-induced cell growth suggested a potential role of NAD(P)H oxidase in vascular hypertrophy. In the present study, we postulate that NAD(P)H oxidase is functionally involved in Ang II-induced ICAM-1 expression, macrophage infiltration, and vascular growth, and that oxidase inhibition attenuates these processes independently of a reduction in blood pressure. Methods and Results-Rats were infused subcutaneously with vehicle or Ang II (750 g/kg per day) for 1 week in the presence or absence of gp91 docking sequence (gp91ds)-tat peptide (1 mg/kg per day), a cell-permeant inhibitor of NAD(P)H oxidase. Immunohistochemical staining for ICAM-1 and ED1, a marker of monocytes and macrophages, showed that both were markedly increased with Ang II compared with vehicle and were reduced in rats receiving Ang II plus gp91ds-tat. This effect was accompanied by an Ang II-induced increase in medial hypertrophy that was attenuated by coinfusion of gp91ds-tat; however, gp91ds-tat had no effect on blood pressure. Key Words: NADPH oxidoreductase Ⅲ NAD(P)H oxidase Ⅲ hypertrophy Ⅲ inflammation Ⅲ angiotensin II A ngiotensin II (Ang II) has been shown to increase vascular adhesion molecule expression by stimulating the production of reactive oxygen species (ROS). 1,2 Mediators of increased adhesion molecule expression include activation of nuclear factor-B (NF-B) and activator protein-1 transcription factors. 3 Ang II has been implicated in vascular dysfunction, acting via a variety of mechanisms, including (1) stimulation of superoxide anion (O 2 ·Ϫ ) production by large and small blood vessels 4 through activation of vascular NAD(P)H oxidases, 5,6 leading to impairment of endothelial function 7,8 ; (2) induction of adhesion molecules, such as vascular cell adhesion molecule-1, via activation of NF-Bdependent gene expression 9 ; and (3) hypertrophy and remodeling. 10,11 Conclusions-Ang See page 707There is substantial evidence indicating that the cellular actions of Ang II are proinflammatory and potentially injurious to the blood vessel. In hypertension, medial hypertrophy is a normal response, 12,13 yet the mechanisms mediating this hypertrophy are still not clear. Reports have demonstrated that Ang II can induce medial thickening and increase the vascular cross-sectional area independently of blood pressure elevation. 14 -16 In smooth muscle cell cultures, Ang II has been shown to induce hypertrophy, 17 which appears to be mediated by the stimulation of NAD(P)H oxidase-derived H 2 O 2 , which in turn activates proto-oncogenes, mitogenactivated protein kinases, and transcription factors, leading to the growth response. 5,18,19 A recent study by Wang et al 16 also posited an in vivo role for NAD(P)H oxidase in medial hypertrophy in response to Ang II, but this int...

Benign changes ranging from atrophy and inflammation to high-grade prostatic intraepithelial neoplasia (HGPIN) are common findings on prostate core needle biopsies. Although atrophy and inflammation may be precursors of prostate cancer, only HGPIN is currently recommended to be included in surgical pathology reports. To determine whether these benign findings increase prostate cancer risk, we conducted a case–control study nested within a historical cohort of 6692 men with a benign prostate specimen collected between 1990 and 2002. The analytic sample included 574 case–control pairs comprised of cases diagnosed with prostate cancer a minimum of 1 year after cohort entry and controls matched to cases on date and age at cohort entry, race, and type of specimen. The initial benign specimen was reviewed for presence of HGPIN, atrophy (simple, lobular, and partial) and inflammation (glandular and/or stromal). HGPIN significantly increased risk for prostate cancer (odds ratio (OR) = 2.00; 95% confidence interval (CI) = 1.25–3.20). Inflammation within the stromal compartment was associated with decreased risk (OR = 0.66; CI = 0.52–0.84), and diffuse stromal inflammation of severe grade had the strongest inverse association with risk (OR = 0.21; CI = 0.07–0.62). In a model adjusted for prostate-specific antigen (PSA) level at cohort entry and inflammation, simple atrophy was associated with a 33% increased prostate cancer risk that was marginally significant (P = 0.03). Clinicians should consider patterns and extent of inflammation when managing high-risk patients with negative biopsy results. Identifying benign inflammatory processes that underlie high PSA levels would help to reduce the number of unnecessary repeated prostate biopsies.

Objectives-Metabolic syndrome refers to cluster of conditions serving as risk factors for cardiovascular disease. Metabolic syndrome is prevalent in the United States and the spectrum of specific features has been shown to differ by race and ethnicity. A number of recent reports link metabolic syndrome to prostate cancer, however most studies do not have racially diverse populations to explore differences in risk.Methods-A case-control study was conducted to test the association between metabolic syndrome features and prostate cancer among 637 cases and 244 controls, with African Americans comprising 43% of the study population.Results-Metabolic syndrome, defined using a modified version of the ATP III criteria, was marginally associated with increased risk of prostate cancer in African Americans (OR=1.71; 95% CI=0.97, 3.01), but not Caucasians (OR=1.02; 95%CI=0.64, 1.62). After stratifying cases on stage at diagnosis, African American men with organ confined disease were more likely to have a history of metabolic syndrome compared to controls (OR=1.82; 95% CI=1.02, 3.23), but no association was observed among those with advanced stage disease (OR=0.93; 95%CI=0.31, 2.77). When evaluating specific features of metabolic syndrome, obesity was inversely related to prostate cancer among Caucasians (OR = 0.51, 95% CI=0.33, 0.80), but unrelated to risk among African Americans (OR=1.15; 95% CI=0.70, 1.89).Conclusions-In this investigation, metabolic syndrome was associated with prostate cancer risk in African American men, but not Caucasians. The prevalence of this syndrome, coupled with the racial disparity and prostate cancer incidence and outcomes after diagnosis warrant further investigation.

Purpose Higher socio-economic status (SES) men are at higher risk of prostate cancer (PCa) diagnosis, an association commonly interpreted as a function of higher rates of prostate screening among higher-SES men. However, the extent to which screening explains this association has not been well quantified. Methods Within a Detroit-area cohort of 6,692 men followed up after a benign prostate procedure, a case-control study was conducted of 494 PCa cases and controls matched on age, race, duration of follow-up, and date of initial benign finding. 2000 Census data were used in a principal component analysis to derive a single factor, labeled the Neighborhood SES Index (NSESI), representing zip code-level SES. Results Among cases, higher SES was associated with a younger age at initial biopsy: −1.48 years (95% CI, −2.32, −0.64) per unit NSESI. After adjustment for confounders and duration of follow-up, higher SES was associated with more PSA tests and DRE during follow-up; 9% (95% CI, 2, 16) and 8% (95% CI, 1, 15) more respectively, per unit NSESI. Higher SES was associated with a higher risk of PCa diagnosis during follow-up, multivariable adjusted OR = 1.26 per unit increase in NSESI (95% CI, 1.04, 1.49). Further adjustment for screening frequency somewhat reduced the association between SES and PCa risk (OR = 1.19 per unit NSESI, 95% CI, 0.98, 1.44). Conclusions Differences in screening frequency only partially explained the association between higher zip code SES and PCa risk; other health care related factors should also be considered as explanatory factors.

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BACKGROUND: Few data are available on the long-term course and predictors of quality of life (QoL) following acute pulmonary embolism (PE). RESEARCH QUESTION: What are the kinetics and determinants of disease-specific and generic health-related QoL 3 and 12 months following an acute PE? STUDY DESIGN AND METHODS: The Follow-up after Acute Pulmonary Embolism (FOCUS) study prospectively followed up consecutive adult patients with objectively diagnosed PE. Patients were considered for study who completed the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire at predefined visits 3 and 12 months following PE. The course of disease-specific QoL as assessed using the PEmb-QoL and the impact of baseline characteristics using multivariable mixed effects linear regression were studied; also assessed was the course of generic QoL as evaluated by using the EuroQoL Group 5-Dimension 5-Level utility index and the EuroQoL Visual Analog Scale. RESULTS: In 620 patients (44% women; median age, 62 years), overall disease-specific QoL improved from 3 to 12 months, with a decrease in the median PEmb-QoL score from 19.4% to 13.0% and a mean individual change of -4.3% (95% CI, -3.2 to -5.5). Female sex, cardiopulmonary disease, and higher BMI were associated with worse QoL at both 3 and 12 months. Over time, the association with BMI became weaker, whereas older age and previous VTE were associated with worsening QoL. Generic QoL also improved: the mean AE SD EuroQoL Group 5-Dimension 5-Level utility index increased from 0.85 AE 0.22 to 0.87 AE 0.20 and the visual analog scale from 72.9 AE 18.8 to 74.4 AE 19.1. INTERPRETATION: In a large cohort of survivors of acute PE, the change of QoL was quantified between months 3 and 12 following diagnosis, and factors independently associated with lower QoL and slower recovery of QoL were identified. This information may facilitate the planning and interpretation of clinical trials assessing QoL and help guide patient management.

The MAAS is a valid and reliable sedation scale for use with mechanically ventilated patients in the SICU. Further studies are warranted regarding the effect of MAAS implementation in our SICU on patient outcomes, such as quality of sedation and length of mechanical ventilation, as well as the use of the MAAS in other patient populations (e.g., medical).