Endothelial-dependent vasodilation is reduced in mesenteric arteries from superoxide dismutase knockout mice

OBJECTIVE: Oxidative stress has increasingly been implicated in the development and progression of many vascular diseases. Previous work from our laboratory indicated that peroxynitrite alters vasoactive pathways in endothelial cells, which could potentially reduce vascular relaxation. To test this hypothesis in vivo, we utilized an animal model of endogenous oxidative stress, the CuZn superoxide dismutase (SOD) knockout mouse, to assess vascular function. METHODS: Vascular reactivity of mouse mesenteric arteries was assessed in the presence or absence of inhibitors to nitric oxide synthase (NOS) and/or prostaglandin H synthase (PGHS). Endothelial-dependent function was also measured after the addition of exogenous SOD. Peroxynitrite formation was detected by nitrotyrosine immunofluorescence in mesenteric arteries. RESULTS: Our data indicate that endothelial-dependent relaxation responses to methacholine are highly reduced in SOD-/- mice (P<0.01, ANOVA). In only the wild-type mice, NOS or PGHS inhibition significantly blunted relaxation, suggesting that vasodilators from these pathways are present only in the controls and not in SOD-/- mice. A combination of NOS and PGHS inhibitors reduced methacholine relaxation in both wild type and SOD-/- mice. This residual EDHF-like relaxation was not different between groups. After incubation with exogenous SOD, endothelial-dependent relaxation could be partially restored in SOD-/- mice, due to increased NOS-mediated vasodilation. In addition, peroxynitrite formation was significantly elevated in mesenteric arteries from SOD-/- mice. CONCLUSION: Our data suggest that in a novel animal model of oxidative stress, vessel function is compromised due to alterations in NOS and PGHS-dependent relaxation responses.     

Human papillomavirus-negative ileostomal chronic papillomatous dermatitis

BACKGROUND: Papillomatous stoma-related skin lesions may result from irritant reactions or infection with epidermodysplasia verruciformis human papillomavirus (HPV) types. METHODS: We report upon a papillomatous lesion at the ileostoma of a 63-year-old male with familial adenomatous polyposis and colorectal adenocarcinoma. We thoroughly tested the lesion for HPV using immunohistochemistry, transmission electron microscopy, and polymerase chain reaction analyses. RESULTS: The lesion was a fleshy, multilobulated, and verrucous plaque, with hyperkeratosis, hypergranulosis, acanthosis and marked papillomatosis. The clinical and light microscopic features were suggestive of a condyloma. However, no HPV was detected. CONCLUSIONS: We suggest that the lesion most likely represents chronic papillomatous dermatitis, a reaction to mechanical and/or chemical irritation usually associated with urostomies and only rarely observed with ileostomies. This case highlights the clinical, diagnostic and therapeutic aspects of an unusual cutaneous morbidity associated with ileostomies.     

Physical performance and longevity in aged rats

In humans, physical performance declines with increasing age, and in nondisabled older persons, scores on standardized performance measures, such as walking speed, repeated chair stands, and a balance test, predict the incidence of disability and reduced longevity. Here we show in aged rats (24-month-old Brown Norway x Fischer 344 male rats; n = 48) that conceptually similar performance measures, such as swimming speed and an inclined plane procedure, can be assessed longitudinally, and that over 6 months of follow-up from the age of 24 to 30 months, performance declines progressively with increasing age. High baseline performance scores predict long-term longevity, a relationship that is also found in humans. The application of standardized physical performance measures to a variety of animal models of aging may help to define similarities between species in the underlying mechanisms of the age-related decline in performance, disability, and longevity.     

Politically connected: increasing the political competency of healthcare executives in health policy

In this article we provide a teaching frame of reference for healthcare management students, to more effectively engage in the health policy-making process. We show how future executives can direct or transfer their management skills and abilities to the health policy arena. In doing so, healthcare executives attain a proactive stance in the political process, which is essential to the overall strategic management of healthcare organizations. Using organization theory as a pedagogical tool, we outline the similarities and differences in the management of hospitals versus state legislatures. We identify areas of common ground, and suggest components to frame political advocacy strategy for healthcare executives that strengthen their political competency. Thus, the article provides a teaching framework for health services management students about key intersections between management and policymaking.     

The cost and yield of photoscreening: impact of photoscreening on overall pediatric ophthalmic costs

BACKGROUND: Approximately 5% of preschool-age children suffer from amblyopia. Many of them have high or unequal hyperopia. Amblyogenic risk factors frequently can be detected by photoscreening. METHODS: Free photoscreening was offered to Alaskan children ages 1 to 5 from urban and rural screening hubs. Screened images were mailed to the Alaska Blind Child Discovery coordinating center for physician photoscreen interpretation, specifically seeking latent or anisometropic hyperopia. Parents and screeners then were mailed results and information about amblyopia. Follow-up examination data were tallied, and a cost-consequence analysis was developed for various vision screening paradigms and eye care. RESULTS: From 1996 through 2003, a total of 13,255 screenings were performed with a positive interpretation rate of 4.7%. Penetrance of screening was 22% in urban and 44% in rural communities. Positive predictive value was estimated to be more than 90%. Average cost to screen and inform an Alaskan preschooler was approximately 10.67 dollars, and cost to detect amblyogenic risk factors by photoscreening in an Alaskan was approximately 206 dollars. Compared to American Academy of Pediatrics (AAP) 1995 guidelines, implementing photoscreening added 9%, while mandating complete prekindergarten examination added 49% to overall eye care. CONCLUSIONS: MTI photoscreening achieved high community penetrance and high positive predictive value for latent hyperopia and other amblyogenic factors. When follow-up costs are considered, adding photoscreening to current AAP guidelines may add 112 dollars per child over 10 years, but probably would assist in the reduction of amblyopia. Penetrance of urban photoscreening likely will remain low unless pediatric vision screening guidelines and reimbursement are revised.     

A prospective 3-year longitudinal study of cognitive predictors of relapse in first-episode schizophrenic patients

BACKGROUND: Cognitive predictors of relapse have been extensively explored only in few long term longitudinal studies of first-episode schizophrenia. METHOD: This study prospectively followed 93 patients with first-episode schizophrenia, schizophreniform disorder, and schizoaffective disorder for 3 years after their first-episode illness. Cognitive domains including verbal intelligence, verbal and visual memory, verbal fluency, and Wisconsin Card Sorting Test performance were investigated as potential predictors of relapse. RESULTS: We found that by the first year 21% patients had relapsed, by the second year 33% had relapsed, and by the third year 40% had relapsed. There was a significant difference in the relapse rate between patients with good adherence and patients with poor adherence to medication regimes. A multiple logistic regression analysis revealed that after controlling for medication adherence, perseverative error in the Wisconsin Card Sorting Test was the only cognitive function that significantly predict relapse with an odds ratio of 2.4. CONCLUSIONS: Cognitive flexibility in set shifting is related to tendency towards relapse in first-episode schizophrenic patients. Other cognitive factors appear not to be related to relapse. Possible mechanisms included the link between prefrontal dysfunction and sub-cortical dopamine system stability, as well as the effects of executive dysfunction on insight impairment and adherence behavior.