Adrenoceptor stimulation does not affect ICAM-1 and VCAM-1 expression in vitro

BACKGROUND: Endothelial adhesion molecules ICAM-1 (CD54) and VCAM-1 (CD106) mediate cellular adhesion and transcellular migration. Cell adhesion and diapedesis have a key role in the course of shock and sepsis. During severe sepsis, adrenoceptor agonist levels may be increased due to endogenous production or due to intensive care treatment. As yet, the influence of β1 or β2 agonists on adhesion molecule formation on endothelial cells has remained unclear. METHODS: Cultured human umbilical vein endothelial cells were stimulated with E. coli. Following bacterial stimulation the cells were incubated with either β2 receptor agonist terbutaline or β1 agonist norepinephrine. ICAM-1 and VCAM-1 expression were examined using flow cytometry. RESULTS: Administration of norepinephrine did not cause increases of both CD54 and CD106 in stimulated HUVEC. Compared to negative controls the bacterial stimulation itself led to an increase of adhesion molecules. Following administration of terbutaline no significant increase in CD54 expression was found. CONCLUSIONS: Bacterial stimulation led to an increase of adhesion molecule expression. Adrenoceptor stimulation of activated endothelial cells did not cause significant increases of cellular adhesion molecules

The Association of Ambulatory Care with Breast Cancer Stage at Diagnosis Among Medicare Beneficiaries

OBJECTIVE: Although nearly all elderly Americans are insured through Medicare, there is substantial variation in their use of services, which may influence detection of serious illnesses. We examined outpatient care in the 2 years before breast cancer diagnosis to identify women at high risk for limited care and assess the relationship of the physicians seen and number of visits with stage at diagnosis. DESIGN: Retrospective cohort study using cancer registry and Medicare claims data. PATIENTS: Population-based sample of 11,291 women aged ≥67 diagnosed with breast cancer during 1995 to 1996. MEASUREMENTS AND MAIN RESULTS: Ten percent of women had no visits or saw only physicians other than primary care physicians or medical specialists in the 2 years before diagnosis. Such women were more often unmarried, living in urban areas or areas with low median incomes (all P≥.01). Overall, 11.2% were diagnosed with advanced (stage III/IV) cancer. The adjusted rate was highest among women with no visits (36.2%) or with visits to physicians other than primary care physicians or medical specialists (15.3%) compared to women with visits to either a primary care physician (8.6%) or medical specialist (9.4%) or both (7.8%) (P <.001). The rate of advanced cancer also decreased with increasing number of visits (P <.001). CONCLUSIONS: Even within this insured population, many elderly women had limited or no outpatient care in the 2 years before breast cancer diagnosis, and these women had a markedly increased risk of advanced-stage diagnosis. These women, many of whom were unmarried and living in poor and urban areas, may benefit from targeted outreach or coverage for preventive care visits

Introducing responsible innovation in health: a policy-oriented framework

Abstract The scholarship on responsible research and innovation (RRI) aims to align the processes and outcomes of innovation with societal values by involving a broad range of stakeholders from a very early stage. Though this scholarship offers a new lens to consider the challenges new health technologies raise for health systems around the world, there is a need to define the dimensions that specifically characterise responsible innovation in health (RIH). The present article aims to introduce an integrative RIH framework drawing on the RRI literature, the international literature on health systems as well as specific bodies of knowledge that shed light on key dimensions of health innovations. Combining inductive and deductive theory-building strategies and concomitant with the development of a formal tool to assess the responsibility of innovations, we developed a framework that is comprised of nine dimensions organised within five value domains, namely population health, health system, economic, organisational and environmental. RIH provides health and innovation policy-makers with a common framework that supports the development of innovations that can tackle significant system-level challenges, including sustainability and equity