Analysis 01.01. Comparison 01 Active intervention versus control, Outcome 01 Self monitoring (systolic blood pressure) Analysis 01.02. Comparison 01 Active intervention versus control, Outcome 02 Self monitoring (diastolic blood pressure

Objective-To see whether care provided by general practitioners to non-emergency patients in an accident and emergency department differs significantly from care by usual accident and emergency staff in terms ofprocess, outcome, and comparative cost.Design-A randomised controlled trial. Setting-A busy inner city hospital's accident and emergency department which employed three local general practitioners on a sessional basis.Patients-All new attenders categorised by the triage system as "semiurgent" or "delay acceptable." 66% ofall attenders were eligible for inclusion.Main outcome measures-Numbers of patients undergoing investigation, referral, or prescription; types of disposal; consultation satisfaction scores; reattendance to accident and emergency department within 30 days of index visit; health status at one month; comparative cost differences.Results-4684 patients participated. For semiurgent patients, by comparison with usual accident and emergency staff, general practitioners investigated fewer patients (relative difference 20%; 95% confidence interval 16% to 25%), referred to other hospital services less often (39%; 28% to 47%/6), admitted fewer patients (45%; 32% to 56%), and prescribed more often (41%; 30% to 54%/6). A similar trend was found for patients categorised as delay acceptable and (in a separate analysis) by presenting complaint category. 393 (17%) patients who had been seen by general practitioner staff reattended the department within 30 days of the index visit; 418 patients (18%) seen by accident and emergency staff similarly reattended. 435 patients (72% of those eligible) completed the consultation satisfaction questionnaire and 258 (59% of those eligible) provided health status information one month after consultation. There were no differences between patients managed by general practitioners and those managed by usual staff regarding consultation satisfaction questionnaire scores or health status. For all patients seen by general practitioners during the study, estimated marginal and total savings were £Ir1427 and £Ir117 005 respectively.Conclusion-General practitioners working as an integral part of an accident and emergency department manage non-emergency accident and emergency attenders safely and use fewer resources than do usual accident and emergency staff.

Blood-brain barrier (BBB) regulation involves the coordinated interaction of intercellular adherens and tight junctions in response to stimuli. One such stimulus, shear stress, has been shown to upregulate brain microvascular endothelial cell (BMvEC) barrier function, although our knowledge of the signaling mechanisms involved is limited. In this article, we examined the hypothesis that VE-cadherin can transmit shear signals to tight junction occludin with consequences for pTyr-occludin and barrier function. In initial studies, chronic shear enhanced membrane localization of ZO-1 and claudin-5, decreased pTyr-occludin (in part via a dephostatin-sensitive mechanism), and reduced BMvEC permeability, with flow reduction in pre-sheared BMvECs having converse effects. In further studies, VE-cadherin inhibition (VE-cad ΔEXD) blocked shear-induced Rac1 activation, pTyr-occludin reduction, and barrier upregulation, consistent with an upstream role for VE-cadherin in transmitting shear signals to tight junctions through Rac1. As VE-cadherin is known to mediate Rac1 activation via Tiam1 recruitment, we subsequently confirmed that Tiam1 inhibition (Tiam1-C580) could elicit effects similar to VE-cad ΔEXD. Finally, the observed attenuation of shear-induced changes in pTyr-occludin level and barrier phenotype following Rac1 inhibition (NSC23766, T17N) establishes a downstream role for Rac1 in this pathway. In summary, we describe for the first time in BMvECs a role for VE-cadherin in the transmission of physiological shear signals to tight junction occludin through engagement of Tiam1/Rac1 leading to barrier stabilization. A downstream role is also strongly indicated for a protein tyrosine phosphatase in pTyr-occludin modulation. Importantly, these findings suggest an important route of inter-junctional signaling cross-talk during BBB response to flow.

The physiological role of the platelet-secreted protein thrombospondin (TSP) is poorly understood, although it has been postulated to be involved in platelet aggregation and cellular adhesion. In this report, TSP isolated from human platelets was found to promote, in vitro, the cell-substratum adhesion of a variety of cells, including platelets, melanoma cells, muscle cells, endothelial cells, fibroblasts, and epithelial cells. The adhesion-promoting activity of TSP was species independent, specific, and not due to contamination by fibronectin, vitronectin, laminin, or platelet factor 4. The cell surface receptor for TSP is protein in nature and appears distinct from that for fibronectin.

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