Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation

Heparin is known to have anti-inflammatory effects, yet the mechanisms are not completely understood. In this study, we tested the hypothesis that heparin has a direct effect on activated polymorphonuclear leukocytes (PMNLs), changing their activation state, and can explain its anti-inflammatory effect. To test our hypothesis, we designed both in vitro and ex vivo studies to elucidate the mechanism by which heparin modulates PMNL functions and therefore the inflammatory response. We specifically tested the hypothesis that priming of PMNLs renders them more susceptible to heparin. Amplified levels of CD11b and increased rate of superoxide release manifested PMNL priming. Increase in cell priming resulted in a dose-dependent increase in heparin binding to PMNLs followed by augmented apoptosis. Blocking antibodies to CD11b inhibited heparin binding and abolished the apoptotic response. Moreover, heparin caused a significant dose-dependent decrease in the rate of superoxide release from PMNLs, which was blunted by blocking antibodies to CD11b. Altogether, this study shows that the interaction of heparin with the PMNL CD11b results in cell apoptosis and explains heparin’s anti-inflammatory effects

The dependability of students\u27 ratings of preceptors

No abstract provided

The effect of a domestic violence interclerkship on the knowledge, attitudes, and skills of third-year medical students

PURPOSE: To determine whether participation in an intensive domestic violence interclerkship (DVI) improved the knowledge, attitudes, and skills of two successive cohorts of students at the University of Massachusetts Medical School. METHOD: The authors measured the knowledge, attitudes, and skills pertaining to domestic violence of third-year students in the classes of 1997 and 1998 using a validated written examination administered before, immediately after, and six months after participation in a 3.5-day or two-day DVI, respectively; they compared the scores using paired t-tests. Nine months after the DVI, the students\u27 domestic violence screening skills were measured by a performance-based assessment (OSCE); using unpaired t-tests, the authors compared the OSCE scores with those of a previous third-year class that had not participated in a DVI. Immediately after the OSCE, the students reported their levels of confidence in domestic violence screening and their satisfaction with the domestic violence curriculum; using chi-square analysis, those self-reports were compared with those of the class with no DVI. RESULTS: The students who participated in the DVIs immediately and significantly improved their knowledge, attitudes, and skills (p \u3c .001), and fully or partially sustained those improvements six months later (p \u3c .001). Nine months after the DVI, the students performed domestic violence screening more effectively (p \u3c .001), expressed greater comfort with domestic violence screening (p \u3c .001), and felt better-prepared by the curriculum to address domestic violence issues (p \u3c .001) than did the students with no DVI. CONCLUSION: Participation in a short, focused DVI curriculum produced sustainable improvements in knowledge, attitudes, and skills that were successfully applied by third-year medical students to effective domestic violence screening. Interclerkships are an effective way to fit into the clinical curriculum those subjects that transcend the traditional biomedical domain and intersect all areas of medical practice

An exploration of the implementation of open disclosure of adverse events in the UK : a scoping review and qualitative exploration

Background: In 2009 the UK National Patient Safety Agency relaunched its Being Open framework to facilitate the open disclosure of adverse events to patients in the NHS. The implementation of the framework has been, and remains, challenging in practice. Aim: The aim of this work was to both critically evaluate and extend the current evidence base relating to open disclosure, with a view to supporting the implementation of a policy of open disclosure of adverse events in the NHS. Methods: This work was conducted in three phases. The first phase comprised two focused systematic literature reviews, one summarising empirical research on the effectiveness of interventions to enhance open disclosure, and a second, broader scoping review, looking at reports of current opinion and practice and wider knowledge. The second phase involved primary qualitative research with the objective of generating new knowledge about UK-based stakeholders' views on their role in and experiences of open disclosure. Stakeholder interviews were analysed using the framework approach. The third phase synthesised the findings from the first two phases to inform and develop a set of short pragmatic suggestions for NHS trust management, to facilitate the implementation and evaluation of open disclosure. Results: A total of 610 papers met the inclusion criteria for the broad review. A large body of literature discussed open disclosure from a number of related, but sometimes conflicted, perspectives. Evidential gaps persist and current practice is based largely on expert consensus rather than evidence. There appears to be a tension between the existing pragmatic guidance and the more in-depth critiques of what being consistent and transparent in health care really means. Eleven papers met the inclusion criteria for the more focused review. There was little evidence for the effectiveness of disclosure alone on organisational or individual outcomes or of interventions to promote and support open disclosure. Interviews with stakeholders identified strong support for the basic principle of being honest with patients or relatives when someone was seriously harmed by health care. In practice however, the issues are complex and there is confusion about a number of issues relating to disclosure policies in the UK. The interviews generated insights into the difficulties perceived within health care at individual and institutional levels, in relation to fully implementing the Being Open guidance. Conclusions: There are several clear strategies that the NHS could learn from to implement and sustain a policy of openness. Literature reviews and stakeholder accounts both identified the potential benefits of a culture that was generally more open (not just retrospectively open about serious harm). Future work could usefully evaluate the impact of disclosure on legal challenges within the NHS, best practice in models of support and training for open disclosure, embedding disclosure conversations in critical incident analysis and disclosure of less serious events

Which medical error to disclose to patients and by whom? Public preference and perceptions of norm and current practice

<p>Abstract</p> <p>Background</p> <p>Disclosure of near miss medical error (ME) and who should disclose ME to patients continue to be controversial. Further, available recommendations on disclosure of ME have emerged largely in Western culture; their suitability to Islamic/Arabic culture is not known.</p> <p>Methods</p> <p>We surveyed 902 individuals attending the outpatient's clinics of a tertiary care hospital in Saudi Arabia. Personal preference and perceptions of norm and current practice regarding which ME to be disclosed (5 options: don't disclose; disclose if associated with major, moderate, or minor harm; disclose near miss) and by whom (6 options: any employee, any physician, at-fault-physician, manager of at-fault-physician, medical director, or chief executive director) were explored.</p> <p>Results</p> <p>Mean (SD) age of respondents was 33.9 (10) year, 47% were males, 90% Saudis, 37% patients, 49% employed, and 61% with college or higher education. The percentage (95% confidence interval) of respondents who preferred to be informed of harmful ME, of near miss ME, or by at-fault physician were 60.0% (56.8 to 63.2), 35.5% (32.4 to 38.6), and 59.7% (56.5 to 63.0), respectively. Respectively, 68.2% (65.2 to 71.2) and 17.3% (14.7 to 19.8) believed that as currently practiced, harmful ME and near miss ME are disclosed, and 34.0% (30.7 to 37.4) that ME are disclosed by at-fault-physician. Distributions of perception of norm and preference were similar but significantly different from the distribution of perception of current practice (P < 0.001). In a forward stepwise regression analysis, older age, female gender, and being healthy predicted preference of disclosure of near miss ME, while younger age and male gender predicted preference of no-disclosure of ME. Female gender also predicted preferring disclosure by the at-fault-physician.</p> <p>Conclusions</p> <p>We conclude that: 1) there is a considerable diversity in preferences and perceptions of norm and current practice among respondents regarding which ME to be disclosed and by whom, 2) Distributions of preference and perception of norm were similar but significantly different from the distribution of perception of current practice, 3) most respondents preferred to be informed of ME and by at-fault physician, and 4) one third of respondents preferred to be informed of near-miss ME, with a higher percentage among females, older, and healthy individuals.</p

Intergenerational Justice Today

UID/FIL/00183/2013A theory of intergenerational justice consists in the study of the moral and political status of the relations between present and past or future people, more specifically, of the obligations and entitlements they can potentially generate. The challenges that justify talking about responsibilities between generations are myriad (e.g., the amount of public debt that is fair to incur; the funding of future pensions; reparations for past wrongs; climate change). And the disputes they prompt can focus on the past just as much as on the present, even though the fact that the human species has reached a state of technological progress that enables it to have an irredeemable impact on the planet and perhaps even endanger future human existence tends to make concerns about the future more pressing. Debates on intergenerational justice are twofold. The first revolves around the issue of whether claims of justice across generations whose members' lifetimes do not necessarily overlap could be justified. And the second revolves around the specific conception of justice in play, that is, around the nature of the standard that must be applied as well as around the identification of the contents of the duties that present generations supposedly have vis‐à‐vis past or future generations. This survey article depicts the conceptual and argumentative framework in which these debates are set. It aims to outline certain of the main features shared by the most influential contemporary theories of intergenerational justice, and the problems inherent in them. It concludes by suggesting that, even though the idea of succeeding generations is merely an abstraction, there are specific empirical states of affairs that require different theoretical responses to intergenerational justice.authorsversionpublishe

Heparanase Levels Are Elevated in the Urine and Plasma of Type 2 Diabetes Patients and Associate with Blood Glucose Levels

Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains of heparan sulfate proteoglycans. Utilizing an ELISA method capable of detection and quantification of heparanase, we examined heparanase levels in the plasma and urine of a cohort of 29 patients diagnosed with type 2 diabetes mellitus (T2DM), 14 T2DM patients who underwent kidney transplantation, and 47 healthy volunteers. We provide evidence that heparanase levels in the urine of T2DM patients are markedly elevated compared to healthy controls (1162±181 vs. 156±29.6 pg/ml for T2DM and healthy controls, respectively), increase that is statistically highly significant (P<0.0001). Notably, heparanase levels were appreciably decreased in the urine of T2DM patients who underwent kidney transplantation, albeit remained still higher than healthy individuals (P<0.0001). Increased heparanase levels were also found in the plasma of T2DM patients. Importantly, urine heparanase was associated with elevated blood glucose levels, implying that glucose mediates heparanase upregulation and secretion into the urine and blood. Utilizing an in vitro system, we show that insulin stimulates heparanase secretion by kidney 293 cells, and even higher secretion is observed when insulin is added to cells maintained under high glucose conditions. These results provide evidence for a significant involvement of heparanase in diabetic complications