ß-blocker withdrawal among patients presenting for surgery from home.

OBJECTIVE: This study sought to measure the prevalence of perioperative ß-blocker noncompliance by patients who were prescribed long-term ß-blocker therapy and presented for surgery from home. The effect of patient noncompliance on the presenting heart rate on the day of surgery also was examined. DESIGN: Prospective observational study with outcome data obtained from reviews of medical records. SETTING: The preoperative clinic and operating rooms of a Veterans Administration hospital. PARTICIPANTS: Patients on long-term ß-blocker therapy who presented from home for surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic and comorbidity data and data on self-reported compliance to ß-blocker therapy, vital signs on the initial day of surgery, and recent ambulatory vital signs were collected. Ten of 50 subjects (20%; 95% confidence interval, 9-31) reported not taking their ß-blocker on the day of surgery. These self-reported nonadherers exhibited a higher presenting heart rate on the day of surgery than adherent subjects (median, 78 v 65 beats/min; p = 0.02 by Wilcoxon rank-sum test). The difference-in-difference analysis in heart rate between baseline primary care and the day of surgery also was statistically significant between compliant and noncompliant subjects (-7 v + 12.5 beats/min; p < 0.00001). CONCLUSIONS: Patient self-report and physiologic data documented a failure to take ß-blockers and possible ß-blocker withdrawal in 20% of patients who presented for surgery from home. If these findings are confirmed in larger studies, improved patient understanding of and compliance with medication instructions during preoperative visits should be a focus of future quality improvement initiatives.

Netrins and neogenin promote myotube formation.

Differentiation of skeletal myoblasts into multinucleated myotubes is a multistep process orchestrated by several families of transcription factors, including myogenic bHLH and NFAT proteins. The activities of these factors and formation of myotubes are regulated by signal transduction pathways, but few extracellular factors that might initiate such signals have been identified. One exception is a cell surface complex containing promyogenic Ig superfamily members (CDO and BOC) and cadherins. Netrins and their receptors are established regulators of axon guidance, but little is known of their function outside the nervous system. We report here that myoblasts express the secreted factor netrin-3 and its receptor, neogenin. These proteins stimulate myotube formation and enhance myogenic bHLH- and NFAT-dependent transcription. Furthermore, neogenin binds to CDO in a cis fashion, and myoblasts lacking CDO are defective in responding to recombinant netrin. It is proposed that netrin-3 and neogenin may promote myogenic differentiation by an autocrine mechanism as components of a higher order complex of several promyogenic cell surface proteins.

Promyogenic members of the Ig and cadherin families associate to positively regulate differentiation.

Determination and differentiation of cells in the skeletal muscle lineage is positively regulated by cell-cell contact. Cell-surface proteins proposed to mediate this effect include both classical cadherins and Ig superfamily members; potential interactions between the promyogenic activities of these classes of protein, however, are unknown. We show here that CDO and BOC, two promyogenic Ig superfamily members that bind to each other in a cis fashion, form complexes with N- and M-cadherin. These complexes contain beta-catenin and are enriched at sites of cell-cell contact between myoblasts. In transient expression assays, the ectodomains and intracellular regions of CDO, BOC, and N-cadherin each interact independently, suggesting that the interactions occur in a cis fashion; consistent with this conclusion, cadherin-mediated cell adhesion is not required for them to occur. Stable expression in myoblasts of a CDO deletion mutant deficient in its ability to associate with N-cadherin interferes with differentiation as assessed by biochemical, morphological, and reporter gene assays, suggesting that this interaction is functionally important in myogenesis. Thus, some of the cell-cell contact-mediated activities that are required for myogenesis seem to be based on interdependent activities of promyogenic classical cadherins and Ig superfamily members.