A combined care model using early access to specialists off-hours to reduce cardiac admissions.

Despite the implementation of diagnostic and treatment algorithms for many common cardiovascular (CV) complaints, identifying low- and intermediate-risk cardiac patients presenting to the emergency department (ED) who could be managed without hospital admission remains difficult. We hypothesized that the presence of an attending cardiologist in the ED after normal working hours would decrease the proportion of these patients admitted to the hospital. We conducted a retrospective study of patients seen in the ED with cardiac diagnoses identified by ICD-9 codes during the time period when the cardiologist was available (6 p.m.-midnight) compared with patients seen at other times of the day in the 12 months before and after the consultation program was implemented. The primary outcome was disposition at the time of discharge from the ED. Logistic regression was used to model the primary outcome. A difference-in-differences approach was used as the primary statistical test .Following the start of the consultation program, the odds of discharge home from the ED with or without observation increased (OR 1.69, 95% CI [1.45-1.96]). There was a significant interaction between pre-/post-intervention status and time of day in the odds of discharge home from the ED (P = 0.04) suggesting an association between the consultation program and disposition patterns that is independent of concurrent programs aimed to reduce utilization. An ED-based cardiology consultation program may reduce the need for inpatient stays by identifying low- to intermediate-risk patients safe for discharge from the ED with or without a period of active management/observation.

Aspirin dosing in cardiovascular disease prevention and management: an update.

Aspirin has been in use for prevention and management of cardiovascular diseases for several decades. Clinical and epidemiological literature suggests that while net benefits of aspirin in primary prevention of CVDs are less clear, the benefits of aspirin in acute scenarios and secondary prevention settings are well established. However, its optimum dosing requirements have been up for debate especially in various settings of acute coronary syndrome and stable ischemic heart disease. The role of clinician in stratifying individual risk score to achieve net clinical benefit is an important determinant of initiating aspirin therapy. The purpose of this article is to review association of aspirin and CVD in general, and to review its dosing regimens in acute settings as well as primary and secondary prevention as suggested by various established guidelines. We also aim to provide the readers an update on recent changes and current evidence based practice trends.

ST elevation myocardial infarction: recent advances and updates.

ST elevation myocardial infarction (STEMI) remains a leading cause of morbidity, mortality and disability worldwide. Statistically, a trend towards improvements in morbidity and mortality has been consistent over the years, which is attributed primarily to the modification of risk factors, healthier lifestyles, treatment advances and better management of door-to-balloon times via STEMI systems. However, a major challenge in the coming years will be the baby boomers (born between the years 1946 and 1964) coming into old age. The first baby boomers turned 65 in year 2011. As the baby boomers age in the coming years, the incidence of coronary heart disease is likely to increase, and so there will be a greater need to have major advances in the management of coronary heart disease in order to deal with this additional incidence. The scope of this article is to review recent advances in the management of STEMI and to provide an updated overview.

Orthostatic hypotension as a manifestation of vitamin B12 deficiency.

A 90-year-old woman with orthostatic hypotension and near-syncope was found to have a low-normal level of vitamin B(12) and no other medical findings that could explain her orthostasis. Her symptoms responded to vitamin B(12) replacement therapy. This case shows that vitamin B(12) deficiency can induce orthostatic hypotension and syncope that are correctable by vitamin B(12) replacement.

Marked attenuation of shock burden by the use of antitachycardia pacing therapy in a patient with an implanted cardioverter-defibrillator.

A 76-year-old man was admitted to our institution for elective exchange of his implanted cardioverter-defibrillator generator. Nine years earlier, he had been diagnosed with nonischemic cardiomyopathy and nonsustainable ventricular tachycardia. At that time, he had received a single-chamber implanted cardioverter-defibrillator, which was upgraded to a dual-chamber implanted cardioverter-defibrillator 3 years later. In the course of the current admission, routine device interrogation during exchange of the patient's implanted cardioverter-defibrillator generator revealed 150 episodes of ventricular tachycardia in the preceding 7 months, 137 of which had been successfully treated by antitachycardia pacing therapy without shock. These findings show the remarkable effectiveness of antitachycardia pacing in terminating ventricular tachycardia while preventing the delivery of shocks, minimizing patient discomfort, and avoiding implanted cardioverter-defibrillator battery depletion.

Integrin α2ß1 mediates tyrosine phosphorylation of vascular endothelial cadherin induced by invasive breast cancer cells.

The molecular mechanisms that regulate the endothelial response during transendothelial migration (TEM) of invasive cancer cells remain elusive. Tyrosine phosphorylation of vascular endothelial cadherin (VE-cad) has been implicated in the disruption of endothelial cell adherens junctions and in the diapedesis of metastatic cancer cells. We sought to determine the signaling mechanisms underlying the disruption of endothelial adherens junctions after the attachment of invasive breast cancer cells. Attachment of invasive breast cancer cells (MDA-MB-231) to human umbilical vein endothelial cells induced tyrosine phosphorylation of VE-cad, dissociation of ß-catenin from VE-cad, and retraction of endothelial cells. Breast cancer cell-induced tyrosine phosphorylation of VE-cad was mediated by activation of the H-Ras/Raf/MEK/ERK signaling cascade and depended on the phosphorylation of endothelial myosin light chain (MLC). The inhibition of H-Ras or MLC in endothelial cells inhibited TEM of MDA-MB-231 cells. VE-cad tyrosine phosphorylation in endothelial cells induced by the attachment of MDA-MB-231 cells was mediated by MDA-MB-231 α(2)ß(1) integrin. Compared with highly invasive MDA-MB-231 breast cancer cells, weakly invasive MCF-7 breast cancer cells expressed lower levels of α(2)ß(1) integrin. TEM of MCF-7 as well as induction of VE-cad tyrosine phosphorylation and dissociation of ß-catenin from the VE-cad complex by MCF-7 cells were lower than in MDA-MB-231 cells. These processes were restored when MCF-7 cells were treated with ß(1)-activating antibody. Moreover, the response of endothelial cells to the attachment of prostatic (PC-3) and ovarian (SKOV3) invasive cancer cells resembled the response to MDA-MB-231 cells. Our study showed that the MDA-MB-231 cell-induced disruption of endothelial adherens junction integrity is triggered by MDA-MB-231 cell α(2)ß(1) integrin and is mediated by H-Ras/MLC-induced tyrosine phosphorylation of VE-cad.

Atorvastatin preserves the integrity of endothelial adherens junctions by inhibiting vascular endothelial cadherin tyrosine phosphorylation.

Vascular endothelial cadherin (VE-cad) tyrosine (Tyr) phosphorylation has been implicated in the disruption of adherens junctions (AJs) induced by inflammatory reactions. The impacts of statins on integrity of AJs and VE-cad Tyr phosphorylation have not been explored. The effects of atorvastatin on IL-1ß and monocyte-induced VE-cad Tyr phosphorylation in human umbilical vein endothelial cells (ECs) were studied. In ECs treated with interleukin (IL)-1ß for 30 min, VE-cad Tyr phosphorylation, dissociation of the VE-cad/ß-catenin complex and transendothelial migration (TEM) of monocytes were increased. These processes were mediated by activation of HRas and RhoA that leads to phosphorylation of myosin light chain (MLC). Atorvastatin inhibited IL-1ß-induced Tyr phosphorylation of VE-cad by inhibiting RhoA and by dephosphorylating MLC. The attenuating effect of atorvastatin on VE-cad Tyr phosphorylation was reversed when RhoA was activated or MLC phosphatase was inhibited. Furthermore, inhibiting farnesyl transferase or geranylgeranyl transferase reproduced the inhibitory effects of atorvastatin on VE-cad Tyr phosphorylation. In addition, atorvastatin inhibited monocyte-induced VE-cad Tyr phosphorylation in ECs and attenuated IL-1ß-induced TEM of monocytes. Our study introduces a novel pleiotropic effect of atorvastatin and suggests that statins protect the integrity of AJs in ECs by inhibiting RhoA-mediated Tyr phosphorylation of VE-cad.

Myosin light chain phosphorylation facilitates monocyte transendothelial migration by dissociating endothelial adherens junctions.

AIMS: Transendothelial migration (TEM) of monocytes is a crucial step in inflammatory processes such as atherogenesis. Tyrosine phosphorylation of vascular endothelial cadherin (VE-cad) has been implicated in the dissociation of adherens junctions and the increased paracellular permeability of endothelial cells (ECs) that occur during TEM of monocytes. However, the underlying molecular mechanism has not been determined. We tested the hypothesis that the phosphorylation of myosin light chain (MLC) in ECs is crucial for the dissociation of adherens junctions during TEM of monocytes. METHODS AND RESULTS: Using a combination of biochemical and cellular techniques, we provide evidence for the signal transduction pathways that regulate tyrosine phosphorylation of VE-cad in ECs after the attachment of monocytes. Our findings indicate that after interaction of integrins on THP-1 cells with adhesion molecules on ECs, the induction of the HRas\Raf\MEK\ERK signalling cascade leads to the phosphorylation of MLC. This results in the recruitment of Src to the VE-cad complex and tyrosine phosphorylation of VE-cad, which leads to dissociation of ß-catenin from the VE-cad complex, formation of gaps between ECs, and enhancement of THP-1 cell TEM. CONCLUSION: Our studies suggest that monocyte-induced phosphorylation of MLC in ECs enhances TEM of monocytes through dissociation of EC adherens junctions.

Inhibition of MLC phosphorylation restricts replication of influenza virus--a mechanism of action for anti-influenza agents.

Influenza A viruses are a severe threat worldwide, causing large epidemics that kill thousands every year. Prevention of influenza infection is complicated by continuous viral antigenic changes. Newer anti-influenza agents include MEK/ERK and protein kinase C inhibitors; however, the downstream effectors of these pathways have not been determined. In this study, we identified a common mechanism for the inhibitory effects of a significant group of anti-influenza agents. Our studies showed that influenza infection activates a series of signaling pathways that converge to induce myosin light chain (MLC) phosphorylation and remodeling of the actin cytoskeleton. Inhibiting MLC phosphorylation by blocking RhoA/Rho kinase, phospholipase C/protein kinase C, and HRas/Raf/MEK/ERK pathways with the use of genetic or chemical manipulation leads to the inhibition of influenza proliferation. In contrast, the induction of MLC phosphorylation enhances influenza proliferation, as does activation of the HRas/Raf/MEK/ERK signaling pathway. This effect is attenuated by inhibiting MLC phosphorylation. Additionally, in intracellular trafficking studies, we found that the nuclear export of influenza ribonucleoprotein depends on MLC phosphorylation. Our studies provide evidence that modulation of MLC phosphorylation is an underlying mechanism for the inhibitory effects of many anti-influenza compounds.

Accuracy of radiological features for predicting extracorporeal shock wave lithotripsy success for treatment of kidney calculi.

INTRODUCTION: Our aim was to assess the accuracy of radiological characteristics observed by the urologist in estimating the success rate of extracorporeal shock wave lithotripsy (SWL) in patients with kidney calculi. MATERIALS AND METHODS: Patients with kidney calculi sized 10 mm to 15 mm who underwent SWL in our center were enrolled. One urologist estimated the success chance of SWL based on plain abdominal radiography. Accordingly, the patients were categorized into 2 groups with more than 75% chance of fragmentation (group 1) and with 50% to 75% estimated chance of fragmentation (group 2). Factors used for estimation included calculus shape, homogeneity, and density as compared with the adjacent 12th rib. The estimations were compared with the resulted stone-free rate after a 3-month follow-up. RESULTS: A total of 137 patients were studied, of whom, 92 (67.2%) were categorized in group 1 and 45 (32.8%) in group 2, before the lithotripsy. Successful treatment was recorded in 101 patients (73.7%). Eighty-five patients with favorable estimated chance of successful lithotripsy (92.4%) had successful SWL, and 29 with less favorable estimate (64.4%) did not have successful fragmentation following 2 sessions of SWL (P < .001). The sensitivity and specificity of radiological parameters for prediction of treatment success were 84.2% and 80.6%, respectively. CONCLUSION: We found that certain radiographic features of urinary calculi such as calculus density, as compared with the adjacent bone, and calculus shape could have predictive impression for the success rate of SWL.