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Biomedical subjects

Marc Cohen

Publications and source records attributed to Marc Cohen.

At least 19 recordsLinked to original sources
PubMed2007

Bleeding complications in patients with acute coronary syndrome undergoing early invasive management can be reduced with radial access, smaller sheath sizes, and timely sheath removal.

OBJECTIVES: Our objective was to analyze the impact of arterial access site, sheath size, timing of sheath removal, and use of access site closure devices on high-risk patients with acute coronary syndromes (ACS). BACKGROUND: In the SYNERGY trial, 9,978 patients with ACS were randomly assigned to receive enoxaparin or unfractionated heparin. METHODS: This analysis includes 9,404 patients for whom sheath access information was obtained for the first PCI procedure or diagnostic catheterization. Comparisons of baseline, angiographic, and procedural characteristics were carried out according to access site and sheath size. RESULTS: Overall, 9,404 (94%) patients underwent angiography at a median of 21 hr (25th and 75th percentiles: 5, 42) and 4,687 (50%) underwent PCI at a median of 23 hr (6,49) of enrollment. The access site was femoral for 94.9% of cases, radial for 4.4%, and brachial for 0.7%. Radial access was associated with fewer transfusions than femoral access (0.9% vs. 4.8%, P=0.007). For femoral access, the rates of noncoronary artery bypass grafting (CABG)-related TIMI major bleeding by sheath size was 1.5% for 4 or 5 French (Fr), 1.6% for 6 Fr, 3.3% for 7 Fr, and 3.8% for >or=8 Fr (P<0.0001). After adjustment for baseline characteristics, femoral access site, larger sheath size, and delayed sheath removal were independent predictors of need for transfusion. CONCLUSIONS: Smaller sheaths, radial access, and timely sheath removal may mitigate the bleeding risk associated with potent antithrombotic/platelet therapy and early catheterization.

Aged↗
PubMed2006

A subgroup analysis of the impact of prerandomization antithrombin therapy on outcomes in the SYNERGY trial: enoxaparin versus unfractionated heparin in non-ST-segment elevation acute coronary syndromes.

OBJECTIVES: The purpose of this study was to compare the effect of receiving pretreatment with antithrombin before randomization as well as overall efficacy and safety of enoxaparin versus unfractionated heparin (UFH) in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) trial. BACKGROUND: The SYNERGY trial results demonstrated noninferiority in outcomes with enoxaparin compared with UFH. Randomized treatment was independent of prerandomization treatment. METHODS: Analyses were first performed on the 4 prerandomization subgroups: patients who received no antithrombin therapy and those who were treated with enoxaparin or UFH or both. Then, we focused on the subgroup of patients who received no pretreatment or were pretreated with and randomized to the same drug. Of the 9,978 patients, 2,440 did not receive prerandomization therapy and 6,138 received consistent therapy through randomization. The primary end point was the composite of death and nonfatal myocardial infarction (MI) at 30 days. RESULTS: After adjustment for differences among the subgroups, no significant difference in the association between the 4 pretreatment groups and death or MI remained (p = 0.171). The randomized treatment effect on 30-day death or MI tended to vary with pretreatment (p = 0.055 for interaction test after adjustment). Patients who received consistent therapy with enoxaparin had significantly less death or MI than patients randomized to UFH (adjusted p = 0.041) with a trend toward increased bleeding. CONCLUSIONS: Treatment with antithrombin therapy before randomization had potential impact on comparison of study drug effects. After adjustment for differences in baseline characteristics between subgroups, consistent therapy with enoxaparin might be superior to UFH in reducing death or nonfatal MI, with a modest excess in bleeding.

Aged↗
PubMed2006

Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention.

BACKGROUND: Despite its limitations, unfractionated heparin has been the standard anticoagulant used during percutaneous coronary intervention (PCI). Several small studies have suggested that intravenous enoxaparin may be a safe and effective alternative. Our primary aim was to assess the safety of enoxaparin as compared with that of unfractionated heparin in elective PCI. METHODS: In this prospective, open-label, multicenter, randomized trial, we randomly assigned 3528 patients with PCI to receive enoxaparin (0.5 or 0.75 mg per kilogram of body weight) or unfractionated heparin adjusted for activated clotting time, stratified according to the use or nonuse of glycoprotein IIb/IIIa inhibitors. The primary end point was the incidence of major or minor bleeding that was not related to coronary-artery bypass grafting. The main secondary end point was the percentage of patients in whom the target anticoagulation levels were reached. RESULTS: Enoxaparin at a dose of 0.5 mg per kilogram was associated with a significant reduction in the rate of non-CABG-related bleeding in the first 48 hours, as compared with unfractionated heparin (5.9% vs. 8.5%; absolute difference, -2.6; 95% confidence interval [CI], -4.7 to -0.6; P=0.01), but the higher enoxaparin dose was not (6.5% vs. 8.5%; absolute difference, -2.0; 95% CI, -4.0 to 0.0; P=0.051). The incidence of major bleeding was significantly reduced in both enoxaparin groups, as compared with the unfractionated heparin group. Target anticoagulation levels were reached in significantly more patients who received enoxaparin (0.5-mg-per-kilogram dose, 79%; 0.75-mg-per-kilogram dose, 92%) than who received unfractionated heparin (20%, P<0.001). CONCLUSIONS: In elective PCI, a single intravenous bolus of 0.5 mg of enoxaparin per kilogram is associated with reduced rates of bleeding, and a dose of 0.75 mg per kilogram yields rates similar to those for unfractionated heparin, with more predictable anticoagulation levels. The trial was not large enough to provide a definitive comparison of efficacy in the prevention of ischemic events. (ClinicalTrials.gov number, NCT00077844 [ClinicalTrials.gov].).

Aged↗
PubMed2006

The use of a HEMOCHRON JR. HEMONOX point of care test in monitoring the anticoagulant effects of enoxaparin during interventional coronary procedures.

BACKGROUND: Enoxaparin is increasingly used for the anticoagulation of patients undergoing percutaneous coronary intervention (PCI). Several reports have suggested the utility of using point of care tests in monitoring the anticoagulation levels of enoxaparin in patients undergoing PCI. The objective of this study was to evaluate a new point-of-care test (POCT) HEMONOX in monitoring the anticoagulant effect of enoxaparin in non citrated fresh whole blood samples from patients undergoing elective PCI procedure. METHODS: Following IRB approval, blood samples were obtained from fifty-four patients who received two sequential intravenous doses of enoxaparin; 0.1 mg/kg followed 5 min later by 0.4 mg/kg for a total of 0.5 mg/kg. Blood was drawn at baseline and at 5, 10, 30 and 60 min post first bolus for evaluation in the clot-based POCT HEMONOX, ACT and aPTT and the chromogenic anti-Xa activity assay. RESULTS: HEMONOX clotting time (CT) at baseline was 62.6 +/- 6.2 secs, (n = 32) in healthy donors and statistically higher in PCI patients (71.6 +/- 9.1 secs, p = 0.0001). The peak HEMONOX response that was always achieved at 10 min post bolus was >100 secs in all 54 patients, of these 83% yielded CT >150 secs (range: 150-466). There was no detectable anti-Xa activity level at baseline while peak HEMONOX CT corresponded to therapeutic levels (0.85 +/- 0.14 U/ml; range: 0.61-1.34). Both HEMONOX CT and anti-Xa level significantly decreased at the time of sheath removal. HEMONOX CT at peak response suggested 3 patient subgroups with different levels of sensitivity to enoxaparin: low, intermediate and high responders. The correlation between anti-Xa activity level and HEMONOX CT was >or=0.85 in each patient subgroup when data from the 3 critical time points; baseline (absence of drug), peak response (10 min post bolus) and sheath removal (60 min post bolus) were analyzed. The correlation diminished to >or=0.83 when the analyses included data from all 5 time points [baseline, 5, 10, 30, and 60 min post bolus]. The HEMONOX test was the most sensitive POCT to measure the anticoagulant effects of enoxaparin. All patients completed PCI successfully. CONCLUSION: The HEMONOX test may be able to guide anticoagulation with enoxaparin during PCI. The HEMONOX assay is a one step whole blood coagulation test performed on the HEMOCHRON Jr. Signature + POC system. The method was evaluated to monitor the anticoagulant level of enoxaparin in blood samples from patients undergoing PCI after receiving an intravenous dose of 0.5 mg/kg. The results suggest a clear distinction of HEMONOX CT between the baseline value of untreated patients and patients achieving therapeutic enoxaparin levels.

Adult↗
PubMed2006

The greatest benefit of enoxaparin over unfractionated heparin in acute coronary syndromes is achieved in patients presenting with ST-segment changes: the Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) Electrocardiogram Core Laboratory Substudy.

BACKGROUND: We undertook a prospective electrocardiogram (ECG) substudy in the ESSENCE trial and hypothesized that patient subgroups with ST-segment deviation would experience greater benefit from enoxaparin, as compared with unfractionated heparin (UFH). METHODS: Of the 3171 patients in the trial, 3087 had a qualifying ECG available for analysis by the core laboratory. Patients were divided into 4 mutually exclusive groups based upon the qualifying ECG: (1) ST-segment elevation, (2) ST-segment depression, (3) T-wave inversions, or (4) others. RESULTS: The 30-day and 1-year primary outcomes (death, myocardial infarction, or recurrent angina) were significantly lower among patients with ST elevation or ST depression who received enoxaparin, as compared with UFH (20.8% vs 28.0%, P = .0019 and 32% vs 40.4%, P = .0011, respectively). The greatest absolute benefit of enoxaparin over UFH was seen in patients with ST depression (primary end point at 30 days, 24.6% vs 32.4%, P = .018; at 1 year, 35.5% vs 44.5%, P = .012). CONCLUSION: Specific recognition of patients with ST-segment depression appears to identify those not only at high risk for adverse outcome, but also patients most likely to derive the greatest benefit from enoxaparin, as compared with UFH therapy.

Angina, Unstable↗
PubMed2006

Efficacy and safety of enoxaparin compared with unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention in the Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial.

BACKGROUND: Enoxaparin reduces ischemic events more effectively than unfractionated heparin (UFH) in patients treated conservatively for non-ST-segment elevation acute coronary syndrome. The SYNERGY trial compared these agents in high-risk patients undergoing early invasive treatment. Enoxaparin was noninferior to UFH for the 30-day primary end point of death/myocardial infarction (MI), but modestly increased bleeding. METHODS AND RESULTS: This article compares the outcomes of the 4687 SYNERGY patients (47%) undergoing percutaneous coronary intervention, who were randomized to receive enoxaparin or UFH. Antithrombotic therapy was administered prerandomization in 78%. Crossover (usually in the catheterization laboratory) to the alternative antithrombotic occurred in 14.6% of enoxaparin patients and 2.9% of UFH-treated patients (P < .0001). Stenting was performed in 86.3%. Abrupt vessel closure occurred in 1.3% of enoxaparin patients and 1.7% of UFH-treated patients (P = .318). The rates of death/MI were similar at 30 days (13.1% with enoxaparin vs 14.2% with UFH, P = .289). GUSTO severe bleeding occurred with similar frequency in both groups (1.5% vs 1.6%, P = .688). TIMI major bleeding was more common with enoxaparin (3.7% vs 2.5% with UFH, P = .028). Transfusions were more frequent with enoxaparin than with UFH (6.8% vs 5.4%, P = .047). TIMI major bleeding increased with crossover from enoxaparin to UFH (from 3.7% to 7.8%) and from UFH to enoxaparin (from 2.5% to 8.6%). Statistical adjustment to model reasons for crossover did not affect the overall safety and efficacy outcomes. CONCLUSIONS: In high-risk patients undergoing early percutaneous coronary intervention for acute coronary syndrome, enoxaparin avoids the need for monitoring and achieves similar effectiveness to UFH but is associated with more bleeding.

Acute Disease↗
PubMed2006

The use of virtual patients to teach medical students history taking and communication skills.

BACKGROUND: At most institutions, medical students learn communication skills through the use of standardized patients (SPs), but SPs are time and resource expensive. Virtual patients (VPs) may offer several advantages over SPs, but little data exist regarding the use of VPs in teaching communication skills. Therefore, we report our initial efforts to create an interactive virtual clinical scenario of a patient with acute abdominal pain to teach medical students history-taking and communication skills. METHODS: In the virtual scenario, a life-sized VP is projected on the wall of an examination room. Before the virtual encounter, the student reviews patient information on a handheld tablet personal computer, and they are directed to take a history and develop a differential diagnosis. The virtual system includes 2 networked personal computers (PCs), 1 data projector, 2 USB2 Web cameras to track the user's head and hand movement, a tablet PC, and a microphone. The VP is programmed with specific answers and gestures in response to questions asked by students. The VP responses to student questions were developed by reviewing videotapes of students' performances with real SPs. After obtaining informed consent, 20 students underwent voice recognition training followed by a videotaped VP encounter. Immediately after the virtual scenario, students completed a technology and SP questionnaire (Maastricht Simulated Patient Assessment). RESULTS: All participants had prior experience with real SPs. Initially, the VP correctly recognized approximately 60% of the student's questions, and improving the script depth and variability of the VP responses enhanced most incorrect voice recognition. Student comments were favorable particularly related to feedback provided by the virtual instructor. The overall student rating of the virtual experience was 6.47 +/- 1.63 (1 = lowest, 10 = highest) for version 1.0 and 7.22 +/- 1.76 for version 2.0 (4 months later) reflecting enhanced voice recognition and other technological improvements. These overall ratings compare favorably to a 7.47 +/- 1.16 student rating for real SPs. CONCLUSIONS: Despite current technological limitations, virtual clinical scenarios could provide students a controllable, secure, and safe learning environment with the opportunity for extensive repetitive practice with feedback without consequence to a real or SP.

Clinical Competence↗
PubMed2006

Periprocedural bridging therapy in patients receiving chronic oral anticoagulation therapy.

BACKGROUND: In patients receiving chronic oral anticoagulation with vitamin K antagonists (VKAs) it may be necessary to temporarily discontinue VKA therapy to allow surgery or other invasive procedures to be performed, as maintaining treatment may increase the risk of bleeding during the procedure. This, however, creates a clinical dilemma, since discontinuing VKAs may place the patient at risk of thromboembolism. SCOPE: We undertook a systematic narrative review of patients on chronic oral anticoagulation, requiring a periprocedural bridging therapy with heparin during invasive procedures. FINDINGS AND RECOMMENDATIONS: For patients requiring temporary discontinuation of VKA, current guidelines recommend the use of 'bridging' therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) in patients considered to be at intermediate-to-high risk of thromboembolism, such as those with prosthetic heart valves or atrial fibrillation. Recent studies show that LMWHs are associated with low rates of thromboembolism and, when compared with UFH, are as effective and safe as UFH when used as periprocedural bridging therapy in such patients. LMWHs also offer advantages such as ease of administration and predictable anticoagulant effects. Moreover, outpatient-based periprocedural bridging therapy with LMWH has been shown to result in significant cost savings compared with in-hospital UFH. CONCLUSIONS: The decision to provide bridging therapy requires careful consideration of the relative risks of thromboembolism and bleeding in each patient. Based upon the studies reviewed we recommend a therapeutic dose of UFH or LMWH for patients at intermediate-to-high thromboembolic risk requiring interruption of VKA, especially for low bleeding risk procedures. We would like to propose upgrading the American College of Chest Physicians (ACCP) guideline recommendations from 2C to 1C. However, there is still a need for a randomized controlled trial on the efficacy and safety of the available bridging strategies, including heparin and placebo comparators, in preventing thromboembolism for specific patients and procedures.

Anticoagulants↗
PubMed2006

Early ambulation and variability in anticoagulation during elective coronary stenting with a single intravenous bolus of low-dose, low-molecular weight heparin enoxaparin.

BACKGROUND: The best anticoagulation strategy for patients undergoing percutaneous coronary intervention (PCI) remains controversial. The primary objective of this study was to assess the feasibility of immediate sheath removal post-PCI in patients given a single low-dose intravenous (IV) bolus of enoxaparin as the sole anticoagulant. METHODS: In 53 patients with stable coronary disease undergoing elective PCI, a single IV bolus of 0.5 mg per kg enoxaparin was administered 10 minutes before PCI. Patients were pretreated with aspirin 100 mg and clopidogrel 300 mg. The femoral access sheaths were removed immediately after PCI by manual compression. Major and minor bleeding and coronary thrombosis were recorded. Anti-Xa levels were measured before, during and after PCI. RESULTS: One patient had an intracoronary thrombus 60 minutes after enoxaparin administration, and there was 1 ischemic stroke. Fifty-one of the 53 patients had their sheaths successfully pulled immediately post-PCI. One patient had a pseudoaneurysm requiring surgical repair, and 1 patient had a minor bleed. Postprocedural elevation of CK-MB > 3 times the upper limit of normal occurred in 7 patients (13.2%). Anti-Xa activity was 0.56 +/- 0.16 at 10 minutes post-IV injection, and then progressively decreased to 0.14 +/- 0.09 IU/ml at 6 hours after injection. Ten minutes after IV enoxaparin, 12 patients (23.5%) had anti-Xa levels < 0.5 IU/ml. CONCLUSIONS: Immediate removal of femoral sheaths, after a single low-dose of IV enoxaparin for elective stenting appears feasible. However, a sizeable proportion of patients achieved anti-Xa levels below the widely agreed upon "therapeutic" level after injection.

Aged↗
PubMed2006

Managing the expanded use of biologics across therapeutic areas: an example from b-cell targeted therapies.

Greater understanding of disease pathology at the molecular and cellular level has enhanced the roles of various proteins in disease pathogenesis. Because so many diseases have common physiologic pathways, many biologic therapies have been found to work in multiple therapeutic areas, particularly cancer, inflammation, infections, and metabolic and blood disorders. Thus, the search for agents to inhibit or block these critical therapeutic agents has been accelerated. This supplement reviews the factors contributing to the enormous growth of biotechnology drugs--both those currently marketed and those in late-stage development--from a clinical and managed care perspective. Specifically, the growth of expanded indications for drugs approved by the US Food and Drug Administration (FDA) will be examined, along with the challenges of managing biotechnology therapies being used beyond their original indications. A review of currently marketed biologics under investigation for new indications will be presented, along with a discussion of the implications of expanding indications and the resultant impact on managed care organizations in terms of cost, benefit design, access management strategy, safety and efficacy, and other pertinent issues. Managed care executives will face the challenge of making critical formulary decisions within the context of ever-increasing biologic options, including greater utilization of biotechnology drugs, more biologics for common conditions, and expanded indications for FDA-approved drugs.

B-Lymphocytes↗
PubMed2006

Strategies for optimizing outcomes in the NSTE-ACS patient The CATH (cardiac catheterization and antithrombotic therapy in the hospital) Clinical Consensus Panel Report.

This paper provides a comprehensive up-to-date review of the medical and invasive management of patients with non- ST-segment elevation acute coronary syndromes (NSTE-ACS). The authors have summarized findings from key clinical trials published recent years that contribute to clinicians' understanding of how best to optimize therapy. The goals for the management of NSTE-ACS are rapid and accurate risk stratification, appropriate and institution-specific triage to interventional versus medical strategies and optimal pharmacologic therapy--all of which provide for a smooth and seamless transition of care between the emergency department and the cardiology service. High-risk features or absolute treatment trigger criteria that support more aggressive medical therapy (i.e., addition of small-molecule GP IIb/IIIa inhibitor to a core regimen of aspirin, enoxaparin, and in most cases, clopidogrel) and/or that would direct clinicians toward percutaneous, mechanical/interventional strategies as the preferred modality include, but are not limited to, the presence of one or more of the following: (1) elevated cardiac markers (troponin and/or CK-MB); (2) elevated levels of inflammatory markers (particularly CRP > 3 microg/dl); (3) age > 65 years; (4) presence of ST-T wave changes; (5) TIMI Risk Score greater than or equal to 4; (6) diabetes; and/or (7) clinical instability in the setting of suspected NSTE-ACS. Specific clinical, ECG and/or biochemical trigger points modulate the aggressiveness of both the medical therapy and the propensity to perform early angiography with or without subsequent revascularization in patients with NSTE-ACS. Although additional refinements and changes in ACS management are still to come, evidence-based strategies suggest that prompt mechanical revascularization is associated with the best possible clinical outcomes, particularly for patients with high-risk features and in whom benefits of adjunctive, pharmacoinvasive antithrombotic therapies can be consolidated. Patient transfer for cardiac catheterization/percutaneous coronary intervention (PCI) is strongly recommended in patients who manifest high-risk features and/or aggressive treatment trigger criteria, so that this high-risk subgroup may receive definitive, interventional and/or cardiology-directed specialty care at appropriate sites of care. When available, interventional management is preferred in these patients. The importance of safe and effective anticoagulation in the spectrum of management strategies has been confirmed, and the evidence in support of enoxaparin and other antithrombotic agents has been reviewed. Dosing recommendations for enoxaparin use in the setting of PCI have been issued by the CATH Panel and have been summarized in this consensus report. Similar recommendations have been presented for the use of oral antiplatelet agents and GP IIb/IIIa antagonists. The addition of statins, ACE-inhibitors and beta-blockers is also stressed as part of a comprehensive secondary cardioprotective strategy for patients with coronary heart disease.

Acute Disease↗
PubMed2005

High-risk patients with acute coronary syndromes treated with low-molecular-weight or unfractionated heparin: outcomes at 6 months and 1 year in the SYNERGY trial.

CONTEXT: The SYNERGY trial comparing enoxaparin and unfractionated heparin in high-risk patients with acute coronary syndromes (ACS) showed that enoxaparin was not inferior to unfractionated heparin in reducing death or nonfatal myocardial infarction (MI) at 30 days. OBJECTIVE: To evaluate continued risk in this patient cohort through 6-month and 1-year follow-up. DESIGN, SETTING, AND PATIENTS: Overall, 9978 patients were randomized from August 2001 through December 2003 in 487 hospitals in 12 countries. Patients were followed up for 6 months and for 1 year. MAIN OUTCOME MEASURES: Six-month outcomes were death, nonfatal MI, revascularization procedures, stroke, and site-investigator-reported need for rehospitalization; 1-year outcome was all-cause death. RESULTS: Six-month and 1-year follow-up data were available for 9957 (99.8%) and 9608 (96.3%) of 9978 patients, respectively; 541 patients (5.4%) had died at 6 months and 739 (7.4%) at 1 year. Death or nonfatal MI at 6 months occurred in 872 patients receiving enoxaparin (17.6%) vs 884 receiving unfractionated heparin (17.8%) (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.89-1.07; P = .65). In the subgroup of patients receiving consistent therapy, ie, only enoxaparin or unfractionated heparin during the index hospitalization (n = 6138), a reduction in death or nonfatal MI with enoxaparin was maintained at 180 days (HR, 0.85; 95% CI, 0.75-0.95; P = .006). Rehospitalization within 180 days occurred in 858 patients receiving enoxaparin (17.9%) and 911 receiving unfractionated heparin (19.0%) (HR, 0.94; 95% CI, 0.85-1.03; P = .17). One-year all-cause death rates were similar in the 2 treatment groups (380/4974 [7.6%] for enoxaparin vs 359/4948 [7.3%] for unfractionated heparin; HR, 1.06; 95% CI, 0.92-1.22; P = .44). One-year death rates in patients receiving consistent therapy were also similar (251/3386 [7.4%] for enoxaparin vs 213/2720 [7.8%] for unfractionated heparin; HR, 0.95; 95% CI, 0.79-1.14; P = .55). CONCLUSIONS: In the SYNERGY trial, patients continued to experience adverse cardiac events through long-term follow-up. The effect of enoxaparin on death or MI compared with that of unfractionated heparin at 6 months was similar to that observed at 30 days in the overall trial and in the consistent-therapy group. One-year death rates were also similar in both groups. High-risk patients with ACS remain susceptible to continued cardiac events despite aggressive therapies.ClinicalTrials.gov Identifier: NCT00043784.

Enoxaparin↗
PubMed2005

C-type natriuretic peptide inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of P-selectin expression.

The multifaceted process of immune cell recruitment to sites of tissue injury is key to the development of an inflammatory response and involved in the pathogenesis of numerous cardiovascular disorders. We recently identified C-type natriuretic peptide (CNP) as an important endothelium-derived mediator that regulates vascular tone and protects against myocardial ischemia/reperfusion injury. Herein, we investigated whether CNP inhibits leukocyte recruitment and platelet aggregation and thereby exerts a potential antiinflammatory influence on the blood vessel wall. We assessed the effects of CNP on leukocyte-endothelial cell interactions in mouse mesenteric postcapillary venules in vivo in animals with high basal leukocyte activation (endothelial nitric oxide synthase knockout mice, eNOS(-/-)) or under acute inflammatory conditions (induced by interleukin-1beta or histamine). CNP suppressed basal leukocyte rolling in eNOS(-/-) mice in a rapid, reversible, and concentration-dependent manner. These effects of CNP were mimicked by the selective natriuretic peptide receptor-C agonist cANF(4-23). CNP also suppressed leukocyte rolling induced by IL-1beta or histamine, inhibited platelet-leukocyte interactions, and prevented thrombin-induced platelet aggregation of human blood. Furthermore, analysis of human umbilical vein endothelial cells, leukocytes, and platelets revealed that CNP selectively attenuates expression of P-selectin. Thus, CNP is a modulator of acute inflammation in the blood vessel wall characterized by leukocyte and platelet activation. These antiinflammatory effects appear to be mediated, at least in part, via suppression of P-selectin expression. These observations suggest that endothelial CNP might maintain an anti-atherogenic influence on the blood vessel wall and represent a target for therapeutic intervention in inflammatory cardiovascular disorders.

Analysis of Variance↗
PubMed2005

The role of gender and other factors as predictors of not receiving reperfusion therapy and of outcome in ST-segment elevation myocardial infarction.

BACKGROUND: The standard of care for ST-segment elevation myocardial infarction (STEMI) is prompt coronary reperfusion with thrombolysis or percutaneous coronary intervention. Women have higher mortality rates than men following STEMI and fewer women are considered eligible for reperfusion therapy. We analyzed the impact of gender, and other factors, on the outcome and treatment of STEMI in the TETAMI trial and registry. METHODS: This exploratory analysis included 2741 patients from Treatment with Enoxaparin and Tirofiban in Acute Myocardial Infarction (TETAMI) presenting with STEMI within 24 hours of symptom onset. The primary composite end point was the combined incidence of all-cause death, recurrent myocardial infarction, and recurrent angina, at 30 days. Three multivariate analyses were performed to determine predictors of not receiving reperfusion therapy, the composite end point, or death. RESULTS: The triple end point occurred in 17.8% of women versus 13.3% of men. Reperfusion therapy was utilized in 38.2% of women versus 47.3% in men. However, age > 75 years, delayed presentation, high systolic blood pressure (> 100) and region (South Africa), were significant, independent predictors of not receiving reperfusion therapy. Significant predictors of the triple end point included not receiving reperfusion therapy, age > 60 years, and higher Killip class. Predictors of death included age > 60 years, low systolic blood pressure, higher Killip class, high heart rate, delayed presentation, and region (South Africa and South America). CONCLUSION: Female gender was not an independent predictor of outcome or underutilization of reperfusion therapy. Factors more common in female STEMI patients (advanced age and delayed presentation) were associated with not receiving reperfusion therapy and adverse outcome. Increased awareness is needed to reduce delayed presentation after symptom onset, especially among women. Abbreviated abstract. In this analysis of 2741 ST-segment elevation myocardial infarction patients in the TETAMI trial and registry, a trend was observed for women being less likely to receive reperfusion therapy and more likely to have an adverse outcome than men. This was related to factors more common in female patients (advanced age and delayed presentation), and showed that an increased awareness is needed to reduce delayed presentation after symptom onset, especially among women.

Age Factors↗
PubMed2005

Internet-based health promotion and disease control in the 8 cities: successes, barriers, and future plans.

OBJECTIVES: The objective of this paper is to provide a detailed description of Internet-based sexually transmitted disease/human immunodeficiency virus prevention in the 8 US cities most affected by syphilis in men who have sex with men. GOAL: By reviewing the efforts under way in these 8 cities, we will understand the barriers and facilitators associated with Internet-based prevention efforts. STUDY: This is a review of Internet activities taking place in 8 major US cities. RESULTS: Efforts in the 8 cities vary, with some cities reporting little or no Internet-based prevention activities. Other cities have attempted banner advertising, online outreach, online partner notification, online laboratory slips for syphilis testing, and auditorium-style chat sessions. CONCLUSION: Though a number of policy-related barriers prevent some cities from engaging in Internet-based prevention, these activities are clearly important to the overall prevention effort. In order to surmount local policy barriers, it is essential to obtain evaluation data from the programs initiated.

Cities↗