Objectives-The objective of this study was to determine whether adjunctive therapy during percutaneous coronary intervention (PCI) affects markers of systemic inflammation or platelet activation. Despite different mechanisms of action, direct-thrombin inhibition with bivalirudin during PCI provided similar protection from periprocedural and chronic ischemic complications as compared with unfractionated heparin (UFH) plus planned use of GPIIb/IIIa antagonists in the REPLACE-2 and ACUITY trials. Methods and Results-Patients undergoing nonurgent PCI of a native coronary artery were randomized to receive adjunctive therapy with bivalirudin or UFHϩeptifibatide. Interleukin (IL)-6 and C-reactive protein (CRP) transiently increased in both groups after PCI. In the UFHϩeptifibatide, but not the bivalirudin group, myeloperoxidase (MPO) levels were elevated 2.3-fold above baseline (Pϭ0.004) immediately after PCI. In an in vitro assay, heparin and to a lesser extent enoxaparin, but not bivalirudin or eptifibatide, stimulated MPO release from and binding to neutrophils and neutrophil activation. A mouse model of endoluminal femoral artery denudation was used to investigate further the importance of MPO in the context of arterial injury. Key Words: platelets Ⅲ neutrophils Ⅲ myeloperoxidase Ⅲ percutaneous coronary intervention Ⅲ adjunctive therapy A ggressive antithrombotic therapy, in particular antiplatelet therapy with glycoprotein (platelet glycoprotein [GP]) IIb/IIIa antagonists, thienopyridines, and aspirin used in conjunction with unfractionated heparin, have consistently been shown to decrease the risk of periprocedural thrombotic complications associated with percutaneous coronary interventions (PCI). 1,2 Bivalirudin, a direct thrombin inhibitor, was approved for use in PCI as an alternative to heparin before to widespread use of GPIIb/IIIa antagonists. Recently, the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 and the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trials demonstrated that bivalirudin used with GPIIb/IIIa antagonists on a provisional basis provided similar protection from periprocedural ischemic and hemorrhagic complications compared with heparin plus planned use of GPIIb/IIIa antagonists. 3,4 In the REPLACE-2 trial of low-to moderate-risk patients undergoing PCI, the primary composite end point at 30 days (incidence of death, myocardial infarction, urgent repeat revascularization, or in-hospital major bleeding) occurred in 9.2% of patients in the bivalirudin group versus 10.0% of patients in the unfractionated heparin (UFH) plus GPIIb/IIIa antagonist group. 3 At 1 year, a nonsignificant trend toward lower mortality with bivalirudin was observed (1.9% in bivalirudin group and 2.5% in heparin plus GPIIb/ IIIa antagonist group). 3 The results from the ACUITY trial also suggest that in patients with acute coronary syndromes undergoing PCI, routine use of bivalirudin is associated with similar ischemic outcomes as UFH or low-molecular weight...
A B S T R A C T When human, canine, or bovine factor VIII preparations are chromatographed on 4% agarose at ionic strength 0.2, the factor VIII activity elutes as a single peak in the void volume with slight tailing. Incubation of such preparations with dilute (0.01 U/ml) highly purified thrombin results in some activation of factor VIII. Chromatography of such incubation mixtures, under the same conditions as before, results in elution of two peaks of factor VIII activity, one in the void volume and one much later with marked tailing. The void volume peak has most of the protein and some factor VIII activity. These void volume fractions also contain all the von Willebrand factor activity of thrombin-treated human factor VIII preparations and all of the platelet aggregating factor activity of thrombin-treated bovine preparations. Longer treatment with thrombin, or treatment with stronger thrombin, appears to shift much more of the procoagulant activity to the later eluting peak. Also, when the peak of factor VIII activity, found in the void volume after thrombin treatment, was again incubated with dilute thrombin, an increase in factor VIII activity occurred. Chromatography of this incubation mixture demonstrated only a small amount of activity in the void volume, while the bulk of the activity was present in the second peak. On the other hand, thrombin treatment of factor VIII activity from peak 2 caused a rapid decline of activity instead of a further increase. It is proposed that the residual factor VIII activity found in the void volume represents unreacted factor
Two concurrent criterion-related validity studies were conducted with blue-collar workers employed in Australia. The first sample consisted of 77 unskilled and semi-skilled manufacturing employees. The second sample consisted of 243 stockpeople who worked in piggeries. A range of work-related criteria was used, and this range differed across the two studies. The results showed that Employment Inventory-Performance was a reasonable predictor of some aspects of supervisor ratings of work performance but unrelated to other aspects. A similar pattern of findings emerged with self-ratings of work performance. Employment Inventory-Tenure was weakly related to turnover intentions and actual turnover.
Objective-To examine, using nationally representative data, which patient, hospital, and county characteristics influence rural residents' urban hospitalization.Methods-Rural residents hospitalized in urban hospitals (crossovers) are compared with those hospitalized in rural hospitals (noncrossovers). National Hospital Discharge Survey data were merged with Area Resource File and Centers for Medicare & Medicaid Services data to study rural inpatients' characteristics; hospital descriptors; and county or state socioeconomic and health service variables. Multivariate logistic regression analysis identified covariates of the likelihood of being a crossover.Findings-About one-third of the rural resident hospitalizations in 2003 were in urban hospitals. Other factors constant, those requiring greater resources had higher odds of crossing over, as did younger inpatients, those transferred from other hospitals, receiving surgery, and with mental diagnoses or congenital anomalies. Males, emergency admissions, and intervertebral disk disorder inpatients had lower odds of crossing over compared with those who were not in these categories. Crossover patients' hospitals had higher Medicare case mix indices than hospitals used by noncrossovers. Rural inpatients in government hospitals, rather than proprietary or non-profit hospitals, had greater odds of crossing over, as did rural patients from counties with lower population density, fewer hospital beds, more hospitals, more commuters, and lower per capita income compared with those in other categories.Conclusions-Rural hospitals continue to be an important source of inpatient care, but rural residents travel to urban hospitals in some specific instances.
National data on the broad scope of patients served and inpatient services provided by rural hospitals illustrate one important role these hospitals play in serving rural communities.
Several well-known anticoagulants are in use for blood sample tubes, each having some special application, but there is little doubt that the naturally occurring anticoagulant, heparin, would find wider application were it not so difficult to prepare and consequently expensive. Chemically prepared sulphuric esters of polysaccharides are known to have anticoagulant action. One of these, dextran sulphate, has recently been prepared (Ricketts, 1952) in a form suitable for therapeutic use (Walton, 1951 In the field of haematology the requirements of an anticoagulant are somewhat more critical. It was quickly established that there was no effect on the haematocrit determination, but there appears to be a slight though probably negligible effect on the erythrocyte sedimentation rate. Walton (1951) reports that the ordinary haematological determinations, haemoglobin, red cell and white cell counts, are not interfered with.In the field of physiological research there appears to be scope for an anticoagulant of the heparin type in experiments involving the perfusion of tissue with blood. Since it is not prepared from tissue, dextran sulphate is not contaminated with pharmacologically active substances, e.g., histamine. No doubt other specialized applications will suggest themselves to the research workers concerned. Where a sodium salt is unsuitable it is a comparatively simple matter to exchange the sodium for hydrogen by passage through a column of ion exchange resin. The acid solution of dextran sulphate may then be neutralized with any selected base.
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