Circulating endothelial cells in malignant disease

Cancer is a disease largely dependent on neoangiogenesis. Cancer neoangiogenesis is often disordered and abnormal, with evidence of coexisting vascular endothelial dysfunction. A novel method of assessing vascular endothelial function in cancer is via the quantification of circulating endothelial cells (CEC). Unusual in healthy individuals, their presence in elevated numbers often indicates substantial vascular endothelial perturbation. Another interesting cell type is the endothelial progenitor cell (EPC), whose numbers increase in the presence of vascular damage. Recent research suggests that EPCs have an important role in tumor vasculogenesis. Another marker being investigated in the context of vascular dysfunction and coagulopathy is the endothelial microparticle (EMP). Thus, CECs, EPCs and EMPs may represent potentially novel methods for evaluating the vascular status of cancer patients. This review will summarize the current position of CECs, EPCs and EMPs in cell biology terms, with particular emphasis on their relationship to malignant disease.     

Rheumatoid disease and the heart: from epidemiology to echocardiography

Rheumatoid disease (RD) is a common chronic inflammatory condition associated with progressive joint destruction. Sufferers of RD experience reduced life expectancy, reflected in the increased standardised mortality rates reported in several studies over the last 50 years. Most studies indicate that the increased mortality affecting this population is mainly due to cardio-vascular disease. Epidemiological data have revealed an increased risk of developing ischaemic heart disease and heart failure in RD. The increased risk of ischaemic heart disease may result from traditional risk factors but data suggest that RD may confer risk independently. Although pericardial involvement, valvopathy and myocarditis are the most well-recognised cardiac manifestations of RD, and constitute a rheumatoid heart disease, these features are relatively benign. The current prevalence of rheumatoid heart disease in the era of early administration of disease-modifying therapy requires evaluation.     

Electrostatic charge characteristics of aerosols produced from metered dose inhalers

The electrostatic charge properties of aerosols produced by commercial metered dose inhalers (MDIs), including Ventolin, QVAR, Flixotide, Intal Forte, and Tilade were studied using a modified 13-stage electrical low pressure impactor (ELPI) with aerodynamic diameter cutoff ranging from 0.028 to 10.07 microm. All the stages are electrically insulated from each other with the last 12 stages connected individually to electrometers with sensitivity at femtoampere levels. Aerosol particles deposited on the impactor stages according to their aerodynamic diameters and their charges were measured by the electrometers. The deposited drug mass was assayed chemically using HPLC. The results show that particles of bipolar charge distribution were produced reproducibly from Intal Forte, Tilade, and Flixotide. In contrast, those from Ventolin and QVAR displayed charge variation, depending on the time lapse between actuations. This suggests that charge relaxation may influence the charging of these two MDIs. Mass distributions were reproducible for all MDIs except for Ventolin, the first puff from which was always the highest in dose. The different charge characteristics of the MDIs could be attributed to differences in the drug and formulation as well as valve materials. In general, submicron particles showed a larger variation in the charge-to-mass ratio (q/m). This indicated charge contribution by propellant/excipients (which produce submicron particles) rather than the drug itself. The calculated number of elementary charges per drug particle of size 相似文献   

Antithrombotic therapy in hypertension: a Cochrane Systematic review

Although elevated systemic blood pressure (BP) results in high intravascular pressure, the main complications of hypertension are related to thrombosis rather than haemorrhage. It therefore seemed plausible that use of antithrombotic therapy may be useful in preventing thrombosis-related complications of elevated BP. The objectives were to conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with BP, to address the following hypotheses: (i) antiplatelet agents reduce total deaths and/or major thrombotic events when compared to placebo or other active treatment; and (ii) oral anticoagulants reduce total deaths and/or major thromboembolic events when compared to placebo or other active treatment. A systematic review of randomised studies in patients with elevated BP was performed. Studies were included if they were >3 months in duration and compared antithrombotic therapy with control or other active treatment. One meta-analysis of antiplatelet therapy for secondary prevention in patients with elevated BP reported an absolute reduction in vascular events of 4.1% as compared to placebo. Acetylsalicylic acid (ASA) did not reduce stroke or 'all cardiovascular events' compared to placebo in primary prevention patients with elevated BP and no prior cardiovascular disease. Based on one large trial, ASA taken for 5 years reduced myocardial infarction (ARR, 0.5%, NNT 200 for 5 years), increased major haemorrhage (ARI, 0.7%, NNT 154), and did not reduce all cause mortality or cardiovascular mortality. In two small trials, warfarin alone or in combination with ASA did not reduce stroke or coronary events. Glycoprotein IIb/IIIa inhibitors as well as ticlopidine and clopidogrel have not been sufficiently evaluated in patients with elevated BP. To conclude for primary prevention in patients with elevated BP, antiplatelet therapy with ASA cannot be recommended since the magnitude of benefit, a reduction in myocardial infarction, is negated by a harm of similar magnitude, an increase in major haemorrhage. For secondary prevention in patients with elevated BP, antiplatelet therapy is recommended because the magnitude of the absolute benefit is many times greater. Warfarin therapy alone or in combination with aspirin in patients with elevated BP cannot be recommended because of lack of demonstrated benefit. Further trials of antithrombotic therapy are required in patients with elevated BP.     

Elevated platelet microparticles in stable coronary artery disease are unrelated to disease severity or to indices of inflammation

Platelet microparticles (PMPs), procoagulant membrane vesicles derived from activated platelets, are elevated in acute myocardial infarction and unstable angina but their relationship to inflammation and indices of coronary artery disease are unclear. We therefore hypothesised that PMPs are related to scores of coronary atheroma and/or coronary stenosis. Our study was completed by comparing PMP data with other platelet markers and with hs-CRP, marking inflammation. We recruited 54 patients attending for coronary angiography, comparing them to 35 age- and sex-matched controls. Peripheral blood was analysed for PMPs, percent platelets positive for CD62P and CD63 (all flow cytometry), soluble P selectin and hsCRP (both immunoassay). Patients exhibited higher PMPs, increased platelet %CD62P, %CD63 and soluble P selectin (all P < 0.01) and hs-CRP (P = 0.0167) than healthy controls. However, analysing only patients with an unequivocal classification, there were no significant (P 相似文献