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Biomedical subjects

A Blann

Publications and source records attributed to A Blann.

At least 37 records · Page 2Linked to original sources
PubMed1998

von Willebrand factor, fibrinogen and other plasma proteins as determinants of plasma viscosity.

Plasma viscosity and fibrinogen are risk factors for cardiovascular disease and on rheological grounds, it is widely believed that the latter is a major determinant of the former. However, other plasma constituents may also be important determinants of plasma viscosity. Our aim was to determine whether or not levels of von Willebrand factor contributed to plasma viscosity. We measured plasma viscosity, fibrinogen, von Willebrand factor, immunoglobulins G, A and M, total, HDL- and LDL-cholesterol, triglycerides and albumin in 95 patients with peripheral arterial disease and in 120 healthy controls. A stepwise multivariate analysis was performed to determine the major influences of plasma viscosity. We also measured fibrinogen, von Willebrand factor, immunoglobulins G, A and M, total, HDL- and LDL-cholesterol, triglycerides, albumin and viscosity in 32 smokers as they successfully progressed to being non-smokers. The level of von Willebrand factor was an independent influence on plasma viscosity in the controls (P < 0.05), patients (P < 0.01) and in the combined group (P < 0.001). von Willebrand factor, fibrinogen and plasma viscosity, but not the immunoglobulins, lipoproteins or albumin, fell (P < 0.05) in smokers as they became non-smokers. We find that von Willebrand factor contributes to plasma viscosity, hence a reduction in levels of von Willebrand factor should result in a reduction in viscosity. These data may have implications for the pathogenesis of cardiovascular disease.

Adult↗
PubMed1998

Von Willebrand factor, P-selectin and fibrinogen levels in patients with acute ischaemic and haemorrhagic stroke, and their relationship with stroke sub-type and functional outcome.

Although ischaemic stroke is associated with accentuated platelet function, it remains unclear whether this applies to all sub-types, especially lacunar infarcts, which differ from cortical infarction in their patho-aetiology. Similarly, conflicting evidence suggests that haemorrhagic stroke may, or may not, be associated with a hypothrombotic state. Levels of von Willebrand factor (vWF), fibrinogen, and P-selectin were measured within 48 h of ictus in 163 patients with acute ischaemic stroke and 40 patients with acute primary intracerebral haemorrhage, and 33 age, gender and race matched-controls. vW F (IU/dl) was significantly increased in both cortical and lacunar ischaemic stroke, and haemorrhagic stroke, as compared with controls, median (semiquartile range): 158 (25) vs 144 (19) vs 147 (24) vs 114 (16), respectively. Similarly, fibrinogen (g/litre) was increased: 4.80 (0.90) vs 4.65 (0.70) vs 4.35 (0.83) vs 3.70 (0.70). In contrast, soluble P-selectin (ng/ml) was increased in cortical stroke as compared with lacunar infraction patients or controls: 408 (101) vs 300 (108) vs 324 (121), respectively; P-selectin was not increased in haemorrhagic stroke, 360 (153). Both vW F and fibrinogen correlated with 3-month functional outcome (modified Rankin score): r = 0.371 (2 P = 0.0006), and r = 0.195 (2 P = 0.042), respectively; however, P-selectin was not associated with outcome: r = 0.188 (2 P = 0.084). The results suggest that increases in vW F and fibrinogen in all types of stroke reflect an acute phase response; in contrast, increased soluble P-selectin levels in cortical stroke, but not lacunar infarction, suggest that platelets contribute to the patho-aetiology of some subtypes of ischaemic stroke.

Journal Article↗
PubMed1997

von Willebrand factor: a marker of endothelial dysfunction in vascular disorders?

The vascular endothelium is involved in the production of many important substances which are involved in a cardiovascular pathophysiology. One such substance which is synthesised by, and stored in, endothelial cells is von Willebrand factor (vWf). When released, vWf appears to mediate platelet aggregation and adhesion. Numerous clinical and experimental reports suggest that high vWf levels reflect damage to the endothelium or endothelial dysfunction. The close association between vWf and the processes of thrombus formation (thrombogenesis) or atherogenesis also suggests that high vWf levels may be a useful indirect indicator of atherosclerosis and/or thrombosis. The availability of a useful marker of endothelial dysfunction may have potential clinical value. The measurement of such a marker can perhaps be a non-invasive way of assisting in clinical diagnosis or as an indicator of disease progression. High vWf levels have also been shown to have prognostic value in patients with ischaemic heart disease, peripheral vascular disease and inflammatory vascular disease. However, there is limited information that increased vWf is actually casual in the progression of vascular disease and that measures aimed at reducing vWf levels will be beneficial. In addition, interpretation of raised plasma vWf levels is complicated by the fact that vWf may be an acute phase reactant. Further research is indicated to explore the predictive value of this marker in population studies and, perhaps, therapeutic approaches in (and the value of) modifying vWf levels or function.

Arteriosclerosis↗
PubMed1997

Soluble adhesion molecules and endothelial cell damage in HIV infected patients.

Endothelial damage is present in HIV infection but our understanding of markers and mechanisms is incomplete. We found increased levels of markers of endothelial cell damage such as von Willebrand factor (vWf), soluble thrombomodulin (sTM) and adhesion molecule E-selectin in 90 subjects seropositive for HIV relative to healthy controls. sTM was strongly raised in those patients with the lowest CD4+ cell count (p < 0.001), but levels of vWf increased at each incremental fall in CD4+ cell count and the two indices correlated significantly (r = -0.485, p < 0.001). vWf correlated strongly with levels of the inflammatory cytokines tumor necrosis factor (TNF-alpha) and alpha interferon (IFN-alpha) but sTM correlated only weakly with IFN-alpha. We suggest that increased vWf is largely the result of inflammatory stimulus of the endothelium but that sTM is found only in those patients with more severe disease, and so truly represents endothelial damage.

Adolescent↗
PubMed1996

Soluble L-selectin in peripheral arterial disease: relationship with soluble E-selectin and soluble P-selectin.

Soluble L-selectin, E-selectin and P-selectin were measured in a small case control study of 42 patients with peripheral arterial disease and 42 age and sex matched controls. Levels of soluble L-selectin were 1204 +/- 221 ng/ml (mean +/- S.D.) in the patients compared to 1256 +/- 271 ng/ml in the controls (P = 0.37). There was also no difference in levels of soluble E-selectin (57 +/- 17 ng/ml versus 51 +/- 20 ng/ml, P = 0.15) but levels of soluble P-selectin were increased (249 +/- 101 ng/ml versus 198 +/- 98 ng/ml, P = 0.011). There were no significant correlations between any of the selectins and the risk factors for atherosclerosis or with any leucocyte index. The data point to different mechanisms of release of the soluble selectins in peripheral atherosclerosis and may have important implications for leukocyte/endothelial cell interactions.

Arteriosclerosis↗
PubMed1996

Von Willebrand factor, thrombomodulin, thromboxane, beta-thromboglobulin and markers of fibrinolysis in primary Raynaud's phenomenon and systemic sclerosis.

OBJECTIVE: To determine whether measurement of different markers of endothelial damage, activation of coagulation, and platelet activation might differentiate between patients with primary Raynaud's phenomenon (PRP), limited cutaneous and diffuse systemic sclerosis (lcSSc and dSSc), and healthy control subjects. METHODS: Under carefully controlled conditions, fasting blood was drawn from 19 healthy control subjects, 10 patients with PRP, 17 with lcSSc and nine with dSSc for measurement of the following: von Willebrand factor (VWF) and soluble thrombomodulin as markers of endothelial damage/activation, thromboxane (as thromboxane B2) and beta-thromboglobulin as markers of platelet activation, and tissue plasminogen activator antigen, tissue plasminogen activator activity and plasminogen activator inhibitor-1 (PAI-1) as markers of fibrinolysis. RESULTS: VWF was increased significantly in patients with SSc, and there was also a linear trend for thromboxane and tissue plasminogen activator antigen (in addition to VWF) to differentiate between different subgroups of patients with Raynaud's phenomenon. Patients with dSSc had the highest values. A combined index of VWF and thromboxane showed a highly significant trend across the four groups studied. CONCLUSION: VWF, and to a lesser extent thromboxane and tissue plasminogen activator antigen, are associated with disease severity in patients with Raynaud's phenomenon. Prospective studies are now required to establish if these parameters can be used as markers of disease progression.

Adult↗
PubMed1996

Vascular endothelial lesion in patients undergoing bone marrow transplantation.

Changes in endothelial cell activity are likely to play a role in the thrombotic complications of bone marrow transplantation (BMT) such as the development of veno-occlusive disease. Accordingly, we measured established plasma endothelial cell markers von Willebrand factor (vWf), soluble thrombomodulin (sTM), soluble ICAM-1 (sICAM-1), and possible inducers of these molecules, TNF alpha and elastase, in the plasma of 25 patients, 1 week before as well as 1 and 3 weeks after BMT. Compared to healthy age and sex-matched controls, patients exhibited increased vWf and sTM. One week after transplantation, there were significant increases in vWf and sICAM-1, with a significant fall in elastases. Three weeks after the transplantation, sICAM-1 and, to a lesser extent, vWf increased still further, whereas elastases were unchanged. There were no significant changes in sTM and in TNF alpha through the serial study. Our data suggest that before conditioning, vascular endothelium is damaged by both injury and activation, as seen by the variations of vWf and sTM. After transplantation, the enhancement of this damage seems to be more specifically related to activation, since we observed a strong subsequent increase in vWf and markedly in sICAM-1.

Adolescent↗
PubMed1994

Antioxidant status in controlled and uncontrolled hypertension and its relationship to endothelial damage.

Hypertension is associated with an increased risk of atherosclerosis. Free radical oxidative damage has been implicated in the atherogenic process. We measured levels of the antioxidants uric acid, thiols, vitamins C, A and E as well as the total antioxidant capacity in 21 normotensive controls, 22 patients whose hypertension was controlled on drugs and 30 patients with uncontrolled hypertension. Mean BPs in the groups were 125/76, 132/80 and 181/98 mmHg, respectively. When compared with controls, both hypertensive groups had significantly lower serum ascorbic acid (54 +/- 5 vs. 37 +/- 6 vs. 38 +/- 5 mumol/l, P < 0.05) and albumin-corrected thiol levels (9.91 +/- 0.18 vs. 8.69 +/- 0.20 vs. 8.92 +/- 0.19 mumol/g, P < 0.05). The levels of the other antioxidants did not differ significantly between the groups. Levels of von Willebrand factor, a marker of endothelial damage, were correlated with SBP but not with antioxidant status. We conclude that hypertensive subjects have lower levels of the antioxidants vitamin C and thiols and this may reflect greater oxidative consumption. The implications for atherogenesis and endothelial function and integrity in hypertension are discussed.

Adult↗
PubMed1993

Free radicals, antioxidants, and endothelial cell damage after percutaneous transluminal coronary angioplasty.

BACKGROUND: Oxygen-derived free radicals (ODFRs) and subsequent lipid peroxidation may be responsible for myocardial damage associated with ischaemia/reperfusion after percutaneous transluminal coronary angioplasty (PTCA). These potentially cytotoxic ODFRs are likely to be generated in the plasma, where the primary target organ or cell may be the endothelium. Some of these toxic effects may be limited by the action of antioxidant enzymes such as glutathione peroxidase (GPx). The aim of this study was to determine whether there was evidence of ODFR-mediated damage to the endothelium after PTCA and to examine the roles of lipid peroxides and GPx. METHODS: Serial samples of plasma were obtained at the time of catheter insertion, at the time of balloon inflation, 10 min after inflation, and 60 min after inflation, from 16 patients undergoing PTCA. We measured levels of von Willebrand factor (vWf, a specific product of the endothelium and a marker of damage), thiobarbituric acid reactive substances (TBARS, an indirect measure of the activity of ODFRs in peroxidizing lipoproteins), and the antioxidant GPx. RESULTS: There was a simultaneous peak in the levels of TBARS (P = 0.0096) with a fall in the levels of GPx (P = 0.004) 10 min after balloon deflation. Sixty min after balloon deflation, GPx levels were still reduced (P = 0.005) but there was a rise in levels of vWf (P = 0.038). CONCLUSIONS: Our interpretation of these data is that an early peak in ODFR activity associated with PTCA causes an endothelial injury 1 h after inflation. This may be related to the reduced ability of GPx to scavenge ODFRs.

Adult↗
PubMed1993

von Willebrand factor and the endothelium in vascular disease.

von Willebrand factor (vWF), first described in a bleeding disorder, has numerous other roles, some of which can be viewed in terms of the pathogenesis of atherosclerosis and others in the formation of thrombus. As a marker of endothelial cell injury it provides a unique opportunity to observe the events involved in conditions where vasculitis may occur, e.g. inflammatory vascular disease and diabetes. Just as low levels predispose to disease, so excessively high levels may lead to adverse cardiovascular events such as myocardial infarction and femoral artery occlusion, which may both be precipitated by thrombus. It is possible that intervention (possibly with drugs, peptides or other agents) that reduces circulating vWF, perhaps by interfering with its activity in aggregating platelets and mediating their adhesion to the sub-endothelium, or reducing its release from the endothelium, may lead to a reduction in thrombotic disease.

Arteriosclerosis↗