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Title: Microcirculation of chronic venous disease : role of leucocyte-endothelial activation and effects of pharmacological intervention
Author: Howlader, M. H.
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2004
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Many theories have been advanced to explain the development of venous ulceration in the lower limb. In recent years, the hypothesis of inappropriate leucocyte activation with the release of free radicals causing damage to the microcirculation in patients with CVD has gained popularity. No drug has so far been found to ameliorate these effects. In this thesis I have investigated a series of inflammatory markers in patients with various CEAP stages of venous disease. The aim was to asses which, if any, inflammatory markers were associated with worsening stages of venous disease. I also used a flavonoid drug, Daflon , in a randomised, controlled clinical trial and assessed the efficacy of treatment using the markers of systemic inflammation studied. Neutrophil and monocyte activation were investigated by measuring CD 11b and CD62L by flow cytometry. Soluble CD62L and endothelial adhesion molecules (VCAM-1, ICAM-1, E-selectin and P-selectin) and vWf were measured by commercially available ELISAs. The cytokines (IL-l , IL-l , IL-6 and TNF- ) and VEGF by ELISA and total NO using the Griess reaction were also measured. Patients' symptoms were assessed by using a visual analogue scale, and the correlation of these with inflammatory markers was also investigated. Capillary morphology was studied using a capillary videomicroscope and changes were graded and correlated with the severity and CEAP stages of CVD. In my study, I found evidence of a modest relationship between CEAP clinical stage and plasma level of VCAM-1 and neutrophil CD11b as well as monocyte CD62L data using multi-variate logistic regression. There was elevation of VEGF and total NO in patients with skin changes, although multi-variate analysis failed to show the significance of plasma nitrate. Capillary morphology changes were seen in the form of convolutions in advanced stages of venous disease. These have been classified in four grades. Daflon failed to down regulate plasma levels of these markers and to improve the symptoms. This study demonstrates a low-grade inflammatory response to venous disease but give no definite clue as to the role of leucocyte in the pathogenesis of venous disease. The capillary morphology changes I have observed suggest that angiogenesis is upregulated in skin affected by chronic venous disease. This may be attributable to increased VEGF expression.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available