Journal of IiME Volume 1 Issue 1 Biomedical Research into ME/CFS Dr Vance A. Spence and Dr Neil C. Abbot Chairman of ME Research UK (charity number SC036942), and Hon Senior Research Fellow, Institute of Cardiovascular Research, University of Dundee, UK Specific research findings from the University of Dundee As a supplement to the talks you are to hear during the IiME Conference 2007, this hand-out presents a brief overview of the recent research findings from the Vascular Diseases Unit in the University Dundee,. One of the cardinal facts about research work generally is that breakthroughs follow funding (since without it there is no possibility of starting the exploration!). This group, with Research UK, has uncovered several blood vessel sensitivity to acetylcholine? c) Increased neutrophil apoptosis of Also, we also have new data indicating that ME/CFS patients have detectable abnormalities in a type of white blood cell (called neutrophil) – specifically a larger proportion of dying (apoptotic) cells than in healthy subjects – consistent with an activated inflammatory funding from ME interesting findings in people with ME/CFS. These findings have been reported in a series of scientific papers published from 2003–2006. a) Increased oxidative stress In our experiments, we have found a pattern of significantly increased oxidative stress – increased oxLDL and isoprostanes with decreased HDL and GSH – in ME/CFS patients (Kennedy et al, 2004). As isoprostanes also act as vasoconstrictors, for ME/CFS patients their presence, accompanied by additional free radicals during exercise may be responsible for some of the symptoms – such as pain - seen after exercise. These findings have now been confirmed by at least four other research groups worldwide who have also shown excessive free radicals in blood, urine and muscle tissues of ME/CFS patients. Isn't it important to discover the source(s) of these molecules, whether from excessive immune activity, chronic infections or abnormalities within muscle tissue? b) Abnormal acetylcholine metabolism Acetylcholine is a substance produced by the layer of endothelial cells lining all blood vessels, causing them to open. Our group has found that vascular responses to acetylcholine are increased compared with matched control subjects (Spence et al 2000; Khan et al, 2004, a and b). This finding is in contrast with research into a wide variety of cardiovascular diseases – such as diabetes, stroke and high cholesterol – where blood flow responses to acetylcholine are normally blunted. Why should ‘CFS’ patients have this thumbprint of increased Invest in ME Charity Nr 1114035 seemingly unique (continued on page 20) www.investinme.org process which is possibly the consequence of a past or present infection (Kennedy et al 2003, 2004a). Accompanying these markers of neutrophil apoptosis, we found that highsensitivity C-reactive protein levels, recognised as a marker of the inflammatory process, were also significantly increased. Might some people with ‘CFS’ disorder, albeit an unusual one? d) Presence of "signs" of physical illness Importantly, a high proportion of the patients investigated in this unit have had measurable signs of muscle weakness in the arms and/or legs, indicating that clinical signs (rather than self-reported symptoms) can, in fact, be detected in these patients if physicians take care to do a full physical examination (Kennedy et al 2004b). Intriguingly, reports in the older literature (1950s and 1960s) on epidemics of ‘classical’ ME included the presence of clinical signs (e.g., muscle weakness/swelling; sensory nerve changes; observable recurrences of flulike illness, etc). Will the presence of clinical signs - believed by many healthcare professionals today to be non-existent in ME patients - come to be recognised as important markers of physical illness? Our purpose here is not to answer these questions, but to show that biomedical investigation can uncover, within a proportion of ME/CFS patients, biological anomalies that might well help to explain many of the clinical features associated with the illness, and might also indicate areas for therapeutic treatment. 19 have a chronic inflammatory
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