Neil R. McGregor

Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome

Abstract Full blood counts, ESR, CRP, haematinics and markers for oxidative stress were measured for 33 patients diagnosed with chronic fatigue syndrome (CFS) and 27 age and sex matched controls. All participants also completed symptom questionnaires. CFS patients had increases in malondialdehyde (P <0.006), methaemoglobin (P <0.02), mean erythrocyte volume (P <0.02) and 2,3-diphosphoglycerate (P <0.04) compared with controls. Multiple regression analysis found methaemoglobin to be the principal component that differentiated between CFS patients and control subjects. Methaemoglobin was found to be the major component associated with variation in symptom expression in CFS patients (R2 = 0.99, P <0.00001), which included fatigue, musculoskeletal symptoms, pain and sleep disturbance. Variation in levels of malondialdehyde and 2,3-diphosphoglycerate were associated with variations in cognitive symptoms and sleep disturbance (R2 = 0.99, P <0.00001). These data suggest that oxidative stress due to excess free radical formation is a contributor to the pathology of CFS and was associated with symptom presentation.

ERYTHROCYTE ANTIOXIDANT SYSTEMS PROTECT CULTURED ENDOTHELIAL CELLS AGAINST OXIDANT DAMAGE.

A study was undertaken to assess the ability of the erythrocyte to protect other tissues against oxidative damage. Radiolabelled (51Cr) human umbilical vein endothelial cells (HUVEC) were incubated with erythrocytes and neutrophils activated with phorbol myristate acetate (PMA). Damage to the endothelial cells was indicated by release of radioactivity into the suspending medium. We found that the co‐incubation of HUVEC with an increasing range of erythrocyte concentrations resulted in a dose‐dependent reduction in the release of radioactivity. When the ability of superoxide to cross the erythrocyte membrane or the glutathione systems was inhibited, the extent of endothelial cell damage increased. Inhibition of the catalase system did not affect results. It was concluded that the erythrocytes afforded some protection against oxidative damage to the endothelial cells by taking up and deactivating the superoxide ions. This protection depends upon intact erythrocyte antioxidant systems. These data support the hypothesis that erythrocytes can provide antioxidant protection to other tissues in vivo.

A definition-based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome

Abstract. De Becker P, MCGregor N, De Meirleir K (VUB, Vakgroep Interne Geneeskunde, Brussels, Belgium; and University of Newcastle, Callaghan, New South Wales, Australia). A definition‐based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome. J Intern Med 2001; 250: 234–240.

The role of erythrocytes in the inactivation of free radicals

We propose that, in addition to its function of gas exchange, the erythron provides a mechanism for the inactivation of reactive oxygen and oxide radicals in vivo. In carrying out this function, individual erythrocytes undergo changes in biochemical and structural properties, which are reflected by shape and functional alterations. The changes indicate damage to the labile components of the red cell and demonstrate the expendable nature of the individual red cell. We propose that a superoxide anion channel allows the transport of superoxide and other free radicals into the red cell, where they are deactivated by the erythrocyte antioxidant system which effectively prevents extensive oxidative damage to tissues.

A Biochemical Analysis of People with Chronic Fatigue Who Have Irlen Syndrome: Speculation concerning Immune System Dysfunction

This study investigated the biological basis of visual processing disabilities in adults with Chronic Fatigue Syndrome. The study involved 61 adults with symptoms of Chronic Fatigue Syndrome who were screened for visual processing problems (Irlen Syndrome) and divided into two groups according to the severity of symptoms of Irlen Syndrome. Significant variations were identified in blood lipids and urine amino and organic acids of the two groups, which may be indicative of activation of the immune system due to some infective agent. It was suggested that metabolic profiling may help the development of more valid diagnostic categories and allow more investigation of immune system dysfunction as a possible causal factor in a range of learning and behaviour disorders.

Understanding the causal mechanisms of visual processing problems: A possible biochemical basis for Irlen syndrome?

Abstract This paper discusses potential causes for the visual‐perceptual dysfunction known as Irlen Syndrome (IS), and describes a preliminary investigation into the possible biochemical basis for this dysfunction. A review of studies revealed that there is a sub‐group of people with chronic fatigue syndrome (CFS) who have visual‐perceptual problems similar to those identified as IS, and specific biochemical anomalies have been identified for CFS. This investigation found a variety of biochemical anomalies in 143 subjects with CFS who had been identified on a questionnaire as likely to have symptoms of IS. It was suggested that the broad diagnostic categories currently in use, such as CFS, dyslexia and attention deficit hyperactivity disorder may include a range of overlapping clinical disorders. The analysis of biochemical anomalies in particular may be important in the development of more valid diagnostic categories and treatment strategies for these disorders, as it goes beyond observed behavioural sym...

Changes in Plasma Lipid Homeostasis Observed in Chronic Fatigue Syndrome Patients

A study of 60 CDC-defined chronic fatigue syndrome (CFS) patients and 39 age- and sex-matched controls was undertaken to determine whether there were any alterations in plasma lipid profiles from CFS patients compared with control subjects. Plasma samples were taken from fasted (12 h) subjects and the lipid components were extracted, saponified and analyzed by capillary gas chromatography-mass spectrometry (GC-MS). It was found that CFS patients had different plasma saponified lipid profiles compared with control subjects (standard discriminant function analysis p < 0.02). The first and second most important factors, discriminating the CFS patients from the controls, were a decrease in trans -9-octadecenoic acid and an increase in octadecenoic acid, respectively. The relative abundance of trans -9-octadecenoic acid in the CFS patients was 0.74% compared with 0.99% in the controls ( p< 0.02) and the trans -9-octadecenoic acid:octadecenoic acid ratio was 0.15 in the CFS patients compared with 0.27 in contro...

Chronic fatigue syndrome: a risk factor for osteopenia?

No data documenting a possible depletion of bone mineral density in patients with chronic fatigue syndrome (CFS) are currently available. However, recent pathophysiological observations in CFS patients may have deleterious consequences on bone density. Firstly, the deregulation of the 2,5A synthetase RNase L antiviral pathway and its associated channelopathy, implicates increased demands for calcium and consequent increased calcium-re-absorption from the skeletal system. Secondly, Mycoplasma fermentans which has been frequently associated with CFS, produces a lipopeptide, named 2-kDa macrophage-activating lipopeptide (MALP-2), which stimulates macrophages. MALP-2 has been shown to enhance bone resorption in a dose-dependent manner, at least in part by stimulating the formation of prostaglandins. Thirdly, decreased levels of insulin-like growth factor I (IGF-I) have been reported in CFS-patients. IGF-I is critical to the proliferation of osteoblasts. Consequently, depleted levels of IGF-I may shift the balance between osteoclastic and osteoblastic activity towards bone resorption.

Assessment of Plasma Fatty Acids and Sterols in Sudden - and Gradual - Onset Chronic Fatigue Syndrome Patients

Purpose: To determine whether sudden - and gradual - onset groups of chronic fatigue syndrome (CFS) patients had characteristic lipid profiles which may be indicative of specific viruses or cytokine responses. Design: Laboratory-based survey. Materials and methods: A study was undertaken in 60 CFS patients and 39 age and sex-matched non-CFS control subjects. Plasma saponified lipid products were assessed using capillary gas chromatography-mass spectrometry (GC-MS) to measure qualitative changes in plasma lipid profiles. Results: Twenty of the CFS patients reported an acute viral-like infection at onset and were assessed for antibodies to Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) whereas the remaining 40 CFS patients reported a gradual onset (G-CFS). None of the sudden-onset patients (S-CFS) had immunological evidence of a current common viral infection. The S-CFS, G-CFS and control groups were well resolved by discriminant function analysis of their lipid profiles (p < 0.0001), where trans-9-octa...