Neil McGregor

Neil R. McGregor, BDS, MDSc, PhD is a periodontist with an interest in ME/CFS research stemming from treating ME/CFS patients with temporomandibular dysfunction syndrome. He is a senior researcher at the Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia and an Adjunct Professor at Victoria University, Melbourne, Australia. Dr. McGregor was a former co-editor of the Journal of Chronic Fatigue Syndrome.

Books

 * 2014, Chapter Five in Advances in Clinical Chemistry, Vol. 66, published by Elsevier; "Metabolism in Chronic Fatigue Syndrome," by [[Christopher Armstrong | Christopher W. Armstrong], Neil R. McGregor, Henry L. Butt, and Paul R. Gooley]
 * 2006, Pediatric Chronic Fatigue Syndrome by [[Kenny de Meirleir], Neil McGregor, and Elke L.S. Van Hoof]

Notable studies
1996, Preliminary determination of the association between symptom expression and urinary metabolites in subjects with chronic fatigue syndrome
 * 2017, The association of fecal microbiota and fecal, blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome "Abstract - Introduction: The human gut microbiota has the ability to modulate host metabolism. Metabolic profiling of the microbiota and the host biofluids may determine associations significant of a host–microbe relationship. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disorder of fatigue that is poorly understood, but has been linked to gut problems and altered microbiota. Objectives: Find changes in fecal microbiota and metabolites in ME/CFS and determine their association with blood serum and urine metabolites. Methods: A workflow was developed that correlates microbial counts with fecal, blood serum and urine metabolites quantitated by high-throughput ¹H NMR spectroscopy. The study consists of thirty-four females with ME/CFS (34.9 ± 1.8 SE years old) and twenty-five non-ME/CFS female (33.0 ± 1.6 SE years old). Results: The workflow was validated using the non-ME/CFS cohort where fecal short chain fatty acids (SCFA) were associated with serum and urine metabolites indicative of host metabolism changes enacted by SCFA. In the ME/CFS cohort a decrease in fecal lactate and an increase in fecal butyrate, isovalerate and valerate were observed along with an increase in Clostridium spp. and a decrease in Bacteroides spp. These differences were consistent with an increase in microbial fermentation of fiber and amino acids to produce SCFA in the gut of ME/CFS patients. Decreased fecal amino acids positively correlated with substrates of gluconeogenesis and purine synthesis in the serum of ME/CFS patients. Conclusion: Increased production of SCFA by microbial fermentation in the gut of ME/CFS patients may be associated with deleterious effects on the host energy metabolism
 * 2016, Widespread pain and altered renal function in ME/CFS patients "Abstract - 'Background: Widespread pain is noted in many patients with chronic fatigue syndrome (ME/CFS), fibromyalgia and temporomandibular disorders. These conditions usually start as a localized condition and spread to a widespread pain condition with increasing illness duration. Purpose: To aim was to assess the changes in biochemistry associated with pain expression and alterations in renal function. Methods: Forty-seven ME/CFS patients and age/sex-matched controls had a clinical examination, completed questionnaires, standard serum biochemistry, glucose tolerance tests and serum and urine metabolomes in an observational study. Results: Increases in pain distribution were associated with reductions in serum essential amino acids, urea, serum sodium and increases in serum glucose and the 24-hour urine volume; however the biochemistry was different for each pain area. Regression modelling revealed potential acetylation and methylation defects in the pain subjects. Conclusions: These findings confirm and extend our earlier findings. These changes appear consistent with repeated minor inflammatory-mediated alterations in kidney function resulting in essential amino acid deprivation and inhibition of protein synthesis and genetic translation within tissues.'"
 * 2015, Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients "'Abstract - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating long-term multisystem disorder with a central and inexplicably persistent fatigue symptom that is unable to be relieved by rest. Energy metabolism and oxidative stress have been recent focal points of ME/CFS research and in this study we were able to elucidate metabolic pathways that were indicative of their dysfunction. Blood and urine samples were collected from 34 females with ME/CFS (34.9 ± 1.8 SE years old) and 25 non-ME/CFS female participants (33.0 ± 1.6 SE years old). All samples underwent metabolic profiling via 1D 1H Nuclear magnetic resonance spectroscopy and quantitated metabolites were assessed for significance. Blood glucose was elevated while blood lactate, urine pyruvate, and urine alanine were reduced indicating an inhibition of glycolysis that may potentially reduce the provision of adequate acetyl-CoA for the citric acid cycle. We propose that amino acids are being increasingly used to provide an adequate carbohydrate source for the citric acid cycle. We suggest that this is via glutamate forming 2-oxoglutarate through an enzyme that deaminates it and subsequently elevates blood aspartate. Dysfunctional energy metabolism appears to have impacted creatinine and its elevation in urine suggests that it may be used as an alternative for anaerobic ATP production within muscle. A decrease in blood hypoxanthine and an increase in urine allantoin further suggest the elevation of reactive oxygen species in ME/CFS patients. These findings bring new information to the research of energy metabolism, chronic immune activation and oxidative stress issues within ME/CFS.'"
 * 2012, NMR metabolic profiling of serum identifies amino acid disturbances in chronic fatigue syndrome"'Abstract - Chronic fatigue syndrome (CFS) is a debilitating multisystem disorder characterised by long-term fatigue with a variety of other symptoms including cognitive dysfunction, unrefreshing sleep, muscle pain, and post-exertional malaise. It is a poorly understood condition that occurs in ~ 5 in every 1000 individuals. We present here a preliminary study on the analysis of blood samples from 11 CFS and 10 control subjects through NMR metabolic profiling. Identified metabolites that were found to be significantly altered between the groups were subjected to correlation analysis to potentially elucidate disturbed metabolic pathways. Our results showed a significant reduction of glutamine (P = 0.002) and ornithine (P < 0.05) in the blood of the CFS samples. Correlation analysis of glutamine and ornithine with other metabolites in the CFS sera showed relationships with glucogenic amino acids and metabolites that participate in the urea cycle. This indicates a possible disturbance to amino acid and nitrogen metabolism. It would be beneficial to identify any potential biomarkers of CFS for accurate diagnosis of the disorder.'"
 * 2011, The Biochemistry of Chronic Pain and Fatigue
 * 2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome
 * 2004, Membrane Damaging Toxins from Coagulase-Negative Staphylococcus Are Associated with Self-Reported Temporomandibular Disorder (TMD) in Patients with Chronic Fatigue Syndrome''"'Abstract - Objective: To assess whether there is any association between membrane damaging toxin production by Staphylococcus spp. and self-reported TMD symptom expression in a group of patients selected to have CFS. Methods: Thirty-three defined Chronic Fatigue Syndrome (CFS) patients and 33 age- and sex-matched controls were assessed to evaluate the relationship between carriage of membrane damaging toxin producing Staphylococcus, CFS and temporomandibular dysfunction (TMD) symptoms. Results: The CFS patients had an increased prevalence of face pain (Odds Ratio = 21.0, 95% CL 4.2-106, P < .001) and temporomandibular joint (TMJ) clicking/locking (OR = 5.7, 95% CL 1.4- 23.5, P < .007), and the coagulase-negative Staphylococcus maximum % βtoxin haemolysis per patient. Both multivariate and univariate analyses revealed an association between the membrane damaging δtoxin producing CoNS (MDT-CoNS) species per subject and face pain prevalence and intensity within both the CFS patients and the control subjects. No association was found between CoNS toxin production and TMJ clicking/locking. Importantly, α- and βtoxin production by CoNS was associated with patient reporting of arthritis. Conclusions: These data confirm the original observations of the association between MDT-CoNS and facial muscle pain (Butt et al., 1998; McGregor et al., 2003). These data also suggest that MDT-CoNS associated facial muscle pain expression represents a distinct clinical entity, which has an increased prevalence in CFS patients.'"
 * 2004, Association Between Oxidative Damage Markers and Self-Reported Temporomandibular Dysfunction Symptoms in Patients with Chronic Fatigue Syndrome"'Abstract - Full blood counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), haematinics and markers for oxidative stress were measured on thirty-three patients diagnosed with chronic fatigue syndrome (CFS) and twenty-seven age and sex matched controls. The CFS patients had increased prevalence of symptoms of temporomandibular dysfunction (TMD). Jaw muscle pain was associated with increases in methaemoglobin (P < .002), ferritin (P < .02) and malondialdehyde (P < .007) whilst temporomandibular joint (TMJ) clicking and/or locking was associated with increases in methaemoglobin (P < .001), malondialdehyde (P < .05) and vitamin B12 (P < .02) levels. Multiple regression analysis found methaemoglobin to be the principle component associated with TMD symptoms in the CFS patients. Increases in scalar severity responses to jaw muscle pain and TMJ clicking and/or locking were positively correlated with methaemoglobin by multiple regression. These data indicate that oxidative stress due to excess free radical formation was associated with jaw muscle pain in CFS patients and suggest that these symptoms were likely to be associated with a pathogen-associated aetiology.'"
 * 2003, Comparison of Activity Limitations/Participation Restrictions Among Fibromyalgia and Chronic Fatigue Syndrome Patients"'Abstract - Fibromyalgia (FM) and Chronic Fatigue Syndrome (CFS) are related yet overlapping disorders; the current case definitions prohibit a clear-cut differential diagnosis. These diagnostic criteria mainly address the impairment level of the World Health Organization's International Classification of Functioning, Disability and Health. This study aimed at comparing activity limitations and participation restrictions in patients with FM (n = 90) and CFS (n = 47). The Chronic Fatigue Syndrome Activities and Participation Questionnaire (CFS-APQ) was used for assessing functionality in both groups. The convergent validity of the scores obtained with the questionnaire with visual analogue scales for pain, fatigue and concentration was investigated in FM patients, as well as the content validity. No differences in total scores and 25 out of 26 individual items on the CFS-APQ were observed between the 2 groups (independent samples Mann-Whitney U test). This sample of FM patients reported to be more disabled in ‘sitting for two hours’ as compared to the CFS group (mean scores 3.0 ± 1.0 and 2.3 ± 1.0; P = .004). Four hundred and thirty-seven of the 497 (87.9%) responses to the request to list difficult activities matched the content of the CFS-APQ. The overall scores of the CFS-APQ correlated statistically significant in respect to visual analogue scales for pain and concentration (Spearman rho for the total scores ranged between .44 and .49). These data question the disease specificity of the CFS-APQ for CFS, but suggests its applicability in ‘the Chronic Pain-Fatigue Syndromes.’ The present report provides evidence for both the content and convergent validity of the CFS-APQ in FM patients."
 * 2002, Activity Limitations and Participation Restrictions in Patients with Chronic Fatigue Syndrome—Construction of a Disease Specific Questionnaire"'Abstract - Review of the literature indicated the lack of disease specific measures for assessing activity limitations and participation restriction in patients with Chronic Fatigue Syndrome. Retrospective analysis of Karnofsky Performance Status questionnaires and Activities of Daily Living questionnaires (a Dutch version of the Barthel index, modified for CFS) of 141 subjects was performed to create a new questionnaire. Data analysis resulted in the following item selection, based on most frequently reported activity limitations and participation restriction; cleaning, washing dishes and returning them to cupboard, iron, do the wash, gardening, replace light bulb, walking, climb one flight of stairs, stand one hour, sit two hours, doing groceries, thirty minutes of computer work, carrying heavy objects, write a full page letter, use a screwdriver, hammer a nail, make one bed, reading, social activities, doing sports, studying, driving a car, going to school/working, preparing meals and caring for a child. These data were used to create the CFS-Activities and Participation Questionnaire (CFS-APQ). The reliability and different aspects of validity of this new measure still need to be established.'"
 * 2002, Possible Triggers and Mode of Onset of Chronic Fatigue Syndrome"'Abstract - To identify the possible triggering events of CFS, we collected data on 1546 CFS patients and 309 excluded fatigued patients. Using extensive present and past medical history and lab reports as close as possible to the date of onset, an attempt was made to identify the agents that could play a role in the disease process. Significant differences were found between the events at onset, between the Fukuda or Holmes definitions and a sudden as distinct from a gradual onset. We further found a series of subgroups of events that occurred at onset of CFS. Each of these onset event clusters was associated with an infectious event, blood transfusion or hepatitis B vaccination. In a large percentage of our study group an infectious event was combined with a non-infectious event. In summary, we can conclude that a number of different stressors and consequent immunological and neuroendocrinological changes can contribute to the onset of CFS.'"
 * 2000, Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome
 * 2000, Erythrocyte Morphology in Rheumatoid Arthritis and Chronic Fatigue Syndrome: A Preliminary Study"Abstract - 'Erythrocyte deformability and erythrocyte membrane stability are dependent on the erythrocyte cytoskeleton and its relationship with the contents of the cell. Certain internal occurrences such as oxidation of sulphydryl groups on the membrane cytoskeleton or the haemoglobin molecule could alter this relationship and as a consequence, alter the membrane properties and the shape of the cell. It is thus conceivable that in conditions where there is a potential increase in the generation of free radicals, erythrocyte shape could be altered. We investigated the possibility that predictable shape changes occur in erythrocytes from patients with rheumatoid arthritis (RA), a condition associated with free radical damage. We also investigated this possibility in patients with chronic fatigue syndrome (CFS) and whether any such change could be correlated with those seen in RA. Patients with CFS could be divided into two groups based on their erythrocyte morphology. Patients in one of these groups had increased numbers of stomatocytes. Patients with RA had increased numbers of leptocytes.'"
 * 2000, Investigation of Erythrocyte Oxidative Damage in Rheumatoid Arthritis and Chronic Fatigue Syndrome"Abstract - 'A role of free radical scavenging for erythrocytes has previously been demonstrated, which is additional to their established role of gas exchange. In carrying out this role, erythrocytes become damaged by oxidation, which consumes endogenous reducing substances. It was therefore proposed that there exists a link between erythrocyte metabolism (particularly redox metabolism) and erythro-cyte shape and that both of these should be related to erythrocyte deformability. To look for evidence of oxidative damage in vivo, the erythrocytes were assessed for reduced glutathione (GSH), malondial-dehyde (MDA), methaemoglobin (metHb) and 2,3-diphosphoglyceric acid (2,3-DPG) in patients suffering from rheumatoid arthritis (RA), chronic fatigue syndrome (CFS) and healthy control subjects. Full blood counts, serum vitamin B12, erythrocyte folate, serum ferritin, serum iron, serum iron binding capacity and erythrocyte magnesium were also performed on all samples. Patients with RA had increased 2,3-DPG, GSH and metHb when compared with the control group as well as the expected decreased haemoglobin, haematocrit, and serum iron. There was evidence of oxidative damage in CFS with 2,3-DPG metHb and MDA increased in this group. An increase in GSH could also be demonstrated in a sub-group of the CFS patients. This damage may explain the shape changes (presumably accompanied by increased rigidity) that have been reported in erythrocytes in patients suffering from CFS and suggests a role for free radicals in the pathogenesis of CFS.'"
 * 1998, Immunological and Haematological Parameters in Patients with Chronic Fatigue Syndrome "Abstract - 'Red and white blood cell parameter profiles and poke-weed mitogen responses were investigated in 57 CDC-dcfined CFS patients and 34 age-and sex-matched controls. CFS patients had significantly different red and white blood cell profiles compared with controls. Red cell distribution width (RDW) was the primary regression factor differentiating the groups. RDW was positively associated with mean platelet volume (MPV) in control subjects, but negatively correlated with MPV in CFS patients, indicating a reversal of the functional relationship between these parameters in CFS patients. Hematological parameters, and not the immunological parameters studied, were more important in differentiating CFS patients from healthy control subjects. Female CFS patients had significant increases in RDW and mean platelet volume, and decreases in the numbers of T-helper cells, T-cells and lymphocytes compared with control females. These alterations were not observed in corresponding mate comparisons. There were no differences in the pokeweed mitogen (PWM) response between the CFS and control groups. However, in control subjects, a significant association was observed between pokeweed mitogen responses and Rh(D) antigen status, whereas no similar association was measured in CFS patients. Rh(D)-negative control subjects had a significantly increased mitogen response compared with Rh(D)-positive subjects, whereas in CFS patients, no difference was found. It was concluded that future blood parameter and lymphocyte mitogen response studies in CFS patients should be controlled for sex and Rh status, respectively.'"
 * 1997, A Preliminary Assessment of the Association of SCL-90-R Psychological Inventory Responses with Changes in Urinary Metabolites in Patients with Chronic Fatigue Syndrome"Abstract - 'A previous investigation of a cohort of 20 chronic fatigue syndrome (CFS) patients revealed an increased urinary excretion of an unusual metabolite, tentatively identified as amino-hydroxy-N-methyl-pyrrolidine (coded CFSUM1) and β-alanine, compared with 45 control subjects. The relative abundances of both CFSUM1 and β-alanine were positively associated with the core diagnostic symptoms of CFS and associated changes in amino and organic acid excretion. The psychological attributes of these CFS patients and controls were assessed in this study by using the Symptom Check List-90-revised (SCL-90-R) psychological inventory. The CFS patients had increases in the SCL-90-R. somatization, obsessive compulsive, depression, anxiety and phobic anxiety dimension scores. Nineteen of 20 CFS patients had somatization T-scores ≥ 63 (P < 0.0001), suggestive of a somatization disorder. Multiple regression analysis indicated that somatization was the most important SCL-90-R-defined dimension discriminating CFS from control subjects. Depression and anxiety were not found to be important inter-group determinants. The dimension scores were each related to specific changes in the urinary excretion of organic and amino acids, suggesting that each is biochemically distinct and has an organic basis. Cluster analysis of dimension profiles revealed that the profile with increased prevalence (P < 0.0001) in CFS patients was associated with increased excretion of CFSUM1 (P < 0.005) and had increases in somatization, obsessive compulsion and depression dimension scores. The PSDI as a measure of SCL-90-R symptom severity was positively correlated with CFSUM1 (model P < 0.003). CFSUM1 was also the primary correlate for the somatization dimension (model P < 0.0008), but was not associated with any other SCL-90-R-defined dimension. Another unidentified urinary metabolite, coded UM 15, was the primary correlate for depression (model P < 0.0004) and was associated with multiple dimension elevations by both cluster and logistic regression analysis; the excretion of this compound was unrelated to CFSUM1. These results indicated that, in this CFS cohort, the SCL-90-R defined psychological changes were strongly associated with changes in the biochemical homeostasis of patients, suggestive of an organic basis to CFS.'"

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