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CFS and FMS Research
Published Abstracts
[Association between symptom expression and urinary metabolites]
[Bioaccumulated chlorinated hydrocarbons and red/white blood cell parameters]
[Immunological and haematological parameters in patients with CFS]
PRELIMINARY DETERMINATION OF A MOLECULAR BASIS TO CHRONIC FATIGUE SYNDROME
Neil R. McGregor , R. Hugh Dunstan, Mariann Zerbes, Henry L. Butt, Timothy K. Roberts, Iven J. Klineberg © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
Abstract
Chronic fatigue syndrome (CFS/ME) is a debilitating illness that has a poorly understood aetiology. The team studied 20 chronic fatigue syndrome (CFS) patients, who complied with both the Oxford and American CDC definitions, and 45 non-CFS subjects.
Participants completed questionnaires, were clinically examined and had their first morning urine specimens collected. These specimens were analysed by gas chromatography - mass spectrometry for changes in metabolite excretion.
Statistical analysis of the urinary metabolite profiles differed significantly in the CFS patients compared to the non-CFS patients.
The CFS patients had significant increases in amino-hydroxy-N -methyl-pyrrolidine. This chemical is commonly known as chronic fatigue symptom urinary marker 1 (CFSUM1). Increased levels of tyrosine (p<0.02), beta-alanine (p<0.02), aconitic acid (p<0.05) and succinic acid (p<0.05) were also recorded. © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
The patients in this study had reductions in CFSUM2 (p<0.0007), alanine (p<0.005) and glutamic acid (p<0.02).
CFSUM1, beta-alanine and CFSUM2 were found by discriminant function analysis to be the most important metabolites for discriminating between CFS and non-CFS subjects.
The abundances of CFSUM1 and b-alanine positively correlated with symptom incidence, symptom severity, core CFS symptoms and SCL-90-R somatization, suggesting a molecular basis for CFS.
PRELIMINARY DETERMINATION OF THE ASSOCIATION BETWEEN SYMPTOM EXPRESSION AND URINARY METABOLITES IN SUBJECTS WITH CHRONIC FATIGUE SYNDROME. [1996]
Neil R. McGregor, R. Hugh Dunstan, Mariann Zerbes, Henry L. Butt, Timothy K. Roberts
Abstract:
This study found that CFS patients had a urinary metabolite labelled CFSUM1 with increased incidence (P<0.004) and relative abundance (P<0.00003). The relative abundances of urinary CFSUM1 and beta-alanine were associated with alterations in metabolite excretion and symptom incidence. © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
In 20 CFS patients and 45 non-CFS subjects, symptom/metabolite associations were investigated by assessing:
1. Symptom sensitivity and specificity.
2. Symptom indices of total symptom incidence.
3. CFS core symptoms that included cognitive, neurological, musculoskeletal, gastrointestinal, infection-related and genitourinary symptom indices.
4. Visual analogue pain scale of average pain intensity (VAPS).
Thirty-three symptoms had significant (P<0.005) sensitivity and specificity in the CFS patients compared to non-CFS controls.
Severe fatigue was the only symptom with 100% sensitivity and specificity, with CFSUM1 excretion being the primary metabolite for expression of this symptom. All 9 symptom indices had elevated responses in the CFS patients (all P<0.0000001). Statistical analyses indicated that all the symptom indices had significant correlations with changes in the urinary excretion of metabolites (P<0.0001).
CFSUM1 and beta-alanine were the 1st and 2nd metabolites that correlated with the CFS core symptom index. CFSUM1 was primarily associated with infection-related and musculoskeletal indices. Beta-alanine was primarily associated with gastrointestinal and genitourinary indices. The strong associations of CFSUM1 and beta-alanine with CFS symptom expression provides a molecular basis for developing an objective test for CFS.
A PRELIMINARY INVESTIGATION OF CHLORINATED HYDROCARBONS AND CHRONIC FATIGUE SYNDROME [1995]
R. Hugh Dunstan, Mark Donohoe, Warren Taylor, Timothy K. Roberts, Raymond N. Murdoch, Jennifer A. Watkins, Neil R. McGregor
Objective:
To determine whether chlorinated hydrocarbons are significantly elevated in serum from patients with chronic fatigue syndrome compared to control subjects.
Method:
Chlorinated hydrocarbon pesticides were measured in serum samples from patients with chronic fatigue syndrome (n=22) that met the CDC diagnostic criteria.
The second group included patients with CFS symptoms who were excluded from the research definition of CFS, on the basis of a reported history of exposure to toxic chemicals (n=17). The pesticide levels in these patient groups were compared to those obtained from a group of non-CFS age/sex matched controls (n=34). © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
Results:
The pesticide DDE was detected in all serum samples at levels greater than 0.4 parts per billion. The incidence of HCB (hexachlorobenzene) contamination was 45% in the CFS group. This was significantly higher than the 21% incidence observed in the non-CFS control group.
The CFS group had a significantly higher total organochlorine level than the control group.
The toxic exposure group also had a higher mean organochlorine level than the control group, but the difference was not statistically significant. DDE and HCB comprised more than 90% of the total organochlorines measured in each of the sample groups.
Conclusions:
The organochlorine levels measured in serum from CFS patients were higher than those in control subjects, suggesting that these chemicals have an aetiological role in CFS. There were no significant differences in serum organochlorine concentrations between CFS patients and chronic fatigue patients with a history of toxic chemical exposure.
Therefore, the exclusion of patients from the CDC research definition of CFS on the basis of a patient’s history of exposure to toxic chemicals could not be supported. The role of low level organochlorine bioaccumulation in the development of CFS symptoms requires further investigation.
BIOACCUMULATED CHLORINATED HYDROCARBONS AND RED/WHITE BLOOD CELL PARAMETERS [1996]
R. Hugh Dunstan, Timothy K. Roberts, Mark Donohoe, Neil R. McGregor, Darren Hope, Warren G. Taylor, Jennifer A. Watkins, Raymond N. Murdoch, Henry L. Butt
The relationships between chlorinated hydrocarbon contamination in serum and red/white blood cell parameters were investigated by multivariate techniques. This involved the assessment of the cellular response patterns to high and low organochlorine levels.
Twenty-three healthy control subjects and 14 patients with unexplained and persistent fatigue were divided on the basis of:
(a) high or low total organochlorine content
(b) high or low DDE (1,1-dichloro-2,2-bis (p-chlorophenyl) ethene) content
(c) high or low HCB (hexachlorobenzene) content
Discriminant function analysis revealed that the groups with high organochlorine content had significantly altered red/white blood cell statistical profiles compared to the low organochlorine groups. © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
As a variable, % neutrophils was the most important discriminant parameter for differentiating between the high and low total organochlorine groups. Thirteen of the 14 chronic fatigue patients were characterised as "high total organochlorine content". The red cell distribution width was elevated in the high DDE group and was the most important parameter for differentiating between the high and low DDE groups.
The % eosinophils and the haemoglobin content were both reduced in the high HCB group. The % eosinophils was the most important parameter for differentiating between the high and low HCB groups.
Those patients with unexplained and persistent fatigue had significantly higher levels of DDE compared to the controls. These people also had different specific blood cell responses to organochlorines compared to control subjects.
[Note: high levels of DDE and/or HCB have since been found to be significant factors in type 1 CFS, as determined by the blood lipid test].
A PRELIMINARY ASSESSMENT OF THE ASSOCIATION OF SCL-90-R PSYCHOLOGICAL INVENTORY RESPONSES WITH CHANGES IN THE URINARY METABOLITES IN PATIENTS WITH CFS [1997]
N.R.McGregor, R.H.Dunstan, H.L.Butt ,T.K.Roberts, I.J.Klineberg, M.Zerbes
A previous investigation of a group of 20 CFS patients revealed an increased urinary excretion of an unusual metabolite, identified as amino-hydroxy -N-methyl-pyrrolidine (CFSUM1) and beta-alanine, compared to 45 control subjects.
The relative abundances of both CFSUM1 and beta-alanine were positively associated with the core CFS symptoms 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. © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
Nineteen of 20 CFS patients had somatization T-scores 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. This suggested that each was biochemically distinct and had an organic basis.
CFSUM1 was also the primary correlate for the somatization dimension, but was not associated with any other SCL-90-R defined dimension. Another unidentified urinary metabolite, coded UM15, was the primary correlate for depression.
These results indicated that, in this CFS study, the SCL-90-R defined psychological changes were strongly associated with changes in the biochemical homeostasis of patients, strongly suggestive of an organic basis to CFS.
ASSESSMENT OF PAIN (DISTRIBUTION & ONSET), SYMPTOMS, SCL-90-R INVENTORY RESPONSES AND THE ASSOCIATION WITH INFECTIOUS EVENTS IN PATIENTS WITH CHRONIC OROFACIAL PAIN. [1997]
Neil McGregor, Henry Butt, Mariann Zerbes, Iven Klineberg, Hugh Dunstan, Timothy Roberts
This study assessed the clinical characteristics and histories of 43 chronic orofacial muscle pain patients and 40 control subjects. Patients and control subjects were interviewed, completed questionnaires and were clinically examined. The visual analogue pain scale (VAS) and scalar responses to 13 pain/symptom indicator SCL-90-R questions were used to assess symptom prevalence and pain severity. © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
The orofacial muscle pain group reported:
1. Pain in an axial skeletal distribution
2. Neurocognitive, gastro-genitourinary and musculoskeletal symptoms
3. Infectious events at, or preceding, onset
4. Similar symptoms in sexual partners
5. Low prevalence of trauma at onset.
Sudden onset was reported by 30.2% of chronic orofacial muscle pain patients with the remaining 69.8% reporting gradual onset of symptoms. Gradual onset with no identifiable triggering event was reported by 27.7%.
Strong associations were found between chronic orofacial muscle pain and:
1. Onset related infections
2. Increased prevalence of a history of respiratory and gastro-genitourinary infections
3. High prevalences of similar pain symptoms in long term sexual partners.
High SCL-90-R somatization scores were common in the chronic orofacial muscle pain group. No association between depression scores and pain/symptom indicators was found.
This data suggest that:
1. Patients with recurrent systemic infectious events have a higher prevalence of reporting of chronic orofacial muscle pain compared to control subjects.
2. These infectious events are associated with the onset of chronic orofacial muscle pain in 67% of patients. © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
AN ASSOCIATION OF MEMBRANE DAMAGING TOXINS FROM COAGULASE NEGATIVE STAPHYLOCOCCUS AND OROFACIAL MUSCLE PAIN [1998]
Henry Butt, Hugh Dunstan, Neil McGregor, Timothy Roberts, Mariann Zerbes, Iven Klineberg
Forty-six patients presenting with chronic orofacial muscle pain and 8 age/sex matched control subjects were investigated for the prevalence and exotoxin production of coagulase negative staphylococcus (CNS) bacteria. © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
There was a significantly higher prevalence of CNS in patients with chronic muscle pain than in control subjects. In addition, multiple strains of CNS were commonly detected in patients with chronic muscle pain. It was found that pyrogenic (fever producing) toxins did not significantly contribute to the aetiology of chronic muscle pain.
There was a significantly higher prevalence of delta-haemolysin and ‘horse’-haemolysin production by CNS strains in chronic muscle pain patients compared to controls.
The results strongly suggest that membrane damaging toxins, like delta and ‘horse’ haemolysin, may have a role in the aetiology of chronic orofacial muscle pain.
IMMUNOLOGICAL AND HAEMATOLOGICAL PARAMETERS IN PATIENTS WITH CHRONIC FATIGUE SYNDROME [1998]
Roberts TK, McGregor NR, Dunstan RH, Donohoe M, Murdoch RN, Hope D, Zhang S, Butt HL, Watkins JA, Taylor WG © Bioscreen, CPRU, S Ashton and F Bartosy 1999 - 2001
Red and white cell profiles and pokeweed mitogen responses were investigated in 57 CDC-defined CFS patients and 34 age/sex matched control subjects. It was found that CFS patients had different red and white blood cell profiles when compared to control subjects, with the red cell distribution width (RDW) being the primary differentiating factor.
RDW was positively associated with mean platelet volume (MPV) in control subjects, but negatively correlated with MPV in CFS patients. This indicated a reversal of the functional relationship between these parameters in the CFS patients. Haematological parameters were found to be more important than immunological parameters in differentiating CFS patients from healthy control subjects.
Female CFS patients had increases in RDW and mean platelet volume, and decreases in the numbers of T-helper cells, T-cells and lymphocytes compared to control females. These alterations were not observed in corresponding male comparisons. There were no differences in the pokeweed mitogen (PWM) response between the CFS and the control groups.
It was found that control subjects had an association between pokeweed mitogen responses and Rh(D) antigen status. No similar association was measured in CFS patients.
It was therefore concluded that future haematological studies in CFS patients should be controlled for sex and Rh status respectively.
© CPRU and F Bartosy 2000
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