Tag: Dunstan

Hematologic and urinary excretion anomalies in patients with chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) have a broad and variable spectrum of signs and symptoms with variable onsets. This report outlines the results of a single-blind, cross-sectional research project that extensively investigated a large cohort of 100 CFS patients and 82 non fatigued control subjects with the aim of performing a case-control evaluation of alterations in standard blood parameters and urinary amino and organic acid excretion profiles.

Blood biochemistry and full blood counts were unremarkable and fell within normal laboratory ranges. However, the case-control comparison of the blood cell data revealed that CFS patients had a significant decrease in red cell distribution width and increases in mean platelet volume, neutrophil counts, and the neutrophil-lymphocyte ratio.

Evaluation of the urine excretion parameters also revealed a number of anomalies. The overnight urine output and rate of amino acid excretion were both reduced in the CFS group (P < 0.01). Significant decreases in the urinary excretion of asparagine (P < 0.0001), phenylalanine (P < 0.003), the branch chain amino acids (P < 0.005), and succinic acid (P < 0.0001), as well as increases in 3-methylhistidine (P < 0.05) and tyrosine (P < 0.05) were observed.

It was concluded that the urinary excretion and blood parameters data supported the hypothesis that alterations in physiologic homeostasis exist in CFS patients.

 

Source: Niblett SH, King KE, Dunstan RH, Clifton-Bligh P, Hoskin LA, Roberts TK, Fulcher GR, McGregor NR, Dunsmore JC, Butt HL, Klineberg I, Rothkirch TB. Hematologic and urinary excretion anomalies in patients with chronic fatigue syndrome. Exp Biol Med (Maywood). 2007 Sep;232(8):1041-9. https://www.ncbi.nlm.nih.gov/pubmed/17720950

 

A biochemical analysis of people with chronic fatigue who have Irlen Syndrome: speculation concerning immune system dysfunction

Abstract:

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.

 

Source: Robinson GL, McGregor NR, Roberts TK, Dunstan RH, Butt H. A biochemical analysis of people with chronic fatigue who have Irlen Syndrome: speculation concerning immune system dysfunction. Percept Mot Skills. 2001 Oct;93(2):486-504. http://www.ncbi.nlm.nih.gov/pubmed/11769907

 

Free radicals in chronic fatigue syndrome: cause or effect?

Abstract:

We have demonstrated that certain morphological and biochemical changes occur in chronic fatigue syndrome (CFS) and in rheumatoid arthritis (RA). These changes in RA can be explained by the well-established inappropriate increase in free radical generation. The similar changes in CFS suggest a similar explanation and a possible role for free radicals in the aetiology of this condition.

 

Source: Richards RS, Roberts TK, Dunstan RH, McGregor NR, Butt HL. Free radicals in chronic fatigue syndrome: cause or effect? Redox Rep. 2000;5(2-3):146-7. http://www.ncbi.nlm.nih.gov/pubmed/10939298

 

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 (R(2) = 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 (R(2) = 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.

 

Source: Richards RS, Roberts TK, McGregor NR, Dunstan RH, Butt HL. Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep. 2000;5(1):35-41. http://www.ncbi.nlm.nih.gov/pubmed/10905542

 

Preliminary determination of the association between symptom expression and urinary metabolites in subjects with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) patients have a urinary metabolite labeled 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.

In 20 CFS patients and 45 non-CFS subjects, symptom/metabolite associations were investigated by assessing symptom sensitivity and specificity, and symptom indices of total symptom incidence, CFS core symptoms, cognitive, neurological, musculoskeletal, gastrointestinal, infection-related and genitourinary symptom indices, as well as a visual analogue pain scale of average pain intensity. Thirty-three symptoms had significant (P < 0.005) sensitivity and specificity in the CFS patients compared to that in the non-CFS controls.

Severe fatigue was the only symptom with 100% sensitivity and specificity and CFSUM1 excretion was the primary metabolite for expression of this symptom. All nine symptom indices had elevated responses in the CFS patients (all P < 0.0000001). Multiple regression analyses indicated that all the symptom indices had significant correlations (R) with changes in the urinary excretion of metabolites (P < 0.0001).

CFSUM1 and beta-alanine were the first and second metabolites correlated with the CFS core symptom index and CFSUM1 was primarily associated with infection-related and musculoskeletal indices whereas beta-alanine was primarily associated with gastrointestinal and genitourinary indices. The strong associations of CFSUM1 and beta-alanine with CFS symptom expression provide a molecular basis for developing an objective test for CFS.

 

Source: McGregor NR, Dunstan RH, Zerbes M, Butt HL, Roberts TK, Klineberg IJ. Preliminary determination of the association between symptom expression and urinary metabolites in subjects with chronic fatigue syndrome. Biochem Mol Med. 1996 Jun;58(1):85-92. http://www.ncbi.nlm.nih.gov/pubmed/8809350

 

Bioaccumulated chlorinated hydrocarbons and red/white blood cell parameters

Abstract:

The potential relationships between chlorinated hydrocarbon contamination in human serum and red/white blood cell profiles were investigated by multivariate techniques to assess the cellular response patterns to high and low organochlorine levels in the serum.

Twenty-three healthy control subjects and fourteen 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, and (c) high or low HCB (hexachlorobenzene) content. Discriminant function analysis revealed that the groups with high organochlorine content had significantly different red/white blood cell profiles compared with the low organochlorine groups ((a) P < 0.017, (b) P < 0.015, and (c) P < 0.0002). As a variable, the percentage of neutrophils was the most important discriminant parameter for differentiating between the high and low total organochlorine groups.

Thirteen of the fourteen fatigued patients were characterized as “high total organocholorine content” (P < 0.04). The red cell distribution width was elevated in the high DDE group (P < 0.04) and was the most important discriminant parameter for differentiating between the high and low DDE groups. The percentage of eosinophils and the hemoglobin content were both reduced in the high HCB group (P < 0.009,P < 0.003, respectively) and the percentage of eosinophils was the most important discriminant parameter for differentiating between the high and low HCB groups. Those patients with unexplained and persistent fatigue had significantly higher levels of DDE compared with the controls and had different specific blood cell responses to organochlorines compared with control subjects.

 

Source: Dunstan RH, Roberts TK, Donohoe M, McGregor NR, Hope D, Taylor WG, Watkins JA, Murdoch RN, Butt HL. Bioaccumulated chlorinated hydrocarbons and red/white blood cell parameters. Biochem Mol Med. 1996 Jun;58(1):77-84. http://www.ncbi.nlm.nih.gov/pubmed/8809349

 

Preliminary determination of a molecular basis of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS/ME) is a debilitating fatigue illness that has an unknown etiology. We studied 20 chronic fatigue syndrome (CFS) patients, who complied with the Oxford and American CDC definitions, and 45 non-CFS subjects.

Participants completed questionnaires, were clinically examined, and had first morning urine specimens collected, which were screened by gas chromatography-mass spectrometry for changes in metabolite excretion.

Multivariate analysis of the urinary metabolite profiles differed significantly in the CFS patients compared to the non-CFS patients (P < 0.004). The CFS patients had increases in aminohydroxy-N-methylpyrrolidine (P < 0.00003, referred to as chronic fatigue symptom urinary marker 1, or CFSUM1), tyrosine (P < 0.02), beta-alanine (P < 0.02), aconitic acid (P < 0.05), and succinic acid (P < 0.05) and reductions in an unidentified urinary metabolite, 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 first, second, and third most important metabolites, respectively for discriminating between CFS and non-CFS subjects.

The abundances of CFSUM1 and beta-alanine were positively correlated with symptom incidence (P < 0.01 and P < 0.001, respectively), symptom severity, core CFS symptoms, and SCL-90-R somatization (P < 0.00001), suggesting a molecular basis for CFS.

 

Source: McGregor NR, Dunstan RH, Zerbes M, Butt HL, Roberts TK, Klineberg IJ. Preliminary determination of a molecular basis of chronic fatigue syndrome. Biochem Mol Med. 1996 Apr;57(2):73-80. http://www.ncbi.nlm.nih.gov/pubmed/8733884

 

A preliminary investigation of chlorinated hydrocarbons and chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine whether serum levels of chlorinated hydrocarbons are elevated in patients with chronic fatigue syndrome.

METHODS: Chlorinated hydrocarbon levels were measured in 22 patients with chronic fatigue syndrome (CFS) (as defined by the Centers for Disease Control [CDC]); in 17 patients with CFS symptoms whose history of exposure to toxic chemicals excluded them from the research definition of CFS; and in 34 non-CFS control subjects matched for age and sex.

RESULTS: DDE (1,1-dichloro-2,2-bis (p-chlorophenyl) ethene) was detected in all serum samples at levels over 0.4 ppb. The incidence of hexachlorobenzene (HCB) contamination (> 2.0 ppb) was 45% in the CFS group, compared with 21% in the non-CFS control group (P < 0.05). The CFS group had a significantly higher total organochlorine level (15.9 ppb; SEM, 4.4) than the control group (6.3 ppb; SEM, 1.1; P < 0.05). The toxic exposure group also had a higher mean organochlorine level (13.6 ppb; SEM, 6.2) 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 groups.

CONCLUSION: The results suggest that recalcitrant organochlorines may 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, exclusion of patients from the CDC research definition of CFS on the basis of a reported history of known exposure to toxic chemicals is not valid. The role of low-level organochlorine bioaccumulation in the development of CFS symptoms requires further investigation.

 

Source: Dunstan RH, Donohoe M, Taylor W, Roberts TK, Murdoch RN, Watkins JA, McGregor NR. A preliminary investigation of chlorinated hydrocarbons and chronic fatigue syndrome. Med J Aust. 1995 Sep 18;163(6):294-7. http://www.ncbi.nlm.nih.gov/pubmed/7565234