Webmaster
last revised 5 Aug 2004for Sydney Conference abstracts, visit the Alison Hunter Memorial Foundation website
Maximal oxygen uptake and lactate metabolism are normal in chronic fatigue syndrome.
Regional Cerebral Blood Flow in Fibromyalgia
Regional cerebral bloodflow in chronic fatigue syndrome (CFS)
Activity Limitations and Participation Restrictions in Patients with Chronic Fatigue Syndrome 2002
Possible Triggers and Mode of Onset of Chronic Fatigue Syndrome 2002
A biochemical analysis of people with chronic fatigue who have Irlen syndrome 2001
Chronic Fatigue Syndrome: Overcoming the Attitudinal Impasse 2001
A definition-based analysis of symptoms in a large cohort of patients with CFS. 2001
An investigation of the association between toxin-producing staphylococcus, biochemical changes and jaw muscle pain Neil R McGregor. University of Sydney (2000). (Doctorate thesis - full text)
The Biochemistry of Chronic Pain and Fatigue 2000
Exercise Capacity in Chronic Fatigue Syndrome 2000
Preliminary Determination of a molecular basis to Chronic Fatigue Syndrome 1996
Bioaccumulated Chlorinated Hydrocarbons and Red/White Blood Cell Parameters 1996
A Preliminary Investigation Of Chlorinated Hydrocarbons And Chronic Fatigue Syndrome 1995Med Sci Sports Exerc 2002 Jan;34(1):51-56
Sargent C, Scroop GC, Nemeth PM, Burnet RB, Buckley JD.
Exercise Physiology Research Unit, Department of Physiology, University of Adelaide, South Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, South Australia; and the Centre for Research in Education and Sports Science, School of Physical Education, Exercise and Sport Studies, University of South Australia.
PMID: 11782647
PURPOSE: Previous studies in chronic fatigue syndrome (CFS) have reported reductions in maximal oxygen uptake (VO2max), yet often the testing procedures have not followed accepted guidelines, and gender data have been pooled. The present study was undertaken to reevaluate exercise capacity in CFS patients by using "gold standard" maximal exercise testing methodology and stratifying results on a gender basis.
METHODS: Sixteen male and 17 female CFS patients and their gender-, age-, and mass-matched sedentary controls performed incremental exercise to volitional exhaustion on a stationary cycle ergometer while selected cardiorespiratory and metabolic variables were measured.
RESULTS: VO2max in male CFS patients was not different from control values (CFS: 40.5 +/- 6.7; controls: 43.3 +/- 8.6; mL.kg-1.min-1) and was 96.3 +/- 17.9% of the age-predicted value, indicating no functional aerobic impairment (3.7 +/- 17.9%). In female CFS patients, VO2max was lower than control values (CFS: 30.0 +/- 4.7; controls: 34.2 +/- 5.6; mL.kg-1.min-1, P = 0.002), but controls were higher than the age-predicted value (112.6 +/- 15.4%, P = 0.008) whereas the CFS patients were 101.2 +/- 20.4%, indicating no functional aerobic impairment (-1.2 +/- 20.4%). Maximal heart rate (HRmax) in male CFS patients was lower than their matched controls (CFS: 184 +/- 10; controls: 192 +/- 12; beats.min-1; P = 0.016) but was 99.1 +/- 5.5% of their age-predicted value. In female CFS patients, HRmax was not different from controls (CFS: 183 +/- 11; controls: 186 +/- 10; beats.min-1) and was 98.9 +/- 5.1% of the age-predicted value. The VO2 at the lactate threshold (LT) in each gender group, whether expressed in mL.kg-1.min-1 or as a percentage of VO2max, was not different between CFS patients and controls.
CONCLUSIONS: In contrast to most previous reports, the present study found that VO2max, HRmax, and the LT in CFS patients of both genders were not different from the values expected in healthy sedentary individuals of a similar age.
R. Casse, P. Delfante, L.Barnden, R. Burnett, M. Kitchener, R Kwiatek
The Queen Elizabeth Hospital, Adelaide, 5011, Australia
[ Sydney CFS Conference 2001]
Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterised by profound fatigue and neuropsychiatric dysfunction. The neuropsychiatric symptoms are often associated with a mental fatigue, consisting of impaired concentration and slowness of thinking. Patients with this disorder have been studied with radionuclide cerebral perfusion scans with conflicting results. Most previous studies were performed with inhomogeneous patient populations and were not analysed with Statistical Parametric Mapping (SPM). We performed a pilot study to address these issues with Tc-99m HMPAO SPECT and a triple head gamma-camera. A uniform group of 13 female subjects (16-53y) with moderate CFS based on established criteria, pain free, not on medication and not depressed was compared with a group of 11 patients (18-60y) who were scanned for other conditions and reported as normal. Visually, a deficit in regional cerebral bloodflow (rCBF) in the medial temporal lobe was definite in 7 (5L, 1R, 1 bilateral) and equivocal in 3 CFS patients. SPM99 with proportional scaling to the global mean was applied for quantitative analysis. The location, amplitude and corrected p-value of significant focal deficits in CFS were: brainstem (19%, 0.009), left medial temporal lobe (17%, 0.004), right medial temporal lobe (22%, 0.002), frontal lobe (17%, 0.002) and anterior cingulate gyrus (12%, 0.001). These results are to be confirmed against a "true normal" group of volunteers. There appears to be objective evidence that patients with moderately severe CFS have focal cortical and brainstem hypoperfusion.
Richard Kwiatek, MBBS, FRACP, Leighton Barnden, PhD, Jenni Chew, BAppSc, Christopher Rowe, MD, FRACP, Kevin Pile, MD, FRACP: The Queen Elizabeth Hospital, Adelaide, Australia; Raymond Tedman, PhD, Richard Jarrett, PhD: The University of Adelaide, Adelaide, Australia.
Journal of Arthritis & Rheumatism, Volume 43(12) December 2000 pp 2823-2833
Objective. To determine whether regional cerebral blood flow (rCBF) is abnormal in any cerebral structure of women with fibromyalgia (FM), following a report that rCBF is reduced in the thalami and heads of caudate nuclei in FM.
Methods. Seventeen women with FM and 22 healthy women had a resting single-photon-emission computed tomography (SPECT) brain scan to assess rCBF and a T1-weighted magnetic resonance imaging (MRI) scan to enable precise anatomic localization. Additionally, all participants underwent 2 manual tender point examinations and completed a set of questionnaires evaluating clinical features. SPECT scans were analyzed for differences in rCBF between groups using statistical parametric mapping (SPM) and regions of interest (ROIs) manually drawn on coregistered MRI.
Results. Compared with control subjects, the rCBF in FM patients was significantly reduced in the right thalamus (P = 0.006), but not in the left thalamus or head of either caudate nucleus. SPM analysis indicated a statistically significant reduction in rCBF in the inferior pontine tegmentum (corrected P = 0.006 at the cluster level and corrected P = 0.023 for voxel of maximal significance), with consistent findings from ROI analysis (P = 0.003). SPM also detected a reduction in rCBF on the perimeter of the right lentiform nucleus. No correlations were found with clinical features or indices of pain threshold.
Journal: J of Chronic Fatigue Syndrome, Vol. 10(3/4) 2002, pp. 3-23
Authors: Jo Nijs, PT, MSc MT; Peter Vaes, PT, PhD; Elke Van Hoof, Clin Psych; Pascale De Becker, PhD; Neil McGregor, PhD, MDSc; Kenny De Meirleir, MD, PhD
Affiliations: Jo Nijs, Elke Van Hoof, and Pascale De Becker are affiliated with the Department of Human Physiology, Faculty of Physical Education and Physical Therapy, Vrije Universiteit Brussel, Belgium.
Peter Vaes is affiliated with the Department of Physical Therapy, Faculty ofPhysical Education and Physical Therapy, Vrije Universiteit Brussel, Belgium.
Neil McGregor is affiliated with Collaborative Pain Research Unit, Department of Biological Sciences, Faculty of Science, University of Newcastle, Callaghan, New South Wales, Australia.
Kenny De Meirleir is affiliated with Fatigue Clinic, Vrije Universiteit Brussel, Belgium, and the Department of Human Physiology, Faculty of Physical Education and Physical Therapy, Vrije Universiteit Brussel, Belgium.
Address of correspondence to: Jo Nijs, Vakgroep MFAB/Sportgeneeskunde, AZ-VUB KRO gebouw-l, Laarbeeklaan 101, 1090 Brussel, Belgium (E-mail: mailto:Jo.Nijs@vub.ac.be ).
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.
KEYWORDS. Chronic Fatigue Syndrome, activity limitations, participation restriction, CFS-APQ, questionnaire, ICIDH2-B2
INTRODUCTION Chronic Fatigue Syndrome is characterized by "a new onset of persistent or relapsing, debilitating fatigue in a person without a previous history of such symptoms that does not resolve with bed rest and that is severe enough to reduce or impair average daily activity to less than 50% of the patients premorbid activity level for at least 6 months" (63). The 1994 Center for Disease Control case definition for Chronic Fatigue Syndrome (1) dropped the require- ment of an average daily activity below 50%, because it was too difficult to verify. Indeed, exercise capacity testing appears to be a valid (36,64) albeit an expensive and time consuming option. Nevertheless, maximal workload at exhaustion averaged 53% of normal in a large sample of patients (65), suggesting severe disability in Chronic Fatigue Syndrome. Therefore, a cheap, quick and valid measure for assessing daily activity level might be of great value. Klimas (1997) suggested more work should be done to develop objective measures that would actually reflect the patient's degree of disability (66). Disease specific questionnaires are designed for clear-cut populations (for instance the Fibromyalgia Impact Questionnaire (70)), while general measures permit comparisons among populations. Although general measures for assessing health status are widely used in CFS-research, there seems to be a lack of a disease-specific measures for assessing functionality in Chronic Fatigue Syndrome.
In 1980, the World Health Organisation presented taxonomy of disability, the international classification of impairments, disabilities and handicaps(ICIDH)(67). Recently, this classification was revised into the international classification of functioning, disability and health (ICIDH2-BI, see http://www.who.ch/icidh ), and it represents an underlying biopsychosocial model. Two dimensions of this health classification were used to define a clear-cut area of quality of life: activity limitations and participation restriction. According to the ICIDH2-BI, activity is the execution of a task or action by an individual, while participation is defined as involvement in a life situation. Activity limitations are defined as difficulties an individual may have in executing activities. Participation restrictions are defined as problems an individual may experience in involvement in life situations, and it broadens the range from the mundane (taking care of one's physical appearance) to the highest planes of human existence (employment, education, spirituality and cultural, social and political involvement) (69). Generally, activities and participation are considered as one component of functioning and disability.
A literature review was performed to ascertain the lack of a disease specific measure for assessing activity limitations and participation restriction in Chronic Fatigue Syndrome (see methods). Appendix III presents an overview of the different questionnaires for assessing functional disability in Chronic Fatigue Syndrome patients. The Medical Outcomes Short Form 36 Health Status Survey (45,36,14,19,41,56,20,22,15,44,16,30,40,31,35), the Sickness Impact Profile (23,39,25,50,51,52,53,34,43,23) and the Karnofsky Performance Status questionnaire (33,32,55,48,57,43,37,38) appear to be the most widely used measures for assessing outcome in CFS. No disease specific measures were found. The results of this review clearly indicate the lack of a reliable, valid and disease specific measure for assessing activities and participation in Chronic Fatigue Syndrome patients.
In this study, a retrospective analysis of Karnofsky Performance Status questionnaires and Activities of Daily Living questionnaires of 141 CFS-patients was performed to monitor activity limitations and participation restriction in CFS. These data were used to create a new questionnaire for assessing activity limitations and participation restrictions in Chronic Fatigue Syndrome.
© 2002 by The Haworth Press, Inc. All rights reserved.
[Copies of the complete article are available for a fee from The Haworth Document Delivery Service: 1-800-HAWORTH. E-mail address: mailto:getinfo@haworthpressinc.com - Website: http://www.haworthpressinc.com/store/product.asp?sku=J092 ]
[Note: It is also possible that your local library can help you obtain a copy of this article via one of its interlibrary loan agreements.]
Journal: J of Chronic Fatigue Syndrome, Vol. 10(2) 2002, pp. 3-18
Authors: P. De Becker, PhD; N. McGregor, PhD; K. De Meirleir, MD, PhD
Affiliations: P. De Becker, VUB, Vakgroep Interne Geneeskunde, KRO gebouw niv.-1, Laarbeeklaan 101, 1090 Brussels, Belgium. N. McGregor, Collaborative Pain Research Unit, Department of Biological Sciences, Faculty of Science, University of Newcastle, Callaghan, New South Wales, Australia. K. De Meirleir, VUB, Vakgroep Interne Geneeskunde, KRO gebouw niv.-I, Laarbeeklaan 101, 1090 Brussels, Belgium. Address correspondence to: P. De Becker, AZ-VUB, KRO gebouw niv-1, Dienst Sportgeneeskunde, Laarbeeklaan 101, 1090 Brussels, Belgium (E-mail: mailto:pdbeck@minf.vub.ac.be ).
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.
KEYWORDS. Chronic fatigue syndrome, etiology, onset, infectious agents, triggering events
INTRODUCTION
CFS is diagnosed using a clinical case definition established in 1988 (1) and revised in 1994 (2). The major distinguishing symptom is debilitating fatigue of more than 6 month's duration associated with a marked decrease in daily activity, that cannot be attributed to any known medical cause, and a constellation of other non-specific symptoms.
Over the years, a large number of studies have been conducted to unravel the pathogenesis of CFS. CFS has been attributed to a variety of infectious agents, including Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), Cytomegalovirus, enteroviruses, retroviruses, stealth viruses, Borna virus and Ross River virus (3-13). However, the results of these studies are not consistent (14-19). Many of these viruses (EBV and HHV-6) are endemic within human beings with infections occurring early in life (4).
Therefore, new primary infection by these viruses is unlikely. Most evidence points to a reactivation of these endemic viruses, rather than primary infection (14,16,20.)
Not being able to identify a viral agent does not mean per se that a new viral infection did not take place. Levy proposed a "hit and run" effect, whereby, a virus might infect the host, cause immune abnormalities leading to CFS, and then be eliminated, leaving the immune system in an activated state (20). Alternate hypotheses suggest that bacterial stealth infections, including Brucella species (12), Mycoplasma species (21,22) and Chlamydia pneumoniae (23) may be important in patient morbidity. Thus, although it is clear that no single etiologic agent can be unequivocally associated with most cases of CFS, a number of infections do seem to precede the development of CFS.
Studies investigating the precipitating factors for CFS revealed a high percentage of patients who attributed their disorder to some kind of infectious agent. Salit reported that 72% of CFS patients reported an apparently infectious illness associated with the development of CFS (24). Earlier studies also reported a similar percentage of viral illnesses preceding the onset of CFS (13,25-28). Alternatively, other investigators have suggested that non-infectious factors may also play a role in the etiopathogenesis of CFS. In the three months to a year preceding CFS, stressful and negative life events took place very commonly in patients who later developed CFS (24,29). It is clear that there is no consensus among researchers and clinicians regarding the onset of CFS and there is a high degree of heterogeneity in the results.
As CFS is a defined condition with a definitive or sudden onset, it should be possible to trace the factors that may have been precipitants (24,30). In this study, we examined a large group of CFS patients and explored the events prior to the development of CFS. No attempt was made to identify any specific pathogen. In this descriptive study we report the various modes of onset in a large Belgian study population.
© 2002 by The Haworth Press, Inc. All rights reserved.
[Copies of the complete article are available for a fee from The Haworth Document Delivery Service: 1-800-HAWORTH. E-mail address: mailto:getinfo@haworthpressinc.com Website: www.HaworthPress.com ]
Perceptual and Motor Skills Vol. 93 (2): 486-504, October 2001
Robinson GL, McGregor NR, Roberts TK, Dunstan RH, Butt H Robinson GL, Univ Newcastle, Special Educ Ctr, Univ Dr, Callaghan, NSW 2308, Australia Univ Newcastle, Special Educ Ctr, Callaghan, NSW 2308, Australia
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.
(c) 2002 Perceptual and Motor Skills, Box 9229, Missoula, Montana
E. Stein, MD FRCP(C) Journal of Chronic Fatigue Syndrome, Vol. 8. No. 3/4. 2001. pp. 53-61
Affiliation: E. Stein is Staff Specialist in Psychiatry, Community Adolescent Team, The Junction, New South Wales. He [sic] is also Lecturer in Psychiatry, University of Newcastle, Callaghan, New South Wales.
The full text of Dr Ellie Stein's paper can be viewed at http://www.best.com/~cfids/Stein.pdf (412 kb) - Webmaster
SUMMARY. Context: Patients with Chronic Fatigue Syndrome and their physicians are often in conflict about the etiology and treatment of CFS.
Objectives: 1. Survey the literature regarding physician's attitudes towards CFS; 2. Examine the contributing factors to physician's attitude towards the disorder; and 3. Suggest solutions.
Data Sources: The relevant medical and psychological literature (years 1988-2000) was searched using the search term "Chronic Fatigue Syndrome." This was supplemented with papers from the bibliographies of the retrieved papers, additional related literature, and clinical experience.
Data Synthesis: Forty-six to ninety percent of GPs accept CFS as a discrete clinical entity and 30-82% are willing to make the diagnosis in qualifying patients.
Conclusions: CFS is a heterogeneous, multifactorial host response disorder that is inadequately described by the biomedical model. Despite substantial evidence of multisystemic physical abnormality in CFS, the lack of pathognomic tests and the female gender predominance cause some physicians to continue to treat CFS as a psychosocial disorder. This leads to conflict between patients and physicians. CFS challenges physicians to think beyond current disease models, to tolerate diagnostic and therapeutic uncertainty, and to work collaboratively with patients rather than taking the role of expert.
KEY WORDS. Attitudes, etiology, diagnosis
INTRODUCTION Despite a large and growing evidence of immune, endocrine, autonomic and cognitive dysfunction in CFS, a precise understanding of CFS etiology and mechanism has not yet been reached (1). Inadequate definition, the heterogeneous presentation of patients with CFS and physician's discomfort with disorders which do not conform to a linear biomedical model have contributed to uncertainty among physicians as to the legitimacy of CFS as a discrete medical entity. Many physicians continue to formulate and treat CFS as a psychosocial disorder. Patients, on the other hand, believe their problems to be primarily of physical origin and are dissatisfied with treatment that does not address physical issues. The objective of this paper is to review the literature about physician's attitudes towards CFS, to examine the contributors to these attitudes and to suggest solutions to the current impasse
Quantitative data was gathered through a search of the literature (MEDLINE and PSYCHLIT 1988-2000) using the search term "Chronic Fatigue Syndrome" in it. All abstracts (n > 1500) were searched. The full text of all relevant papers was retrieved. The bibliographies of the retrieved papers and the full holdings of the Journal of Chronic Fatigue Syndrome (not in Medline) were searched by hand. This paper is not intended as a thorough review of the etiology or treatment of CFS but does include relevant examples to highlight useful conceptions and some of the common misconceptions about the disorder.
[Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address: mailto:getinfo@haworthpressinc.com Website: http://www.HaworthPress.com ]
© 2001 by The Haworth Press, Inc. All rights reserved.
De Becker P, MCGregor N, De Meirleir K (VUB, Vakgroep Interne Geneeskunde, Brussels,
Belgium; and University of Newcastle, Callaghan, New South Wales, Australia).
J Intern Med 2001; 250: 234-240.
Abstract
Objective. The Holmes and Fukuda criteria are widely used criteria all over the world, yet a specific European study regarding chronic fatigue syndrome (CFS) patient symptomatology has not been conducted so far. This study was performed to answer the need to assess the homogeneity of a large CFS population in relationship to the Fukuda or Holmes definitions and to assess the importance of a symptom severity scale.
Design. Multivariate analyses were performed to assess the symptom presentation within a fatigued population and the differences between the Fukuda and Holmes definitions compared with an excluded chronic fatigued group in a large cohort of fatigued patients.
Setting. An outpatient tertiary care setting fatigue clinic in Brussels.
Main outcome measures. Prevalence and severity of symptoms and signs in a CFS population and in a chronic fatigued population.
Subjects and methods. A total of 2073 consecutive patients with major complaints of prolonged fatigue participated in this study. Multivariate analyses were performed to assess the symptom presentation and severity and the differences between the Fukuda and Holmes definitions.
Results. Of the 2073 patients complaining of chronic fatigue (CF), 1578 CFS patients fulfilled the Fukuda criteria (100% of CFS group) and 951 (60.3% of the CFS group) fulfilled the Holmes criteria. Discriminant function analysis revealed that the Fukuda and Holmes definitions can be differentiated by symptom severity and prevalence. The Holmes definition was more strongly associated than the Fukuda definition with the symptoms that differentiated the CFS patients from the patients that did not comply with the CFS definitions. The inclusion of 10 additional symptoms was found to improve the sensitivity/specificity and accuracy for selection of CFS patients.
Conclusions. The CFS patients fulfilling the Holmes criteria have an increased symptom prevalence and severity of many symptoms. Patients fulfilling the Fukuda criteria were less severely affected patients which leads to an increase in clinical heterogeneity. Addition of certain symptoms and removal of others would strengthen the ability to select CFS patients.
An investigation of the association between toxin-producing staphylococcus, biochemical changes and jaw muscle pain Neil R McGregor. University of Sydney (2000). [PDF]
Jed Gallagher wrote to Co-Cure:
The thesis investigates jaw muscle pain (temporomandibular disorder type 1a) in three patient groups and a control group. Group 1: patients with TMD type 1a muscle pain ONLY. Group 2: CFS patients WITH TMD type 1a muscle pain. Group 3: CFS patients WITHOUT TMD type 1a muscle pain.
All three patient groups were found to have nasal colonisation with toxin-producing coagulase-negative staphylococcus bacteria and coresponding urinary metabolite changes.
Dr McGregor's thesis proposes a completely new disease entity: coagulase-negative staphylococcal toxaemia.
In the summary chapter (chapter 5), he explains how the symptoms and "alternative" treatments for CFS are consistent with staph. toxaemia.
The Group 1 (jaw pain only) patients were given oral antibiotics: 45% were cured permanently of pain and staph. colonisation, 35% were pain-free during treatment but then relapsed following re-colonisation with staph, and 20% found no benefit.
Although not proposed in the thesis, the fact that jaw muscle pain is a co-morbid factor in CFS and FM but not present in all patients suggests that nasal co-ag negative staph L-forms (small-colony variants) may be involved in intracellular infection of jaw muscle. The wide-range of symptoms of CFS suggests that symptoms may be related to the different cell types infected with staph in individual patients.
Dr McGregors thesis is, in my opinion, the most important publication so far written on CFS/ME and I would urge everyone to read Chapter 5 at least.
Jed Gallagher
Wakefield, England
April 2002
Journal of Chronic Fatigue Syndrome, Vol. 7(1) 2000 pp. 3-21
Neil R. McGregor, MDSc; Suzanne Niblett, BSc; Phillip Clifton Bligh, MB BS, BSc (Mcd); R. Hugh Dunstan, DPhil; Greg Fuicher, MB BS, MD; Leigh Hoskin, MPH; Henry L. Butt, PhD; Timothy K. Roberts, PhD; Katrina King, PhD; Iven Klineberg, PhD
Affiliations: Neil R. McGregor, Suzanne Niblett, R. Hugh Dunstan, Henry L. Butt, Timothy K. Roberts and Katrina King are all affiliated with the Bioanalytical Research Group, Department of Biological Sciences, University of Newcastle, Callaghan, NSW 2308, Australia. Neil R. McGregor is also with the Neurobiology Research Unit, Centre for Oral Health Research, University of Sydney, Westmead Hospital, Westmead, NSW 2084, Australia. Phillip Clifton Bligh, Greg Fulcher, and Leigh Hoskin are affiliated with the Department of Endocrinology, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia. Iven Klineberg is affiliated with the Neurobiology Research Unit, Centre for Oral Health Research, University of Sydney, Westmead Hospital, Westmead, NSW 2084, Australia.
ABSTRACT. Background: Chronic pain and fatigue represent major reasons for seeking medical treatments, however, the mechanisms are poorly understood. Onset of these disorders has been associated with events (infections, trauma, stress) which initiate a host response requiring increased energy demands.
Objectives: To investigate the biochemical mechanisms of chronic pain and fatigue.
Methods: Data will be presented from 4 separate investigations of CFS and myofascial pain syndrome (MFPS) patients, and from age/sex-matched controls, using metabolite profiling techniques.
Results: Several types of chronic pain and fatigue disorders were discerned on the basis of their biochemistry. The metabolic events associated with chronic pain were distinct from those associated with chronic fatigue. The investigations have shown that chronic pain was associated with reductions in serum sodium, changes in urinary volume and output of amino and organic acids, increases in levels of markers of tissue damage (ALT, AST), and increases in the tyrosine: leucine ratio, which represents alterations in protein turnover. Fatigue was associated with alterations in urine excretion of amino and organic acids associated with tricarboxylic acid cycle (TCA) function. Levels of RNase-L were correlated with the expression of chronic fatigue related symptoms and were a good marker for CFS. Increased carriage of toxin-producing coagulase negative staphylococci was evident in MFPS and CFS patients, and this carriage was correlated with increased tyrosine: leucine ratios and pain severity. The toxin producing staphylococci appear to be a co-morbid pathogen that contributes to CFS patient morbidity.
Conclusion: These studies indicated that changes in nitrogen homeostasis were associated with pain and fatigue symptoms and carriage of certain pathogens may sustain or exaggerate the chronic disorder.
KEYWORDS. Nitrogen metabolism, RNase-L, staphylococci, tyrosine, chronic pain, fatigue
INTRODUCTION
Chronic pain and fatigue are major reasons for seeking medical treatment in general practice. The biochemical mechanisms leading to these symptoms are poorly understood. Three major diagnosed polysymptomatic illnesses are myofascial pain syndrome (MFPS) (1), fibromyalgia (FM) (2) and chronic fatigue syndrome (CFS) (3-5). Importantly these separate clinical conditions may occur in one patient and provides a significant problem in diagnosis and research. Bombardier and Buchwald (6) showed that of 402 patients who attended a fatigue clinic, CFS and FM were diagnosed in 52% and 22%, respectively. Thirty-seven percent had CFS alone, 7% FM alone whilst 15% had to have both CFS and FM. The patients with both CFS and FM had a greater disability than patients with CFS, major depression or acute infectious mononucleosis (7). Both FM and CFS patients have increases in myofascial pain and other common pain conditions. Plesh et al. (8) found that 18% of Temporomandibular Dysfunction (TMD) patients (1) had fibromyalgia whilst 75% of fibromyalgia patients had TMD symptoms. They concluded that TMD was a distinct disorder that occurred with increased prevalence in fibromyalgia patients. Our group has also reported that CFS patients have an increased prevalence of TMD and MFPS symptoms yet these conditions also occur in the normal general population. The findings of these studies (6,8) suggest that each of these clinically diagnosable conditions may be separate clinical conditions that simply occur with greater frequency in CFS patients and in turn increase morbidity and symptom heterogeneity.
Therefore, a major problem associated with diagnosis of CFS is the symptom and biochemical heterogeneity that may result from multiple confounding conditions such as MFPS and FM. Fukuda et al. (9) assessed Gulf war syndrome patients using factor analysis and found that three symptom groupings were present: (1) fatigue; (2) altered cognition and mood and; (3) musculoskeletal symptoms. Patients with CFS could be divided into those who suffered: (1) fatigue; (2) fatigue and pain; and (3) fatigue and mood change. The aim of this paper was to assess the differences in biochemistry between these different symptom sets.
© 2000 by The Haworth Press, Inc. All rights reserved
[Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address: mailto:getinfo@haworthpressinc.com Website: http://www.haworthpressinc.com ]
Journal of Chronic Fatigue Syndrome, Vol. 7(2) 2000, pp. 53-57
R. H. Dunstan, DPhil; N. R. McGregor, MDSc; T.K. Roberts, PhD; H. Butt, PhD; S.H. Niblett, BSc; T. Rothkirch, BSc Affiliation: Collaborative Pain Research Unit, Department of Biological Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.
ABSTRACT.
Background: The diagnosis of chronic fatigue syndrome (CFS) requires the exclusion of other known fatigue-related diseases because the core symptoms of CFS represent a general host response to many well-defined diseases. The patient set derived by this process is heterogeneous in their polysymptomatic presentation and has proved very difficult to study clinically and scientifically.
Objectives: To investigate the alterations in urine excretion and microbiology in patients with CFS.
Results: CFS patients had multiple anomalies in their amino acid and organic acid homeostasis. Sub-groups of CFS patients could be delineated on the basis of their urine excretion and their symptom presentation. The most common feature was an active muscle catabolism resulting in a depletion of amino acids and associated organic and keto-acids. The extent of muscle catabolism was directly correlated to pain severity. The carriage of toxin-producing coagulase negative staphylococci (MDT-C0NS) was strongly correlated with the catabolic response and pain severity.
Conclusions: An hypothesis has been constructed where an occult pathogen, such as MDT-CoNS, may be an aetiological agent contributing to the sustenance of a chronic fatigue/pain disorder, a comorbid pathogen. Urine analysis offers an opportunity for assessment of muscle catabolism and sub-classification of chronic fatigue patients leading to a number of management options. The detection of MDTCoNS identifies potentially treatable agents that contribute to the fatigue and pain condition.
KEYWORDS. Staphylococcus, toxin, pain, fatigue, urine
INTRODUCTION Chronic fatigue syndrome (CFS) represents a group of patients with a commonality of a prolonged severe and debilitating fatigue, for which there is no clear aetiology. However, the core symptoms of CFS (1) can be defined as host-response symptoms which occur when the body is challenged by potential pathogens and can be associated with a large number of disease states. Any cohort of CFS patients is therefore likely to represent a heterogeneous group of subjects varying in aetiology and symptom expression.
[Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address: mailto:getinfo@haworthpressinc.com Website: http://www.HaworthPress.com © by The Haworth Press, Inc. All rights reserved. ]
Archives of Internal Medicine Nov 27 2000; 160(21): 3270-3277
De Becker P, Roeykens J, Reynders M, McGregor N (Newcastle University, Australia), De Meirleir K -- Human Performance Laboratory and Department of Internal Medicine, Faculty of Physical Education and Physical Therapy, Vrije Universiteit Brussel
BACKGROUND: Patients with chronic fatigue syndrome (CFS) suffer from various symptoms, including debilitating fatigue, muscle pain, and muscle weakness. Patients with CFS can experience marked functional impairment. In this study, we evaluated the exercise capacity in a large cohort of female patients with CFS.
METHODS: Patients with CFS and matched sedentary control subjects performed a maximal test with graded increase on a bicycle ergometer. Gas exchange ratio was continuously measured. In a second stage, we examined only those persons who achieved a maximal effort as defined by 2 end points: a respiratory quotient of at least 1.0 and an age-predicted target heart rate of at least 85%. Data were assessed using univariate and multivariate statistical methods.
RESULTS: The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects. The maximal workload and maximal oxygen uptake attained by the patients with CFS were almost half those achieved by the control subjects. Analyzing only those persons who performed a maximal exercise test, similar findings were observed.
CONCLUSIONS: When compared with healthy sedentary women, female patients with CFS show a significantly decreased exercise capacity. This could affect their physical abilities to a moderate or severe extent. Reaching the age-predicted target heart rate seemed to be a limiting factor of the patients with CFS in achieving maximal effort, which could be due to autonomic disturbances.
Biochemical & Molecular Medicine 57:73-80 (1996)
Neil R. McGregor, R. Hugh Dunstan, Mariann Zerbes, Henry L. Butt, Timothy K. Roberts, Iven J. Klineberg
ABSTRACT Chronic fatigue syndrome (CFS/ME) is a debilitating fatigue illness that has an unknown aetiology. 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 amino-hydroxy-N-methyl-pyrrolidine (p<.00003, referred to as chronic fatigue symptom urinary marker 1, or CFSUM1), tyrosine (p<.02), (-alanine (p<.02), aconitic acid (p<.05) and succinic acid (p<.05) and reductions in an unidentified urinary metabolite, CFSUM2 (p<.0007), alanine (p<.005) and glutamic acid (p<.02). CFSUM1, (-alanine and CFSUM2 were found by discriminant function analysis to be the 1st, 2nd and 3rd most important metabolites, respectively, for discriminating between CFS and non-CFS subjects. The abundances of CFSUM1 and b-alanine were positively correlated with symptom incidence (p<.01 and p<.001, respectively), symptom severity, core CFS symptoms and SCL-90-R somatization (p<.00001) suggesting a molecular basis for CFS.
Biochemical & Molecular Medicine (1996) 58:85-92
Neil R. McGregor, R. Hugh Dunstan, Mariann Zerbes, Henry L. Butt, Timothy K. Roberts,
ABSTRACT Chronic fatigue syndrome (CFS) patients have 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. 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 symptom, cognitive, neurological, musculoskeletal,
gastrointestinal, infection-related and genitourinary symptom indices, as well
as a 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 and CFSUM1 excretion was the primary metabolite
for expression of this symptom. All 9 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 (R2) with changes
in the urinary excretion of metabolites (P<0.0001). CFSUM1 and beta-alanine
were the 1st and 2nd 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.
Med J. Australia 1995 163:294-297.
R. Hugh Dunstan, D Phil , Senior Lecturer Mark Donohoe1, MB BS, Medical Practitioner Warren Taylor, BSc, Research Assistant Timothy K. Roberts, PhD, Associate Professor Raymond N. Murdoch, PhD, Associate Professor Jennifer A. Watkins, BSc(Hon), Research Assistant Neil R. McGregor, MDSc, Periodontist
Abstract
OBJECTIVES: To determine whether chlorinated hydrocarbons are significantly elevated in serum from patients with chronic fatigue syndrome compared with healthy age- and sex-matched controls.
METHODS: Chlorinated hydrocarbon pesticides were measured in serum samples from patients with chronic fatigue syndrome (CFS, n=22) as defined by the Centres for Disease Control (CDC, Atlanta, USA). A 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 with those obtained from a group of non-CFS age- and sex-matched control subjects (n=34).
RESULTS: DDE (1,1-dichloro-2,2-bis (p-chlorophenyl) ethene) was detected in all serum samples at levels greater than 0.4pbb. The incidence of HCB (hexachlorobenzene) contamination (at levels >2.0 ppb) was 45% in the CFS group which was significantly higher than the 21% incidence observed in the non-CFS control group (P<.05). The CFS group had a significantly higher total organochlorine level (15.9 4.4 ppb) than the control group (6.31.1 ppb, P<.05). The toxic exposure group also had a higher mean organochlorine level (13.6 6.2 ppb) 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.
CONCLUSION: The levels of recalcitrant 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, 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.
Biochemical & Molecular Medicine (1996) 58:77-84
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
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 14 patients with unexplained and persistent fatigue were divided on the basis of * high or low total organochlorine content, * high or low DDE (1,1-dichloro-2,2-bis (p-chlorophenyl) ethene) content, and * 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<.017, (b) P<.015, and (c) P<.0002). As a variable, % neutrophils was the most important discriminant parameter for differentiating between the high and low total organochlorine groups. Thirteen of the 14 fatigued patients were char acterised as "high total organochlorine content" (P<.04). The red cell distribution width was elevated in the high DDE group (P<.04) and was the most important discriminant parameter for differentiating between the high and low DDE groups. The % eosinophils and the haemoglobin content were both reduced in the high HCB group (P<.009, P<.003, respectively) and % 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.
Australian information || Australian/NZ Research Links
the url for this page is www.masmith.inspired.net.au/aus_info/abstract.htm
Webmaster
last revised 5 Aug 2004