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Posted to Co-Cure Mon, 11 Dec 2000 15:52:35 -0500 by Fred Springfield

The Effectiveness of MCT in the Treatment of CFS

Full Title: A Preliminary Study into the Effectiveness of Multi-Convergent Therapy in the Treatment of Heterogeneous Patients with Chronic Fatigue Syndrome
Journal: Journal of Chronic Fatigue Syndrome, Vol. 7(1) 2000, pp. 93-101
Authors: Michael Sadlier, Dip Phil, MCSP, SRP; Jonathan R. Evans, MCSP, SRP; Ceri Phillips, PhD; Adrian Broad, MCSP, SRP
Affiliation: MCT Clinic, Physiotherapy Department, University Hospital of Wakes, UK, Heath Park, Cardiff CF4 4XW.
Address correspondence to: Michael Sadlier at the above address (E-mail:

In this preliminary study twenty-eight heterogeneous Chronic Fatigue Syndrome (CFS) patients were treated with Multi-Convergent Therapy (MCT). This form of therapy has been used successfully for over ten years in the treatment of Irritable Bowel Syndrome, Tinnitus, Hyperventilation Syndrome, Chronic Pain and Anxiety Disorders.

This small study was undertaken to assess whether MCT is effective in the treatment of CFS and to examine whether a more extensive investigation is warranted. Due to heterogeneity of symptoms, outcome measures were established on the basis of a shared decision-making process between patient and therapist. One patient dropped out of the study. All twenty-seven remaining patients achieved significant recoveries. Twelve patients recorded a mean improvement on baseline symptoms of 61%, eight patients who completed a Quality of Life questionnaire demonstrated a mean change from 2.4 to 6.3 (out of 10). Five patients reported a return to full normal function and two patients returned to school or work and regular exercise. At follow up nine-months to one-year later all eighteen patients who responded reported either continued improvements or maintenance of a well state.

The findings of this study support the use of MCT in the management of patients with Chronic Fatigue Syndrome and justify the implementation of a major clinical trial.

KEYWORDS. Multi-Convergent Therapy, chronic fatigue syndrome, heterogeneous, acceptability, shared decision-making


Physical and mental fatigue of a severe disabling nature is the hallmark of Chronic Fatigue Syndrome (CFS). The symptoms are exacerbated by minimal exertion and no satisfactory explanation for the condition exists. The prognosis is uncertain, with the lay literature suggesting an incurable lifelong course whilst others report that recovery usually occurs (1). Increasing length of time suffered and a rising number of associated symptoms appear to worsen the prognosis (2).

The extent of the problem and the lack of appropriate management of many patients were highlighted in a recent National Task Force report (3). The report called for specialist paramedical therapists to support GPs and, importantly, to oversee the management of those patients whose needs cannot be met within primary care.

Promising results from several studies have been produced but these have been for limited patient groups and even within these studies outcomes have varied widely according to the type of patient seen (4-6). The heterogeneous nature of CFS sufferers remains a stumbling block in the development of management strategies. Typically, and perhaps not surprisingly, those patients with longer histories coupled with psychological and/or sleep problems seem not to do so well as patients without these additional complications. Some commentators have pointed out that perhaps there are several sub-groups among CFS and that whilst an approach might work for one group it may have little effect on another.

The debate about aetiology will no doubt continue, meanwhile Deale et a!. (7) have called for a pragmatic approach to CFS in the community where time, reduced funds, a limited number of trained specialists and the existence of heterogeneous symptoms are difficult to control for. The approach needs to have the flexibility to allow for the manifold presentation of CFS, and yet be malleable enough to be tailored to suit each individual patient. Importantly, the approach has to be acceptable to all stakeholders, especially the patients.

Multi-Convergent Therapy (MCT) could well be such an approach. Demonstrated to be clinically effective over 10-year period in the treatment of Irritable Bowel Syndrome (8) refractory to medication and severe Tinnitus, (9) MCT combines aspects of Cognitive Behavioural Therapy (CBT), Connective Tissue Massage (10), Meditation, and Fitness Training. Additionally, therapists from the MCT clinic interact closely with referring agents on the use of relevant medication (psychotropics included) where appropriate. The advantage of having one person as Change Master working in close liaison with the referring agent is the speed at which any strategic drift can be corrected.

The aim of this pilot study was to provide an initial evaluation of the role of MCT in the management of patients with CFS. In particular it was intended to establish whether MCT was acceptable to patients and support groups by seeing if patients would remain in therapy.

Selection Criteria:
Twenty-eight patients were included in the study, nine male and nineteen female. Age range nineteen to seventy-six years (mean 38, SD 15.5). Twenty-four out of the twenty-eight patients were recruited from a Chronic Fatigue Clinic. The remaining patients were referred from Rheumatology, Neurology and Psychiatry. All patients met operationalized ‘Oxford’ research criteria (11). They also met the CDC criteria 1994.

© 2000 by The Haworth Press, Inc. All rights reserved.

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Posted to Co-Cure Tue, 5 Dec 2000 19:00:39 -0500 by Fred Springfield

Immunologic Status Correlates with Severity of Physical Symptoms and Perceived Illness Burden in CFS

Full Title: Immunologic Status Correlates with Severity of Physical Symptoms and Perceived Illness Burden in Chronic Fatigue Syndrome Patients
Journal: Journal of Chronic Fatigue Syndrome, Vol. 7(1) 2000 pp. 39-52
Authors: Stacy E. Cruess, PhD; Nancy Klimas, MD; Michael H. Antoni, PhD; Lynn Helder, PhD; Kevin Maher, PhD; Robert Keller, MD; Mary Ann Fletcher, PhD
Stacy E. Cruess and Michael H. Antoni are affiliated with the Department of Psychology, University of Miami. Michael H. Antoni is also with the Department of Psychiatry and Behavioral Sciences, University of Miami.
Nancy Klimas, Kevin Maher and Mary Ann Fletcher are affiliated with the Department of Medicine, University of Miami.
Lynn Helder and Robert Keller are affiliated with Biodoran Medical Center, Ft. Lauderdale, FL.
Address correspondence to: Nancy Klimas, MD, 200 BMRC - Section 6D, c/o VA Medical Center, 1201 NW 16th Street, Miami, FL 33125.

The purpose of the present study was to investigate the relationship between immunologic status and physical symptoms in Chronic Fatigue Syndrome (CFS) patients. Twenty-seven patients diagnosed with CFS were included. Participants completed a questionnaire including selected subscales of the Sickness Impact Profile, the Cognitive Difficulties Scale, and frequency and severity of CFS-related physical symptoms. Cellular immune markers measured included number and percent of T-helper/inducer cells (CD3+CD4+), T-cytotoxic/ suppressor cells (CD3+CD8+), activated T-lymphocytes (CD26+CD2+ CD3+), activated T cytotoxic/suppressor cells (CD38÷HLA-DR+CD8+), and CD4/CD8 ratio. Spearman’s correlation coefficients revealed significant associations between a number of immunologic measures and severity of illness suggesting that the degree of cellular immune activation was associated with the severity of CFS-related physical symptoms, cognitive complaints, and perceived impairment secondary to CFS. Specifically, elevations in T-helper/inducer cells, activated T-cells, activated cytotoxic/suppressor T-cells, and CD4/CD8 ratio were associated with greater severity of several symptoms. Furthermore, reductions in T-suppressor/cytotoxic cells also appeared related to greater severity of some CFS-related physical symptoms and illness burden. Multiple regression analyses demonstrated that decreased percentage of CD3+CD8+ cells and increased number of CD38+HLA-DR+CD8+ cells were the strongest predictors of total illness burden and fatigue severity, accounting for almost 30% of the variance in these measures.

KEYWORDS. Chronic fatigue syndrome, immune activation, symptom severity

Recent research indicates the prevalence of Chronic Fatigue Syndrome may be greater than had been previously estimated, with over 800,000 afflicted with the condition in the United States alone (1). The symptoms of this potentially debilitating syndrome are often the result of a sudden-onset illness with “flu-like” symptoms that persist over time (2) including unexplained persistent or recurrent fatigue. Symptoms such as arthralgias, myalgias, headaches, tender lymph nodes and a sore throat are also common (3). Although the exact etiology of CFS is not known at this time, it has been suggested that the clinical symptoms of CFS are a result of chronic immune system activation and the over-production of cytokines (4).

However, research examining immune activation in individuals with CFS has yielded mixed results. Of the studies that have documented differences from healthy comparison groups, some of the immune abnormalities observed include decreased natural killer cell cytotoxicity (NKCC), decreased proliferative responses to plant mitogens, decreased gamma interferon production, increased number of activated lymphocytes, increased neopterin, and decreased DTH skin responses (e.g., 5-11). Other identified abnormalities have included decreased naïve T lymphocytes, increased adhesion molecules in memory cells, decreased lymphocyte proliferation in response to antigenic challenge (12), persisting T suppressor cell activity (13), and suppressed immunoglobulin production (14). However, other researchers have failed to find evidence of immune activation in CFS patients when compared to normals or case controls (e.g., 15-17). Furthermore, in studies where there are significant differences between CFS patients and normal controls, patterns of abnormalities have been fairly consistent for only a few immune markers (e.g., activated cytotoxic T cells, NKCC) (4).

The influence of illness-related variables such as length of illness and symptom severity at the time of immunologic assessment may account for some of these discrepancies, as CFS often presents with symptom exacerbations and remissions that cycle over time. For example, Mawle and colleagues (15) found few immunologic differences between CFS and control patients, but did observe more pronounced differences between groups when the patients were broken down by gradual versus sudden onset, length of illness, and how well they were feeling on the day of the assessment. Specifically, patients with a sudden-onset illness demonstrated decreased proliferative response to a candida antigen and produced increased levels of IL-2 and CD8 cells expressing the CD11b marker (often seen in acute infection) than matched controls (15). Immunologic status also varied as a function of symptom status. Those patients feeling ill on the day of assessment produced higher levels of IL-2 and lower levels of IL-6 and CD8 cells expressing the activation marker CD25 (15). In addition, several other studies have found relationships among CFS symptoms and immunologic function, such as natural killer cell activity (18), as well as among illness burden/quality of life and HLA-DR and CD28 marker expression (19). However, several other studies have failed to find such relationships (e.g., 17,20).

The purpose of the present study was to help clarify the relationship between immunologic activation and physical symptoms in individuals diagnosed with CFS using a 3-color panel of lymphocyte populations and self-report measures of symptom severity, symptom frequency, and perceived illness burden. In particular, we chose to examine specific activated lymphocyte subsets as well as overall levels of circulating CD4 and CD8 lymphocytes to investigate the theorized relationship between immunologic activation and ongoing CFS-specific clinical symptoms and illness burden.

[Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address: Website: ]

© 2000 by The Haworth Press, Inc. All rights reserved.

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Posted to Co-Cure Fri, 1 Dec 2000 12:29:05 +0100 by Dr. Marc-Alexander Fluks

Ocular manifestations in chronic fatigue syndrome

Full Title: Ocular manifestations in chronic fatigue syndrome
Authors: Mastropasqua L, Ciancaglini M, Carpineto P, Iezzi A, Racciatti D, Falconio G, Zuppardi E, Pizzigallo E
Journal: Annals of Ophthalmology 32: (3) 219-224 Fall 2000
Affiliations: Univ Chieti, Inst Ophthalmol, Chieti, Italy
Univ Chieti, Clin Infect Dis, Chieti, Italy.

A case-control masked study was performed in 37 patients with chronic fatigue syndrome (CFS) to evaluate ocular signs, symptoms, and functional parameters. A significant association was found between CFS and blurred vision at near, foggy vision, shadowed vision, headaches, and photophobia. Blurred vision, foggy vision, and headaches were associated with abnormal oculomotor function, and shadowed vision and photophobia were associated with tear deficiency. These data suggest that CFS affects the ocular system.

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Posted to Co-Cure Mon, 20 Nov 2000 18:48:25 -0500 by Fred Springfield

Chronic Fatigue Syndrome and Cancer

Full Title: Chronic Fatigue Syndrome and Cancer
Journal: Journal of Chronic Fatigue Syndrome, Vol. 7(1) 2000 pp. 29-38
Authors: Paul H. Levine, MD; Deborah Pilkington, RN; Paula Strickland, PhD; Daniel Peterson, MD
Paul H. Levine and Paula Strickland are affiliated with the George Washington University School of Public Health and Health Services, Washington, DC.
Deborah Pilkington and Daniel Peterson are affiliated with Sierra Internal Medicine Associates, Incline Village, NV.
Address correspondence to: Paul H. Levine, MD, George Washington University School of Public Health and Health Services, Washington, DC 20037 (E-mail:

Several studies have indicated a link between chronic fatigue syndrome (CFS) and cancer, most of them based on anecdotal observations. We have attempted to use more population-based data to determine if the reported relationship is meaningful. Two outbreaks of a fatiguing illness which included well documented cases of CFS were evaluated ten years after the reported outbreak for long-term effects, particularly cancer. We found an unusual pattern of cancer which, in view of an increased incidence of brain tumors and non-Hodgkin’s lymphoma (NHL) reported in other studies involving CFS, indicates the need for further study. At the present time this link, which is often presumed to be due to immune dysfunction, has not yet been documented. Not all CFS patients have apparent dysregulation of the immune system and a single causative agent is highly unlikely, making the study of two heterogeneous illnesses, CFS and cancer, highly problematic. With the continuing focus on subgroups, however, this area of research may prove to be more productive.

KEYWORDS. Cancer, chronic fatigue syndrome, Epstein-Barr virus, human herpesvirus-6, natural killer cells

INTRODUCTION Chronic fatigue syndrome (CFS) is currently defined by a case definition derived from clinical experience rather than systematically collected data (1). It is apparent to both clinicians and laboratory investigators that the recognition of CFS as a syndrome does not imply a single etiology or a single pathogenesis. We have recently utilized a cohort of 30,000 veterans to show that factor analysis can be an important tool in distinguishing different entities of possible etiologic importance in Gulf War Syndrome (2), another disorder that shares with CFS the absence of objective signs or laboratory tests, and subsequently identified by factor analysis three distinct subgroups of CFS in this same cohort (3). Therefore we agree with those investigators who believe that CFS is a heterogeneous disorder which contains many different subtypes with different clinical patterns and different laboratory features.

One of the subtypes that has been well recognized is CFS associated with immune dysfunction (4-9). The laboratory test most consistently identified as being abnormal in CFS patients, the natural killer (NK) cell assay (4-7), involves a part of the immune system apparently related to control of cancer cells (10). Early epidemiologic studies also suggested a link between CFS and cancer (6,7), leading to our interest in studying well described outbreaks of fatigue (11,12) which resulted in patients developing CFS (13,14).

In order to evaluate this potential association on a systematic basis, we followed up the outbreak of the fatiguing illness in northern Neva da/California (11,13) and, using data from a population based Nevada Cancer Registry, noted an increased rates of brain tumors and NHL in northern Nevada, where the outbreak was reported, as compared to a control population of similar composition in southern Nevada, where no similar illness was reported (15). Since our report with the Nevada Cancer Registry was not able to focus on patients with CFS, we subsequently turned to a ten-year follow-up of the outbreak (16) to determine if we could see an association between CFS and cancer in this particular cohort.

While previous reports have suggested that CFS may predispose to cancer (6,7), these reports are anecdotal. CFS is now more often considered an immunologic or endocrinologic disorder (17) rather than an infectious disease, although it frequently is reported as a consequence of infection. The best documented precipitating agent is Epstein-Barr virus (EBV) (18-20), which is suspected of causing a number of human tumors (21), but CFS also has been noted to occur after infection with a variety of other organisms, including cytomegalovirus, human herpesvirus-6 (HHV-6), and giardiasis (22). Apparent outbreaks of infectious disease, often described as epidemic neuromyasthenia (23-25), have resulted in a significant number of cases meeting the criteria for CFS (13,14). In this report we describe an unusual pattern of cancer in the cohort identified in northern California/Nevada.

Reported in part at the Second World Congress on Chronic Fatigue Syndrome, Brussels, Belgium, September 9-11, 1999.

[Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678.   E-mail address:   Website:]

© 2000 by The Haworth Press, Inc. All rights reserved.

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Posted to Co-Cure Sun, 10 Dec 2000 18:13:54 -0500

Depression in Medical Illness: The Role of the Immune System

Full Title: Depression in Medical Illness: The Role of the Immune System
Journal: West J Med 173(5):333-336, 2000. © 2000 BMJ, Inc.
Author: Raz Yirmiya
Affiliation: Department of Psychology, Hebrew University of Jerusalem, Mount Scopus Jerusalem 91905, Israel.
E-Mail: Correspondence to: Prof Yirmiya
Funding: Supported by grant 94-204 from the United-States-Israel Binational Science Foundation, the German-Israeli Foundation for Research and Development, and the Eric Roland Center for Neurodegenerative Diseases.


Many interactions occur between the immune, neural, and psychological systems. These interactions include communication pathways from the brain to the immune system, particularly the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system, that mediate the influence of psychological variables, such as stress and emotions, on immunity and resistance to disease.[1]

In addition, when the body is confronted by pathogens, the immune system serves as a sensory organ, alerting the brain to the presence of infection-induced immune activation.[2] The communication from the immune system to the brain is mediated by cytokines, which are peptides that orchestrate the immune response with a wide range of other biologic activities. During immune stimulation, cytokines such as interleukins and interferons are produced both in the periphery and in the brain, where they can affect neural, neuroendocrine, and behavioral functions through specific receptors.[2, 3]

In addition to physiologic responses, such as fever, and hormonal responses, such as activation of the HPA axis, brain cytokines also produce behavioral changes. A person with a physical illness may show depressed mood, anorexia, weight loss, sleepiness and altered sleep patterns, fatigue and retardation of motor activity, reduced interest in the physical and social environment, and impaired cognitive abilities.[3, 4] During an acute infection, these behavioral symptoms, collectively termed "sickness behavior," are considered to be an adaptive response, rather than due to the disease process itself and the fever that accompanies it. However, during chronic infections and other chronic medical conditions associated with intense immune activation, the sickness behavior syndrome can develop into a depressive episode. Illness-associated depression can cause high levels of distress in a sick person and may further complicate the existing physical symptoms and compliance with therapy.

In this review, I present the current knowledge on the role of cytokines in mediating the depressive symptoms that accompany various medical conditions. I also consider the possible use of antidepressant drugs—and their mechanism of action—in the treatment of illness-associated depression.

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Posted to Co-Cure Sun, 12 Nov 2000 20:41:58 -0500 by Fred Springfield

The Development of Laboratory-Based Tests in Chronic Pain and Fatigue...

Full Title: The Development of Laboratory-Based Tests in Chronic Pain and Fatigue: 1. Muscle Catabolism and Coagulase Negative Staphylococci Which Produce Membrane Damaging Toxins
Journal: Journal of Chronic Fatigue Syndrome, Vol. 7(1) 2000 pp. 23-27
Authors: R. H. Dunstan, DPhil; N. R. McGregor, MDSc; T. K. Roberts, PhD; H. Butt, PhD; S. H. Niblett, BSc; T. Rothkirch, Dip App Sc
Affiliation: Collaborative Pain Research Unit, Department of Biological Sciences, University of Newcastle, Callaghan, NSW 2308, Australia

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 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-CoNS) 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. Staphylococci, muscle catabolism, chronic pain, fatigue


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.

© 2000 by The Haworth Press, Inc. All rights reserved
Dedicated to the memory of Alison Hunter.

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Note: All abstract summaries, unless otherwise noted, were prepared by Margaret Bailey.

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