Articles journal of chronic fatigue syndrome

Table of Contents for Volume: 13 Issue: 1

zondag 3 september 2006, 6:00:00

Cover Date: 2006
Publication Date: 2006
Copyright Date: 2006

Article: EDITORIAL

Article: Prevalence of Chronic Fatigue Syndrome and Chronic Fatigue Within Families of CFS Patients
The prevalence of CFS (Chronic Fatigue Syndrome) and chronic fatigue were investigated in family members of CFS patients using a questionnaire-based study. Significant differences were seen between the prevalence of CFS in all groups of family members relative to the published community prevalence of 0.422% (spouses/partners: 3.2%, p < 0.001; offspring: 5.1%, p < .001; parents and siblings: 1.1%, p < 0.02; second and third degree blood relatives 0.8%, p < 0.02). The prevalence of CFS was higher in genetically unrelated household contacts and in nonresident genetic relatives than in the community, indicating that both household contact and genetic relationship are risk factors for CFS.

Article: Unexplained Prolonged Fatigue in Primary Care
Background: Unexplained prolonged fatigue (UPF) is one of the most common complaints in primary care. UPF is difficult to manage because of its nonspecific nature and unknown mechanism. UPF frequently frustrates health care professionals and has negative impacts on the physician-patient relationship. Although it is nonfatal, fatigueassociated functional impairments and economic consequences are substantial, negatively impacting patients' quality of life. Objectives: To evaluate current knowledge development of UPF and to help focus the direction of future investigations. Methods: A literature review was undertaken with the MEDLINE databases chosen as the primary electronic resources to retrieve the literature. Results: Current understanding of UPF is limited. Lack of consistent scientific language is a major problem. There is no consensus about the case definition of UPF even for the most widely studied chronic fatigue syndrome (CFS). Various sets of classification have been developed, each with similar but not identical criteria. Clinicians are dubious about perceiving fatigue as a clinical entity and ignore the diagnosis criteria. Many more patients are excluded than included from the current classifications and lack appropriate evaluation and treatment. The predisposing factors are not well established with the exception of being female and relatively young. Laboratory testing and immune and endocrine abnormalities are inconsistent in determining the causes. Psychological and social factors play an important but inconclusive role in mediating fatigue status. Conclusions: The high prevalence, persistence, and disability-associated consequences of UPF warrant more attention. Further investigations of the symptoms, psychosocial-based symptom experiences, and a search for effective management are needed.

Article: Antibodies to Herpes Simplex Types 1 and 2 in Chronic Fatigue Syndrome
Background. It has been suggested that Herpes simplex virus (HSV) could play a role in the aetiology of chronic fatigue syndrome (CFS). An immune system that has been compromised, could account for HSV reactivating or infecting for the first time, and also being insufficiently under control in the body. Another consequence of inadequate control could be that several strains of HSV could simultaneously infect the body. Objectives. To look for the presence of antibodies to HSV-1 and HSV-2 in patients with CSF and in controls. The presence of antibodies to both types of HSV could reflect infection by multiple strains of HSV. Methods. Antibodies to HSV-1 and HSV-2 were measured in sera from 27 CSF patients and 26 ageand sex-matched controls. CFS was diagnosed using the CDC criteria. Results. More CFS patients had antibodies to HSV-1, HSV-2 and both types simultaneously, than did the controls (all p < .019). Conclusions. More CFS patients have antibodies to both HSV-1 and HSV-2 than do controls. The possibility that multiple strains could

Article: Rehabilitation Programs for Individuals with Chronic Fatigue Syndrome A Review
Over the past two decades, a small but growing number of rehabilitation programs for individuals with chronic fatigue syndrome (CFS) have been initiated. The aims of this paper were to review existing literature on these programs, to compare and contrast findings emerging from inpatient and outpatient programs, and to comment on the rigor and quality of methodologies used in outcomes research in this area. The studies reviewed herein varied widely in case selection criteria, program intensity, length of participation, program content, and outcome variables measured. Moreover, many were limited by selection bias, the absence of valid and reliable measures, and the absence of a control group. These limitations made it difficult to draw definitive conclusions regarding the effectiveness of any single approach to rehabilitation (whether inpatient or outpatient). However, there is some preliminary evidence that both inpatient and outpatient rehabilitation programs may lead to improvements in physical and occupational functioning, decreased perception of symptom severity, improved quality of life, and greater resource acquisition-at least for certain subgroups of individuals with CFS that participate in specific types of programs. Taken together, these preliminary findings support the need for additional funding and support for the development of comprehensive rehabilitative program centers that include both inpatient and outpatient programs with follow-up sessions and ongoing evaluation. Recommendations for future program development and outcomes research in this area are discussed.

Article: Lipid Replacement and Antioxidant Nutritional Therapy for Restoring Mitochondrial Function and Reducing Fatigue in Chronic Fatigue Syndrome and Other Fatiguing Illnesses
Evidence in the literature indicates that diminished mitochondrial function through loss of efficiency in the electron transport chain caused by oxidation occurs during aging and in fatiguing illnesses. Lipid Replacement Therapy (LRT) administered as a nutritional supplement with antioxidants can prevent oxidative membrane damage, and LRT can be used to restore mitochondrial and other cellular membrane functions via delivery of undamaged replacement lipids to cellular organelles. Recent clinical trials using patients with chronic fatigue have shown the benefit of LRT plus antioxidants in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue. These studies indicate the benefits of LRT plus antioxidants in reducing fatigue and preventing loss of mitochondrial function, most likely by protecting mitochondrial and other cellular membranes from oxidative and other damage and removing damaged lipids by lipid replacement. In one clinical study we determined if mitochondrial function is reduced in subjects with mild to severe chronic fatigue, and if this can be reversed with NT Factor(r), a nutritional supplement that replaces damaged cellular lipids. With the use of the Piper Fatigue Scale, there was a significant time-dependent reduction in overall fatigue in moderately or severely fatigued subjects while on the dietary supplement for 4-8 weeks. Analysis of mitochrondrial function indicated that four and eight weeks of the dietary supplement in moderately or severely fatigued subjects significantly increased mitochondrial function. Similarly, chronic fatigue syndrome patients administered antioxidants plus LRT also show reductions in fatigue. The results indicate that LRT plus antioxidants can significantly reduce moderate to severe chronic fatigue and restore mitochondrial function. Dietary use of unoxidized membrane lipids plus antioxidants is recommended for patients with moderate to severe chronic fatigue.

Article: Chronic Fatigue Syndrome: Editorial Bias in the British Medical Journal

Article: Response to the Letter to the Editor

Table of Contents for Volume: 12 Issue: 4

dinsdag 4 oktober 2005, 6:00:00

Cover Date: 2004
Publication Date: 2005
Copyright Date: 2004

Article: EDITORIAL

Article: Cognitive Function Index for Patients with Chronic Fatigue Syndrome
Background: A comprehensive approach to assessing neuropsychological deficits in CFS patients is developed by assessing cognitive function across a number of domains using a battery of tests, rather than relying on any single instrument. Objective: A factor analytic approach was employed to examine the underlying dimensionality of 15 standard cognitive function related test variables in CFS patients. A cognitive function index (CFI) was then developed using appropriately weighted and interpreted factors. Methods: Factor analysis was applied to an initial sample of 65 CFS patients, identifying eight factors accounting for over 70% of total variation. This factor structure was then independently verified on a separate sample of 124 CFS patients. An overall combined CFS sample of 212 was then used to derive the CFI using an appropriately interpreted and weighted average of the derived factors. Results: After including age and education as separate factors, the CFI consists of nine factors accounting for 70% of total variation in the overall CFS group. The CFI was not affected by the presence of current psychiatric comorbidity. A cut-off score for cognitive dysfunction was established using the lower quartile value of a group of sedentary controls on the same index. Conclusions: The CFI will provide a useful summary measure for researchers investigating cognitive function performance in CFS patients. It does not replace existing individual specialized tests.

Article: Family Medical History of Persons with Chronic Fatigue Syndrome
Background: Little research has examined the family history of persons with CFS, although a few studies have found people with CFS may be more likely to have family members with fatigue or CFS-like conditions, cancers, autoimmune illness, and early parental death. Research into the family history of fatigue, chronic fatigue syndrome, and other medical or psychiatric illness may help inform the etiology of this illness. Objectives: The present investigation examined the occurrence of medical and psychiatric illness in the family history of persons with CFS, and then compared these results with the family history of medical illness reported by a control group of persons without fatigue. Methods: Family medical history data was obtained from questionnaire responses, a medical assessment, and medical records, and were then classified into specific illness categories, using the International Classification of Diseases, Tenth Revision (ICD-10). Family history data was compared among three groups using logistic regression analyses. Results: Results indicated that persons with chronic fatigue syndrome were significantly more likely to report a family history of endocrine/ metabolic disorders when compared to the control group. Conclusions: Findings suggest an underlying familial predisposition toward the development of both CFS and endocrine/metabolic disorders. This finding is consistent with the hypothesis that CFS represents a deregulation of the endocrine system.

Article: Hypnosis in the Management of Chronic Fatigue Syndrome
During the past 30 years hypnosis has become recognised as a useful adjunct to traditional medical therapies, and has become part of mainstream medicine. Hypnosis societies provide training for health professionals to obtain registrable qualifications. The modality has been incorporated in the management of many medical conditions and diseases, with opportunities for symptom control, building confidence and enhancing the benefits of regular therapies. There are many opportunities for using hypnosis as an adjunctive therapy in the management of Chronic Fatigue Syndrome, despite some early difficulties. Problems likely to be encountered are discussed and the structure of the hypnosis session is outlined. Suggestions are given for practitioners to construct useful scripts, which can be used to teach self-hypnosis.

Article: Chronic Fatigue Syndrome Editorial Bias in the British Medical Journal
A literature search identified all papers published on chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) in the British Medical Journal between 1995 and 2000. Analysis of the findings revealed a bias towards the views of one school of thought and a lack of papers on the immunological or virological aspects of CFS. This contrasts with the mainstream American journals, which generally covered a much wider range of subjects and views. We examine the arguments for and against covert editorial policies, and summarise the results of discussions with the relevant individuals and organisations.

Article: Report on the AACFS 7th International Conference

Table of Contents for Volume: 12 Issue: 3

dinsdag 4 oktober 2005, 6:00:00

Cover Date: 2004
Publication Date: 2005
Copyright Date: 2004

Article: EDITORIAL

Article: Major Depressive Disorder in Chronic Fatigue Syndrome A CDC Surveillance Study
Background: Controversy continues to exist as to whether Chronic Fatigue Syndrome is a psychological/psychiatric disorder. To further understand this condition the Centers for Disease Control (CDC) conducted a Surveillance Study. The CDC partitioned 565 subjects with fatiguing illnesses into four diagnostic groups, one of which met the 1988 CDC criteria for CFS. The non-CFS groups had either insufficient severity (idiopathic), medical exclusions or prior psychiatric disorders. Objectives: The present study reports on the psychiatric features in that study, estimates the time of onset of Major Depressive Disorder (MDD) and looks for possible relationships between 1988 CDC criteria for Chronic Fatigue Syndrome and psychiatric disorders. Methods: The study design is cross-sectional. The Diagnostic Interview Schedule (DIS) assessed for four Axis I psychiatric disorders. Time of onset ofMDDwas estimated from the DIS and validated by an examination of the medical records. Odds ratios and confidence intervals were calculated as tests of association between 1988 CDC criteria and psychiatric disorders. Results: Subjects classified as CFS and non-CFS had similar rates of psychiatric disorders. A minority of subjects had preexisting MDD. Three 1988 CDC criteria were associated with current MDD whilst no criteria were associated with prior MDD. Conclusions: CFS subjects did not demonstrate any unique patterns of psychiatric disorders. MDD may not be an important predisposing factor for CFS or the other fatiguing illnesses. Some 1988 CDC criteria may be preferentially endorsed by subjects with current MDD.

Article: Membrane Damaging Toxins from Coagulase-Negative Staphylococcus Are Associated with Self-Reported Temporomandibular Disorder (TMD) in Patients with Chronic Fatigue Syndrome
Aim: To assess whether there is any association between membrane damaging toxin production by Staphylococcus spp. and self-reported TMD symptom expression in a group of patients selected to have CFS. Methods: Thirty-three defined Chronic Fatigue Syndrome (CFS) patients and 33 ageand sex-matched controls were assessed to evaluate the relationship between carriage of membrane damaging toxin producing staphylococcus, CFS and temporomandibular dysfunction (TMD) symptoms. Results: The CFS patients had an increased prevalence of face pain (Odds Ratio = 21.0, 95% CL 4.2-106, P < .001) and temporomandibular joint (TMJ) clicking/locking (OR = 5.7, 95% CL 1.423.5, P < .007), and the coagulase-negative staphylococcus maximum% B*-toxin haemolysis per patient. Both multivariate and univariate analyses revealed an association between the membrane damaging o*-toxin producing CoNS (MDT-CoNS) species per subject and face pain prevalence and intensity within both the CFS patients and the control subjects. No association was found between CoNS toxin production and TMJ clicking/locking. Importantly, and B*-toxin production by CoNS was associated with patient reporting of arthritis. Conclusions: These data confirm the original observations of the association between MDTCoNS and facial muscle pain (Butt et al, 1998; McGregor et al, 2003). These data also suggest that MDT-CoNS associated facial muscle pain expression represents a distinct clinical entity, which has an increased prevalence in CFS patients.

Article: Association Between Oxidative Damage Markers and Self-Reported Temporomandibular Dysfunction Symptoms in Patients with Chronic Fatigue Syndrome
Full blood counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), haematinics and markers for oxidative stress were measured on thirty-three patients diagnosed with chronic fatigue syndrome (CFS) and twenty-seven age and sex matched controls. The CFS patients had increased prevalence of symptoms of temporomandibular dysfunction (TMD). Jaw muscle pain was associated with increases in methaemoglobin (P < .002), ferritin (P < .02) and malondialdehyde (P < .007) whilst temporomandibular joint (tmj) clicking and/or locking was associated with increases in methaemoglobin (P < .001), malondialdehyde (P < .05) and vitamin B₁₂ (P < .02) levels. Multiple regression analysis found methaemoglobin to be the principle component associated with TMD symptoms in the CFS patients. Increases in scalar severity responses to jaw muscle pain and TMJ clicking and/or locking were positively correlated with methaemoglobin by multiple regression. These data indicate that oxidative stress due to excess free radical formation was associated with jaw muscle pain in CFS patients and suggest that these symptoms were likely to be associated with a pathogen-associated aetiology.

Article: The Influence of Chronic Fatigue Syndrome on the Personality Profile A Case Report
Objective: Chronic fatigue syndrome (CFS) functionally impairs many patients. Despite numerous studies and reviews in CFS, little is known about the behavioral consequences. Several researchers have already suggested the influential role of personality as a possible predisposing or perpetuating factor. Method: Acase study is presented of a 34-year-old man with a history of CFS. Psychological profiling using the MMPI-2 was performed during the course of his condition. Results: His passive-aggressive manner during the medical encounter was underscored by his personality profile (code type 3-2). After his recovery, however, a spike 3 profile emerged indicating a fulfilled individual. Somatic items included in the inventory, created a secondary increase of the clinical scales. Physical complaints diminished as his condition improved and subsequently, decreased the clinical scales. Conclusion: The relevance of classifying personality characteristics in CFS patients as traits could not be supported by this case report.

Article: Long-Term Effectiveness of Pool Exercise Therapy and Education in Patients with Fibromyalgia

Table of Contents for Volume: 12 Issue: 2

woensdag 4 mei 2005, 6:00:00

Cover Date: 2004
Publication Date: 2005
Copyright Date: 2004

Article: Evidence forpp. Co-Infections in Blood of Chronic Fatigue Syndrome Patients
We examined the blood of 94 North American Chronic Fatigue Syndrome (CFS) patients using forensic polymerase chain reaction and found that a subset (10.6%) of CFS patients show evidence of Brucella spp. infections compared to one of 70 control subjects (Odds Ratio = 8.2; 95% Confidence Limits (CL) 1-66; P < .01). Rural patients showed a higher incidence of Brucella spp. infections over urban patients (OR = 5.5, 95% CL 1.3-23.5, P < .02). Since CFS patients also have a high prevalence of one of four Mycoplasma species and sometimes show evidence of infections with Chlamydia pneumoniae, we examined Brucella-positive patients for other bacterial infections. Previously we found that 8% of the CFS patients showed evidence of C. pneumoniae and about 50% show evidence of Mycoplasma spp. infections. Since the presence of one or more chronic systemic infections may predispose patients to other infections, we examined the prevalence of C. pneumoniae and Mycoplasma spp. infections in Brucella-positive patients. We found only one Brucella-positive patient with C. pneumoniae and four other patients with evidence of Mycoplasma spp., suggesting that such bacterial infections occur independently in CFS patients. Control subjects (N = 70) had low rates of Brucella spp. (1.4%), Mycoplasma spp. (7.2%) or C. pneumoniae (1.4%) infections, and there were no co-infections in control subjects. The results indicate that a subset of CFS patients show evidence of infection with Brucella spp., and some of these patients also have other bacterial infections.

Article: Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome A Pilot Study
Background: The chronic fatigue syndrome (CFS) is characterized by post-exertional malaise and fatigue. We designed this pilot study to explore whether the illness was associated with alterations in immunological markers following exercise. Methods: We measured immunological markers before and up to three days after either a sub-maximal or maximal bicycle exercise test.We studied nine patients with CFS and nine ageand sex-matched healthy but sedentary controls. We also studied the same patients with CFS at home after a night's sleep and then after traveling to the study center. Results: There were no significant differences in any of the cell markers after a sub-maximal exercise test compared to a maximal test. However, we found elevated concentrations of plasma transforming growth factor beta (TGF-), even before exercise, in subjects with CFS (median (IQR) of 904 (182-1072) pg/ml) versus controls (median (IQR) of 50 (45-68) pg/ml) (P < .001). Traveling from home to the hospital significantly elevated TGF- concentrations from a resting median (IQR) concentration of 1161 (130-1246) pg/ml to a median (IQR) concentration of 1364 (1155-1768) pg/ml (P < .02). There was also a sustained increase in plasma tumor necrosis factor alpha (TNF-a) after exercise in CFS patients, but not in controls (P = .004 for the area under the curve), although traveling had no such effect. CD3, CD4 and HLA DR-expressing lymphocyte counts were lower in CFS patients, but exercise had the same effect in both groups, causing an immediate increase in circulating cell numbers that lasted less than three hours. Conclusions: These results suggest that the relationship between physical activity and both pro-inflammatory and anti-inflammatory cytokines merits further investigation in patients with CFS. The results also emphasize the importance of defining a truly resting baseline condition in such studies.

Article: Enterovirus Related Myopathy in a Subset of Chronic Fatigue Syndrome?

Article: BOOK REVIEW

Table of Contents for Volume: 12 Issue: 1

dinsdag 5 oktober 2004, 6:00:00

Cover Date: 2004
Publication Date: 2004
Copyright Date: 2004

Article: EDITORIAL

Article: Clinical and Biochemical Characteristics Differentiating Chronic Fatigue Syndrome from Major Depression and Healthy Control Populations: Relation to Dysfunction and RNase L Pathway
Patterns of immune dysfunction have emerged in chronic fatigue syndrome (CFS) that include an immune activation state (evidenced by increased activated T lymphocytes and circulating cytokines) and poor cellular function (low natural killer (NK) cell cytotoxicity and impaired T lymphocyte response to mitogens). Therefore, the aim of the current study was to examine the relationship between clinical and functional characteristics, immune abnormalities and status of the RNase L pathway in CFS compared with healthy control and depression control populations. All study participants were assessed with respect to their general health, functional status, blood count and chemistry, biochemical and immune parameters. The CFS group (N = 66) demonstrated clinical, functional and biochemical abnormalities distinct from the healthy (N = 62) and depression (N = 51) control groups. The CFS group showed marked functional impairment compared with both control groups (P < .001) as measured by the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) (P < .001). The CFS group also showed decreased cognitive performance on a computerized test battery compared to healthy (P < .001) and depression controls (P < .009) and significantly higher 37/80 kDa RNase L ratio (P < .001) compared with both control groups. The odds ratios of a 37/80 kDa RNase L ratio > 2 compared with the CFS patients were 3.9 for the healthy controls (95% confidence limit (CL) 1.0-15.2, P < .05) and 65.8 for the depression controls (95% CL 10.7-406.6, P < .001). The CFS group demonstrated low NK cell cytotoxicity compared to healthy controls (P = .045). The correlation between abnormalities in the RNase L pathway and impaired NKcell function (r = .21, P < .006) suggests that both may be part of the same underlying disease mechanism, at least in this homogeneous population of very disabled CFS patients. Healthy contact-control subjects who had exposure to CFS patients showed a number of characteristics similar to the CFS patients, including an increased mean 37/80 kDa RNase L ratio (P < .04) and prevalence of the 37/80 kDa RNase L ratio > 2 (P < .03). In these contact-control subjects, the 37/80 kDa RNase L ratio was correlated with the interferon- levels (r = .58, P < .02), suggestive of activation of the interferon pathway. The results of the present study support the cytokine/immune activation model in this well-characterized CFS patient group.

Article: Comparing the Fukuda et al. Criteria and the Canadian Case Definition for Chronic Fatigue Syndrome
Because the pathogenesis of Chronic Fatigue Syndrome (CFS) has yet to be determined, case definitions have relied on clinical observation in classifying signs and symptoms for diagnosis. The selection of diagnostic signs and symptoms has major implications for which individuals are diagnosed with CFS and how seriously the illness is viewed by health care providers, disability insurers and rehabilitation planners, and patients and their families and friends. Diagnostic criteria also have implications for whether research based on varying definitions can be synthesized. The current investigation examined differences between CFS as defined by Fukuda et al. (1994) and a set of criteria that has been proposed for a clinical Canadian Case definition. There were twentythree participants who met the Canadian criteria, 12 in the CFS (Fukuda et al. (7) criteria) group and the 33 from the chronic fatigue (CF)-psychiatric group. Dependent measures included: work status, psychiatric comorbidity, symptoms, and functional impairment (measured by the Medical Outcomes Study). People meeting the Fukuda et al. and Canadian criteria were compared with people who had a chronically fatiguing illness explained by a psychiatric condition. Statistical tests used included binomial logistic regression and analysis of variance. The Canadian criteria group, in contrast to the Fukuda et al. criteria group, had more variables that statistically significantly differentiated them from the psychiatric comparison group. Overall, there were 17 symptom differences between the Canadian and CF-psychiatric group, but only 7 symptom differences between the CFS and CF-psychiatric group. The findings suggest that both the Canadian and Fukuda et al. case definitions select individuals who are statistically significantly different from psychiatric controls with chronic fatigue, with the Canadian criteria selecting cases with less psychiatric co-morbidity, more physical functional impairment, and more fatigue/weakness, neuropsychiatric, and neurological symptoms.

Article: The Fennell Phase Inventory in a Belgian Sample
The present study is a follow-up of the research conducted by Jason, Fennell et al. (1995, 1999, 2000) on a multistage theory for chronic fatigue syndrome (CFS). This multistage model is a very promising method for the evaluation of patients suffering from CFS and could facilitate the appropriate selection of various psychosocial therapies that improve the patient's ability to cope with their illness. Four predictive factors emerged with moderate to excellent reliability. A Spearman's rank correlation revealed positive correlations between our four-factor model and the three-factor model identified by Jason et al. (1999). A correlation matrix between the dimensional psychological investigation and the Fennell Phases revealed characteristics as suggested by previous research. Biological parameters varied over the different phases suggesting an important interaction between body and psyche.

Article: Abnormal Pain Processing in Patients with Fibromyalgia Syndrome
Fibromyalgia syndrome (FMS) is characterized by widespread pain, fatigue, sleep abnormalities, and distress. Because FMS lacks consistent evidence for tissue abnormalities, recent investigations have focused on central nervous system mechanisms of pain. Abnormal temporal summation of second pain (AWindup@) and central sensitization (CS) have recently been described in FMS patients. Windup (WU) and central sensitization, which rely on central pain mechanisms, occur after prolonged C-nociceptor input and depend on activation of nociceptor specific neurons as well as wide dynamic range neurons in the dorsal horn of the spinal cord. The important role of WU is also supported by its ability to predict the clinical pain intensity of FMS patients. Furthermore, brain-imaging techniques that can detect neuronal activation following nociceptive stimuli have provided additional evidence for abnormal central pain mechanisms in FMS. Most importantly, brain images have corroborated the augmented reported pain experience of FMS patients during experimental pain stimuli. These findings may have important implications for future research as well as the treatment of FMS pain.

Article: Gulf War Veterans: Evidence for Chromosome Alternations and Their Significance

Table of Contents for Volume: 11 Issue: 4

dinsdag 2 maart 2004, 6:00:00

Cover Date: 2003
Publication Date: 2004
Copyright Date: 2003

Article: Editorial

Article: Comparison of Activity Limitations/Participation Restrictions Among Fibromyalgia and Chronic Fatigue Syndrome Patients
Fibromyalgia (FM) and Chronic Fatigue Syndrome (CFS) are related yet overlapping disorders; the current case definitions prohibit a clear-cut differential diagnosis. These diagnostic criteria mainly address the impairment level of the World Health Organization's International Classification of Functioning, Disability and Health. This study aimed at comparing activity limitations and participation restrictions in patients with FM (n = 90) and CFS (n = 47). The Chronic Fatigue Syndrome Activities and Participation Questionnaire (CFS-APQ) was used for assessing functionality in both groups. The convergent validity of the scores obtained with the questionnaire with visual analogue scales for pain, fatigue and concentration was investigated in FM patients, as well as the content validity. No differences in total scores and 25 out of 26 individual items on the CFS-APQ were observed between the 2 groups (independent samples Mann-Whitney U test). This sample of FM patients reported to be more disabled in 'sitting for two hours' as compared to the CFS group (mean scores 3.0 1.0 and 2.3 1.0; P = .004). Four hundred and thirty-seven of the 497 (87.9 %) responses to the request to list difficult activities matched the content of the CFS-APQ. The overall scores of the CFS-APQ correlated statistically significant in respect to visual analogue scales for pain and concentration (Spearman rho for the total scores ranged between .44 and .49). These data question the disease specificity of the CFS-APQ for CFS, but suggests its applicability in 'the Chronic Pain-Fatigue Syndromes'. The present report provides evidence for both the content and convergent validity of the CFS-APQ in FM patients.

Article: Test-Retest Reliability of the Aerobic Power Index Test in Patients with Chronic Fatigue Syndrome
Use of maximal aerobic exercise testing in a chronically ill population may not only deter potential subjects from participating in trials, or returning for repeat trials, but may also result in the exacerbation of symptoms related to CFS. The Aerobic Power Index represents a submaximal exercise test that forms the aerobic component of the Trilevel Fitness Profile. This incremental bike test has a predetermined termination point based on a target heart rate (THR) of 75% of age predicted heart rate maximum, making successful completion of the test more likely in chronically ill subjects. The aim of this study was to determine reliability of the Aerobic Power Index in 20 CFS subjects. Results for the 17 subjects who reached THR for both trials, demonstrated high reliability for watts per kilogram and oxygen uptake (mlkg^-1min^-1), as demonstrated by an intraclass correlation coefficient (ICC) of .97 and .91 respectively, while RPE resulted in moderate reliability (ICC = .87). The results of this study indicate that that the Aerobic Power Index is a reliable submaximal test for use in a CFS population.

Article: The Frequency of HLA Class II Antigens in Chronic Fatigue Syndrome
Chronic fatigue syndrome is a condition characterized by unexplained, persistent fatigue in conjunction with other generalized symptoms. However, the patients as a group are more likely to have objective abnormalities of the immune system than control subjects. We measured the frequency of certain HLA antigens in a representative group of 35 patients. We restricted our analysis to class II molecules as these appear to be more specific predictors of susceptibility to immunologicallybased disorders. The frequency of the HLA-DQ1 antigen was increased in patients compared to general population Caucasian controls. This association between chronic fatigue syndrome and the HLA-DQ1 antigen translates into a relative risk of 3.2. This association has not been reported previously in chronic fatigue syndrome. Differences in the ethnic sub-grouping of patients in this study and in previous studies also could have contributed to the difference between our findings and those of previous investigators. Conversely, this study did not find HLA associations that have been reported by previous studies. The sample size of this study could have led to type II statistical errors and a failure to recognize certain HLA associations as significant.

Article: Cognitive Behavioural Therapy as Cure-All for CFS

Article: CURRENT PAPERS IN ME/CFS

Table of Contents for Volume: 11 Issue: 2

vrijdag 7 maart 2003, 6:00:00

Table of Contents for Volume: 11 Issue: 1

zondag 5 januari 2003, 6:00:00

Cover Date: 2003
Publication Date: 2003
Copyright Date: 2003

Simultaneously published as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols

Article: Chronic Fatigue Syndrome Guidelines

Article: Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
Recent years have brought growing recognition of the need for clinical criteria for myalgic encephalomyelitis (ME), which is also called chronic fatigue syndrome (CFS). An Expert Subcommittee of Health Canada established the Terms of Reference, and selected an Expert Medical Consensus Panel representing treating physicians, teaching faculty and researchers. A Consensus Workshop was held on March 30 to April 1, 2001 to culminate the review process and establish consensus for a clinical working case definition, diagnostic protocols and treatment protocols. We present a systematic clinical working case definition that encourages a diagnosis based on characteristic patterns of symptom clusters, which reflect specific areas of pathogenesis. Diagnostic and treatment protocols, and a short overview of research are given to facilitate a comprehensive and integrated approach to this illness. Throughout this paper, ?myalgic encephalomyelitis? and ?chronic fatigue syndrome? are used interchangeably and this illness is referred to as ?ME/CFS.?

Article: Monitoring a Hypothetical Channelopathy in Chronic Fatigue Syndrome: Preliminary Observations
This study was aimed at monitoring of a previously suggested channelopathy in Chronic Fatigue Syndrome, and at searching for possible explanations by means of immune system characteristics. Twenty-seven CFS patients and 20 age and sex matched healthy volunteers were recruited. RNase L-ratio, percent of the norm of whole body potassium content, serum electrolytes (sodium, calcium and potassium), immune cells, blood cell count and erythrocyte sedimentation rate were determined. More than fifty percent of our patients presented with abnormal whole body potassium content. Eight patients had increased, while six had depleted potassium content. Discriminant function analysis revealed that the CFS patients and control subjects could be differentiated on immunophenotyping with the predominant cell differences being the increase in CD19+ CD5+ (mature B-) cells and the decrease in CD3CD16+ CD56+ (NK) cells in both the percentage and count distributions. The fall in NK-cells was very strongly associated with increases in the RNase L-ratio and falls in serum calcium levels. In addition, four patients with low serum calcium levels showed lower whole body potassium levels. In conclusion, these observations suggest a channelopathy in a subset of CFS patients, probably induced by the deregulated 2-5A RNase L antiviral pathway.

Article: Gulf War Illnesses: Chemical, Biological and Radiological Exposures Resulting in Chronic Fatiguing Illnesses Can Be Identified and Treated
Gulf War illnesses involve multiple, complex chronic signs and symptoms that loosely fit the clinical criteria for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and/or Fibromyalgia Syndrome (FMS). Most Gulf War illness patients had multiple exposures: (a) complex chemical mixtures, including organophosphate pesticides, anti-nerve agents, carbamates and possibly nerve and blister agents, (b) radiological sources, subjecting patients to both heavy metal and radiation effects, and (c) biological sources, including bacteria and toxins and the effects of multiple vaccines. Chemically exposed patients may benefit by removing offending chemicals and depleting toxic chemicals from the patient's system and other symptomatic treatments. Patients with systemic infections, including mycoplasma and other chronic bacterial infections, can be treated with antibiotics and additional nutritional supplementation. Some patients may have their illness linked to radiological exposures, and a minority to battlefield stress. The vaccines are a prime suspect for immune dysfunction and chronic infections. The multiple, complex exposures resulted in poorly defined chronic illnesses, but subsets of Gulf War illness can be identified and effectively treated using appropriate procedures.

Table of Contents for Volume: 11 Issue: 3

zaterdag 4 januari 2003, 6:00:00

Cover Date: 2003
Publication Date: 2003
Copyright Date: 2003

Article: Hyperbaric Therapy in Chronic Fatigue Syndrome
The aim of this study was to determine if hyperbaric oxygen treatment (HBOT) could be used as adjunctive therapy and if HBOT could increase the quality of life in such a way that the functional status would improve in patients with an infection. A randomized, controlled trial was conducted on 15 Mycoplasma sp. infected CFS (CDC 1994) patients and 14 CFS (CDC 1994) patients with no evidence of a Mycoplasma infection were enrolled in a convenience randomization sample from our referral clinic. No statistical differences were found by use of univariate repeated measures although Bodily Pain as measured by the SF-36 seems to decrease after hyperbaric therapy (Greenhouse-Geisser: p = .010). Trends were found using paired t-testing for Mycoplasma infected CFS patients. The general perceived fatigue seemed to decrease after hyperbaric therapy (General Fatigue: p = .06). Directly after one week of hyperbaric therapy general fatigue improved (p = .03) but there was a reduction of activity (reduced activity: p = .05) and general perceived health (general health: p = .04). One month later the physical role increased (Role-Physical: p = .07). Although more data is required to make firm conclusions, trends were found. Reduced fatigue, increased levels of activity and an improved reaction time improved significantly their quality of life and therefore, enhanced also their functional status and thus could be used as an adjunctive therapy.

Table of Contents for Volume: 10 Issue: 3/4

vrijdag 7 juni 2002, 6:00:00

Cover Date: 2002
Publication Date: 2002
Copyright Date: 2002

Article: EDITORIAL

Article: Activity Limitations and Participation Restrictions in Patients with Chronic Fatigue Syndrome Construction of a Disease Specific Questionnaire
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.

Article: Influence of Melatonin on Quality of Life in Patients with Chronic Fatigue and Late Melatonin Onset
Medical Outcome Study Short Form-36 (MOS SF-36) qualities of life scores were studied in 38 chronic fatigue patients with late melatonin onset before and after treatment with melatonin. Before start of the treatment, quality of life was assessed twice. Pre-treatment scores were compared with each other and with the scores of 43 patients with Delayed Sleep Phase Syndrome and of 1063 healthy subjects. Melatonin, 5 mg, was taken orally, 5 hours before baseline salivary endogenous dim light melatonin onset. After mean (SD) treatment of 13.7 (0.8) weeks, quality of life scores "physical functioning," "energy/vitality," "bodily pain," and "general health perception" improved (p values, respectively, 0.017, 0.002, 0.002 and 0.009). In the pre-treatment period (mean [SD] interval: 6.5 [0.6] weeks) "social functioning" and "general health perception" improved (p = 0.013 and 0.010, respectively). In the chronic fatigue patients the quality of life scores did not differ from those of the Delayed Sleep Phase Syndrome patients, except for "physical functioning," "energy/vitality" and "general health perception." These were significantly lower. All chronic fatigue patient's scores were significantly lower than those of the healthy subjects except for "health transition."

Article: Levels of Nitric Oxide Synthase Product Citrulline Are Elevated in Sera of Chronic Fatigue Syndrome Patients
Serum levels of citrulline, a product of nitric oxide synthase activity, were measured in 36 CFS patients and 16 controls to determine whether synthase activity may be elevated in CFS patients. Serum citrulline levels were found to be significantly elevated in CFS patients and, in addition, there was a trend towards higher levels in CFS patients with stronger symptoms. These results provide support for the view that nitric oxide synthase activity tends to be elevated in CFS patients, thus supporting a prediction of the elevated nitric oxide/peroxynitrite theory of CFS etiology.

Article: Toxins and Immunity in Chronic Fatigue Syndrome
In this paper, Dr. Richardson illustrates links between exposure, absorption and effects of viruses, bacteria, and inorganic toxins, and their toll on the immune system, as potential causes of chronic symptomatology as seen in chronic fatigue syndrome.

Article: The Paul-Bunnell Heterophile Antibody Determinant in Epstein-Barr Virus-Associated Disease
Reactivation of latent herpes viruses (notably EpsteinBarr virus, human herpesvirus-6) is commonly seen in chronic fatigue syndrome and it is believed to contribute to symptom perpetuation. EpsteinBarr virus (EBV), which was first isolated by Epstein, Barr and Achong (1964) from a cultured Burkitt's lymphoma lymphoblast cell line, is the etiological agent for infectious mononucleosis (IM), polyclonal and oligoclonal lymphomas associated with primary and acquired immunodeficiencies, and the complications of X-linked lymphoproliferative syndrome (XLP) (Cantani and Mastrantoni, 1989; Englund, 1988; Ernberg et al., 1990; Jones and Straus, 1987; Okano et al., 1988; Purtilo, 1987; Purtilo et al., 1981; Rowe et al., 1986; Saemundsen et al., 1981) and nasopharyngeal cancer (Pearson et al., 1984). Furthermore, people who have had IM have higher rates of subsequent development of malignant lymphoproliferative disorders (Abo et al., 1982; Snydman et al., 1982) and Hodgkin's disease (Green et al., 1979; Mueller, 1987; Poppema et al., 1985; Weiss et al., 1989), while patients with XLP have a higher incidence of non-Hodgkin's malignant lymphoma (Harrington et al., 1987). The precise role of EBV in these diseases or in CFS is not well understood. Nonetheless, it is known that EBV infection triggers the formation of heterophile antibodies that, for many decades, have formed the basis for serologic diagnosis of IM. In this review, we discuss the discovery, species variation, and structure of the erythrocyte membrane-associated Paul-Bunnell (PB) heterophile antibody determinant, its implications to IM diagnosis, and its potential contribution to defective immune surveillance, such as that seen in chronic fatigue syndrome.

Article: Effects of Benzalkonium Salts on G-protein-Mediated Processes and Surface Membranes Relevance to Microbial- and Chemical-Induced Diseases
Benzalkonium salts comprise a group of positively charged surface-active alkylamine biocides with the general formula alkyldimethylbenzylammonium chloride or bromide. They interact with guanine nucleotide triphosphate-binding proteins (G proteins), thereby affecting signal transduction in a variety of cell types and processes. The present report reviews the known and potential basic science research and clinical applications and manifestations of benzalkonium salts. Benzalkonium salts have antiproliferative effects on a variety of cells (including T cells) through G-protein-dependent pathways, affect cytokine gene expression (downregulate tumor necrosis factor expression), and are also effective bactericidal, fungicidal, and virucidal agents with multisite (direct and immunologically-mediated) inhibitory activity against many pathogens, including the human immunodeficiency virus (HIV), papillomavirus, and herpesviruses. Therefore, benzalkonium salts not only appear to be effective as disinfectants and spermicides but may also prove useful in the prevention and treatment of several diseases, particularly those linked to viruses and originating at the skin or mucosal surface. The untoward effects of benzalkonium salts are also discussed as a paradigm for chemical-induced diseases.

Table of Contents for Volume: 10 Issue: 2

vrijdag 7 juni 2002, 6:00:00

Cover Date: 2002
Publication Date: 2002
Copyright Date: 2002

Article: EDITORIAL

Article: Possible Triggers and Mode of Onset of Chronic Fatigue Syndrome
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.

Article: Subjective Sleep Quality and Depressive Symptoms in Patients with the Chronic Fatigue Syndrome
Objectives: To evaluate subjective quality of sleep and depressive symptoms of patients with chronic fatigue syndrome (CFS). Methods: Adult patients, who met the criteria for CFS, were recruited by general practitioners in the Leiden area, The Netherlands. Age and sex-matched controls were recruited. Questionnaires were handed out to 59 patients and 56 controls. Results: CFS patients had a significant higher mean score than controls on the Groningen Sleep Quality Score (GSQS) and the Zung-index, i.e., worse sleep and depression scores. In the multivariate logistic regression model, the GSQS had an OR of 1.35 per unit score (CI: 1.07-1.70), and the Zung-index had an OR of 1.21 per unit score (CI: 1.10-1.33). Conclusions: In our study, CFS patients report more subjective sleep impairment and depressive symptoms than controls but these factors appear to be independent. The fact that only a minority of the CFS patients have depressive symptoms suggests it is unlikely that depression is the cause of CFS.

Article: Cytolytic Cells and Their Function
Cytolytic cells play an important role in cellular immunity and their function is compromised in a subgroup of patients with chronic fatigue syndrome. This review summarizes historical, methodological, clinical, therapeutic, and basic immunology aspects of cytolytic cells.

Article: Residential Rehabilitation Courses in the Self-Directed Management of Chronic Fatigue Syndrome: A Preliminary Evaluation
Residential rehabilitation courses in self-directed illness management offer a potentially useful patient-centered and multidiscipliary therapeutic option for Chronic Fatigue Syndrome. A retrospective survey of the data from the courses run by Westcare UK between 1995 and 1998 was undertaken to give a preliminary evaluation of outcomes and acceptability. The outcome results, for 49 participants, show improvements, at 12 months, on the Fatigue and Emotional Distress subscales of the PFRS. (Fatigue: before course: mean 3.66, s.d. 1.14; 12 months later: mean 3.11, s.d. 1.57; F(1,48) = 11.10 p < 0.005. Emotional distress: before course: mean 2.53, s.d. 1.46; 12 months later: mean 2.04, s.d. 1.39; F (1,48) = 5.96 p < 0.01.) Participants also reported a high level of general satisfaction with the course: 89.4% gave a rating of five or six, out of six. These results describe both longand short-term benefits, and support the continued use of these courses and the implementation of a further more rigorous study.

Table of Contents for Volume: 10 Issue: 1

donderdag 3 januari 2002, 6:00:00

Table of Contents for Volume: 09 Issue: 1/2

vrijdag 5 oktober 2001, 6:00:00

Cover Date: 2001
Publication Date: 2001
Copyright Date: 2001

Article: EDITORIAL

Article: Concomitant Environmental Chemical Intolerance Modifies the Neurobehavioral Presentation of Women with Fibromyalgia
Background: This study compared personality, dietary, and psychophysiological characteristics of 3 groups of women: fibromyalgia (FM) with illness from low levels of environmental chemicals (chemical intolerance, CI), FM alone without CI, and normal controls. CI may be a marker for enhanced central nervous system response amplification (sensitization) in limbic and mesolimbic pathways, which play a role in hedonic responses to food and drugs and in pain. Method: Fibromyalgic women with (FM/CI, n = 11) and without CI (FM, n = 10) and normals (NORM, n = 10) participated in the study. Measures included psychological trait questionnaires, a food frequency questionnaire, a taste test for hedonic and sweetness ratings of different sucrose concentrations, pain self-ratings, and resting spectral electroencephalographic alpha over midline sites, averaged over four separate days. Results: FM with CI had the highest scores on the Harm Avoidance dimension of the Tridimensional Personality Questionnaire, Carbohydrate Addicts Test, Limbic Symptom sensory and behavior subscales, and SCL-90-R somatization and obsessiveness subscales. FM groups both had the highest mean pain ratings for 21 tender point sites. Groups did not differ for macronutrient intake or for sweetness and hedonic ratings for sucrose. The combined FM groups had greater EEG alpha activity towards posterior midline sites than did normals. Conclusion: The pattern of findings may reflect impaired serotonergic function and/or elevated dopaminergic receptor activation by endogenous and/or exogenous agents. The data could have implications for pharmacological and dietary interventions in different subsets of FM patients.

Article: Increased Eosinophil Protein X Levels in Chronic Fatigue Syndrome
Chronic fatigue syndrome is a condition of unknown etiology characterized by severe fatigue and accompanied by symptoms including cognitive difficulties, myalgias, and headaches. Studies of this illness have found chronic activation of the immune system, including one reporting elevated levels of eosinophil cationic protein, considered an eosinophil activation marker. The aim of this study was to measure serum levels of eosinophil protein X, a cationic protein not measured previously in this illness. Measurements are reported on serum samples from 29 patients meeting the Centers for Disease Control and Prevention criteria for chronic fatigue syndrome, and 30 healthy controls of similar age and gender. The median serum eosinophil protein X level in patients was higher than controls: 37.9 vs. 25.3 g/L (p = 0.037). Forty-eight percent of patients versus 23% of controls had levels above the normal range. The marked increase in serum levels of eosinophil protein X in chronic fatigue syndrome patients could reflect eosinophil activation in this illness.

Article: Prevalence of IgM and IgG Antibody to HHV-6 and HHV-8 and Results of Plasma PCR to HHV-6 and HHV-7 in a Group of CFS Patients and Healthy Donors
Human herpes virus-6 (HHV-6) is a beta herpes virus that was first described in 1986 and which occurs in the form of at least two variants, A and B. Healthy donors in the general population are carriers for mainly the B variant, in whom 90% harbor the DNA of this type in their peripheral blood mononuclear cells (PBMNC). A higher prevalence of this virus has been detected by testing of plasma and PBMNCs by IFA, ELISA and by the nested PCR technique, in addition to direct culture for HHV-6 in certain groups of immunesuppressed patients such as those with multiple sclerosis and HIV. It has also been isolated to a greater degree using these techniques from patients who meet the case definition for the chronic fatigue syndrome (CFS). We determined IgG and IgM antibody titers to HHV-6; IgG to HHV-8 and performed PCR testing for HHV-6 on the plasma of 46 patients with CFS and on 7 healthy donors (HD). We also performed PCR testing for HHV-7 on 15 CFS patients and on 4 HD(s). We found a higher prevalence of IgM antibody in CFS patients 23/36 (50%) versus 2/7 (28.5%) of HD. The prevalence of IgG antibody to HHV-8 was zero among both CFS patients and HD. Three out of forty six (6.5%) of CFS patients demonstrated a positive plasma by PCR to HHV-6 compared to zero out of 7 HD(s). Finally, four out of fifteen (26.7%) CFS patients and zero out of four HD(s) demonstrated a positive plasma PCR to HHV-7. Our results were influenced by the presence of various subpopulations of CFS patients among our study group, in addition to our reliance on the results of single specimens as opposed to a series of multiple samples over time in individual subjects, and by methodological variability (decreasing our yield because of diminished viral shedding in cell-free samples or increasing it compared to other research groups who failed to co-culture the PBMNCs with indicator cells, e.g., PHA-stimulated human cord blood cells or human fibroblasts for short-term culture [15 day]). Nevertheless, it is clear that the study of plasma and perhaps other tissue samples, such as cerebral spinal fluid and gastric mucosa from patients with CFS in better defined subgroups, as well as defined population of HDs using a variety of methodological techniques will increase our knowledge about the role of HHV-6 in this complex disorder.

Article: Prevalence in the Cerebrospinal Fluid of the Following Infectious Agents in a Cohort of 12 CFS Subjects: Human Herpes Virus-6 and 8; Chlamydia Species; Mycoplasma Species; EBV; CMV; and Coxsackievirus
Over the last decade a wide variety of infectious agents has been associated with the chronic fatigue syndrome (CFS) as potential etiologies for this disorder by researchers from all over the world. Many of these agents are neurotrophic and have been linked previously to other diseases involving the central nervous system (CNS). Human herpes virus-6 (HHV-6), especially the B variant, has been found in autopsy specimens of patients who suffered from multiple sclerosis. Because patients with CFS manifest a wide range of symptoms involving the CNS as shown by abnormalities on brain MRIs, SPECT scans of the brain and results of tilt table testing we sought to determine the prevalence of HHV-6, HHV-8, Epstein-Barr virus (EBV), cytomegalovirus (CMV), Mycoplasma species, Chlamydia species, and Coxsackie virus in the spinal fluid of a group of 12 patients with CFS. Although we intended to search mainly for evidence of actively replicating HHV-6, a virus that has been associated by several researchers with this disorder, we found evidence of HHV-8, Chlamydia species, CMV and Coxsackie virus in 6/12 samples. Attempts were made to correlate the clinical presentations of each of these patients, especially the neurological exams and results of objective testing of the CNS, with the particular infectious agent isolated. It was also surprising to obtain such a relatively high yield of infectious agents on cell free specimens of spinal fluid that had not been centrifuged. Future research in spinal fluid analysis, in addition to testing tissue samples by polymerase chain reaction (PCR) and other direct viral isolation techniques will be important in characterizing subpopulations of CFS patients, especially those with involvement of the CNS.

Article: Nevada Chronic Fatigue Syndrome Consensus Conference

Article: Fibromyalgia: Literature in Review (1999-2000)

Table of Contents for Volume: 09 Issue: 3/4

vrijdag 7 september 2001, 6:00:00

Cover Date: 2001
Publication Date: 2001
Copyright Date: 2001

Article: EDITORIAL

Article: Viral Isolation from Brain in Myalgic Encephalomyelitis

Article: Fibromyalgia
Although much has been learned over the last decade about fibromyalgia, much remains to be learned about its causes, nosology, treatment, and overlap with a variety of rheumatic and nonrheumatic conditions. Advances in rheumatology, cardiovascular medicine, endocrinology, epidemiology, immunology, infectious diseases, neurology, psychiatry, and psychology have served as the basis for the formulation of new lines of research and novel therapeutic interventions. The purpose of this review is to summarize the knowledge gained and published mainly within the last decade.

Table of Contents for Volume: 08 Issue: 2

maandag 7 mei 2001, 6:00:00

Cover Date: 2001
Publication Date: 2001
Copyright Date: 2001

Article: EDITORIAL

Article: Effective Treatment of Chronic Fatigue Syndrome and Fibromyalgia- A Randomized, Double-Blind, Placebo-Controlled, Intent-To-Treat Study
Background: Hypothalamic dysfunction has been suggested in fibromyalgia (FMS) and chronic fatigue syndrome (CFS). This dysfunction may result in disordered sleep, subclinical hormonal deficiencies, and immunologic changes. Our previously published open trial showed that patients usually improve by using a protocol which treats all the above processes simultaneously. The current study examines this protocol using a randomized, double-blind design with an intent-to-treat analysis. Methods: Seventy-two FMS patients (38 active:34 placebo; 69 also met CFS criteria) received all active or all placebo therapies as a unified intervention. Patients were treated, as indicated by symptoms and/or lab testing, for: (1) subclinical thyroid, gonadal, and/or adrenal insufficiency, (2) disordered sleep, (3) suspected neurally mediated hypotension (NMH), (4) opportunistic infections, and (5) suspected nutritional deficiencies. Results: At the final visit, 16 active patients were ?much better,? 14 ?better,? 2 ?same,? 0 ?worse,? and 1 ?much worse? vs. 3, 9, 11, 6, and 4 in the placebo group (p < .0001, Cochran-Mantel-Haenszel trend test). Significant improvement in the FMS Impact Questionnaire (FIQ) scores (decreasing from 54.8 to 33.2 vs. 51.4 to 47.7) and Analog scores (improving from 176.1 to 310.3 vs. 177.1 to 211.9) (both with p < .0001 by random effects regression), and Tender Point Index (TPI) (31.7 to 15.5 vs. 35.0 to 32.3, p < .0001 by baseline adjusted linear model) were seen. Long term follow-up (mean 1.9 years) of the active group showed continuing and increasing improvement over time, despite patients being able to discontinue most treatments. Conclusions: Significantly greater benefits were seen in the active group than in the placebo group for all primary outcomes. An integrated treatment approach appears effective in the treatment of FMS/CFS.

Article: Chronic Fatigue Syndrome and Abnormal Biological Rhythms in School Children
Chronic fatigue syndrome occurring in previously healthy children and adolescents is one of the most vexing problems encountered by pediatric practitioners. To investigate the biological rhythms in the pediatric patients with CFS, we examined sleep pattern, circadian rhythm of core body temperature (CBT), and plasma cortisol in 41 patients, aged between 10 and 19 years, who did not have any physical or psychiatric disorders, but had non-specific complaints, and were suspected to have a circadian rhythm disturbance. They were diagnosed as having CFS on the basis of published criteria. Circadian variation of CBT in the CFS patients did not present a clear rhythm, and appearance time of their lowest CBT was significantly delayed compared to healthy subjects. Amplitude of circadian CBT changes, fitted to a cosinor curve by the least square method, was significantly smaller in the patients than in healthy subjects. Moreover, circadian rhythm of plasma cortisol in the patients appeared to be quite different, compared to healthy subjects. These findings suggest that their clinical psychosomatic symptoms (e.g., fatigue and sleep disturbance) might be closely related to the desynchronization of their biorhythms, particularly the circadian rhythm of body temperature and cortisol rhythm.

Article: Cobalamin Used in Chronic Fatigue Syndrome Therapy Is a Nitric Oxide Scavenger
Cobalamin (vitamin B₁₂) in the form of hydroxocobalamin or cyanocobalamin injections has been widely used to treat chronic fatigue syndrome (CFS). Hydroxocobalamin is a nitric oxide scavenger and is proposed here to act as such a scavenger in CFS treatment. Its possible efficacy in CFS treatment, if further substantiated, may provide confirmation of a prediction of the elevated nitric oxide/peroxynitrite theory of CFS etiology. This interpretation of the possible role of cobalamin in CFS treatment suggests a useful perspective for confirming and optimizing this treatment.

Article: Orthostatic Intolerance: A Review with Application to the Chronic Fatigue Syndrome
The symptoms of the chronic fatigue syndrome closely match those of chronic orthostatic intolerance and research suggests that orthostatic intolerance plays a role in the symptomatology of CFS. Recent investigations support the hypothesis that findings in CFS patients result at least in part from impaired blood pressure and heart rate regulation. Orthostatic intolerance has been implicated. Effective and specific treatment for chronic orthostatic intolerance can only be developed when a specific etiology or etiologies are discovered.

Article: Effect of Modafinil on Fatigue Associated with Neurological Illnesses
Fatigue is a common symptom of a variety of neurological illnesses, such as Alzheimer's disease, chronic fatigue syndrome, multiple sclerosis, Parkinson's disease, and stroke. Fatigue severely impairs productivity, performance, social functioning, and quality of life. Modafinil (PROVIGIL) has been shown to significantly improve fatigue associated with multiple sclerosis and depression. Here, a retrospective review of the medical charts of 25 patients treated with modafinil for fatigue associated with various neurological illnesses was conducted. Modafinil was effective for the treatment of fatigue in 21 of 25 patients (84%), and was well tolerated. Therefore, modafinil appears to be a potentially attractive candidate for the treatment of fatigue associated with neurological disorders.

Article: Chronic Fatigue Syndrome: The Yeast Concept
Many theories abound as to the cause of CFS, but none have been proven conclusively. Because of the prevalence of the condition in many different countries throughout the world, it is becoming increasingly necessary to find a common link in the causative mechanism. The cause must be present at an international level. The overgrowth of bowel yeast and its infiltration through the bowel wall into the blood stream would appear to be the starting point in the development of CFS. This invasion of yeast can occur for different reasons. Therapeutic interventions based on the years of hypothesis are suggested.

Table of Contents for Volume: 08 Issue: 3/4

woensdag 6 september 2000, 6:00:00

Cover Date: 2001
Publication Date: 2000
Copyright Date: 2001

Simultaneously published as Innovations in Chronic Fatigue Syndrome Research and Clinial Practice

Article: Preface

Article: Depressive Comorbidity in the Fatiguing Illnesses
Objective: The present study seeks to examine whether subjects with fatiguing illnesses and comorbid Major Depressive Disorder (MDD) have more symptoms than those without MDD. Methods: The data was based on the Chronic Fatigue Syndrome (CFS) Surveillance System of the Centers for Disease Control and Prevention (CDC). Each of the 565 subjects enrolled in the study had a fatiguing illness and some had CFS. Subjects were evaluated for the duration and severity of the 11 symptoms and 3 physical signs listed in the 1988 CDC case definition (symptoms). They completed the Diagnostic Interview Schedule for the DSM-III-R which provided a diagnosis of several psychiatric disorders including MDD. Symptoms were compared in subjects with and without comorbid MDD. Results: The mean number of symptoms was similar in the two groups. Three symptoms were found to be associated with MDD: neurobiological (cognitive complaints), sleep disturbance, and headache. Conclusions: Comorbid MDD in the fatiguing illnesses is not associated with a higher mean number of symptoms. In the present study a pattern of three individual symptoms emerged that was associated with comorbid MDD. It is suggested that subjects with fatiguing illnesses who have this symptom pattern be evaluated for comorbid MDD.

Article: Chronic Fatigue Syndrome, Ampligen, and Quality of Life: A Phenomenological Perspective
The purpose of this investigation was to identify significant quality-of-life issues for two women previously diagnosed with chronic fatigue syndrome (CFS), and their families. Both women were participants in a cost-recovery, clinical trial of the antiviral and immunomodulatory drug, Ampligen. A qualitative, case study approach was adopted to access information not normally available from clinical trials. Specifically, semi-structured, in-depth interviews were conducted with the CFS patients, and their spouses, to discover if these families perceived any changes in their patterns of daily living contingent with participation in the Ampligen trial. Patient diaries were also analyzed for the purpose of triangulation. Content analysis of the interview transcripts and diary entries revealed a number of significant quality of life improvements for the women and their families, for which they perceived the drug therapy responsible. After an initial acclimation period, and with the exception of the day when the drug was administered, both women reported a reduction in pain, increased energy levels, and improved cognitive functioning. They each cited numerous cases to illustrate their improvement.

Table of Contents for Volume: 08 Issue: 1

vrijdag 7 januari 2000, 6:00:00

Cover Date: 2001
Publication Date: 2000
Copyright Date: 2001

Article: EDITORIAL

Article: Immunotherapy of Chronic Fatigue Syndrome: Therapeutic Interventions Aimed at Modulating the Th1/Th2 Cytokine Expression Balance
Based on the postulates of viral and autoimmune etiologies of CFS, several interventions have been designed and tested by different research groups around the world, including the United States, Sweden, United Kingdom, Italy, and Japan. This review addresses those interventions aimed at altering the balance of certain cytokines, the mediators of immune responses. Patients with CFS who show evidence of activation of the immune system have poor immune cell function and a predominance of what is called a T-helper (Th)2-type cytokine response when their lymphocytes are activated. A Th2-type response, which is characterized by production of cytokines such as interleukin (IL)-4, -5, and -10, favors the function of B lymphocytes, the cellular factories of immunoglobulins. A predominance of a Th2-type response is therefore consistent with pathologies, such as autoimmunity and atopy, which are based on inappropriate production of immunoglobulins. Many of the CFS therapies discussed decrease the Th2-type predominance seen at baseline in CFS patients, thereby allowing a greater predominance of a Th1-type response, which favors the function of macrophages and natural killer cells. The function of the latter cells, which have the natural ability of directly destroying invading microbes and cancer cells, is defective in untreated CFS patients. Typical Th1-type cytokines include IL-2 and interferon-gamma, and some of the therapies induce their production. The interventions discussed in this review cover a wide spectrum of therapeutic tools ranging from lymph node cell immunotherapy, herbal products, and small molecules to vaccines. Despite the controversies on the etiology of CFS, immunotherapy research is useful and necessary.

Article: Clinical and Immunologic Effects of Autologous Lymph Node Cell Transplant in Chronic Fatigue Syndrome
An open labeled, phase 1, safety and feasibility study using lymph node extraction, ex vivo lymph node cell expansion, followed by autologous cell reinfusion was evaluated as a potential immunomodulatory treatment strategy in patients with chronic fatigue syndrome (CFS). The experimental therapy utilized the cells of the lymph node, activated and grown in culture with defined media, interleukin-2 (IL-2) and anti-CD3 to activate and enhance cellular immunological functions. This procedure was designed to change the cytokine pattern of the lymph node lymphocytes to favor expression of T-helper (Th)1-type over Th2-type cytokines. The mixed population of ex vivo immune-enhanced cells were reinfused into the donor, who was carefully monitored for adverse events and possible clinical benefit. There were no adverse events. There were significant improvements in clinical status in association with a significant decrease in Th2-type cytokine production.

Article: Nickel Allergy Is Found in a Majority of Women with Chronic Fatigue Syndrome and Muscle Pain- And May Be Triggered by Cigarette Smoke and Dietary Nickel Intake
Two hundred and four women with chronic fatigue and muscle pain, with no signs of autoimmune disorder, received immune stimulation injections with a Staphylococcus vaccine at monthly intervals over 6 months. Good response was defined as a decrease by at least 50% of the total score on an observer's rating scale. Nickel allergy was evaluated as probable if the patient had a positive history of skin hypersensitivity from cutaneous exposure to metal objects. The patient's smoking habits were recorded. Fifty-two percent of the patients had a positive history of nickel contact dermatitis. There were significantly more good responders among the non-allergic non-smokers (39%) than among the allergic smokers (6%). We also present case reports on nickel-allergic patients who apparently improved after cessation of cigarette smoking and reducing their dietary nickel intake. Our observations indicate that exposure to nickel, by dietary intake or inhalation of cigarette smoke, may trigger systemic nickel allergy and contribute to syndromes of chronic fatigue and muscle pain.

Table of Contents for Volume: 07 Issue: 4

zaterdag 4 december 1999, 6:00:00

Cover Date: 2000
Publication Date: 1999
Copyright Date: 2000

Article: EDITORIAL

Article: Doctor-Patient Relationship in Primary Care of Chronic Fatigue Syndrome: Perspectives of the Doctor and the Patient
Background: Chronic Fatigue Syndrome (CFS) is characterized by severe debilitating fatigue for at least six months. The lack of a known origin could have consequences for the way general practitioners deal with the diagnosis CFS and their perception of CFS patients. The aims of the study were to investigate the use of the diagnosis CFS by GPs and their reactions to self-diagnosis and to explore opinions of GPs about causes of CFS and the communication with CFS patients as well as opinions of CFS patients about their GPs. Method: One hundred twenty-one GPs completed questionnaires and 12 were interviewed. Data of 211 CFS patients were analyzed as well. Results: Only half of the GPs used the diagnosis CFS. The main reason for not diagnosing CFS was ignorance of the criteria. GPs reported self-diagnosis in 68% of the CFS patients. More than half of the GPs could sympathize less with the complaints of CFS patients compared with other patients. These GPs experienced more problems in communicating with CFS patients and judged co-operation and contact as poor. As to the causes for CFS a discrepancy was found. GPs mainly attributed the complaints to psychosocial factors, whereas patients mainly had physical attributions. Conclusion: In CFS, GPs should be explicit about the diagnosis. As to the discrepancy in presumed causes of CFS between GPs and CFS patients, it may be helpful for GPs to discuss the distinction between initiating and perpetuating factors of CFS. We argue that this attitude of GPs would be beneficial to the course of the complaints of CFS patients.

Article: Differential Diagnosis: The Challenge of Chronic Fatigue
The chronic fatigue syndrome comprises one of the most challenging issues in contemporary medicine. The condition remains distressing for patients and perplexing to medical science. Clinicians face a management path which has no ''gold standard'' of investigational mileposts; and are locked into a progression where the extremes of either undertreatment or over-investigation may lead to iatrogenic disaster. The themes of investigation, diagnosis and management of patients with the chronic fatigue syndrome remain controversial. This condition joins in historical perspective a series of other diseases such as pink disease, post-traumatic stress disorder (by a variety of names), the Royal Free disease, Q Fever, Ross River disease and chronic ciguateraall of which have occupied windows of historical time in the twentieth century during which their genesis remained an enigma. In some cases, they still do. New and puzzling diseases will undoubtedly arise in the future. Both patients and medical science are best served if the formal discipline of differential diagnosis is followed unswervingly under these circumstances or ''new'' diseases. The rigour of this discipline -the rank listing of formal possibilities after the clinical history and objective signs have been elicited-forms the pivot of best-practice contemporary medicine. An example of its power is no more dramatically illustrated by the example of a ''new'' enigmatic disease, chronic ciguatera, which ''reappeared'' in the 1950s. Ciguatoxins are some of the most potent biological substances known. Their neurotropic effects produce a protean array of symptoms which are distressing in the acutephase syndrome and which are enervating throughout the often-prolonged progression of convalescence. It is now appreciated that such effects are due to sodium channel activation and subsequent dysfunction at the receptor sites on the cell surface of all excitable tissues. Dr. A. Melvin Ramsay, the Honorary Consultant Physician in Infectious Diseases at the Royal Free Hospital in London, was at the clinical epicentre of the presentation of another new disease in July 1955. His approach to its diagnosis, in the best traditions of differential diagnosis, is an exemplar of the objective response to the appearance of a new or enigmatic disease; and especially to that type in which experience has not generated sufficient case familiarity to define syndrome barriers or to establish pathogenesis. Under such conditions, the correct diagnostic paradigm is to follow the discipline of differential diagnosis, an evolved phenomenon of the last one hundred years of medicine. This paper traces the evolution of the process of differential diagnosis, in the perspective of the enigma of chronic fatigue, which remains an unmet challenge today.

Article: Psychiatric Comorbidity and Somatic Distress in Sudden and Gradual Onset Chronic Fatigue Syndrome
The purpose of this study was to examine if type of Chronic Fatigue Syndrome (CFS) onset suggested two distinct illness patterns within CFS. One hundred and seventeen patients diagnosed with CFS by a multidisciplinary team were divided into two groups: sudden versus gradual onset of symptoms. These two subgroups were compared on the presence of lifetime comorbid Axis I diagnoses, the pattern of medically unexplained symptoms, and the number of patients who met criteria for Somatization Disorder (SD). The two subgroups did not differ in any of the experimental variables indicating that onset type is not distinguished by either comorbid psychopathology or medically unexplained symptoms. Implications of these findings are discussed.

Article: Elevated Peroxynitrite as the Cause of Chronic Fatigue Syndrome: Other Inducers and Mechanisms of Symptom Generation
In an earlier paper, I proposed that chronic fatigue syndrome (CFS) is caused by a response to infection, involving the induction of inflammatory cytokines which induce, in turn, the inducible nitric oxide synthase, producing elevated nitric oxide. Nitric oxide reacts with superoxide to form the potent oxidant, peroxynitrite. Six positive feedback loops were proposed by which peroxynitrite may stay elevated, acting to increase levels of both nitric oxide and superoxide, which react to form more peroxynitrite. This vicious cycle based on known biochemistry is proposed to be the central cause of CFS. The current paper discusses additional inducers which may act by increasing nitric oxide (physical or psychological trauma) or increasing superoxide (hypoxia) and the role of orthostatic intolerance, Ehlers-Danlos syndrome, excessive exercise, exercise intolerance and carbon monoxide in inducing hypoxia and consequently superoxide and peroxynitrite. The major symptoms of CFS can all be interpreted as relatively direct consequences of the pathophysiology predicted by the elevated peroxynitrite theory of CFS. Attractive mechanisms are proposed by which elevated peroxynitrite, nitric oxide and/or related physiological changes may induce CFS symptoms including fatigue, immune dysfunction, learning and memory dysfunction, multi-organ pain, exercise intolerance/ postexertional malaise and orthostatic intolerance. Roles are discussed for six factors likely to influence the frequency of CFS induction in response to infection or other inducing events.

Article: LITERATURE IN REVIEW

Table of Contents for Volume: 07 Issue: 3

zaterdag 4 september 1999, 6:00:00

Table of Contents for Volume: 07 Issue: 2

donderdag 3 juni 1999, 6:00:00

Cover Date: 2000
Publication Date: 1999
Copyright Date: 2000

Article: EDITORIAL

Article: Irritant Rhinitis in Allergic, Nonallergic, Control and Chronic Fatigue Syndrome Populations
Background: Irritation symptoms after exposure to ''nonspecific'' stimuli are often attributed to nonallergic rhinitis (vasomotor rhinitis). This is a heterogeneous syndrome of exclusion based on nasal symptoms with negative allergy skin tests. Method: Control (n = 114) and Chronic Fatigue Syndrome (CFS, n = 120) subjects scored the severity of nasal congestion and rhinorrhea sensations that they attributed to 9 irritants. The sum was the ''Irritant Rhinitis Score'' (IRS, maximum 72). A positive IRS of = 19 defined ''Irritant Rhinitis.'' Demographic, allergy skin test and other assessments were done to characterize the Irritant Rhinitis population. Results: Irritant Rhinitis was present in 11% of control and 47% of CFS subjects. In multivariate analysis, positive IRS was correlated with a history of rhinitis complaints, systemic complaints such as fatigue, sensations of congestion and rhinorrhea induced by meteorological conditions, tobacco smoke, odors, perfumes, and other volatile materials, and diagnoses of CFS and Multiple Chemical Sensitivity (MCS). Although atopy was not correlated to Irritant Rhinitis, 51% of allergic rhinitis subjects had a positive IRS. Conclusions: The Irritant Rhinitis Score defined a population with irritant-induced nasal congestion and rhinorrhea who also had significant systemic complaints. Similar neural mechanisms may underlie the spectrum of Irritant Rhinitis, CFS and MCS.

Article: Tobacco Sensitivity in Chronic Fatigue Syndrome (CFS)
Background: Mechanisms responsible for sensitivity to irritants such as tobacco smoke are poorly understood. A Tobacco Score questionnaire was developed to identify and characterize subjects with this sensitivity. For this pilot study, scores were assessed in populations of self-selected controls and a group with irritant sensitivity (Chronic Fatigue Syndrome, CFS). Method: Subjects graded the severity of 21 symptoms associated with tobacco exposure. Results were compared with other instruments and a measure of pain sensitivity (dolorimetry) in 116 control and 103 CFS subjects. Results: The Tobacco Score was positive in 16% of control and 51% of CFS subjects. Significant correlations were found between Tobacco Score, Irritant Rhinitis Score, and history of sinusitis. Intermediate relationships were found with history of allergic rhinitis, Systemic Complaints Score, and Multiple Chemical Sensitivity. Factors having no influence included gender, the severity of CFS symptoms, pain thresholds, and allergy skin tests. Conclusions: Tobacco sensitivity was correlated with measures of upper airway irritation and nonallergic sensitivity to triggers such as weather changes. The spectrum of symptoms, high prevalence in CFS, and absence of a relationship to atopy suggest that these nonallergic irritant syndromes may share a common neuropathophysiology.

Article: The Development of Laboratory-Based Tests in Chronic Pain and Fatigue: 1. Muscle Catabolism and Coagulase Negative Staphylococci Which Produce Membrane Damaging Toxins
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-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.

Article: The Development of Laboratory-Based Tests in Chronic Pain and Fatigue: 2. Essential Fatty Acids and Cholesterol
Objectives: To investigate fatty acid and sterol homeostasis in patients with CFS. Methods: Plasma samples were collected from CFS and control subjects and analyzed for lipid composition by GC-MS metabolic profiling techniques. Results: CFS patients had significantly different profiles of fatty acids and sterols compared with control subjects. The 1st and 2nd most important factors discriminating the CFS patients from the controls, were a decrease in elaidic acid (trans-9-octadecenoic acid) and an increase in stearic acid (octadecanoic acid), respectively. The CFS patients also had lower levels of cholesterol, which has potential impact on membrane integrity and function, steroid hormone synthesis, energy metabolism and bile production. The CFS patients could also be subdivided into subgroups based on their fatty acid and sterol composition. The results of cluster analyses and multivariate analyses revealed that several types of homeostasis exist in different types of CFS patients, whereas the control group was largely homogeneous. Viral infections can contribute to the nature of the lipid-based anomalies in CFS patients and lipid profiles from patients with prior viral infections could be differentiated from those without viral histories. Conclusions: The assessment of fatty acids and sterols in fasting plasma samples can indicate essential fatty acid deficits, suggest appropriate types of essential fatty acid oils for formulations, indicate potential cholesterol deficit-associated anomalies, provide evidence for mitochondrial dysfunction and categorize CFS patients into biochemical subgroups. These evaluations provide a basis for devising individually tailored patient management protocols.

Article: Chronic Fatigue Syndrome: A Dysfunction of the Hypothalamic-Pituitary-Adrenal Axis
Chronic fatigue syndrome is a severe, often disabling disorder with prevalence as high as 422 cases per 100,000 in the United States. Aside from the adverse effects to patients' quality of life, sequela of the disorder include a negative impact on the economy as well as a burden on public health care costs. Some avenues of current research into the possible genesis of the syndrome are neurally mediated hypotension, viral pathogen, immunological disorders, lymphocyte enzyme system abnormalities, or a purely psychological root. This paper is a review of the literatures as to a neuroendocrinologic cause, namely dysfunction of the hypothalamic-pituitary-adrenal axis.

Article: Functional Somatic Syndromes-
This hypothesis deals with reactions described in functional somatic syndromes and postulates that these reactions be described in terms of active/passive and external/internal. The reflex character of these reactions explain the variation in symptom intensity which in turn is projected to doctors as feelings of lacking understanding, especially when disease parameters are normal.

Article: BOOK REVIEW

Table of Contents for Volume: 07 Issue: 1

woensdag 6 januari 1999, 6:00:00

Cover Date: 2000
Publication Date: 1999
Copyright Date: 2000

Article: EDITORIAL

Article: The Biochemistry of Chronic Pain and Fatigue
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.

Article: The Development of Laboratory-Based Tests in Chronic Pain and Fatigue: 1. Muscle Catabolism and Coagulase Negative Staphylococci Which Produce Membrane Damaging Toxins
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.

Article: Chronic Fatigue Syndrome and Cancer
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.

Article: Immunologic Status Correlates with Severity of Physical Symptoms and Perceived Illness Burden in Chronic Fatigue Syndrome Patients
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.

Article: Silicone Breast Implants, Chronic Fatigue Syndrome and Fibromyalgia
Clinical studies have continued to suggest a relationship between silicone breast implants and chronic fatigue syndrome. Extensive epidemiologic studies, however, indicate that such a relationship is likely to be by chance and the successful lawsuits against producers of silicone breast implants are based on factors other than scientific proof. We present several perspectives on this issue which are probably relevant to other reports of putative etiologic agents for chronic fatigue syndrome.

Article: Health Care Workers, Predominant Gender Females at High Risk: Turning the Spotlight on the Endocrine System
''Cluster Outbreaks'' of Chronic Fatigue (Immune Dysfunction) Syndrome (CFIDS)/Myalgic Encephalomyelitis (ME) have been well documented in the Healthcare professions. Large bodies of scientific evidence suggest that the endocrine system is very involved. In fact, it may be the most critical piece of the puzzle that needs to be examined in all future research. Although some subtle immunologic changes have been documented in persons with ME/CFIDS, recent studies on the endocrine system suggest that several hormonal abnormalities may account for the myriad of symptoms. Calkins and colleagues at Johns Hopkins have found that most patients have delayed orthostatic hypotension. Streeten and Bell extended these studies finding that most patients studied have severe hypovolemia. Hormones that prevent these conditions in healthy people are controlled by the pituitary and hypo-thalamus. It is interesting that the symptoms experienced by patients with Pan-Hypothyroidism are virtually identical to CFIDS/ME. Endocrine research shows that most patients have low cortisol levels. Overwhelming research shows a similar pattern to the many autoimmune diseases that occur predominantly in females. What looks like a multi-systemic disease, therefore, could be an endocrine disorder and could possibly explain the predisposition of the female gender. As health care professionals living with the disease, we would like to bridge the gap and help you help us return to our normal, pre-CFIDS/ME lives as best we can.

Article: A Preliminary Study into the Effectiveness of Multi-Convergent Therapy in the Treatment of Heterogeneous Patients with Chronic Fatigue Syndrome
In this preliminary study twenty-eight heterogeneous Chronic Fatigue Syndrome (CFS) patients were treated with MultiConvergent 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.

Article: Announcement: MPWME & AMERICAN BRAME (A.K.A. MPWC/ME)

Table of Contents for Volume: 04 Issue: 4

maandag 5 oktober 1998, 6:00:00

Cover Date: 1998
Publication Date: 1998
Copyright Date: 1998

Article: Editorial

Article: Increased Resting Energy Expenditure in the Chronic Fatigue Syndrome
It has been suggested that resting energy expenditure may be raised in chronic fatigue syndrome due to an upregulation of transmembrane ion transport. We measured resting energy expenditure by indirect calorimetry in 11 women with chronic fatigue and in 11 healthy women. Total body potassium, by whole body counting, and total body water, extracellular water and intracellular water, by a bioelectrical impedance method, were also measured. When individual resting energy expenditure was predicted on the basis of total body potassium values for the chronic fatigue group, 5 out of 11 of these subjects had resting energy expenditure above the upper limit of normal as defined by the control group data. This is consistent with the hypothesis that there is upregulation of the sodium-potassium pump in chronic fatigue syndrome.

Article: Physiopathological Significance of 99mTc HMPAO SPECT Scan Anomalies in Chronic Fatigue Syndrome A Replication Study
Regional cerebral blood flow as measured by 99mTc HMPAO SPECT imaging was compared between chronic fatigue syndrome (CFS) and healthy controls (HC). Larger right(R) > left(L) asymmetry at the parietotemporal level in CFS as compared to HC was observed in accordance with several previous studies. On the contrary, in most regions of interest, hypoperfusion was not confirmed in CFS, and hyperperfusion was demonstrated in several frontal and temporal regions. No significant correlations were found between frontal tracer uptake and R-L parietotemporal asymmetry, on the one hand, and clinically relevant CFS dimensions, on the other.

Article: Fatigue Syndromes and the Aetiology of Autoimmune Disease
In the last decade or so, an impairment of HypothalamicPituitary-Adrenal (HPA) axis activity has been observed in fatigue syndromes. Elevated levels of glucocorticoids help to prevent the immune system From over-reacting and generating a damaging autoimmune proccss. The corollary should be that reduced activity of the HPA axis and diminished levels of plasma cortisol could be associated with autoimmune (AI) disease. Experimental work in mice and rats supports this view. Furthermore, plasma levels of cortisol have been found to be low in the early stages of rheumatoid arthritis. There is some clinical evidence that connective tissue disorders (many of which are regarded as autoimmune diseases) occur approximately one year after the onset of prolonged or chronic fatigue, with the implication that fatigue is not merely a symptom of these disorders but precedes them. Many workers have found changes in the immune system of subjects suffering from CFS (mainly immune activation) which could be conducive to the development of AI disease. It has recently been found that there is, in the CFS, some deficiency of another adrenal steroid, namely that of dehydroepiandrosterone. This steroid exerts a regulatory activity on the immune system and a deficiency may well be an additional factor in the genesis of AI disease. If an association can be established between fatigue syndromes and autoimmune disease then these syndromes will need to be addressed in a more concerned manner and prophylactic measures undertaken to to forestall AI disease.

Article: Immunological and Haematological Parameters in Patients with Chronic Fatigue Syndrome
Red and white blood cell parameter profiles and pokeweed mitogen responses were investigated in 57 CDC-defined CFS patients and 34 age-and sex-matched controls. CFS patients had significantly different red and white blood cell profiles compared with controls. Red cell distribution width (RDW) was the primary regression factor differentiating the groups. RDW was positively associated with mean platelet volume (MPV) in control subjects, but negatively correlated with MPV in CFS patients, indicating a reversal of the functional relationship between these parameters in CFS patients. Hematological parameters, and not the immunological parameters studied, were more important in differentiating CFS patients from healthy control subjects. Female CFS patients had significant increases in RDW and mean platelet volume, and decreases in the numbers of T-helper cells, T-cells and lymphocytes compared with control females. These alterations were not observed in corresponding male comparisons. There were no differences in the pokeweed mitogen (PWM) response between the CFS and control groups. However, in control subjects, a significant association was observed between pokeweed mitogen responses and Rh(D) antigen status, whereas no similar association was measured in CFS patients. Rh(D)-negative control subjects had a significantly increased mitogen response compared with Rh(D)-positive subjects, whereas in CFS patients, no difference was found. It was concluded that future blood parameter and lymphocyte mitogen response studies in CFS patients should bc controlled for sex and Rh status, respectively.

Article: Severe CFS/ME of Juvenile Onset- A Report from the CHROME Database
CHROME has been collecting data since 1995 on very severely disabled patients in the UK with ME, in order to assess aspects of physical and cognitive levels of disability at the onset of the illness and to monitor progress. Results of the first two years data (225 cases) collection are reported. The modal age of onset for this severe group of patients was 11-15, and the proportion increased with more recent years of onset. Patients tended to deteriorate between onset and recruitment in cognitive and functional ability, and in sensory and sleep disturbance. Statistical significance was assessed using McNemar's Test for comparing correlated proportions.

Article: Review of Neuroendocrine Disturbances in the Chronic Fatigue Syndrome Indications for a Role of the Growth Hormone-IGF-1 Axis in the Pathogenesis
The investigation of the growth hormone (GH)-IGF-1 axis in patients with chronic fatigue syndrome (CFS) may be important for different reasons. Some of the disturbances of the hypothalamic-pituitaryadrenal axis and central serotoninergic (5-HT) function in CFS will be reviewed, before elaborating on three hypotheses that may explain thc role of a disturbed GH axis activity in CFS. Firstly, the disturbed central 5-HT receptor activity may be the cause of GH axis dysfunction. Secondly, CFS may be considered as a "stress-related illness," in which the disturbed central 5-HT function is a result rather than the cause of impaired neuroendocrine stress responses. Finally, by analogy with fibromyalgia, sleep abnormalities in CFS may impair nocturnal GH secretion. Whether the disturbed GH axis activity is a primary or secondary phenomenon in the pathogenesis of CFS, should be elucidated by future clinical investigations.

Article: Letter to the Editor

Table of Contents for Volume: 06 Issue: 3/4

donderdag 3 september 1998, 6:00:00

Table of Contents for Volume: 05 Issue: 3/4

donderdag 3 september 1998, 6:00:00

Table of Contents for Volume: 04 Issue: 3

zaterdag 4 juli 1998, 6:00:00

Cover Date: 1998
Publication Date: 1998
Copyright Date: 1998

Article: Editorial

Article: Measurement of C02 in Chronic Fatigue Syndrome Patients
This study has two goals: one, to compare the resting end-tidal pCO2 (PetCO2) and heart rate (HR) of chronic fatigue syndrome patients (CFS) with controls; two, to examine the effects of a mouthpiece and noseclips upon measurements of PetC02 and HR. Patients from the CFS Center came to the University Hospital pulmonary function laboratory for one testing session. Arterial (PaCO2), PetCO2, end-nasal (PenC02) and HR were measured twice; both with and again without the subject breathing through the mouthpiece. We found that PenCO2 was greater and HR lower for both CFS and non-CFS groups when subjects were not confined by the mouthpiece. We conclude that there is no abnormality in the regulation of respiration in CFS patients. Changes in HR accompany changes in PetCO2 in this study. Most likely, both result from anxiety associated with mouthpiece breathing.

Article: Pain Perception in Chronic Fatigue Syndrome
Pain complaints (myalgia, arthralgia, headache, sore throat) are commonly associated with chronic fatigue syndrome (CFS), yet to date, these patients' responses to standardized measures of pain perception have not been investigated. Pain perception was measured by pressure dolorimeter and ice water cold pressor tests, and the McGill Pain Questionnaire among 15 female subjects with CFS, 11 suhjects with Major Depression and 11 healthy controls. No differences were found between the groups for pain threshold or intolerance levels on the pressure dolorimeter and cold pressor tests. CFS and depressed subjects endorsed significantly more self-reported pain complaints than did control subjects. Although more pain complaints were predicted by greater somatization and lower health perceptions, pain threshold and intolerance were not associated with psychiatric symptoms or functional status. The study yielded some interesting preliminary observations related to variability in pain tolerance among CFS patients. These preliminary observations are discussed in terms of the need for future research and their potential implications for treatment and coping with the illness.

Article: Relationship Between SPECT Scans and Buspirone Tests in Patients with ME/CFS
The purpose of this exercise was to study the relationship between the detail shown on the SPECT brain scans with those seen in the buspirone tests. Thirty-nine patients are included in this study. These patients were selected from a large number who had been referred to Dr. Richardson from various parts of the country by their doctors because of a tentative diagnosis of ME/CFS. All the selected patients were confirmed by Dr. Richardson as suffering from ME/CFS taking into account the subjective scoring methods, clinical examination, virology and buspirone tests. This study is an attempt to link together the results of the previously described techniques to investigate possible areas of impaired cellular function in brain which may have purely neuroncural effects or possibly neurohormonal effects. All patients within this study displayed hypoperfusion in some brain area as shown by their SPECT scans (see Appendix, Table 1.1). Thirty-five (90%) showed hypoperfusion in the regions comprising: Twenty-four (62%) in the Brain Stem Twenty (51%) in tlic Caudate Nuclei Nine (23%) showed hypoperfusion in both Brain Stem and Caudate Nuclei regions Thirty (77%) cased demonstrated hypoperfusion in the regions comprising: Tweny-four (62%) in the Temporal Lobes Twelve (31%) in the Parietal Lobes Nine (23%) in the Frontal Lobes. The significance of these results is to confirm that there is actual evidence of neurological dysfunction which results in the continuing morbidity in these ME/CFS patients. The completion of this buspirone test and SPECT scan can be deemed to be basic complementary evidence for the positive diagnosis of ME/CFS.

Article: Chronic Fatigue Syndrome An Atopic State
The cause of the tiredness and depression, may be due to a virus in the acute or recuperative phase, but in the long-term fatigue must be due to other mechanisms. As varied as are our size, shape, skin and eye colour so are the more subtle nuances of antibodies and enzymes which each cell produces. It is postulated that it is mostly atopic patients who will also react abnormally to certain foods, inhalants and skin applications. Sugars (refined foods) play a major role in leading to fatigue by their chemical, physiological, pharmacological and glycosylogical properties. Bread plays a major role in provoking the symptoms of depression in the chronic fatigue syndrome. What is suggested is that in a genetically predisposed group of people food intolerance causes symptoms akin to both the major and minor criteria of CFS.

Article: Chronic Fatigue Syndrome Among School Children and Their Special Educational Needs
Objectives: To determine the prevalence of Chronic Fatigue Syndrome (CFS) in school children. To explore their Special Educational Needs (SEN) arrangements. To evaluate the views of their parents, the educational and medical professionals involved in the process of special education needs assessment. Design: A postal questionnaire survey. Setting: The Merton and Sutton Junior and High Schools. Subjects: Pupils diagnosed with CFS. Main Outcome Measures: Responses to CFS about special educational needs and case details. Results: With a 53.8% return rate, 22 cases were identified giving an overall point prevalence of 0.07%. Of these 22 cases, 21 were in Sutton and one in Merton. There were equal numbers of boys and girls. Although the respondent groups generally agreed about Special Educational Needs arrangements, differences existed on home tuition and physical education (PE) at school. Parents were more against PE, 5 (71%) vs. 2 (14%) and 4 (11%) of doctors and educational staff, respectively (P = 0.001). Four out of seven parents (57%) said home tuition was necessary, while only one doctor (7%) and nine educational staffs (25.7%) agreed with this (P = 0.044). Conclusion: The estimated overall prevalence is consistent with previous paediatric studies. Two different findings, however, emerged. The equal prevalence in boys and girls (in contrast to previous studies) and the highly significant difference of case numbers between these two neighbouring boroughs (21 vs. 1). Further research is needed for possible explanation of these differences.

Article: Characteristics of Fatigued Persons Associated with Features of Chronic Fatigue Syndrome
Background: Characteristics of persons with chronic fatigue syndrome (CFS) have previously been studied by comparing subjects with CFS to subjects with other conditions or no symptoms of fatigue. In the present study of subjects with idiopathic chronic fatigue we examined the association between the number and severity of the features of CFS with other characteristics of the subjects. Methods: Data were obtained from a registry of persons over the age of 17 with fatigue for at least six months. All subjects in the registry completed an extensive questionnaire that provided information about fatigue, demographic characteristics, medical conditions, life style, sleeping habits, and psychological characteristics. The characteristics of the subjects were tested for an association with the number of CFS symptoms and the severity of individual CPS symptoms that are considered to be of fundamental importance and may identify more homogeneous subjects with chronic fatigue. Results: The number of CFS symptoms had a bell shaped distribution. This number was strongly associated with the severity of fatigue, the response of fatigue to mental and physical activity, and the following subject characteristics: a greater frequency of sinus and respiratory infections, a higher frequency of migraine headaches, a greater number of somatoform symptoms that were not included as criteria for CFS, and not drinking alcohol. These same subject characteristics were generally associated with at least one of the individual CFS symptoms but more weakly. Psychological complaints only had a statistically significant positive association with one feature of CFS, neurocognitive complaints. Conclusions: Persons with fatigue can be usefully characterized by the extent to which they meet the CFS criteria.

Table of Contents for Volume: 06 Issue: 2

dinsdag 2 juni 1998, 6:00:00

Table of Contents for Volume: 05 Issue: 2

dinsdag 2 juni 1998, 6:00:00

Cover Date: 1999
Publication Date: 1998
Copyright Date: 1999

Article: EDITORIAL

Article: Differing Patterns of Cognitive Dysfunction and Heart Rate Reactivity in Chemically-Intolerant Individuals With and Without Lifestyle Changes
The purpose of the present study was to compare specific neuropsychological, psychological, and family history patterns, as well as cardiovascular reactivity of three community-recruited groups of nonsmoking, nonalcoholic middle-aged individuals with and without the symptom of intolerance to low levels of environmental chemicals (CI). CI is a common symptom in chronic fatigue syndrome and fibromyalgia. The groups included: (i) CI who had made associated lifestyle changes because of the CI (CI/LSC); (ii) CI who had not made such changes (CI); and (iii) normals without CI (N). All subjects underwent an evaluation session followed by two laboratory cognitive and psychophysiological test sessions one week apart. The CI/LSC diverged from the other groups in exhibiting poorer performance on the Continuous Visual Memory Test (CVMT) in terms of more false alarms and fewer correct hits, but normal performance on a visuospatial test of divided attention (DAT). In contrast, the CI group showed progressively poorer performance on the DAT with practice, but were like the N on the CVMT. The CI group showed a complex sensitization (amplification) of heart rate response to the DAT over time. In addition, the CI/LSC had the highest rate of family histories of alcohol problems and of attention deficit disorder, as well as of antihypertensive medication treatment and self-reported past emotional/physical abuse. Taken together, the data suggest that individuals with CI comprise a heterogeneous population requiring careful definition of subtypes for future studies.

Article: Coping Differences Between Chronic Fatigue Syndrome Sufferers and Their Carers
The main objective of the present study was to describe the extent to which CFS sufferers and their carers reported to have used a number of coping strategies over the course of the illness, and to find out if reports of coping differed between groups of these. In addition, associations between married sufferers and carers were investigated. From a methodological point of view, the factorial structure and the usefulness of the Ways of Coping Questionnaire (Folkman & Lazarus, 1988) in CFS was studied. The results indicated no gender differences. There were also no differences between sufferers supported and not supported by a carer. However, the results indicated reduced coping responses of carer husbands. From a methodological point of view, the emergence of comparable factors for sufferers and carers, which were also closely related to the original emotion and problem-focused factors, suggested that the use of the questionnaire was appropriate. The importance of these findings for coping research and therapy are discussed.

Article: Stigma and Chronic Fatigue Syndrome
We predicted that the largely female population seeking relief from the incapacitating symptoms of chronic fatigue syndrome (CFS), an enigmatic illness, would feel stigmatized, and that attribution of CFS symptoms to psychological causes by physicians would contribute significantly to the CFS-related stigma. Most subjects scored high on measures of stigma: 95% had feelings of estrangement, 70% believed that others attributed their CFS symptoms to psychological causes, 77% coped by using an educational strategy (disclosure) and 39% saw a need to be secretive about their symptoms in some circumstances. Most subjects (77%) were labeled as 'psychological cases' by one or more of the physicians (mean = 8) consulted, but of the 4 stigma measures, only disclosure was related to physician labeling. Such factors as duration of illness and unemployment, dissatisfaction with spouse, and symptom severity correlated significantly with measures of stigma. That many physicians were reportedly ignorant or skeptical of CFS (male more so than female MD's) may influence attempts of CFS patients to legitimize their symptoms by disclosure and lead to high rates of health care system use.

Article: Latency Immunity and Therapy: A Clinical Study of Latent Epstein Barr Virus Incidence in 297 Idiopathic Chronic Fatigue Patients with Plausible Hypotheses
Organ cells of the body retain an Immune Activity System comparable to protozoa. The cells' immunity memory templates are latent proteins, microbes, their toxins and chemicals (latentees). Excess latentees are detected and excreted by latency therapy. Their excretion induces immediate and/or delayed symptoms and signs recognized by the patient. Foreign latent materials (latentors) enter the body and bypass the natural immune system to be taken up selectively by organ cell groups. Active infection/disease and allergens (antigens) involve the natural immune system antibodies. Latent infection/disease and allergens (latentors) involve the Organ Cell Immunity as intracellular latentees. Clinical laboratory testing is inappropriate. This Clinical Anecdotal Study compiles 297 patients who obtained little or no relief from conventional and alternative medicine (duration: 63% > three years). Patients provoked symptoms to two or more of 16 viruses, in particular Epstein Barr Virus. Latency therapy (heat, saunas, massage, tolerated exercise and sweating during sleep, the auto-sauna) dilutions stimulated excretion until symptoms/signs cleared. The principals were Epstein Barr Virus 67.3%, 200 patients; 13 individual viruses 30.0%, 89 patients; non-viral 2.6%, 8 patients. Latency therapy < 50% improvement = 16.5%; 50% to 80% = 26.6%; 80% to 100% = 46.7%; failures = 11%. Fourteen patients gave positive Epstein Barr Virus serology. A latency immunity concept explains affected subjective symptoms and illnesses and offers a treatment which complements related medical therapies.

Article: LETTER TO THE EDITOR

Article: The Philosophy of Pain: New Concepts
This article examines the concept of physical pain and its relationship to philosophy within the context of ethics. The first question posing a problem is: should pain be added to or included in the list of the five senses? Whether sensation is present or not, pain does exist. Pain is part of the ''immediate data of consciousness'' dear to philosophers. Pain is at the heart of ontology, philosophy of the being and existential ontology, which places existence above essence. Pain is mine and teaches me that I exist. Pain conveys my existence more than thought. Why shouldn't we enrich Descartes's cogito? ''I suffer, therefore I exist'' rather than ''I think, therefore I exist'' or even ''I am something which suffers'' rather than ''I am a thing which thinks'' by Descartes. As pain is the witness of their existence, other beings resemble me. The use of physical pain to cause harm is the best transition towards the following question, that is, what is the relationship between pain and evil or harm? This is a question which is primordial and concerns philosophers, moralists and theologians. There is just pain which is harmful and is our enemy to be conquered. This would seem to be what philosophy has to teach those of us who are doctors fighting pain.

Article: Registry of Physicians with CFS/FM

Article: Information Regarding the Registry of Physicians with Chronic Fatigue, Chronic Fatigue Syndrome, and Fibromyalgia

Table of Contents for Volume: 04 Issue: 2

dinsdag 5 mei 1998, 6:00:00

Cover Date: 1998
Publication Date: 1998
Copyright Date: 1998

Article: Editorial

Article: The Role of Glutamine in the Aetiology of the Chronic Fatigue Syndrome A Prospective Study
Background: Recent studies have observed low plasma glutamine concentrations in chronic fatigue syndrome (CFS) subjects. Glutamine has been shown to be essential for immune function and a key substrate in brain neurochemistry. A dysfunctional immune response to infection and/or neurotransmitter dysfunction may be associated with CFS. Objective: To compare the glutamine status of CFS subjects to matched controls and to test the effect of L-glutamine supplementation on the symptoms associated with CFS. Design: A 26-week, randomised, double-blind, placebo-controlled trial. Patients: Sixteen subjects diagnosed with CFS and 16 ageand sex-matched, healthy controls. Intervention: L-glutamine or placebo (2000 mg/day for 26 weeks). Measurements: Plasma and muscle glutamine concentrations, complete haematology counts, lymphocyte surface marker analysis, serum cortisol and testosterone concentrations, and self-reported symptomatic status. Results: Plasma and muscle glutamine concentrations were lower in CFS subjects than controls (P < 0.001 and P = 0.027, respectively). Significant increases in plasma (P = 0.020) and muscle (P = 0.037) glutamine concentration were observed following L-glutamine, but not placebo (P > 0.05), supplementation. However, improvements in symptomatic status were not observed in the L-glutamine group. Although six subjects showed clinical improvements during the trial, there was no change in their plasma or muscle glutamine concentrations. Conclusions: These data suggest that while low plasma glutamine concentrations may occur coincident with CFS, they may not be directly causative of fatigue or other symptoms.

Article: Prolongation of Central Motor Conduction Time in Chronic Fatigue Syndrome
We compared the central motor conduction time (CMCT) obtained by magnetic stimulation of the central nervous system (CNS) of 181 patients who filfilled the criteria (see Fukuda 1994) for CFS with those of 27 healthy control subjects. A cortical and a cervical stimulation was performed on each person under standardised conditions, and the motor evoked potentials (MEP) either from Musculus Abductor Pollicis Brevis (M. APB) or from Musculus Abductor Digiti Minimi (M. ADM) was recorded. For the CFS patients a significant prolongation of the central motor conduction time (M. APB right: p < 0.0001; M. ADP left: p < 0.00005; M. ADM right: p < 0.00005; M. ADM left: p < 0.005) was observed compared to controls. The results presented in this study suggest a central nervous system dysfunction in CFS.

Article: The Physiological Response to Exercise in Chronic Fatigue Syndrome
Background: The chronic fatigue syndrome (CFS) is characterised by a limited exercise capacity. Studies have reported reduced muscle oxidative capacity in CFS, evidenced by abnormal acidosis during exercise and reduced aerobic capacity and exercise endurance. Objective: To compare physiological responses to walking exercise in CFS subjects, sedentary controls, and clinically improved CFS subjects. Design: Ageand sex-matched pairs, with repeated measures. Subjects: Sixteen subjects diagnosed with CFS and 16 ageand sex-matched sedentary controls. Measurements: Heart rate (HR), oxygen uptake (VO2), ventilation (VE) and relative perceived exertion (RPE) responses to incremental walking exercise to volitional exhaustion. Results: CFS subjects reached significantly lower HRpeak (P = 0.023) and achieved nonsignificantly (P > 0.05) lower VO2peak than control subjects. Despite no differences in submaximal exercise responses, CFS subjects reported higher RPE scores than controls (P = 0.003) at submaximal workloads. RPE scores correlated with symptomatic scores for emotionality (r = 0.642) and general fatigue (r = 0.568). Symptomatic recovery in six CFS subjects was associated with nonsignificant increases in HRpeak, VO2peak and VEpeak, and nonsignificant decreases in RPE scores at submaximal workloads. Conclusions: These data suggested that the limited exercise capacity in CFS subjects may be explained by deconditioning due to the sedentary lifestyle necessitated bv the condition. coupled with an increased perception of exertion, potentially linked to psychological symptoms associated with CFS.

Article: Pilot Study of a Multidisciplinary Inpatient Rehabilitation of Severely Incapacitated Patients with the Chronic Fatigue Syndrome
The outcome of severely incapacitated patients with the chronic fatigue syndrome is poor. We examined the outcome of the first 19 such patients admitted to a psychiatric ward in a general hospital for a multidisciplinary rehabilitation programme. Seventeen (89%) patients had functionally improved by discharge, the median Karnofsky score improvement being 15 points in all 19 patients. All fourteen patients who were followed up had maintained or exceeded their improvement by one year, with a median Karnofsky score improvement of 25 in all 16 followed up patients, compared to admission. Only two patients had not improved by discharge and they were the same or worse at one year. A randomised controlled trial is necessary to confirm the efficacy and acceptability of this form of rehabilitation.

Article: Elevated Plasma Prolactin and EEG Slow Wave Power in Post-Polio Fatigue Implications for a Dopamine Deficiency Underlying Post-Viral Fatigue Syndromes
To test the hypothesis that plasma prolactin and electroencephalographic (EEG) slow wave activity are correlated with fatigue, 33 polio survivors without medical or psychologic comorbidities were studied. Subjects were administered the Post-Polio Fatigue Questionnaire (PFQ) and had resting measurement of both plasma prolactin and bilateral temporal-occipital power across the EEG frequency spectrum. Typical daily fatigue severity on the PFQ was significantly correlated with daily difficulty with attention, staying awake and motivation, but not with measures of acute polio severity or the number of limbs affected by late-onset Post-Polio Sequelae symptoms. Prolactin was significantly correlated with daily fatigue severity on the PFQ (r = .39; p < .05). EEG power was equal between the two hemispheres across all frequency bands. However, EEG slow wave power in the right hemisphere was significantly correlated with daily fatigue severity and prolactin level (r = .37; p < .05). Using multiple linear regression, age at acute polio, frequency of difficulty with attention on the PFQ, prolactin and right hemisphere slow wave power predicted 72% of the variance of the daily fatigue severity rating (r = 85; p < .0001). These data suggest that increased prolactin secretion and EEG slowing are related to the severity of post-polio fatigue, findings similar to those in patients with acute paralytic and non-paralytic poliomyelitis and with chronic fatigue syndrome. A primary role is suggested for a dopamine deficiency (versus serotonergic receptor supersensitivity) underlying impaired cortical activation and the symptoms associated with putative post-viral fatigue syndromes.

Article: Review and Hypothesis Might Patients with the Chronic Fatigue Syndrome Have Latent Tetany of Magnesium Deficiency
The latent tetany syndrome (LTS) parallels CFS in its neuromuscular and psychiatric manifestations, as well as in inner ear disturbances: vestibular in CFS and FM, as well as in LTS, and increased vulnerability to noise-induced deafness in LTS. Microvascular damage to the cochlea is seen in Mg deficiency, noise-induced deafness, and might be a factor in migraine and other severe headaches in both LTS and in CFS and FM. Abnormal sleep patterns occur in both LTS and CFS; impaired cognition more in CFS than in LTS. However, some brain and neurotransmitter dysfunctions seen with Mg deficiency might be contributory to cognitive disorders of CFS. Mg loss caused by enhanced catecholamine release produced by stress may well be contributory to stress-induced acute episodes of CFS. Malfunctions of the cellular and humoral immunological systems are caused by experimental Mg deficiency. Whether allergies in CFS patients and abnormal response to antigenic challenge are results of low Mg remains to be proven. Mitral valve prolapse is seen in many LTS and CFS patients; whether a putative Mg deficiency predisposes to this abnormality is not known. Clinical improvement with Mg treatment has been proven in LTS, and seemed helpful in the rare cases of CFS and FM in whom it has been tried. The Mg status should be determined in patient with CFS and FM, but methodology is a handicap. Serum Mg is an inaccurate index. Three methods show promise. Percentage retention of a Mg load is accurate but requires patient's cooperation. Free ionic Mg measurement requires ion-selective electrodes. Blood cell Mg is reliable in a little more than half the patients; sublingual cell Mg seems more accurate. More intensive, and controlled studies of the Mg status of CFS and FM patients, and of their response to Mg therapy is desirable.

Table of Contents for Volume: 04 Issue: 1

dinsdag 3 februari 1998, 6:00:00

Cover Date: 1998
Publication Date: 1998
Copyright Date: 1998

Article: Editorial

Article: Circulating Blood Volume in Chronic Fatigue Syndrome
Chronic fatigue syndrome (CFS) is an illness associated with severe activity limitation and a characteristic pattern of symptoms despite a relatively normal physical examination and routine laboratory evaluation. The recent description of delayed orthostatic hypotension in patients with CFS, and previous findings of reduced red blood cell (RBC) mass in other patients with orthostatic hypotension not known to have CFS, led us to measure RBC mass and plasma volume in 19 individuals (15 female, four male) with well characterized, severe CFS. RBC mass was found to be significantly reduced (p < 0.001) below the published normal range in the 16 women, being subnormal in 15 (93.8%) of them as well as in two of the four men. Plasma volume was subnormal in 10 (52.6%) patients and total blood volume was below normal in 12 (63.2%). The high prevalence and frequent severity of the low RBC mass suggest that this abnormality might contribute to the symptoms of CFS by reducing the oxygen-carrying power of the blood reaching the brain in many of these patients.

Article: IgE Concentrations in Chronic Fatigue Syndrome
Hypothesis: Allergies have been proposed as a cause or contributing factor of chronic Fatigue syndrome (CFS). If this is so, then the stigmata of atopy, such as symptoms of allergic rhinitis and high serum IgE, should be present in CFS subjects. Methods: Medical records from an allergy and immunology clinic were retrospectively reviewed. All subjects who had had a serum IgE measurement performed over a 4-year period were identified, and allergy history and skin test data reviewed. Patients were then classified as: (a) allergic rhinitis (n = 51), (b) CFS (n = 113, 1992 criteria), and (c) normal subjects without atopy, CFS or immunodeficiency (n = 76). IgE levels were compared between groups. Results: A clinical history of allergic rhinitis was present in 31% (35/113) of thc CFS subjects. The IgE levels of allergic rhinitis subjects and the subset of CPS subjects with allergic rhinitis were 392 73 and 406 123 IU/ml, respectively. In contrast, normal subjects and CFS subjccts who did not give a history of allergic rhinitis had normal IgE levels of 49 9 and 33 4 IU/ml, respectively. Conclusion: Atopy with clinically defined allergic rhinitis, high IgE, positive allergy skin tests and the presumed TH2 lymphocyte-IgE-mast cell-eosinophil axis overactivity and immediate hypersensitivity (Type I) immune response was present in a minority of CFS subjects. While atopy may coexist in some CFS subjects, it is unlikely that atopy plays a causal role in CFS pathogenesis.

Article: Daytime Sleepiness and REM Sleep Abnormalities in Chronic Fatigue A Case Series
Objective: To describe a subgroup of patients with chronic fatigue in whom there is increased physiological sleep tendency. Design: Prospective case series. Setting and Patients: Fifty-six consecutive patients with a working diagnosis of chronic fatigue syndrome underwent a sleep interview, overnight polysomnography and a Multiple Sleep Latency Test in a regional Sleep Disorders Center. Results: Of the 56 patients, 14 satisfied the current International Classification of Sleep Disorders criteria for the diagnosis of narcolepsy. Four of these patients had both excessive somnolence and clear-cut cataplexy and 10 pathological somnolence and polysomnographic criteria for narcolepsy. A further 35 had either increased daytime sleepiness, abnormal REM sleep regulation or both. Despite the objective evidence of daytime increased sleep tendency, the majority of the patients complained of fatigue and not of sleepiness. Twenty-nine patients were treated with either dexamphetamine or methylphenidate with good results in about half. Conclusion: We conclude that among patients investigated for chronic fatigue syndrome it is possible to identify a subgroup with significant daytime sleepiness and REM sleep abnormalities. Symptomatic treatment of these patients is often rewarding.

Article: Coincidental Splenectomy in Chronic Fatigue Syndrome
A unique case of coincidental splenectomy for trauma during chronic fatigue syndrome (CFS) is presented. The patient had a two-year history of CFS prior to her involvement in a road crash. Delayed rupture of the spleen ten days later necessitated urgent laparotomy. At operation, the splenic parenchyma was spongy and friable. Splenorrhaphy was considered inadvisable and a splenectomy was performed. Histological examination of the spleen revealed chronic inflammatory changes of uncertain etiology. One year post-operatively, the patient recovered from her CFS symptoms and returned to work. These histopathological changes in the spleen of a patient with CFS have not been described before.

Article: Gastrointestinal Manifestations of Chronic Fatigue Syndrome (CFS) Symptom Perceptions and Quality of Life
Objectives: This study examines the differences in symptoms and Quality of Life (QOL) among patients presenting to a gastrointestinal (GI) service with combinations of chronic fatigue syndrome (CFS) and GI complaints. Methods: We conducted a clinical examination of patients from a private GI practice and divided them into three groups: A combination group consisting of patients diagnosed with both CFS and functional bowel disease (FBD) (Group 1, n = 5); those positively diagnosed with CFS, who also reported GI symptoms, but without a prior GI diagnosis (Group 2, n = 6); and those with FBD, but without a diagnosis of CFS (Group 3, n = 11). These groups were prospectively surveyed, using the Medical Outcomes Study Short Form-36 (SF-36) and the Symptom Index Survey (SIS). Results: Data indicate CFS patients report more symptoms than non-CFS patients, as measured by the SIS, in these areas: Allergies, Digestive Tract, Ears, Eyes, Head, Immune, Joints/Muscles and Metabolism/Endocrine. SF-36 data indicated lower QOL for CFS patients compared to FBD alone (Group 3) patients in the General Health and Energy/Fatigue subscales. Conclusions: CFS patients with GI complaints demonstrate a significant relationship between both diagnoses. Since the observed differences occur between Groups 1 and 3, both with GI diagnoses, this indicates that these differences are a result of the presence or absence of CFS. Also, since these differences occur between CFS/ FBD and FBD-only, the classification of irritable bowel syndrome (IBS) should be modified to include a subset of patients who have a combination of CFS and IBS.

Article: Interleukin-6 and Disease Two Case Reports that Point to the Usefulness of Measuring Cytokine Levels in Clinical Settings
Chronic fatigue syndrome has been associated with patterns of cytokine imbalances whose relevance to disease status remains to be documented. We present here two case reports that illustrate thc relevance of measuring interleukin-6 levels in biological fluids in two clinical entities: hypothermia and Sjgren's syndrome. Further studies of this nature in extended patient populations will allow to discern the relevant contribution among the pleiotropy of roles of each particular cytokine in different clinical settings. It becomes apparent from the cases presented that the clinical manifestation of the imbalance in the expression of a particular cytokine is contingent upon the compartment where it occurs and upon levels of other cytokines. Similar studies will allow to define signature cytokine imbalances for each disease condition and may also shed light on thus far uncharacterized etiological agents.

Article: The Blood-Brain Barrier and Stress

Article: Clinical Trials

Article: Epidemiology/Natural History Studies

Article: General Management of CFS

Article: Immunology

Article: Neuroendocrinology

Article: Virology

Article: Neurocognitive and Neuropsychiatric Studies

Table of Contents for Volume: 06 Issue: 1

maandag 5 januari 1998, 6:00:00

Cover Date: 2000
Publication Date: 1998
Copyright Date: 2000

Article: EDITORIAL

Article: Prevalence of Fatigue and Chronic Fatigue Syndrome-Like Illness in Children and Adolescents
A community-based screening of over 12,000 households was conducted in order to determine the prevalence of fatigue and CFS-like illness in a sample of 5to 17-year olds. Results indicate that over 4% of the sample was fatigued and that 2.05% were diagnosed with CFS-like illness. Adolescents had a slightly higher rate of CFSlike illness (2.91%) than did pre-pubescent children (1.96%). Those with CFS-like illness were almost evenly divided between male (47.5%) and female (52.5%). Youngsters of Latino origin had the highest representation in the CFS-like group. Symptom data, family patterns, and other data are presented for both the CFS-like group and the entire sample.

Article: Erythrocyte Morphology in Rheumatoid Arthritis and Chronic Fatigue Syndrome: A Preliminary Study
Erythrocyte deformability and erythrocyte membrane stability are dependent on the erythrocyte cytoskeleton and its relationship with the contents of the cell. Certain internal occurrences such as oxidation of sulphydryl groups on the membrane cytoskeleton or the haemoglobin molecule could alter this relationship and as a consequence, alter the membrane properties and the shape of the cell. It is thus conceivable that in conditions where there is a potential increase in the generation of free radicals, erythrocyte shape could be altered. We investigated the possibility that predictable shape changes occur in erythrocytes from patients with rheumatoid arthritis (RA), a condition associated with free radical damage. We also investigated this possibility in patients with chronic fatigue syndrome (CFS) and whether any such change could be correlated with those seen in RA. Patients with CFS could be divided into two groups based on their erythrocyte morphology. Patients in one of these groups had increased numbers of stomatocytes. Patients with RA had increased numbers of leptocytes.

Article: Investigation of Erythrocyte Oxidative Damage in Rheumatoid Arthritis and Chronic Fatigue Syndrome
A role of free radical scavenging for erythrocytes has previously been demonstrated, which is additional to their established role of gas exchange. In carrying out this role, erythrocytes become damaged by oxidation, which consumes endogenous reducing substances. It was therefore proposed that there exists a link between erythrocyte metabolism (particularly redox metabolism) and erythrocyte shape and that both of these should be related to erythrocyte deformability. To look for evidence of oxidative damage in vivo, the erythrocytes were assessed for reduced glutathione (GSH), malondialdehyde (MDA), methaemoglobin (metHb) and 2,3-diphosphoglyceric acid (2,3-DPG) in patients suffering from rheumatoid arthritis (RA), chronic fatigue syndrome (CFS) and healthy control subjects. Full blood counts, serum vitamin B12, erythrocyte folate, serum ferritin, serum iron, serum iron binding capacity and erythrocyte magnesium were also performed on all samples. Patients with RA had increased 2,3-DPG, GSH and metHb when compared with the control group as well as the expected decreased haemoglobin, haematocrit, and serum iron. There was evidence of oxidative damage in CFS with 2,3-DPG metHb and MDA increased in this group. An increase in GSH could also be demonstrated in a sub-group of the CFS patients. This damage may explain the shape changes (presumably accompanied by increased rigidity) that have been reported in erythrocytes in patients suffering from CFS and suggests a role for free radicals in the pathogenesis of CFS.

Article: An Empirical Verification of the Fennell Phases of the CFS Illness
The Fennell Phase Inventory is an instrument designed to measure the phases typically experienced by individuals with chronic fatigue syndrome. In a previous study, a three-factor solution emerged. A cluster analysis was then conducted using the three mean scores for each individual, and four clusters emerged. These clusters matched the four phases predicted by Fennell. The Fennell Phase Inventory appears to be a promising way of differentiating the phases that are experienced by individuals with CFS.

Article: LITERATURE IN REVIEW

Article: LETTER TO THE EDITOR

Table of Contents for Volume: 05 Issue: 1

maandag 5 januari 1998, 6:00:00

Cover Date: 1999
Publication Date: 1998
Copyright Date: 1999

Article: EDITORIAL

Article:Study of Muscle Aerobic Metabolism in Chronic Fatigue Syndrome
The purpose of this study was to establish if muscle aerobic metabolism is abnormal in chronic fatigue syndrome (CFS). Myoblast cultures from muscle biopsies of 16 patients with CFS and 10 healthy controls were established. Micromethods were used to determine the lactate/pyruvate (L/P) ratio, respiratory chain function and cytochrome oxidase and lactic dehydrogenase activities. Mitochondrial DNA (mtDNA) volume was measured and mtDNA rearrangements sought. The results showed that myoblasts from ten of 16 cases of CFS had defects in aerobic metabolism: two had increased L/P ratios, suggestive of a defect in oxidative phosphorylation while eight had decreased ratios, consistent with a deficiency in pyruvate dehydrogenase. There was a statistically significant broader range of L/P ratios in the patients' cultures, compared to controls (p = 0.011). No mtDNA rearrangements were present. This in vitro study confirms that there is convincing evidence of mild aerobic defects in skeletal muscle in some cases of CFS.

Article: Chronic Fatigue Syndrome in Psychiatric Patients: Evidence of Premorbid Anomalous Patterns of Brain Organization
Forty-six patients with chronic fatigue syndrome (CFS) were matched with two control groups: one chosen on the basis of relatively good physical health (N = 92) and the other without regard to physical health (N = 46). All patients were from the same psychiatric practice. The groups were compared on 20 anomalous brain conditions or phenomena (ABCP) used as markers of patterns of brain organization. The results suggest that psychiatric patients who subsequently develop CFS have a higher number of pre-CFS ABCP, of both childhood and adult onset, than psychiatric patients who have not developed this condition.

Article: Cytokine Expression and Morphology ofGrown Monocytes from Patients with Chronic Fatigue Syndrome
Although the underlying metabolic cause of chronic fatigue syndrome (CFS) is unknown, specific defects have been proposed to exist in the skeletal muscle, the immune system and the neuroendocrine system. Peripheral blood mononuclear cells from CFS patients and healthy controls were fractionated as adherent cells (monocyte-enriched fraction) and non-adherent cells. We have investigated some activities of the former during in vitro culture. It was observed that the morphology (shape and size) of adherent cells from CFS patients, cocultivated with homologous non-adherent cells, differed between CFS patients and healthy controls for 21 out of 25 (84%) paired samples (i.e., CFS patient and healthy control). Cytokine expression was examined for the adherent cell population collected from 14 CFS patients and 12 healthy controls. Unstimulated and LPS stimulated tumour necrosis factor-a (TNFa) expression was higher for monocytes from 7 out of 14 CFS patients. Unstimulated interleukin-1 (IL-1) expression was higher for monocytes from 10 out of 14 CFS patients, whereas LPS-stimulated IL-1 expression was higher for 8 out of 14 CFS patients. The proportional increase of IL-1 and TNFa following LPS stimulation was lower for the majority of the CFS patients studied, suggesting that the monocytes from CFS patients were less responsive to LPS than the respective healthy controls. The basis for the abnormal in vitro monocyte maturation, the elevated unstimulated levels of IL-1 expression and the abnormal response of the monocytes to LPS is unknown. The relevance of these findings to CFS pathogenesis is discussed.

Article: Treatment of Chronic Fatigue Syndrome with Chinese Medicine
Chronic fatigue syndrome (CFS) is a severe, debilitating disorder, which prominently features self-reported impairments in concentration and short-term memory, and disturbances in sleep and emotions, all of which can affect any one and seriously affect quality of life. In 1987, the Centers for Disease Control and Prevention (CDC) defined CFS as persistent or relapsing fatigue, with at least 50% reduction of baseline activity level lasting for at least 6 months, as one of the main symptoms. Since its cause is still unknown, treatment of CFS has been palliative and has included usually orally administered products, such as vitamin B12, vitamin C, folic acid, iron, magnesium, essential fatty acids, coenzyme Q10 and nicotinamide adenine dinucleotide (NADH), among others. The latter therapeutic modalities can only relieve some symptoms to some extent, but cannot fundamentally eliminate fatigue. It is, therefore, urgent to seek safe and effective drugs for the treatment of fatigue. We propose here that regulating homeostasis and enhancing immunity are important for the treatment of fatigue. In China, many Chinese herbs with such functions have been proven effective, an observation which opens the possibility of a new therapeutic method of eliminating fatigue with traditional Chinese medicine (TCM).

Article: A Nutrient/Toxin Interaction Theory of the Etiology and Pathogenesis of Chronic Pain-Fatigue Syndromes: Part I
Recent research suggests that Chronic Fatigue Syndrome (CFS), Fibromyalgia Syndrome (FMS), and Persian Gulf Syndrome (PGS) may represent the effects of dysfunctions involving the central and/or peripheral nervous system, neuroendocrine system, neuromuscular system, immune system, metabolism, or sleep patterns. Each systemic dysfunction is accepted here as being central to these syndromes but not causal. This two-part review introduces the theory that the syndromes listed above represent finitely variable combinations of multiple systemic dysfunctions which all share a common underlying etiology at the subcellular level: magnesium deficiency plus concomitant fluoride excess (MDFE). The theory is introduced in Part I; detailed evidence which supports the theory is presented in Part II. Treatment suggestions are listed at the end of Part II through a call for clinical trials to test this theory.

Article: A Nutrient/Toxin Interaction Theory of the Etiology and Pathogenesis of Chronic Pain-Fatigue Syndromes: Part II
This second part of the review paper covers the evidence in favor of the theory which proposes that Chronic Fatigue Syndrome, Fibromyalgia Syndrome, and Persian Gulf Syndrome represent finitely variable combinations of multiple systemic dysfunctions which share a common underlying etiology at the subcellular level: magnesium deficiency plus concomitant fluoride excess (MDFE). Treatment suggestions are listed at the end of the manuscript through a call for clinical trials to test the theory presented.

Article: LETTER TO THE EDITOR

Article: PATIENT COLUMN

Table of Contents for Volume: 03 Issue: 4

zondag 2 november 1997, 6:00:00

Table of Contents for Volume: 03 Issue: 3

vrijdag 5 september 1997, 6:00:00

Table of Contents for Volume: 03 Issue: 2

dinsdag 6 mei 1997, 6:00:00

Cover Date: 1997
Publication Date: 1997
Copyright Date: 1997

Article: Guest Editorial

Article: Research with Children and Adolescents with Chronic Fatigue Syndrome Methodologies, Designs, and Special Considerations
Chronic fatigue syndrome (CFS) in children and adolescents presents unique challenges and opportunities to researchers. Issues specific to research conducted on children and adolescents with CFS are discussed. Such issues include the importance of utilizing a consistent definition of CFS and ascertaining that all participants meet the criteria, the need for attention to wading of questions regarding fatigue, and the significance of medical evaluations as part of a research study. Considerations pertaining to research with minors, such as confidentiality and assent, are explored. Finally, suggestions for future research on children are made.

Article: The Prevalence of Chronic Fatiguing Illnesses Among Adolescents in the United States
Objective. To compare the prevalence of unexplained chronic fatigue (CF) and chronic fatigue syndrome (CFS) among adolescents in three studies conducted by the Centers for Disease Control and Prevention and to compare these estimates with those for adults in two of the studies. Design. Thc studies used the following three designs: (i) a physicianbased CFS surveillance system, (ii) a random, cross-sectional community telephone survey and (iii) a cross-sectional survey of school nurses. Setting. Surveillance included all patients with unexplained fatigue seen by participating physicians in four communities over a 2-year period; the community survey was conducted in a defined, urban population; and the survey of nurses included all middle, junior, and high school nurses in two communities. Patients or other participants. Twenty-three adolescent cases of unexplained chronic fatiguing illness were reported to the surveillance system, 7 of whom were classified with CFS. The community survey screened 2,249 persons between the ages of 2 and 17 years and identified 5 with unexplained chronic fatiguing illness, only one of whom might have had CFS. The school nurses identified 22 students with unexplained fatiguing illness, 10 of whom had received a diagnosis of CFS. Main outcome measures. The prevalence of unexplained chronic fatiguing illness was estimated in all three studies. The prevalence of CFS was estimated in one study, the prevalence of CFS-like illness was estimated in another, and the prevalence of a reported diagnosis of CFS was estimated in the third. Results. In general, the prevalence estimates of CF, CFS-like illness, and CFS for adolescents were lower than those for adults. One study also included children ages 2 to 11 years and found very little CF and no CFS. Cases of CFS among adolescents were evenly distributed across individual years of age. Conclusions. CFS was clearly present among adolescents, although the prevalence for this group was lower than for most adult age groups: Differences in prevalence estimates among the three studies were consistent with differences in study designs. The validity of adolescent/adult comparisons within each study should not be affected by the study design. Further study of the applicability of the current CFS case definition to adolescents is warranted.

Article: Long-Term Sickness Absence Due to ME/CFS in UK Schools An Epidemiological Study with Medical and Educational Implications
A study was made to determine whether the recognition of multiple cases of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in one school is a unique experience. A five-year retrospective period prevalence survey (1991-1995) was collated from sequential reports made in six English Local Education Authority (LEA) areas. By means of a confidential questionnaire circulated to 2,942 school principals via internal mail, 1,098 schools, comprising 27,327 staff and 333,024 pupils, were investigated. Details were obtained on age, gender, location in school sector, work pattern and morbidity. Forty-two percent of all medically certified long-term sickness absence was ascribed to ME/CFS, this figure being well in excess of all other causes. This diagnosis was significantly associated with case clustering, variable geographical prevalence, a marked increase in the female:male case ratio at puberty and prolonged disturbance of educational potential. We conclude that ME/CFS in schools leads to serious economic and career problems. Redirection of research to special educational needs and to early diagnosis of infectious agents which can trigger ME/CFS in schools might prevent, at low cost, much chronic illness and education deficit.

Article: Illness Onset Characteristics in Children with Chronic Fatigue Syndrome and Idiopathic Chronic Fatigue
Twenty-three children and adolescents with unexplained chronic fatigue were evaluated with emphasis upon illness-onset characteristics. Ten subjects had an acute, "flu-like" onset, and four of these subjects had episodes of mild fatigue in the year prior to onset. The thirteen remaining subjects had a gradual onset of chronic fatigue, the majority describing increasing episodes of apparent infectious illnesses associated with fatigue. In these subjects, the fatigue eventually became constant, causing reduction in overall activity levels. In a comparison of subjects who did and did not meet diagnostic criteria for chronic fatigue syndrome, there were no differences in onset characteristics, but differences were noted in illness severity. The majority of children and adolescents with unexplained chronic fatigue had a gradual onset of debilitating symptoms.

Article: Chronic Fatigue Syndrome in Adolescents-An Opinion

Article: Management of Chronic Fatigue Syndrome in Children A Practicing Clinician's Approach

Article: Literature in Review

Table of Contents for Volume: 03 Issue: 1

zondag 5 januari 1997, 6:00:00

Cover Date: 1997
Publication Date: 1997
Copyright Date: 1997

Article: Introduction

Article: Chronic Fatigue Syndrome A Disorder of Central Cholinergic Transmission

Article: A Preliminary Assessment of the Association of SCL-90-R Psychological Inventory Responses with Changes in Urinary Metabolites in Patients with Chronic Fatigue Syndrome
A previous investigation of a cohort of 20 chronic fatigue syndrome (CFS) patients revealed an increased urinary excretion of an unusual metabolite, tentatively identified as amino-hydroxyN-methyl-pyrrolidine (coded CFSUMl) and -alanine, compared with 45 control subjects. The relative abundances of both CFSUM1 and -alanine were positively associated with the core diagnostic symptoms of CFS and associated changes in amino and organic acid excretion. The psychological attributes of these CFS patients and controls were assessed in this study by using the Symptom Check List-90-revised (SCL-90-R) psychological inventory. The CFS patients had increases in the SCL-90-R somatization, obsessive compulsive, depression, anxiety and phobic anxiety dimension scores. Nineteen of 20 CFS patients had somatization T-scores = 63 (P < 0.0001), suggestive of a somatization disorder. Multiple regression analysis indicated that somatization was the most important SCL-90-R defined dimension discriminating CFS from control subjects. Depression and anxiety were not found to be important inter-group determinants. The dimension scores were each related to specific changes in the urinary excretion of organic and amino acids, suggesting that each is biochemically distinct and has an organic basis. Cluster analysis of dimension profiles revealed that the profile with increased prevalence (P < 0.0001) in CFS patients was associated with increased excretion of CFSUM1 (P < 0.005) and had increases in somatization, obsessive compulsion and depression dimension scores. The PSDI as a measure of SCL-90-R symptom severity was positively correlated with CFSUM1 (model P < 0.003). CFSUM1 was also the primary correlate for the somatization dimension (model P < 0.0008), but was not associated with any other SCL-90-R-defined dimension. Another unidentified urinary metabolite, coded UM15, was the primary correlate for depression (model P < 0.0004) and was associated with multiple dimension elevations by both cluster and logistic regression analysis; the excretion of this compound was unrelated to CFSUM1. These results indicated that, in this CFS cohort, the SCL-90-R defined psychological changes were strongly associated with changes in the biochemical homeostasis of patients, suggestive of an organic basis to CFS.

Article: A Screening Instrument for Chronic Fatigue Syndrome Reliability and Validity
Because estimates of the prevalence of Chronic Fatigue Syndrome (CFS) have been quite variable, there is a need for a screening instrument and second stage medical assessment that will produce the most valid estimate of the CFS prevalence. In the present study, four groups of 15 subjects each were recruited: patients diagnosed with (1) CFS, (2) Lupus, (3) Multiple Sclerosis (MS), and (4) a healthy control group. Participants were interviewed twice over a two week period of time with a screening instrument comprising The Fatigue Scale and a newly configured section. The screening instrument had excellent test-retest and interrater reliability. This screening instrument therefore has utility for CFS community-based epidemiologic research. However, while the instrument differentiates with CFS from those who are healthy, it is less likely to distinguish CFS from other autoimmune diseases (especially Lupus). Thus, future community-based CFS prevalence studies should encompass both a screening and a medical examination to adequately differentiate CFS from other illnesses with overlapping symptomatology. We recommend a two-stage research design with (1) a screening instrument with good sensitivity and (2) medical assessments of CFS positives from stage 1 to deal with the specificity problem.

Article: NeuroSPECT Findings in Children - with Chronic Fatigue Syndrome
Background NeuroSPECT studies have described specific abnormalities in cerebral perfusion in adults with criteria for Chronic Fatigue Syndrome. This reports findings in 13 children with criteria for Chronic Fatigue Syndrome. Objective. NeuroSPECT findings in 13 CFS/CFIDS children. Methods. Thirteen children meeting CDC criteria for CFS/CFIDS, were evaluated using NeuroSPECT imaging utilizing Xenon 133 and Tc-99m-HMPAO (1). Results. In 13 children, hypoperfusion was observed at 42 10 ml/min/100g, p < 0.0001 in the left temporal lobe and at 45 11, p < .001 in right temporal lobe. Statistically significant hypoperfusion was also observed in both parietal lobes and at 50 and 53 ml/ min/100g, p < 0.05 in the frontal lobe of the right hemisphere. Quantitatcd HMPAO demonstrated bilateral orbitofrontal and anterior temporal hypoperfusion. There was also hypoperfusion in the dorsal aspects of both frontal lobes and both parietooccipital lobes. Conclusion. NeuroSPECT is presented as a quantifiable, reproducible tool that can allow us to document a cohort of children defined as CFS/CFIDS.

Article: Pteridines and Neuroimmune Function and Pathology

Article: Literature in Review

Table of Contents for Volume: 02 Issue: 4

zaterdag 2 november 1996, 6:00:00

Cover Date: 1996
Publication Date: 1996
Copyright Date: 1996

Article: Editorial

Article: Chronic Fatigue Syndrome (CFS): A Critical Evaluation of Testing for Active Human Herpesvirus-6 (HHV-6) Infection Review of Data of 107 Cases
Aim: To conduct a virologic study in patients with chronic fatigue syndrome (CFS, ICD-10: G 93.3) for identification of reactivated human herpesvirus-6 (HHV-6) infection. Patients and Method: One hundred seven patients (60 women, 47 men, f/m ratio: 1.27/1; age: between 7 and 76 years, medium 41.8 years) with clinical CFS were studied with follow-up periods from 10 months to 7.5 years. Patients were recruited for the study by answering a standard questionnaire and by matching the Holmes' criteria for CFS. This was followed by physical examination, conventional hematological and chemistry testing, lymphocyte phenotyping, and control of other immunologic parameters. Testing for HHV-6 infection included indirect immunofluorescence assays (IFA), antigen capture enzyme linked immunosorbent assay (antigen capture ELISA, ACE), nested polymerase chain reaction (nPCR) on peripheral blood cells, and virus isolation. Results: HHV-6 seroprevalence in CFS patients was 97%. Seventy-two percent of the CFS patients had elevated serum anti-HHV-6 IgG titers, but active HHV-6 infection was detected in only 38.6% of the cases as identified by ACE, nPCR, and virus isolation. In absence of anti-HHV-6-IgM, anti-HHV-6-IgG titers were less reliable for monitoring virus activity. Among other infections EBV was seen in 19.6% of the cases and, less frequently, HSV, Chlamydia, Campylobacter, coxsackie, CMV, Yersinia or Candida. In 46% of the patients there were evident signs of immune deficiency. In additional 20% evidence was less clear (e.g., decreased lymphocyte stimulation: PHA/ConA 46%; low NK cell levels: 35%; and low CD4/CD8 cell ratio: 21%). Conclusion: Active HHV-6 infection was prevalent in one third of our CFS patients, much less than expected. Additional testing besides routine IFA is necessary for confirminig virus activity.

Article: Risk Factors for Chronic Fatigue Syndrome A Case-Control Study
Objective: To study various risk factors previously reported to be associated with chronic fatigue syndrome (CFS). Design: Case-control study. Setting: Metropolitan Atlanta CFS surveillance registry consisting of physicians and clinics that evaluate patients with fatiguing illness. Patients: Twenty-five CFS patients identified from the Centers for Disease Control and Prevention, Atlanta CFS study site, were matched by race, sex, and age to two randomly selected controls. Cases were further subgrouped by type of illness onset-sudden, occurring within a few days, or gradual, occurring over a longer time period. Main outcome measures: A broad panel of risk factors previously associated with CFS. Results: CFS patients were significantly more likely than controls to report a history of stress, persistent nasal symptoms, ear infections, and ingestion of B-complex vitamins during the year prior to the case's onset of illness. In addition, women patients were significantly more likely to have had a hysterectomy. The subset of patients (n = 17) who reported a gradual onset were significantly more likely than patients reporting a sudden onset of illness or controls to report stressful events in the year prior to onset, certain dental procedures, sinusitis, exposures to herbicides, pesticides, or insecticides, and a history of hysterectomy. We could not confirm previously reported associations of CFS with a history of asthma or eczema; exposure to sick animals; exposure to solvents, paint, or other chemicals; ingestion of raw-milk, or travel, occupation, or recreational activity. Conclusions: While no risk factors were identified that effectively distinguish CFS cases from controls, the data do suggest that gradual and sudden onset CFS constitute distinct subclasses of the syndrome. Future studies should subgroup patients based on type of illness onset and further evaluate risk factors of interest, focusing on the role of stress, exposure to herbicides, pesticides, insecticides, and dental and medical histories.

Article: Chronic Fatigue Syndrome Evaluation of a 30-Criteria-Score and Correlation with Immune Activation
Objective: The development of a score for severity of Chronic Fatigue Syndrome (CFS), the correlation of CFS with parameters of immune activation and the association with pathogens. Methods: Five hundred five patients with suspicion of Chronic Fatigue Syndrome and no other definitive diagnosis were checked by a 45-criteria-score, basic laboratory programs and immunological profiles. In most of the patients further tests concerning complement system, immune activation markers, hormones and serology of herpesviruses, Chlamydia and Borrelia could be evaluated. Comparison of the symptoms of CFS patients with healthy controls lead to a 30-criteria-score and this score was correlated with laboratory parameters (Spearman rank-correlation-coefficient rs, ties corrected). Results: Three hundred eighty-five patients fulfilling stronger criteria according to the Centers for Disease Control (CDC) definition showed significant differences to 53 healthy controls in 40 of the 45 criteria (p < 0.001, twitches and food allergies p < 0.05). Thirteen symptoms corresponding to CDC criteria were all significant (p < 0.001), 17 further significant criteria of descending precision were added: respiratory infections, palpitations, dizziness, dyspepsia, dryness of mouth/eyes, allergies, nausea, paresthesia, loss of hair, skin alterations, dyscoordination, chest pain, personality changes, eczema, general infections, twitches, urogenital infections. A correlation between the 30-criteria-score and immunological parameters could be evaluated in 472 of the 505 patients. Significant positive correlation with the 30-criteria-score was found in numbers of CD8+ T-lymphocytes, HLA-DR+ T-lymphocytes, gamma globulins, IgM, IgG, and for the number of types of autoantibodies (mainly ANA, ACA, antithyroid and antiparietal cell antibodies). Significant negative correlation was found in albumin-globulin-ratio, eosinophils and IgE. Most of these parameters also correlated with one another. On the other hand, in subgroups of the 505 patients the Frequency of positivity in serological tests for HHV-6 (49.9%), EBV (35.4%), HSV (29.2%), CMV (12.5%) and Chlamydia (35.0%) was striking. Borrelia Western blots showed 3 or more specific IgG-bands in 54 of 131 patients (41.2%). In some cases infection with EBV, HHV-6 and CMV, respectively, was confmed by DNA-PCR-test and antigen detection. Summary: In increasingly larger groups of patients with CFS and related constellations we often see clinical signs and longer anamnesis of other symptoms besides the classical criteria of CFS, especially a high prevalence of local and general susceptibility to infections and hints to prolonged inflammation processes. Together with other results, the data confirm the hypothesis that a reduced or unstable immune control or delayed immune reaction to persisting viruses or bacterial intracellular pathogens, possibly triggered by common infections or other environmental factors, can lead to a chronic neuroimmune activation state and auto-immune disorders. Hypersensitivity symptoms of the patients might not be mediated by classical allergies alone but also result from a type-lV-hypersensitivity.

Article: The Neuroendocrinology of Chronic Fatigue Syndrome
Since the introduction of operationalized criteria, there has been considerable interest in the pathophysiology of chronic fatigue syndrome (CFS). There is an increasing volume of evidence to support the view that patients with this syndrome have unique neuroendocrinology patterns. Central to this endocrine dysfunction is altered hypothalamic-pituitary-adrenal axis (HPA) activity. The cardinal findings include attenuated adrenocorticotrophic hormone (ACTH) responses to corticotropin-releasing hormone (CRH) and low 24-hour urinary cortisol. These are compatible with a mild central adrenal insufficiency. Adrenal steroids have widespread impact in the brain, and of particular importance is their dense concentration on serotonergic and noradrenergic neurotransmitter pathways. Using a variety of different challenge drugs, a supersensitivity of the serotonergic 5-HT 1A receptor has been demonstrated although the results have not been entirely consistent. A blunting of dexamethasone-induced growth hormone release has been described and may reflect a relative subsensitivity of the steroid receptor. It is proposed that the disruption of the HPA, which may be triggered by a number of stressors including infections, may represent a primary phenomenon, and that the neurotransmitter abnormalities described are in fact secondarily heralded by prolonged HPA dysregulation.

Article: Literature in Review

Table of Contents for Volume: 02 Issue: 2/3

zaterdag 3 augustus 1996, 6:00:00

Cover Date: 1996
Publication Date: 1996
Copyright Date: 1996

Article: Introduction

Article: Polioencephalitis and the Brain Fatigue Generator Model of Post-Viral Fatigue Syndromes
Fatigue is the most commonly reported and most debilitating Post-Polio Sequelae (PPS), affecting millions of polio survivors world-wide. Post-polio fatigue is associated with: (1) subjective reports of difficulty with attention, cognition, word-finding and maintaining wakefulness; (2) clinically significant deficits on neuropsychological tests of information processing speed and attention; (3) gray and white matter hyperintensities in the reticular activating system on magnetic resonance imaging of the brain; (4) neuroendocrine evidence of impaired activation of the HPA axis. Many of these findings are identical to those documented following a variety of viral encephalitides, including acute poliovirus infection, lethargic encephalitis, Iceland Disease, myalgic encephalomyelitis, and, most recently, Chronic Fatigue Syndrome. The clinical, historic, neuropsychologic, neuroanatomic and physiologic parallels between poliovirus infection, post-polio fatigue and post-viral fatigue syndromes (PVFS) will be explored in an attempt to describe the pathophysiology of PVFS. The disinhibition of a putative Brain Fatigue Generator will be implicated as a cause of the subjective symptoms and objective signs that accompany PVFS. The results of a pilot placebo-controlled study of a dopamine 2 receptor agonist to treat post-polio fatigue will also be described.

Article: Chronic Ciguatera One Organic Cause of the Chronic Fatigue Syndrome
Ciguatera is a distressing form of fish poisoning, caused by the ingestion of one or more of a series of ciguatoxins. These poisons, some of the most potent mammalian neurotoxins known, are manufactured in reef-dwelling dinoflagellates and concentrated up the piscine food chain. Human victims, not uncommon in the Pacific, Atlantic and Indian Ocean tropical and subtropical littorals, become poisoned by eating risk species of fish. The acute intoxication is clinically dramatic, resulting in paraesthesiae, dysaesthesiae, prostration, myalgia and arthralgia. In some 20 percent of cases, symptoms of fatigue, reduced exercise tolerance and non-specific aches and pains persist for months and, in a small percentage of cases, for years. Such cases would, in the absence of the prior episode of acute poisoning, satisfy the diagnostic criteria for the chronic fatigue syndrome (CFS). Occasionally, patients are encountered who have been diagnosed as having CFS because of lack of awareness of the ciguatera syndrome, but in whom in retrospect the episode of acute fish poisoning can be established. The fact that at least one potent mammalian toxin can cause a chronic syndrome indistinguishable from CFS opens the way for further research into this enigmatic condition.

Article: Trial of a Selective Acetylcholinesterase Inhibitor, Galanthamine Hydrobromide, in the Treatment of Chronic Fatigue Syndrome
The purpose of the study was to search for a means of diminishing the plight of patients with chronic fatigue syndrome (CFS) and to test the hypothesis that central to the pathogenesis of CFS is a cholinergic defect. Forty-nine patients who fulfilled consensus criteria for CFS were treated with the acetylcholinesterase inhibitor, galanthamine hydrobromide. Thirty-nine patients finished the study according to the protocol with 43% reporting 50% improvement in fatigue, myalgia and sleep and 70% reporting 30% improvement whereas patients in the placebo group reported only 10% improvement in the same parameters of CFS. The improvement of patients on galanthamine was in most cases gradual and reached significance for the group only after four to eight weeks. The improvement was stable, and no patients who reported over 50% improvement on galanthamine relapsed to a pretrial level of any symptom. One of the most surprising effects was the dramatic improvement of sleep disturbances that occurred in most patients on this medication: more than 60% of the patients who finished the study reported over 70% improvement in sleep deficit. If the subjective report by patients can be proved by objective means, this would be the first demonstration of a drug that can be used to correct a sleep disturbance that also influences a specific stage in normal sleep. The most common adverse effect of galanthamine, as given in this study, was nausea that was dose-dependent and reversible. Galanthamine hydrobromide is relatively safe and appears to be an effective medication against many symptoms of CFS. But the positive results of this study have to be interpreted cautiously because of methodological limitations of this trial. First, this study was originally organized as a double-blind, placebo-controlled trial but was changed to an optional crossover after two weeks of treatment. Also, the adverse effects of the active drug in 30% of patients could compromise the double-blind. With these limitations in mind, it is nevertheless tempting to conclude that this study lends an indirect support to our hypothesis that a cholinergic deficit may play a role in the pathogenesis of the syndrome.

Article: The Elusive Gulf War Syndrome
In 1990/1991, approximately 697,000 U.S. service members joined coalition forces in the Middle East for Operations Desert Shield and Desert Storm (ODS/S). Following the military action, a number of service men and women reported a variety of signs and symptoms which they attributed to their participation in the operation; the term Gulf War Syndrome was proposed to facilitate evaluation of what was perceived as a possible new entity. Subsequent studies failed to identify a discrete syndrome, and a series of reports have raised questions as to whether or not Gulf War Syndrome exists or if indeed any of the reported disorders can be attributed to participation in ODS/S. This report reviews the history of U.S. participation in the Gulf War, the medical threats and exposures considered by the U.S. Armed Services, and the U.S. Government's approach to investigating the complaints of the returning servicemen. In the context of the reports from non-U.S. veterans with similar complaints, the elusive Gulf War Syndrome is an important unresolved issue that could provide a model for a number of disorders, including chronic fatigue syndrome.

Article: Section I CFS - Assessment

Article: Session II CFS - Neuro-Endocrinology

Article: Section III CFS - Muscle

Article: Symposium A Related Disorders - Post-Polio Syndrome

Article: Session IV CFS - Microbiologic Pathogenesis

Article: Session V CFS - Immunology

Article: Session VI CFS - Functional Neuro-Imaging

Article: Session VII CFS - Neuropsychology

Article: Session VIII CFS - Clinical Observations

Article: Poster Session I

Article: Session IX CFS - Treatment

Article: Session X CFS - Natural History and Epidemiology

Article: Symposium B Related Disorders - Gulf War Syndrome

Article: Poster Session II

Table of Contents for Volume: 02 Issue: 1

dinsdag 2 april 1996, 6:00:00

Cover Date: 1996
Publication Date: 1996
Copyright Date: 1996

Article: Editorial

Article: Active HHV-6 Infection in Chronic Fatigue Syndrome Patients from Italy New Data
Primary Human Herpesvirus-6 (HHV-6) infection has been related to different clinical pictures and, notably, to Chronic Fatigue Syndrome (CFS). We studied 52 patients fulfilling the criteria of Centers for Disease Control (CDC) for CFS and a control group of 51 matched healthy blood donors. HHV-6 was recovered by culture and confirmed by immunofluorescence assay (IFA) and by PCR in 30/52 patients (57.7%) and in 6/51 (11.7%) of blood donors.

Article: Interindividual Immune Status Variation Patterns in Patients with Chronic Fatigue Syndrome Association with Gender and the Tumor Necrosis Factor System
Changes in soluble immune mediator levels in association with the chronic fatigue syndrome (CFS) usually occur within normal ranges and are apparent mainly as changes in the skewness of population distributions. The latter finding undermines the usefulness of cytokine levels as clinical tools at the individual level as has been seen in sepsis syndrome where a similar overlap occurs. Nonetheless, changes in cytokine levels at the population level can contribute to an understanding of the disease process. For example, we reported previously that significant proportions of CFS patients showed elevated serum levels of either soluble tumor necrosis factor-receptor I (sTNF-RI, sCD120a) or TNF-a as compared to controls. The latter results could reflect different disease processes or extremes of a common disease process. Using sera collected over a five-year period, we have now studied an extended cohort of 108 CFS patients and our results are consistent with a common graded disease process. When we assessed the effect of gender on the distributions of serum levels of immune mediators, levels of sTNF-RI, sTNF-RII (sCD 12Ob), sIL-6R (sCDl26), and sICAM-1 were found to be consistently higher among males than females and among CFS patients as compared to controls regardless of gender. Moreover, differences in soluble immune mediator levels between CFS and control individuals were more clearly defined when restricting the analysis to the female gender. These observations are consistent with endocrine influences on immunological changes.

Article: Gulf War Syndrome Polysormographic Study of Eight Cases
Our purpose was to explore whether patients complaining of the "Gulf War Syndrome" might have hidden sleep disorders, or psychiatric disorders, similar to what has been described in patients with chronic fatigue syndrome and fibromyalgia. Eight consecutive Gulf War veterans from the VA Gulf War Registry and Evaluation program complaining of fatigue, as well as other symptoms, were psychiatrically and polysomnographically screened. One was found to have major depression and Post-traumatic Stress Disorder (PTSD), while another had PTSD alone. The sleep diagnoses assigned to the 8 patients were as follows: Three had sleep apnea syndrome, one of whom also had periodic limb movements of sleep disorder. Four others met criteria for periodic limb movements (PLMs) of sleep disorder. Four of the patients had clinically significant sleep state-misperceptions. All of the patients' symptoms were reported as occurring subsequent to Gulf War deployment, and not prior to deployment. As with the classic fatigue syndromes such as chronic fatigue syndrome and fibromyalgia, Gulf War Syndrome patients may benefit from a more thorough investigation of their sleep and psychiatric status. In view of these findings, consideration of polysomnographic screening would appear appropriate in Gulf War Veterans with fatigue or sleep-related complaints.

Article: Race and Ethnicity in Patients with Chronic Fatigue
Purpose: Chronic fatigue (CF) is a common complaint in ambulatory settings. Chronic fatigue syndrome (CFS) is characterized by profound fatigue associated with other symptoms that is rarely reported in racial/ethnic minorities. Our objectives were to determine if differences exist between Caucasian and minority patients presenting with CF, particularly in the frequency meeting criteria for CFS. Patients: 690 patients with CF seen in a university-based referral clinic. Design/Methods: Demographic, historical, physical examination, laboratory, and psychosocial information was prospectively collected and compared. Psychosocial assessment consisted of a structured psychiatric interview, the Medical Outcomes Study Short-Form Health Survey to assess functional status, the General Health Questionnaire to ascertain psychological distress, and measures of health locus of control, illness attribution, social support, and coping. Results: With the exception of less social support from friends, no significant race/ethicity-related differences were identified. Minority patients tended less commonly to report a moderate level of fatigue, and to have poorer social function, less social support from families, and lower rates of lifetime major depression and alcohol abuse. Conclusions: Demographic, clinical, and psychosocial factors do not distinguish Caucasian from minority CF patients. Help-seeking behaviors, access to care, and the significance attributed to the central complaints should be examined as potentially competing explanations for these findings.

Article: Viruses and Chronic Fatigue Syndrome

Article: Immunologic Abnormalities in Chronic Fatigue Syndrome

Article: Literature in Review

Table of Contents for Volume: 01 Issue: 3/4

woensdag 6 december 1995, 6:00:00

Table of Contents for Volume: 01 Issue: 2

dinsdag 3 oktober 1995, 6:00:00

Cover Date: 1995
Publication Date: 1995
Copyright Date: 1995

Article: EDITORIAL

Article: Viruses and Chronic Fatigue Syndrome Current Status
Because of the sudden onset of "flu-like" symptoms in he vast majority of cases, followed by persistent illness and fatigue over several years, bolh RNA (retroviruses) and DNA (herpesviruses and enteroviruses) viruses have been suspected to be implicated in the pathogenesis of CFS. In recent years, evidence of the association of some viruses wilh CFS has progressed, whereas, with some others it has weakened considerably. Thus far, no single virus has been found to be the causative agent of CFS. Reactivation, however, of latent virus or viruses could contribute to the symptomatology of CFS by damaging the immune system either directly or indirectly. In this report we have provided a comprehensive review of the status of research on viral agents which have been investigated for their role in the pathogenesis of CFS.

Article: Relationships of Cognitive Difficulties to Immune Measures, Depression and Illness Burden in Chronic Fatigue Syndrome
Objective. We related the subjective assessment of cognitive difficulties with lymphocyte phenotypes, cellmediated immunity (CMI), cytokine and neopterin levels in patients with chronic fatigue syndrome (CFS), in order to determine if CFS patients complaining of greater cognitive difficulties would show greater impairments in cell-mediated immunity and a greater degree of immune system dysregulation, and to determine if these cognitive difficulties would correlate with the other non-affective measures of CFS associated illness burden. We also assessed whether these relationships would hold independent of depression in two ways, by statistically covarying depression severity scores and by comparing subsets of CFS patients with and without a concurrent diagnosis of major depressive disorder. Design. A case series of CFS patients. Setting. Outpatient tertiary referral clinic at the University of Miami School of Medicine, Miami, FL. Patienrs. Consecutive sample of 65 patients who were referred as CFS to the University of Miami Diagnostic Immunology Clinic, who met the Centers for Disease Control and Prevention (CDC) criteria for diagnosis of CFS and consented to participate. Main Measures. Self-assessment of cognitive difficulties, depression and illness burden, clinician-assessed depression and CFS symptoms, lymphocyte phenotype, proliferative response to mitogens, serum levels of cytokines and neopterin. Results. Among CFS patients, high Cognitive Difficulty Scale (CDS) scores were significantly related to lower lymphocyte proliferative responses to mitogens, higher neopterin levels, and higher CD4 and lower CD8 lymphocyte counts. These relationships, with the exception of T cell subset percentages, were maintained when depression severity was used as a co-variate. High CDS scores were also significantly related to lower Karnofsky scores, and greater illness burden as measured by the Sickness Impact Profile. Conclusions. Evidence is presented that CFS patients with higher cognitive difficulty scores have more immune and clinical dysfunction than those patients with less cognitive difficulty, and that these relationships are independent of depression. These observations provide support for the concept that although both cognitive difficulties and immunologic abnormalities, such as immune activation and impaired cell-mediated immunity, may represent secondary sequence to the same event(s), they are not likely to be secondary sequence to depression.

Article: Physical, Behavioral, and Psychological Risk Factors for Chronic Fatigue Syndrome A Central Role for Stress?
In spite of the distinct epidemiologic features of chronic fatigue syndrome, its cause remains unknown and no risk factors for the illness have been identified. In order to better characterize CFS, we conducted a case-control study of well-defined CFS cases to identify physical, behavioral, and psychological factors related to the occurrence of CFS. The study, conducted in the metropolitan area surrounding Newark, New Jersey, USA, included 20 patients who fulfilled the CFS case definition and 20 matched controls. All subjects completed a self-administered questionnaire. The greatest difference between cases and controls was the reported level of stress from any of five sources in the 5 years prior to onset of illness (95% vs. 55%; P = 0.01 1). In addition, the risk of CFS was significantly related to the number of sources of stress, especially

Article: Disturbance of Hypothalamic Function and Evidence for Persistent Enteroviral Infection in Patients with Chronic Fatigue Syndrome
It has been suggested that one of the major effects of persistent virus infections in the production of disorders such as the chronic fatigue syndrome/myalgic encephalomyelitis (CFSFIE) is on the hypothalamus (1). Buspirone, which is one of the anxiolytic drugs of the azapyrone group, causes a release of prolactin by stimulation of serotonin 5-hydroxytryptamine (5-HT) receptors. The buspironeprolactin response was studied in a subgroup of patients with CFS/ME and evidence of persistent enteroviral infection, as shown by the repealed detection of the groupspecific protein of enteroviruses, VPI, in the blood. Family controls who were asymptomatic were studied at the same time. In addition to the response to buspirone, diurnal variations in cortisol and prolactin levels were studied. It was found that the patients with CFS/ME had much greater rises in prolactin levels one hour after buspirone compared to controls. Cortisol levels were elevated in the patients, but the rise was not signiftcantly different between the two groups. There was a significant association between the pattern of sleep disturbance, which we speak of as the OWL syndrome, and the ratio of preand post-buspirone prolactin levels. This study shows that there is a hypothalamic disturbance in the patients who also had evidence of enteroviral infection as part of the disorder of CFSME. It represents a quantifiable biochemical alteration to be found in this group of patients.8

Article: The Chronic Fatigue Syndrome A Comprehensive Approach to Its Definition and Study

Article: LITERATURE IN REVIEW

Table of Contents for Volume: 01 Issue: 1

dinsdag 6 september 1994, 6:00:00

Cover Date: 1995
Publication Date: 1994
Copyright Date: 1995

Article: The Birth of a Journal

Article: Psychoneuroimmunology and Chronic Fatigue Syndrome: Toward New Models of Disease

Article: Chronic Fatigue Syndrome in Children
Chronic fatigue syndrome (CFS), formerly called chronic Epstein-Barr virus syndrome, chronic mononucleosis, and numerous other names, is a symptom complex characterized by marked functional limitation which affects children as well as adults. The symptom complex, physical examination, laboratory evaluation, clinical course, and differential diagnosis are reviewed with particular emphasis upon CFS in children. Management consists of a comprehensive treatment plan including medical, educational, and psychosocial support wiih the aim of reducing both symptom and activity limitation. While etiology is unknown, the use of the term "chronic fatigue syndrome" is appropriate for children with marked functional limitation due to unexplained fatigue who have the associated symptom complex and physical examination findings characteristic of this condition.

Article: Long Term Improvements in Patients with Chronic Fatigue Syndrome Treated with Ampligen
Fifteen patients who fit the CDC definition of chronic fatigue syndrome (CFS) and had evidence of severe reduction in performance levels by low Kamofsky performance scores (KPS) of 20-60 were treated with Ampligen. At baseline most patients showed evidence of cerebral dysfunction by neuropsychological testing, were antigen positive by cell culture assay for human herpesvirus-6 (HHV-6), and displayed reduced performance during exercise tolerance testing, as measured by oxygen consumption. These patients represented a subset of CFS patients with especially severe and sustained symptomatology. Following 1248 weeks of Ampligen therapy, sustained improvements were noted in KPS (p < 0.01). Cognitive function improved including IQ and memory. Oxygen uptake and treadmill duration during exercise tolerance testing was also improved after 24 weeks of treatment (p < 0.01). Reduction in HHV-6 expression as measured by the giant cell assay was significant (p < 0.001). Patients continued to show significant improvement late in therapy, taking 8 to 12 weeks as baseline. It was concluded that while receiving Ampligen, the severely afflicted patients studied here derived long-lasting clinical benefit from the Ampligen therapy.

Article: The Assessment of Vascular Abnormalities in Late Life Chronic Fatigue Syndrome by Brain SPECT: Comparison with Late Life Major Depressive Disorder
We report on brain SPECT analysis of regional cerebral blood flow (rCBF) in late life chronic fatigue syndrome (CFS) patients and compare their results with patients with late life depression and elderly normal controls 45 years and older. We attempted to distinguish CFS from normals and patients with depression and applied the findings to understand the pathophysiology of the illness. We studied 33 patients with CFS (55 10 years), 26 patients with late life depression (62 8 years), and 19 normal controls (66 8 years); 43 other normal controls had only Xe rCBF measurements (66 8 years). We evaluated rCBF quantitatively with Xe images and qualitatively with high resolution imaging using 99mTc-HMPAO. We found that rCBF in CFS measured by Xe varied between 35 and 41 ml/min/l00g in both hemispheres, p < 0.0001 and 0.05; similar findings were observed in depression. In CFS ^99mTc-HMPAO imagain demonstrated right orbitofrontal and marked right dorsofrontal hypoperfusion at 58% to 66% of the maximal activity in the brain, p , 0.001. In late life depression, hypoperfusion was primarily limited to the right orbitofrontal lobe, 42% and 57%, p , 0.001. In depression, the abnormalities were most striking in the left temporal lobe and particularly in the left anterior frontal lobes. CFS patients with major depressive disorder by DMS-III-R criteria did not differ in regional cerebral hypoperfusion from those without major depression. The pathophysiology of the illness may involve the dysregulation of a neural network which includes circuits between the hippocampus (located in the anterior temporal lobe) and the dorsolateral prefrontal cortex.

Article: Dysregulated Expression of Soluble Immune Mediator Receptors in a Subset of Patients with Chronic Fatigue Syndrome: Cross-Sectional Categorization of Patients by Immune Status
Individuals with chronic fatigue syndrome (CFS) have significantly increased proportions of activated CD8⁺T cells, decreased natural killer (NK) cell cytotoxic and lymphoproliferative activities, elevated serum levels of tumor necrosis factor (TNF)-a and detectable TNF-, interleukin (IL)-l, and IL-6 mRNA in peripheral blood mononuclear cells (PBMC). We report here that CFS patients as a group also have significantly higher levels, as compared to controls, of soluble TNF receptor type I (sTNF-RI or sCDl20a), sIL-6R (sCD126) and 2-microglobulin (2-m), but not of IL-1 receptor antagonist (IL-1Ra). Correlative and population distribution studies that included lymphoid phenotypic distributions and function as well as soluble immune mediator expression levels revealed the existence of at least two mainly nonoverlapping immunological categories among CFS patients with either: (1) dysregulaled TNF-a/ expression in association with changes in the serum levels of IL-la, IL-4, sIL-2R and IL-lRa, PBMC-associated expression of IL-1, IL-6 and TNF- mRNA, and T cell activation; or, (2) interrelated and dysregulated expression of sTNF-RI, sIL-6R, and 2-m and significantly decreased lymphoproliferative and NK cell cytotoxic activities. This preliminary systematization is of usefulness in the diagnosis, follow-up, and characterization of possible etiological agents for CFS.

Article: National Institutes of Health Workshop StatementApril 27-29,1994

Article: LITERATURE IN REVIEW

Table of Contents for Volume: 14 Issue: 1

Cover Date: 2007
Prepublication
Copyright Date: 2006

Article: Table of Contents/Front Matter

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