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This paper describes the assessment of physical activity in chronic fatigue syndrome (CFS) and investigated the following questions: Do patients with CFS have low levels of physical activity; is there a relationship between actual level of physical activity and fatigue; can self-report measures adequately assess actual level of physical activity; what is the role of cognitions with respect to physical activity; and are results with respect to physical activity specific to CFS? Three different types of activity measures were used: self-report questionnaires, a 12-day self-observation list, and a motion-sensing device (Actometer) which was used as a reference for actual activity level. Fifty-one patients with CFS, 50 fatigued patients with multiple sclerosis (MS), and 53 healthy subjects participated in this study. Although none of the self-report questionnaires showed high correlations with the Actometer, questionnaires that require simple ratings of specified activities were related to the Actometer and can be used as acceptable substitutes, in contrast to instruments that require general subjective interpretations of activity that had low or non-significant correlations with the Actometer. Actometer results showed that CFS patients and MS patients had similar activity levels and both groups were significantly less active than healthy subjects. Compared to MS patients, CFS patients were more likely to indicate that they had been less active than other persons they knew. Activities which patients expected to result in higher fatigue levels were less frequently performed. Patients with CFS had significantly higher scores on this measure than MS patients and healthy subjects. Low levels of physical activity were related to severe fatigue in CFS but not in MS. In conclusion, although CFS patients have similar low activity levels than MS patients, there are also important differences between both groups: in CFS cognitive factors are more prominently involved in producing the low activity levels than in MS and in CFS patients activity level is related to fatigue but not in MS.

Summary Background No somatic treatment has been found to be effective for chronic fatigue syndrome (CFS). Antidepressant therapy is commonly used. Fluoxetine is recommended in preference to tricyclic agents because it has fewer sedative and autonomic nervous system effects. However, there have been no randomised, placebo-controlled, double-blind studies showing the effectiveness of antidepressant therapy in CFS. We have carried out such a study to assess the effect of fluoxetine in depressed and non-depressed CFS patients. Methods In this randomised, double-blind study, we recruited 44 patients to the depressed CFS group, and 52 to the non-depressed CFS group. In each group participants were randomly assigned to receive either fluoxetine (20 mg once daily) or placebo for 8 weeks. The effect of fluoxetine was assessed by questionnaires, self-observation lists, standard neuropsychological tests, and a motion-sensing device (Actometer), which were applied on the day treatment started and on the last day. Findings The two groups were well matched in terms of age, sex distribution, employment and marital status, and duration of CFS. There were no significant differences between the placebo and fluoxetine-treated groups in the change during the 8-week treatment period for any dimension of CFS. There was no change in subjective assessments of fatigue, severity of depression, functional impairment, sleep disturbances, neuropsychological function, cognitions, or physical activity in the depressed or the non-depressed subgroup. Interpretation Fluoxetine in a 20 mg daily dose does not have a beneficial effect on any characteristic of CFS. The lack of effect of fluoxetine on depressive symptoms in CFS suggests that processes underlying the presentation of depressive symptoms in CFS may differ from those in patients with major depressive disorder.

In 1992 and 1993, Dutch military personnel were deployed in the peace operation UNTAC in Cambodia. Since returning, Cambodia veterans have reported health complaints which they perceive to be related to their service. Their symptoms strikingly resemble health problems reported by Gulf War veterans. Four years post-return, a cross-sectional survey on health symptoms in Cambodia veterans was initiated. Questionnaires were sent to all Cambodia veterans and four comparison groups. Forgetfulness, difficulty concentrating and fatigue were the symptoms most commonly endorsed. An operational case definition was constructed using a validated fatigue severity questionnaire. Cases were not uniquely found in Cambodia veterans (17%). In Rwanda and Bosnia veterans, respectively, 28% and 11% also met our case definition. Fatigue severity level was predicted by pre-mission, during-mission and post-mission variables, of which retrospective recollection of side-effects of vaccines and causal attributions also have been shown to be relevant in studies on Gulf-related illness.

Background: Patients with chronic fatigue syndrome (CFS) complain of muscle pain and impaired exercise tolerance. Previous studies show that this is due to systemic carnitine deficiency. We investigated the hypothesis that carnitine deficiency plays an important role in CFS in female CFS patients and compared their results with neighbourhood controls. Methods: The level of total carnitine, free carnitine, acylcarnitine and carnitine esters were measured in 25 female CFS patients and 25 healthy matched neighbourhood controls in a blinded fashion. Results: The previously reported decreased level of acylcarnitine in CFS patients was not confirmed. There were also no significant differences in levels of total carnitine, free carnitine and 20 carnitine esters between CFS patients and controls. Conclusions: The present study demonstrates that serum carnitine deficiency does not contribute to or causes the symptoms in many CFS patients.

Subtle signs of autonomic dysfunction and orthostatic intolerance have been reported in patients with chronic fatigue syndrome (CFS). To assess cardiovascular autonomic function noninvasively in an unselected group of patients with CFS, we examined responsiveness to several cardiovascular reflex tests in 37 CFS patients and 38 healthy control subjects. Blood pressure and heart rate (HR) were recorded continuously by a Finapres device before and during forced breathing, standing up, Valsalva maneuver, and sustained handgrip exercise (HG). In addition, a mental arithmetic test was carried out and questionnaires to assess the severity of CFS symptoms were completed. At rest, there were no significant differences in blood pressure or in HR between the two groups. The in- and expiratory difference in HR tended to be lower in CFS patients (28.4 +/- 10.5 beats) than in healthy controls (32.2 +/- 9.5) (p = 0.11). The maximal increase in HR during standing up was not significantly different between the CFS group (37.6 +/-8.9 beats) and the control group (40.2 +/- 8.9 beats). There were no significant differences between both groups with regard to the Valsalva ratio, but the systolic and diastolic blood pressure responses were significantly larger in CFS patients, despite the fact that many CFS patients were not able to sustain the Valsalva maneuver. The HR response to MA was significantly less in the CFS group (22.6 +/- 9.9) than in the control group (29.5 +/- 16.7) (p < 0.05), suggesting impaired cardiac sympathetic responsiveness to mental stress. The lower HR responses could not be explained by the level of concentration in the CFS group. During HG exercise, the hemodynamic responses were lower in the CFS group than in the control group, but this might be attributed to the lower level of muscle exertion in CFS patients. There were no significant differences between CFS patients with and without symptoms of autonomic dysfunction regarding the hemodynamic responses to the cardiovascular reflex tests. The findings of the study suggest that there are no gross alterations in cardiovascular autonomic function in patients with CFS.

Objectives: To investigate the potential role of Yersinia enterocolitica in patients with chronic fatigue syndrome (CFS). Methods: An immunoblot technique was used to detect antibodies to various Yersinia outer membrane proteins (YOPs) in serum samples from 88 patients with CFS and 77 healthy neighbourhood controls, matched for gender and age. Results: The prevalence of IgG and IgA antibodies to various Yersinia outer membrane proteins (YOPs) did not differ between patients with CFS and healthy controls. Twenty-four patients (27%) and nineteen controls (25%) had IgG antibodies to one or more YOPs. Four patients and two controls had both serum IgG and IgA antibodies to at least two different YOPs, compatible with a recent or persistent infection. Although all patients with positive IgG and IgA reactions to two or more YOPs had symptoms that could point to persistent Yersinia infection, these symptoms were also found frequently in patients without antibodies to YOPs. Conclusions: We conclude that Y. enterocolitica is unlikely to play a major role in the aetiology of CFS.

Background—Little is known about the comparability of outpatients with irritable bowel syndrome (IBS) and patients with IBS in primary care with regard to severity of complaints, perceived limitations, other aspects of the complaints, and sex differences.Aims—To compare outpatients with IBS with primary care patients with IBS.Patients—One hundred and nine patients with IBS were recruited from general practices in Amsterdam and 86 patients with IBS were recruited from the outpatient clinic of the Department of Internal Medicine of the University Hospital in Nijmegen.Methods—Each patient completed a questionnaire on demographic variables, abdominal complaints, related complaints, and attributed causes of their abdominal complaints. The scores of the two groups were compared by univariate and multivariate analysis.Results—The outpatient group contained significantly more men, reported more severe abdominal pain, more frequent complaints, more interference with daily activities, and a higher degree of avoidance of activities (pConclusions—Female outpatients consider their complaints to be more serious and interfering than do patients with IBS in primary care. Male outpatients were comparable to primary care patients with IBS. More research needs to be done into sex specific differences in IBS and into the factors that influence the decision to refer a patient with IBS.

OBJECTIVE--To determine spontaneous improvement after a follow up interval of 18 months in patients with chronic fatigue syndrome and to identify factors that predict improvement. METHODS--A longitudinal study was used. Of 298 initially assessed self referred patients fulfilling criteria for chronic fatigue syndrome, 246 patients completed self report questionnaires at follow up (response rate 83%). A multidimensional assessment method was used, measuring behavioural, emotional, cognitive, and social functioning. Comparison data from 53 healthy subjects matched for age, sex, and educational level were available. RESULTS--Three per cent of patients reported complete recovery and 17% reported improvement. At follow up, there were considerable problems at work and consumption of medication was high. Subjective improvement was confirmed by dimensional change: at follow up recovered patients had similar scores to healthy subjects and improved patients showed significant improvement on four out of seven outcome measures and had higher scores than healthy subjects in all dimensions. Sociodemographic variables or treatment by specialists and alternative practitioners did not predict improvement. Predictors of improvement were: subjective sense of control over symptoms, less fatigue, shorter duration of complaints, and a relative absence of physical attributions. CONCLUSION--The improvement rate in patients with a relatively long duration of complaints is small. Psychological factors are related to improvement, especially cognitive factors.

Objective. To investigate the relation between severity of complaints, laboratory data and psychological parameters in patients with chronic fatigue syndrome (CFS). Subjects. Eighty-eight patients with CFS and 77 healthy controls matched for age, sex and geographical area. Methods. Patients and controls visited our outpatient clinic for a detailed medical history, physical examination and psychological tests: Checklist Individual Strength (CIS), Beck Depression Inventory (BDI) and Sickness Impact Profile (SIP). Venous blood was drawn for a complete blood cell count, serum chemistry panel, C-reactive protein and serological tests on a panel of infectious agents. Results. All patients fulfilled the criteria for CFS as described by Sharpe et al. (J R Soc Med 1991; 84: 118–21), only 18 patients (20.5%) fulfilled the CDC criteria. The outcome of serum chemistry tests and haematological tests were within the normal range. No significant differences were found in the outcome of serological tests. Compared to controls, significant differences were found in the results on the CIS, the BDI, and the SIP. These results varied with the number of complaints (CDC criteria). When the number of complaints was included as the covariate in the analysis, there were no significant differences on fatigue severity, depression, and functional impairment between patients who fulfilled the CDC criteria and patients who did not. Conclusion. It is concluded that the psychological parameters of fatigue severity, depression and functional impairment are related to the clinical severity of the illness. Because the extensive panel of laboratory tests applied in this study did not discriminate between patients and controls, it was not possible to investigate a possible relation between the outcomes of psychological and laboratory testing.

The etiology of chronic fatigue syndrome (CFS) is unknown. Some patients have high antibody titers to viral capsid antigen (VCA) and early antigen (EA) of Epstein-Barr virus (EBV), suggesting that reactivation of EBV is involved. We investigated virus load (spontaneous transformation) and immunologic regression of EBV-induced transformation in peripheral blood mononuclear cells (PBMCs) from 10 selected patients with CFS who had high antibody titers to VCA and EA. The outcome was compared with that for nine healthy controls and one patient with severe chronic active EBV infection (SCAEBV). There were no significant differences in viral load between patients and healthy controls. Immunologic regression of in vitro-transformed PBMCs was also equally efficient in patients and controls. The SCAEBV-infected patient and two controls, who were all seronegative for EBV, showed impaired regression. In conclusion, we were unable to demonstrate a role for reactivation of EBV in CFS, even in selected patients with high titers of antibody to VCA and EA of EBV.