Comparison of two commercial molecular assays for simultaneous detection of respiratory viruses in clinical samples using two automatic electrophoresis detection systems.

Two molecular assays were compared with real-time RT-PCR and viral culture for simultaneous detection of common viruses from respiratory samples: a multiplex ligation-dependant probe amplification (MLPA) and a dual priming oligonucleotide system (DPO). In addition, the positive detections of MLPA and DPO were identified using two different automatic electrophoresis systems. A panel of 168 culture-positive and negative samples was tested by the molecular assays for the presence of influenza A and B virus, respiratory syncytial virus, human metapneumovirus, rhinovirus, coronaviruses, parainfluenza viruses and adenovirus. One hundred and twenty-nine (77%) samples were positive as detected by at least one method. Sixty-nine (41%) samples were positive by cell culture (excluding human metapneumovirus and coronaviruses), 116 (69%) by RT-PCR, 127 (76%) by MLPA and 100 (60%) by DPO. The MLPA yielded results in one attempt for all samples included while 12 (7.2%) samples had to be repeated by the DPO assay due to inconclusive results. The MLPA assay performed well in combination with either electrophoresis system, while the performance of the DPO assay was influenced by the electrophoresis systems. Both molecular assays are comparable with real-time RT-PCR, more sensitive than viral culture and can detect dual infections easily. Results can be obtained within 1 day.

Clostridium glycolicum isolated from a patient with otogenic brain abscesses.

We describe a case of brain abscesses with gas formation following otitis media, for which the patient treated himself by placing clay in his ear. Several microorganisms, including Clostridium glycolicum, were cultured from material obtained from the patient. This is the first report of an infection in an immunocompetent patient associated with this microorganism.

Primary haemochromatosis: a missed cause of chronic fatigue syndrome?

OBJECTIVE: To determine whether patients previously diagnosed as chronic fatigue syndrome (CFS) actually have primary haemochomatosis (PH). METHODS: The setting was a Dutch referral centre. Transferrin saturation (TS) was retrospectively evaluated in banked blood samples of 88 patients diagnosed as CFS. Patients with elevated TS values were asked to provide a new overnight fasting blood sample for a second determination of TS and measurement of serum ferritin. The DNA was investigated for mutations in the HFE gene when one of these iron parameters was elevated. RESULTS: For 19 out of 88 patients with CFS an elevated TS was found. A new blood sample was obtained from 11 of these 19: six had increased TS and two had elevated serum ferritin values. These eight patients were neither C282Y homozygotes nor compound C282Y-H63D heterozygotes. In the eight cases where no new blood samples could be obtained, the TS was > 50% for two of the five men and < 45% for the three female patients. CONCLUSION: In a group of 88 CFS patients we could exclude PH in all but two of them (prevalence 2.3%; 95% confidence interval 0-5.5%). In our population of CFS patients PH is not more common than in a control population of northern European descent (prevalence 0.25-0.50%).

Chronic Fatigue Syndrome and Primary Fibromyalgia Syndrome as recognized by GPs.

BACKGROUND: Prevalence studies on Chronic Fatigue Syndrome (CFS) are rare. Because of the similarity in symptoms, the prevalence of Primary Fibromyalgia Syndrome (PFS) was investigated at the same time. OBJECTIVES: To determine the prevalence of CFS and PFS as recognized by GPs in The Netherlands and to inform them of the existence of CFS. METHODS: A postal questionnaire was sent to all GPs. RESULTS: The questionnaire was returned by 60% of the GPs. Seventy-three per cent reported one or more CFS patients and 83% one or more PFS patients in their practice. CONCLUSION: The estimated prevalence of CFS as recognized by GPs of 112 (PFS 157) patients per 100,000 is a minimum estimate.

The persistence of fatigue in chronic fatigue syndrome and multiple sclerosis: development of a model.

The cause of chronic fatigue syndrome (CFS) is unknown. With respect to factors perpetuating fatigue, on the other hand, a model has been postulated in the literature in which behavioral, cognitive, and affective factors play a role in perpetuating fatigue. In the present study, this hypothesized model was tested on patients with CFS and on fatigued patients with multiple sclerosis (MS). The model was formulated in terms of cause-and-effect relationships and an integral test of this model was performed by the statistical technique, "structural equation modeling," in 51 patients with chronic fatigue syndrome and 50 patients with multiple sclerosis matched for age, gender, and education. Attributing complaints to a somatic cause produced low levels of physical activity, which in turn had a causal effect on fatigue severity. Depression had to be deleted from the model. Sense of control over symptoms and focusing on bodily symptoms each had a direct causal effect on fatigue. The model showed an excellent fit for CFS patients, but was rejected for MS patients. Therefore, a new model for MS patients had to be developed in which sense of control had a causal effect on fatigue. In the MS model, no causal relationship was found between the physical state as measured by the Expanded Disability Status Score (EDSS) and fatigue or functional impairment. The present study shows that cognitive and behavioral factors are involved in the persistence of fatigue. Treatment should be directed at these factors. The processes involved in the subjective experience of fatigue in CFS were different from the processes related to fatigue in MS.

Yersinia enterocolitica and the chronic fatigue syndrome.

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.

Evaluating neuropsychological impairment in chronic fatigue syndrome.

This study was designed to provide an estimate of the prevalence of neuropsychological impairment in chronic fatigue syndrome (CFS), to evaluate the concordance between impairment found on standardized tests and self-reported neuropsychological problems, and to study the relationship between neuropsychological functioning and fatigue severity and psychological processes. We adopted an individual approach to determine neuropsychological impairment as contrasted with the group-comparisons approach used in previous studies. Also, correction for premorbid functioning and confounders was done on an individual basis. The results show that a minority of participants were impaired in neuropsychological functioning. There was no relationship between neuropsychological impairment on standardized tests and self-reported memory and concentration problems. Neuropsychological functioning was not related to fatigue or depression. Slowed speed of information processing and motor speed were related to low levels of physical activity.

Specificity of a sandwich enzyme-linked immunosorbent assay for detecting Aspergillus galactomannan.

The specificity of a sandwich enzyme-linked immunosorbent assay (ELISA) for detecting Aspergillus galactomannan was tested with exoantigens of 29 fungi cultured from clinical specimens. Cross-reactivity was observed with Penicillium chrysogenum, Penicillium digitatum, and Paecilomyces variotii. Furthermore, 40 serum samples obtained from bacteremic patients with hematologic malignancies were retrospectively tested by sandwich ELISA. False-positive reactions with the serum were reproducible but did not correspond with the results of culture of specific microorganisms. Moreover, the microorganisms cultured from the blood showed no reactivity by the sandwich ELISA.

[Infections in elderly patients]. / Infecties bij de bejaarde patiënt.

Infections are an increasing problem in the elderly population, because of the often atypical presentation and the more frequent occurrence of complications, which lead to increased morbidity and mortality. The increased prevalence of infections in the elderly is due to a number of factors: increased exposure to micro-organisms (especially in nursing homes); degeneration of various organs (atherosclerosis, pulmonary emphysema, diverticulosis, prolapse); decreased immune response; concomitant diseases (e.g. diabetes mellitus) and (or) use of medication. There is often a delay in the diagnosis because the presentation of infection in the elderly is frequently atypical and symptoms are attributed to old age, rather than to infection. Treatment may be hampered by increased resistance of micro-organisms, interaction with other drugs and toxicity problems.

Physical activity in chronic fatigue syndrome: assessment and its role in fatigue.

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.

Respiratory syncytial virus pneumonia in an AIDS patient.

Pneumonia caused by respiratory syncytial virus in an AIDS patient is reported. A co-infection with cytomegalovirus was also demonstrated. Treatment with ribavirin and foscarnet produced good clinical response. The patient, known to have serious obstructive lung disease, suffered from bronchial hyperreactivity for some time afterwards. The dilemma of antiviral therapy is discussed.

The measurement of fatigue in patients with multiple sclerosis. A multidimensional comparison with patients with chronic fatigue syndrome and healthy subjects.

OBJECTIVE: To provide a multidimensional characterization of fatigue in patients with multiple sclerosis (MS). DESIGN: Cross-sectional design. Fifty patients with clinically definite MS were compared on the dimensions of fatigue with 51 patients with chronic fatigue syndrome (CFS) and 53 healthy subjects. RESULTS: Fourty-six percent of the patients with MS reported fatigue to be present at least once a week. Patients with MS and patients with CFS had significantly higher subjective fatigue severity scores than healthy subjects. Patients with MS and patients with CFS had significantly higher scores on measures of psychological well-being than healthy subjects. Patients with MS had scores similar to those of patients with CFS, except that patients with CFS had significantly higher somatization scores. High somatization scores reflect strong focusing on bodily sensations. Both groups of patients were significantly less active than the healthy subjects. The Kurtzke Expanded Disability Status Scale (EDSS) and the Beck Depression Inventory scores were not related to subjective fatigue severity. In patients with MS and in patients with CFS, subjective fatigue severity was related to impairment in daily life, low sense of control over symptoms, and strong focusing on bodily sensations. In CFS, but not in MS, evidence was found for a relationship between low levels of physical activity and attributing symptoms to a physical cause and between subjective fatigue severity and physical activity. CONCLUSIONS: Patients with MS experienced significant fatigue, which had a significant impact on daily functioning and was not related to depression on Expanded Disability Status Scale score. Psychological factors, such as focusing on bodily sensations and low sense of control play a role in the experience of fatigue in MS and CFS.

Prognosis in chronic fatigue syndrome: a prospective study on the natural course.

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.

Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome.

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.

Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome.

Whether immunologic abnormalities correlate with fatigue severity and functional impairment in chronic fatigue syndrome (CFS) was investigated. Blood mononuclear cells were immunophenotyped and circulating ex vivo-produced cytokines were measured in 76 CFS patients and 69 healthy matched controls. Expression of CD11b on CD8 cells was significantly decreased in CFS patients. However, the previously reported increased expression of CD38 and HLA-DR was not confirmed. There was no obvious difference in apoptosis in leukocyte cultures, circulating cytokines, and ex vivo production of interleukin (IL)-1 alpha and IL-1 receptor antagonist. Endotoxin-stimulated ex vivo production of tumor necrosis factor-alpha and IL-beta was significantly lower in CFS. The immunologic test results did not correlate with fatigue severity or psychologic well-being was measured by Checklist Individual Strength, Beck Depression Inventory, and Sickness Impact Profile. Thus, these immunologic tests cannot be used as diagnostic tools in individual CFS patients.

Epstein-Barr virus (EBV) and the chronic fatigue syndrome: normal virus load in blood and normal immunologic reactivity in the EBV regression assay.

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.

Chronic fatigue syndrome: a clinical and laboratory study with a well matched control group.

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.

Enteroviruses and the chronic fatigue syndrome.

The possible role of enteroviral persistence in the etiology of the chronic fatigue syndrome (CFS) was investigated by serological testing, VP-1 antigen testing, and polymerase chain reaction (PCR) analysis of stool specimens as well as by viral cultures of stool--both direct and after acid treatment. No differences between 76 patients with disabling unexplained fatigue and 76 matched controls were found by serological or antigen testing. Furthermore, no enteroviruses were isolated from any stool culture. Enterovirus was detected by PCR in one stool specimen from a patient with CFS but was not detectable in a second sample obtained from the same patient 3 months later. All stool specimens from controls were PCR-negative. These results argue against the hypothesis that enteroviruses persist in patients with CFS and that their persistence plays a role in the pathogenesis of this syndrome.